Neuroengineering Tools/Applications for Bidirectional Interfaces, Brain–Computer Interfaces, and Neuroprosthetic Implants – A Review of Recent Progress
---
paper_title: Vision based interface system for hands free control of an intelligent wheelchair

paper_content:

BackgroundDue to the shift of the age structure in today's populations, the necessities for developing the devices or technologies to support them have been increasing. Traditionally, the wheelchair, including powered and manual ones, is the most popular and important rehabilitation/assistive device for the disabled and the elderly. However, it is still highly restricted especially for severely disabled. As a solution to this, the Intelligent Wheelchairs (IWs) have received considerable attention as mobility aids. The purpose of this work is to develop the IW interface for providing more convenient and efficient interface to the people the disability in their limbs.MethodsThis paper proposes an intelligent wheelchair (IW) control system for the people with various disabilities. To facilitate a wide variety of user abilities, the proposed system involves the use of face-inclination and mouth-shape information, where the direction of an IW is determined by the inclination of the user's face, while proceeding and stopping are determined by the shapes of the user's mouth. Our system is composed of electric powered wheelchair, data acquisition board, ultrasonic/infra-red sensors, a PC camera, and vision system. Then the vision system to analyze user's gestures is performed by three stages: detector, recognizer, and converter. In the detector, the facial region of the intended user is first obtained using Adaboost, thereafter the mouth region is detected based on edge information. The extracted features are sent to the recognizer, which recognizes the face inclination and mouth shape using statistical analysis and K-means clustering, respectively. These recognition results are then delivered to the converter to control the wheelchair.Result & conclusionThe advantages of the proposed system include 1) accurate recognition of user's intention with minimal user motion and 2) robustness to a cluttered background and the time-varying illumination. To prove these advantages, the proposed system was tested with 34 users in indoor and outdoor environments and the results were compared with those of other systems, then the results showed that the proposed system has superior performance to other systems in terms of speed and accuracy. Therefore, it is proved that proposed system provided a friendly and convenient interface to the severely disabled people.
---
paper_title: Design and Adsorption of Modular Engineered Proteins to Prepare Customized, Neuron-Compatible Coatings

paper_content:

Neural prosthetic implants are currently being developed for the treatment and study of both peripheral and central nervous system disorders. Effective integration of these devices upon implantation is a critical hurdle to achieving function. As a result, much attention has been directed towards the development of biocompatible coatings that prolong their in vivo lifespan. In this work, we present a novel approach to fabricate such coatings, which specifically involves the use of surface-adsorbed, nanoscale-designed protein polymers to prepare reproducible, customized surfaces. A nanoscale modular design strategy was employed to synthesize six engineered, recombinant proteins intended to mimic aspects of the extracellular matrix proteins fibronectin, laminin, and elastin as well as the cell-cell adhesive protein NCAM (neural cell adhesion molecule). Physical adsorption isotherms were experimentally determined for these engineered proteins, allowing for direct calculation of the available ligand density present on coated surfaces. As confirmation that ligand density in these engineered systems impacts neuronal cell behavior, we demonstrate that increasing the density of fibronectin-derived RGD ligands on coated surfaces while maintaining uniform protein surface coverage results in enhanced neurite extension of PC-12 cells. Therefore, this engineered protein adsorption approach allows for the facile preparation of tunable, quantifiable, and reproducible surfaces for in vitro studies of cell-ligand interactions and for potential application as coatings on neural implants.
---
paper_title: A Novel Concept for a Prosthetic Hand With a Bidirectional Interface: A Feasibility Study

paper_content:

A conceptually novel prosthesis consisting of a mechatronic hand, an electromyographic classifier, and a tactile display has been developed and evaluated by addressing problems related to controllability in prosthetics: intention extraction, perception, and feeling of ownership. Experiments have been performed, and encouraging results for a young transradial amputee are reported.
---
paper_title: Human cortical prostheses: lost in translation?

paper_content:

Direct brain control of a prosthetic system is the subject of much popular and scientific news. Neural technology and science have advanced to the point that proof-of-concept systems exist for cortically-controlled prostheses in rats, monkeys, and even humans. However, realizing the dream of making such technology available to everyone is still far off. Fortunately today there is great public and scientific interest in making this happen, but it will only occur when the functional benefits of such systems outweigh the risks. In this article, the authors briefly summarize the state of the art and then highlight many issues that will directly limit clinical translation, including system durability, system performance, and patient risk. Despite the challenges, scientists and clinicians are in the desirable position of having both public and fiscal support to begin addressing these issues directly. The ultimate challenge now is to determine definitively whether these prosthetic systems will become clinical reality or forever unrealized.
---
paper_title: Brain–machine interfaces: past, present and future

paper_content:

Since the original demonstration that electrical activity generated by ensembles of cortical neurons can be employed directly to control a robotic manipulator, research on brain–machine interfaces (BMIs) has experienced an impressive growth. Today BMIs designed for both experimental and clinical studies can translate raw neuronal signals into motor commands that reproduce arm reaching and hand grasping movements in artificial actuators. Clearly, these developments hold promise for the restoration of limb mobility in paralyzed subjects. However, as we review here, before this goal can be reached several bottlenecks have to be passed. These include designing a fully implantable biocompatible recording device, further developing real-time computational algorithms, introducing a method for providing the brain with sensory feedback from the actuators, and designing and building artificial prostheses that can be controlled directly by brain-derived signals. By reaching these milestones, future BMIs will be able to drive and control revolutionary prostheses that feel and act like the human arm.
---
paper_title: A binary method for simple and accurate two-dimensional cursor control from EEG with minimal subject training

paper_content:

Background ::: Brain-computer interfaces (BCI) use electroencephalography (EEG) to interpret user intention and control an output device accordingly. We describe a novel BCI method to use a signal from five EEG channels (comprising one primary channel with four additional channels used to calculate its Laplacian derivation) to provide two-dimensional (2-D) control of a cursor on a computer screen, with simple threshold-based binary classification of band power readings taken over pre-defined time windows during subject hand movement.
---
paper_title: Using multi-neuron population recordings for neural prosthetics

paper_content:

Classical single-neuron recording methods led to 'neuron-centric' concepts of neural coding, whereas more recent multi-neuron population recordings have inspired 'population-centric' concepts of distributed processing in neural systems. Because most neocortical neurons code information coarsely, sensory or motor processing tends to be widely distributed across neuronal populations. Dynamic fluctuations in neural population functions thus involve subtle changes in the overall pattern of neural activity. Mathematical analysis of neural population codes allows extraction of 'motor signals' from neuronal population recordings in the motor cortices, which can then be used in real-time to directly control movement of a robot arm. This technique holds promise for the development of neurally controlled prosthetic devices and provides insights into how information is distributed across several brain regions.
---
paper_title: Thalamic visual neuroprostheses: Comparison of visual percepts generated by natural stimulation of the eye and electrical stimulation of the thalamus

paper_content:

Thalamic visual neuroprostheses to be implanted in the lateral geniculate nucleus of the thalamus (the intermediate relay station of visual information from the retina to the cortex) could be used to provide visual information to blind people when retinal implants are not feasible. The main objective of the present work was to (i) determine a way to compare visual percepts generated by electrical stimulation of the thalamus and percepts elicited by natural stimulation of the eye and (ii) apply this method to contrast the responses of the cortical neurons under these two conditions.
---
paper_title: An ultra small array of electrodes for stimulating multiple inputs into a single neuron

paper_content:

Abstract We have developed an ultra small, translucent array of electrodes for use in the parasaggital cerebellar slice preparation. This positionable array is capable of stimulating multiple independent bundles of parallel fibers (PFs), which synapse onto a single Purkinje neuron. On a silicon substrate, a low-stress silicon nitride film was used both as a structural layer and as electrical insulation. Evaporated gold pads and interconnects were sandwiched between two such layers. A bulk anisotropic silicon etch released the individual arrays. The electrodes are supported within a 2-μm-thick cantilever of translucent silicon nitride. In one design, eight 4-μm-wide square electrodes are arranged on 8-μm-centers. Another design, half the scale of the first, was also tested. The array was mounted on a micromanipulator and can be visualized by an upright microscope. It can then be positioned in the dendritic arbor of a Purkinje neuron while not disturbing a recording pipette at the soma. Paired-pulse facilitation experiments have confirmed that the electrodes are capable of stimulating non-overlapping bundles of PFs. This device will be useful for exploring spatiotemporal synaptic integration in single neurons. Potential applications in experiments on cerebellar LTD are also discussed.
---
paper_title: A neuroengineering suite of computational tools for visual prostheses

paper_content:

The cooperation between neuroscience and biomedical engineering gave rise to a recent, but growing research field, known as neuroengineering. We follow its principles to have a system providing basic descriptions of the visual world to the brain's cortex. We describe a set of software and hardware tools to interface with neural tissue, in order to transmit visual information encoded into a bioinspired neural-like form. The set is composed of a retina-like encoder, and a platform to optimize electrical stimulation parameters for a multi-electrode implant. The main objective is to progress towards a functional visual neuroprosthesis for the blind.
---
paper_title: A Brain Implantable Microsystem with Hybrid RF/IR Telemetry for Advanced Neuroengineering Applications

paper_content:

A prototype cortical neural interface microsystem has been developed for brain implantable neuroengineering applications, featuring hybrid RF (radio- frequency) inductive and IR (infrared) optical telemetries. The system is aimed at neural recording from primates by converting cortical signals to a digital stream of IR light pulses, while acquiring clock signal and electrical power through RF induction. The implantable unit employs a flexible LCP (liquid crystal polymer) substrate for integration of analog, digital, and optoelectronic components, while adapting to the anatomical and physiological constraints of the environment. An ultra-low power analog CMOS chip, which includes preamplifier and multiplexing circuitry, is directly flip-chip bonded to the microelectrode array to form the immediate cortical neuroprobe device. A 16-channel version of the probe has been tested in various in-vivo animal experiments, including measurements of neural activity in somatosensory cortex of a rat.
---
paper_title: Vision based interface system for hands free control of an intelligent wheelchair

paper_content:

BackgroundDue to the shift of the age structure in today's populations, the necessities for developing the devices or technologies to support them have been increasing. Traditionally, the wheelchair, including powered and manual ones, is the most popular and important rehabilitation/assistive device for the disabled and the elderly. However, it is still highly restricted especially for severely disabled. As a solution to this, the Intelligent Wheelchairs (IWs) have received considerable attention as mobility aids. The purpose of this work is to develop the IW interface for providing more convenient and efficient interface to the people the disability in their limbs.MethodsThis paper proposes an intelligent wheelchair (IW) control system for the people with various disabilities. To facilitate a wide variety of user abilities, the proposed system involves the use of face-inclination and mouth-shape information, where the direction of an IW is determined by the inclination of the user's face, while proceeding and stopping are determined by the shapes of the user's mouth. Our system is composed of electric powered wheelchair, data acquisition board, ultrasonic/infra-red sensors, a PC camera, and vision system. Then the vision system to analyze user's gestures is performed by three stages: detector, recognizer, and converter. In the detector, the facial region of the intended user is first obtained using Adaboost, thereafter the mouth region is detected based on edge information. The extracted features are sent to the recognizer, which recognizes the face inclination and mouth shape using statistical analysis and K-means clustering, respectively. These recognition results are then delivered to the converter to control the wheelchair.Result & conclusionThe advantages of the proposed system include 1) accurate recognition of user's intention with minimal user motion and 2) robustness to a cluttered background and the time-varying illumination. To prove these advantages, the proposed system was tested with 34 users in indoor and outdoor environments and the results were compared with those of other systems, then the results showed that the proposed system has superior performance to other systems in terms of speed and accuracy. Therefore, it is proved that proposed system provided a friendly and convenient interface to the severely disabled people.
---
paper_title: When mind meets machine

paper_content:

A new wave of brain–machine interfaces helps disabled people connect with the outside world
---
paper_title: Form-Function Relations in Cone-Tipped Stimulating Microelectrodes

paper_content:

Metal micro-electrodes are widely used in neuroscience research, and could potentially replace macro-electrodes in various neuro-stimulation applications where their small size, specificity, and their ability to also measure unit activity are desirable. The design of stimulating microelectrodes for specific applications requires knowledge on how tip geometry affects function, but several fundamental aspects of this relationship are not yet well understood. This study uses a combined experimental and physical finite-elements simulation approach to formulate three new relationships between the geometrical and electrical properties of stimulating cone-tipped tungsten microelectrodes: 1. The empirical relationship between microelectrode 1kHz impedance and the exposed tip surface area is best approximated by an inverse square-root function (as expected for a cone-tipped resistive interface). 2. Tip angle plays a major role in determining current distribution along the tip, and as a consequence crucially affects the charge injection capacity of a microelectrode. 3. The critical current for the onset of corrosion is independent of tip surface area in sharp microelectrodes.
---
paper_title: Implantable brain computer interface: Challenges to neurotechnology translation

paper_content:

This article reviews three concepts related to implantable brain computer interface (BCI) devices being designed for human use: neural signal extraction primarily for motor commands, signal insertion to restore sensation, and technological challenges that remain. A significant body of literature has occurred over the past four decades regarding motor cortex signal extraction for upper extremity movement or computer interface. However, little is discussed regarding postural or ambulation command signaling. Auditory prosthesis research continues to represent the majority of literature on BCI signal insertion. Significant hurdles continue in the technological translation of BCI implants. These include developing a stable neural interface, significantly increasing signal processing capabilities, and methods of data transfer throughout the human body. The past few years, however, have provided extraordinary human examples of BCI implant potential. Despite technological hurdles, proof-of-concept animal and human studies provide significant encouragement that BCI implants may well find their way into mainstream medical practice in the foreseeable future.
---
paper_title: Design and Adsorption of Modular Engineered Proteins to Prepare Customized, Neuron-Compatible Coatings

paper_content:

Neural prosthetic implants are currently being developed for the treatment and study of both peripheral and central nervous system disorders. Effective integration of these devices upon implantation is a critical hurdle to achieving function. As a result, much attention has been directed towards the development of biocompatible coatings that prolong their in vivo lifespan. In this work, we present a novel approach to fabricate such coatings, which specifically involves the use of surface-adsorbed, nanoscale-designed protein polymers to prepare reproducible, customized surfaces. A nanoscale modular design strategy was employed to synthesize six engineered, recombinant proteins intended to mimic aspects of the extracellular matrix proteins fibronectin, laminin, and elastin as well as the cell-cell adhesive protein NCAM (neural cell adhesion molecule). Physical adsorption isotherms were experimentally determined for these engineered proteins, allowing for direct calculation of the available ligand density present on coated surfaces. As confirmation that ligand density in these engineered systems impacts neuronal cell behavior, we demonstrate that increasing the density of fibronectin-derived RGD ligands on coated surfaces while maintaining uniform protein surface coverage results in enhanced neurite extension of PC-12 cells. Therefore, this engineered protein adsorption approach allows for the facile preparation of tunable, quantifiable, and reproducible surfaces for in vitro studies of cell-ligand interactions and for potential application as coatings on neural implants.
---
paper_title: Review of Wireless and Wearable Electroencephalogram Systems and Brain-Computer Interfaces – A Mini-Review

paper_content:

Biomedical signal monitoring systems have rapidly advanced in recent years, propelled by significant advances in electronic and information technologies. Brain-computer interface (BCI) is one of the important research branches and has become a hot topic in the study of neural engineering, rehabilitation, and brain science. Traditionally, most BCI systems use bulky, wired laboratory-oriented sensing equipments to measure brain activity under well-controlled conditions within a confined space. Using bulky sensing equipments not only is uncomfortable and inconvenient for users, but also impedes their ability to perform routine tasks in daily operational environments. Furthermore, owing to large data volumes, signal processing of BCI systems is often performed off-line using high-end personal computers, hindering the applications of BCI in real-world environments. To be practical for routine use by unconstrained, freely-moving users, BCI systems must be noninvasive, nonintrusive, lightweight and capable of online signal processing. This work reviews recent online BCI systems, focusing especially on wearable, wireless and real-time systems.
---
paper_title: Human cortical prostheses: lost in translation?

paper_content:

Direct brain control of a prosthetic system is the subject of much popular and scientific news. Neural technology and science have advanced to the point that proof-of-concept systems exist for cortically-controlled prostheses in rats, monkeys, and even humans. However, realizing the dream of making such technology available to everyone is still far off. Fortunately today there is great public and scientific interest in making this happen, but it will only occur when the functional benefits of such systems outweigh the risks. In this article, the authors briefly summarize the state of the art and then highlight many issues that will directly limit clinical translation, including system durability, system performance, and patient risk. Despite the challenges, scientists and clinicians are in the desirable position of having both public and fiscal support to begin addressing these issues directly. The ultimate challenge now is to determine definitively whether these prosthetic systems will become clinical reality or forever unrealized.
---
paper_title: Early Interfaced Neural Activity from Chronic Amputated Nerves

paper_content:

Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation, currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative on-dependent multi-electrode arrays of open design allow the early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. .
---
paper_title: A binary method for simple and accurate two-dimensional cursor control from EEG with minimal subject training

paper_content:

Background ::: Brain-computer interfaces (BCI) use electroencephalography (EEG) to interpret user intention and control an output device accordingly. We describe a novel BCI method to use a signal from five EEG channels (comprising one primary channel with four additional channels used to calculate its Laplacian derivation) to provide two-dimensional (2-D) control of a cursor on a computer screen, with simple threshold-based binary classification of band power readings taken over pre-defined time windows during subject hand movement.
---
paper_title: Thalamic visual neuroprostheses: Comparison of visual percepts generated by natural stimulation of the eye and electrical stimulation of the thalamus

paper_content:

Thalamic visual neuroprostheses to be implanted in the lateral geniculate nucleus of the thalamus (the intermediate relay station of visual information from the retina to the cortex) could be used to provide visual information to blind people when retinal implants are not feasible. The main objective of the present work was to (i) determine a way to compare visual percepts generated by electrical stimulation of the thalamus and percepts elicited by natural stimulation of the eye and (ii) apply this method to contrast the responses of the cortical neurons under these two conditions.
---
paper_title: Single-trial classification of NIRS signals during emotional induction tasks: towards a corporeal machine interface

paper_content:

