34. Ibid. See also J. N. Sanes and J. P. Donoghue, “Plasticity and Primary Motor Cortex,” Annual Review of Neuroscience 23 (2000): 393–415; available online at tinyurl.com/8oyl87x (accessed September 2012).
35. E. Dayan and L. G. Cohen, “Neuroplasticity Subserving Motor Skill Learning,” Neuron 72 (2011): 443–54.
36. R. A. Poldrack et al., “The Neural Correlates of Motor Skill Automaticity,” Journal of Neuroscience 25 (2005): 5356–64.
37. C. J. Steele and V. B. Penhune, “Specific Increases within Global Decreases: A Functional Magnetic Resonance Imaging Investigation of Five Days of Motor Sequence Learning,” Journal of Neuroscience 30 (2010): 8332–41.
Chapter Nine: Memory without Remembering II
1. I. P. Pavlov, Conditioned Reflexes: An Investigation of the Physiological Activity of the Cerebral Cortex (London: Oxford University Press, 1927). Psychologist Edwin B. Twitmyer made a similar finding in humans nearly simultaneously. In 1902, he happened to observe that when a bell sounded just before a reflex hammer struck a person’s knee and caused an involuntary kneejerk, the individual also exhibited this reflex on hearing the bell, even when the hammer did not strike. Throughout the century following Pavlov and Twitmyer’s discoveries, researchers examined classical conditioning in many species, including rats, crickets, fruit flies, fleas, and sea hares. E. B. Twitmyer, “Knee Jerks without Stimulation of the Patellar Tendon,” Psychological Bulletin 2 (1905): 43–44; I. Gormezano et al., “Twenty Years of Classical Conditioning Research with the Rabbit,” in Progress in Physiological Psychology, ed, J. M. Sprague et al. (New York: Academic Press, 1983), 197–275.
2. D. Woodruff-Pak, “Eyeblink Classical Conditioning in H.M.: Delay and Trace Paradigms,” Behavioral Neuroscience 107 (1993): 911–25.
3. Ibid.
4. Ibid.
5. Ibid.
6. Ibid.
7. Ibid.
8. R. E. Clark et al., “Classical Conditioning, Awareness, and Brain Systems,” Trends in Cognitive Sciences 6 (2002): 524–31.
9. Ibid.
10. Perceptual learning in amnesia was first reported in 1968 by neuropsychologists Elizabeth Warrington and Lawrence Weiskrantz. This discovery was almost as revolutionary as Milner’s initial demonstration of Henry’s preserved mirror-tracing skill. Five of their six amnesic patients had Korsakoff syndrome, in which cell loss occurs in the thalamus and hypothalamus, raising the question whether Henry’s medial temporal-lobe lesions spared this ability. We eventually showed that he was indeed capable of perceptual learning. E. K. Warrington and L. Weiskrantz, “New Method of Testing Long-Term Retention with Special Reference to Amnesic Patients,” Nature 217 (1968): 972–74.; B. Milner et al., “Further Analysis of the Hippocampal Amnesic Syndrome: 14-Year Follow-up Study of H.M.,” Neuropsychologia 6 (1968): 215–34, available online at www.psychology.uiowa.edu/Faculty/Freeman/Milner_68.pdf (accessed November 2012).
11. E. S. Gollin,” Developmental Studies of Visual Recognition of Incomplete Objects,” Perceptual and Motor Skills 11 (1960): 289–98; Milner et al., “Further Analysis of the Hippocampal Amnesic Syndrome.”
12. Milner et al., “Further Analysis of the Hippocampal Amnesic Syndrome.”
13. Ibid.
14. Ibid.
15. J. Sergent et al., “Functional Neuroanatomy of Face and Object Processing. A Positron Emission Tomography Study,” Brain 115 (1992): 15–36; N. Kanwisher, “Functional Specificity in the Human Brain: A Window into the Functional Architecture of the Mind,” Proceedings of the National Academy of Sciences 107 (2010): 11163–70.
16. I. Gauthier et al., “Expertise for Cars and Birds Recruits Brain Areas Involved in Face Recognition,” Nature Neuroscience 3 (2000): 191–97; available online at http://www.systems.neurosci.info/FMRI/gauthier00.pdf (accessed November 2012).
17. C. D. Smith et al., “MRI Diffusion Tensor Tracking of a New Amygdalo-Fusiform and Hippocampo-Fusiform Pathway System in Humans, Journal of Magnetic Resonance Imaging 29(2009): 1248–61.
