Penfield was particularly curious why a scar in the brain caused by birth injury or head trauma could lead to epilepsy in some patients. He had the opportunity to pursue this question four years after his visit to Spain. His fascination with epilepsy spurred another European trip, a six-month visit to Otfrid Foerster’s laboratory at the University of Breslau in Germany. Foerster had been carrying out operations on epileptic patients, extracting the scarred brain tissue that was causing their seizures. This procedure was the exact one Penfield wished to perform himself, and he was eager to observe Foerster’s work, step by step, in the operating room.
In 1928, Foerster invited Penfield to watch him remove from a patient’s brain a scar resulting from a gunshot wound sustained sixteen years earlier. Penfield was able to take the scar tissue to a small laboratory specially equipped to apply the new Spanish staining techniques. There he discovered what he had been searching for: glia. He saw the cells he had viewed before in other injured brains, but this time could see them in greater detail, with all their complex branches clearly discernible. This exciting breakthrough was one of the highlights of Penfield’s life. He was face to face with the cellular aberrations that caused the patient’s seizures, a discovery fundamental to understanding how disease or injury to the brain, and scar formation during healing, caused epilepsy. Understanding the cause opened the door to finding a cure.
Penfield’s findings excited Foerster, who proposed that they collaborate to publish descriptions of twelve cases of similar operations he had performed, all of which had led to improvements in his patients. Foerster wanted Penfield to examine microscopically the brain specimens he had extracted during his successful operations for epilepsy. This tissue held evidence on the cause of the patients’ seizures.4
During the rest of his stay in Breslau, Penfield documented the presence of microscopic abnormalities in brain tissue from twelve patients who experienced excellent seizure control for up to five years after their operation. In their joint paper, Penfield and Foerster combined the positive results of the surgery with descriptions of the abnormal brain tissue, thereby linking the cause and the cure. Foerster’s operation seemed a promising way to provide seizure control for desperate patients, and it gave Penfield a vital tool for the future. He now had the scientific justification he wanted for removing abnormal tissue, as Foerster had done, using only local anesthesia. With the patient conscious and cooperating during the operation, Penfield could stimulate the brain to map out motor and language areas, which he would not remove, and identify areas of abnormality to be excised. With the expectation of curing their epilepsy, Penfield would use this approach with a large group of patients. This epiphany set the stage for the rest of his career.
In 1928, Penfield took up residence in Montreal to pursue a long-held dream, establishing a specialized neurological institute at McGill University. His plan—which became his life’s mission—was to build an institute near, but independent of, a general teaching hospital. He envisioned a neurological institute that would combine facilities for patients and researchers in the same building, providing a central point of research and discovery for the region. A major asset in this ambitious effort was neurosurgeon William V. Cone, Penfield’s first student and a close collaborator in New York, who moved with him to Montreal. Penfield described Cone as a “brilliant operator and technician”—a scholarly man dedicated to patient care, to perfecting the discipline of surgery, and to discovering innovations in pathology. In Penfield’s view, they were “fellow explorers,” and working with Cone made him “twice as effective.”
Penfield was a skilled collaborator, and one of his early successes was bringing neurologists from different hospitals in Quebec together for a weekly conference to exchange insights about puzzling or unusual cases. Those discussions forged a new bond between English-Canadian and French-Canadian neurologists. Penfield’s vision for a neurological institute extended this sort of collaboration on a more ambitious scale. But this plan could be realized only with major financial backing, and after initially being denied a grant from the Rockefeller Foundation, Penfield obtained his funding from two unlikely sources.
The first gift came from the mother of a sixteen-year-old boy who had uncontrolled major epileptic attacks from injuries likely sustained by the use of forceps during his birth. In gratitude for Penfield’s taking on her son’s case, the boy’s mother sent him an unsolicited check for $10,000 to expand his research efforts in epilepsy. Before operating on the boy, Penfield used her money to consult several senior colleagues about the surgical options. He then performed what he termed a “frankly exploratory operation,” in which he removed an artery from the left side of the boy’s brain, believing it was causing the attacks. The procedure was successful and relieved the boy’s seizures. Eighteen months later, the mother died of cancer and left Penfield $50,000 to pursue his mission.
