Physiology_Levy

Physiology_Levy. Fig. 9.26 ). Thus nystagmus can be defined as oscillatory or rhythmic movements of the eye in which there is a fast phase and a slow phase. The nystagmus is named according to the direction of the fast phase because the fast phase is more easily observed. In addition to being induced physiologically by VOR or OKR stimuli, nystagmus can result from damage to the vestibular circuits, either in the periphery (e.g., cranial nerve •Fig. 9.26 Nystagmogram Showing Eye Movements That Occur During Nystagmus. Theplotshowsaleftnystagmusbecausethefastphaseisdirectedtowardtheleft(downwardonthegraph). VIII) or centrally (e.g., vestibular nuclei), and can be an informative diagnostic symptom.


Physiology_Levy

Physiology_Levy. VIII) or centrally (e.g., vestibular nuclei), and can be an informative diagnostic symptom. Conjugate eye movement is movement of both eyes in the same direction and in an equal amount. Such coordination allows a target to be maintained on both foveae during eye movement and is necessary to maintain binocular vision without diplopia (double vision). However, when objects are close (<30 m), maintaining a target on both foveae requires non-identical movements of the two eyes. Such disjunctive, or vergence, movements are also necessary for fixation of both eyes on objects that are approaching or receding. Stimuli that trigger vergence movements are diplopia and blurry images. It should be noted that when tracking an approaching object in addition to convergence movements, the lens accommodates for near vision, and pupillary constriction occurs. Motor Neurons of the Extraocular Muscles


Physiology_Levy

Physiology_Levy. Motor Neurons of the Extraocular Muscles Three cranial nerve nuclei supply the extraocular muscles: oculomotor, trochlear, and abducens nuclei. These three nuclei are sometimes referred to collectively as the oculomotor nuclei; however, the context (the specific nucleus or all three) should be clear. Motor neurons for the ipsilateral medial and inferior recti, ipsilateral inferior oblique, and contralateral superior rectus muscles reside in the oculomotor nucleus; those for the contralateral superior oblique muscle reside in the trochlear nucleus; and those for the ipsilateral lateral rectus muscle are located in the abducens nucleus. These motor neurons form some of the smallest motor units (1 : 10 nerve-to-muscle ratio), which is consistent with the very fine control needed for precise eye movement.


Physiology_Levy

Physiology_Levy. An important point regarding motor neurons innervating the extraocular muscles is that most have spontaneous activity when the eye is in the primary position (looking straight ahead), and their firing rate is correlated with eye position and velocity. This spontaneous activity allows the antagonist muscle pairs to act in a push-pull manner, which increases the responsiveness of the system. That is, as motor neurons innervating one muscle are activated and cause increased contraction, those innervating its antagonist are inhibited, which leads to relaxation. In addition to motor neurons, the abducens nuclei have internuclear neurons. These neurons project, via the medial longitudinal fasciculus, to medial rectus motor neurons in the contralateral oculomotor nucleus. As described later, this projection facilitates the coordinated action of the medial and lateral recti muscles that is needed for conjugate movements, such as those that occur in the VOR.


Physiology_Levy

Physiology_Levy. Circuits Underlying the Vestibuloocular Reflex The VOR acts to counter head motion by causing rotation of the eyes in the opposite direction. There are separate circuits for rotational and translational movement of the head. The sensors for the former are the semicircular canals, and the sensors for the latter are the otoliths (the utricle and saccule). The circuits for the angular VOR are more straightforward (but still complex), and this section focuses on these pathways to illustrate how this reflex works; however, the basic scheme is the same: Vestibular afferent fibers go to vestibular nuclei, the vestibular nuclei in turn project to the various oculomotor nuclei, and motor neurons in the oculomotor nuclei give rise to axons that innervate the extraocular muscles. What varies are the specific vestibular and oculomotor nuclei that are involved.


Physiology_Levy

Physiology_Levy. With regard to the angular VOR pathways, the pathway for generating horizontal eye movement originates in the horizontal canals, and the analogous one for vertical movement originates in the anterior and posterior canals. Fig.


Physiology_Levy

Physiology_Levy. Fig. 9.27A shows the basic circuit for the horizontal VOR. Note that only the major central circuits originating in the left horizontal canal and vestibular nuclei are shown; however, mirror image pathways arise from the right canal and vestibular nuclei. Vestibular afferent fibers involved in the horizontal VOR pathway synapse primarily in the medial vestibular nucleus, which projects to the abducens nucleus bilaterally; inhibitory neurons project ipsilaterally, and excitatory ones project contralaterally. Control of the medial rectus muscle is achieved by abducens internuclear neurons that project from the abducens to the part of the oculomotor nucleus controlling the medial rectus muscle. Note the double decussation of this pathway results in aligning of the responses of functional synergists (e.g., the left medial rectus with the right lateral rectus).


Physiology_Levy

Physiology_Levy. The vertical VOR pathway involves primarily the superior vestibular nucleus, which has direct bilateral projections to the oculomotor nucleus. Consider what happens in the horizontal canal pathway when there is head rotation to the left, as shown in Fig. 9.27B. Leftward head rotation would cause the visual image to slip to the right. However, compensation by the VOR would be triggered by depolarization of the hair cells of the left canal in response to the angular acceleration


Physiology_Levy

Physiology_Levy. CHAPTER 9 Organization of Motor Function •Fig. 9.27 Circuits Underlying the Horizontal Vestibuloocular Reflex (VOR). A, Thevestibularnucleireceiveexcitatoryinputfromtheafferentfibersofthehorizontalcanalandprojecttotheabducens(cranialnerveVI)nucleus.Thisnucleusinnervatesthelateralrectusmuscleandprojectstothecontralateraloculomotor(cranialnerveIII)nucleus,whichcontrolsthemedialrectusmuscle.Excitatoryneuronsareshowninred; inhibitoryones,inblue. Notethatonlythemajorpathwaysoriginatingintheleftvestibularnucleiareshown.Forclarity,onlythebeginningsofmirrorimagepathwaysfromtherightvestibularnucleiareshown(dotted lines). B, FlowofactivityintheVORcircuitryinducedbyleftwardheadrotation.Increasedaxonalthicknessindicatesincreasedactivity;thinneraxonsindicatedecreasedactivityincomparisonwithlevelsatrest(A).


Physiology_Levy


Physiology_Levy

Physiology_Levy. Fig. 8.27 ). The depolarized hair cells cause increased activity in the left vestibular afferent fibers and thereby excite neurons of the left medial vestibular nucleus. These include excitatory neurons that project to the contralateral abducens nucleus and synapse with both motor neurons and internuclear neurons. Excitation of the motor neurons leads to contraction of the right lateral rectus muscle and rotation of the right eye to the right, whereas excitation of the internuclear neurons of the right abducens nucleus leads to excitation of the medial rectus motor neurons in the left oculomotor nucleus, thus causing the left eye to rotate to the right as well.


Physiology_Levy

Physiology_Levy. Along the pathway starting with the inhibitory vestibular neurons that project from the left medial vestibular nucleus to the ipsilateral abducens nucleus, the activity of these cells leads to inhibition of motor neurons to the left lateral rectus muscle and motor neurons to the right medial rectus muscle (the latter via internuclear neurons to the right oculomotor nucleus). Consequently, these muscles relax, thereby facilitating rotation of the eyes to the right. Thus the eye is being pulled by the increased tension of one set of muscles and “pushed” by the release of tension in the antagonist set of muscles. Note again that the mirror image pathways originating from the right canal have been left out of


Physiology_Levy

Physiology_Levy. Note again that the mirror image pathways originating from the right canal have been left out of Fig. 9.27 for clarity, but the changes in activity through them with leftward head rotation would be exactly the opposite, and thus they would function synergistically with those that are shown. As an exercise, work out the resulting changes in activity through these circuits. Remember that leftward head rotation hyper-polarizes the hair cells of the right canal, thereby leading to a decrease in right vestibular afferent activity and disfacilitation of the right vestibular nuclear neurons.


Physiology_Levy

Physiology_Levy. Now, consider the commissural fibers that connect the two medial vestibular nuclei are excitatory but end on local inhibitory interneurons of the contralateral vestibular nucleus and thus inhibit the projection neurons of that nucleus. This pathway reinforces the actions of the contra-lateral vestibular afferent fibers on their target vestibular nuclear neurons. In the aforementioned example, commissural cells in the left vestibular nucleus are activated and therefore cause active inhibition of the right medial vestibular nuclei projection neurons, which reinforces the disfacilitation caused by the decrease in right afferent activity. In fact, this commissural pathway is powerful enough to modulate the activity of the contralateral vestibular nuclei even after unilateral labyrinthectomy, which destroys the direct vestibular afferent input to these nuclei.


Physiology_Levy

Physiology_Levy. Of importance is that superimposed on the brainstem circuits is the cerebellum. Parts of the vermis and flocculonodular lobe receive primary vestibular afferent fibers or secondary vestibular afferent fibers (axons of the vestibular nuclear neurons), or both, and in turn project back to the vestibular nuclei directly and via a disynaptic pathway involving the fastigial nucleus. The exact role of these cerebellar circuits in generating the VOR is much debated, but they are critical inasmuch as damage to them leads to abnormal eye movement, such as spontaneous nystagmus, and other symptoms of vestibular dysfunction.


Physiology_Levy

Physiology_Levy. The stimulus eliciting the OKR is visual (retinal slip), and so photoreceptors are the start of the reflex arc. Key brainstem centers for this reflex lie in the tegmentum and pretectal region of the rostral midbrain. They are the nucleus of the optic tract (NOT) and a group of nuclei collectively known as the accessory optic nuclei (AON). Direction-selective, motion-sensitive retinal ganglion cells are a major afferent source carrying visual information to these nuclei. In addition, input comes from primary and higher order visual cortical areas in the occipital and temporal lobes. These latter afferent sources are particularly important in primates and humans. Cells of the NOT and AON have large receptive fields, and their responses are selective for the direction and speed of movement of the visual scene. Of interest is that the preferred directions of movement of the NOT/AON cells correspond closely to motion caused by rotation about axes perpendicular to the semicircular canals,


Physiology_Levy

Physiology_Levy. of the visual scene. Of interest is that the preferred directions of movement of the NOT/AON cells correspond closely to motion caused by rotation about axes perpendicular to the semicircular canals, thereby facilitating coordination of the VOR and OKR to produce stable retinal images.