18. Warrington and Weiskrantz published the first report of repetition priming in 1970, when they discovered that their amnesic patients could complete a three-letter stem—MET—to a previously studied word—METAL—just as often as control participants. The stimuli for this study were two fragmented versions of each word and the completed word. The investigators created the fragmented words by photographing them with patches covering parts of each letter. In an initial study phase, participants first saw the most-fragmented version of all the words, next the less-fragmented version of each, and then the complete word—METAL. They were asked to identify the word as quickly as possible. The purpose of the study was to compare three measures of memory retention: two of them—recall and recognition—were declarative, and the third—partial completion—was nondeclarative. The amnesic group, as expected, had trouble recalling and recognizing the words they had seen before—the hallmark of amnesia. The big shock came in the subsequent test phase, when participants viewed the first three letters of each word and then thought of a five-letter word—retrieval by partial completion. On this measure, the amnesic patients reported as many studied words as the control participants.
Although the researchers did not at the time interpret this result as evidence of spared priming in amnesia, they still published the first demonstration of word-stem completion priming. The method they used gave scientists a way to explore learning without awareness in healthy individuals and in patients with a variety of neurological and psychiatric disorders. See E. K. Warrington and L. Weiskrantz, “Amnesic Syndrome: Consolidation or Retrieval?,” Nature 228 (1970): 628–30.
During the 1980s and ’90s, hundreds of research reports on repetition priming appeared. Memory researchers examined priming effects in healthy participants and amnesic patients, using a wide assortment of text stimuli: words, pseudowords (made-up words that obey the rules of English orthography), word fragments, categories of objects, homophones (words that sound the same but have different meanings, such as bear and bare), pictures, fragmented pictures, and patterns. These elegant studies elucidated the cognitive intricacies of the priming effect, particularly in healthy young adults.
As the body of knowledge on repetition priming grew, the question of preserved repetition-priming in amnesia continued to engage memory experts. In 1984, Peter Graf, Larry Squire, and George Mandler wrote a high-profile paper in which they reported the results of three experiments. Their intent was to compare the performance of amnesic and control participants on four measures of learning: three of them—free recall, recognition, and cued recall—were declarative, whereas the fourth—word completion—was nondeclarative. Participants initially studied a list of words and then took one of the four tests just mentioned. P. Graf et al., “The Information That Amnesic Patients Do Not Forget,” Journal of Experimental Psychology: Learning, Memory, and Cognition 10 (1984): 164–78.
For the free-recall test, participants wrote the words they could remember from the study list on a sheet of paper. For the recognition test, they saw one of the studied words with two others that began with the same three-letter stem. When the studied word was MARket, the distractor words were MARy and MARble. Participants had to pick out the word they had seen previously. For the cued-recall and word-completion tests, participants received the first three letters of the studied words as cues. The critical difference between these two tasks was in the instructions. For cued recall, participants were asked to recall intentionally the list of words with the help of the cues. It was clear to all participants that that this was a memory test. For word completion, participants were told that the three-letter stem was the beginning of an English word, and were asked to make each into a word. They were encouraged to write the first word that came to mind, and were unaware that their memory was being tested.
The findings validated the 1970 results of Warrington and Weiskrantz. The free-recall, recognition, and cued-recall tasks all measured declarative memory, and performance on those tasks, no
t surprisingly, was severely impaired in the amnesic participants. The key issue was whether amnesic patients would perform the word-completion task like controls—and they did. With reference to the explanation of priming as activation of an established representation of the studied words, the scientists concluded that this kind of activation was intact in amnesia. This experiment illustrated the crucial role of instructions in the distinction between declarative ad nondeclarative memory. When the amnesic patients were explicitly asked to recall the list of words with the help of the three-letter stem, they had to access their declarative knowledge, and therefore failed to perform comparably to healthy participants. When they were allowed to rely on their nondeclarative knowledge, however, and simply complete the three-letter stem with the first word that leaped to mind, they could accomplish the task just as successfully as the controls. See Warrington and Weiskrantz, “Amnesic Syndrome: Consolidation or Retrieval?”; R. Diamond and P. Rozin, “Activation of Existing Memories in Anterograde Amnesia,” Journal of Abnormal Psychology 93 (1984): 98–105, available online at http://www.psych.stanford.edu/~jlm/pdfs/DiamondRozin84.pdf (accessed November 2012).
These findings raised a pivotal question: Does the priming effect last as long in amnesic patients as it does in controls? For the amnesic patients’ performance to be considered normal, the answer to this question would have to be yes. Examiners showed participants the study list and then tested them either immediately, after fifteen minutes, or after 120 minutes, using a different set of words at each delay. The patients achieved as many correct responses as controls, and the performance of the two groups was comparable across the three delays. This result meant that the priming effect lasted the same amount of time—two hours—in amnesic patients and in controls. See Warrington and Weiskrantz, “Amnesic Syndrome: Consolidation or Retrieval?”; Graf et al., “The Information That Amnesic Patients Do Not Forget.”