BackgroundCorporeal machine interfaces (CMIs) are one of a few available options for restoring communication and environmental control to those with severe motor impairments. Cognitive processes detectable solely with functional imaging technologies such as near-infrared spectroscopy (NIRS) can potentially provide interfaces requiring less user training than conventional electroencephalography-based CMIs. We hypothesized that visually-cued emotional induction tasks can elicit forehead hemodynamic activity that can be harnessed for a CMI.MethodsData were collected from ten able-bodied participants as they performed trials of positively and negatively-emotional induction tasks. A genetic algorithm was employed to select the optimal signal features, classifier, task valence (positive or negative emotional value of the stimulus), recording site, and signal analysis interval length for each participant. We compared the performance of Linear Discriminant Analysis and Support Vector Machine classifiers. The latency of the NIRS hemodynamic response was estimated as the time required for classification accuracy to stabilize.ResultsBaseline and activation sequences were classified offline with accuracies upwards of 75.0%. Feature selection identified common time-domain discriminatory features across participants. Classification performance varied with the length of the input signal, and optimal signal length was found to be feature-dependent. Statistically significant increases in classification accuracy from baseline rates were observed as early as 2.5 s from initial stimulus presentation.ConclusionNIRS signals during affective states were shown to be distinguishable from baseline states with classification accuracies significantly above chance levels. Further research with NIRS for corporeal machine interfaces is warranted.
---
paper_title: Neuroengineering: Building interfaces from neurons to brain

paper_content:

Neuroengineering is emerging as an exciting new field with wide ranging research opportunities to contribute to both basic and clinical neurosciences. Armed with training and diverse research tools, engineers are now contributing to technologies to interface to neurons and to the whole brain. The research on modern neural and brain interface technologies has culminated in very recent, exciting programs to develop brain-machine interfaces such as neutrally controlled prostheses.
---
paper_title: Carbon Nanotube Electrodes for Effective Interfacing with Retinal Tissue

paper_content:

We have investigated the use of carbon nanotube microelectrodes as an interface material for retinal recording and stimulation applications. Test devices were micro-fabricated and consisted of 60 pristine 30 um electrodes coated with chemical vapor deposited carbon nanotubes, resulting in conducting, three dimensional surfaces with a high effective interfacial area. These attributes are important both for the quality of the cell-surface coupling as well as for electro-chemical interfacing efficiency. The entire chip was packaged to fit a commercial multielectrode recording and stimulation system. Electrical recordings of spontaneous spikes from whole-mount neonatal mouse retinas were consistently obtained minutes after retinas were placed over the electrodes, exhibiting typical bursting and propagating waves. Most importantly, the signals obtained with carbon nanotube electrodes have exceptionally high signal to noise ratio, reaching values as high as 75. Moreover, spikes are marked by a conspicuous gradual increase in amplitude recorded over a period of minutes to hours, suggesting improvement in cell-electrode coupling. This phenomenon is not observed in conventional commercial electrodes. Electrical stimulation using carbon nanotube electrodes was also achieved. We attribute the superior performances of the carbon nanotube electrodes to their three dimensional nature and the strong neuro-carbon nanotube affinity. The results presented here show the great potential of carbon nanotube electrodes for retinal interfacing applications. Specifically, our results demonstrate a route to achieve a reduction in the electrode size down to few micrometers in order to achieve high efficacy local stimulation needed in retinal prosthetic devices.
---
paper_title: A brain-computer interface with vibrotactile biofeedback for haptic information

paper_content:

BackgroundIt has been suggested that Brain-Computer Interfaces (BCI) may one day be suitable for controlling a neuroprosthesis. For closed-loop operation of BCI, a tactile feedback channel that is compatible with neuroprosthetic applications is desired. Operation of an EEG-based BCI using only vibrotactile feedback, a commonly used method to convey haptic senses of contact and pressure, is demonstrated with a high level of accuracy.MethodsA Mu-rhythm based BCI using a motor imagery paradigm was used to control the position of a virtual cursor. The cursor position was shown visually as well as transmitted haptically by modulating the intensity of a vibrotactile stimulus to the upper limb. A total of six subjects operated the BCI in a two-stage targeting task, receiving only vibrotactile biofeedback of performance. The location of the vibration was also systematically varied between the left and right arms to investigate location-dependent effects on performance.Results and ConclusionSubjects are able to control the BCI using only vibrotactile feedback with an average accuracy of 56% and as high as 72%. These accuracies are significantly higher than the 15% predicted by random chance if the subject had no voluntary control of their Mu-rhythm. The results of this study demonstrate that vibrotactile feedback is an effective biofeedback modality to operate a BCI using motor imagery. In addition, the study shows that placement of the vibrotactile stimulation on the biceps ipsilateral or contralateral to the motor imagery introduces a significant bias in the BCI accuracy. This bias is consistent with a drop in performance generated by stimulation of the contralateral limb. Users demonstrated the capability to overcome this bias with training.
---
paper_title: Adhesion Molecule-Modified Biomaterials for Neural Tissue Engineering

paper_content:

Adhesion molecules (AMs) represent one class of biomolecules that promote central nervous system regeneration. These tethered molecules provide cues to regenerating neurons that recapitulate the native brain environment. Improving cell adhesive potential of non-adhesive biomaterials is therefore a common goal in neural tissue engineering. This review discusses common AMs used in neural biomaterials and the mechanism of cell attachment to these AMs. Methods to modify materials with AMs are discussed and compared. Additionally, patterning of AMs for achieving specific neuronal responses is explored.
---
paper_title: Atomic force microscopy analysis of central nervous system cell morphology on silicon carbide and diamond substrates.

paper_content:

Brain machine interface (BMI) devices offer a platform that can be used to assist people with extreme disabilities, such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease. Silicon (Si) has been the material of choice used for the manufacture of BMI devices due to its mechanical strength, its electrical properties and multiple fabrication techniques; however, chronically implanted BMI devices have usually failed within months of implantation due to biocompatibility issues and the fact that Si does not withstand the harsh environment of the body. Single crystal cubic silicon carbide (3C-SiC) and nanocrystalline diamond (NCD) are semiconductor materials that have previously shown good biocompatibility with skin and bone cells. Like Si, these materials have excellent physical characteristics, good electrical properties, but unlike Si, they are chemically inert. We have performed a study to evaluate the general biocompatibility levels of all of these materials through the use of in vitro techniques. H4 human neuroglioma and PC12 rat pheochromocytoma cell lines were used for the study, and polystyrene (PSt) and amorphous glass were used as controls or for morphological comparison. MTT [3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide] assays were performed to determine general cell viability with each substrate and atomic force microscopy (AFM) was used to quantify the general cell morphology on the substrate surface along with the substrate permissiveness to lamellipodia extension. 3C-SiC was the only substrate tested to have good viability and superior lamellipodia permissiveness with both cell lines, while NCD showed a good level of viability with the neural H4 line but a poor viability with the PC12 line and lower permissiveness than 3C-SiC. Explanations pertaining to the performance of each substrate with both cell lines are presented and discussed along with future work that must be performed to further evaluate specific cell reactions on these substrates.
---
paper_title: A neuroengineering suite of computational tools for visual prostheses

paper_content:

The cooperation between neuroscience and biomedical engineering gave rise to a recent, but growing research field, known as neuroengineering. We follow its principles to have a system providing basic descriptions of the visual world to the brain's cortex. We describe a set of software and hardware tools to interface with neural tissue, in order to transmit visual information encoded into a bioinspired neural-like form. The set is composed of a retina-like encoder, and a platform to optimize electrical stimulation parameters for a multi-electrode implant. The main objective is to progress towards a functional visual neuroprosthesis for the blind.
---
paper_title: A Brain Implantable Microsystem with Hybrid RF/IR Telemetry for Advanced Neuroengineering Applications

paper_content:

A prototype cortical neural interface microsystem has been developed for brain implantable neuroengineering applications, featuring hybrid RF (radio- frequency) inductive and IR (infrared) optical telemetries. The system is aimed at neural recording from primates by converting cortical signals to a digital stream of IR light pulses, while acquiring clock signal and electrical power through RF induction. The implantable unit employs a flexible LCP (liquid crystal polymer) substrate for integration of analog, digital, and optoelectronic components, while adapting to the anatomical and physiological constraints of the environment. An ultra-low power analog CMOS chip, which includes preamplifier and multiplexing circuitry, is directly flip-chip bonded to the microelectrode array to form the immediate cortical neuroprobe device. A 16-channel version of the probe has been tested in various in-vivo animal experiments, including measurements of neural activity in somatosensory cortex of a rat.
---
paper_title: Review of Wireless and Wearable Electroencephalogram Systems and Brain-Computer Interfaces – A Mini-Review

paper_content:

Biomedical signal monitoring systems have rapidly advanced in recent years, propelled by significant advances in electronic and information technologies. Brain-computer interface (BCI) is one of the important research branches and has become a hot topic in the study of neural engineering, rehabilitation, and brain science. Traditionally, most BCI systems use bulky, wired laboratory-oriented sensing equipments to measure brain activity under well-controlled conditions within a confined space. Using bulky sensing equipments not only is uncomfortable and inconvenient for users, but also impedes their ability to perform routine tasks in daily operational environments. Furthermore, owing to large data volumes, signal processing of BCI systems is often performed off-line using high-end personal computers, hindering the applications of BCI in real-world environments. To be practical for routine use by unconstrained, freely-moving users, BCI systems must be noninvasive, nonintrusive, lightweight and capable of online signal processing. This work reviews recent online BCI systems, focusing especially on wearable, wireless and real-time systems.
---
paper_title: A binary method for simple and accurate two-dimensional cursor control from EEG with minimal subject training

paper_content:

Background ::: Brain-computer interfaces (BCI) use electroencephalography (EEG) to interpret user intention and control an output device accordingly. We describe a novel BCI method to use a signal from five EEG channels (comprising one primary channel with four additional channels used to calculate its Laplacian derivation) to provide two-dimensional (2-D) control of a cursor on a computer screen, with simple threshold-based binary classification of band power readings taken over pre-defined time windows during subject hand movement.
---
paper_title: Using multi-neuron population recordings for neural prosthetics

paper_content:

Classical single-neuron recording methods led to 'neuron-centric' concepts of neural coding, whereas more recent multi-neuron population recordings have inspired 'population-centric' concepts of distributed processing in neural systems. Because most neocortical neurons code information coarsely, sensory or motor processing tends to be widely distributed across neuronal populations. Dynamic fluctuations in neural population functions thus involve subtle changes in the overall pattern of neural activity. Mathematical analysis of neural population codes allows extraction of 'motor signals' from neuronal population recordings in the motor cortices, which can then be used in real-time to directly control movement of a robot arm. This technique holds promise for the development of neurally controlled prosthetic devices and provides insights into how information is distributed across several brain regions.
---
paper_title: Massively Parallel Signal Processing using the Graphics Processing Unit for Real-Time Brain–Computer Interface Feature Extraction

paper_content:

The clock speeds of modern computer processors have nearly plateaued in the past 5 years. Consequently, neural prosthetic systems that rely on processing large quantities of data in a short period of time face a bottleneck, in that it may not be possible to process all of the data recorded from an electrode array with high channel counts and bandwidth, such as electrocorticographic grids or other implantable systems. Therefore, in this study a method of using the processing capabilities of a graphics card [graphics processing unit (GPU)] was developed for real-time neural signal processing of a brain–computer interface (BCI). The NVIDIA CUDA system was used to offl oad processing to the GPU, which is capable of running many operations in parallel, potentially greatly increasing the speed of existing algorithms. The BCI system records many channels of data, which are processed and translated into a control signal, such as the movement of a computer cursor. This signal processing chain involves computing a matrix–matrix multiplication (i.e., a spatial fi lter), followed by calculating the power spectral density on every channel using an auto-regressive method, and fi nally classifying appropriate features for control. In this study, the fi rst two computationally intensive steps were implemented on the GPU, and the speed was compared to both the current implementation and a central processing unit-based implementation that uses multi-threading. Signifi cant performance gains were obtained with GPU processing: the current implementation processed 1000 channels of 250 ms in 933 ms, while the new GPU method took only 27 ms, an improvement of nearly 35 times.
---
paper_title: An auditory oddball (P300) spelling system for brain‐computer interfaces

paper_content:

This study was designed to develop and test an auditory event-related potential (ERP) based spelling system for a brain-computer interface (BCI) and to compare user’s performance between the auditory and visual modality. The spelling system, where letters in a matrix were coded with acoustically presented numbers, was tested on a group of healthy volunteers. The results were compared with a visual spelling system. Nine of the 13 participants presented with the auditory ERP spelling system scored above a predefined criterion level control for communication. Compared to the visual spelling system, users’ performance was lower and the peak latencies of the auditorily evoked ERPs were delayed. It was concluded that auditorily evoked ERPs from the majority of the users could be reliably classified. High accuracies were achieved in these users, rendering item selection with a BCI based on auditory stimulation feasible for communication. Descriptors: Electroencephalogram, Auditory stimulation, Event-related potential, P300, Brain-computer interface
---
paper_title: Brain–computer interface using a simplified functional near-infrared spectroscopy system

paper_content:

A brain–computer interface (BCI) is a device that allows a user to communicate with external devices through thought processes alone. A novel signal acquisition tool for BCIs is near-infrared spectroscopy (NIRS), an optical technique to measure localized cortical brain activity. The benefits of using this non-invasive modality are safety, portability and accessibility. A number of commercial multi-channel NIRS system are available; however we have developed a straightforward custom-built system to investigate the functionality of a fNIRS-BCI system. This work describes the construction of the device, the principles of operation and the implementation of a fNIRS-BCI application, 'Mindswitch' that harnesses motor imagery for control. Analysis is performed online and feedback of performance is presented to the user. Mindswitch presents a basic 'on/off' switching option to the user, where selection of either state takes 1 min. Initial results show that fNIRS can support simple BCI functionality and shows much potential. Although performance may be currently inferior to many EEG systems, there is much scope for development particularly with more sophisticated signal processing and classification techniques. We hope that by presenting fNIRS as an accessible and affordable option, a new avenue of exploration will open within the BCI research community and stimulate further research in fNIRS-BCIs.
---
paper_title: Iridium Oxide Microelectrode Arrays for In Vitro Stimulation of Individual Rat Neurons from Dissociated Cultures

paper_content:

We present the first in-vitro extracellular stimulation of individual neurons from dissociated cultures with iridium oxide (IrOx) electrodes. Microelectrode arrays with sputtered IrOx films (SIROF) were developed for electrophysiological investigations with electrogenic cells. The microelectrodes were characterized with scanning electron and atomic force microscopy, revealing rough and porous electrodes with enlarged surface areas. As shown by cyclic voltammetry and electrochemical impedance spectroscopy, the large surface area in combination with the good electrochemical properties of SIROF resulted in high charge storage capacity and low electrode impedance. Thus, we could transfer the good properties of IrOx as material for in-vivo stimulation electrodes to MEAs with electrode diameters as small as 10 µm for in-vitro applications. Single rat cortical neurons from dissociated cultures were successfully stimulated to fire action potentials using single or trains of biphasic rectangular voltage-controlled stimulation pulses. The stimulated cell’s membrane potential was simultaneously monitored using whole-cell current-clamp recordings. This experimental configuration allowed direct evaluation of the influence of pulse phase sequence, amplitude, and number on the stimulation success ratio and action potential latency. Negative phase first pulses were more effective for extracellular stimulation and caused reduced latency in comparison to positive phase first pulses. Increasing the pulse amplitude also improved stimulation reliability. However, in order to prevent cell or electrode damage, the pulse amplitude is limited to voltages below the threshold for irreversible electrochemical reactions at the electrode. As an alternative to increasing the amplitude, a higher number of stimulation pulses was also shown to increase stimulation success.
---
paper_title: Early Interfaced Neural Activity from Chronic Amputated Nerves

paper_content:

Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation, currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative on-dependent multi-electrode arrays of open design allow the early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. .
---
paper_title: Nanostructured surface modification of ceramic-based microelectrodes to enhance biocompatibility for a direct brain-machine interface

paper_content:

Many different types of microelectrodes have been developed for use as a direct Brain-Machine Interface (BMI) to chronically recording single neuron action potentials from ensembles of neurons. Unfortunately, the recordings from these microelectrode devices are not consistent and often last for only a few weeks. For most microelectrode types, the loss of these recordings is not due to failure of the electrodes but most likely due to damage to surrounding tissue that results in the formation of nonconductive glial-scar. Since the extracellular matrix consists of nanostructured microtubules, we have postulated that neurons may prefer a more complex surface structure than the smooth surface typical of thin-film microelectrodes. We, therefore, investigated the suitability of a nano-porous silicon surface layer to increase the biocompatibility of our thin film ceramic-insulated multisite electrodes. In-vitro testing demonstrated, for the first time, decreased adhesion of astrocytes and increased extension of neurites from pheochromocytoma cells on porous silicon surfaces compared to smooth silicon surfaces. Moreover, nano-porous surfaces were more biocompatible than macroporous surfaces. Collectively, these results support our hypothesis that nano-porous silicon may be an ideal material to improve biocompatibility of chronically implanted microelectrodes. We next developed a method to apply nano-porous surfaces to ceramic insulated, thin-film, microelectrodes and tested them in vivo. Chronic testing demonstrated that the nano-porous surface modification did not alter the electrical properties of the recording sites and did not interfere with proper functioning of the microelectrodes in vivo.
---
paper_title: Flexible polymer substrate and tungsten microelectrode array for an implantable neural recording system

paper_content:

This paper describes the process flow and testing of a substrate for a fully implantable neural recording system. Tungsten microwires are hybrid-packaged on a micromachined flexible polymer substrate forming an intracortical microelectrode array for brain machine interfaces. The microelectrode array is characterized on the bench top and tested in vivo. The microelectrode noise floor is less than 2 μV and acute recording results show a signal to noise ratio of 9.9–17.3 dB. The technique of hybrid fabrication of the electrodes on a flexible substrate provides a general platform for the development of an implantable neural recording system
---
paper_title: Atomic force microscopy analysis of central nervous system cell morphology on silicon carbide and diamond substrates.

paper_content:

