Credit: Cam Cottrill

It's never been easy to study the human brain. The 19th-century French scientists who theorized that different brain functions corresponded to different brain regions often had to rely on terrible happenstance for their research. In 1861, Dr. Ernest Aubertin gained access to a man who had attempted to commit suicide by shooting himself in the head. The shot had torn away the front of his skull, and Aubertin was able to manipulate the man's frontal lobe with a small spatula before he died. When the doctor tapped the left frontal lobe, the man lost the ability to speak, but tapping the right side had no such effect. Evidence began to accumulate for what became known as the "localization" of the brain's various functions.

Mapping the brain remains one of biology's biggest challenges. The rubbery, motionless organ gives no clues on its surface to how it works. With today's technology, of course, neurologists like myself are able to see images of the brain in action. We can use scans to safely track the maturation of the brain from birth to old age and to see its functions at work in real time. No suicides or spatulas are required.

And yet, paradoxically, the easy availability of these images threatens to distort our view of the brain and our understanding of it. Brain scans have huge limitations. For the most part, they are just static photographs. Though they have given us new insights into the brain's control over complex cognitive functions, many claims about their capabilities - that they can read minds, for example, or measure empathy or act as a lie detector - are exaggerated. By themselves, scans tell us nothing about how well different aspects of the brain are working. For that there is still only one method, which risks falling into the shadows of science: the old-fashioned, personal process of gathering information directly from a patient.

A scan can't tell you how well a patient lifts his or her arms, or climbs stairs, or reads or speaks, nor can it indicate personality or intelligence or sense of humor. Only patients can do that. The interpretation of test results depends entirely on what we learn from the details of their stories, comparisons to other patients and our own intuition. Dr. Rita Charon, founder of the narrative medicine program at Columbia University, neatly summarized her own approach to a patient's story in a 2004 lecture: "I listen not only for the content of his narrative but for its form - its temporal course, its images, its associated subplots, its silences." Technology just complements these clinical skills.

The case of Phineas Gage, seen posing with the tamping iron
that went through his brain and behind his left eye in 1848,
prompted intense efforts to understand the functions of regions
of the brain. Photo: Alamy

For millennia, scientists had guessed that the functions of the brain were laid out according to a similar plan in each of us. The only way to determine that plan was to observe the effect of brain injury and disease. More than a decade before the French suicide case, the American railway worker Phineas Gage became famous when an iron rod was driven through his left frontal lobe, leaving him otherwise healthy but changing his personality from quiet to aggressive. His case prompted intense research into localized brain functions.

But relying on such awful events was never going to deliver all the answers. A better approach was needed. Enter one of the oldest recorded brain diseases: epilepsy.

A century ago, the stories that people with epilepsy told their doctors became an exploratory tool for neuroscientists. They led the early brain explorers directly into the functional anatomy of the brain.

For the English neurologist John Hughlings Jackson, a crucial insight came from watching an experiment in which a colleague electrically stimulated the brain of a living monkey. When the experimenter stimulated a particular section of the monkey's frontal cortex, a contraction spread progressively through the muscles of the monkey's arm, causing it to jerk.

'Many people with epilepsy have an experience of seizures uniquely their own, so strange that no doctor has seen anything like it before.'

The neurologist had seen a similar movement in some of his patients with epilepsy. It occurred to him that epilepsy could be explained by the spread of electrical activity through the brain. If that was right, it followed that the manifestations of an epileptic seizure represented the function of the brain area where the seizure happened.

His intuition was exactly right, and it continues to shape modern medical practice. Consider Maya, who was 59 and had suffered from epilepsy for 40 years when I first examined her. A small delicate lady born in Uganda, she was a patient in the early days of my work as a consulting neurologist at the Royal London Hospital in East London. Listening to the progression of her symptoms was like being taken on an anatomical tour of the brain.

At the start of any seizure, the first thing that Maya experienced was fear. The amygdala is the brain's early warning system. It alerts us to danger. When electrically stimulated, it can cause a person to feel frightened. Maya's fear implicated the amygdala as a possible source of her seizures.

But there are two amygdala, left and right. So which was causing the problem? Maya gave the next clue. After experiencing this fear, her right arm stiffened and rose unnaturally. This indicated that the electrical discharge had moved to the part of the brain that controls the muscles of the right arm. That control lies in the frontal lobe of the opposite side of the brain. Maya's rigid right arm suggested that she had a diseased left frontal lobe.

Maya also lost the ability to speak during and after her seizures. She could understand what was being said but couldn't find the words to answer. That was the same problem experienced by the suicide victim in Paris when the spatula was pressed to his exposed left frontal lobe. It was also the same area that another French physician at the time, Pierre Paul Broca, identified by studying the autopsy of a patient who could say only one word.

Maya's seizure had arrived at the center for expressing language, and her story described its passage. It started as a discrete electrical discharge in the region of the left amygdala, then moved forward into the left frontal lobe, affecting movement and speech.

Maya underwent an operation to remove her left amygdala (her right amygdala compensated for the missing piece), and the seizures stopped. Modern technology had confirmed our clinical suspicions - but the real weight of Maya's assessment rested on the clinical picture. Listening to Maya and watching her gave every clue needed to understand her disease and make her better.

A nurse sets electrodes in a functional neurological exploration
unit. Patients are subjected to various stimuli while having an
EEG (electroencephalogram) taken. Patterns are then analyzed
by a neurologist. Photo: Getty Images

Many people think of an epileptic seizure as a convulsion. That is certainly a type of seizure, but like anything to do with the brain, it is the smallest part of a much more complex picture. A seizure occurs when the normal electrical activity of the brain is disrupted by an unwanted synchronized electrical discharge coming from diseased brain matter. When the whole brain is involved, it causes a convulsion. But often the discharge only engulfs a small section of the cortex. If it is the part of the cortex that moves the big toe, the big toe will start to twitch; if it is an area where a memory is stored, the person affected will relive something from his or her past.

