2. The Story of H.M.: Findings Indicating More than Memory Deficits Lori E. James, PhD Psychology Department University of Colorado Colorado Springs

3.  Henry Molaison from Connecticut  Henry (better known as “H.M.”, so that is what I call him) had severe, life threatening epilepsy Possibly due to accident in childhood Major seizures started at age 16  His hippocampus was surgically removed at age 27 (in 1953) to reduce his seizures Who was “H.M.”?

4.  Surgery worked to some extent, but had an unintended side effect: H.M. became densely amnesic  Two types of amnesia Retrograde amnesia: person cannot recall their past (“soap opera amnesia”) Anterograde amnesia: person cannot form new memories (the more common type of amnesia)  H.M. had severe anterograde amnesia with some retrograde amnesia too Brief History of Patient H.M.

5. From Meyers’ Psychology (10 th edition) textbook: “For 55 years…[H.M.] was unable to form new conscious memories. Has was, as before his surgery, intelligent and did daily crossword puzzles… For about 20 seconds he could keep something in mind. When distracted, he would lose what was just said or what had just occurred. Thus, he never figured out how to use a TV remote.” Typical Descriptions of H.M.

6. From Reisberg’s Cognition (5 th edition) textbook: “… he couldn’t recall anything that had taken place since the surgery. Episodes he had experienced, people he had met, books he had read– all seemed to leave no enduring record… If you spoke with him for a while, then (for example) left the room and came back 3 or 4 minutes later, he seemed to have totally forgotten that the earlier conversation ever took place…” (pp. 230-231)

7.  Upon meeting H.M., anyone would very quickly realize that he had a memory problem  His pre-surgery verbal and performance IQ scores were average and his post-surgical IQ scores were average (verbal) or higher (performance)  H.M. was not given a standardized memory measure prior to surgery, but his post-surgical memory scores were dramatically lower than his overall IQ H.M.’s Memory Deficit

8.  H.M. could learn a string of numbers (digit span) or a block pattern to report back immediately  But he could not reliably learn stories, lists of words, new vocabulary words, new people, etc.  Occasionally, H.M. would learn some piece of frequently-repeated information, but this was usually fleeting  Some evidence that H.M. could form long-term implicit memories Research on H.M.’s Memory Abilities

9.  H.M. knew who he was and many basic facts about himself  Reports indicated that H.M. had lost memories for about 11 years pre-operation but it may actually be more  H.M. did not produce a wide variety of memories but instead produced the same memories many times H.M.’s Autobiographical Memory

10.  Examples I heard about: The accident related to epilepsy Past employment history (example) Wanting to be a brain surgeon! H.M.’s Autobiographical Stories

11.  H.M.’s surgery involved tissue removal from both of his medial temporal lobes (presumed site of seizure activity)  After his death, his brain was scanned intact and dissected to gain highly detailed information about the nature and extent of the damage  Results have begun to be disseminated (e.g., that H.M. had more remaining hippocampal tissue than once thought), but are beyond the scope of this talk The Cause of the Problem: H.M.’s Lesion

12.  Severity and duration: H.M. had extremely dense anterograde amnesia with which he lived for over 50 years  H.M.’s case provided one of the first and strongest arguments that the medial temporal lobe (including the hippocampus) is critical for formation of new long term memories Why was H.M. So Famous?

13. Why Test More than Memory?  Given the severity of H.M.’s amnesia, it may seem surprising to test cognitive functions other than memory  However: cognitive psychologists often view cognitive processes as highly interactive and interrelated there was some existing evidence that H.M.’s language function was not normal

14. H.M.’s Language Performance  Two papers reported problems with H.M.’s language (when he was a younger man, in his 40s) :  MacKay, Stewart, & Burke (1998) found that H.M. was less able to identify and comprehend two meanings of ambiguous sentences than controls’  MacKay, Burke, & Stewart (1998) found that H.M.’s language production was less clear than controls’ for descriptions of the meaning of ambiguous sentences as well as for conversational speech

15. The Purpose of this Talk I hope to:  convince you that H.M. exhibited deficits on several types of non-memory cognitive tasks  show you that H.M.’s impairments in cognitive function, while less noticeable than his memory problem, were real and should be acknowledged  encourage you to keep these findings in mind when you read about or discuss H.M. as a “pure amnesic” I doubt I will:  convince you of the explanation I offer of H.M.’s deficits (although if you read the papers, you will see some detailed and sound arguments for it!!)