Brain machine interface (BMI) devices offer a platform that can be used to assist people with extreme disabilities, such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease. Silicon (Si) has been the material of choice used for the manufacture of BMI devices due to its mechanical strength, its electrical properties and multiple fabrication techniques; however, chronically implanted BMI devices have usually failed within months of implantation due to biocompatibility issues and the fact that Si does not withstand the harsh environment of the body. Single crystal cubic silicon carbide (3C-SiC) and nanocrystalline diamond (NCD) are semiconductor materials that have previously shown good biocompatibility with skin and bone cells. Like Si, these materials have excellent physical characteristics, good electrical properties, but unlike Si, they are chemically inert. We have performed a study to evaluate the general biocompatibility levels of all of these materials through the use of in vitro techniques. H4 human neuroglioma and PC12 rat pheochromocytoma cell lines were used for the study, and polystyrene (PSt) and amorphous glass were used as controls or for morphological comparison. MTT [3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide] assays were performed to determine general cell viability with each substrate and atomic force microscopy (AFM) was used to quantify the general cell morphology on the substrate surface along with the substrate permissiveness to lamellipodia extension. 3C-SiC was the only substrate tested to have good viability and superior lamellipodia permissiveness with both cell lines, while NCD showed a good level of viability with the neural H4 line but a poor viability with the PC12 line and lower permissiveness than 3C-SiC. Explanations pertaining to the performance of each substrate with both cell lines are presented and discussed along with future work that must be performed to further evaluate specific cell reactions on these substrates.
---
paper_title: Motor imagery and action observation: Modulation of sensorimotor brain rhythms during mental control of a brain–computer interface

paper_content:

Abstract Objective This study investigates the impact of a continuously presented visual feedback in the form of a grasping hand on the modulation of sensorimotor EEG rhythms during online control of a brain–computer interface (BCI). Methods Two groups of participants were trained to use left or right hand motor imagery to control a specific output signal on a computer monitor: the experimental group controlled a moving hand performing an object-related grasp (‘realistic feedback’), whereas the control group controlled a moving bar (‘abstract feedback’). Continuous feedback was realized by using the outcome of a real-time classifier which was based on EEG signals recorded from left and right central sites. Results The classification results show no difference between the two feedback groups. For both groups, ERD/ERS analysis revealed a significant larger ERD during feedback presentation compared to an initial motor imagery screening session without feedback. Increased ERD during online BCI control was particularly found for the lower alpha (8–10 Hz) and for the beta bands (16–20, 20–24 Hz). Conclusions The present study demonstrates that visual BCI feedback clearly modulates sensorimotor EEG rhythms. When the feedback provides equivalent information on both the continuous and final outcomes of mental actions, the presentation form (abstract versus realistic) does not influence the performance in a BCI, at least in initial training sessions. Significance The present results are of practical interest for classifier development and BCI use in the field of motor restoration.
---
paper_title: Brain–machine interfaces: past, present and future

paper_content:

Since the original demonstration that electrical activity generated by ensembles of cortical neurons can be employed directly to control a robotic manipulator, research on brain–machine interfaces (BMIs) has experienced an impressive growth. Today BMIs designed for both experimental and clinical studies can translate raw neuronal signals into motor commands that reproduce arm reaching and hand grasping movements in artificial actuators. Clearly, these developments hold promise for the restoration of limb mobility in paralyzed subjects. However, as we review here, before this goal can be reached several bottlenecks have to be passed. These include designing a fully implantable biocompatible recording device, further developing real-time computational algorithms, introducing a method for providing the brain with sensory feedback from the actuators, and designing and building artificial prostheses that can be controlled directly by brain-derived signals. By reaching these milestones, future BMIs will be able to drive and control revolutionary prostheses that feel and act like the human arm.
---
paper_title: A binary method for simple and accurate two-dimensional cursor control from EEG with minimal subject training

paper_content:

Background ::: Brain-computer interfaces (BCI) use electroencephalography (EEG) to interpret user intention and control an output device accordingly. We describe a novel BCI method to use a signal from five EEG channels (comprising one primary channel with four additional channels used to calculate its Laplacian derivation) to provide two-dimensional (2-D) control of a cursor on a computer screen, with simple threshold-based binary classification of band power readings taken over pre-defined time windows during subject hand movement.
---
paper_title: A brain-computer interface with vibrotactile biofeedback for haptic information

paper_content:

BackgroundIt has been suggested that Brain-Computer Interfaces (BCI) may one day be suitable for controlling a neuroprosthesis. For closed-loop operation of BCI, a tactile feedback channel that is compatible with neuroprosthetic applications is desired. Operation of an EEG-based BCI using only vibrotactile feedback, a commonly used method to convey haptic senses of contact and pressure, is demonstrated with a high level of accuracy.MethodsA Mu-rhythm based BCI using a motor imagery paradigm was used to control the position of a virtual cursor. The cursor position was shown visually as well as transmitted haptically by modulating the intensity of a vibrotactile stimulus to the upper limb. A total of six subjects operated the BCI in a two-stage targeting task, receiving only vibrotactile biofeedback of performance. The location of the vibration was also systematically varied between the left and right arms to investigate location-dependent effects on performance.Results and ConclusionSubjects are able to control the BCI using only vibrotactile feedback with an average accuracy of 56% and as high as 72%. These accuracies are significantly higher than the 15% predicted by random chance if the subject had no voluntary control of their Mu-rhythm. The results of this study demonstrate that vibrotactile feedback is an effective biofeedback modality to operate a BCI using motor imagery. In addition, the study shows that placement of the vibrotactile stimulation on the biceps ipsilateral or contralateral to the motor imagery introduces a significant bias in the BCI accuracy. This bias is consistent with a drop in performance generated by stimulation of the contralateral limb. Users demonstrated the capability to overcome this bias with training.
---
paper_title: An Implantable 64-Channel Wireless Microsystem for Single-Unit Neural Recording

paper_content:

This paper reports an implantable microsystem capable of recording neural activity simultaneously on 64 channels, wirelessly transmitting spike occurrences to an external interface. The microsystem also allows the user to examine the spike waveforms on any channel with 8 bit resolution. Signals are amplified by 60 dB with a programmable bandwidth from < 100 Hz to 10 kHz. The input-referred noise is 8 ?Vrms. The channel scan rate for spike detection is 62.5 kS/sec using a 2 MHz clock. The system dissipates 14.4 mW at 1.8 V, weighs 275 mg, and measures 1.4 cm 1.55 cm.
---
paper_title: Design and Adsorption of Modular Engineered Proteins to Prepare Customized, Neuron-Compatible Coatings

paper_content:

Neural prosthetic implants are currently being developed for the treatment and study of both peripheral and central nervous system disorders. Effective integration of these devices upon implantation is a critical hurdle to achieving function. As a result, much attention has been directed towards the development of biocompatible coatings that prolong their in vivo lifespan. In this work, we present a novel approach to fabricate such coatings, which specifically involves the use of surface-adsorbed, nanoscale-designed protein polymers to prepare reproducible, customized surfaces. A nanoscale modular design strategy was employed to synthesize six engineered, recombinant proteins intended to mimic aspects of the extracellular matrix proteins fibronectin, laminin, and elastin as well as the cell-cell adhesive protein NCAM (neural cell adhesion molecule). Physical adsorption isotherms were experimentally determined for these engineered proteins, allowing for direct calculation of the available ligand density present on coated surfaces. As confirmation that ligand density in these engineered systems impacts neuronal cell behavior, we demonstrate that increasing the density of fibronectin-derived RGD ligands on coated surfaces while maintaining uniform protein surface coverage results in enhanced neurite extension of PC-12 cells. Therefore, this engineered protein adsorption approach allows for the facile preparation of tunable, quantifiable, and reproducible surfaces for in vitro studies of cell-ligand interactions and for potential application as coatings on neural implants.
---
paper_title: Nanostructured surface modification of ceramic-based microelectrodes to enhance biocompatibility for a direct brain-machine interface

paper_content:

Many different types of microelectrodes have been developed for use as a direct Brain-Machine Interface (BMI) to chronically recording single neuron action potentials from ensembles of neurons. Unfortunately, the recordings from these microelectrode devices are not consistent and often last for only a few weeks. For most microelectrode types, the loss of these recordings is not due to failure of the electrodes but most likely due to damage to surrounding tissue that results in the formation of nonconductive glial-scar. Since the extracellular matrix consists of nanostructured microtubules, we have postulated that neurons may prefer a more complex surface structure than the smooth surface typical of thin-film microelectrodes. We, therefore, investigated the suitability of a nano-porous silicon surface layer to increase the biocompatibility of our thin film ceramic-insulated multisite electrodes. In-vitro testing demonstrated, for the first time, decreased adhesion of astrocytes and increased extension of neurites from pheochromocytoma cells on porous silicon surfaces compared to smooth silicon surfaces. Moreover, nano-porous surfaces were more biocompatible than macroporous surfaces. Collectively, these results support our hypothesis that nano-porous silicon may be an ideal material to improve biocompatibility of chronically implanted microelectrodes. We next developed a method to apply nano-porous surfaces to ceramic insulated, thin-film, microelectrodes and tested them in vivo. Chronic testing demonstrated that the nano-porous surface modification did not alter the electrical properties of the recording sites and did not interfere with proper functioning of the microelectrodes in vivo.
---
paper_title: Early Interfaced Neural Activity from Chronic Amputated Nerves

paper_content:

Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation, currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative on-dependent multi-electrode arrays of open design allow the early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. .
---
paper_title: A binary method for simple and accurate two-dimensional cursor control from EEG with minimal subject training

paper_content:

Background ::: Brain-computer interfaces (BCI) use electroencephalography (EEG) to interpret user intention and control an output device accordingly. We describe a novel BCI method to use a signal from five EEG channels (comprising one primary channel with four additional channels used to calculate its Laplacian derivation) to provide two-dimensional (2-D) control of a cursor on a computer screen, with simple threshold-based binary classification of band power readings taken over pre-defined time windows during subject hand movement.
---
paper_title: Massively Parallel Signal Processing using the Graphics Processing Unit for Real-Time Brain–Computer Interface Feature Extraction

paper_content:

The clock speeds of modern computer processors have nearly plateaued in the past 5 years. Consequently, neural prosthetic systems that rely on processing large quantities of data in a short period of time face a bottleneck, in that it may not be possible to process all of the data recorded from an electrode array with high channel counts and bandwidth, such as electrocorticographic grids or other implantable systems. Therefore, in this study a method of using the processing capabilities of a graphics card [graphics processing unit (GPU)] was developed for real-time neural signal processing of a brain–computer interface (BCI). The NVIDIA CUDA system was used to offl oad processing to the GPU, which is capable of running many operations in parallel, potentially greatly increasing the speed of existing algorithms. The BCI system records many channels of data, which are processed and translated into a control signal, such as the movement of a computer cursor. This signal processing chain involves computing a matrix–matrix multiplication (i.e., a spatial fi lter), followed by calculating the power spectral density on every channel using an auto-regressive method, and fi nally classifying appropriate features for control. In this study, the fi rst two computationally intensive steps were implemented on the GPU, and the speed was compared to both the current implementation and a central processing unit-based implementation that uses multi-threading. Signifi cant performance gains were obtained with GPU processing: the current implementation processed 1000 channels of 250 ms in 933 ms, while the new GPU method took only 27 ms, an improvement of nearly 35 times.
---
paper_title: Principles of neural ensemble physiology underlying the operation of brain–machine interfaces

paper_content:

Research on brain-machine interfaces has been ongoing for at least a decade. During this period, simultaneous recordings of the extracellular electrical activity of hundreds of individual neurons have been used for direct, real-time control of various artificial devices. Brain-machine interfaces have also added greatly to our knowledge of the fundamental physiological principles governing the operation of large neural ensembles. Further understanding of these principles is likely to have a key role in the future development of neuroprosthetics for restoring mobility in severely paralysed patients.
---
paper_title: Carbon Nanotube Electrodes for Effective Interfacing with Retinal Tissue

paper_content:

We have investigated the use of carbon nanotube microelectrodes as an interface material for retinal recording and stimulation applications. Test devices were micro-fabricated and consisted of 60 pristine 30 um electrodes coated with chemical vapor deposited carbon nanotubes, resulting in conducting, three dimensional surfaces with a high effective interfacial area. These attributes are important both for the quality of the cell-surface coupling as well as for electro-chemical interfacing efficiency. The entire chip was packaged to fit a commercial multielectrode recording and stimulation system. Electrical recordings of spontaneous spikes from whole-mount neonatal mouse retinas were consistently obtained minutes after retinas were placed over the electrodes, exhibiting typical bursting and propagating waves. Most importantly, the signals obtained with carbon nanotube electrodes have exceptionally high signal to noise ratio, reaching values as high as 75. Moreover, spikes are marked by a conspicuous gradual increase in amplitude recorded over a period of minutes to hours, suggesting improvement in cell-electrode coupling. This phenomenon is not observed in conventional commercial electrodes. Electrical stimulation using carbon nanotube electrodes was also achieved. We attribute the superior performances of the carbon nanotube electrodes to their three dimensional nature and the strong neuro-carbon nanotube affinity. The results presented here show the great potential of carbon nanotube electrodes for retinal interfacing applications. Specifically, our results demonstrate a route to achieve a reduction in the electrode size down to few micrometers in order to achieve high efficacy local stimulation needed in retinal prosthetic devices.
---
paper_title: Bridging the Divide between Neuroprosthetic Design, Tissue Engineering and Neurobiology

paper_content:

Neuroprosthetic devices have made a major impact in the treatment of a variety of disorders such as paralysis and stroke. However, a major impediment in the advancement of this technology is the challenge of maintaining device performance during chronic implantation (months to years) due to complex intrinsic host responses such as gliosis or glial scarring. The objective of this review is to bring together research communities in neurobiology, tissue engineering, and neuroprosthetics to address the major obstacles encountered in the translation of neuroprosthetics technology into long-term clinical use. This article draws connections between specific challenges faced by current neuroprosthetics technology and recent advances in the areas of nerve tissue engineering and neurobiology. Within the context of the device-nervous system interface and central nervous system (CNS) implants, areas of synergistic opportunity are discussed, including platforms to present cells with multiple cues, controlled delivery of bioactive factors, three-dimensional constructs and in vitro models of gliosis and brain injury, nerve regeneration strategies, and neural stem/progenitor cell (NPC) biology. Finally, recent insights gained from the fields of developmental neurobiology and cancer biology are discussed as examples of exciting new biological knowledge that may provide fresh inspiration towards novel technologies to address the complexities associated with long-term neuroprosthetic device performance.
---
paper_title: Bioactive properties of nanostructured porous silicon for enhancing electrode to neuron interfaces

paper_content:

Many different types of microelectrodes have been developed for use as a direct brain–machine interface (BMI) to chronically recording single-neuron action potentials from ensembles of neurons. Unfortunately, the recordings from these microelectrode devices are not consistent and often last for only on the order of months. For most microelectrode types, the loss of these recordings is not due to failure of the electrodes, but most likely due to damage to surrounding tissue that results in the formation of non-conductive glial scar. Since the extracellular matrix consists of nanostructured fibrous protein assemblies, we have postulated that neurons may prefer a more complex surface structure than the smooth surface typical of thin-film microelectrodes. This porous structure could then act as a drug-delivery reservoir to deliver bioactive agents to aid in the repair or survival of cells around the microelectrode, further reducing the glial scar. We, therefore, investigated the suitability of a nano-porous s...
---
paper_title: Adhesion Molecule-Modified Biomaterials for Neural Tissue Engineering

paper_content:

Adhesion molecules (AMs) represent one class of biomolecules that promote central nervous system regeneration. These tethered molecules provide cues to regenerating neurons that recapitulate the native brain environment. Improving cell adhesive potential of non-adhesive biomaterials is therefore a common goal in neural tissue engineering. This review discusses common AMs used in neural biomaterials and the mechanism of cell attachment to these AMs. Methods to modify materials with AMs are discussed and compared. Additionally, patterning of AMs for achieving specific neuronal responses is explored.
---
paper_title: Atomic force microscopy analysis of central nervous system cell morphology on silicon carbide and diamond substrates.

paper_content:

Brain machine interface (BMI) devices offer a platform that can be used to assist people with extreme disabilities, such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease. Silicon (Si) has been the material of choice used for the manufacture of BMI devices due to its mechanical strength, its electrical properties and multiple fabrication techniques; however, chronically implanted BMI devices have usually failed within months of implantation due to biocompatibility issues and the fact that Si does not withstand the harsh environment of the body. Single crystal cubic silicon carbide (3C-SiC) and nanocrystalline diamond (NCD) are semiconductor materials that have previously shown good biocompatibility with skin and bone cells. Like Si, these materials have excellent physical characteristics, good electrical properties, but unlike Si, they are chemically inert. We have performed a study to evaluate the general biocompatibility levels of all of these materials through the use of in vitro techniques. H4 human neuroglioma and PC12 rat pheochromocytoma cell lines were used for the study, and polystyrene (PSt) and amorphous glass were used as controls or for morphological comparison. MTT [3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide] assays were performed to determine general cell viability with each substrate and atomic force microscopy (AFM) was used to quantify the general cell morphology on the substrate surface along with the substrate permissiveness to lamellipodia extension. 3C-SiC was the only substrate tested to have good viability and superior lamellipodia permissiveness with both cell lines, while NCD showed a good level of viability with the neural H4 line but a poor viability with the PC12 line and lower permissiveness than 3C-SiC. Explanations pertaining to the performance of each substrate with both cell lines are presented and discussed along with future work that must be performed to further evaluate specific cell reactions on these substrates.
---
paper_title: Nanostructured surface modification of ceramic-based microelectrodes to enhance biocompatibility for a direct brain-machine interface

paper_content:

Many different types of microelectrodes have been developed for use as a direct Brain-Machine Interface (BMI) to chronically recording single neuron action potentials from ensembles of neurons. Unfortunately, the recordings from these microelectrode devices are not consistent and often last for only a few weeks. For most microelectrode types, the loss of these recordings is not due to failure of the electrodes but most likely due to damage to surrounding tissue that results in the formation of nonconductive glial-scar. Since the extracellular matrix consists of nanostructured microtubules, we have postulated that neurons may prefer a more complex surface structure than the smooth surface typical of thin-film microelectrodes. We, therefore, investigated the suitability of a nano-porous silicon surface layer to increase the biocompatibility of our thin film ceramic-insulated multisite electrodes. In-vitro testing demonstrated, for the first time, decreased adhesion of astrocytes and increased extension of neurites from pheochromocytoma cells on porous silicon surfaces compared to smooth silicon surfaces. Moreover, nano-porous surfaces were more biocompatible than macroporous surfaces. Collectively, these results support our hypothesis that nano-porous silicon may be an ideal material to improve biocompatibility of chronically implanted microelectrodes. We next developed a method to apply nano-porous surfaces to ceramic insulated, thin-film, microelectrodes and tested them in vivo. Chronic testing demonstrated that the nano-porous surface modification did not alter the electrical properties of the recording sites and did not interfere with proper functioning of the microelectrodes in vivo.
---
paper_title: Early Interfaced Neural Activity from Chronic Amputated Nerves

paper_content:

Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation, currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative on-dependent multi-electrode arrays of open design allow the early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. .
---
paper_title: Bioactive properties of nanostructured porous silicon for enhancing electrode to neuron interfaces

paper_content:

