The Concussion Crisis

by Linda Carroll

  Molaison’s surgeon, Dr. William Scoville, had done his share of lobotomies and was mostly happy with the results. They seemed to quiet unruly mental patients. But he’d heard about the personality distortions associated with destruction of the frontal lobes and had recently opted to focus on a different part of the brain: the hippocampus. It was a small structure located deep within the brain consisting of two seahorse-shaped lobes. At the time, no one knew what role the hippocampus played, but scientists suspected that it was somehow involved with the sense of smell because it seemed to connect directly with structures that originated in the nose. Scoville figured it would be better to lose your sense of smell than to have your personality distorted.

  Figure 7.3: Location of hippocampus

  Molaison lay awake during the entire operation. Scoville anesthetized the area above his patient’s eyes, cut a flap of skin to expose the skull, and then, with a hand drill, bored two holes through Molaison’s forehead. Scoville slid a thin metal spatula through each hole so that he could lift the front part of Molaison’s brain out of the way. Then the surgeon inserted a long metal straw attached to a suction device into Molaison’s head and sucked out nearly all of the man’s hippocampus.

  The unintended impact of the surgery was immediately obvious. After the operation, Molaison could no longer recognize any of the hospital staff or find his way to the bathroom. He couldn’t seem to keep anything that occurred after the operation in his head. And yet, the patient seemed to remember the most trivial details from the days leading up to his surgery. Further, memories from his life before the operation had been undisturbed.

  Scoville was horrified. He’d never seen anything like this. He quickly realized that the problem might be that he had suctioned out all of Molaison’s hippocampus. He’d done operations before where he’d suctioned out the left or right lobe of the hippocampus and there hadn’t been any serious repercussions—of course, it was difficult to tell in some cases because the patients who had the surgeries were psychotic and weren’t particularly revealing when interviewed by specialists. But now, he had a patient whose ability to form new memories seemed to have been destroyed. Scoville put in a call to Dr. Wilder Penfield, a renowned professor at Montreal’s McGill University who had years of experience with brain surgery.

  Penfield was shocked and angry when Scoville told him about the surgery. He thought it was reckless to have completely removed a part of the brain whose function was unknown. Nevertheless, he saw Molaison’s disaster as an opportunity to learn about the hippocampus and immediately dispatched a young researcher to study the case.

  Brenda Milner had been looking for patients who’d received surgeries to remove or destroy limited regions of the brain. She was hoping that these cases might help extend the existing research that linked localized areas of the brain to specific functions. Milner grabbed a few memory tests and hopped the next train from Montreal to Hartford. First thing the next morning, she was talking with Molaison.

  Milner’s tests confirmed Scoville’s worst fears. Molaison appeared to have completely lost the ability to form new memories. At first meeting, he would seem perfectly normal. He could keep up his side of a conversation and would even make jokes. But if his new acquaintance got up and walked away, he wouldn’t remember a word they’d exchanged—he wouldn’t even remember meeting the person in the first place. Milner saw this for herself after lunching with Molaison. Half an hour after they left the cafeteria, Molaison not only had forgotten what he’d eaten for lunch, but also that he’d eaten lunch at all. It was as if a computer suddenly lost the ability to transfer what appeared onscreen to its hard drive. So long as information was on the screen, it existed; once it disappeared from view, it was gone forever.

  Strangely, Molaison’s memory of the past was perfect. He could remember his childhood. He could remember the day before his surgery, but nothing that came afterward. The operation didn’t appear to have affected his ability to think, however. He actually had gained a few IQ points after the surgery. Milner would later tell a magazine reporter, “This was an intelligent, kind, amusing man. But he couldn’t acquire the slightest new piece of knowledge. He lives today chained to his past, in a sort of childlike world. You could say his personal history stopped with the operation.”

  Milner realized that Molaison could provide science with enormous insights into how memory worked. Prior to his operation, scientists thought that multiple parts of the brain participated in the process through which new information is permanently filed away. From her research on Molaison, Milner deduced that the hippocampus played an essential role in transcribing experiences or episodes from a person’s life into permanent memory. This is the kind of memory that accounts for our being able to summon up specific scenes from the mental video collection that makes up our past. Scientists in the 1970s would dub this kind of remembrance “episodic memory.”

  Milner wondered if her subject’s memory loss extended to all kinds of learning. Would the loss of the hippocampus mean that Molaison wouldn’t be able to pick up new skills? A simple experiment answered that question. Each day, Milner would ask Molaison to perform an exercise: he was given a sheet of paper with the outlines of two five-point stars, one inscribed within the other, and asked to draw a line that ran in between the outlines of the two stars. The tough part was that he couldn’t look directly at his hand or the stars while drawing. He had to do everything while watching his progress in a mirror. It’s the kind of task that practice can improve and, sure enough, Molaison got better with each passing day. But each day he needed to have the task explained to him because he had no recollection of having ever done it before. So, theoretically, Molaison could have learned to play the piano by having a lesson a day. He wouldn’t be able to remember having taken any of the lessons—so he’d be surprised that he could actually do it. This kind of skill memory was later labeled “procedural memory.”

