In addition to providing insight into mental illnesses such as schizophrenia and dementia, my experience gave me a greater understanding of other brain disabilities, including the mental declines that many of us encounter as we age. Many people may someday face in themselves, their partners, or their parents the bewildering mental changes I had—memory loss, disinhibited and inappropriate behaviors, altered personality, and the inability to recognize these problems in oneself. The frontal cortex, the part of my brain that was most affected by my tumors and treatment-induced swelling, is one of the regions that often begin to fail as we enter our senior years (the hippocampus is another). It’s one of the many ironies of my story that if I live long enough to see old age, there’s a good chance I will experience many of the same mental changes all over again.
In the course of losing and regaining my sanity, I’ve come to identify with other people who have known mental illnesses firsthand. This sense of connection with others who suffer has spurred me to share my story. While more attention is being given to mental illness than ever before, it nonetheless continues to be stigmatized by society. Even though mental disorders are physiological in nature—they are diseases of the brain, just as coronary problems are diseases of the heart—the mentally ill are often treated as if they are to blame, as if they have done something wrong. Their families are frequently stigmatized as well. If nothing else, I hope my experience helps others recognize that mental illness is no more the patient’s fault than cancer is and that the best response to mental illness is empathy and a greater commitment to finding cures.
After losing my mind and regaining it, I like to think I am more attuned to other people’s feelings and troubles, that I am more understanding as a mother, wife, friend—and scientist. While I believe that I’ve always been compassionate toward people with mental illness, since my own brush with madness, the quality of my compassion has deepened. I also live my life more consciously, aware of how lucky I am to be reunited with my family and able to continue my life’s work.
This book is an account of what mental illness looks like from the inside. But it is also a map of my evolution as a scientist and a person. It is the story of an incredible journey, one from which I could not have imagined I would ever return. It is a story that I never thought I would be able to tell, of how I went from being a scientist studying mental disorders to being a mental patient myself—and how, remarkably, I came back.
1
The Rat’s Revenge
I sit among a thousand brains, a thousand brains of the mentally ill.
As director of the Human Brain Collection Core at the National Institute of Mental Health, I work surrounded by brains; a library of brains, a bank of brains, a compendium of brains that for any number of reasons hadn’t worked the way they should have. Brains that saw hallucinations, heard mysterious voices, were buffeted by wild mood swings, or were deeply depressed. Brains that have been collected, cataloged, and stored here for the past thirty years.
About a third of these brains come from suicides. That desperate and heartbreaking act is the ultimate cost for so many people who suffer from mental illness, and my colleagues and I are reminded of this grim fact each and every day.
Each specimen arrives to us fresh and bloody, glistening inside a clear plastic bag placed carefully inside a cooler of ice. It looks like a piece of red meat, unconnected to any real humanness. Yet just a day earlier, it had directed every movement and thought of the person from whom it came.
To understand mental illness—and to treat and one day cure it—researchers need a steady supply of brains. This is where institutions like the NIMH, the leading federal agency in the United States for research on mental health, come in. At the brain bank, we gather these incredible organs, slice them into usable tissue samples, and share them with scientists around the world.
But collecting brains isn’t easy. It’s especially difficult to get brains that come from people with schizophrenia, bipolar disorder, major depression, anxiety disorders, and addictions to various substances—cocaine, opioids, alcohol, and even cannabis—that attract abuse. What’s more, we can’t use brains of mentally ill people who died of serious illnesses, who were in hospitals on ventilators, or who were heavily medicated before taking their last breath. Brains marked by other illnesses or medical issues would only add complexity to the already overwhelming puzzle that we are trying to solve: What causes mental disorders?
In order to begin to understand this, we also need brains from people without mental illness (control brains), so we can examine and compare them with diseased brains. In short, we need clean and healthy brains both with and without the terrible presence of madness.
We get most of our brains from the morgues in nearby medical examiners’ offices, where bodies typically arrive because people have died under suspicious or mysterious circumstances. And so, in addition to receiving the brains of suicides, we are also the unintentional beneficiaries of homicides and unexplained deaths.
First thing each morning, the technicians in our brain bank telephone local medical examiners’ offices and ask, Do you have any brains for us today?
We’re in a rush. If a person has been dead more than three days, we can’t use the brain. We need the brains before the tissue begins to decompose, before their proteins and other molecules, the ribonucleic acid (RNA) and deoxyribonucleic acid (DNA), begin to break down, rendering them useless for molecular studies.
The morgue workers tell the techs about the bodies that have arrived in the past twenty-four hours, sharing what information they have. Often, it isn’t much, just the barest of facts: A young man who overdosed on heroin. A middle-aged woman with a heart attack. A teen who hanged herself. At this point, it may be all we know about each person.
Once the technicians have compiled their list of candidates, they come to me, and together we narrow it down. Do we want this one, a drug overdose? Or this one, an elderly man whose wife told morgue investigators he was an alcoholic? Here’s a man who died in a car accident. There’s no indication he had mental illness, so maybe researchers will be able to use his brain as a control in their studies. But he might have sustained a head injury; do we still want him?
