Amazing technological progress since 2005 has made it feasible to map the cognitive and neural mechanisms that underlie memory formation at the level of individual brain cells. The discipline of neuroscience is experiencing a series of transformative events driven by advanced technology. We can now observe with greater specificity the mysterious happenings inside the living brain. Sophisticated techniques will provide new kinds of information: optogenetic technology for precisely controlling specific neurons using genes, molecular engineering for fast and direct readout of neural activity, and connectomics to map the 100 trillion connections that make up the brain’s neural networks. In parallel, cognitive scientists continue to advance theories about the fractionation and organization of memory processes, inviting researchers to map precisely defined computations onto discrete brain circuits.
Although each of these innovative technologies is fascinating in its own right, more important is what they can accomplish collectively. After spending decades mapping the overall anatomy of the brain and accumulating information at several levels, from behavioral to cellular, scientists are now striving to connect all that information into a comprehensive picture. In the field of memory research, we want to know how something so intangible as a thought or fact can lodge itself for decades in the living tissue of the brain. The ultimate goal of neuroscience is to understand how the billions of neurons in the brain, each with roughly 10,000 synapses, interact to create the workings of the mind.
We will, of course, never fully achieve that goal. Even as I type these words, I wonder what exactly is going on in my overcrowded brain. How do my networks of neurons marshal together the pieces of complex technical information I have learned, synthesize them into thoughts and perspectives, and put the total sum into words my fingers are then directed to type? How remarkable that the brain can fashion simple sentences out of such chaos. We will never have a formula to fully explain how the noisy activity of our brains gives rise to thoughts, emotions, and behavior. But the magnitude of the goal makes pursuing it all the more exciting. This challenge attracts brilliant adventurers and risk takers to our field. And even if we will never completely understand the way the brain works, whatever small part of the truth we are able to learn will bring us one step closer to understanding who we are.
Acknowledgments
Henry Gustave Molaison was the subject of wide-ranging experimental scrutiny for more than five decades. This research began in 1955 in Brenda Milner’s laboratory at the Montreal Neurological Institute and moved to MIT in 1966. From 1966 until 2008, one hundred twenty-two physicians and scientists had the opportunity to study Henry, either as members of my lab or as our collaborators at other institutions. We all understand what a rare gift it was to work with him, and we are profoundly grateful for his dedication to research. He taught us a great deal about the cognitive and neural organization of memory. The research with Henry described in this book draws from these five decades of investigation.
During Henry’s fifty visits to the MIT Clinical Research Center he received VIP treatment from many nurses and from the diet staff, headed by Rita Tsay; they deserve high praise for the wonderful care they gave him. For the last twenty-eight years of Henry’s life, he lived at Bickford Health Care Center where he was affectionately looked after. Rich information about Henry’s activities came from staff members at Bickford, and their accounts greatly enriched my telling of his story. Every time I had the slightest question about Henry, Eileen Shanahan provided an answer, and I thank her for that. Meredith Brown did a superb job of sorting through twenty-eight years of details in Henry’s Bickford charts and summarizing the important points.
My gratitude for crucial suggestions and corrections goes to Paymon Ashourian, Jean Augustinack, Carol Barnes, Sam Cooke, Damon Corkin, Leyla de Toledo-Morrell, Howard Eichenbaum, Guoping Feng, Matthew Frosch, Jackie Ganem, Isabel Gautier, Maggie Keane, Elizabeth Kensinger, Mark Mapstone, Bruce McNaughton, Chris Moore, Richard Morris, Peter Mortimer, Morris Moscovitch, Lynn Nadel, Ross Pastel, Russel Patterson, Brad Postle, Molly Potter, Nick Rosen, Peter Schiller, Reza Shadmehr, Brian Skotko, André van der Kouwe, Matt Wilson, and David Ziegler. Their sharp minds gave me brilliant and frank feedback, which greatly improved the book.
I benefitted enormously from stimulating discussions with colleagues in neuroscience who graciously agreed to let me record their views on the importance of Henry’s contributions and the future direction of memory research. I intended to weave this exciting material into chapter 14, but alas it ended up on the cutting room floor. Nevertheless, I am obliged to Carol Barnes, Mark Bear, Ed Boyden, Emery Brown, Martha Constantine-Paton, Bob Desimone, Michale Fee, Guoping Feng, Mickey Goldberg, Alan Jasanoff, Yingxi Lin, Troy Littleton, Carlos Lois, Earl Miller, Peter Milner, Mortimer Mishkin, Chris Moore, Richard Morris, Morris Moscovitch, Ken Moya, Elisabeth Murray, Elly Nedivi, Russel Patterson, Tommy Poggio, Terry Sejnowski, Sebastian Seung, Mike Shadlen, Carla Shatz, Edie Sullivan, Mriganka Sur, Locky Taylor, Li-Huei Tsai, Chris Walsh, and Matt Wilson. I thank Leya Booth for transcribing these interviews quickly and accurately.