With the realization that a seizure was a symptom of a bit of diseased brain, scientists began to correlate seizure symptoms with brain lesions to create a brain map. By the end of the 1930s the advent of antibiotics made it possible to perform on people the neurostimulation techniques that had been used on animals. Physicians opened the skulls of willing subjects with epilepsy and applied electrical current directly to the cortex, moving the stimulus around to try to reproduce the patient's seizures and to test reactions in the normal parts of the brain.

Patients reported what each stimulation made them feel. Some stimuli made muscles stiffen or move. Others resulted in a sensory or emotional experience. In one experiment, stimulation of part of the temporal lobe caused a man to report that he heard an orchestra strike up. Stimulation of another brain area caused him to experience an hallucination. Researchers were thus able to identify the brain regions responsible for movement, sensation, and auditory and visual processing.

Diagnosis depends on the ability of patients to evoke their symptoms for their doctor and on the doctor's ability to hear what they say. That is true for any illness but especially for epilepsy, because a seizure is fleeting; it's gone by the time the patient and doctor meet.

'In one woman in a study of brain activity, a single neuron fired every time she was shown a picture of Jennifer Aniston.'

Consider the case of Donal, whom I met soon after Maya. His seizures manifested in a very specific way: He had periodic hallucinations of seven cartoon dwarfs running past him.

When the early brain explorers electrically stimulated patients' temporal lobes, several of their subjects reported visual hallucinations as vivid as Donal's. The doctors assumed these were memories and speculated that the temporal lobes must be important to memory, but they could only begin to guess how memory was stored. That is a question that we are only now beginning to answer.

In 2005, Rodriga Quian Quiroga and colleagues from the University of Leicester published a study in the journal Nature that updated the earlier electrical studies. The team used microelectrodes to record activity from neurons in the temporal lobes of patients undergoing surgery for epilepsy. The scientists showed the patients a selection of pictures and measured the electrical activity. It turned out that some specific neurons responded to specific pictures.

For example, in one woman, a single neuron fired every time she was shown a picture of Jennifer Aniston. The "Jennifer Aniston neuron" did not show activity for unrelated pictures. This suggested that specific neurons represent the memory of specific objects, people or concepts. It's not that one memory lives in one neuron, but we do seem to store memories in the connections between dedicated neurons.

All of Donal's scans were normal - his brain looked healthy - but the scans were done when he was asymptomatic. I wanted to see what happened to his brain when the hallucinations appeared, so I admitted him to the hospital for observation. Painless metal discs placed on his scalp made a continuous recording of Donal's brain waves using electroencephalography. Then we waited.

Three days in, Donal reported the appearance of the seven unwelcome cartoon dwarfs. Just as they appeared, his brain waves showed a burst of electrical activity in his right temporal lobe. It was there for a mere 90 seconds - long enough to prove that Donal's seizures were due to epilepsy.

The temporal lobe's role in memory suggests that the hallucination might have represented something from Donal's past. Perhaps he had a "seven dwarfs neuron" stored in his long-term memory. But he didn't recognize the dwarfs as a memory, so he may have constructed the hallucination from his imagination. Memory and imagination are closely related, and the temporal lobe plays a vital role in each.

'During a seizure, a teenager named August once ran straight into a stranger's house and woke up surrounded by puzzled faces of a large family.'

Perhaps the biggest challenge for people with brain disease is the vast array of possible symptoms. The manifestations can be as varied and unpredictable as the activities of a healthy brain. Many people with epilepsy have an experience of seizures that is uniquely their own, sometimes so strange that no doctor has seen anything like it before. When that happens, the patient and doctor must learn together.

When a woman named August was 16, she started to have running attacks: She runs manically and beyond her own control for three minutes at a time and then blacks out. The attacks are caused by a seizure in the area of the brain responsible for coordinating complex movement, and they have proved to be untreatable.

During her seizures, August has encountered the best and the worst of the strangers that she literally runs into. Once she jumped from a bus, leaving her belongings behind. She ran straight into a stranger's house and woke up surrounded by the puzzled faces of a large family. They were kind to her and helped her to get home.

Another time she woke up to find herself standing face to face with a furious neighbor who was shouting at her. She learned that, during her run, she had dragged his baby's stroller along with her. She was arrested for attempted child abduction, and it took months for the charges to be dropped.

I have never looked after a patient with running attacks before. August has never met another person with her problem. I have no idea how to advise her, so instead she teaches me. She has learned to negotiate with the terms of her disability. Largely housebound, she set up a business making cakes in her kitchen. She sculpts flowers out of icing sugar. She loves music and drawing and fills her home with friends. Her life is fuller than that of many healthy people, and I stand in awe of her.

The ongoing technological advances in brain science are very exciting, but we still depend on patients' narratives - and not just for clinical diagnoses. Listening to patients who have overcome the most perplexing of disabilities has a lot to teach us - and not just doctors - about our own humanity and the power of resilience.

- This essay is adapted from Dr. O'Sullivan's new book, "Brainstorm: Detective Stories from the World of Neurology," which will be published by Other Press on Oct. 30. She is a consulting neurologist at the National Hospital for Neurology and Neurosurgery in London.

Appeared in the October 6, 2018, print edition as 'Confessions Of the Miswired Brain The Storytelling Of Brain Disease.'

→ This Essay was last updated 13 Oct 2018 21:15 PDT ←