Behavioral evidence suggestive of frontal lobe ...

Brain and Cognition 123 (2018) 136–141

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Behavioral evidence suggestive of frontal lobe pathology in the amnesic H.M.

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William Winter Department of Behavioral Sciences, Kingsborough Community College of the City University of New York, Brooklyn, NY 11235, United States

A R T I C LE I N FO

A B S T R A C T

Keywords: H.M. Hippocampus Mid-temporal lobe Frontal lobe Confabulation

From the earliest published reports, Henry Gustav Molaison—who until his death in 2008 was known simply by his initials H.M.—was characterized as having a profound anterograde amnesia subsequent to mid temporal lobe resection, and that this amnestic condition was uncomplicated by other cognitive or behavioral impairments. Post-mortem neuropathological examination has detected—in addition to the expected temporal lobe lesions—previously unreported frontal lobe and white matter pathology, inviting questions concerning the behavioral and cognitive consequences that might result from such lesions. The purpose of this article is to recount published descriptions of a range of anomalous behaviors by H.M. that can not be explained by the memory impairments typically associated with anterograde amnesia, to counter previous claims that these behaviors are attributable to amygdalar damage, and to advance the interpretation that these behaviors are instead consistent with well-documented effects of frontal lobe pathology. Transcripts of interviews with H.M. which feature disjointed, often contradictory, and arguably confabulatory responses are presented in support of this argument.

1. Introduction The profound amnesia that resulted from the bilateral resection of much of the mid-temporal lobes of Henry Gustav Molaison (H.M.) in 1953 initiated the modern era of memory research. Concepts central to memory psychology, such as the distinctions between short term, long term, semantic, episodic, declarative and non-declarative forms of memory are grounded in dozens of his neuropsychological evaluations (see Squire, 2009 for an overview). Since his death in 2008, numerous newspaper articles, magazine features, blog entries, television and radio reports, books —and, notably, the live web-cast of the dissection of H.M.’s brain—have launched his story into the domain of popular conversation. From the earliest reports (e.g., Milner, Corkin, & Teuber, 1968; Scoville & Milner, 1957) H.M.'s amnestic condition has been characterized as “pure”; that is, his cognitive impairments secondary to surgery were held to be limited to a long term memory deficit. Scoville and Milner (1957) described H.M.'s post-surgical condition as:…”a complete loss of memory for events subsequent to bilateral medial temporal lobe resection… with a partial retrograde amnesia for the three years leading up to his operation; but early memories are seemingly normal and there is no impairment of personality or general intelligence (p.17).” As recently as 2014, Corkin and her colleagues reaffirmed that “H.M.'s bilateral medial temporal lobe resection was circumscribed and the resulting amnesia was pure” (Augustinack et al.,

2014). This interpretation of H.M.'s condition has been reinforced by similar descriptions in numerous journal articles and codified in standard introductory psychology texts. At the same time, however, many of those publications offered descriptions of H.M.'s behavior that are clearly not a matter of simple or uncomplicated memory impairment. These include disorganized cognition, as evidenced by irrelevant, confabulatory, or disjointed responses to questions, disruptions of affect and motivation, and a striking insensitivity to autonomic signals related to hunger, thirst, and even pain induced by electric shock and heat source. Detailed examples and interpretations of these behaviors are reviewed in the following sections. 2. Motivation, emotion, autonomic and nocioceptive responses H.M.'s clearly abnormal motivational and affective condition have been reported in numerous accounts. Corkin (1984) described him as complacent and lacking in basic initiative to a truly remarkable degree. For example, If asked to sit in a particular place, he would stay there indefinitely without complaint and without attempt to move somewhere else. His nursing home attendants reported that H.M. ate well at meals, but they also recount that he never spontaneously asked for food or drink, and never complained about, or volunteered information about, his well-being or physical condition. If attendants suspected that he was in some discomfort, it was necessary to question him with a list

E-mail address: [email protected]. https://doi.org/10.1016/j.bandc.2018.03.005 Received 11 January 2018; Received in revised form 27 February 2018; Accepted 11 March 2018 0278-2626/ © 2018 Elsevier Inc. All rights reserved.