Helpful historical information came from conversations and emails with Brenda Milner, Bill Feindel, and Sandra McPherson at the Montreal Neurological Institute, and Marilyn Jonesgotman generously shared her 1977 interview with Henry. Alan Baddeley, Jean Gotman, Jake Kennedy, Ronald Lesser, Yvette Wong Penn, Arthur Reber, and Anthony Wagner contributed insights about cognitive and neural processes related to memory. Myriam Hyman imparted her advanced knowledge of ancient Greek, while Emilio Bizzi educated me about brain surgery, and Larry Squire advised me about terminology. Edie Sullivan helped me reconstruct the testing protocols we designed and carried out with Henry in the 1980s, and Mary Foley and Larry Wald helped document the activities of the epic night when Henry died.
For providing information about Hartford landmarks, I thank Brenda Miller, Manager of the Hartford History Center and Curator of the Hartford Collection at the Hartford Public Library, and Bill Faude, Project Historian at the Hartford History Center of the Hartford Public Library. At the MIT Science Library, Peter Norman was helpful in facilitating our research. I received a helpful analysis of Henry’s memorable plane ride from Sandra Martin McDonough, pilot and flight instructor. Helen and Bob Sak and Gyorgy Buzsaki kindly sent me their reviews of the off-Broadway play about Henry.
For their help with the figures and photos, I am grateful to Henry’s conservator Mr. M., Robert Ajemian, Jean Augustinack, Evelina Busa, Henry Hall, Sarah Holt, Producer for NOVA/PBS & Holt Productions, Bettiann McKay, Alex McWhinnie, Laura Pistorino, David Salat, André van der Kouwe, Victoria Vega, and Diana Woodruff-Pak.
Several people have been with me for the long haul and deserve special mention. Bettiann McKay is my administrative assistant and more importantly my friend and lifeline. Her contributions to my work would fill another book of this size. Suffice it to say that she was always there to give any kind of help whenever I needed it, and I will always be thankful for her generosity. John Growdon, my colleague for more than three decades, gave me sage advice, starting with my fledgling book proposal and continuing to the final draft of the book. Heaps of credit also go to Kathleen Lynch, a superb editor, who read every chapter more than once and gave me perceptive feedback as well as advice about all aspects of publishing.
Many friends offered encouragement. Over memorable dinners together, Lisa Scoville Dittrich helped me recapture our privileged childhood. My former students and postdocs gave their enthusiastic endorsement as did many others, including Edna Baginsky, Carol Christ, Holiday Smith Houck, David Margolis, Kerry Tribe, and Steve Pinker. Welcome inspiration also came from Susan Safford Andrews, Bobbi Topor Butler, Becky Crane Rafferty, Nancy Austin Reed, and Pat McEnroe Reno in Connecticut; from Doris, Jean-Claude, and Karine Welter in Paris; and from my fabulous Pier 7 neighbors in the Navy Yard. Warmest thanks also to my Smith College classmates who are always an amazing source of support.
I am pleased to salu
te my fellow faculty members in MIT’s Department of Brain and Cognitive Sciences. I have benefitted greatly from decades of interactions with them and am excited and inspired by their extraordinary work. I also want to acknowledge the wonderful graduate students and postdocs in our department who responded quickly and cheerfully to my emails asking for miscellaneous information that had nothing to do with science.
An affectionate thank you goes to my children, Zachary Corkin, Jocelyn Corkin Mortimer, and Damon Corkin for their love, encouragement, and praise—and for keeping me humble. They and their families are a source of energy and delight. One of the great joys of writing this book was the discovery that Jocelyn is a superb editor. She meticulously read many drafts and caught countless errors that others had missed. Her contributions improved the telling of Henry’s story by many orders of magnitude, and I thank her most sincerely. I also greatly appreciate the endless interest and enthusiasm of other family members—Jane Corkin, Donald Corkin, and Patricia and Jake Kennedy and their family.