Many different types of microelectrodes have been developed for use as a direct brain–machine interface (BMI) to chronically recording single-neuron action potentials from ensembles of neurons. Unfortunately, the recordings from these microelectrode devices are not consistent and often last for only on the order of months. For most microelectrode types, the loss of these recordings is not due to failure of the electrodes, but most likely due to damage to surrounding tissue that results in the formation of non-conductive glial scar. Since the extracellular matrix consists of nanostructured fibrous protein assemblies, we have postulated that neurons may prefer a more complex surface structure than the smooth surface typical of thin-film microelectrodes. This porous structure could then act as a drug-delivery reservoir to deliver bioactive agents to aid in the repair or survival of cells around the microelectrode, further reducing the glial scar. We, therefore, investigated the suitability of a nano-porous s...
---
paper_title: Design and Adsorption of Modular Engineered Proteins to Prepare Customized, Neuron-Compatible Coatings

paper_content:

Neural prosthetic implants are currently being developed for the treatment and study of both peripheral and central nervous system disorders. Effective integration of these devices upon implantation is a critical hurdle to achieving function. As a result, much attention has been directed towards the development of biocompatible coatings that prolong their in vivo lifespan. In this work, we present a novel approach to fabricate such coatings, which specifically involves the use of surface-adsorbed, nanoscale-designed protein polymers to prepare reproducible, customized surfaces. A nanoscale modular design strategy was employed to synthesize six engineered, recombinant proteins intended to mimic aspects of the extracellular matrix proteins fibronectin, laminin, and elastin as well as the cell-cell adhesive protein NCAM (neural cell adhesion molecule). Physical adsorption isotherms were experimentally determined for these engineered proteins, allowing for direct calculation of the available ligand density present on coated surfaces. As confirmation that ligand density in these engineered systems impacts neuronal cell behavior, we demonstrate that increasing the density of fibronectin-derived RGD ligands on coated surfaces while maintaining uniform protein surface coverage results in enhanced neurite extension of PC-12 cells. Therefore, this engineered protein adsorption approach allows for the facile preparation of tunable, quantifiable, and reproducible surfaces for in vitro studies of cell-ligand interactions and for potential application as coatings on neural implants.
---
paper_title: An Implantable Microactuated Intrafascicular Electrode for Peripheral Nerves

paper_content:

Important advancements have been recently achieved in the field of neural interfaces to restore lost sensory and motor functions. The aim of this letter was to develop an innovative approach to increase the selectivity and the lifetime of polyimide-based intrafascicular electrodes. The main idea was to obtain a neural interface that is able to restore a good signal quality by improving the electrical connection between the active sites and the surrounding axons. The high flexibility of polyimide-based neural interfaces allows to embed microactuators in the interface core and achieve desired microdisplacements of the active sites. Nearly equiatomic nickel-titanium alloy was selected as a microactuator because of its shape memory effect. A single TiNi thin film was obtained by dc magnetron sputtering, and was segmented into four distinct sectors. This solution allowed the independent actuation of the different active sites (multiactuation). A corrugated profile was impressed to the new actuated intraneural (ACTIN) interface. The active sites were positioned in correspondence to the peaks of the corrugation, thus maximizing the effects of the single actuations. The technological results, the electrical properties, the thermal behavior, and eventually, the actuation performances of the current ACTIN prototype are shown and discussed. The actuation cycle was thermally compatible for biomedical applications. Promising results were obtained from the current ACTIN prototype with an average controlled movement of 7 mum of the peaks.
---
paper_title: Nanostructured surface modification of ceramic-based microelectrodes to enhance biocompatibility for a direct brain-machine interface

paper_content:

Many different types of microelectrodes have been developed for use as a direct Brain-Machine Interface (BMI) to chronically recording single neuron action potentials from ensembles of neurons. Unfortunately, the recordings from these microelectrode devices are not consistent and often last for only a few weeks. For most microelectrode types, the loss of these recordings is not due to failure of the electrodes but most likely due to damage to surrounding tissue that results in the formation of nonconductive glial-scar. Since the extracellular matrix consists of nanostructured microtubules, we have postulated that neurons may prefer a more complex surface structure than the smooth surface typical of thin-film microelectrodes. We, therefore, investigated the suitability of a nano-porous silicon surface layer to increase the biocompatibility of our thin film ceramic-insulated multisite electrodes. In-vitro testing demonstrated, for the first time, decreased adhesion of astrocytes and increased extension of neurites from pheochromocytoma cells on porous silicon surfaces compared to smooth silicon surfaces. Moreover, nano-porous surfaces were more biocompatible than macroporous surfaces. Collectively, these results support our hypothesis that nano-porous silicon may be an ideal material to improve biocompatibility of chronically implanted microelectrodes. We next developed a method to apply nano-porous surfaces to ceramic insulated, thin-film, microelectrodes and tested them in vivo. Chronic testing demonstrated that the nano-porous surface modification did not alter the electrical properties of the recording sites and did not interfere with proper functioning of the microelectrodes in vivo.
---
paper_title: Brain–machine interfaces: past, present and future

paper_content:

Since the original demonstration that electrical activity generated by ensembles of cortical neurons can be employed directly to control a robotic manipulator, research on brain–machine interfaces (BMIs) has experienced an impressive growth. Today BMIs designed for both experimental and clinical studies can translate raw neuronal signals into motor commands that reproduce arm reaching and hand grasping movements in artificial actuators. Clearly, these developments hold promise for the restoration of limb mobility in paralyzed subjects. However, as we review here, before this goal can be reached several bottlenecks have to be passed. These include designing a fully implantable biocompatible recording device, further developing real-time computational algorithms, introducing a method for providing the brain with sensory feedback from the actuators, and designing and building artificial prostheses that can be controlled directly by brain-derived signals. By reaching these milestones, future BMIs will be able to drive and control revolutionary prostheses that feel and act like the human arm.
---
paper_title: Early Interfaced Neural Activity from Chronic Amputated Nerves

paper_content:

Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation, currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative on-dependent multi-electrode arrays of open design allow the early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. .
---
paper_title: Biomaterials for the central nervous system

paper_content:

Biomaterials are widely used to help treat neurological disorders and/or improve functional recovery in the central nervous system (CNS). This article reviews the application of biomaterials in (i) shunting systems for hydrocephalus, (ii) cortical neural prosthetics, (iii) drug delivery in the CNS, (iv) hydrogel scaffolds for CNS repair, and (v) neural stem cell encapsulation for neurotrauma. The biological and material requirements for the biomaterials in these applications are discussed. The difficulties that the biomaterials might face in each application and the possible solutions are also reviewed in this article.
---
paper_title: Carbon Nanotube Electrodes for Effective Interfacing with Retinal Tissue

paper_content:

We have investigated the use of carbon nanotube microelectrodes as an interface material for retinal recording and stimulation applications. Test devices were micro-fabricated and consisted of 60 pristine 30 um electrodes coated with chemical vapor deposited carbon nanotubes, resulting in conducting, three dimensional surfaces with a high effective interfacial area. These attributes are important both for the quality of the cell-surface coupling as well as for electro-chemical interfacing efficiency. The entire chip was packaged to fit a commercial multielectrode recording and stimulation system. Electrical recordings of spontaneous spikes from whole-mount neonatal mouse retinas were consistently obtained minutes after retinas were placed over the electrodes, exhibiting typical bursting and propagating waves. Most importantly, the signals obtained with carbon nanotube electrodes have exceptionally high signal to noise ratio, reaching values as high as 75. Moreover, spikes are marked by a conspicuous gradual increase in amplitude recorded over a period of minutes to hours, suggesting improvement in cell-electrode coupling. This phenomenon is not observed in conventional commercial electrodes. Electrical stimulation using carbon nanotube electrodes was also achieved. We attribute the superior performances of the carbon nanotube electrodes to their three dimensional nature and the strong neuro-carbon nanotube affinity. The results presented here show the great potential of carbon nanotube electrodes for retinal interfacing applications. Specifically, our results demonstrate a route to achieve a reduction in the electrode size down to few micrometers in order to achieve high efficacy local stimulation needed in retinal prosthetic devices.
---
paper_title: Bridging the Divide between Neuroprosthetic Design, Tissue Engineering and Neurobiology

paper_content:

Neuroprosthetic devices have made a major impact in the treatment of a variety of disorders such as paralysis and stroke. However, a major impediment in the advancement of this technology is the challenge of maintaining device performance during chronic implantation (months to years) due to complex intrinsic host responses such as gliosis or glial scarring. The objective of this review is to bring together research communities in neurobiology, tissue engineering, and neuroprosthetics to address the major obstacles encountered in the translation of neuroprosthetics technology into long-term clinical use. This article draws connections between specific challenges faced by current neuroprosthetics technology and recent advances in the areas of nerve tissue engineering and neurobiology. Within the context of the device-nervous system interface and central nervous system (CNS) implants, areas of synergistic opportunity are discussed, including platforms to present cells with multiple cues, controlled delivery of bioactive factors, three-dimensional constructs and in vitro models of gliosis and brain injury, nerve regeneration strategies, and neural stem/progenitor cell (NPC) biology. Finally, recent insights gained from the fields of developmental neurobiology and cancer biology are discussed as examples of exciting new biological knowledge that may provide fresh inspiration towards novel technologies to address the complexities associated with long-term neuroprosthetic device performance.
---
paper_title: Bioactive properties of nanostructured porous silicon for enhancing electrode to neuron interfaces

paper_content:

Many different types of microelectrodes have been developed for use as a direct brain–machine interface (BMI) to chronically recording single-neuron action potentials from ensembles of neurons. Unfortunately, the recordings from these microelectrode devices are not consistent and often last for only on the order of months. For most microelectrode types, the loss of these recordings is not due to failure of the electrodes, but most likely due to damage to surrounding tissue that results in the formation of non-conductive glial scar. Since the extracellular matrix consists of nanostructured fibrous protein assemblies, we have postulated that neurons may prefer a more complex surface structure than the smooth surface typical of thin-film microelectrodes. This porous structure could then act as a drug-delivery reservoir to deliver bioactive agents to aid in the repair or survival of cells around the microelectrode, further reducing the glial scar. We, therefore, investigated the suitability of a nano-porous s...
---
paper_title: Adhesion Molecule-Modified Biomaterials for Neural Tissue Engineering

paper_content:

Adhesion molecules (AMs) represent one class of biomolecules that promote central nervous system regeneration. These tethered molecules provide cues to regenerating neurons that recapitulate the native brain environment. Improving cell adhesive potential of non-adhesive biomaterials is therefore a common goal in neural tissue engineering. This review discusses common AMs used in neural biomaterials and the mechanism of cell attachment to these AMs. Methods to modify materials with AMs are discussed and compared. Additionally, patterning of AMs for achieving specific neuronal responses is explored.
---
paper_title: Atomic force microscopy analysis of central nervous system cell morphology on silicon carbide and diamond substrates.

paper_content:

Brain machine interface (BMI) devices offer a platform that can be used to assist people with extreme disabilities, such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease. Silicon (Si) has been the material of choice used for the manufacture of BMI devices due to its mechanical strength, its electrical properties and multiple fabrication techniques; however, chronically implanted BMI devices have usually failed within months of implantation due to biocompatibility issues and the fact that Si does not withstand the harsh environment of the body. Single crystal cubic silicon carbide (3C-SiC) and nanocrystalline diamond (NCD) are semiconductor materials that have previously shown good biocompatibility with skin and bone cells. Like Si, these materials have excellent physical characteristics, good electrical properties, but unlike Si, they are chemically inert. We have performed a study to evaluate the general biocompatibility levels of all of these materials through the use of in vitro techniques. H4 human neuroglioma and PC12 rat pheochromocytoma cell lines were used for the study, and polystyrene (PSt) and amorphous glass were used as controls or for morphological comparison. MTT [3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide] assays were performed to determine general cell viability with each substrate and atomic force microscopy (AFM) was used to quantify the general cell morphology on the substrate surface along with the substrate permissiveness to lamellipodia extension. 3C-SiC was the only substrate tested to have good viability and superior lamellipodia permissiveness with both cell lines, while NCD showed a good level of viability with the neural H4 line but a poor viability with the PC12 line and lower permissiveness than 3C-SiC. Explanations pertaining to the performance of each substrate with both cell lines are presented and discussed along with future work that must be performed to further evaluate specific cell reactions on these substrates.
---
paper_title: Carbon Nanotube Electrodes for Effective Interfacing with Retinal Tissue

paper_content:

We have investigated the use of carbon nanotube microelectrodes as an interface material for retinal recording and stimulation applications. Test devices were micro-fabricated and consisted of 60 pristine 30 um electrodes coated with chemical vapor deposited carbon nanotubes, resulting in conducting, three dimensional surfaces with a high effective interfacial area. These attributes are important both for the quality of the cell-surface coupling as well as for electro-chemical interfacing efficiency. The entire chip was packaged to fit a commercial multielectrode recording and stimulation system. Electrical recordings of spontaneous spikes from whole-mount neonatal mouse retinas were consistently obtained minutes after retinas were placed over the electrodes, exhibiting typical bursting and propagating waves. Most importantly, the signals obtained with carbon nanotube electrodes have exceptionally high signal to noise ratio, reaching values as high as 75. Moreover, spikes are marked by a conspicuous gradual increase in amplitude recorded over a period of minutes to hours, suggesting improvement in cell-electrode coupling. This phenomenon is not observed in conventional commercial electrodes. Electrical stimulation using carbon nanotube electrodes was also achieved. We attribute the superior performances of the carbon nanotube electrodes to their three dimensional nature and the strong neuro-carbon nanotube affinity. The results presented here show the great potential of carbon nanotube electrodes for retinal interfacing applications. Specifically, our results demonstrate a route to achieve a reduction in the electrode size down to few micrometers in order to achieve high efficacy local stimulation needed in retinal prosthetic devices.
---
paper_title: Criteria for the Selection of Materials for Implanted Electrodes

paper_content:

There are four criteria that must be considered when choosing material for an implanted electrode: (1) tissue response, (2) allergic response, (3) electrode-tissue impedance, and (4) radiographic visibility. This paper discusses these four criteria and identifies the materials that are the best candidates for such electrodes. For electrodes that make ohmic contact with tissues: gold, platinum, platinum–iridium, tungsten, and tantalum are good candidates. The preferred insulating materials are polyimide and glass. The characteristics of stimulator output circuits and the importance of the bidirectional wave- form in relation to electrode decomposition are discussed. The paper concludes with an analysis, the design criteria, and the special properties and materials for capacitive recording and stimulating electrodes. © 2003 Biomedical Engineering Society.
---
paper_title: Neuroprosthetic devices: how far are we from recovering movement in paralyzed patients?

paper_content:

In October 2008, Eberhard Fetz’s group from the University of Washington dem-onstrated that a direct artificial connection from a region of the brain associated with the control of movement to muscles in the limb could restore movement induced by electrical stimulation in monkeys whose arms had been temporarily anesthetized. The report of this progress created tremen-dous public interest as a perceived mile-stone in the development of a seamless neurotechnological solution for restoring function in paralysis. This work relied on the combination of an implanted electrode array in the motor cortex and functional electrical stimulation (FES) to muscles in the paralyzed wrist. Indeed, the combina-tion of FES, a technique that has achieved a track record of clinical utility, with brain–machine interfaces (BMIs) has become the subject of study for several research groups. Based on progress from these groups, we suggest that the technology has reached sufficient maturation that the proof-of-concept clinical demonstration could be accomplished within the next 5 years. In this editorial, we provide a brief overview of the key technologies and several key issues that are being explored, and also discuss the importance of supporting translational neuroprosthetics research and development to achieve this goal.Paralysis resulting from neurological injury or disease places a significant burden on patients, their families and caregivers. Neuroprostheses offer the promise of restoring movement to paralyzed patients by bypassing damaged regions of the ner-vous system, ultimately giving patients the ability to live with greater indepen-dence and improving their quality of life. Indeed, the coordinated stimulation of paralyzed muscles through FES has been shown to be effective and safe for restoring hand grasp
---
paper_title: Form-Function Relations in Cone-Tipped Stimulating Microelectrodes

paper_content:

Metal micro-electrodes are widely used in neuroscience research, and could potentially replace macro-electrodes in various neuro-stimulation applications where their small size, specificity, and their ability to also measure unit activity are desirable. The design of stimulating microelectrodes for specific applications requires knowledge on how tip geometry affects function, but several fundamental aspects of this relationship are not yet well understood. This study uses a combined experimental and physical finite-elements simulation approach to formulate three new relationships between the geometrical and electrical properties of stimulating cone-tipped tungsten microelectrodes: 1. The empirical relationship between microelectrode 1kHz impedance and the exposed tip surface area is best approximated by an inverse square-root function (as expected for a cone-tipped resistive interface). 2. Tip angle plays a major role in determining current distribution along the tip, and as a consequence crucially affects the charge injection capacity of a microelectrode. 3. The critical current for the onset of corrosion is independent of tip surface area in sharp microelectrodes.
---
paper_title: Design and Adsorption of Modular Engineered Proteins to Prepare Customized, Neuron-Compatible Coatings

paper_content:

Neural prosthetic implants are currently being developed for the treatment and study of both peripheral and central nervous system disorders. Effective integration of these devices upon implantation is a critical hurdle to achieving function. As a result, much attention has been directed towards the development of biocompatible coatings that prolong their in vivo lifespan. In this work, we present a novel approach to fabricate such coatings, which specifically involves the use of surface-adsorbed, nanoscale-designed protein polymers to prepare reproducible, customized surfaces. A nanoscale modular design strategy was employed to synthesize six engineered, recombinant proteins intended to mimic aspects of the extracellular matrix proteins fibronectin, laminin, and elastin as well as the cell-cell adhesive protein NCAM (neural cell adhesion molecule). Physical adsorption isotherms were experimentally determined for these engineered proteins, allowing for direct calculation of the available ligand density present on coated surfaces. As confirmation that ligand density in these engineered systems impacts neuronal cell behavior, we demonstrate that increasing the density of fibronectin-derived RGD ligands on coated surfaces while maintaining uniform protein surface coverage results in enhanced neurite extension of PC-12 cells. Therefore, this engineered protein adsorption approach allows for the facile preparation of tunable, quantifiable, and reproducible surfaces for in vitro studies of cell-ligand interactions and for potential application as coatings on neural implants.
---
paper_title: Surface Engineering of Poly(dl-lactide) via Electrostatic Self-Assembly of Extracellular Matrix-like Molecules

paper_content:

We report the development of new biomacromolecule coatings on biodegradable biomaterials based on electrostatic assembly of extracellular matrix-like molecules. Poly(ethylene imine) (PEI) was employed to engineer poly(DL-lactide) (PDL-LA) substrate to obtain a stable positively charged surface. An extracellular matrix- (ECM-) like biomacromolecule, gelatin, was selected as the polyelectrolyte to deposit on the activated PDL-LA substrate via the electrostatic assemble technique. The extracellular matrix-like multilayer on the PDL-LA substrate was investigated by attenuated total reflection (ATR-FTIR), X-ray photoelectron spectrscopy (XPS), contact angle, and atomic force microscopy (AFM). The gradual buildup of the protein layer was investigated by UV-vis spectra, and it was further given a quantitative analysis of the protein layer on the PDL-LA substrate via the radioiodination technique. The stability of the protein layer under aqueous condition was also tested by the radiolabeling method. Chondrocyte was selected as the model system for testing the cell behavior and morphology on modified PDL-LA substrates. The chondrocyte test about cell attachment, proliferation, cell activity and cell morphology by SEM, and confocal laser scanning microscopy (CLSM) investigation on extracellular matrix-like multilayer modified PDL-LA substrate was shown to promote chondrocyte attachment and growth. Comparing conventional coating methods, polyelectrolyte multiplayers are easy and stable to prepare. It may be a good choice for the modification of 3-D scaffolds used in tissue engineering. These very flexible systems allow broad medical applications for drug delivery and tissue engineering.
---
paper_title: Nanostructured surface modification of ceramic-based microelectrodes to enhance biocompatibility for a direct brain-machine interface

paper_content:

Many different types of microelectrodes have been developed for use as a direct Brain-Machine Interface (BMI) to chronically recording single neuron action potentials from ensembles of neurons. Unfortunately, the recordings from these microelectrode devices are not consistent and often last for only a few weeks. For most microelectrode types, the loss of these recordings is not due to failure of the electrodes but most likely due to damage to surrounding tissue that results in the formation of nonconductive glial-scar. Since the extracellular matrix consists of nanostructured microtubules, we have postulated that neurons may prefer a more complex surface structure than the smooth surface typical of thin-film microelectrodes. We, therefore, investigated the suitability of a nano-porous silicon surface layer to increase the biocompatibility of our thin film ceramic-insulated multisite electrodes. In-vitro testing demonstrated, for the first time, decreased adhesion of astrocytes and increased extension of neurites from pheochromocytoma cells on porous silicon surfaces compared to smooth silicon surfaces. Moreover, nano-porous surfaces were more biocompatible than macroporous surfaces. Collectively, these results support our hypothesis that nano-porous silicon may be an ideal material to improve biocompatibility of chronically implanted microelectrodes. We next developed a method to apply nano-porous surfaces to ceramic insulated, thin-film, microelectrodes and tested them in vivo. Chronic testing demonstrated that the nano-porous surface modification did not alter the electrical properties of the recording sites and did not interfere with proper functioning of the microelectrodes in vivo.
---
paper_title: Compact self-wiring in cultured neural networks.

paper_content:

We present a novel approach for patterning cultured neural networks in which a particular geometry is achieved via anchoring of cell clusters (tens of cells/each) at specific positions. In addition, compact connections among pairs of clusters occur spontaneously through a single non-adherent straight bundle composed of axons and dendrites. The anchors that stabilize the cell clusters are either poly-D-lysine, a strong adhesive substrate, or carbon nanotubes. Square, triangular and circular structures of connectivity were successfully realized. Monitoring the dynamics of the forming networks in real time revealed that the self-assembly process is mainly driven by the ability of the neuronal cell clusters to move away from each other while continuously stretching a neurite bundle in between. Using the presented technique, we achieved networks with wiring regions which are made exclusively of neuronal processes unbound to the surface. The resulted network patterns are very stable and can be maintained for as long as 11 weeks. The approach can be used to build advanced neuro-chips for bio-sensing applications (e.g. drug and toxin detection) where the structure, stability and reproducibility of the networks are of great relevance.
---
paper_title: Brain–machine interfaces: past, present and future

paper_content:

Since the original demonstration that electrical activity generated by ensembles of cortical neurons can be employed directly to control a robotic manipulator, research on brain–machine interfaces (BMIs) has experienced an impressive growth. Today BMIs designed for both experimental and clinical studies can translate raw neuronal signals into motor commands that reproduce arm reaching and hand grasping movements in artificial actuators. Clearly, these developments hold promise for the restoration of limb mobility in paralyzed subjects. However, as we review here, before this goal can be reached several bottlenecks have to be passed. These include designing a fully implantable biocompatible recording device, further developing real-time computational algorithms, introducing a method for providing the brain with sensory feedback from the actuators, and designing and building artificial prostheses that can be controlled directly by brain-derived signals. By reaching these milestones, future BMIs will be able to drive and control revolutionary prostheses that feel and act like the human arm.
---
paper_title: Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex

paper_content:

The Utah Intracortical Electrode Array (UIEA) is an array of 100 penetrating silicon microelectrodes designed to focally electrically stimulate or record neurons residing in a single layer up to 1.5 mm beneath the surface of the cerebral cortex. Apart from its use as a unique tool to study parallel processing in the central nervous system, this array could form the platform for a cortical neuroprosthetic system. Although the UIEA has been used extensively in acute neural recording and stimulation experiments, its long-term performance in a chronic application has yet to be demonstrated. As an initial investigation into the feasibility of long-term cortical recording with an array of microelectrodes, we have hard-wired a subset of 11 electrodes of the UIEA to a percutaneous connector. This chronic UIEA assembly was then implanted into the cerebral cortices of ten cats for durations ranging from 2 to 13 months; over which time, both random and stimulus-evoked single and multiple unit action potentials were periodically recorded. On average, after a 6-month implant period, 60% of implanted arrays could still record some type of activity. Post-sacrifice dissections revealed a fibrous encapsulation of the UIEA. Although most implanted cortex was histologically normal, evidence of a chronic astroglial response was seen in a few cases. The results of the reported experiments indicate that the UIEA can be successfully used for limited times in a chronic recording application.
---
paper_title: Enhancement of neurite outgrowth using nano-structured scaffolds coupled with laminin

paper_content:

Abstract Cell interactions with scaffolds are important for cell and tissue development in the process of repairing and regeneration of damaged tissue. Scaffolds that mimic extracellular matrix (ECM) surface topography, mechanical stiffness, and chemical composition will be advantageous to promote enhanced cell interactions. Electrospinning can easily produce nano-structured synthetic polymer mats with architecture that structurally resembles the ECM of tissue. Although electrospinning can produce sub-micron fibrous scaffolds, modification of electrospun scaffolds with bioactive molecules is beneficial as this can create an environment that consists of biochemical cues to further promote cell adhesion, proliferation and differentiation. Incorporation of laminin, a neurite promoting ECM protein, onto the nanofibers is an alternative to further mimic the biochemical properties of the nervous tissue to create a biomimetic scaffold. In this study, we investigated the feasibility to functionalize scaffolds by coupling laminin onto poly( l -lactic acid) (PLLA) nanofibers. Laminin was successfully added to nanofibers using covalent binding, physical adsorption or blended electrospinning procedures. PC12 cell viability and neurite outgrowth assays confirmed that the functionalized nanofibers were able to enhance axonal extensions. Significantly, compared to covalent immobilization and physical adsorption, blended electrospinning of laminin and synthetic polymer is a facile and efficient method to modify nanofibers for the fabrication of a biomimetic scaffold. Using these functionalization techniques, nanofibers can be effectively modified with laminin for potential use in peripheral nerve regeneration applications.
---
paper_title: Peptide hormone covalently bound to polyelectrolytes and embedded into multilayer architectures conserving full biological activity.

paper_content:

We report the development of new bioactive coatings of biomaterials based on the alternate deposition of oppositely charged polyelectrolytes. We selected polylysine (PLL) and poly(glutamic acid) (PGA) for the polyelectrolytes and murine melanoma cells as a biological test model system. These cells respond specifically to a small peptide hormone, alpha-melanocortin, which is a potent stimulator of melanogenesis. We show that a synthetic alpha-melanocortin derivative, covalently coupled to PLL forming the outer layer of a multilayer film remains as biologically active as the free hormone. Furthermore, the long time activity of the hormone is maintained when embedded in multilayer architectures whereas its short time activity depends on integration depth. The embedding of bioactive molecules not only anchors them irreversibly on the biomaterial, but opens also the possibility to control their activity. In comparison to conventional coating methods, polyelectrolyte multilayers are easy to prepare and retain their biological activity after storage as dry material. These very flexible systems allow broad medical applications for implant and tissue engineering.
---
paper_title: Bioactive materials for biomedical applications using sol–gel technology

paper_content:

This review paper focuses on the sol?gel technology that has been applied in many of the potential research areas and highlights the importance of sol?gel technology for preparing bioactive materials for biomedical applications. The versatility of sol?gel chemistry enables us to manipulate the characteristics of material required for particular applications. Sol?gel derived materials have proved to be good biomaterials for coating films and for the construction of super-paramagnetic nanoparticles, bioactive glasses and fiberoptic applicators for various biomedical applications. The introduction of the sol?gel route in a conventional method of preparing implants improves the mechanical strength, biocompatibility and bioactivity of scaffolds and prevents corrosion of metallic implants. The use of organically modified silanes (ORMOSILS) yields flexible and bioactive materials for soft and hard tissue replacement. A novel approach of nitric-oxide-releasing sol?gels as antibacterial coatings for reducing the infection around orthopedic implants has also been discussed.
---
paper_title: Carbon Nanotube Electrodes for Effective Interfacing with Retinal Tissue

paper_content:

We have investigated the use of carbon nanotube microelectrodes as an interface material for retinal recording and stimulation applications. Test devices were micro-fabricated and consisted of 60 pristine 30 um electrodes coated with chemical vapor deposited carbon nanotubes, resulting in conducting, three dimensional surfaces with a high effective interfacial area. These attributes are important both for the quality of the cell-surface coupling as well as for electro-chemical interfacing efficiency. The entire chip was packaged to fit a commercial multielectrode recording and stimulation system. Electrical recordings of spontaneous spikes from whole-mount neonatal mouse retinas were consistently obtained minutes after retinas were placed over the electrodes, exhibiting typical bursting and propagating waves. Most importantly, the signals obtained with carbon nanotube electrodes have exceptionally high signal to noise ratio, reaching values as high as 75. Moreover, spikes are marked by a conspicuous gradual increase in amplitude recorded over a period of minutes to hours, suggesting improvement in cell-electrode coupling. This phenomenon is not observed in conventional commercial electrodes. Electrical stimulation using carbon nanotube electrodes was also achieved. We attribute the superior performances of the carbon nanotube electrodes to their three dimensional nature and the strong neuro-carbon nanotube affinity. The results presented here show the great potential of carbon nanotube electrodes for retinal interfacing applications. Specifically, our results demonstrate a route to achieve a reduction in the electrode size down to few micrometers in order to achieve high efficacy local stimulation needed in retinal prosthetic devices.
---
paper_title: Bioactive properties of nanostructured porous silicon for enhancing electrode to neuron interfaces

paper_content:

Many different types of microelectrodes have been developed for use as a direct brain–machine interface (BMI) to chronically recording single-neuron action potentials from ensembles of neurons. Unfortunately, the recordings from these microelectrode devices are not consistent and often last for only on the order of months. For most microelectrode types, the loss of these recordings is not due to failure of the electrodes, but most likely due to damage to surrounding tissue that results in the formation of non-conductive glial scar. Since the extracellular matrix consists of nanostructured fibrous protein assemblies, we have postulated that neurons may prefer a more complex surface structure than the smooth surface typical of thin-film microelectrodes. This porous structure could then act as a drug-delivery reservoir to deliver bioactive agents to aid in the repair or survival of cells around the microelectrode, further reducing the glial scar. We, therefore, investigated the suitability of a nano-porous s...
---
paper_title: Iridium Oxide Microelectrode Arrays for In Vitro Stimulation of Individual Rat Neurons from Dissociated Cultures

paper_content:

We present the first in-vitro extracellular stimulation of individual neurons from dissociated cultures with iridium oxide (IrOx) electrodes. Microelectrode arrays with sputtered IrOx films (SIROF) were developed for electrophysiological investigations with electrogenic cells. The microelectrodes were characterized with scanning electron and atomic force microscopy, revealing rough and porous electrodes with enlarged surface areas. As shown by cyclic voltammetry and electrochemical impedance spectroscopy, the large surface area in combination with the good electrochemical properties of SIROF resulted in high charge storage capacity and low electrode impedance. Thus, we could transfer the good properties of IrOx as material for in-vivo stimulation electrodes to MEAs with electrode diameters as small as 10 µm for in-vitro applications. Single rat cortical neurons from dissociated cultures were successfully stimulated to fire action potentials using single or trains of biphasic rectangular voltage-controlled stimulation pulses. The stimulated cell’s membrane potential was simultaneously monitored using whole-cell current-clamp recordings. This experimental configuration allowed direct evaluation of the influence of pulse phase sequence, amplitude, and number on the stimulation success ratio and action potential latency. Negative phase first pulses were more effective for extracellular stimulation and caused reduced latency in comparison to positive phase first pulses. Increasing the pulse amplitude also improved stimulation reliability. However, in order to prevent cell or electrode damage, the pulse amplitude is limited to voltages below the threshold for irreversible electrochemical reactions at the electrode. As an alternative to increasing the amplitude, a higher number of stimulation pulses was also shown to increase stimulation success.
---
paper_title: Adhesion Molecule-Modified Biomaterials for Neural Tissue Engineering

paper_content:

Adhesion molecules (AMs) represent one class of biomolecules that promote central nervous system regeneration. These tethered molecules provide cues to regenerating neurons that recapitulate the native brain environment. Improving cell adhesive potential of non-adhesive biomaterials is therefore a common goal in neural tissue engineering. This review discusses common AMs used in neural biomaterials and the mechanism of cell attachment to these AMs. Methods to modify materials with AMs are discussed and compared. Additionally, patterning of AMs for achieving specific neuronal responses is explored.
---
paper_title: Biofunctional coatings via targeted covalent cross-linking of associating triblock proteins.

paper_content:

A method for creating tailorable bioactive surface coatings by targeted cross-linking of network-forming CRC protein polymers is presented. The proteins are triblock constructs composed of two self-associating leucine zipper end domains (C) separated by a soluble, disordered central block (R) containing a cell or molecular binding sequence. The end domains preferentially form trimeric bundles, leading to the formation of a regular, reversible hydrogel network in a wide range of solution conditions. These hydrogel-forming proteins are useful for creating bioactive surface coatings because they self-assemble into networks, physically adsorb to a variety of substrate materials, and can be tailored to display numerous extracellular matrix (ECM)-derived peptides that interact with cells and biological macromolecules. Moreover, due to the close proximity of complementary Glu and Lys residues in the trimeric C bundles, these protein coatings can be stabilized in a targeted manner by covalent cross-linking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). Here, we demonstrate that such EDC-cross-linked protein coatings are stable in cell culture media and maintain a significant level of biofunctionality when various ECM-derived peptides are embedded in the central soluble block of the proteins. First, we show that EDC cross-linking enables bioinert CRC protein coatings (those without embedded cell binding domains) to resist the adhesion of human foreskin fibroblasts in normal serum medium, but does not impair the ability of cross-linked coatings of CRC-RGDS (proteins with an embedded RGDS integrin binding domain) to promote cellular attachment, focal adhesion formation, and proliferation of these cells. Next, we show that the ability of cross-linked coatings of several new CRC-based proteins containing embedded heparin-binding sequences to bind biotinylated heparin is not significantly impacted over a range of EDC concentrations. The ability to target specific functional groups for covalent cross-linking is made possible by the specificity of protein-protein interactions and represents an important advantage of protein-based materials.
---
paper_title: Analysis of High-Perimeter Planar Electrodes for Efficient Neural Stimulation

paper_content:

Planar electrodes are used in epidural spinal cord stimulation and epidural cortical stimulation. Electrode geometry is one approach to increase the efficiency of neural stimulation and reduce the power required to produce the level of activation required for clinical efficacy. Our hypothesis was that electrode geometries that increased the variation of current density on the electrode surface would increase stimulation efficiency. High-perimeter planar disk electrodes were designed with sinuous (serpentine) variation in the perimeter. Prototypes were fabricated that had equal surface areas but perimeters equal to 2, 3 or 4 times the perimeter of a circular disk electrode. The interface impedance of high-perimeter prototype electrodes measured in vitro did not differ significantly from that of the circular electrode over a wide range of frequencies. Finite element models indicated that the variation of current density was significantly higher on the surface of the high-perimeter electrodes. We quantified activation of 100 model axons randomly positioned around the electrodes. Input-output curves of the percentage of axons activated as a function of stimulation intensity indicated that the stimulation efficiency was dependent on the distance of the axons from the electrode. The high-perimeter planar electrodes were more efficient at activating axons a certain distance away from the electrode surface. These results demonstrate the feasibility of increasing stimulation efficiency through the design of novel electrode geometries.
---
paper_title: Extracellular recordings from patterned neuronal networks using planar microelectrode arrays

paper_content:

Neuronal cell networks have been reconstructed on planar microelectrode arrays (NMAs) from dissociated hippocampal pyramidal neurons. Microcontact printing (pCP) and a photoresist-liftoff method were used to selectively localize poly-L-lysine (PLL) on the surface of NWAs. Haptotaxis led to the organization of the neurons into networks localized adjacent to microelectrodes. Various grids of PLL with 2-25-pm-wide lines spaced by 50-200 pm with 15-25-pm nodes at intersection points were used to guide cell body attachment and neurite outgrowth. Bursting activity with spike attenuation was observed, and multichannel recordings detected instances of coincident firing activity. Finally, we present here an extracellular recording from a -2 pm bundle of guided neurites.
---
paper_title: Implantable brain computer interface: Challenges to neurotechnology translation

paper_content:

This article reviews three concepts related to implantable brain computer interface (BCI) devices being designed for human use: neural signal extraction primarily for motor commands, signal insertion to restore sensation, and technological challenges that remain. A significant body of literature has occurred over the past four decades regarding motor cortex signal extraction for upper extremity movement or computer interface. However, little is discussed regarding postural or ambulation command signaling. Auditory prosthesis research continues to represent the majority of literature on BCI signal insertion. Significant hurdles continue in the technological translation of BCI implants. These include developing a stable neural interface, significantly increasing signal processing capabilities, and methods of data transfer throughout the human body. The past few years, however, have provided extraordinary human examples of BCI implant potential. Despite technological hurdles, proof-of-concept animal and human studies provide significant encouragement that BCI implants may well find their way into mainstream medical practice in the foreseeable future.
---
paper_title: Analysis of High-Perimeter Planar Electrodes for Efficient Neural Stimulation

paper_content:

Planar electrodes are used in epidural spinal cord stimulation and epidural cortical stimulation. Electrode geometry is one approach to increase the efficiency of neural stimulation and reduce the power required to produce the level of activation required for clinical efficacy. Our hypothesis was that electrode geometries that increased the variation of current density on the electrode surface would increase stimulation efficiency. High-perimeter planar disk electrodes were designed with sinuous (serpentine) variation in the perimeter. Prototypes were fabricated that had equal surface areas but perimeters equal to 2, 3 or 4 times the perimeter of a circular disk electrode. The interface impedance of high-perimeter prototype electrodes measured in vitro did not differ significantly from that of the circular electrode over a wide range of frequencies. Finite element models indicated that the variation of current density was significantly higher on the surface of the high-perimeter electrodes. We quantified activation of 100 model axons randomly positioned around the electrodes. Input-output curves of the percentage of axons activated as a function of stimulation intensity indicated that the stimulation efficiency was dependent on the distance of the axons from the electrode. The high-perimeter planar electrodes were more efficient at activating axons a certain distance away from the electrode surface. These results demonstrate the feasibility of increasing stimulation efficiency through the design of novel electrode geometries.
---
paper_title: A Novel Concept for a Prosthetic Hand With a Bidirectional Interface: A Feasibility Study

paper_content:

A conceptually novel prosthesis consisting of a mechatronic hand, an electromyographic classifier, and a tactile display has been developed and evaluated by addressing problems related to controllability in prosthetics: intention extraction, perception, and feeling of ownership. Experiments have been performed, and encouraging results for a young transradial amputee are reported.
---
paper_title: Brain–machine interfaces: past, present and future

paper_content:

Since the original demonstration that electrical activity generated by ensembles of cortical neurons can be employed directly to control a robotic manipulator, research on brain–machine interfaces (BMIs) has experienced an impressive growth. Today BMIs designed for both experimental and clinical studies can translate raw neuronal signals into motor commands that reproduce arm reaching and hand grasping movements in artificial actuators. Clearly, these developments hold promise for the restoration of limb mobility in paralyzed subjects. However, as we review here, before this goal can be reached several bottlenecks have to be passed. These include designing a fully implantable biocompatible recording device, further developing real-time computational algorithms, introducing a method for providing the brain with sensory feedback from the actuators, and designing and building artificial prostheses that can be controlled directly by brain-derived signals. By reaching these milestones, future BMIs will be able to drive and control revolutionary prostheses that feel and act like the human arm.
---
paper_title: Early Interfaced Neural Activity from Chronic Amputated Nerves

paper_content:

Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation, currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative on-dependent multi-electrode arrays of open design allow the early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. .
---
paper_title: Transcranial magnetic stimulation, synaptic plasticity and network oscillations

paper_content:

Transcranial magnetic stimulation (TMS) has quickly progressed from a technical curiosity to a bona-fide tool for neurological research. The impetus has been due to the promising results obtained when using TMS to uncover neural processes in normal human subjects, as well as in the treatment of intractable neurological conditions, such as stroke, chronic depression and epilepsy. The basic principle of TMS is that most neuronal axons that fall within the volume of magnetic stimulation become electrically excited, trigger action potentials and release neurotransmitter into the postsynaptic neurons. What happens afterwards remains elusive, especially in the case of repeated stimulation. Here we discuss the likelihood that certain TMS protocols produce long-term changes in cortical synapses akin to long-term potentiation and long-term depression of synaptic transmission. Beyond the synaptic effects, TMS might have consequences on other neuronal processes, such as genetic and protein regulation, and circuit-level patterns, such as network oscillations. Furthermore, TMS might have non-neuronal effects, such as changes in blood flow, which are still poorly understood.
---
paper_title: Design and Adsorption of Modular Engineered Proteins to Prepare Customized, Neuron-Compatible Coatings

paper_content:

Neural prosthetic implants are currently being developed for the treatment and study of both peripheral and central nervous system disorders. Effective integration of these devices upon implantation is a critical hurdle to achieving function. As a result, much attention has been directed towards the development of biocompatible coatings that prolong their in vivo lifespan. In this work, we present a novel approach to fabricate such coatings, which specifically involves the use of surface-adsorbed, nanoscale-designed protein polymers to prepare reproducible, customized surfaces. A nanoscale modular design strategy was employed to synthesize six engineered, recombinant proteins intended to mimic aspects of the extracellular matrix proteins fibronectin, laminin, and elastin as well as the cell-cell adhesive protein NCAM (neural cell adhesion molecule). Physical adsorption isotherms were experimentally determined for these engineered proteins, allowing for direct calculation of the available ligand density present on coated surfaces. As confirmation that ligand density in these engineered systems impacts neuronal cell behavior, we demonstrate that increasing the density of fibronectin-derived RGD ligands on coated surfaces while maintaining uniform protein surface coverage results in enhanced neurite extension of PC-12 cells. Therefore, this engineered protein adsorption approach allows for the facile preparation of tunable, quantifiable, and reproducible surfaces for in vitro studies of cell-ligand interactions and for potential application as coatings on neural implants.
---
paper_title: Human cortical prostheses: lost in translation?

paper_content:

Direct brain control of a prosthetic system is the subject of much popular and scientific news. Neural technology and science have advanced to the point that proof-of-concept systems exist for cortically-controlled prostheses in rats, monkeys, and even humans. However, realizing the dream of making such technology available to everyone is still far off. Fortunately today there is great public and scientific interest in making this happen, but it will only occur when the functional benefits of such systems outweigh the risks. In this article, the authors briefly summarize the state of the art and then highlight many issues that will directly limit clinical translation, including system durability, system performance, and patient risk. Despite the challenges, scientists and clinicians are in the desirable position of having both public and fiscal support to begin addressing these issues directly. The ultimate challenge now is to determine definitively whether these prosthetic systems will become clinical reality or forever unrealized.
---
paper_title: A brain-computer interface with vibrotactile biofeedback for haptic information

paper_content:

BackgroundIt has been suggested that Brain-Computer Interfaces (BCI) may one day be suitable for controlling a neuroprosthesis. For closed-loop operation of BCI, a tactile feedback channel that is compatible with neuroprosthetic applications is desired. Operation of an EEG-based BCI using only vibrotactile feedback, a commonly used method to convey haptic senses of contact and pressure, is demonstrated with a high level of accuracy.MethodsA Mu-rhythm based BCI using a motor imagery paradigm was used to control the position of a virtual cursor. The cursor position was shown visually as well as transmitted haptically by modulating the intensity of a vibrotactile stimulus to the upper limb. A total of six subjects operated the BCI in a two-stage targeting task, receiving only vibrotactile biofeedback of performance. The location of the vibration was also systematically varied between the left and right arms to investigate location-dependent effects on performance.Results and ConclusionSubjects are able to control the BCI using only vibrotactile feedback with an average accuracy of 56% and as high as 72%. These accuracies are significantly higher than the 15% predicted by random chance if the subject had no voluntary control of their Mu-rhythm. The results of this study demonstrate that vibrotactile feedback is an effective biofeedback modality to operate a BCI using motor imagery. In addition, the study shows that placement of the vibrotactile stimulation on the biceps ipsilateral or contralateral to the motor imagery introduces a significant bias in the BCI accuracy. This bias is consistent with a drop in performance generated by stimulation of the contralateral limb. Users demonstrated the capability to overcome this bias with training.
---
paper_title: Neuroprosthetic devices: how far are we from recovering movement in paralyzed patients?

paper_content:

In October 2008, Eberhard Fetz’s group from the University of Washington dem-onstrated that a direct artificial connection from a region of the brain associated with the control of movement to muscles in the limb could restore movement induced by electrical stimulation in monkeys whose arms had been temporarily anesthetized. The report of this progress created tremen-dous public interest as a perceived mile-stone in the development of a seamless neurotechnological solution for restoring function in paralysis. This work relied on the combination of an implanted electrode array in the motor cortex and functional electrical stimulation (FES) to muscles in the paralyzed wrist. Indeed, the combina-tion of FES, a technique that has achieved a track record of clinical utility, with brain–machine interfaces (BMIs) has become the subject of study for several research groups. Based on progress from these groups, we suggest that the technology has reached sufficient maturation that the proof-of-concept clinical demonstration could be accomplished within the next 5 years. In this editorial, we provide a brief overview of the key technologies and several key issues that are being explored, and also discuss the importance of supporting translational neuroprosthetics research and development to achieve this goal.Paralysis resulting from neurological injury or disease places a significant burden on patients, their families and caregivers. Neuroprostheses offer the promise of restoring movement to paralyzed patients by bypassing damaged regions of the ner-vous system, ultimately giving patients the ability to live with greater indepen-dence and improving their quality of life. Indeed, the coordinated stimulation of paralyzed muscles through FES has been shown to be effective and safe for restoring hand grasp
---
paper_title: Decoding Visual Inputs From Multiple Neurons in the Human Temporal Lobe

paper_content:

We investigated the representation of visual inputs by multiple simultaneously recorded single neurons in the human medial temporal lobe, using their firing rates to infer which images were shown to subjects. The selectivity of these neurons was quantified with a novel measure. About four spikes per neuron, triggered between 300 and 600 ms after image onset in a handful of units (7.8 on average), predicted the identity of images far above chance. Decoding performance increased linearly with the number of units considered, peaked between 400 and 500 ms, did not improve when considering correlations among simultaneously recorded units, and generalized to very different images. The feasibility of decoding sensory information from human extracellular recordings has implications for the development of brain–machine interfaces.
---
paper_title: Implantable brain computer interface: Challenges to neurotechnology translation

paper_content:

This article reviews three concepts related to implantable brain computer interface (BCI) devices being designed for human use: neural signal extraction primarily for motor commands, signal insertion to restore sensation, and technological challenges that remain. A significant body of literature has occurred over the past four decades regarding motor cortex signal extraction for upper extremity movement or computer interface. However, little is discussed regarding postural or ambulation command signaling. Auditory prosthesis research continues to represent the majority of literature on BCI signal insertion. Significant hurdles continue in the technological translation of BCI implants. These include developing a stable neural interface, significantly increasing signal processing capabilities, and methods of data transfer throughout the human body. The past few years, however, have provided extraordinary human examples of BCI implant potential. Despite technological hurdles, proof-of-concept animal and human studies provide significant encouragement that BCI implants may well find their way into mainstream medical practice in the foreseeable future.
---
paper_title: Review of Wireless and Wearable Electroencephalogram Systems and Brain-Computer Interfaces – A Mini-Review

paper_content:

Biomedical signal monitoring systems have rapidly advanced in recent years, propelled by significant advances in electronic and information technologies. Brain-computer interface (BCI) is one of the important research branches and has become a hot topic in the study of neural engineering, rehabilitation, and brain science. Traditionally, most BCI systems use bulky, wired laboratory-oriented sensing equipments to measure brain activity under well-controlled conditions within a confined space. Using bulky sensing equipments not only is uncomfortable and inconvenient for users, but also impedes their ability to perform routine tasks in daily operational environments. Furthermore, owing to large data volumes, signal processing of BCI systems is often performed off-line using high-end personal computers, hindering the applications of BCI in real-world environments. To be practical for routine use by unconstrained, freely-moving users, BCI systems must be noninvasive, nonintrusive, lightweight and capable of online signal processing. This work reviews recent online BCI systems, focusing especially on wearable, wireless and real-time systems.
---
paper_title: Non-invasive control of neuroprostheses for the upper extremity: Temporal coding of brain patterns

paper_content:

Spinal cord injury (SCI) results in deficits of sensory, motor and autonomous functions, with tremendous consequences for the patients. The loss of motor functions, especially grasping, leads to a dramatic decrease in quality of life. With the help of neuroprostheses, the grasp function can be substantially improved in cervical SCI patients. Nowadays, systems for grasp restoration can only be used by patients with preserved voluntary shoulder and elbow function. In patients with lesions above the 5th vertebra, not only the voluntary movements of the elbow are restricted, but also the overall number of preserved movements available for control purposes decreases. A Brain-Computer Interface (BCI) offers a method to overcome this problem. This work gives an overview of the Graz BCI used for the control of grasp neuroprostheses as well as a new control method for combining grasp and elbow function is introduced.
---
paper_title: A Novel Concept for a Prosthetic Hand With a Bidirectional Interface: A Feasibility Study

paper_content:

A conceptually novel prosthesis consisting of a mechatronic hand, an electromyographic classifier, and a tactile display has been developed and evaluated by addressing problems related to controllability in prosthetics: intention extraction, perception, and feeling of ownership. Experiments have been performed, and encouraging results for a young transradial amputee are reported.
---
paper_title: Application to robot control using brain function measurement by near-infrared spectroscopy

paper_content:

In recent years, study of brain computer interface (BCI) is conducted actively and many researches of implementation using electro encephalic gram (EEG) are reported. On the other hand, some realization of BCI based on near- infrared spectroscopy (NIRS) also had been reported. Since a measurement instrument for NIRS is comparatively small- scale and it can perform noninvasive measurements, NIRS is expected as one of useful tool in order to realize versatile BCIs. In this paper, the estimation method is shown the possibility of applications to the ON/OFF control of BCI by NIRS. We measured regional cerebral blood flow during tapping movement of the right hand by NIRS and we propose a method to quantitatively estimate start and end timing of movement by using a neural network.
---
paper_title: Brain–machine interfaces: past, present and future

paper_content:

Since the original demonstration that electrical activity generated by ensembles of cortical neurons can be employed directly to control a robotic manipulator, research on brain–machine interfaces (BMIs) has experienced an impressive growth. Today BMIs designed for both experimental and clinical studies can translate raw neuronal signals into motor commands that reproduce arm reaching and hand grasping movements in artificial actuators. Clearly, these developments hold promise for the restoration of limb mobility in paralyzed subjects. However, as we review here, before this goal can be reached several bottlenecks have to be passed. These include designing a fully implantable biocompatible recording device, further developing real-time computational algorithms, introducing a method for providing the brain with sensory feedback from the actuators, and designing and building artificial prostheses that can be controlled directly by brain-derived signals. By reaching these milestones, future BMIs will be able to drive and control revolutionary prostheses that feel and act like the human arm.
---
paper_title: Early Interfaced Neural Activity from Chronic Amputated Nerves

paper_content:

Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation, currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative on-dependent multi-electrode arrays of open design allow the early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. .
---
paper_title: A binary method for simple and accurate two-dimensional cursor control from EEG with minimal subject training

paper_content:

Background ::: Brain-computer interfaces (BCI) use electroencephalography (EEG) to interpret user intention and control an output device accordingly. We describe a novel BCI method to use a signal from five EEG channels (comprising one primary channel with four additional channels used to calculate its Laplacian derivation) to provide two-dimensional (2-D) control of a cursor on a computer screen, with simple threshold-based binary classification of band power readings taken over pre-defined time windows during subject hand movement.
---
paper_title: Using multi-neuron population recordings for neural prosthetics

paper_content:

Classical single-neuron recording methods led to 'neuron-centric' concepts of neural coding, whereas more recent multi-neuron population recordings have inspired 'population-centric' concepts of distributed processing in neural systems. Because most neocortical neurons code information coarsely, sensory or motor processing tends to be widely distributed across neuronal populations. Dynamic fluctuations in neural population functions thus involve subtle changes in the overall pattern of neural activity. Mathematical analysis of neural population codes allows extraction of 'motor signals' from neuronal population recordings in the motor cortices, which can then be used in real-time to directly control movement of a robot arm. This technique holds promise for the development of neurally controlled prosthetic devices and provides insights into how information is distributed across several brain regions.
---
paper_title: Thalamic visual neuroprostheses: Comparison of visual percepts generated by natural stimulation of the eye and electrical stimulation of the thalamus

paper_content:

Thalamic visual neuroprostheses to be implanted in the lateral geniculate nucleus of the thalamus (the intermediate relay station of visual information from the retina to the cortex) could be used to provide visual information to blind people when retinal implants are not feasible. The main objective of the present work was to (i) determine a way to compare visual percepts generated by electrical stimulation of the thalamus and percepts elicited by natural stimulation of the eye and (ii) apply this method to contrast the responses of the cortical neurons under these two conditions.
---
paper_title: Biomaterials for the central nervous system

paper_content:

Biomaterials are widely used to help treat neurological disorders and/or improve functional recovery in the central nervous system (CNS). This article reviews the application of biomaterials in (i) shunting systems for hydrocephalus, (ii) cortical neural prosthetics, (iii) drug delivery in the CNS, (iv) hydrogel scaffolds for CNS repair, and (v) neural stem cell encapsulation for neurotrauma. The biological and material requirements for the biomaterials in these applications are discussed. The difficulties that the biomaterials might face in each application and the possible solutions are also reviewed in this article.
---
paper_title: Carbon Nanotube Electrodes for Effective Interfacing with Retinal Tissue

paper_content:

We have investigated the use of carbon nanotube microelectrodes as an interface material for retinal recording and stimulation applications. Test devices were micro-fabricated and consisted of 60 pristine 30 um electrodes coated with chemical vapor deposited carbon nanotubes, resulting in conducting, three dimensional surfaces with a high effective interfacial area. These attributes are important both for the quality of the cell-surface coupling as well as for electro-chemical interfacing efficiency. The entire chip was packaged to fit a commercial multielectrode recording and stimulation system. Electrical recordings of spontaneous spikes from whole-mount neonatal mouse retinas were consistently obtained minutes after retinas were placed over the electrodes, exhibiting typical bursting and propagating waves. Most importantly, the signals obtained with carbon nanotube electrodes have exceptionally high signal to noise ratio, reaching values as high as 75. Moreover, spikes are marked by a conspicuous gradual increase in amplitude recorded over a period of minutes to hours, suggesting improvement in cell-electrode coupling. This phenomenon is not observed in conventional commercial electrodes. Electrical stimulation using carbon nanotube electrodes was also achieved. We attribute the superior performances of the carbon nanotube electrodes to their three dimensional nature and the strong neuro-carbon nanotube affinity. The results presented here show the great potential of carbon nanotube electrodes for retinal interfacing applications. Specifically, our results demonstrate a route to achieve a reduction in the electrode size down to few micrometers in order to achieve high efficacy local stimulation needed in retinal prosthetic devices.
---
paper_title: An auditory oddball (P300) spelling system for brain‐computer interfaces

paper_content:

This study was designed to develop and test an auditory event-related potential (ERP) based spelling system for a brain-computer interface (BCI) and to compare user’s performance between the auditory and visual modality. The spelling system, where letters in a matrix were coded with acoustically presented numbers, was tested on a group of healthy volunteers. The results were compared with a visual spelling system. Nine of the 13 participants presented with the auditory ERP spelling system scored above a predefined criterion level control for communication. Compared to the visual spelling system, users’ performance was lower and the peak latencies of the auditorily evoked ERPs were delayed. It was concluded that auditorily evoked ERPs from the majority of the users could be reliably classified. High accuracies were achieved in these users, rendering item selection with a BCI based on auditory stimulation feasible for communication. Descriptors: Electroencephalogram, Auditory stimulation, Event-related potential, P300, Brain-computer interface
---
paper_title: Design Optimization for Integrated Neural Recording Systems

paper_content:

Power and chip area are the most important parameters in designing a neural recording system in vivo. This paper reports a design methodology for an optimized integrated neural recording system. Electrode noise is considered in determining the ADC's resolution to prevent over-design of the ADC, which leads to unnecessary power consumption and chip area. The optimal transconductance and gain of the pre-amplifiers, which minimizes the power-area product of the amplifier, are mathematically derived. A numerical example using actual circuit parameters is shown to demonstrate the design methodology. A tradeoff between the power consumption of the system and the chip area in terms of the multiplexing ratio is investigated and the optimal number of channels per ADC is selected to achieve the minimum power-area product for the entire system. Following the proposed design methodology, a chip has been designed in 0.35 mum CMOS process, with the multiplexing ratio of 16:1, resulting in total chip area of 2.5 mm times 2.0 mm and power consumption of 5.3 mW from plusmn1.65 V.
---
paper_title: Compressed sensing

paper_content:

Suppose x is an unknown vector in Ropfm (a digital image or signal); we plan to measure n general linear functionals of x and then reconstruct. If x is known to be compressible by transform coding with a known transform, and we reconstruct via the nonlinear procedure defined here, the number of measurements n can be dramatically smaller than the size m. Thus, certain natural classes of images with m pixels need only n=O(m1/4log5/2(m)) nonadaptive nonpixel samples for faithful recovery, as opposed to the usual m pixel samples. More specifically, suppose x has a sparse representation in some orthonormal basis (e.g., wavelet, Fourier) or tight frame (e.g., curvelet, Gabor)-so the coefficients belong to an lscrp ball for 0<ples1. The N most important coefficients in that expansion allow reconstruction with lscr2 error O(N1/2-1p/). It is possible to design n=O(Nlog(m)) nonadaptive measurements allowing reconstruction with accuracy comparable to that attainable with direct knowledge of the N most important coefficients. Moreover, a good approximation to those N important coefficients is extracted from the n measurements by solving a linear program-Basis Pursuit in signal processing. The nonadaptive measurements have the character of "random" linear combinations of basis/frame elements. Our results use the notions of optimal recovery, of n-widths, and information-based complexity. We estimate the Gel'fand n-widths of lscrp balls in high-dimensional Euclidean space in the case 0<ples1, and give a criterion identifying near- optimal subspaces for Gel'fand n-widths. We show that "most" subspaces are near-optimal, and show that convex optimization (Basis Pursuit) is a near-optimal way to extract information derived from these near-optimal subspaces
---
paper_title: A brain-computer interface with vibrotactile biofeedback for haptic information

paper_content:

BackgroundIt has been suggested that Brain-Computer Interfaces (BCI) may one day be suitable for controlling a neuroprosthesis. For closed-loop operation of BCI, a tactile feedback channel that is compatible with neuroprosthetic applications is desired. Operation of an EEG-based BCI using only vibrotactile feedback, a commonly used method to convey haptic senses of contact and pressure, is demonstrated with a high level of accuracy.MethodsA Mu-rhythm based BCI using a motor imagery paradigm was used to control the position of a virtual cursor. The cursor position was shown visually as well as transmitted haptically by modulating the intensity of a vibrotactile stimulus to the upper limb. A total of six subjects operated the BCI in a two-stage targeting task, receiving only vibrotactile biofeedback of performance. The location of the vibration was also systematically varied between the left and right arms to investigate location-dependent effects on performance.Results and ConclusionSubjects are able to control the BCI using only vibrotactile feedback with an average accuracy of 56% and as high as 72%. These accuracies are significantly higher than the 15% predicted by random chance if the subject had no voluntary control of their Mu-rhythm. The results of this study demonstrate that vibrotactile feedback is an effective biofeedback modality to operate a BCI using motor imagery. In addition, the study shows that placement of the vibrotactile stimulation on the biceps ipsilateral or contralateral to the motor imagery introduces a significant bias in the BCI accuracy. This bias is consistent with a drop in performance generated by stimulation of the contralateral limb. Users demonstrated the capability to overcome this bias with training.
---
paper_title: On the Use of Longitudinal Intrafascicular Peripheral Interfaces for the Control of Cybernetic Hand Prostheses in Amputees

paper_content:

Significant strides have been recently made to develop highly sensorized cybernetic prostheses aimed at restoring sensorimotor limb functions to those who have lost them because of a traumatic event (amputation). In these cases, one of the main goals is to create a bidirectional link between the artificial devices (e.g., robotic hands, arms, or legs) and the nervous system. Several human-machine interfaces (HMIs) are currently used to this aim. Among them, interfaces with the peripheral nervous system and in particular longitudinal intrafascicular electrodes can be a promising solution able to improve the current situation. In this paper, the potentials and limits of the use of this interface to control robotic devices are presented. Specific information is provided on: 1) the neurophysiological bases for the use peripheral nerve interfaces; 2) a comparison of the potentials of the different peripheral neural interfaces; 3) the possibility of extracting and appropriately interpreting the neural code for motor commands and of delivering sensory feedback by stimulating afferent fibers by using longitudinal intrafascicular electrodes; 4) a preliminary comparative analysis of the performance of this approach with the ones of others HMIs; 5) the open issues which have to be addressed for a chronic usability of this approach.
---
paper_title: Silicon ribbon cables for chronically implantable microelectrode arrays

paper_content:

Describes the design, fabrication, and testing of miniature ultraflexible ribbon cables for use with micromachined silicon microprobes capable of chronic recording and/or stimulation in the central nervous system (CNS). These interconnects are of critical importance in reliably linking these microelectrodes to the external world through a percutaneous connector. The silicon cables allow the realization of multilead, multistrand shielded local interconnects that are extremely flexible and yet strong enough to withstand normal handling and surgical manipulation. Cables 5 /spl mu/m thick, 1-5 cm long, and from 60 to 250 /spl mu/m wide have been fabricated with up to eight leads. The series lead resistance is typically 4 k/spl Omega//cm for polysilicon and 500 /spl Omega//cm for tantalum with shunt capacitance values of 5-10 pF/cm and an interlead capacitance below 10 fF/cm. Soak tests in buffered saline performed under electrical and mechanical stress have been underway for over three years and show subpicoampere leakage levels. Silicon microprobes with built-in ribbon cables have remained functional for up to one gear in the guinea pig CNS, recording driven single-unit activity and maintaining impedance levels in the 1-7 M /spl Omega/ range. >
---
paper_title: A neuroengineering suite of computational tools for visual prostheses

paper_content:

The cooperation between neuroscience and biomedical engineering gave rise to a recent, but growing research field, known as neuroengineering. We follow its principles to have a system providing basic descriptions of the visual world to the brain's cortex. We describe a set of software and hardware tools to interface with neural tissue, in order to transmit visual information encoded into a bioinspired neural-like form. The set is composed of a retina-like encoder, and a platform to optimize electrical stimulation parameters for a multi-electrode implant. The main objective is to progress towards a functional visual neuroprosthesis for the blind.
---
paper_title: An Implantable 64-Channel Wireless Microsystem for Single-Unit Neural Recording

paper_content:

This paper reports an implantable microsystem capable of recording neural activity simultaneously on 64 channels, wirelessly transmitting spike occurrences to an external interface. The microsystem also allows the user to examine the spike waveforms on any channel with 8 bit resolution. Signals are amplified by 60 dB with a programmable bandwidth from < 100 Hz to 10 kHz. The input-referred noise is 8 ?Vrms. The channel scan rate for spike detection is 62.5 kS/sec using a 2 MHz clock. The system dissipates 14.4 mW at 1.8 V, weighs 275 mg, and measures 1.4 cm 1.55 cm.
---
paper_title: Analysis of High-Perimeter Planar Electrodes for Efficient Neural Stimulation

paper_content:

Planar electrodes are used in epidural spinal cord stimulation and epidural cortical stimulation. Electrode geometry is one approach to increase the efficiency of neural stimulation and reduce the power required to produce the level of activation required for clinical efficacy. Our hypothesis was that electrode geometries that increased the variation of current density on the electrode surface would increase stimulation efficiency. High-perimeter planar disk electrodes were designed with sinuous (serpentine) variation in the perimeter. Prototypes were fabricated that had equal surface areas but perimeters equal to 2, 3 or 4 times the perimeter of a circular disk electrode. The interface impedance of high-perimeter prototype electrodes measured in vitro did not differ significantly from that of the circular electrode over a wide range of frequencies. Finite element models indicated that the variation of current density was significantly higher on the surface of the high-perimeter electrodes. We quantified activation of 100 model axons randomly positioned around the electrodes. Input-output curves of the percentage of axons activated as a function of stimulation intensity indicated that the stimulation efficiency was dependent on the distance of the axons from the electrode. The high-perimeter planar electrodes were more efficient at activating axons a certain distance away from the electrode surface. These results demonstrate the feasibility of increasing stimulation efficiency through the design of novel electrode geometries.
---
paper_title: A Brain Implantable Microsystem with Hybrid RF/IR Telemetry for Advanced Neuroengineering Applications

paper_content:

A prototype cortical neural interface microsystem has been developed for brain implantable neuroengineering applications, featuring hybrid RF (radio- frequency) inductive and IR (infrared) optical telemetries. The system is aimed at neural recording from primates by converting cortical signals to a digital stream of IR light pulses, while acquiring clock signal and electrical power through RF induction. The implantable unit employs a flexible LCP (liquid crystal polymer) substrate for integration of analog, digital, and optoelectronic components, while adapting to the anatomical and physiological constraints of the environment. An ultra-low power analog CMOS chip, which includes preamplifier and multiplexing circuitry, is directly flip-chip bonded to the microelectrode array to form the immediate cortical neuroprobe device. A 16-channel version of the probe has been tested in various in-vivo animal experiments, including measurements of neural activity in somatosensory cortex of a rat.
---
paper_title: When mind meets machine

paper_content:

A new wave of brain–machine interfaces helps disabled people connect with the outside world
---
paper_title: Implantable brain computer interface: Challenges to neurotechnology translation

paper_content:

This article reviews three concepts related to implantable brain computer interface (BCI) devices being designed for human use: neural signal extraction primarily for motor commands, signal insertion to restore sensation, and technological challenges that remain. A significant body of literature has occurred over the past four decades regarding motor cortex signal extraction for upper extremity movement or computer interface. However, little is discussed regarding postural or ambulation command signaling. Auditory prosthesis research continues to represent the majority of literature on BCI signal insertion. Significant hurdles continue in the technological translation of BCI implants. These include developing a stable neural interface, significantly increasing signal processing capabilities, and methods of data transfer throughout the human body. The past few years, however, have provided extraordinary human examples of BCI implant potential. Despite technological hurdles, proof-of-concept animal and human studies provide significant encouragement that BCI implants may well find their way into mainstream medical practice in the foreseeable future.
---
paper_title: Human cortical prostheses: lost in translation?

paper_content:

Direct brain control of a prosthetic system is the subject of much popular and scientific news. Neural technology and science have advanced to the point that proof-of-concept systems exist for cortically-controlled prostheses in rats, monkeys, and even humans. However, realizing the dream of making such technology available to everyone is still far off. Fortunately today there is great public and scientific interest in making this happen, but it will only occur when the functional benefits of such systems outweigh the risks. In this article, the authors briefly summarize the state of the art and then highlight many issues that will directly limit clinical translation, including system durability, system performance, and patient risk. Despite the challenges, scientists and clinicians are in the desirable position of having both public and fiscal support to begin addressing these issues directly. The ultimate challenge now is to determine definitively whether these prosthetic systems will become clinical reality or forever unrealized.
---
paper_title: Using multi-neuron population recordings for neural prosthetics

paper_content:

Classical single-neuron recording methods led to 'neuron-centric' concepts of neural coding, whereas more recent multi-neuron population recordings have inspired 'population-centric' concepts of distributed processing in neural systems. Because most neocortical neurons code information coarsely, sensory or motor processing tends to be widely distributed across neuronal populations. Dynamic fluctuations in neural population functions thus involve subtle changes in the overall pattern of neural activity. Mathematical analysis of neural population codes allows extraction of 'motor signals' from neuronal population recordings in the motor cortices, which can then be used in real-time to directly control movement of a robot arm. This technique holds promise for the development of neurally controlled prosthetic devices and provides insights into how information is distributed across several brain regions.
---
paper_title: Principles of neural ensemble physiology underlying the operation of brain–machine interfaces

paper_content:

Research on brain-machine interfaces has been ongoing for at least a decade. During this period, simultaneous recordings of the extracellular electrical activity of hundreds of individual neurons have been used for direct, real-time control of various artificial devices. Brain-machine interfaces have also added greatly to our knowledge of the fundamental physiological principles governing the operation of large neural ensembles. Further understanding of these principles is likely to have a key role in the future development of neuroprosthetics for restoring mobility in severely paralysed patients.
---
paper_title: An auditory oddball (P300) spelling system for brain‐computer interfaces

paper_content:

This study was designed to develop and test an auditory event-related potential (ERP) based spelling system for a brain-computer interface (BCI) and to compare user’s performance between the auditory and visual modality. The spelling system, where letters in a matrix were coded with acoustically presented numbers, was tested on a group of healthy volunteers. The results were compared with a visual spelling system. Nine of the 13 participants presented with the auditory ERP spelling system scored above a predefined criterion level control for communication. Compared to the visual spelling system, users’ performance was lower and the peak latencies of the auditorily evoked ERPs were delayed. It was concluded that auditorily evoked ERPs from the majority of the users could be reliably classified. High accuracies were achieved in these users, rendering item selection with a BCI based on auditory stimulation feasible for communication. Descriptors: Electroencephalogram, Auditory stimulation, Event-related potential, P300, Brain-computer interface
---
paper_title: On the Use of Longitudinal Intrafascicular Peripheral Interfaces for the Control of Cybernetic Hand Prostheses in Amputees

paper_content:

Significant strides have been recently made to develop highly sensorized cybernetic prostheses aimed at restoring sensorimotor limb functions to those who have lost them because of a traumatic event (amputation). In these cases, one of the main goals is to create a bidirectional link between the artificial devices (e.g., robotic hands, arms, or legs) and the nervous system. Several human-machine interfaces (HMIs) are currently used to this aim. Among them, interfaces with the peripheral nervous system and in particular longitudinal intrafascicular electrodes can be a promising solution able to improve the current situation. In this paper, the potentials and limits of the use of this interface to control robotic devices are presented. Specific information is provided on: 1) the neurophysiological bases for the use peripheral nerve interfaces; 2) a comparison of the potentials of the different peripheral neural interfaces; 3) the possibility of extracting and appropriately interpreting the neural code for motor commands and of delivering sensory feedback by stimulating afferent fibers by using longitudinal intrafascicular electrodes; 4) a preliminary comparative analysis of the performance of this approach with the ones of others HMIs; 5) the open issues which have to be addressed for a chronic usability of this approach.
---
paper_title: A critical review of interfaces with the peripheral nervous system for the control of neuroprostheses and hybrid bionic systems

paper_content:

Considerable scientific and technological efforts have been devoted to develop neuroprostheses and hybrid bionic systems that link the human nervous system with electronic or robotic prostheses, with the main aim of restoring motor and sensory functions in disabled patients. A number of neuroprostheses use interfaces with peripheral nerves or muscles for neuromuscular stimulation and signal recording. Herein, we provide a critical overview of the peripheral interfaces available and trace their use from research to clinical application in controlling artificial and robotic prostheses. The first section reviews the different types of non-invasive and invasive electrodes, which include surface and muscular electrodes that can record EMG signals from and stimulate the underlying or implanted muscles. Extraneural electrodes, such as cuff and epineurial electrodes, provide simultaneous interface with many axons in the nerve, whereas intrafascicular, penetrating, and regenerative electrodes may contact small groups of axons within a nerve fascicle. Biological, technological, and material science issues are also reviewed relative to the problems of electrode design and tissue injury. The last section reviews different strate- gies for the use of information recorded from peripheral interfaces and the current state of control neuroprostheses and hybrid bionic systems.
---
paper_title: Vision based interface system for hands free control of an intelligent wheelchair

paper_content:

BackgroundDue to the shift of the age structure in today's populations, the necessities for developing the devices or technologies to support them have been increasing. Traditionally, the wheelchair, including powered and manual ones, is the most popular and important rehabilitation/assistive device for the disabled and the elderly. However, it is still highly restricted especially for severely disabled. As a solution to this, the Intelligent Wheelchairs (IWs) have received considerable attention as mobility aids. The purpose of this work is to develop the IW interface for providing more convenient and efficient interface to the people the disability in their limbs.MethodsThis paper proposes an intelligent wheelchair (IW) control system for the people with various disabilities. To facilitate a wide variety of user abilities, the proposed system involves the use of face-inclination and mouth-shape information, where the direction of an IW is determined by the inclination of the user's face, while proceeding and stopping are determined by the shapes of the user's mouth. Our system is composed of electric powered wheelchair, data acquisition board, ultrasonic/infra-red sensors, a PC camera, and vision system. Then the vision system to analyze user's gestures is performed by three stages: detector, recognizer, and converter. In the detector, the facial region of the intended user is first obtained using Adaboost, thereafter the mouth region is detected based on edge information. The extracted features are sent to the recognizer, which recognizes the face inclination and mouth shape using statistical analysis and K-means clustering, respectively. These recognition results are then delivered to the converter to control the wheelchair.Result & conclusionThe advantages of the proposed system include 1) accurate recognition of user's intention with minimal user motion and 2) robustness to a cluttered background and the time-varying illumination. To prove these advantages, the proposed system was tested with 34 users in indoor and outdoor environments and the results were compared with those of other systems, then the results showed that the proposed system has superior performance to other systems in terms of speed and accuracy. Therefore, it is proved that proposed system provided a friendly and convenient interface to the severely disabled people.
---
paper_title: Infrared thermography as an access pathway for individuals with severe motor impairments

paper_content:

BackgroundPeople with severe motor impairments often require an alternative access pathway, such as a binary switch, to communicate and to interact with their environment. A wide range of access pathways have been developed from simple mechanical switches to sophisticated physiological ones. In this manuscript we report the inaugural investigation of infrared thermography as a non-invasive and non-contact access pathway by which individuals with disabilities can interact and perhaps eventually communicate.MethodsOur method exploits the local temperature changes associated with mouth opening/closing to enable a highly sensitive and specific binary switch. Ten participants (two with severe disabilities) provided examples of mouth opening and closing. Thermographic videos of each participant were recorded with an infrared thermal camera and processed using a computerized algorithm. The algorithm detected a mouth open-close pattern using a combination of adaptive thermal intensity filtering, motion tracking and morphological analysis.ResultsHigh detection sensitivity and low error rate were achieved for the majority of the participants (mean sensitivity of all participants: 88.5% ± 11.3; mean specificity of all participants: 99.4% ± 0.7). The algorithm performance was robust against participant motion and changes in the background scene.ConclusionOur findings suggest that further research on the infrared thermographic access pathway is warranted. Flexible camera location, convenience of use and robustness to ambient lighting levels, changes in background scene and extraneous body movements make this a potential new access modality that can be used night or day in unconstrained environments.
---
paper_title: A brain-actuated wheelchair: Asynchronous and non-invasive Brain–computer interfaces for continuous control of robots

paper_content:

Objective: To assess the feasibility and robustness of an asynchronous and non-invasive EEG-based Brain-Computer Interface (BCI) for continuous mental control of a wheelchair. Methods: In experiment 1 two subjects were asked to mentally drive both a real and a simulated wheelchair from a starting point to a goal along a pre-specified path. Here we only report experiments with the simulated wheelchair for which we have extensive data in a complex environment that allows a sound analysis. Each subject participated in 5 experimental sessions, each consisting of 10 trials. The time elapsed between two consecutive experimental sessions was variable (from one hour to two months) to assess the system robustness over time. The pre-specified path was divided in 7 stretches to assess the system robustness in different contexts. To further assess the performance of the brain-actuated wheelchair, subject 1 participated in a second experiment consisting of 10 trials where he was asked to drive the simulated wheelchair following 10 different complex and random paths never tried before. Results: In experiment 1 the two subjects were able to reach 100% (subject 1) and 80% (subject 2) of the final goals along the pre-specified trajectory in their best sessions. Different performances were obtained over time and path stretches, what indicates that performance is time and context dependent. In experiment 2, subject 1 was able to reach the final goal in 80% of the trials. Conclusions: The results show that subjects can rapidly master our asynchronous EEG-based BCI to control a wheelchair. Also, they can autonomously operate the BCI over long periods of time without the need for adaptive algorithms externally tuned by a human operator to minimize the impact of EEG non-stationarities. This is possible because of two key components: first, the inclusion of a shared control system between the BCI system and the intelligent simulated wheelchair; second, the selection of stable user-specific EEG features that maximize the separability between the mental tasks. Significance: These results show the feasibility of continuously controlling complex robotics devices using an asynchronous and non-invasive BCI.
---
paper_title: Vision based interface system for hands free control of an intelligent wheelchair

paper_content:

BackgroundDue to the shift of the age structure in today's populations, the necessities for developing the devices or technologies to support them have been increasing. Traditionally, the wheelchair, including powered and manual ones, is the most popular and important rehabilitation/assistive device for the disabled and the elderly. However, it is still highly restricted especially for severely disabled. As a solution to this, the Intelligent Wheelchairs (IWs) have received considerable attention as mobility aids. The purpose of this work is to develop the IW interface for providing more convenient and efficient interface to the people the disability in their limbs.MethodsThis paper proposes an intelligent wheelchair (IW) control system for the people with various disabilities. To facilitate a wide variety of user abilities, the proposed system involves the use of face-inclination and mouth-shape information, where the direction of an IW is determined by the inclination of the user's face, while proceeding and stopping are determined by the shapes of the user's mouth. Our system is composed of electric powered wheelchair, data acquisition board, ultrasonic/infra-red sensors, a PC camera, and vision system. Then the vision system to analyze user's gestures is performed by three stages: detector, recognizer, and converter. In the detector, the facial region of the intended user is first obtained using Adaboost, thereafter the mouth region is detected based on edge information. The extracted features are sent to the recognizer, which recognizes the face inclination and mouth shape using statistical analysis and K-means clustering, respectively. These recognition results are then delivered to the converter to control the wheelchair.Result & conclusionThe advantages of the proposed system include 1) accurate recognition of user's intention with minimal user motion and 2) robustness to a cluttered background and the time-varying illumination. To prove these advantages, the proposed system was tested with 34 users in indoor and outdoor environments and the results were compared with those of other systems, then the results showed that the proposed system has superior performance to other systems in terms of speed and accuracy. Therefore, it is proved that proposed system provided a friendly and convenient interface to the severely disabled people.
---
paper_title: Motor imagery and action observation: Modulation of sensorimotor brain rhythms during mental control of a brain–computer interface

paper_content:

Abstract Objective This study investigates the impact of a continuously presented visual feedback in the form of a grasping hand on the modulation of sensorimotor EEG rhythms during online control of a brain–computer interface (BCI). Methods Two groups of participants were trained to use left or right hand motor imagery to control a specific output signal on a computer monitor: the experimental group controlled a moving hand performing an object-related grasp (‘realistic feedback’), whereas the control group controlled a moving bar (‘abstract feedback’). Continuous feedback was realized by using the outcome of a real-time classifier which was based on EEG signals recorded from left and right central sites. Results The classification results show no difference between the two feedback groups. For both groups, ERD/ERS analysis revealed a significant larger ERD during feedback presentation compared to an initial motor imagery screening session without feedback. Increased ERD during online BCI control was particularly found for the lower alpha (8–10 Hz) and for the beta bands (16–20, 20–24 Hz). Conclusions The present study demonstrates that visual BCI feedback clearly modulates sensorimotor EEG rhythms. When the feedback provides equivalent information on both the continuous and final outcomes of mental actions, the presentation form (abstract versus realistic) does not influence the performance in a BCI, at least in initial training sessions. Significance The present results are of practical interest for classifier development and BCI use in the field of motor restoration.
---
paper_title: When mind meets machine

paper_content:

A new wave of brain–machine interfaces helps disabled people connect with the outside world
---
paper_title: Portable single-channel NIRS-based BMI system for motor disabilities' communication tools

paper_content:

A portable near-infrared spectroscopy (NIRS) -based brain-machine Interface (BMI) system featuring single-channel probe, BMI controller and Infrared-emission apparatus was developed. As a switching technology for external devices, the threshold logic was proposed, which detects the blood volume change in the operator's frontal lobe. Experiments showed that the operator was able to change the TV programs or get forward the toy robot within 16 s (the mean is 11.77 s and the standard deviation is 2.35 s) after the mental calculation. In addition, the menu selection program was proposed for motor disabilities and the preliminary test showed that he could successively select the sentence from several candidates. It was shown that this system would provide the external device's control capabilities for motor disabilities.
---
paper_title: A binary method for simple and accurate two-dimensional cursor control from EEG with minimal subject training

paper_content:

Background ::: Brain-computer interfaces (BCI) use electroencephalography (EEG) to interpret user intention and control an output device accordingly. We describe a novel BCI method to use a signal from five EEG channels (comprising one primary channel with four additional channels used to calculate its Laplacian derivation) to provide two-dimensional (2-D) control of a cursor on a computer screen, with simple threshold-based binary classification of band power readings taken over pre-defined time windows during subject hand movement.
---
paper_title: Brain–computer interface using a simplified functional near-infrared spectroscopy system

paper_content:

A brain–computer interface (BCI) is a device that allows a user to communicate with external devices through thought processes alone. A novel signal acquisition tool for BCIs is near-infrared spectroscopy (NIRS), an optical technique to measure localized cortical brain activity. The benefits of using this non-invasive modality are safety, portability and accessibility. A number of commercial multi-channel NIRS system are available; however we have developed a straightforward custom-built system to investigate the functionality of a fNIRS-BCI system. This work describes the construction of the device, the principles of operation and the implementation of a fNIRS-BCI application, 'Mindswitch' that harnesses motor imagery for control. Analysis is performed online and feedback of performance is presented to the user. Mindswitch presents a basic 'on/off' switching option to the user, where selection of either state takes 1 min. Initial results show that fNIRS can support simple BCI functionality and shows much potential. Although performance may be currently inferior to many EEG systems, there is much scope for development particularly with more sophisticated signal processing and classification techniques. We hope that by presenting fNIRS as an accessible and affordable option, a new avenue of exploration will open within the BCI research community and stimulate further research in fNIRS-BCIs.
---
paper_title: A brain-computer interface with vibrotactile biofeedback for haptic information

paper_content:

BackgroundIt has been suggested that Brain-Computer Interfaces (BCI) may one day be suitable for controlling a neuroprosthesis. For closed-loop operation of BCI, a tactile feedback channel that is compatible with neuroprosthetic applications is desired. Operation of an EEG-based BCI using only vibrotactile feedback, a commonly used method to convey haptic senses of contact and pressure, is demonstrated with a high level of accuracy.MethodsA Mu-rhythm based BCI using a motor imagery paradigm was used to control the position of a virtual cursor. The cursor position was shown visually as well as transmitted haptically by modulating the intensity of a vibrotactile stimulus to the upper limb. A total of six subjects operated the BCI in a two-stage targeting task, receiving only vibrotactile biofeedback of performance. The location of the vibration was also systematically varied between the left and right arms to investigate location-dependent effects on performance.Results and ConclusionSubjects are able to control the BCI using only vibrotactile feedback with an average accuracy of 56% and as high as 72%. These accuracies are significantly higher than the 15% predicted by random chance if the subject had no voluntary control of their Mu-rhythm. The results of this study demonstrate that vibrotactile feedback is an effective biofeedback modality to operate a BCI using motor imagery. In addition, the study shows that placement of the vibrotactile stimulation on the biceps ipsilateral or contralateral to the motor imagery introduces a significant bias in the BCI accuracy. This bias is consistent with a drop in performance generated by stimulation of the contralateral limb. Users demonstrated the capability to overcome this bias with training.
---
paper_title: When mind meets machine

paper_content:

A new wave of brain–machine interfaces helps disabled people connect with the outside world
---
paper_title: Review of Wireless and Wearable Electroencephalogram Systems and Brain-Computer Interfaces – A Mini-Review

paper_content:

Biomedical signal monitoring systems have rapidly advanced in recent years, propelled by significant advances in electronic and information technologies. Brain-computer interface (BCI) is one of the important research branches and has become a hot topic in the study of neural engineering, rehabilitation, and brain science. Traditionally, most BCI systems use bulky, wired laboratory-oriented sensing equipments to measure brain activity under well-controlled conditions within a confined space. Using bulky sensing equipments not only is uncomfortable and inconvenient for users, but also impedes their ability to perform routine tasks in daily operational environments. Furthermore, owing to large data volumes, signal processing of BCI systems is often performed off-line using high-end personal computers, hindering the applications of BCI in real-world environments. To be practical for routine use by unconstrained, freely-moving users, BCI systems must be noninvasive, nonintrusive, lightweight and capable of online signal processing. This work reviews recent online BCI systems, focusing especially on wearable, wireless and real-time systems.
---
paper_title: Surgeon responsibility in the era of “outrageous science”

paper_content:

Numerous times in the history of mankind there has been a prolific outpouring of scientific discovery, recently and most notably during the Renaissance and the Industrial Revolution. Currently, with the Information Age, another revolution in science is occurring. However, the nature of current discoveries is so far beyond the innovations of the past that the term ‘‘outrageous science’’ aptly applies. The term outrageous means ‘‘exceeding established or reasonable limits; improbable; extraordinary’’ [12]. Why should this be of concern to surgeons? First and most importantly, there are numerous technologies outside the immediate interest or view of surgeons that will either require surgeons to implement or have an impact on the way surgery is performed, possibly even replacing current methods. However, this is a rather egocentric approach to the problem. The changes taking place go directly to the heart of medicine, which is the care and nurturing of our fellow man. Medical technologies are accelerating exponentially, such that the moral and ethical issues provoked will require decades to resolve (Fig. 1). These issues focus on the most fundamental questions, for example: What does it mean to be human? How long should a person live? The following discourse samples some of the incredible discoveries emerging from the laboratory, speculates on their development trajectory, and posits the fundamental moral and ethical issues that pose the major challenges for the coming decades. Other technologies with equally profound effects, such as teleportation, cold fusion for energy, and direct communication from the mind, do not have a scientific basis at this time, and are therefore beyond current speculation, although a sudden scientific breakthrough could instantly project them into the middle of controversy. As an example of such a disruptive change, exactly such an event occurred with human cloning. Seemingly from out of nowhere, the cloning of Dolly the sheep was announced. Shortly thereafter, the French scientist Brigett Boisselier proclaimed the first human clone. There was an immediate public outcry and a political knee-jerk reaction. All nations of the world, except three, agreed not to do research in human cloning. However, three nations currently have state-sponsored human cloning (including embryonic stem cells): China, Korea, and Switzerland. The moral and ethical consequences are profound and currently are being discussed worldwide. What happens if the clone has a severe abnormality? Will it be discarded? Should clones have all the same rights as natural born humans? Will we make clones without brains in order to have ‘‘spare parts’’? Why does China need to create clones? Do they not already have enough children born every day? Human cloning is happening in the present, but what might the future hold? We touch on a number of technologies currently emerging from the laboratories and speculate on the possible inevitable consequence of their full development, as well as the profound moral and ethical issues associated with these technologies.
---
paper_title: Principles of neural ensemble physiology underlying the operation of brain–machine interfaces

paper_content:

Research on brain-machine interfaces has been ongoing for at least a decade. During this period, simultaneous recordings of the extracellular electrical activity of hundreds of individual neurons have been used for direct, real-time control of various artificial devices. Brain-machine interfaces have also added greatly to our knowledge of the fundamental physiological principles governing the operation of large neural ensembles. Further understanding of these principles is likely to have a key role in the future development of neuroprosthetics for restoring mobility in severely paralysed patients.
---
paper_title: Assistive technology and robotic control using motor cortex ensemble-based neural interface systems in humans with tetraplegia

paper_content:

This review describes the rationale, early stage development, and initial human application of neural interface systems (NISs) for humans with paralysis. NISs are emerging medical devices designed to allow persons with paralysis to operate assistive technologies or to reanimate muscles based upon a command signal that is obtained directly from the brain. Such systems require the development of sensors to detect brain signals, decoders to transform neural activity signals into a useful command, and an interface for the user. We review initial pilot trial results of an NIS that is based on an intracortical microelectrode sensor that derives control signals from the motor cortex. We review recent findings showing, first, that neurons engaged by movement intentions persist in motor cortex years after injury or disease to the motor system, and second, that signals derived from motor cortex can be used by persons with paralysis to operate a range of devices. We suggest that, with further development, this form of NIS holds promise as a useful new neurotechnology for those with limited motor function or communication. We also discuss the additional potential for neural sensors to be used in the diagnosis and management of various neurological conditions and as a new way to learn about human brain function.
---

Title: Neuroengineering Tools/Applications for Bidirectional Interfaces, Brain–Computer Interfaces, and Neuroprosthetic Implants – A Review of Recent Progress

Section 1: Introduction
Description 1: This section introduces the central nervous system damage and the emerging field of neuroengineering, outlining the scope of the review and the potential clinical applications of neuroengineering tools.

Section 2: Bidirectional Interfaces
Description 2: This section elaborates on the mechanisms and techniques for recording and relaying information from and to the brain, including the challenges and solutions related to long-term clinical viability and biocompatibility.

Section 3: Data Recording
Description 3: This section discusses how brain-computer interfaces receive information, including the differences between non-invasive and invasive techniques and the requirements for extracting neural activity patterns.

Section 4: Non-Invasive Measuring of Brain Activity
Description 4: This section details non-invasive methods for recording brain activity, emphasizing their temporal and spatial resolutions and summarizing the common techniques used.

Section 5: Invasive Measuring of Brain Activity
Description 5: This section covers invasive methods for recording brain activity, highlighting the benefits of high signal-to-noise ratios and the surgical requirements.

Section 6: The Glial Response
Description 6: This section describes the acute and chronic injury responses of the central nervous system to implanted devices, explaining the role of gliosis and other immune responses.

Section 7: Producing Long-Term Clinical Viability
Description 7: This section examines the major obstacles to achieving long-term clinical viability for neuroprosthetics, focusing on biocompatibility and innovative solutions.

Section 8: Coatings
Description 8: This section explores the use of biomaterials and coatings to enhance the integration and performance of neural implants.

Section 9: Implant Fabrication Materials
Description 9: This section provides an overview of the materials used for fabricating neural implants and their properties.

Section 10: Physical Shapes, Geometries, and Characteristics
Description 10: This section discusses the impact of electrode shapes, geometries, and surface characteristics on their performance and biocompatibility.

Section 11: The Transfer of Recorded Data
Description 11: This section details the methods for transferring recorded data from neural implants, including the use of IPGs and wireless telemetry.

Section 12: Sensory Feedback to the CNS
Description 12: This section investigates the techniques for providing sensory feedback from neuroprosthetic devices to the central nervous system.

Section 13: Neuroprosthetics
Description 13: This section provides an overview of different types of neuroprosthetics, including their operation and the challenges involved.

Section 14: Visual Prosthetics
Description 14: This section focuses on the development and operation of visual prosthetics, discussing the methods for restoring rudimentary vision.

Section 15: Auditory Prosthetics
Description 15: This section discusses cochlear and other auditory implants used for restoring hearing, along with their success rates and limitations.

Section 16: Wheelchair Use
Description 16: This section covers the development and use of intelligent wheelchairs operated by brain activity or other user-dependent interfaces.

Section 17: Interaction with Robots
Description 17: This section examines the control of robotic devices through brain activity, highlighting the potential for real-time operations.

Section 18: Interaction with Personal Computers
Description 18: This section discusses the use of brain-computer interfaces for controlling computers, including cursor and keyboard operations.

Section 19: Conclusion
Description 19: This section summarizes the advancements in neuroengineering, the future potential of various neuroprosthetic applications, and the ongoing challenges in the field.