19. J.D.E. Gabrieli et al., “Dissociation among Structural-Perceptual, Lexical-Semantic, and Event-Fact Memory Systems in Amnesia, Alzheimer’s Disease, and Normal Subjects,” Cortex 30 (1994): 75–103.
20. Ibid.
21. Ibid.
22. Diamond and Rozin, “Activation of Existing Memories in Anterograde Amnesia.”
23. Ibid.
24. J.D.E. Gabrieli et al., “Intact Priming of Patterns Despite Impaired Memory,” Neuropsychologia 28 (1990): 417–27; available online at http://web.mit.edu/bnl/pdf/Gabrieli_Milberg_Keane_Corkin_1990.pdf (accessed November 2012).
25. Ibid.
26. Ibid.
27. Ibid.
28. Ibid.
29. M. M. Keane et al., “Priming in Perceptual Identification of Pseudowords Is Normal in Alzheimer’s Disease,” Neuropsychologia 32 (1994): 343–56.
30. Keane et al., “Priming of Perceptual Identification of Pseudowords Is Normal in Alzheimer’s Disease”; M. M. Keane et al., “Evidence for a Dissociation between Perceptual and Conceptual Priming in Alzheimer’s Disease,” Behavioral Neuroscience 105 (1991): 326–42.
31. Ibid.
32. S. E. Arnold et al., “The Topographical and Neuroanatomical Distribution of Neurofibrillary Tangles and Neuritic Plaques in the Cerebral Cortex of Patients with Alzheimer’s Disease,” Cerebral Cortex 1 (1991): 103–16.
33. M. M. Keane et al., “Double Dissociation of Memory Capacities after Bilateral Occipital-Lobe or Medial Temporal-Lobe Lesions,” Brain 118 (1995): 1129–48.
Chapter Ten: Henry’s Universe
1. J. A. Ogden and S. Corkin, “Memories of H.M.,” in Memory Mechanisms: A Tribute to G. V. Goddard, ed. M. Corballis et al. (Hillsdale, NJ: L. Erlbaum Associates, 1991), 195–215.
2. N. Hebben et al., “Diminished Ability to Interpret and Report Internal States after Bilateral Medial Temporal Resection: Case H.M.,” Behavioral Neuroscience 99 (1985): 1031–39; available online at web.mit.edu/bnl/pdf/Diminished %20Ability.pdf (accessed November 2012).
3. S. Kobayashi, “Organization of Neural Systems for Aversive Information Processing: Pain, Error, and Punishment,” Frontiers in Neuroscience 6 (2012); available online at www.ncbi.nlm.nih.gov/pmc/articles/PMC3448295/ (accessed November 2012).
4. Hebben et al., “Diminished Ability”; W. C. Clark, “Pain Sensitivity and the Report of Pain: An Introduction to Sensory Decision Theory,” Anesthesiology 40 (1974): 272–87.
5. Hebben et al., “Diminished Ability”; C. de Graaf et al., “Biomarkers of Satiation and Satiety,” American Journal of Clinical Nutrition 79 (2004): 946–61.
6. Hebben et al., “Diminished Ability.”
7. N. Butters and L. S. Cermak, “A Case Study of the Forgetting of Autobiographical Knowledge: Implications for the Study of Retrograde Amnesia,” in Autobiographical Memory, ed. D. C. Rubin (New York: Cambridge University Press, 1986), 253–72.
8. W. B. Scoville and B. Milner, “Loss of Recent Memory after Bilateral Hippocampal Lesions,” Journal of Neurology, Neurosurgery, and Psychiatry 20 (1957): 11–21; B. Milner et al., “Further Analysis of the Hippocampal Amnesic Syndrome: 14-Year Follow-up Study of H.M.,” Neuropsychologia 6 (1968): 215–34, available online at www.psychology.uiowa.edu/Faculty/Freeman/Milner_68.pdf (accessed November 2012).
9. H. J. Sagar et al., “Dissociations among Processes in Remote Memory,” Annals of the New York Academy of Sciences 444 (1985): 533–55.
10. Ibid.
11. Sagar et al., “Dissociations among Processes”; H. F. Crovitz and H. Schiffman, “Frequency of Episodic Memories as a Function of Their Age,” Bulletin of the Psychonomic Society 4 (1974): 517–18.