I am fortunate to have the guidance of the Wyley Agency in achieving my dream to write this book. The members of their highly professional and gifted staff do an impressive job in carrying out their various responsibilities. In particular, I want to thank Andrew Wylie, Scott Moyers, Rebecca Nagel, and Kristina Moore, who are exceptional people with whom to work.
At Perseus Books, I received much needed editorial and production help from Lara Heimert, Ben Reynolds, Chris Granville, Katy O’Donnell, and Rachel King. I am grateful for their acumen and patience, and for their willingness to become immersed in the life of Henry Molaison and the neuroscience of memory.
Notes
Prologue
1. Neuroscience is a giant tent that covers diverse disciplines, all intended to advance knowledge about the brain and nervous system. Systems neuroscience is a branch of neuroscience whose mission is to describe the specialization of distinct circuits of interconnected neurons that give rise to specific kinds of behavior, such as declarative and nondeclarative memory. The systems include sensory capacities such as vision, hearing, and touch, and high-order processes such as problem solving, goal-directed behavior, spatial ability, motor control, and language. Studying Henry gave us the extraordinary opportunity to propel the science of human memory forward by examining processes distributed throughout the brain; W. B. Scoville and B. Milner, “Loss of Recent Memory after Bilateral Hippocampal Lesions,” Journal of Neurology, Neurosurgery, and Psychiatry 20 (1957): 11–21.
2. Scoville and Milner, “Loss of Recent Memory after Bilateral Hippocampal Lesions.”
3. Ibid. In previous memory testing with Henry, Milner had used test materials presented through vision and hearing.
4. P. J. Hilts, “A Brain Unit Seen as Index for Recalling Memories,” New York Times (1991, September 24); P. J. Hilts, Memory’s Ghost: The Strange Tale of Mr. M. and the Nature of Memory (New York: Simon & Schuster, 1995).
5. N. J. Cohen and L. R. Squire, “Preserved Learning and Retention of Pattern-Analyzing Skill in Amnesia: Dissociation of Knowing How and Knowing That,” Science 210 (1980): 207–10.
Chapter One: Prelude to Tragedy
1. O. Temkin, The Falling Sickness: A History of Epilepsy from the Greeks to the Beginnings of Modern Neurology (Baltimore, MD: Johns Hopkins Press, 1971).
2. Ibid.
3. Ibid.
4. W. Feindel et al., “Epilepsy Surgery: Historical Highlights 1909–2009,” Epilepsia 50 (2009): 131–51.
5. Ibid.
6. M. D. Niedermeyer et al., “Rett Syndrome and the Electroencephalogram,” American Journal of Medical Genetics 25 (2005): 1096–8628; H. Berger, “Über Das Elektrenkephalogramm Des Menschen” European Archives of Psychiatry and Clinical Neuroscience 87 (1929): 527–70.
7. W. Feindel et al., “Epilepsy Surgery: Historical Highlights 1909-2009,” Epilepsia 50 (2009): 131–51; W. B. Scoville et al., “Observations on Medial Temporal Lobotomy and Uncotomy in the Treatment of Psychotic States; Preliminary Review of 19 Operative Cases Compared with 60 Frontal Lobotomy and Undercutting Cases,” Proceedings for the Association for Research in Nervous and Mental Disorders 31 (1953): 347–73; O. Temkin, The Falling Sickness: A History of Epilepsy from the Greeks to the Beginnings of Modern Neurology (Baltimore, MD: Johns Hopkins Press, 1971); B. V. White et al., Stanley Cobb: A Builder of the Modern Neurosciences (Charlottesville, VA: University Press of Virginia, 1984).
8. W. Feindel et al., “Epilepsy Surgery: Historical Highlights 1909–2009,” Epilepsia 50 (2009): 131–51.
9. Jack Quinlan, October 8, 1945.
10. W. B. Scoville, “Innovations and Perspectives,” Surgical Neurology 4 (1975): 528.
11. W. B. Scoville and B. Milner, “Loss of Recent Memory after Bilateral Hippocampal Lesions,” Journal of Neurology, Neurosurgery, and Psychiatry 20 (1957): 11–21.
12. Liselotte K. Fischer, Unpublished report of psychological testing, Hartford Hospital, August 24, 1953.
Chapter Two: “A Frankly Experimental Operation”
1. J. El-Hai, The Lobotomist: A Maverick Medical Genius and His Tragic Quest to Rid the World of Mental Illness (Hoboken, NJ: J. Wiley, 2005); John F. Kennedy Memorial Library, “The Kennedy Family: Rosemary Kennedy”; www.jfklibrary.org/JFK/The-Kennedy-Family/Rosemary-Kennedy.aspx (accessed November 2012).