If there’s any possibility that a brain may be right for us, I usually say yes. The brains we seek are rare and precious, and we don’t get nearly enough.
Once we have settled on potential candidates, our technicians contact each one’s next of kin to make a wrenching request: Would you consider donating your loved one’s brain to medical research?
It seems a simple question. Yet a few hours earlier, these people were alive. Now they are forever lost, and we are asking parents or spouses or children to see through their own shock and grief to give us the most personal part of their loved ones, the part that made up the very essence of who they were. Not surprisingly, perhaps, only about a third of them agree to donate the brains we seek.
When a brain arrives at our bank, we label it with a number in order to protect confidentiality. Then our job begins in earnest. We can now cut this specimen open and study its inner workings in an attempt to better understand mental illness.
It is among these brains—sliced up and frozen in a slurry of hope and optimism that they will one day reveal their secrets—that I do my work.
Brains are a bloody business. I’ve worked with them for over thirty years, starting with rat brains, each of which is the size of a walnut, smooth, and relatively simple. They have none of the intricate folds and crevices—called gyri and sulci—of the human brain.
By contrast, the human brain is large, elaborate, and far more complex. It is a feat of evolutionary engineering. All of its folds, all of those gyri and sulci, ridges and crevices, help to squeeze more storage and function into the relatively small space of the human skull. Consciousness is one of the many products of this marvelously complicated piece of tissue. Unfortunately, mental illness—an affliction of consciousness—is a product as well.
In our quest to understand what’s wrong in the brains of people with mental illness, we have to dig deep into the brain’s tissues, cells, and molecules. Novel techniques make this a little easier every year. To try to unlock the secrets of schizophrenia, for instance, I examine thin slices of brain stained with radioactive or fluorescent dyes and evaluate the cells’ various molecules, proteins, and types of RNA and DNA. To read their genetic code, I analyze the brain cells’ minute molecular composition with modern sequencing machines.
As a neuroscientist and molecular biologist, I’m an expert on the brain. But I’m not a clinical doctor. Before I became head of the brain bank, I’d never worked with intact human bodies or even identifiable body parts. I did my work in quiet laboratories far from morgues and hospitals, and by the time the brains got to me, they didn’t look like brains at all. They were pulverized bits of frozen tissue that looked like specks of pinkish flour suspended in liquid in little test tubes, or they were thin slices of tissue preserved in foul-smelling chemicals. They could have been almost anything or come from almost any organism.
It never bothered me to be both intimate with and distant from the subjects of my studies. After all, that is the nature of scientific research. Each scientist works on her own small, discrete piece of an overwhelming puzzle that she hopes will someday be solved by researchers’ collective efforts and to which her narrow contribution will have been some significant part.
Before I took this job, I’d never even touched a whole human brain. I’d been to a morgue several times, seen bodies splayed open with their organs removed. But I’d never seen a brain lifted out of a skull. I’d never held a whole brain in my hands, much less cut one apart.
“You have to do it yourself,” my predecessor at the brain bank, Dr. Mary Herman Rubinstein (known as Dr. Herman), urged me in 2013 as she trained me. “When we get the next brain, we’ll slice it up and freeze it together.”
So we do. On a sunny day in September of that year, with the leaves just beginning to turn yellow and red but the air still warm and comforting, we stand in the lab awaiting the arrival of my first brain. We are armored in protective gear—surgical masks strung from ear to ear, plastic shields over our faces, hair caps secured tightly around our foreheads, several layers of latex gloves that cover our arms up to our elbows, white lab coats overlaid with plastic aprons to protect us from splashing blood, and plastic booties covering our shoes.
A technician carries in a large white cooler, the kind that holds beer and steaks for a football tailgate party. This cooler, I know, contains a human brain packed in lots and lots of ice.
It is critical that the brain stays cold, because this helps slow the process by which tissues break down. For our experiments, the brain cells’ RNA—key to how genes are expressed—must be intact. Putting a brain on ice immediately after it’s removed from the body is the first step in preserving the RNA, but for long-term storage, we must quickly deep-freeze the tissue. Keeping the brain at very low temperatures can halt RNA decomposition for decades.
Dr. Herman opens the lid of the cooler and carefully lifts out a clear plastic bag frosted with ice. She slowly takes out the brain and places it in my outstretched palms. It fits comfortably in my hands. Heavy, cold, and wet, it drips with blood just like any other piece of meat. The average brain weighs 1,300 grams, or about three pounds; in time, I will see some that are as large as 1,800 grams, about four pounds. It feels like firm Jell-O, but in fact it’s quite fragile; if I’m not careful, parts might snap off.
Given that the human brain is the most complex structure in our universe, you’d expect it to look more . . . well, complicated. But it just doesn’t appear all that extraordinary. The first time I saw a dead body in a morgue—all the blood, muscles, bones, and skin—I was afraid I would faint. But I find the brain now in my hands much less disturbing. Removed from the body in which it grew, this brain seems almost nonhuman.