Physiology_Levy

Physiology_Levy. The efferent connections of these nuclei are numerous and complex and not fully understood. There are polysynaptic pathways to the oculomotor and abducens nuclei and monosynaptic input to the vestibular nuclei, which allow interaction with the VOR. There are projections to various precerebellar nuclei, including the inferior olivary nucleus and basilar pontine nuclei. These pathways then loop through the flocculus and back to the vestibular nuclei. In sum, via several pathways operating in parallel, activity ultimately arrives at the various oculomotor nuclei whose motor neurons are activated, and proper counterrotation of the eyes results. Saccades are generated in response to activity in the superior colliculus or the cerebral cortex (frontal eye fields and


Physiology_Levy

Physiology_Levy. Saccades are generated in response to activity in the superior colliculus or the cerebral cortex (frontal eye fields and ClinicaltestingoflabyrinthinefunctionisdoneeitherbyrotatingthepatientinaBáránychairtoactivatethelabyrinthsinbothearsorbyintroducingcoldorwarmwaterintotheexternalauditorycanalofoneear(caloric test). WhenapersonisrotatedinaBáránychair,nystagmusdevelopsduringtherotation.Thedirectionofthefastphaseofthenystagmusisinthesamedirectionastherotation.Whentherotationofthechairishalted,nystagmusintheoppositedirectiondevelops(postrotatorynystagmus)becausestoppingarotationhasthesameeffectasacceleratingintheoppositedirection.


Physiology_Levy

Physiology_Levy. (“coldopposite,warmsame”).Inotherwords,coldwaterinoneearresultsinafastphaseofnystagmustowardtheoppositeside,andwarmwatercausesafastphasetowardthesameside.


Physiology_Levy

Physiology_Levy. posterior parietal areas). Activity in the superior colliculus is related to computation of the direction and amplitude of the saccade. Indeed, the deep layers of the superior colliculus contain a topographic motor map of saccade locations. From the superior colliculus, information is forwarded to distinct sites for control of horizontal and vertical saccades, referred to as the horizontal and vertical gaze centers, respectively. The horizontal gaze center consists of neurons in the paramedian pontine reticular formation, in the vicinity of the abducens nucleus (


Physiology_Levy

Physiology_Levy. Fig. 9.28A ). The vertical gaze center is located in the reticular formation of the midbrain: specifically, the rostral interstitial nucleus of the medial longitudinal fasciculus and the interstitial nucleus of Cajal. Because the circuitry and operation of the horizontal gaze center are better understood than those of the vertical gaze center, it is discussed here in detail. However, cells showing analogous activity patterns have been described in the vertical gaze center. Fig. 9.28A is an overview of the neural circuitry by which saccades are generated, and Fig. 9.28B shows the activity of certain types of neurons found in the gaze center that are responsible for horizontal saccades. Each horizontal gaze center has excitatory burst neurons that project to motor neurons in the ipsilateral abducens nucleus and to the internuclear neurons (which excites medial rectus motor


Physiology_Levy

Physiology_Levy. CHAPTER 9 Organization of Motor Function neurons in the contralateral oculomotor nucleus). It also has inhibitory burst neurons that inhibit the contralateral abducens. These burst neurons are capable of extremely high bursts of spikes (up to 1000 Hz). Moreover, the gaze center has neurons showing tonic activity and burst-tonic activity. Normally, both inhibitory and excitatory burst neurons are inhibited by omnipause neurons located in the nucleus of the dorsal raphe. When a saccade is to be made, activity from the frontal eye fields or the superior colliculus, or both, leads to inhibition of the omnipause cells and excitation of the burst cells on the contralateral side. The resulting high-frequency bursts in the excitatory burst neurons provide a powerful drive to motor neurons of the ipsilateral lateral rectus and contralateral medial rectus muscles (see


Physiology_Levy

Physiology_Levy. Fig. 9.28A ); at the same time, inhibitory burst neurons enable relaxation of the antagonists. The initial bursts of these neurons allow strong contraction of the appropriate extraocular muscles, which overcomes the viscosity of the extraocular muscle and enables rapid movement to occur.


Physiology_Levy

Physiology_Levy. Smooth pursuit involves tracking a moving target with the eyes (Fig. 9.29 ). Visual information about target velocity is processed in a series of cortical areas, including the visual cortex in the occipital lobe, several temporal lobe areas, and the frontal eye fields. In the past, the frontal eye fields were thought to be related only to control of saccades, but more recent evidence has shown that there are distinct regions within the frontal eye fields dedicated to either saccade production or smooth pursuit. Indeed, there may be two distinct cortical networks, each specialized for one of these types of eye movement. Cortical activity from multiple cortical areas is fed to the cerebellum via parts of the pontine nuclei and nucleus reticularis tegmenti pontis. Specific areas in the cerebellum—namely, parts of the posterior lobe vermis, the flocculus, and the paraflocculus—receive this input, and they in turn project to the vestibular nuclei. From the vestibular nuclei, activity can


Physiology_Levy

Physiology_Levy. parts of the posterior lobe vermis, the flocculus, and the paraflocculus—receive this input, and they in turn project to the vestibular nuclei. From the vestibular nuclei, activity can then be forwarded to the oculomotor, abducens, and trochlear nuclei, as was described for the VOR earlier.


Physiology_Levy

Physiology_Levy. The neural circuits underlying vergence movements are not well known. There are premotor neurons (neurons that feed onto motor neurons) located in the brainstem areas surrounding the various oculomotor nuclei. In some cortical visual areas and the frontal eye fields, there are neurons whose activity is related to the disparity of the image on the two retinas or to the variation of the image during vergence movements. How vergence signals in these cortical areas feed into the brainstem premotor neurons is not clear. The cerebellum also appears to play a role in vergence movements because cerebellar lesions impair this type of eye movement. Note that lesions of the medial longitudinal fasciculus that result in a loss of the VOR do not compromise vergence.


Physiology_Levy


Physiology_Levy

Physiology_Levy. CHAPTER 9 Organization of Motor Function •Fig. 9.29 Smooth Pursuit Pathways. Thestimulusforsmoothpursuiteyemovementisamovingvisualtarget.Thiscausesactivitytoflowthroughthecircuitrydiagramedinthefigureandleadstomaintenanceofthefoveaonthetarget.FEF,frontaleyefield;LGN,lateralgeniculatenucleus;MSTandMT,higherordervisualassociationareas;MVN,medialvestibularnucleus;NRTP,nucleusreticularistegmentipontis;SEF,supplementaryeyefield;V1,primaryvisualcortex.Retina LGN V1 MT MST Pontine nuclei FEF SEF NRTP Flocculus paraflocculus Vermis MVN y-group Fastigial nucleus Oculomotor nuclei Cortical areas involved in processing object motion Brainstem and cerebellar areas involved in transforming sensory-related signal into motor command Motor commands to eye muscles 1.


Physiology_Levy

Physiology_Levy. The extrafusal skeletal muscle fibers are innervated by α motor neurons. A motor unit consists of a single α motor neuron and all the muscle fibers with which it synapses. Motor unit size varies greatly among muscles; small motor units allow finer control of muscle force. 2. The size principle refers to the orderly recruitment of α motor neurons according to their size, from smallest to largest. Because smaller motor neurons connect to weaker motor units, the relative fineness of motor control is similar for weak and strong contractions. 3. A reflex is a simple, stereotyped motor response to a stimulus. A reflex arc includes the afferent fibers, interneurons, and motor neurons responsible for the reflex. 4.


Physiology_Levy

Physiology_Levy. 3. A reflex is a simple, stereotyped motor response to a stimulus. A reflex arc includes the afferent fibers, interneurons, and motor neurons responsible for the reflex. 4. Muscle spindles are complex sensory receptors found in skeletal muscle. They lie parallel to extrafusal muscle fibers, and they contain nuclear bag and nuclear chain intrafusal muscle fibers. By being in parallel to the main muscle, the spindle can detect changes in muscle length. 5. Group Ia afferent fibers form primary endings on nuclear bag1, bag2, and chain fibers, and group II fibers form secondary endings on nuclear chain and bag2 fibers. 6. Primary endings demonstrate both static and dynamic responses that signal muscle length and rate of change in muscle length. Secondary endings demonstrate only static responses and signal only muscle length. 7.


Physiology_Levy

Physiology_Levy. 7. The intrafusal muscle fibers associated with muscle spindles are innervated by γ motor neurons. Contraction of intrafusal fibers does not directly cause significant changes in muscle tension or length; however, when the level of tension in these fibers is adjusted, γ motor neurons influence the sensitivity of the muscle spindle to stretch. 8. Golgi tendon organs are located in the tendons of muscles and are thus arranged in series with the muscle. They are supplied by group Ib afferent fibers. Their in-series relationship means that tendon organs can detect the force level generated by the muscle, whether it is due to passive stretch or to active contraction of the muscle. 9. The phasic stretch (or myotatic) reflex includes (1) a monosynaptic excitatory pathway from group Ia afferent fibers in muscle spindles to α motor neurons that supply the same and synergistic muscles and (2) a disynaptic inhibitory pathway to antagonistic motor neurons. 10.


Physiology_Levy

Physiology_Levy. 10. The inverse myotatic reflex is evoked by Golgi tendon organs. Afferent volleys in group Ib fibers from a given muscle cause disynaptic inhibition of α motor neurons to the same muscle, and they excite α motor neurons to antagonist muscles. 11. The flexion reflex is an important protective response because it acts to withdraw a limb from damaging stimuli. The reflex is evoked by volleys in afferent fibers that supply various receptors, particularly nociceptors. Via polysynaptic pathways, these volleys cause excitation of flexor motor neurons and inhibition of extensor motor neurons ipsilaterally. Concurrently, the opposite pattern of action (inhibition of flexor and excitation of extensor motor neurons) occurs contralaterally and is referred to as the crossed extension reflex. 12.


Physiology_Levy

Physiology_Levy. 12. Descending pathways can be subdivided into (1) a lateral system, which ends on motor neurons to limb muscles and on the lateral group of interneurons, and (2) a medial system, which ends on the medial group of interneurons. 13. The lateral system includes the lateral corticospinal tract and part of the corticobulbar tract. These pathways influence the contralateral motor neurons that supply the musculature of the limbs, especially of the digits, and the muscles of the lower part of the face and the tongue. 14. The medial system includes the ventral corticospinal, lateral and medial vestibulospinal, reticulospinal, and tectospinal tracts. These pathways affect mainly posture and provide the motor background for movement of the limbs and digits. 15.


Physiology_Levy

Physiology_Levy. 15. Locomotion is triggered by commands relayed through the midbrain locomotor center. However, central pattern generators formed by spinal cord circuits and influenced by afferent input provide for the detailed organization of locomotor activity. 16. Voluntary movements depend on interactions among motor areas of the cerebral cortex, the cerebellum, and the basal ganglia. 17. Motor areas of the cerebral cortex are arranged as a parallel distributed network, in which each contributes to the various descending motor pathways. The areas primarily involved in body and head movement include the primary motor cortex, the premotor area, the supplementary motor cortex, and the cingulate motor areas. The frontal eye fields are important for eye movement and help initiate voluntary saccades. 18.


Physiology_Levy

Physiology_Levy. 18. Individual corticospinal neurons discharge before voluntary contractions of related muscles occur. The discharges are typically related to contractile force rather than to joint position. However, the activity of an individual neuron may encode different parameters of a movement at different times in relation to the execution of that movement. 19. The population activity of motor cortex neurons can be used to predict the direction of upcoming movements. 20. The cerebellum influences the rate, range, force, and direction of movements. It also influences muscle tone and posture, as well as eye movement and balance. 21. The intrinsic circuitry of the cerebellum is remarkably uniform. Differences in function of different parts of the cerebellum arise largely as a result of differing afferent sources and efferent targets. 22.