2. J. L. Stone, “Dr. Gottlieb Burckhardt—The Pioneer of Psychosurgery,” Journal of the History of the Neurosciences 10 (2001): 79–92; El-Hai, The Lobotomist.
3. B. Ljunggren et al., “Ludvig Puusepp and the Birth of Neurosurgery in Russia,” Neurosurgery Quarterly 8 (1998): 232–35.
4. C. F. Jacobsen et al., “An Experimental Analysis of the Functions of the Frontal Association Areas in Primates,” Journal of Nervous and Mental Disorders 82 (1935): 1–14.
5. E. Moniz, Tentatives Opératoires dans le Traitement de Certaines Psychoses (Paris, France: Masson, 1936).
6. Ibid.
7. E. Moniz, “Prefrontal Leucotomy in the Treatment of Mental Disorders,” American Journal of Psychiatry 93 (1937): 1379–85; El-Hai, The Lobotomist.
8. W. Freeman and J. W. Watts, Psychosurgery in the Treatment of Mental Disorders and Intractable Pain (Springfield, IL: C. C. Thomas, 1950); J. D. Pressman, Last Resort: Psychosurgery and the Limits of Medicine (Cambridge Studies in the History of Medicine) (New York: Cambridge University Press, 1998); El-Hai, The Lobotomist.
9. D. G. Stewart and K. L. Davis, “The Lobotomist,” American Journal of Psychiatry 165 (2008): 457–58; El-Hai, The Lobotomist.
10. J. E. Rodgers, Psychosurgery: Damaging the Brain to Save the Mind (New York: HarperCollins, 1992); El-Hai, The Lobotomist.
11. Pressman, Last Resort; El-Hai, The Lobotomist.
12. Pressman, Last Resort.
13. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Psychosurgery: Report and Recommendations (Washington, DC: DHEW Publication No. [OS] 77–0001,1977); available online at videocast.nih.gov/pdf/ohrp_psychosurgery.pdf (accessed November 2012).
14. W. B. Scoville et al., “Observations on Medial Temporal Lobotomy and Uncotomy in the Treatment of Psychotic States: Preliminary Review of 19 Operative Cases Compared with 60 Frontal Lobotomy and Undercutting Cases,” Proceedings for the Association for Research in Nervous and Mental Disorders 31 (1953): 347–73.
15. W. Penfield and M. Baldwin, “Temporal Lobe Seizures and the Technic of Subtotal Temporal Lobectomy,” Annals of Surgery 136 (1952): 625–34, available online at www.ncbi.nlm.nih.gov/pmc/articles/PMC1803045/pdf/annsurg01421–0076.pdf (accessed November 2012); Scoville et al., “Observations on Medial Temporal Lobotomy and Uncotomy.”
16. W. B. Scoville and B. Milner, “Loss of Recent Memory after Bilateral Hippocampal Lesions,” Journal of Neurology, Neurosurgery, and Psychiatry 20 (1957): 11–21, available online at jnnp.bmj.com/content/20/1/11.short (accessed November 2012).
17. Ibid.
18. MacLean, “Some Psychiatric Implications”; Sc
oville and Milner, “Loss of Recent Memory.”
19. Scoville and Milner, “Loss of Recent Memory”; S. Corkin et al., “H.M.’s Medial Temporal Lobe Lesion: Findings from MRI,” Journal of Neuroscience 17 (1997): 3964–79.
20. P. Andersen et al., Historical Perspective: Proposed Functions, Biological Characteristics, and Neurobiological Models of the Hippocampus (New York: Oxford University Press, 2007); J. W. Papez, “A Proposed Mechanism of Emotion. 1937,” Journal of Neuropsychiatry and Clinical Neurosciences 7 (1995): 103–12; MacLean, “Some Psychiatric Implications.”
21. Scoville and Milner, “Loss of Recent Memory.”
Chapter Three: Penfield and Milner
1. W. Penfield and B. Milner, “Memory Deficit Produced by Bilateral Lesions in the Hippocampal Zone,” AMA Arch Neurol Psychiatry 79:5 (May 1958) 475–97; B. Milner, “The Memory Defect in Bilateral Hippocampal Lesions,” Psychiatric Research Reports of the American Psychiatric Association 11 (1959): 43–58.
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