  In another series of experiments, Milner tried to determine how long Molaison could keep information in his head before it evaporated. If she gave him a list of words and immediately asked him to spit it back, he could. On one occasion she asked him to remember a number, waited fifteen minutes, and then asked him what it was. Milner was surprised to see that he was able to remember for that long. Molaison told her that he kept repeating the number in his head. Milner had discovered “working memory.”

  In the fifty-five years he lived after the operation, Molaison gained an odd sort of fame. Research paper after research paper described the insights his brain had provided, with the credit given to the man known to neuroscientists only as “H.M.” The knowledge he gave to scientists was something he himself would never be able to learn.

  • • •

  When brain damage is visible, as it was with Henry Molaison and Phineas Gage, it’s a straightforward task to correlate a specific set of symptoms with injury to a certain part of the brain. When damage to the brain can’t be seen—as is the case with most concussions and even severe closed-head injuries—it’s a lot harder to tie the wide-ranging, and sometimes very subtle, symptoms to the jolt to the head. Not until the 1980s would scientists begin to understand how the brain could be damaged by an injury that was, for all intents and purposes, invisible.

  Chapter 8

  Deciphering the Damage

  John Povlishock peered through his microscope at Virginia Commonwealth University and was stunned by what he saw. The tiny black bulbs of protein ballooning near the ends of the nerve cells under his lens were proof that much of the damage to the brain in a TBI occurred not at impact, but hours after the initial injury.

  Just a short time earlier, Povlishock had been on the verge of giving up. He’d been trying to duplicate the findings of a recent autopsy study by Scottish researchers that had found scattered damage to nerve cells throughout the brains of patients with severe TBIs who’d died within months of their injuries. But when Povlishock looked at tissue from the brains of recently concussed rats, he hadn’t see
n anything like the damage described by J. Hume Adams and his colleagues at the University of Glasgow. Their study had shown photos of axons—the long threadlike structures that emanate from the center of a neuron and function like phone cables to carry information to other cells—stopped up by black balls of protein. Adams’s landmark study, which was published in 1977 in the journal Brain, had gone a long way to explain the disparate and profound symptoms experienced by people who didn’t have any obvious signs of injury to their heads. It was clear now that there could be significant damage to individual cells, and because that damage was scattered throughout the brain with no one focal point, it wouldn’t show up on brain scans or on autopsies that didn’t include inspection with a high-powered microscope.

  One of the most astounding findings from Adams’s study was the presence of healthy neurons and blood vessels running right alongside the dead and damaged cells. That meant the damage wasn’t being caused by a direct hit to the cells. Something else must be going on. Adams and his colleagues suspected that the bulbs of protein suggested that the axons had been torn when the brain slammed around in the skull.

  The study cleared up another perplexing question: How could so many different areas of the brain be affected by a TBI? The answer was in the ubiquity of the injuries. Adams and his colleagues found damaged and dying axons all over the brain. Each one of them signaled a broken connection. It was as if the plugs in a house had been pulled willy-nilly from their wall sockets. You wouldn’t know which plug had been disconnected until you went to use the device that was on the other end of the wire.

  Povlishock’s first attempts to duplicate Adams’s results were a dismal failure: not a single protein bulb could be seen on the slide. At first he thought the problem might be that the rats’ concussions were too mild an injury for them to develop the kind of damage that Adams had observed in his patients with severe TBIs. But as the months passed, he started to wonder if he was just examining the rat brains too soon after the concussions. Perhaps, he thought, a jolt to the head kicked off a sequence of events that culminated in those black bulbs ballooning out hours after the initial injury. Povlishock decided to do his experiment again. Only this time he would wait a day before examining tissue from the concussed rat brains.

  Sure enough, when he peered through his microscope, he saw the same balls of protein that Adams had seen in the human study (Figure 8.1). And just like Adams’s brain-injured patients, the rats had damaged axons scattered all over their brains. What made Povlishock’s study even more compelling was that he had seen damaged axons even in a mild brain injury. By extension, that might mean that concussions created some lasting damage to the brain. Perhaps the difference between a mild brain injury and a more severe one was simply the number of axons that got injured.

  The most profound implication of the research may have been Povlishock’s realization that the axonal damage seemed to occur in slow motion after the original jolt to the head. That meant there was a possibility that scientists could find a treatment and bring the process to a halt before all the damage was done. There wouldn’t be a lot of time to get patients treated, but if researchers could find the right drug, they might be able to save some people from permanent brain damage.

  Figure 8.1: Axons with protein bulbs following a brain injury. (Courtesy of Douglas H. Smith, M.D.)

  Povlishock wrote up his findings and they were published in 1983 in the Journal of Neuropathology & Experimental Neurology. Because the study involved mild TBI, its impact was huge. Newspaper reporters and lawyers deluged his office with requests for interviews and expert testimony. Suddenly there was proof that a bump on the head could cause damage you could see with a microscope.

