Arguably one of the greatest contributions to modern day neuroscience was made in 1953 by Henry Molaison, a 27-year-old man who suffered from debilitating epilepsy.

The summer of that year, a surgeon in Hartford, Conn., removed two slivers of Molaison's brain, an attempt to quell the seizures. The seizures subsided, but Molaison was left lacking the ability to record new memories, a case of severe anterograde amnesia that revolutionized our understanding of how memory works and helped establish the science of it.

Epilepsy and patients like Molaison have frequently been at the center of breakthroughs in understanding the mysteries of the brain. It is a window that has allowed researchers unparalleled access to unearth the ways in which the structure and functions of the brain inform its psychological processes.

One of the most common neurological disorders, epilepsy is really a large number of syndromes, all characterized by recurrent seizures. Sometimes medication can keep a condition under control, other times surgery is necessary, removing the brain tissue or lesions responsible for seizing.

Surgery is where epilepsy provides science with unique entry into the brain.

Accidental discovery

Much has been gleaned - often, as in the case of Molaison, unwittingly - from actually cutting into the brain in the course of treatment.

The studies of the brain in preparation for surgery, though, have also been crucial to research.

"If you trace back most major findings, it all ends up beginning with patients with epilepsy," said Dr. Josef Parvizi, a Stanford neurologist who specializes in the disorder.

In a paper published last week in Nature Communications, Parvizi was among a team of Stanford doctors to uncover the latest nuances of brain functionality. The study utilized a technique increasingly employed by doctors called intracranial electrophysiology to detect the precise areas of the brain in which seizures begin.

Doctors implant dozens of tiny electrodes under the skull, directly onto a patient's brain. The level of functional detail doctors receive as a result is unmatched.

Parvizi and company were able to pinpoint the pattern of brain activity that occurs when people think quantitatively.

With the technique, researchers can measure the ultrafast and extremely subtle electrical reactions of the brain's neurons as they fire away at an extremely high resolution. So, when, for example, a patient thinks about numbers, researchers can see exactly which areas of the brain are stimulated.

Other methods of recording brain activity, such as functional magnetic resonance imaging or electroencephalography, along the surface of the scalp, don't provide the same level of detail, though those methods have also yielded important discoveries on their own.

Epilepsy patients

Their research was performed on the brains of three patient volunteers already under evaluation for surgical treatment of epilepsy. After all, it is not without legitimate occasion that scientists endeavor to slice into someone's skull.

Parvizi's team took their research one step further, recording patients while they were conscious and going about their business in the days in the hospital prior to surgery.

"Monitoring patients with epilepsy through intracranial recording really is the only direct window we have into the conscious human mind," he said.

An understanding of the brain's activity pattern when engaged in quantitative thought might seem like a relatively small discovery, but such discoveries add up and begin to provide a more complete picture of how our mind is linked to the brain's physical structure.

Another Parvizi study of epilepsy patients published last fall uncovered two nerve clusters in the brain that are critical to perceiving faces. At UCSF, a study published in February mapped the parts of the brain which control lips, tongue, jaw and larynx as a person speaks and showed how those parts of the brain work together during speech.

Behind the research

The motivation for understanding these brain functionalities is to eventually find new ways to fix them when they stop working. For example, the UCSF study paved the way for the potential development of computer-brain interfaces to allow for artificial speech or development of new treatments for varying speech disorders. Parvizi's facial recognition findings could lead to methods of treating prosopagnosia, or face blindness, a condition in which a person is unable to distinguish one face from another.

An increase in the use of intracranial recording - a technique that many say is still vastly underutilized - has been at least in part responsible for a rise in the frequency of such breakthroughs in recent years.

"This is really a window into how your brain is thinking, perceiving," said Dr. Bob Knight, a Berkeley neuroscientist. "In the past 10 to 15 years, its use as a research tool has exploded."

These breakthroughs, said Knight, are in a way just a welcome side effect of treating patients.

"The whole impetus is clinical care, none of the impetus is to figure out how the brain works."

Hippocrates was among the first to assert that epilepsy was a disorder of the brain, though for centuries afterward it was still often treated as a spiritual or mental problem.

John Hughlings Jackson, an influential neurologist at the turn of the last century, predicted the disease would provide keys in understanding and studying the mind. He observed a patient's seizure, noting that it seemed to travel from one part of the body to another. He hypothesized that the disease was affecting different parts of the brain, which in turn affected different parts of the body. It was among the first clues that different parts of the brain perform different functions.

Mapping the brain

In the 1940s and 1950s, Wilder Penfield and Herbert Jasper began to create the first maps of the brain's sensory and motor cortices, after treating epilepsy patients by destroying nerve cells in portions of the brain where seizures seemed to begin.

"Epilepsy has always provided a very unique window into brain function," said Knight.

Gordy Slack, a journalist who is writing a book on the role epilepsy has played in the history of neuroscience, said the disease has perhaps not received due credit for its role in our knowledge of the mind.

"It's under-studied as a disease itself, but its contributions are also under-celebrated," said Slack, whose son had epilepsy. Patients with epilepsy, he said, "should be star players in the telling of the story of neuroscience."

If there ever was such a star, it was certainly Henry Molaison.

When Molaison awoke from surgery in 1953, he was unable to identify his nurses. He couldn't remember his way home or really anything after his surgery on in the year or two preceding it. His case debunked many of the then-existing theories about memory.

At the time, scientists believed that memories existed throughout the brain, independent of any one region. When, during his surgery, researchers removed a portion of Molaison's hippocampus, in the medial temporal lobe, they accidentally unearthed the region's key function in memory.

Molaison's intellect and personality were largely intact, as were most of his memories from before the surgery. He was permanently stuck in the present tense, as Suzanne Corkin described in her book about Molaison.

Molaison was known in scientific literature as only HM until his death in 2008. His brain is now frozen in slices at UC San Diego's Brain Observatory. Decades later, scientists are still studying it, examining and re-examining the brain of the epileptic man who showed science just what it is to remember.