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The well-known case of S.M., whose complete, focal, bilateral amygdalar calcification is due to the rare Urbach-Wiethe disease, is an informative comparison case to H.M., and offers insights into the affects of amygdalar pathology. Studies with S.M. have documented a pronounced and isolated impairment with respect to the recognition and experience of fear (Adolphs, Tranel, Damasio, & Damasio, 1994; Feinstein, Adolph, Damasio, & Tranel, 2011; Tranel, Gullickson, Koch, & Adolphs, 2006). A central finding is that S.M. Is impaired in recognizing fearful facial expressions, but not other emotions conveyed by facial expression. Additionally, S.M. does not experience fear while viewing scenes typically regarded as frightening in such movies as Silence of the Lambs, or The Shining, or even under actual experiences of physical danger that have occurred in her life, such as the threat of assault with a weapon (Adolphs et al., 1994; Feinstein et al., 2011; Tranel et al., 2006). No parallel documentation of a similar lack of perception or experience of fear appears in the extensive H.M. literature. With respect to the experience of emotions, incidents of grief, apprehension, and anxiety on the part of H.M. have been reported. H.M. was described as feeling grief at the passing of his father and distress upon the hospitalization of his mother (Corkin, 2013; Dittrich, 2016). Moreover, H.M.'s emotionality extended to episodes of anger and even violence. H.M. was described as intractably angry when shortly after the death of his father, he discovered that his prized gun collection was missing. His mood stabilized after the gun collection – which had been surreptitiously claimed by his uncle – was returned to his home (Milner et al., 1968). Corkin (1984) recounts that in response to his mother's “nagging” H.M. would on occasion kick her in the shins or hit her with his glasses. In another such episode of anger or frustration related to his mother, H.M. hit his fist into a door so violently that he broke his hand. On one occasion, in the setting of his sheltered workshop in Hartford, Connecticut, H.M. reportedly threatened to kill himself, said “that he was going to hell, and would take his mother with him”. When attendants at the center attempted to calm him down, he kicked and shoved them away, and took to smashing his head against a wall until a doctor arrived and injected him with a sedative (Dittrich, 2016). No such outbursts of anger or aggression appear in the descriptions of the behavior of S.M., the patient with complete bilateral amygdalar lesioning. She is consistently described as being emotionally evenkeeled, possessed largely of positive emotions, and lacking negative ones. A study in which S.M. was interviewed separately by two clinical psychologists who were blind to her amygdalar dysfunction reported no evidence of emotional dysregulation. They noted that she spoke dispassionately when relating highly emotional and traumatic life experiences, did not seem to have a normal sense of distrust or danger, and assessed her to be unusually resilient, even “heroic” in the face of exceptional adversity in her life (Tranel et al., 2006). The claim that H.M.'s striking insensitivity to pain can be explained by his amygdalar resection is also called into question by comparison to S.M. None of the published studies of S.M. report aberrations in the experience of pain, or lack of physical pain. Moreover, these studies make no mention of any of disturbances of basic autonomic promptings associated with hunger, thirst and sex drive as have been reported in H.M. Finally, a recent study by Feinstein et al. (2016) casts doubt on the significance of the amygdala in the perception of pain; this study reports a preserved experience of pain in an individual with bilateral medial temporal lobe lesions, similar to those suffered by H.M., which included the amygdala, insula, and anterior cingulate. Taken together, the behavioral evidence detailed here seems to suggest significant residual function, especially with regard to emotional experience and expression, of H.M.'s partially resected amygdala.