Physiology_Levy

Physiology_Levy. 22. Anatomical and physiological techniques have shown that the cerebellar cortex may be divided into many functionally distinct, longitudinally running compartments. 23. Most of the input to the cerebellum is through pathways that end as mossy fibers. Mossy fibers excite granule cells, which in turn can evoke single action potentials, called simple spikes, in Purkinje cells, whose axons form the only output pathway from the cerebellar cortex. 24. The projections of the inferior olivary nucleus to the cerebellum end as climbing fibers and are the only source of them. Each Purkinje cell receives massive input from just one climbing fiber. As a result, each climbing fiber discharge produces a high-frequency burst of several action potentials, known as a complex spike, in the Purkinje cell. 25.


Physiology_Levy

Physiology_Levy. 25. Although complex spike activity is relatively rare in comparison to simple spike activity, complex spikes are precisely synchronized across populations of Purkinje cells, and because of the convergence of these cells onto cerebellar nuclear neurons, this synchronization may allow complex spike activity to significantly affect cerebellar output. Synchronization of complex spikes is the result of electrical coupling of inferior olivary neurons by gap junctions. 26. The basal ganglia include several deep telencephalic nuclei (including the caudate nucleus, putamen, and globus pallidus). The basal ganglia interact with the cerebral cortex, subthalamic nucleus, substantia nigra, and thalamus. 27.


Physiology_Levy

Physiology_Levy. 27. Activity transmitted from the cerebral cortex through the basal ganglia can either facilitate or inhibit the thalamic neurons that project to motor areas of the cortex, depending on the balance between direct and indirect basal ganglia pathways. When there is an imbalance of these two pathways, hyperkinetic or hypokinetic disorders occur. CHAPTER 9 Organization of Motor Function 28. Some types of eye movement help stabilize the view of the visual world. This is critical because visual acuity drops dramatically when the visual world moves, or slips, across the retina. Vestibuloocular and optokinetic movements help stabilize the visual world on the retina by compensating for movement of the head or external world (or both). Smooth pursuit movements allow tracking of a visual target so that it remains centered on the foveae. Eccles JC, Ito M, Szentagothai J. The Cerebellum as a Neuronal Machine. New York: Springer; 2013. (Original work published 1967.)


Physiology_Levy

Physiology_Levy. Eccles JC, Ito M, Szentagothai J. The Cerebellum as a Neuronal Machine. New York: Springer; 2013. (Original work published 1967.) Shadmehr R, Wise SP. The Computational Neurobiology of Reaching and Pointing: A Foundation for Motor Learning. Cambridge, MA: Bradford Books; 2004. Shepherd GM. Spinal cord. In: Synaptic Organization of the Brain. 5th ed. Oxford, UK: Oxford University Press; 2003: Chapter 3. 29. Saccades act to move a specific part of the visual scene to the fovea, the retinal area of highest acuity, for detailed inspection. 30. There are specialized circuits and areas in the brainstem for control of vertical and horizontal eye movements. These areas are used both by the cortex (when voluntary eye movements are made) and by the sensory input that initiates reflexive eye movement. Shepherd GM. Cerebellum. In: Synaptic Organization of the Brain. 5th ed. Oxford, UK: Oxford University Press; 2003: Chapter 7.


Physiology_Levy

Physiology_Levy. Shepherd GM. Cerebellum. In: Synaptic Organization of the Brain. 5th ed. Oxford, UK: Oxford University Press; 2003: Chapter 7. Shepherd GM. Basal ganglia. In: Synaptic Organization of the Brain. 5th ed. Oxford, UK: Oxford University Press; 2003: Chapter 9. Xiao J, Cerminara NL, Kotsurovskyy Y, et al. Systematic regional variations in Purkinje cell spiking patterns. PLoS ONE. 2014;9: e105633. Upon completion of this chapter, the student should be able to answer the following questions: 1. What is the basic layering pattern of the neocortex, and how do cortical inputs and outputs align with this layering pattern? What is the functional significance of the variation in the layering pattern between cortical areas? 2. What are the major functions of each of the lobes of the cerebrum? 3. How does the electroencephalogram (EEG) reflect cortical activity? What are evoked potentials? 4. How does cerebral dominance correlate with language and hand preference? 5.


Physiology_Levy

Physiology_Levy. 3. How does the electroencephalogram (EEG) reflect cortical activity? What are evoked potentials? 4. How does cerebral dominance correlate with language and hand preference? 5. What is aphasia, and what is compromised in the different types of aphasia? 6. How do synaptic and cellular processes support learning and memory? How is memory distributed in the brain? 7. What role does plasticity play in neural development and in response to damage of the nervous system?


Physiology_Levy

Physiology_Levy. n earlier chapters, the interaction of the nervous system with the body and the outside world was discussed in terms of the transduction and analysis of sensory events, the organization of motor function, and relatively simple central processes that link them, such as reflexes (e.g., the stretch reflex and the vestibuloocular reflex). The nervous system has other capabilities, so-called integrative or higher functions, that are less directly tied to specific sensory modalities or motor behavior. These functions, in particular, require interactions between different parts of the cerebral cortex, and, as is being increasingly recognized, between the cerebral cortex and other parts of the brain. The neural basis for some of these higher functions is discussed in this chapter. Because these functions (as well as sensory perception and voluntary motor function) are so highly dependent on the cerebral cortex, its basic organization is described first. The Cerebral Cortex


Physiology_Levy

Physiology_Levy. The Cerebral Cortex The human cerebral cortex occupies a volume of about 600 cm3 and has a surface area of 2500 cm2. The surface of the cortex is highly convoluted and folded into ridges known as gyri. Gyri are separated by grooves called sulci (if shallow) or fissures (if deep; see Fig. 4.7 ). This folding greatly increases the surface area of cortex that can be fit into the limited and fixed volume within the skull. Indeed, most of the cortex cannot be seen from the brain surface because of this folding. The cerebral cortex can be divided into the left and right hemispheres and subdivided into a number of lobes (Fig. 10.1 Fig. 4.7 ), including the frontal, parietal, temporal, and occipital lobes. The frontal and parietal lobes are separated by the central sulcus; both are separated from the temporal lobe by the lateral fissure. The occipital and parietal lobes are separated (on the medial surface of the hemisphere) by the parieto-occipital fissure (see Fig.


Physiology_Levy

Physiology_Levy. Fig. 10.1 ). Buried within the lateral fissure is another lobe, the insula (see Fig. 4.6A). A group of structures that make up the limbic lobe is on the medial aspect of the hemisphere, and its largest part, the hippocampal formation, is folded into the parahippocampal gyrus of the temporal lobe and cannot be seen from the surface of the brain. Activity in the two hemispheres of the cerebral cortex is coordinated by interconnections through the cerebral commissures. The bulk of the cortex is connected through the massive corpus callosum (see Figs. 4.9 10.1), and parts of the temporal lobes connect through the anterior commissure. There are three types of cerebral cortex: neocortex, archicortex, and paleocortex. The neocortex has six cortical layers (Fig. 10.2 ). In contrast, the archicortex has only three layers, and the paleocortex has four to five layers. In humans, approximately 90% of the cerebral cortex is neocortex. The Neocortex Neuronal Cell Types in the Neocortex


Physiology_Levy

Physiology_Levy. The Neocortex Neuronal Cell Types in the Neocortex A number of different neuronal cell types in the neocortex have been described (see Fig. 10.2 ). Pyramidal cells are the most abundant cell type and account for approximately 75% of neocortical neurons. Stellate cells and various other types of nonpyramidal neurons make up the balance. Pyramidal cells have a large triangular cell body, a long •Fig. 10.1 Lateral(A) andmedial(B) illustrationsofthelefthemisphereofthehumancerebrumwiththemajorfeatureslabeledandthelobesindicatedbycolor.R,G,B,andSindicate,respectively,therostrum,genu,body,andspleniumofthecorpuscallosum.(FromHainesDE[ed].Fundamental Neuroscience for Basic and Clinical Applications. 3rded.Philadelphia:ChurchillLivingstone;2006.) I. Molecular layer II. External granular layer III.External pyramidal layer IV. V. VI.Polymorphic layer Outer band of Baillarger Inner band of Baillarger


Physiology_Levy

Physiology_Levy. I. Molecular layer II. External granular layer III.External pyramidal layer IV. V. VI.Polymorphic layer Outer band of Baillarger Inner band of Baillarger Fig. 10.2 An Area of Neocortex Stained by Three Different Methods. TheNisslstain(center) showsthecellbodiesofallneuronsandrevealshowdifferenttypesaredistributedamongthesixlayers.TheGolgistain(left) showsonlyasampleoftheneuronalpopulationbutrevealsdetailsoftheirdendrites.TheWeigertstainformyelin(right) demonstratesverticallyorientedbundlesofaxonsenteringandleavingthecortexandhorizontallycoursingfibersthatinterconnectneuronswithinalayer.(FromBrodmann K.


Physiology_Levy

Physiology_Levy. K. Zellenbaues. Leipzig:JABarth;1909.) apical dendrite directed toward the cortical surface, and several basal dendrites. The cell’s axon emerges from the body opposite the apical dendrite, and those from the larger pyramidal cells project into the subcortical white matter. The axon may give off collateral branches as it descends through the cortex. The neurotransmitter of pyramidal cells is an excitatory amino acid (glutamate or aspartate). Stellate cells, often called granule cells, are interneurons with local connections. They have a small soma and numerous branched dendrites, although many have an apical dendrite and thus look like small pyramidal cells. Some are excitatory interneurons; these cells are abundant in layer IV of the cortex (described in the next section). Their axons remain in the same cortical region, and many ascend into the upper cortical layers. Some stellate cells are inhibitory inter-neurons whose neurotransmitter is gamma-aminobutyric acid (GABA).


Physiology_Levy

Physiology_Levy. Cytoarchitecture of Cortical Layers Each of the six layers of the neocortex has a characteristic cellular content (see Fig. 10.2 ). Layer I (molecular layer) has few neuronal cell bodies and contains mostly axon terminals synapsing on apical dendrites. Layer II (external granular layer) contains mostly stellate cells. Layer III (external pyramidal layer) consists mostly of small pyramidal cells. Layer IV (internal granular layer) contains mostly stellate cells and a dense matrix of axons. Layer V (internal pyramidal layer) is dominated by large pyramidal cells, the main source of cortical efferents to most subcortical regions. Layer VI (multiform layer) contains pyramidal, fusiform, and other types of cells. Most input to the cortex from other regions of the central nervous system (CNS) is relayed by neurons in the thalamus, the paleocortex has four to five layers. The paleocortex is located at the border between the archicortex and neocortex.