The second windfall came from the father of a young man with unlocalized epileptic seizures. Penfield performed a radical operation in which he removed nerves connected to the arteries that entered the skull. Before the surgery, he informed the boy’s parents that he had previously performed this operation in monkeys without ill effect. “The boy was greatly improved by the operation, if not cured,” Penfield later reported. The patient’s father was a member of the Board of Trustees of the Rockefeller Foundation, and after the surgery was over, he discussed Penfield’s work with the new director of the Rockefeller Foundation’s division of medical education, Alan Gregg.
In March 1931, Penfield met with Gregg in his lower Manhattan office, where the panoramic view from the twenty-seventh floor took in the Hudson River, East River, and Long Island Sound. In this delightful setting, the two men had a long, friendly discussion about neurology, neurosurgery, and research in Europe. Being cautious, Penfield did not mention his hopes for a neurological institute, nor did Gregg hint at Rockefeller’s plans for funding. After he returned home, Penfield sent Gregg a warm invitation to visit Montreal.
Seven months later, Gregg visited Penfield at his home and astonished his host when he pulled the original application from his briefcase, placed it on the coffee table, and said, “This is exactly the sort of thing for which we are always searching at the Rockefeller Foundation. . . . I think I understand what you want to do. . . . Don’t ever thank us. We thank you. You will be helping us when you do your job.” Penfield received $1,232,000 from the foundation.
The Montreal Neurological Institute, L’Institut Neurologique de Montréal, opened its doors in 1934. “The Neuro” epitomized the wisdom of advancing science, teaching, and patient care under a single umbrella. Around the Institute, Penfield became known as “The Chief”; he was a skilled and innovative neurosurgeon as well as a strong leader. He further developed the approach he had witnessed in Breslau of operating on epilepsy patients while they were awake and conscious so that he could pinpoint the abnormal tissue responsible for their seizures—a technique that came to be known as the Montreal Procedure. These operations opened up new possibilities for scientific discoveries about specialization in the human brain.5
Brenda Milner, who became a crucial player in the development of memory science, was a graduate student in Psychology at McGill University when she began her collaboration with Penfield. Born in Manchester, England, in 1918, she studied experimental psychology during her undergraduate years at the University of Cambridge. There her mentors included a prominent experimental psychologist and memory theoretician, Sir Frederic Bartlett. Her research supervisor, Oliver Zangwill, also an experimental psychologist, pioneered the study of neurological patients and was keenly interested in memory disorders.6
Milner moved to Montreal in 1944 and two years later had the distinction of being a student in the first seminar at McGill University taught by Donald O. Hebb, a physiological psychologist who was highly influential in the science of learning and memory. Three years later, Milner became Hebb’s graduate student. When Penfield invited Hebb to send someone
from his lab to study his surgical cases, Milner jumped at the opportunity. Her mandate was to design and conduct cognitive research with epileptic patients, creating tests to assess their capabilities both before and after surgery to document its effects on the brain. Thus, one of the great partnerships in the history of science was born.
In the early 1950s, Milner and Penfield undertook a detailed study of two patients whose case histories were highly atypical. The patients, F.C. and P.B., were noteworthy because they provided new data about the vital function of structures in the inner part of each temporal lobe—the same structures that Scoville would eventually remove from Henry’s brain.7
Penfield operated on a great many epileptic patients to control their seizures, and F.C. and P.B. were part of that group. Before their operations, they did not present differently from the other patients. But afterward, both faced a complication that no one had anticipated: a lasting inability to record new experiences. Why this aberrant outcome?