12. Sagar et al., “Dissociations among Processes”; H. J. Sagar et al., “Temporal Ordering and Short-Term Memory Deficits in Parkinson’s Disease,” Brain 111 ( Pt 3) (1988): 525–39. The “last in, first out” theory dates from 1881, when French psychologist Théodule Ribot noted that retrograde memory loss often follows a temporal gradient—newer memories are more likely to be lost, while older memories are more likely to be preserved. T. Ribot, Les Maladies de la Mémoire (Paris: Germer Baillière, 1881).
13. The results of our structured interview with Henry showed that the early clinical reports from the 1950s and 60s had grossly underestimated the length of his retrograde amnesia. The processes needed to retrieve memories from the years before his operation were severely disrupted. One of our tasks, the Crovitz test, was later criticized by us and others on the grounds that it was not sufficiently sensitive in differentiating between memory reports that were just detailed enough to merit the maximum score of three and others that also earned a three but were much richer in detail. We needed a test that would make a finer distinction among the top performers. Our subsequent experiments achieved that goal. Crovitz and Schiffman, “Frequency of Episodic Memories.”
14. Taken together, our early studies of Henry’s retrograde amnesia yielded conflicting results, in part, because they did not distinguish between personal remote memories that reflected general knowledge, such as the name of a high school, and those that relied on reliving an experience, such as a first kiss. As we saw from Henry’s case, he could tell us what high school he had attended, but not what happened on his graduation day. When we questioned him, it was apparent that although he could provide answers to the most general questions, something was missing when we pressed him for more specifics.
15. E. Tulving, “Episodic and Semantic Memory,” in Organization of Memory, ed. E. Tulving and W. Donaldson (New York: Academic Press, 1972), 381–403.
16. L. R. Squire, “Memory and the Hippocampus: A Synthesis from Findings with Rats, Monkeys, and Humans,” Psychological Review 99 (1992): 195–231.
17. L. R. Squire and P. J. Bayley, “The Neuroscience of Remote Memory,” Current Opinion in Neurobiology 17 (2007): 185–96.
18. L. Nadel and M. Moscovitch, “Memory Consolidation, Retrograde Amnesia and the Hippocampal Complex,” Current Opinion Neurobiology 7 (1997): 217–27; also Moscovitch and Nadel, “Consolidation and the Hippocampal Complex Revisited: In Defense of the Mul
tiple-Trace Model,” Current Opinion Neurobiology 8 (1998): 297–300.
19. B. Milner, “The Memory Defect in Bilateral Hippocampal Lesions,” Psychiatric Research Reports of the American Psychiatric Association 11 (1959): 43–58.
20. S. Steinvorth et al., “Medial Temporal Lobe Structures Are Needed to Re-experience Remote Autobiographical Memories: Evidence from H.M. and W.R.,” Neuropsychologia 43 (2005): 479–96.
21. Ibid.; See also E. A. Kensinger and S. Corkin, “Two Routes to Emotional Memory: Distinct Neural Processes for Valence and Arousal,” Proceedings of the National Academy of Sciences 101 (2004): 3310–15; available online at www.pnas.org/content/101/9/3310.full.pdf+html (accessed November 2012).
22. Steinvorth et al., “Medial Temporal Lobe Structures.”
23. L. R. Squire, “The Legacy of Patient H.M. for Neuroscience,” Neuron 61 (2009): 6–9; available online at whoville.ucsd.edu/PDFs/444_Squire _Neuron_2009.pdf (accessed November 2012); S. Corkin et al., “H.M.’s Medial Temporal Lobe Lesion: Findings from MRI,” Journal of Neuroscience 17 (1997): 3964–79.
24. Steinvorth et al., “Medial Temporal Lobe Structures Are Needed”; Nadel and Moscovitch, “Memory Consolidation, Retrograde Amnesia, and the Hippocampal Complex.”
25. Y. Nir and G. Tononi, “Dreaming and the Brain: From Phenomenology to Neurophysiology,” Trends in Cognitive Sciences 14 (2010): 88–100.
26. P. Maquet et al., “Functional Neuroanatomy of Human Rapid-Eye-Movement Sleep and Dreaming,” Nature 383 (1996): 163–66.
27. D. L. Schacter et al., “Episodic Simulation of Future Events: Concepts, Data, and Applications,” Annals of the New York Academy of Sciences 1124 (2008): 39–60.
Chapter Eleven: Knowing Facts
1. E. A. Kensinger et al., “Bilateral Medial Temporal Lobe Damage Does Not Affect Lexical or Grammatical Processing: Evidence from Amnesic Patient H.M.,” Hippocampus 11 (2001): 347–60.
2. J. R. Lackner, “Observations on the Speech Processing Capabilities of an Amnesic Patient: Several Aspects of H.M.’s Language Function,” Neuropsychologia 12 (1974): 199–207.
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