Physiology_Levy

Physiology_Levy. In humans, the hippocampal formation is part of the archicortex. It is folded into the temporal lobe and can be viewed only when the brain is dissected. The hippocampal cortex has three layers: the molecular, pyramidal cell, and polymorphic layers. They resemble layers I, V, and VI of the neocortex. The white matter covering the hippocampus is called the alveus, which contains hippocampal afferent and efferent fibers. The efferent axons coalesce to form the fornix (Fig. 10.4 Functions of the Lobes of the Cerebral Cortex There is no exact correspondence between the folds (lobes and gyri) of the cerebral cortex and function; nevertheless, some with the individual lobes of the cerebral hemispheres have a general association with function that helps clarify cortical organization.


Physiology_Levy

Physiology_Levy. One of the main functions of the frontal lobe is motor behavior. As discussed in , the motor, premotor, cingulate motor, and supplementary motor areas are located •Fig. 10.3 Brodmann’sareasinthehumancerebralcortex.(RedrawnfromCrosbyEC,etal.Correlative Anatomy of the Nervous System. NewYork:Macmillan;1962.)6312578910113825273029262834363523312433321237201919181817B •Fig. 10.4 Thehippocampusandtheamygdalaarelocatedonthemedialaspectofthetemporallobe.Thefornix,themajoroutputpathwayfromthehippocampus,projectstothemammillarybody,whichinturnconnectstotheanteriornucleusofthethalamusviathemammillothalamictract.Alsoillustratedarethecingulategyrus,thebasalforebrainarea(septalnuclei,bednucleusofthestriaterminalis,nucleusaccumbens),andtheprefrontalcortex.(FromPurvesD.Sleepandwakefulness.In:PurvesD,etal[eds].Neuroscience. 3rded.Sunderland,MA:Sinauer;2004.) in the frontal lobe, as is the frontal eye field. These areas are crucial for planning and executing motor behavior. Broca’s area, essential for


Physiology_Levy

Physiology_Levy. 3rded.Sunderland,MA:Sinauer;2004.) in the frontal lobe, as is the frontal eye field. These areas are crucial for planning and executing motor behavior. Broca’s area, essential for the generation of speech, is located in the inferior frontal gyrus of the dominant hemisphere for human language (almost always the left hemisphere, as explained later). In addition, the more anterior prefrontal cortex in plays a major role in personality and emotional behavior.


Physiology_Levy

Physiology_Levy. Bilateral lesions of the prefrontal cortex may be produced either by disease or by a surgical frontal lobotomy. Such lesions produce deficits in attention, difficulty in planning and problem solving, and inappropriate social behavior. Aggressive behavior is also lessened and the motivational-affective component of pain is reduced although pain sensation remains. Frontal lobotomies are rarely performed today because modern drug therapies provide more focal and effective management for mental illness and chronic pain.


Physiology_Levy

Physiology_Levy. The parietal lobe contains the somatosensory cortex (see ) and the adjacent parietal association cortex. The parietal association cortex gets information from somatosensory, visual, and auditory cortices and is involved in the processing, perception, and integration of sensory information. Connections with the frontal lobe allow somatosensory information to aid in voluntary motor activity. Somatosensory, visual, and auditory information can also be transferred to language centers, such as Wernicke’s area, as described later. Lesions in the left parietal lobe can result in Gerstmann’s syndrome, which includes a person’s inability to name his or her fingers (or those of another) and a loss of the ability to perform numerical calculations. The right parietal lobe is involved in determining spatial context. Localized lesions can result in the neglect syndrome, in which the patient seems unaware of the left side of his or her body and of persons, objects, and events on his or her left.


Physiology_Levy

Physiology_Levy. spatial context. Localized lesions can result in the neglect syndrome, in which the patient seems unaware of the left side of his or her body and of persons, objects, and events on his or her left. (See an “


Physiology_Levy

Physiology_Levy. In the Clinic ” box later in this chapter.) The major function of the occipital lobe is visual processing and perception (see ). The primary visual cortex (Brodmann area 17) lines the calcarine sulcus and is flanked by secondary (Brodmann area 18) and tertiary (Brodmann area 19) visual cortices. Lesions of these areas in the cuneus gyrus result in blindness in the lower contralateral visual field; those in the lingual gyrus result in blindness in the upper contralateral visual field. Connections to the frontal eye fields affect direction of gaze, and projections to the midbrain assists in the control of convergent eye


Physiology_Levy

Physiology_Levy. Twoareasimportantforplanningandexecutingmotortasksaretheparietal cortex andthefrontal cortex, theformerbecauseitintegratessensoryinformationneededtodefinethecontextofatask(see ).Mirrorneuronshavebeenfoundinboththeinferior parietal andtheinferior frontal cortices of macaques. Thesecellsrespondduringperformanceofaspecificmotortaskandalsoduringobservationofthesametaskperformedbyanotheranimal.Becausethesemirrorcellsseemtoencodeforandrespondtoveryspecificandparticulartasks,ithasbeenspeculatedthattheymayunderliesuchfunctionsasunderstandingtheintentionsofothersandempathy,aswellastheabilitytolearntasksfromobservation.Inhumans,EEGactivityconsistentwiththebehaviorofsuchmirrorneuronshasbeenlocalizedtotheinferior frontal andsuperior parietal lobes. Autism,whichinvolvesaninabilityto“read”theintentionsandemotionsofothers,hasbeenlinkedtoalackofmirrorneuronsbyEEGevidence. movements, pupillary constriction, and accommodation, all of which occur when the eyes adjust for near vision.


Physiology_Levy

Physiology_Levy. movements, pupillary constriction, and accommodation, all of which occur when the eyes adjust for near vision. The temporal lobe has many different functions, including the processing and perception of sounds and vestibular information and higher order visual processing (see ). For example, the infratemporal cortex, on its inferior surface, is involved in the recognition of faces. In addition, Meyer’s loop, which forms part of the optic pathway, passes through the temporal lobe. As a result, temporal lobe lesions can damage vision in upper part of the visual field. Similarly, a portion of Wernicke’s area, essential for the understanding of language, lies in the posterior region of the temporal lobe. The limbic system dominates the medial temporal lobe (see


Physiology_Levy

Physiology_Levy. The limbic system dominates the medial temporal lobe (see Fig. 10.4 ), and it participates in emotional behavior and in learning and memory (see the “Learning and Memory” section). The limbic system helps control emotional behavior, in part by an influence on the hypothalamus via the Papez circuit. This circuit projects from the cingulate gyrus to the entorhinal cortex and hippocampus, and from there, via the fornix, to the mammillary bodies in the hypothalamus. The mammillothalamic tract then connects the hypothalamus with the anterior thalamic nuclei, which project back to the cingulate gyrus (see Fig. 10.4 ). In addition, the hippocampus and amygdala are connected to the prefrontal cortex, the basal forebrain, and the anterior cingulate cortex.


Physiology_Levy

Physiology_Levy. Fig. 10.4 ). In addition, the hippocampus and amygdala are connected to the prefrontal cortex, the basal forebrain, and the anterior cingulate cortex. Bilateral temporal lobe lesions can produce Klüver-Bucy syndrome, which is characterized by loss of the ability to recognize the meaning of objects from visual cues (visual agnosia); a tendency to examine all objects, even dangerous ones, orally; attention to irrelevant stimuli; hypersexuality; a change in dietary habits; and decreased emotionality.


Physiology_Levy

Physiology_Levy. Although this syndrome was originally described as following large lesions of most or all of the temporal lobe, more recent studies have highlighted the role of the amygdala. The amygdala conditions the association of fear with painful stimuli and may trigger, via connections to the medial frontal cortex and anterior cingulate gyrus, emotional or avoidance responses when these stimuli recur. In addition, the amygdala projects to the nucleus accumbens, a region of the basal ganglia which has been called a “reward center.” The nucleus accumbens signals pleasurable events in response to dopaminergic input from the ventral tegmental area of the brainstem and is also the most common site of the plaques and tangles associated with Alzheimer’s disease.


Physiology_Levy


Physiology_Levy

The Electrical Activity of the Cortex

Physiology_Levy. The Electrical Activity of the Cortex


Physiology_Levy

Physiology_Levy. An electroencephalogram (EEG) is a recording of the neuronal electrical activity of the cerebral cortex made by electrodes placed on the skull. EEG waves normally reflect the summed extracellular currents that result from the generation of synaptic potentials in the pyramidal cells and are thus a type of field potential. Because the currents generated by a single cell are too small to be detected as discrete events by an electrode on the skull (to record the activity of a single neuron, a microelectrode must be placed within microns of the neuron), the EEG waves reflect the combined activity of many pyramidal cells. Moreover, for the activity of a group of neurons to generate an event detectable on EEG, they must be oriented so that their individual currents summate to produce a detectable field. The arrangement of pyramidal neurons, with their apical dendrites aligned in parallel to form a dipole sheet, is particularly favorable for generating large field potentials. One pole of this


Physiology_Levy

Physiology_Levy. field. The arrangement of pyramidal neurons, with their apical dendrites aligned in parallel to form a dipole sheet, is particularly favorable for generating large field potentials. One pole of this sheet is oriented toward the cortical surface and the other toward the subcortical white matter. Thus the currents generated •Fig. 10.5 Electroencephalographictracingsduringdrowsiness;stages1,2,and4ofslow-wave(non–rapideyemovement[non-REM])sleep;andREMsleep.(ModifiedfromShepherdGM.Neurobiology. London:OxfordUniversityPress;1983.) by cortical pyramidal cells have a similar orientation and can therefore summate to produce a field potential that can be detected. The need for summation also explains why EEG signals reflect primarily synaptic potentials rather than action potentials: electrical events must overlap in time in order to sum, and synaptic potentials have much longer durations than do action potentials.


Physiology_Levy

Physiology_Levy. The sign of an EEG wave can be positive or negative, but its direction alone does not indicate whether pyramidal cells are being excited or inhibited. For instance, a negative EEG potential may be generated at the surface of the skull (or cortex) by excitation of apical dendrites or by inhibition near the somas. Conversely, a positive EEG wave can be produced by inhibition of apical dendrites or by excitation near the somas.


Physiology_Levy

Physiology_Levy. A normal EEG tracing consists of waves of various frequencies. The dominant frequencies depend on several factors, including the state of wakefulness, the age of the subject, the location of the recording electrodes, and the absence or presence of drugs or disease. When a normal awake adult is relaxed with the eyes closed, the dominant frequencies of the EEG recorded over the parietal and occipital lobes are about 8 to 12 Hz, the alpha rhythm. If the subject is asked to open the eyes, the wave becomes less synchronized, and the dominant frequency increases to 13 to 30 Hz, which is called the beta rhythm. The delta (0.5 to 2 Hz) and theta (3 to 7 Hz) rhythms are observed during sleep (see the following discussion; Fig. 10.5 ). Also, brief EEG waves do exist and, because of their shape, are sometimes referred to as spikes, but this does not imply that they are associated with action potentials.


Physiology_Levy

Physiology_Levy. Fig. 10.5 ). Also, brief EEG waves do exist and, because of their shape, are sometimes referred to as spikes, but this does not imply that they are associated with action potentials. An EEG change that can be elicited by a stimulus is called a cortical evoked potential. A cortical evoked potential is best recorded from the part of the skull located over the cortical area being activated. For example, a visual stimulus results in an evoked potential that can be recorded best over the occipital bone, whereas a somatosensory evoked potential is recorded most effectively near the junction of the frontal and parietal bones. Evoked potentials reflect the activity in large numbers of cortical neurons. They may also reflect activity in subcortical structures.