16. My Tests of Patient H.M.  As part of my postdoc with Dr. MacKay at UCLA, I tested H.M. in multiple experiments during three visits (in the late 1990s) to follow up on the findings of the 1998 papers  All the data I am going to show you today are selected from published research studies  For each experiment, I tested memory-normal controls matched to H.M. on age, education, and IQ so that we had an appropriate baseline for comparison

17. Notes on Procedure and Results  For each experiment, H.M. and controls had the instructions for the task typed on a note card in front of them the whole time  I will describe H.M.’s performance as being similar to controls’ if his score fell within 2 standard deviations of the controls’ mean

18. Predictions  We expected H.M. to have difficulty forming new representations in a variety of cognitive tasks (not just memory), but to not have difficulty accessing well known and frequently used representations  Our predictions typically involve interactions:  H.M. performing similarly to controls in conditions with familiar materials that do not require representations of novel information, but exhibiting deficits when processing novel, non-cliché representations

19. H.M.’s Word Reading: MacKay and James (2002)  H.M. and controls read aloud high-frequency (HF) words, low-frequency (LF) words, and two types of pseudo-words  H.M. produced HF words (e.g., kitchen; literature) with similar accuracy to controls, but misread LF words (e.g., serrated; abdicate) and pseudowords (pronounceable nonwords, e.g., quintity; retrend) more often than controls

20. H.M.’s Word Reading: MacKay and James (2002)

21.  H.M. reading some HF words:  H.M. reading some LF words: “escape, payment, crowd, international (internal), attract, remark, driver, literature, s- sanctify- satisfy” “sangrate- no, seegrate- had to correct myself (serrated), grovel, embryate (adumbrate), corrupt (crypt), zelyet (zealot), ak-akibo-abko (akimbo)”

22. H.M.’s Word Reading: MacKay and James (2002)  H.M. reading some pseudo-words:  Critically, H.M.’s errors were not of the same types as controls’ errors  He did not have fluency errors, but did misread items as other English words, and he often made failed attempts to correct his misreadings “quantity (quintity), astery, jat, bonide, periodical (pediodical)”

23. H.M.’s Word Reading: MacKay and James (2002)  In sum, H.M. performed well and similarly to controls for reading HF words, but had difficulty reading LF words and particularly pseudowords  We interpret this as reflecting problems forming novel representations for unfamiliar items

24. H.M.’s Sentence Reading: MacKay and James (2001)  H.M. and controls read aloud novel sentences that contained both familiar and unfamiliar phrases  The instructions were to read “as quickly as possible without making errors”  H.M. was much slower to read the sentences, showed unusual pause patterns, and made more production errors than controls

25. H.M.’s Sentence Reading: MacKay and James (2001)  Example of a sentence that H.M. read with few errors but abnormal prosody  Within familiar phrases, H.M.’s pause times were similar to controls, but within unfamiliar phrases, his pause times were almost 3 times longer than controls’ “The police officer, watch- watching the cat run through the dark alley, asked the witness to describe the thief.”

26. H.M.’s Sentence Reading: MacKay and James (2001)

27.  In a second experiment, sentence reading was incidental to a task of determining sentence ambiguity  H.M. committed more reading errors than controls, whether sentences contained no ambiguity, structural ambiguities, or lexical ambiguities

28. H.M.’s Sentence Reading: MacKay and James (2001)  In sum, H.M. performed well and similarly to controls for reading known phrases within sentences, but had difficulty producing novel sentences composed of some familiar units  H.M. was slow, but also generated unusual prosody patterns, even when correctly producing the words in the sentences

29. H.M.’s Word Comprehension: James and MacKay (2001)  H.M. and controls performed an untimed lexical decision task for words and pseudo-words from James and MacKay (2002)  H.M. did not accurately identify LF words (e.g., chameleon) as words or reject pseudowords (e.g., quintity; retrend), but performed like controls for HF words (e.g., noise, marine)

30. H.M.’s Word Comprehension: James and MacKay (2001)  Next, H.M. was given the items he had selected as words in the lexical decision task, and was told to define them.  H.M. and controls had the option of saying an item was not a word, but defined all those they accepted as words

31. H.M.’s Word Comprehension: James and MacKay (2001)  H.M.’s definitions of LF words and pseudowords were sometimes quite incorrect  Examples of correct HF definitions and an incorrect pseudoword definition: “ Scene” is uh what you look at, when you’re outside. “Orchestra” is a band… “Mistake” is error. “Retread” (retrend) would be the tire, on a car, retread, something redone. (LJ: That one’s actually different.) “Retrend” and… that’s different, the way something is done different. Two ways.