To answer this question, Penfield needed to understand how the damage in these two patients differed from that in the other patients in his series. Both men had undergone a standard procedure: a partial left temporal lobectomy. In this operation, Penfield typically removed the cortex—the superficial layer—of the lateral temporal lobe, along with varying amounts of tissue deep in the temporal lobe: the amygdala, hippocampus, and neighboring cortex. Penfield had not done or noticed anything unusual during the operation on either man.
As soon as F.C. recovered from the operation, it was clear that he was unable to form new memories. P.B.’s case was slightly different, in that his surgery was carried out in two stages five years apart, and only after the second stage did he become amnesic. His first operation was similar to F.C.’s, but less tissue was removed: Penfield spared the hippocampus and other deep temporal-lobe structures. But after he went home, P.B. continued to have seizures, so five years later, Penfield operated again, this time removing the hippocampus and surrounding tissue. When P.B. recovered from the procedure, he too was amnesic.
Although the resultant severe memory loss pointed to the hippocampus and surrounding tissue as the culprit, Penfield could not understand why the damage in these two men was different from that of the other patients who underwent a left temporal lobectomy. In most of those cases, as in F.C. and P.B., part of the left hippocampus was included in the removal. Why then were these men amnesic when dozens of other patients who received a similar operation were not?
Penfield and Milner suspected that F.C. and P.B. might have some undetected abnormality in the corresponding area in their right hippocampal region. They reasoned that the abnormality discovered in the left temporal lobe at the time of the operation was likely due to a birth injury, which could have affected the right medial temporal lobe as well. Herbert Jasper, a renowned neurophysiologist at the Neuro, who conducted several EEG studies with F.C. and P.B, ultimately proved this hypothesis correct. In both men, Jasper found clear evidence of damage to the hippocampal region on the non-operated side of their brains. This abnormality, which was related to their epilepsy, was not obvious before surgery but was apparent in the postoperative EEG studies.8
In 1964, researchers obtained further clarity on P.B.’s case. After he died of a heart attack, his wife allowed Penfield to examine P.B.’s brain in the laboratory to probe the cause of her husband’s amnesia. When Gordon Mathieson, a neuropathologist at the Neuro, examined the brain, he found that the right hippocampus was shrunken, with only a small number of neurons surviving. This massive destruction likely stemmed from an injury at the time of his birth.9
Unlike the other patients in Penfield’s series who still had one normal temporal lobe, these men had two abnormal temporal lobes—the one removed during the operation, and the one that remained. It was this double loss that made them exceptional. These cases showed that the anatomical foundation for amnesia is a loss of function in both hippocampi. But if a person has damage to only one hippocampus, either the left or the right, the result is not catastrophic. Subsequent research on hundreds of patients has taught us that the hippocampus can be removed safely on one side with only minor memory impairment, as long as the other hippocampus is intact. One hippocampus by itself apparently can compensate largely for its missing twin, suggesting that the two structures share a general capability for making memories. Details of brain anatomy may explain this sharing of function. We know that the left temporal lobe is specialized to process verbal information and the right temporal lobe visual-spatial information. Anatomical bridges that cross the brain from left to right and right to left give each temporal lobe access to the specialized information from the other side. When one hippocampus is missing, the remaining one can engage multiple kinds of knowledge, both verbal and nonverbal, to support satisfactory learning and memory.10
Milner evaluated F.C. and P.B.’s cognitive capacities before and after their operations, using measures of their overall intelligence and memory. By comparing these two sets of test scores, she identified ways in which their cognitive function was altered, or unaltered, by the left temporal lobectomy. She could then link any deficits she uncovered to the damaged brain structures. Their amnesia, which Milner meticulously documented, was all the more striking because it occurred against a background of normal intelligence. Before their operations, F.C.’s IQ was average and P.B.’s was above average. Both men showed no change in their IQ after their operation—in other words, they were still capable, intelligent men. They could repeat strings of digits forward and backward and do simple arithmetic problems in their head, indicating that they could attend to and accurately perceive test stimuli and keep them in mind for a few seconds. Despite these intact cognitive abilities, however, they both failed to remember new information. Their long-term memory capacities were shot—and would never recover.11
The results for F.C. and P.B. made it clear that their memory loss was not limited to a certain kind of information, but instead encompassed all kinds of test materials, public and private events, and general knowledge. F.C. and P.B. had a global amnesia. As is usually the case, their immediate recall or recognition of the test stimuli and everyday events was better than after several minutes or hours had passed; the passage of time takes its toll on memory. But F.C. and P.B.’s amnesia was not complete; unlike Henry, they each retained a smidgen of long-term memory capacity to guide them through everyday life. F.C. was able to resume his job as a glove cutter, and P.B. his job as a draftsman.