Physiology_Levy

Physiology_Levy. Evoked potentials are small in comparison with the size of the EEG waves. However, their appearance can be enhanced by a process called signal averaging. In this process, the stimulation is repeated, and the EEGs recorded during each trial are electronically averaged. With each repetition of the stimulus, the evoked potential occurs at a fixed time after the stimulus. When the records are averaged, the components of the EEG that have a random temporal association with the stimulus cancel each other, whereas the evoked potentials sum. Evokedpotentialsareusedclinicallytoassesstheintegrityofasensorypathway,atleasttotheleveloftheprimarysensoryreceivingarea.Thesepotentialscanberecordedincomatoseindividuals,aswellasininfantstooyoungtoundergoasensoryexamination.Theinitialpartsoftheauditoryevokedpotentialactuallyreflectactivityinthebrainstem;therefore,thisevokedpotentialcanbeusedtoassessthefunctionofbrainstemstructures.


Physiology_Levy

Physiology_Levy. Sleep and wakefulness are among the many functions of the body that show circadian (about 1-day) periodicity. Characteristic changes in the EEG can be correlated with changes in the behavioral state during the sleep-wake cycle. Beta wave activity dominates in an awake, aroused individual. The EEG is said to be desynchronized; it displays low-voltage, high-frequency activity. In relaxed individuals with their eyes closed, the EEG is dominated by alpha waves (see Fig. 10.5 ). A person falling asleep passes sequentially through four stages of slow-wave sleep (called stages 1 through 4) over a period of 30 to 45 minutes (see


Physiology_Levy

Physiology_Levy. Fig. 10.5 ). A person falling asleep passes sequentially through four stages of slow-wave sleep (called stages 1 through 4) over a period of 30 to 45 minutes (see Fig. 10.5 ). In stage 1, alpha waves are interspersed with lower frequency waves called theta waves. In stage 2, the waves slow further, but the slow-wave activity is interrupted by sleep spindles, which are bursts of activity at 12 to 14 Hz, and by large K complexes (large, slow potentials). Stage 3 sleep is associated with delta waves and with occasional sleep spindles. Stage 4 is characterized by delta waves without spindles. During slow-wave sleep, the muscles of the body relax, but the posture is adjusted intermittently. The heart rate and blood pressure decrease, and gastrointestinal motility increases. The ease with which individuals can be awakened decreases progressively as they pass through these sleep stages. As individuals awaken, they pass through the sleep stages in reverse order.


Physiology_Levy

Physiology_Levy. About every 90 minutes, slow-wave sleep changes to a different form of sleep, called rapid eye movement (REM) sleep. In REM sleep, the EEG again becomes desynchronized. The low-voltage, fast activity of REM sleep resembles that seen in the EEG from an aroused subject (see Fig.


Physiology_Levy

Physiology_Levy. Fig. 10.5 , bottom trace). Because of the similarity of the EEG to that of an awake individual and the difficulty awaking the person, the term paradoxical sleep characterizes this type of sleep. Muscle tone is completely lost, but phasic contractions occur in a number of muscles, most notably the eye muscles. The resulting rapid eye movements are basis of the name for this type of sleep. Many autonomic changes also take place. Temperature regulation is lost, and meiosis occurs. Penile erection may occur during this type of sleep. Heart rate, blood pressure, and respiration change intermittently. Several episodes of REM sleep occur each night. Although it is difficult to arouse a person from REM sleep, internal arousal is common. Most dreaming occurs during REM sleep.


Physiology_Levy

Physiology_Levy. Thesleep-wakecyclehasanendogenousperiodicityofabout25hours,butitnormallybecomesentrainedtotheday-nightcycle.Thesourceofcircadianperiodicityappearstobethesuprachiasmaticnucleusofthehypothalamus.Thisnucleusreceivesprojectionsfromtheretina,anditsneuronsseemtoformabiologicalclockthatadaptstothelight-darkcycle.However,theentrainmentcanbedisruptedwhenthesubjectisisolatedfromtheenvironmentorchangestimezones(jetlag).Destructionofthesuprachiasmaticnucleusdisruptsanumberofbiologicalrhythms,includingthesleep-wakecycle. The proportion of slow-wave (non-REM) sleep to REM sleep varies with age. Newborns spend about half of their sleep time in REM sleep, whereas elderly people have little REM sleep. About 20% to 25% of the sleep of young adults is REM sleep.


Physiology_Levy

Physiology_Levy. The mechanism of sleep is incompletely understood. Stimulation in the brainstem in a large region known as the reticular activating system causes arousal and low-voltage, fast EEG activity. Sleep was once thought to be caused by a reduced level of activity in the reticular activating system. However, substantial data, including the observations that anesthesia of the lower brainstem results in arousal and that stimulation in the medulla near the nucleus of the solitary tract can induce sleep, suggest that sleep is an active process. Investigators have tried to find a relationship between sleep mechanisms and brainstem networks in which particular neurotransmitters, including serotonin, norepinephrine, and acetylcholine, are used; manipulations of the levels of these transmitters in the brain can affect the sleep-wake cycle. However, a detailed neurochemical explanation of the neural mechanisms of sleep is not yet available.


Physiology_Levy

Physiology_Levy. Similarly, the purpose of sleep is still unclear. However, it must have a high value because so much of life is spent in sleep and because lack of sleep can be debilitating. Medically important disorders of the sleep-wake cycle include insomnia, bed-wetting, sleepwalking, sleep apnea, and narcolepsy. •Fig. 10.6 Electroencephalographic (EEG) Abnormalities in Several Forms of Epilepsy. A, EEGtracingsduringthetonic(left) andclonic(right) phasesofatonic-clonic(grandmal)seizure.B, Spikeandwavecomponentsofanabsence(petitmal)seizure.C, EEGtracinginapersonwithtemporallobeepilepsy.D, EEGtracingofafocalseizure.(RedrawnfromEyzaguirreC,FidoneSJ.Physiology of the Nervous System. 2nded.St.Louis:Mosby;1975.) TheEEGbecomesabnormalinavarietyofpathologicalcircumstances.Forexample,duringcoma,theEEGisdominatedbydeltaactivity.Brain death isdefinedbyamaintainedflatEEGwave.


Physiology_Levy

Physiology_Levy. TheEEGbecomesabnormalinavarietyofpathologicalcircumstances.Forexample,duringcoma,theEEGisdominatedbydeltaactivity.Brain death isdefinedbyamaintainedflatEEGwave. Epilepsy commonlycauses,andcanbediagnosedby,specificEEGabnormalities.Therearemanyformsofepilepsy,andexamplesofEEGpatternsfromsomeofthesetypesofepilepsyareshownin Figure10.6 .Epilepticseizurescanbeeitherpartialorgeneralized. Oneformofpartialseizuresoriginatesinthemotorcortexandresultsinlocalizedcontractionsofcontralateralmuscles.Thecontractionsmaythenspreadtoothermuscles;suchspreadfollowsthesomatotopicsequenceofthemotorcortex(see ).ThisstereotypicalprogressioniscalledaJacksonian march. Complexpartialseizures(whichmayoccurinpsychomotor epilepsy)originateinthelimbicstructuresofthetemporallobeandresultinillusionsandsemipurposefulmotoractivity.Duringandbetweenfocalseizures,scalprecordingsmayrevealEEGspikes(see Fig. 10.6C andD Generalizedseizuresinvolvewideareasofthebrainandlossofconsciousness.Twomajortypesarepetit mal and


Physiology_Levy

Physiology_Levy. Fig. 10.6C andD Generalizedseizuresinvolvewideareasofthebrainandlossofconsciousness.Twomajortypesarepetit mal and Although right-handedness represents a sensorimotor dominance of the left hemisphere and left-handedness represents a sensorimotor dominance of the right hemisphere, cerebral dominance is assigned to the hemisphere in which language is to communicate; in humans, the left hemisphere is the dominant hemisphere in more than 90% of both rightand left-handed people. This dominance grand mal seizures. Inpetitmalepilepsy,consciousnessislosttransiently(typicallyforlessthan15seconds),andtheEEGdisplaysspike and wave activity (see Fig.10.6B ).Ingrandmalseizures,consciousnessislostforalongerperiod,andtheaffectedindividualmayfallifstandingwhentheseizurestarts.Theseizurebeginswithageneralizedincreaseinmuscletone(tonic phase), followedbyaseriesofjerkymovements(clonic phase). Thebowelandbladdermaybeevacuated.TheEEGshowswidelydistributedseizureactivity(see Fig.10.6A


Physiology_Levy


Physiology_Levy

Physiology_Levy. has been demonstrated (1) by the effects of lesions of the left hemisphere that produce deficits in language function (aphasia) and (2) by the transient aphasia (inability to speak or write) that results when a short-acting anesthetic is introduced into the left carotid artery. Lesions of the nondominant hemisphere and injection of anesthetic into it do not usually affect language substantially.


Physiology_Levy

Physiology_Levy. Several areas in the left hemisphere are involved in language. Wernicke’s area is a large area in the posterior part of the superior temporal gyrus, extending from behind the auditory cortex into the parietal lobe. Another important language area, Broca’s area, is in the posterior part of the inferior frontal gyrus, close to the face representation of the motor cortex. Damage to Wernicke’s area results in receptive aphasia, in which the person has difficulty comprehending spoken and written language; however, speech production remains fluent, if meaningless. Conversely, a lesion in Broca’s area causes expressive aphasia, in which individuals have difficulty in generating speech and writing, although they can understand language relatively well.


Physiology_Levy

Physiology_Levy. The terms sensory aphasia and motor aphasia are often interchanged with receptive aphasia and expressive aphasia, respectively. The former terms, however, are misleading: A person with receptive aphasia may not have auditory or visual impairment, and one with expressive aphasia may have normal motor control of the muscles responsible for speech or writing. Aphasia does not depend on a deficit of sensation or of motor skill; rather, it is an inability to decode language-encoded sensory information into concepts or to encode concepts into language. However, lesions in the dominant hemisphere may be large enough to result in mixed forms of aphasia, as well as sensory changes or paralysis of some of the muscles used to express language. For example, the latter situation could occur with a lesion of the face representation portion of the motor cortex that results in an inability to manipulate the motor apparatus needed for speaking (vocal cords, jaws, tongue, lips) and would be manifest as


Physiology_Levy

Physiology_Levy. of the face representation portion of the motor cortex that results in an inability to manipulate the motor apparatus needed for speaking (vocal cords, jaws, tongue, lips) and would be manifest as unclear speech because of dysarthria, a mechanical deficit. An affected individual would, however, be able to write if the motor cortex serving the upper limb were unaffected.