32. H.M.’s Word Comprehension: James and MacKay (2001)  In sum, H.M. performed well and similarly to controls for identifying and defining HF words, but had difficulty with LF words and pseudowords  We interpret this as reflecting problems forming novel representations for unfamiliar items  H.M. did not have existing representations for some LF words  H.M. (and controls) definitely did not have existing representations for pseudowords

33. H.M.’s Sentence Comprehension: MacKay, James, Taylor, & Marion (2007)  In Experiment 1, H.M. and controls had to decide whether each of 56 short, novel sentences was grammatical or not  Sample sentences:  The brothers was fixing up the old car (no)  Andy slept on Tuesday (yes)  Our new neighbors moved in but I haven’t met us yet (no)

34. H.M.’s Sentence Comprehension: MacKay, et al. (2007)  Controls were correct for 83% of sentences, whereas H.M. was correct on 70% of sentences  On a subset of scrambled-word sentences, H.M. and all controls were 100% correct  Over all sentences, H.M. exhibited a strong bias toward responding “no” that almost certainly inflated his accuracy

35. H.M.’s Sentence Comprehension: MacKay, et al. (2007)  In Experiment 2, H.M. and controls decided whether each of 24 short, novel sentences was grammatical or not and then described what the problem was and correct it if they judged it ungrammatical  Sample sentences:  Yesterday the man make a chocolate cake (no)  The boy feeds the rabbit carrots (yes)  Will be Harry blamed for the accident? (no)

36. H.M.’s Sentence Comprehension: MacKay, et al. (2007)  Controls correctly identified 98% of sentences, whereas H.M. was correct on 79% of sentences  Controls accurately corrected 100% of the sentences they identified as ungrammatical whereas H.M. only corrected 83%

37. H.M.’s Sentence Comprehension: MacKay, et al.(2007)  Example of H.M.’s “correction” of “Will be Harry blamed for the accident?”, a sentence he identified as ungrammatical: “No, that- that really doesn’t say that he was responsible for the action or blamed for it, so he couldn’t be blamed for it.” LJ: OK, so do you think that sentence has all the words in the right order or not? “No.” LJ: Which words would you move around? “The blame, mostly.” LJ: Where would you put it? What order would you put those in to make a correct sentence? “Well, you have to find out what Harry was blamed for. And it- possible that word b- Harry is blamed, in a way, for the accident and he could be blamed for something else.”

38. H.M.’s Sentence Comprehension: MacKay, et al. (2007)  In sum, H.M. performed well and similarly to controls for identifying scrambled-word sentences, but otherwise had difficulty determining whether novel sentences were grammatical  Even when H.M. accurately identified an ungrammatical sentence, he could not specify what the problem was or how to fix it  Clearly not a standard “memory” issue

39. H.M.’s Visual Cognition: MacKay and James (2009)  Two tests of visual cognition in H.M.  If H.M.’s memory and language deficits were due to general deficits in representing novelty, his ability to represent novel visual forms should be impaired  Alternate explanations (e.g., cortical damage in the language areas of the brain) do not predict impairment in H.M.’s visual cognition

40. H.M.’s Visual Cognition: MacKay and James (2009)  Experiment 1 employed pictures from What’s Wrong Here? books (Tallarico, 1991)  These pictures contain novel visual errors or anomalies embedded in otherwise familiar scenes  H.M. and controls were told to circle and describe all the errors they found

41. H.M.’s Visual Cognition: MacKay and James (2009)  Example to-be-detected error (recreated)

42. H.M.’s Visual Cognition: MacKay and James (2009)  H.M. had difficulty detecting the errors, identifying only 48% of them, compared to 70% for controls  H.M. also incorrectly identified some objects within the scenes (e.g., calling a trash can a “window” and a rabbit a “dog”)

43. H.M.’s Visual Cognition: MacKay and James (2009)  Experiment 2 employed the Thurstone (1949) Hidden Figures Test  These pictures contain visual shapes embedded in complex figures  In the original, the shapes are not very familiar (and don’t have known labels)  We created similar tasks with shapes that are highly familiar (triangle, square)  H.M. and controls were told to find the embedded figure and trace it within the complex figure