In 1954, Milner presented the psychological test results for F.C. and P.B. at the annual meeting of the American Neurological Association in Chicago. Prior to the meeting, Scoville read a long abstract of Milner’s talk and called Penfield to tell him about his two similar cases of amnesia, H.M. and D.C. Penfield was already interested in memory mechanisms, and Scoville’s cases attracted his attention because they supported his ideas on the neural localization of memory. Accordingly, Penfield asked Milner whether she would be interested in testing Scoville’s patients, and she embraced the opportunity. With this collaboration already underway at the time of the meeting, Scoville was asked to lead a formal discussion following Milner’s presentation. He described his operative technique and results for thirty patients, twenty-nine of whom were schizophrenic and one who suffered from intractable seizures. All had the medial temporal-lobe structures removed, but two had received more extensive operations. Henry, the epileptic patient, was one of them.12
The other patient was a forty-seven-year-old physician with paranoid schizophrenia, known by his initials, D.C. Over time, D.C. had become violent and combative, and tried to kill his wife. He was institutionalized, and drastic treatments—insulin-shock therapy to induce a coma, and electroconvulsive therapy to trigger a seizure—failed to improve his situation. In a last-ditch effort to help D.C., Scoville traveled to Manteno State Hospital in Illinois in 1954 and performed his bilateral medial temporal-lobe resection, assisted by John F. Kendrick Jr., a neurosurgeon from Richmond, Virginia
. This operation, in which D.C.’s hippocampus and amygdala were removed on both sides, took place approximately nine months after Henry’s. Postoperatively, D.C.’s aggressive behavior disappeared, and although he still showed signs of paranoia, he became more friendly and manageable. Like Henry, he exhibited profound memory impairment and was unable to find his way to his hospital bed or recognize the staff.13
During his American Neurological Association talk, Scoville highlighted one striking behavioral result, a near-total loss of recent memory in two patients that was unaccompanied by personality change or intellectual decline. Although Scoville’s clinical descriptions of Henry and D.C. were compelling, they lacked the rigor of a thorough, systematic investigation. It was important to probe the cognitive capacities of the two men, one by one in formal experiments. Cognitive deficits are often subtle and can be overlooked without measuring performance numerically and comparing patients’ scores to the scores of healthy individuals. Penfield arranged for Milner to review nine of the thirty patients who had received bilateral or unilateral medial temporal-lobe operations at Scoville’s hand, and who were sufficiently stable to undergo testing. Henry was one of them.
The results of Milner’s psychological evaluation of Scoville’s patients formed the basis of Scoville and Milner’s “Loss of Recent Memory after Bilateral Hippocampal Lesions,” the benchmark Journal of Neurology, Neurosurgery, and Psychiatry paper. This often-cited article provided the scientific evidence for the pattern of memory loss with preserved intelligence Scoville had seen in his initial clinical evaluation of Henry and D.C. This paper has become a classic in neuroscience literature for several reasons: of greatest importance, it informed neurosurgeons that destroying the medial temporal-lobe structures on both sides of the brain would cause amnesia and should be avoided. The results also established, for the first time, that a distinct region of the brain—the hippocampus and its neighbors—was necessary for long-term memory formation. The Scoville and Milner article also inaugurated decades of experimental studies of Henry and other amnesic patients, and inspired animal models of amnesia that yielded a wealth of information on the biology of memory processes.14
Permanent Present Tense Page 6