Physiology_Levy

Physiology_Levy. Interhemispheric Communication and the Corpus Callosum The two cerebral hemispheres can function somewhat independently, as in the control of one hand. However, information must be transferred between the hemispheres to coordinate activity on the two sides of the body. Much of that information is transmitted through the corpus callosum, although some is transmitted through other commissures (e.g., the anterior commissure or the hippocampal commissure). The importance of the corpus callosum for interhemispheric transfer of information is illustrated in Figure 10.7A. An animal with an intact optic chiasm and corpus callosum and with the left eye closed learns a visual discrimination task (see Fig. 10.7A). The information is transmitted to both hemispheres through bilateral connections made by the optic chiasm or through the corpus callosum, or both. When the animal is tested with the left eye open and the right eye closed (see


Physiology_Levy

Physiology_Levy. Fig. 10.7A, center), the task can still be performed because both hemispheres have learned the task. If the optic chiasm is transected before the animal is trained, the result is the same (see Fig. 10.7B). Information is presumably transferred between the two hemispheres through the corpus callosum. This finding can be confirmed by cutting both the optic chiasm and the corpus callosum before training (see Fig. 10.7C ). Then the information is not transferred, and each hemisphere must learn the task independently. A similar experiment was conducted in human patients who had undergone surgical transection of the corpus callosum to prevent the interhemispheric spread of epilepsy (


Physiology_Levy

Physiology_Levy. Fig. 10.8 ). The optic chiasm remained intact, but visual information was directed to one or the other hemisphere by the patient’s fixing vision on the central point of the screen. A picture or name of an object was then flashed to one side of the fixation point, so that visual information about the picture reached only the contralateral hemisphere. An opening beneath the screen allowed the patient to manipulate objects that could not be seen. The objects included those shown in the projected pictures. Normal individuals would be able to locate the correct object with either hand. However, patients with a transected corpus callosum could locate the correct object only with the hand ipsilateral to the projected image (contralateral to the hemisphere that received the visual information). For the hand to explore and recognize the correct object, the visual information must have access to the somatosensory and motor areas of the cortex. With the corpus callosum cut, the visual and motor


Physiology_Levy

Physiology_Levy. the hand to explore and recognize the correct object, the visual information must have access to the somatosensory and motor areas of the cortex. With the corpus callosum cut, the visual and motor areas are interconnected only on the same side of the brain.


Physiology_Levy

Physiology_Levy. Another test was to ask the patient to verbally identify what object was seen in the picture. The patient would make a correct verbal response to a picture that was projected to the right of the fixation point because the visual information reached only the left (language-dominant) hemisphere. However, the patient could not verbally identify a picture that was presented to the left hemifield because visual information reached only the right hemisphere.


Physiology_Levy

Physiology_Levy. Similar observations can be made in patients with a transected corpus callosum when different forms of stimuli are used. For example, when such patients are given a verbal command to raise the right arm, they do so without difficulty. The language centers in the left hemisphere send signals to the ipsilateral motor areas, and these signals produce the movement of the right arm. However, these patients cannot respond to a command to raise the left arm. The language areas on the left side cannot influence the motor areas on the right unless the corpus callosum is intact. Somatosensory stimuli applied to the right side of the body can be described by patients with a transected corpus callosum, but these patients cannot describe the same stimuli applied to the left side of the body. Information that reaches the right somatosensory areas of the cortex cannot reach the language centers if the corpus callosum has been cut.


Physiology_Levy

Physiology_Levy. In addition to language, other differences in the functional capabilities of the two hemispheres can be compared by exploring the performance of individuals with a transected corpus callosum. Such patients solve CHAPTER 10 Integrative Functions of the Nervous System 219 • Fig. 10.7 Role of the Corpus Callosum in the Interhemispheric Transfer of Visual Information When Learning Involves One Eye.A, Discrimination depends on distinguishing between a cross and a circle. B, Discrimination is between triangles oriented with the apex up or down. C, Discrimination is between vertical and horizontal bars.


Physiology_Levy

Physiology_Levy. •Fig. 10.8 Illustration of Tests in a Patient With a Transected Corpus Callosum. A, Thepatientfixesonapointonarearprojectionscreen,andpicturesareprojectedtoeithersideofthefixationpoint.Thehandcanpalpateobjectsthatcorrespondtotheprojectedpictures,buttheseobjectscannotbeseen.B, Responsebythelefthandtoapictureofakeyintheleftfieldofview.However,theverbalresponseisthatthepatientseesapictureofaring.(RedrawnfromSperryRW.In:SchmittFO,WordenFG[eds].The Neurosciences: Third Study Program. Cambridge,MA:MITPress;1974.) three-dimensional puzzles better with the right than with the left hemisphere, which suggests that the right hemisphere has specialized functions for spatial tasks. Other functions that seem to be more associated with the right than the left hemisphere are facial expression, body language, and speech intonation (


Physiology_Levy

Physiology_Levy. Fig. 10.9 ). Patients with a transected corpus callosum lack normal interhemispheric coordination. When they are dressing, for example, one hand may button a shirt while the other tries to unbutton it. Observation of these patients indicates that the two hemispheres can operate quite independently when they are no longer interconnected. However, one hemisphere can express itself with language, whereas the other communicates only nonverbally.


Physiology_Levy

Physiology_Levy. Major functions of the higher levels of the nervous system are learning and memory. Learning is a neural mechanism by which the organism’s behavior changes as a result of experience. Memory is the storage mechanism for what is learned.


Physiology_Levy

Physiology_Levy. The neural circuitry involved in memory and learning in mammals is complex and difficult to study. Alternative approaches are animal studies (especially in the simpler nervous systems of invertebrates), analysis of the functional consequences of lesions, and anatomical/physiological studies at the cellular and pathway level. For example, in the marine mollusk Aplysia, it has been possible to isolate a connection between a single sensory neuron and a motor neuron, which shows aspects of habituation (learning not to respond to repetitions of an insignificant stimulus), sensitization (increased responsiveness to innocuous stimuli that follow the presentation of a strong or noxious stimulus), and even associative conditioning (learning to respond to a previously insignificant event after it has been


Physiology_Levy

Physiology_Levy. Right-side olfaction Memory for shapes Stereognosis, left side Hearing (left-ear preference) Musical ability Recognition of forms, faces, and body image Left visual fieldRight visual field Mathematical ability Understanding language Hearing (right-ear preference) Motor speech Left-side olfaction Verbal memory Stereognosis, right side Right-hand skills (e.g., writing) L Left Right RLR 372 x 49 18228 •Fig. 10.9 Schematicillustrationofthefunctionalspecializationsoftheleftandrighthemispheres,asdeterminedinpatientsaftersectionofthecorpuscallosum.(ModifiedfromSiegelA,SapruHN.Essential Neuroscience. 5thed.Philadelphia:LippincottWilliams&Wilkins;2005.) paired with a significant one). In the case of habituation, the amount of transmitter released in successive responses gradually diminishes. The change involves an alteration in the Ca++ current that triggers release of neurotransmitter. The cause of this change is inactivation of presynaptic Ca++ channels by repeated action potentials.


Physiology_Levy

Physiology_Levy. The change involves an alteration in the Ca++ current that triggers release of neurotransmitter. The cause of this change is inactivation of presynaptic Ca++ channels by repeated action potentials. Long-term habituation can also be produced. In this case, the numbers of synaptic endings and active zones in the remaining terminals decreases.


Physiology_Levy

Physiology_Levy. Additional models of learning, provided by synaptic phenomena, are called long-term potentiation (LTP) and long-term depression (LTD). LTD has been studied most extensively in the cerebellum (see Chapter 9), but it also occurs in the hippocampus and in other regions of the CNS.


Physiology_Levy

Physiology_Levy. LTP has been studied most intensively in slices of the hippocampus in vitro, but it has also been studied in the neocortex, cerebellum, and other parts of the CNS. Repetitive activation of an afferent pathway to the hippocampus or repetitive activation of one of the intrinsic connections increases the responses of pyramidal cells. The increased responses (the LTP) last for hours in vitro (and even days to weeks in vivo). The forms of LTP differ, depending on the particular synaptic system. The mechanism of the enhanced synaptic efficacy seems to involve both presynaptic and postsynaptic events. The neurotransmitters involved in LTP include excitatory amino acids that act on N-methyl-D-aspartate (NMDA) receptors, the responses of which are associated with an influx of Ca++ into the post-synaptic neuron. Second messenger pathways (including G proteins, Ca++/calmodulin-dependent kinase II, protein kinase G, and protein kinase C) are also involved, and these kinases cause protein


Physiology_Levy

Physiology_Levy. post-synaptic neuron. Second messenger pathways (including G proteins, Ca++/calmodulin-dependent kinase II, protein kinase G, and protein kinase C) are also involved, and these kinases cause protein phosphorylation and changes in the responsiveness of neurotransmitter receptors. A retrograde messenger, perhaps nitric oxide (or carbon monoxide), may be released from postsynaptic neurons to act on presynaptic endings in such a way that transmitter release is enhanced. Immediate-early genes are also activated during LTP. Hence, changes in gene expression may also be involved.


Physiology_Levy

Physiology_Levy. With regard to the stages of memory storage, a distinction between short-term memory and long-term memory is useful. Recent events appear to be stored in short-term memory by ongoing neural activity because short-term memory persists for only minutes. Short-term memory is used, for instance, to remember page numbers in a book after looking them up in the index. Long-term memory can be subdivided into an intermediate form, which can be disrupted, and a long-lasting form, which is difficult to disrupt. Memory loss, or amnesia, can be caused by a loss of memory information per se, or it can result from interference with the mechanism for accessing the information. Long-term memory probably involves structural changes because it can remain intact even after events that disrupt short-term memory.


Physiology_Levy

Physiology_Levy. The temporal lobes appear to be particularly important for memory because bilateral removal of the hippocampal formation can severely and permanently disrupt recent memory. Short-term and long-term memories are unaffected, but new long-term memories can no longer be established. Thus patients with such amnesia remember events before their surgery but fail to recall new events, even with multiple exposures, and must be reintroduced repeatedly to people they meet after the surgery. This loss of declarative memory involves the conscious recall of personal events, places, and general history. Such patients, however, can still learn some tasks because they retain procedural memory, which involves associational and motor skills. If such patients are given a complex task to perform (e.g., mirror writing), they not only improve during the first training session but also perform better on subsequent days despite their denial of having any earlier experience with that task. The cerebral


Physiology_Levy

Physiology_Levy. mirror writing), they not only improve during the first training session but also perform better on subsequent days despite their denial of having any earlier experience with that task. The cerebral structures involved in procedural memory are not yet defined.