  Povlishock’s study also fit nicely with some research from the University of Pennsylvania published just a year earlier. Dr. Thomas Gennarelli and his colleagues had shown in animal models that you didn’t need a blow to the head to cause brain damage. All that needed to happen was for the head to rapidly accelerate or decelerate, as it might in a car accident or in an IED explosion. Because the brain isn’t really anchored to anything and floats in fluid, sudden movement could send it slamming into the skull and wrench the axons so severely that their internal scaffolding would be damaged. Gennarelli and his colleagues showed that that kind of damage could result even from a simple rotation of the head, similar to what often happens to boxers when they get punched in the jaw. The researchers coined a name for the damage: “diffuse axonal injury.”

  Though scientists had their theories, they still didn’t know exactly how axons were being hurt. In animal studies, they had examined the brain at various time intervals after a TBI, but that was like looking at a series of snapshots. You couldn’t really understand the process unless you could watch it happening in real time. Then University of Pennsylvania researchers found a way to simulate TBI damage in individual axons while the axons sat on a slide under a microscope.

  • • •

  Dr. Douglas Smith keeps a lump of Silly Putty in the desk drawer of his spacious office at the University of Pennsylvania. He pulls the wad of squishy stuff out whenever he’s asked to explain how brain cells could be injured when there isn’t even a hit to the head. “If you stretch the Silly Putty out slowly, it gives,” he says while pulling the wad into a long, thin thread. “It’s the same in your brain. When you sat down, your brain was wiggling like a Jell-O mold. And because the movement is slow, it’s OK.” Then he gives the wad a yank and it breaks into two pieces. “I can take the same material and stretch it the same amount but faster, and it disconnects because it becomes stiffer with rapid stretching,” he says. “Your axons behave the same way. When they’re rapidly stretched, their internal skeletons can be destroyed.” That, in a nutshell, he says, is all there is to the concept of “fast stretch” and “slow stretch.”

  Years ago, when other scientists were convinced that axons were being torn during a head injury, Smith began to suspect that the real damage was being caused by stretching. He had come to TBI research completely by chance back when he was a postdoctoral fellow in biochemistry. A family friend who had fallen while skiing and hit his head on some ice wasn’t getting better after a concussion—weeks passed and his thinking was still foggy, his memory muddled. Knowing Smith’s medical background, family members had reached out to him for an explanation, and for help. When Smith started looking at the TBI literature, he was shocked to see how little was known, and embarrassed that he could provide no direction. “I couldn’t give them any kind of answer because there was nothing there,” Smith says. “The more I looked into it, the more I realized there really was nothing. Here you had these huge numbers of people who were affected and there was so little knowledge. It didn’t make any sense.”

  Smith was amazed that late in the twentieth century, on the eve of “The Decade of the Brain,” there was an area of brain research that was still in its infancy. While there were plenty of scientists working on stroke, which disabled far fewer people and at an older age, he quickly realized that there was only a small cadre of dedicated researchers teasing out the mechanics of TBI. To a scientist just starting out in his career, this seemed to be the perfect fit. “I saw what a huge challenge it was,” he says. “It was a new field. There was a need that had to be filled.”

  In the early ’90s, Smith came to work with Gennarelli’s group at Penn. “It was the mecca of brain injury research,” Smith says. “They had a multidisciplinary approach to studying TBI; they had bioengineers working with neurosurgeons, neuroscientists, and neurologists, all studying traumatic brain injury with a focus on diffuse axonal injury.” After arriving at Penn, Smith designed the experiments and apparatus to study what happened to individual axons when you pulled on them. Gennarelli left Penn, and Smith eventually took over as director of the Penn Center for Brain Injury and Repair.

  Smith’s lab has been studying axon stretch, both fast and slow, for almost two decades now. He and his colleagues have learned that when axons ar
e stretched gradually, they just grow in length, like the slowly stretched Silly Putty. This explains how a single axon that connects a baby whale’s brain to its tail can lengthen to hundreds of thousands of times its original size as the seafaring mammal matures. That seemingly simple concept may eventually hold promise for people with spinal cord injuries. In a lab setting, Penn researchers have shown that they can coax individual axons to grow longer and longer by gently—and slowly—tugging on them. The theory is that if you can get axons to grow several inches in the lab, you might be able to use these axons as a living bridge to span regions of damaged axons in a person with injury to the brain or spinal cord.

  At the other end of the spectrum is fast stretch. To discover the details of what happens to axons in a closed-head injury, Penn researchers devised a way to subject individual axons to a quick stretch while they observed the process through the lens of a microscope. They start by placing two groups of neurons on a sheet of film, which is fairly stiff but will flex if it’s given a hard, fast push. One group of neurons is lined up in a row on the far left side of the sheet and the other in a row on the far right side. The two rows of neurons are then encouraged to shoot their communication cables—the axons—toward one another across the empty space separating them. Once the left- and right-side neurons have connected, the experiment can begin.

  As the researchers peer through a microscope, a puff of air is blown up from beneath the film, causing it to bend upward in the middle. The force of the air puff on the film is enough to make axons rapidly stretch just as they would in a car wreck. Immediately upon injury, many of the axons go from straight to wavy, which indicates that something broke inside the axons. Although the axons gradually straighten out and appear normal within hours, they begin to show signs of damage that’s more permanent. In particular, they develop black bulbs of protein just like those seen in autopsies of humans and animals with a TBI (Figure 8.2).