Yet the enormous contrast between this ordinary-looking piece of meat and the complexity within it is deeply moving. It is awe-inspiring, marvelous, to realize that everything about a human being can be contained in my hands.
This brain governed a person who was alive less than a day ago. That much I’m sure of. But what else can I know about the brain that I hold? Did it come from a woman or a man? Did this person suffer from mental illness? Did this person kill him- or herself? The likelihood of that is high, given where we get these brains. But it’s also entirely possible that the brain came from an elderly woman who died of pneumonia or a young man who was killed by a gunshot wound to his chest. The person might have suffered from schizophrenia or depression, but he also might have had a clean bill of mental health. There is no way to know from looking at it with the naked eye. The brain does not reveal its secrets easily.
A whole brain is shaped somewhat like a football and is divided by a deep groove down the middle into a left and right hemisphere. Each hemisphere has four lobes: the frontal, temporal, parietal, and occipital.
As I hold this brain in my hands, I stare at the frontal lobes, the largest of the lobes. These regions of the cerebral cortex, the outer covering of the brain, determine much of our species’ conscious existence, from our perceptions of the world to our most private thoughts and imaginings. They are the parts that fascinate me the most and that preoccupy the overwhelming majority of neuroscientists.
The major regions of the human brain.
The frontal lobes—one on the left, one on the right—extend from the bottom of the forehead, right above the eyes, all the way back to the top of the skull. Like the other lobes, they’re wrapped around the more primitive parts located farther inside the brain.
I linger over the frontal cortex, the front top part of the frontal lobe, situated roughly where the hairline is. Large and full of folds and crevices, it is both the youngest and the most evolved part of the human brain. It determines who humans are—thinking, remembering, problem-solving creatures capable of judgment and informed decision-making.
The prefrontal cortex, the foremost part of the frontal cortex, sits just behind the forehead. This relatively small part of the cortex is perhaps the most crucial to our sanity because the prefrontal cortex controls what is known as executive function—the most complex cognitive tasks, such as the ability to differentiate between right and wrong, inhibit inappropriate or impulsive behavior, and predict the future consequences of things that happen in the present. Extensive research into the neuroscience of mental illness leaves little doubt that problems of the prefrontal cortex are central to mental illness. But we don’t know what kinds of problems they are, and just by looking at this brain’s frontal cortex, I certainly can’t tell.
Behind the frontal lobe, separated by a deep sulcus, or groove, I spot the parietal lobe, another large chunk of convoluted cortex. The parietal lobe coordinates sensory information sent to the brain from the rest of the body, allowing us to feel, taste, move, and touch. It places us in space, tells us where we are in relation to things around us, and where our bodies start and end. It also enables us to read and do math.
I turn the brain on its side and peek at the temporal lobe, which lies behind the temple, roughly above where the ear is. This part of the cortex is responsible for high-level auditory processing, for hearing and understanding speech. Beneath it, deep inside the brain, hidden from my eyes and surrounded by layers of cortical tissue, sits the hippocampus, named from the Greek word for “seahorse” because of its unusual curved shape. An evolutionarily primitive part of the brain, the hippocampus stores long-term memories. It also works like a GPS, enabling spatial navigation so we know where we are.
Hidden at the back of the brain is the exquisitely ribbed cerebellum, made of densely packed neurons. It coordinates voluntary movements: how we sit, walk, and speak. Just above it, where one would tie a ponytail, is the fourth and final lobe, the occipital lobe, the structure that processes information from the eyes and enables us to see.
All of the b
rain structures are enormously important to everyday functioning. If you injure the brain stem at the back of your brain—the part that regulates breathing, heart rate, and other basic functions—you could be paralyzed, or die. But the frontal cortex is perhaps the most precious brain region of all. While a person won’t die without a frontal cortex, it is the part that makes us human. Damage to this region of the brain results in a large number of adverse symptoms, from memory loss to the inability to plan and organize actions, from problems with language and speaking to inappropriate behavior and poor judgment.
I would be happy to linger longer in admiration of this brain, the first I’ve ever held, but Dr. Herman and I must work quickly to preserve the specimens for our studies.
I carefully place the brain on a large board that sits atop a bed of ice and pick up the dissecting knife, which is very long with a razor-sharp edge.
“Pretend you’re slicing bread or steak,” Dr. Herman instructs me. “Keep the knife’s edge perpendicular to the top surface of the brain, and try to make each cut parallel to the previous one.”
Holding the brain with my left hand, I lift the knife and then begin to slice. The cold storage has made the tissue firm, and the knife slides through easily.
My first cut is longitudinal along the crevice that separates the brain’s two hemispheres. I then slice into the left hemisphere, from front to back, creating uniform slices about half an inch thick. After a while, I feel the brain becoming mushy as it warms. Instead of falling neatly onto the cutting board, the slices fold over and crumple. I continue, though, getting better with each cut.
The Neuroscientist Who Lost Her Mind Page 2