Physiology_Levy

Physiology_Levy. Plasticity most commonly refers to the ability of the CNS to change its connectivity. Such changes can occur in various contexts, including learning and memory (see previous discussion), damage, and development. Damage to the CNS can induce remodeling of neural pathways and thereby alter behavior. Plasticity is greatest in the developing brain, but


Physiology_Levy


Physiology_Levy

Physiology_Levy. Becausetheentorhinalcortexisamajorsourceofinputtothehippocampus,itisinterestingthatstudiesofLondon’staxidrivers—whomustdemonstrateanextremelydetailedknowledgeofthecity’sstreetsandmostefficientroutesbeforebeinglicensed—indicatethattheposteriorhippocampusintrainedandexperienceddriversislargerthanthatinbeginnersorthegeneralpopulation.“Gettinglost,”acommoncomplaintassociatedwithamnesia,maybeduetothelossofspatialmemoryskills. some degree of plasticity remains in the adult brain, as evidenced by responses to certain manipulations, such as lesions of the brain, sensory deprivation, or even experience.


Physiology_Levy

Physiology_Levy. some degree of plasticity remains in the adult brain, as evidenced by responses to certain manipulations, such as lesions of the brain, sensory deprivation, or even experience. The capability for developmental plasticity may be maximal for some neural systems at a time referred to as the critical period. For example, it is possible to alter some connections formed in the visual pathways during their development by preventing one eye from providing input, but only during a specific critical period early in development. In such visually deprived animals, the visual connections become abnormal (


Physiology_Levy

Physiology_Levy. Fig. 10.10 ), and restoration of normal visual input after the critical period does not undo the abnormality, nor does it restore functional vision from the deprived eye. In contrast, similar visual deprivation later in life does not result in abnormal connections. The plastic changes seen in such experiments may reflect a competition for synaptic connections, whereby the less functional connections are pruned away. Research has shown a correlation between the form of a gene that modulates the efficacy of synaptic pruning and the probability of schizophrenia.


Physiology_Levy

Physiology_Levy. Plastic changes can also occur after injury to the brain in adults. Sprouting of new axons does occur in the damaged CNS; however, the sprouts do not necessarily restore normal function, and many neural pathways do not appear to produce sprouts. Additional knowledge concerning neural plasticity in the adult CNS is vital if medical therapy is to be improved for many diseases of the CNS and after neural trauma. Research is currently being conducted to explore •Fig. 10.10 Plasticity in the Visual Pathway as a Result of Sensory Deprivation During Development. Theoculardominancecolumnsaredemonstratedbyautoradiographyafterinjectionofaradioactivetracerintooneeye.Thetraceristransportedtothelateralgeniculatenucleusandthentransneurallytransportedtothestriatecortex.Thecortexislabeledinbandsthatalternatewithunlabeledbandswhoseinputisfromtheuninjectedeye.A, Normalpattern.B,


Physiology_Levy

Physiology_Levy. Normalpattern.B, Changedpatterninananimalraisedwithmonocularvisualdeprivation.Theinjectionwasmadeintothenondeprivedeye,andtheoculardominancecolumnsforthiseyewereclearlyexpanded.Otherexperimentsshowedthattheoculardominancecolumnsforthedeprivedeyecontracted.(A, FromHubelDH,WieselTN.Proc R Soc Lond B. 1977;198:1.B, FromLeVayS,etal.J Comp Neurol. 1980;191:1.) the potential of human embryonic stem cells for restoring CNS function.


Physiology_Levy

Physiology_Levy. Phantom limb sensation is an example of neural plasticity in adults. A patient whose limb has been amputated often perceives sensations on the missing limb when stimulated elsewhere on the body. Functional imaging studies suggest that this is a result of the spread of connections from the surrounding cortical territories into the cortical region that had served the amputated limb. Itwastraditionalpolicytodelaycorrectivesurgeryforachildbornwithacongenitalcataractuntilthechildwasolderandmoreabletocopewiththestressofsurgery.However,ifthecorrectionisdeferreduntilafterthe“criticalperiod,”fullrecoveryoffunctionisunlikely.Similarly,childrenbornwithamblyopia, aconditioncharacterizedbystrabismus(crosseye)becauseofrelativeweaknessofoneoftheextraocularmuscles,tendtousetheunaffectedeyeinpreference.Inbothcases,earlysurgeryisnowcommonpracticesothatthecorticalcircuitrycanbecorrectlysculptedbybalancedinputfromthetwoeyes.


Physiology_Levy

Physiology_Levy. Such remapping can also occur after surgical amputation of the second and third digits of the hand. Before surgery, each of the digits was represented in discrete and somatotopically organized areas of the postcentral gyrus (SI cortex). After surgery, the area that represented the amputated digits is now mapped with an enlarged representation of the adjacent digits (


Physiology_Levy

Physiology_Levy. Fig. 10.11 ). Conversely, individuals born with syndactyly (fusion of two or more digits of the hand) have a single or mostly overlapping representation of these digits in the SI cortex. After corrective surgery, the independent digits come to have distinctive representations. Even more remarkable is that monkeys that were trained on a sensory discrimination task requiring repeated daily use of their fingertips showed cortical differences after training. Not only were the SI cortical territories of their fingertips larger than before training but also the number of cortically recorded receptive fields on the fingertips was likewise increased.


Physiology_Levy

Physiology_Levy. •Fig. 10.11 Representationofthedigitregionoftheleftfirstsomatosensory(SI)cortex(A) andreorganizationofthisrepresentation (B) afteramputationofthesecondandthirddigits.(FromHainesDE[ed].Fundamental Neuroscience for Basic and Clinical Applications. 3rded.Philadelphia:ChurchillLivingstone;2006.) 1. The cerebral cortex can be divided into lobes on the basis of the pattern of gyri and sulci. Each lobe has distinctive functions, as shown by the effects of lesions. The left cerebral hemisphere is dominant for language in most individuals. Wernicke’s area (in the posterior temporal lobe) is responsible for the understanding of language, and Broca’s area (in the inferior frontal lobe) is responsible for its expression.


Physiology_Levy

Physiology_Levy. 2. The neocortex contains pyramidal cells and several kinds of interneurons. Specific thalamocortical afferent fibers terminate mainly in layer IV of the neocortex; diffuse thalamocortical afferent fibers synapse in layers I and VI. Axons from pyramidal cells in layer V are the major source of output to subcortical targets, including the spinal cord, brainstem, striatum, and thalamus. 3. The cortical structure varies in different regions. Brodmann’s designations reflect these variations in cortical structure and correspond to functionally discrete areas. 4. The EEG reflects electrical fields generated by the activity of pyramidal and varies with the state of the sleep-wake cycle, disease, and other factors. Cortical evoked potentials are stimulus-triggered changes in the EEG and are useful clinical data about sensory transmission. 5.


Physiology_Levy

Physiology_Levy. 5. EEG patterns during sleep are divided into slow-wave and REM forms. Slow-wave sleep progresses through stages 1 through 4, each with a characteristic EEG pattern. Most dreams occur in REM sleep. Sleep is produced actively by a brainstem mechanism, Squire L, Berg D. Fundamental Neuroscience. 4th ed. New York: Academic Press; 2012. and its circadian rhythmicity is controlled by the suprachiasmatic nucleus. 6. Information is transferred between the two hemispheres primarily through the corpus callosum. The right hemisphere is more capable than the left in spatial tasks, facial expression, body language, and speech intonation. The left hemisphere is specialized for the understanding and generation of language, for logic, and for mathematical computation. 7.


Physiology_Levy

Physiology_Levy. 7. Learning and memory can be studied on the cellular level, in invertebrates, and in higher animals. Memory includes short-term (lasting minutes), recent, and long-term storage processes and a retrieval mechanism. The hippocampal formation is important for storing declarative and spatial memory. 8. Lesion studies and behavioral studies indicate that plasticity occurs in the brain throughout life. However, there appears to be more plasticity early in life, and synaptic competition in “critical periods” is important for the establishment of neural circuitry. Upon completion of this chapter, the student should be able to answer the following questions: 1. What are the similarities and differences in the general organizations of the parasympathetic and sympathetic systems? 2. What are the respective actions of the parasympathetic and sympathetic innervation of the eye, and what symptoms arise when the parasympathetic or sympathetic innervation is lost? 3.


Physiology_Levy

Physiology_Levy. 2. What are the respective actions of the parasympathetic and sympathetic innervation of the eye, and what symptoms arise when the parasympathetic or sympathetic innervation is lost? 3. What are the changes in the balance of parasympathetic and sympathetic activity to the bladder that occur during micturation? 4. What is meant by a “servomechanism”? 5. What are the specific feedback loops that regulate body temperature, feeding and body weight, and water intake? 6. What is the role of the hypothalamus in each of these feedback loops?


Physiology_Levy

Physiology_Levy. 5. What are the specific feedback loops that regulate body temperature, feeding and body weight, and water intake? 6. What is the role of the hypothalamus in each of these feedback loops? he main function of the autonomic nervous system is to assist the body in maintaining a constant internal environment (homeostasis). When internal stimuli signal that regulation of the body’s environment is required, the central nervous system (CNS) and its autonomic outflow issue commands that lead to compensatory actions. For example, a sudden increase in systemic blood pressure activates the baroreceptors, which in turn modify the activity of the autonomic nervous system so that the blood pressure is lowered toward its previous level (see


Physiology_Levy

Physiology_Levy. The autonomic nervous system has both sensory and motor divisions. The motor division is further divided into the sympathetic and parasympathetic divisions. Because much of the autonomic nervous system’s actions relate to control of the viscera, it is sometimes called the visceral nervous system. In service of its homeostatic function, the autonomic nervous system mediates visceral reflexes (e.g., the gastrocolic reflex, where stomach distention triggers peristalsis in the intestines) and provides sensory information to the CNS for the perception of the state of our viscera, a percept known to anyone who has eaten too much at a meal. More generally, activation of autonomic receptors can evoke a variety of sensory experiences such as pain, hunger, thirst, nausea, and a sense of visceral distention; these perceptions can then lead to compensatory voluntary behaviors that assist in maintaining homeostasis.


Physiology_Levy

Physiology_Levy. In addition to its central role in homeostasis, the autonomic nervous system also participates in appropriate and coordinated responses to external stimuli that are required for the optimal functioning of the somatic nervous system in performing voluntary behaviors. For example, the autonomic nervous system helps regulate pupil size in response to different intensities of ambient light, thus helping the visual system to operate over a large range of light intensity.


Physiology_Levy

Physiology_Levy. In this chapter, the enteric nervous system is also considered part of the autonomic nervous system, although it is sometimes considered a separate entity (see also ). In addition, because the autonomic nervous system is under CNS control, the central components of the autonomic nervous system are discussed in this chapter. These central components include the hypothalamus and higher levels of the limbic system, which are associated with emotions (see ) and with many visceral types of behavior (e.g., feeding, drinking, thermoregulation, reproduction, defense, and aggression) that have survival value. Organization of the Autonomic Nervous System


Physiology_Levy

Physiology_Levy. Organization of the Autonomic Nervous System The sensory autonomic neurons are located in the dorsal root ganglia and in the cranial nerve ganglia. Like the other neurons of the dorsal root ganglia, they are pseudounipolar cells with a peripheral axonal branch extended to one of the viscera and a central branch that enters the CNS. With regard to autonomic motor output, both the sympathetic and parasympathetic nervous systems use a two-neuron motor pathway, which consists of a preganglionic neuron, whose cell body is located in the CNS, and a postganglionic neuron, whose cell body is located in one of the autonomic ganglia ( Figs. 11.1 11.2 ). The targets of this motor CHAPTER 11 The Autonomic Nervous System and Its Central Control 227 Projections of Parasympathetic parasympathetic nervous system


Physiology_Levy

Physiology_Levy. Figs. 11.1 11.2 ). The targets of this motor CHAPTER 11 The Autonomic Nervous System and Its Central Control 227 Projections of Parasympathetic parasympathetic nervous system Facial (VII) nerve, Glossopharyngeal (IX) nerve • Fig. 11.1 Schematic Illustration of the Sympathetic and Parasympathetic Pathways. Sympathetic pathways are shown in red and parasympathetic pathways in blue. Preganglionic neurons are shown in darker shades, and postganglionic neurons, in lighter shades. pathway are smooth muscle, cardiac muscle, and glands. The enteric nervous system includes the neurons and nerve fibers in the myenteric and submucosal plexuses, which are located in the wall of the gastrointestinal tract.