44. H.M.’s Visual Cognition: MacKay and James (2009)  Example target and complex figure

45. H.M.’s Visual Cognition: MacKay and James (2009)  H.M. had difficulty finding the unfamiliar figures, identifying only 7 of them total, compared to more than 28 for controls  H.M. did as well as controls for the familiar figures, identifying 10, compared to 11.5 for controls

46. H.M.’s Visual Cognition: MacKay and James (2009)  For unfamiliar figures, H.M. sometimes made quite dramatic errors, whereas controls never did  Examples of H.M.’s errors

47. H.M.’s Visual Cognition: MacKay & James (2009)  In sum, H.M. had difficulty detecting novel errors embedded in otherwise familiar scenes  H.M. performed like controls for familiar shapes, but performed poorly for finding unfamiliar shapes within complex arrays of lines  Novel visual representations posed problems for H.M. that mirror his difficulty with forming new memories and comprehending and producing novel language

48. Summary of H.M.’s Performance  H.M. could do some language and perceptual tasks successfully, but if pushed to process novel language or novel visual information, his performance deteriorated quickly  We argue that this is due to a basic deficit in forming representations for unfamiliar information  H.M. could rely on familiar information, so that he seemed unimpaired, much of the time

49. Revisiting The Story of H.M. LJ: You feel comfortable? “I have- I’ve got a ringing all the time.” LJ: That’s really interesting. “Yeah, well I don’t pay any attention to it anymore.” LJ: Starting to ignore it? “Well, you could say ignore it, in a way. But I know sometimes they may find out about it, about me, and from other people too, and it will help them.” LJ: Yeah? “Too. ‘Cause what the doctors and the nurses and everybody will know about it.”

50. The Challenge  Some researchers will continue to provide evidence that on some tasks H.M.’s cognitive function (other than memory) was unimpaired  We argue that when he could access known and frequently-used information, he was unimpaired, so it is not unlikely to find that he performed many tasks successfully

51. The Challenge, Continued  Some researchers will accept that H.M. had a language deficit, but will claim it was due to brain damage separate from his hippocampal lesion, or his low education level, or his memory deficit  These are certainly possible  However, the parallels between his memory, language and visual cognition deficits would be surprising under a “different damage” account  The control features of our experiments make the second two explanations unlikely

52. The Challenge, A Specific Example  “… the half century of research that began with H.M. has shown that profound impairment after medial temporal lobe damage occurs in only one domain, specifically, in what is now termed declarative memory” (p. 282).  Squire & Wixted (2011). Annual Review of Neuroscience, 34, 259-288.

53. H.M.’s Legacy  H.M. was a research participant for 55 years, and the fields of psychology and neuroscience have been irreversibly shaped by what we learned from him  H.M.’s brain donation means that we can continue to learn about his brain damage and about general brain structure and function with greater precision  His contribution to science continues

54. THANK YOU to:  H.M.  Dr. Suzanne Corkin for providing the opportunity to test H.M.  Many research assistants at UCLA and Pomona College who helped with transcription and analyses  Dr. Don MacKay, without whom this work would never have been conceived

55. References James, L.E., & MacKay, D.G. (2001). H.M., word knowledge and aging: Support for a new theory of long-term retrograde amnesia. Psychological Science, 12, 485-492. MacKay, D.G., & James, L.E. (2001). The binding problem for syntax, semantics, and prosody: H.M.'s selective sentence-reading deficits under the theoretical-syndrome approach. Language and Cognitive Processes, 16, 419-460. MacKay, D.G., & James, L.E. (2002). Aging, retrograde amnesia, and the binding problem for phonology and orthography: A longitudinal study of "hippocampal amnesic" H.M. Aging, Neuropsychology, and Cognition, 9, 298-333. MacKay, D.M., & James, L.E. (2009). Amnesic H.M. exhibits selective deficits in visual cognition: Evidence from the what’s-wrong-here and hidden-figure tasks. Journal of Clinical and Experimental Neuropsychology, 31, 769-789. MacKay, D.G., James, L.E., & Hadley, C.B. (2008). Amnesic H.M.'s performance on the Language Competence Test: Parallel deficits in memory and sentence production. Journal of Clinical and Experimental Neuropsychology, 30, 280-300. MacKay, D.G., James, L.E., Taylor, J.K., & Marian, D.E. (2007). Amnesic H.M. exhibits parallel deficits and sparing in language and memory: Systems versus binding theory accounts. Language and Cognitive Processes, 22, 377-452.