Physiology_Levy

Physiology_Levy. Control of the sympathetic and parasympathetic nervous systems of many organs is often antagonistic. To highlight this contrast, the sympathetic and parasympathetic systems are sometimes referred to as the “fight or flight” and the “rest and digest” systems, respectively. Indeed, the fight-orflight response to a threat to the organism reflects an intense activation of the sympathetic nervous system, which leads to a variety of responses, including increased heart rate and blood pressure, redistribution of blood to the muscles, decreased peristalsis and gastrointestinal secretions, pupil dilation, and sweating.


Physiology_Levy

Physiology_Levy. However, under most conditions, the two parts of the autonomic control system work in a coordinated manner—sometimes acting reciprocally and sometimes synergistically—to regulate visceral function. Furthermore, not all visceral structures are innervated by both systems. For example, the smooth muscles and glands in the skin and most of the blood vessels in the body receive sympathetic innervation exclusively; only a small fraction of the blood vessels have parasympathetic innervation. Indeed, the parasympathetic nervous system innervates not the body wall but only structures in the head and in the thoracic, abdominal, and pelvic cavities. The Sympathetic Nervous System


Physiology_Levy

Physiology_Levy. The Sympathetic Nervous System The sympathetic preganglionic neurons are located in the thoracic and upper lumbar segments of the spinal cord. For this reason, the sympathetic nervous system is sometimes referred to as the thoracolumbar division of the autonomic nervous system. Specifically, sympathetic preganglionic neurons are concentrated in the intermediolateral cell column (lateral horn) in the thoracic and upper lumbar segments of the spinal cord (see


Physiology_Levy

Physiology_Levy. Fig. 11.2). Some neurons may also be found in the C8 segment. In addition to the intermediolateral cell column, groups of sympathetic preganglionic neurons are found in other locations, including the lateral funiculus, the intermediate gray matter, and the gray matter dorsal to the central canal. Sympathetic post-ganglionic neurons are generally found in the paravertebral •Fig. 11.2 Details of the Sympathetic Pathway at a Thoracic Spinal Segment. Autonomicsensoryfibersarerepresentedbyblue lines; sympatheticfibers,byred lines; preganglionicaxons,bysolid lines, andpostganglionicaxons,bydashed lines. (RedrawnfromParentA,CarpenterMB.Carpenter’s Human Neuroanatomy. 9thed.Philadelphia:Williams&Wilkins;1996:295.)White ramus Gray ramus Blood vessel Paravertebral ganglion Prevertebral ganglion Visceral sensory fiber Postganglionic fiber Postganglionic fibers Hair glands Skin Arrector pili muscle Preganglionic fibers Lateral horn Spinal ganglion Peripheral nerve Visceral afferent fiber


Physiology_Levy

Physiology_Levy. Visceral sensory fiber Postganglionic fiber Postganglionic fibers Hair glands Skin Arrector pili muscle Preganglionic fibers Lateral horn Spinal ganglion Peripheral nerve Visceral afferent fiber Digestive tube Sympathetic trunk or prevertebral ganglia. The paravertebral ganglia form two sets of ganglia, each lateral to one side of the vertebral column. The individual ganglia on each side are linked by longitudinally running axons that form a sympathetic trunk (see


Physiology_Levy

Physiology_Levy. Figs. 11.1 11.2 ). Prevertebral ganglia are located in the abdominal cavity and include the Celiac and Superior and Inferior Mesenteric Ganglia (see Fig. 11.1 ). Thus paravertebral and prevertebral ganglia are located at some distance from their target organs. The axons of preganglionic neurons are often small, myelinated nerve fibers known as B fibers (see Table 5.1 ). However, some are unmyelinated C fibers. They leave the spinal cord in the ventral root and enter the paravertebral ganglion at the same segmental level through a white communicating ramus. White rami are found only from the levels of T1 to L2. The preganglionic axon may synapse on postganglionic neurons in the ganglion at its level of entry; may travel rostrally or caudally within the sympathetic trunk and give off collaterals to the ganglia that it passes; or may pass through the ganglion, exit the sympathetic trunk, and enter a splanchnic nerve to travel to a prevertebral ganglion (see


Physiology_Levy

Physiology_Levy. Figs. 11.1 11.2 ). Splanchnic nerves innervate the viscera; they contain both visceral afferents and autonomic motor fibers (sympathetic or parasympathetic). Postganglionic neurons whose somata lie in paravertebral ganglia generally send their axons through a gray communicating ramus to enter a spinal nerve (see Fig. 11.2 ). Each of the 31 pairs of spinal nerves has a gray ramus. Postganglionic axons are distributed through the peripheral nerves to effectors, such as piloerector muscles, blood vessels, and sweat glands, located in the skin, muscle, and joints. Postganglionic axons are generally unmyelinated (C fibers), although some exceptions exist. The names white and gray rami reflect the relative contents of myelinated and unmyelinated axons in these rami.


Physiology_Levy

Physiology_Levy. Preganglionic axons in a splanchnic nerve often travel to a prevertebral ganglion and synapse, or they may pass through the ganglion and an autonomic plexus and end in a more distant ganglion. Some preganglionic axons pass through a splanchnic nerve and end directly on cells of the adrenal medulla, which are equivalent to postganglionic cells.


Physiology_Levy

Physiology_Levy. The sympathetic chain extends from the cervical to the coccygeal levels of the spinal cord. This arrangement serves as a distribution system that enables preganglionic neurons, which are limited to the thoracic and upper lumbar segments, to activate postganglionic neurons that innervate all body segments. However, there are fewer paravertebral ganglia than there are spinal segments because some of the segmental ganglia fuse during development. For example, the superior cervical sympathetic ganglion represents the fused ganglia of C1 through C4; the middle cervical sympathetic ganglion is the fused ganglia of C5 and C6; and the inferior cervical sympathetic ganglion is a combination of the ganglia at C7 and C8. The term stellate ganglion refers to fusion of the inferior cervical sympathetic ganglion with the ganglion of T1. The superior cervical sympathetic ganglion provides postganglionic innervation to the head and neck, and the middle cervical and stellate ganglia innervate the


Physiology_Levy

Physiology_Levy. ganglion with the ganglion of T1. The superior cervical sympathetic ganglion provides postganglionic innervation to the head and neck, and the middle cervical and stellate ganglia innervate the heart, lungs, and bronchi.


Physiology_Levy

Physiology_Levy. In general, the sympathetic preganglionic neurons are distributed to ipsilateral ganglia and thus control autonomic function on the same side of the body. Important exceptions are the sympathetic innervation of the intestines and the pelvic viscera, which are both bilateral. As with motor neurons to skeletal muscle, sympathetic preganglionic neurons that control a particular organ are spread over several segments. For example, the sympathetic preganglionic neurons that control sympathetic functions in the head and neck region are distributed at levels C8 to T5, whereas those that control the adrenal gland are distributed at levels T4 to T12. The Parasympathetic Nervous System The parasympathetic preganglionic neurons are found in several of the cranial nerve nuclei of brainstem and in the sacral spinal cord (S3-S4) gray matter (see


Physiology_Levy

Physiology_Levy. Fig. 11.1 ). Hence, this part of the autonomic nervous system is sometimes called the craniosacral division. The cranial nerve nuclei that contain parasympathetic preganglionic neurons are the Edinger-Westphal nucleus (cranial nerve III), the superior (cranial nerve VII) and inferior (cranial nerve IX) salivatory nuclei, and the dorsal motor nucleus of the vagus and nucleus ambiguus (cranial nerve X). Postganglionic parasympathetic cells are located in cranial ganglia, including the ciliary ganglion (preganglionic input is from the Edinger-Westphal nucleus), the pterygopalatine and submandibular ganglia (input is from the superior salivatory nucleus), and the otic ganglion (input is from the inferior salivatory nucleus). The ciliary ganglion innervates the pupillary sphincter and ciliary muscles in the eye. The pterygopalatine ganglion supplies the lacrimal gland, as well as glands in the nasal and oral pharynx. The submandibular ganglion projects to the submandibular and sublingual


Physiology_Levy

Physiology_Levy. muscles in the eye. The pterygopalatine ganglion supplies the lacrimal gland, as well as glands in the nasal and oral pharynx. The submandibular ganglion projects to the submandibular and sublingual salivary glands and to glands in the oral cavity. The otic ganglion innervates the parotid salivary gland and glands in the mouth.


Physiology_Levy

Physiology_Levy. Other parasympathetic postganglionic neurons are located near or in the walls of visceral organs in the thoracic, abdominal, and pelvic cavities. Neurons of the enteric plexus include cells that can also be considered parasympathetic postganglionic neurons. All of these cells receive input from the vagus or pelvic nerves. The vagus nerves innervate the heart, lungs, bronchi, liver, pancreas, and gastrointestinal tract from the esophagus to the splenic flexure of the colon. The remainder of the colon and rectum, as well as the urinary bladder and reproductive organs, is supplied by sacral parasympathetic preganglionic neurons that travel through the pelvic nerves to postganglionic neurons in the pelvic ganglia. The parasympathetic preganglionic neurons that project to the viscera of the thorax and part of the abdomen are located in the dorsal motor nucleus of the vagus (see Fig.


Physiology_Levy

Physiology_Levy. Fig. 4.6E ) and the nucleus ambiguus. The dorsal motor nucleus is largely secretomotor (it activates glands), whereas the nucleus ambiguus is visceromotor (it modifies the activity of cardiac muscle). The dorsal motor nucleus supplies visceral organs in the neck (pharynx, larynx), thoracic cavity (trachea, bronchi, lungs, heart, and esophagus), and abdominal cavity (including much of the gastrointestinal tract, liver, and pancreas). Electrical stimulation of the dorsal motor nucleus results in gastric acid secretion, as well as secretion of insulin and glucagon by the pancreas. Although projections to the heart have been described, their function is uncertain. The nucleus ambiguus contains two groups of neurons: (1) a dorsal group (branchiomotor) that activates striated muscle in the soft palate, pharynx, larynx, and esophagus and (2) a ventrolateral group that innervates and slows the heart (see also