of possible ailments until they hit upon the right one; he would not or could not simply state what the problem was, for example, that he had a headache or a stomachache. H.M.'s mother was quoted in the article: “The trouble with H. is that he doesn't complain – ever. There could be something quite seriously wrong with him, but you would never know” (p.251). Additionally, H.M. “appears to have no interest in sexual relationships, as indicated by the absence of conversation on sexual topics and by his failure to seek sexual satisfaction” (p.251). H.M. admitted to his lack of sexual desire in an interview with psychiatrist George Murray (Corkin, 2013, p. 112). By way of explanation, Corkin mentioned that hyposexuality has previously been associated with temporal lobe lesions, and prolonged use of anticonvulsant medication has been implicated in reduction of testosterone and sexual dysfunction. In 1962, an attempt to demonstrate a classically conditioned aversive response using electric shock as the unconditioned stimulus had to be aborted when H.M. failed to produce the expected galvanic skin response subsequent to shock. Even at intensity levels that the control subjects experienced as painful, H.M. did not complain of any discomfort (Milner et al., 1968). Corkin (1984) noted that cerebellar lesions in animals permanently abolish classical conditioning using aversive unconditioned stimuli, citing Solomon, Vander Schaaf, Thompson, & Weisz (1983), and reported that marked cerebellar atrophy had been documented in H.M., presumably due to his longterm treatment with the anti-convulsant Dilantin. Initially detected by CT scan, cerebellar atrophy was subsequently confirmed by MRI imaging, and conclusively documented by post-mortem examination (e.g., Augustinak et al., 2014). H.M. was subsequently shown to display eye blink conditioning in both delay and trace conditions, although his response was judged to be inferior to that of the normal controls. This result was viewed by Corkin (2013) as evidence that eyeblink conditioning may not be hippocampally dependent; in a later publication, Corkin and her colleagues speculate that H.M.'s residual eye blink conditioning may have been mediated by cerebellar nuclei that remained functional despite the documented atrophy (Augustinack et al., 2014). Milner et al. (1968) attributed H.M.'s insensitivity to pain to the partial bilateral resection of his amygdala, a collateral consequence of his mid-temporal lobe surgery. Hebben, Corkin, Eichenbaum, and Shedlack (1985) explored H.M.'s anomalous pain perception using a heat gun device termed a “dolorimeter”. During these procedures, H.M. reported no pain at any level of exposure to the heat source, even at the highest intensity. The control subjects, on the other hand, were unable to endure the highest heat level for the 3 s required by the protocol (Dittrich, 2016; Hebben et al., 1985). In addition to this marked insensitivity to pain, Augustinack et al. (2014) cite H.M.'s amygdalar resection as a general explanation for his apparent disconnection from the basic autonomic promptings associated with hunger, thirst and sex drive. Moreover, the authors assert here that H.M. “was not fearful of anything” (p. 1283). 2.1. Discussion It is well documented that the amygdala plays a role in the production and perception of fear (Davis, 1992; Fanselow & Gale, 2003; LeDoux, 1996). The claim, as in Augustinack et al. (2014), that H.M. does not experience fear appears to be unsupported by the published research. Despite dozens of studies over nearly five decades, no programmatic research seems to have specifically explored the nature of H.M.'s fear responses. Augustinack et al. (2014) cite Hebben et al. (1985) and also Corkin (2013), but no systematic inquiry into the parameters of fear response in H.M. appear in these sources. Moreover, the fact that H.M. did not produce galvanic skin response in an aversive conditioning protocol does not mean that he could not have the phenomenal experience of fear in the more general sense, as in fear of direct physical threat or harm through assaultive attack or accident.

3. Cognitive disorganization In addition to the anomalous autonomic/motivational and nocioceptive responses described above, there is the matter of H.M.'s often 137


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WW: He was shot? HM: I believe he was shot. WW: Where abouts in the body was he shot? HM: Um? ….…. I think of the stomach area ... um .... they were trying to get in the heart, but it went lower, went to the stomach area and it was ... it was several days before he died. WW: Who was this? HM: ….….. think of Kennedy right off ... that was assassinated in a way...

disjointed, unfocused, and malformed verbalizations, the quality of which suggest a pathology of cognition that is independent of memory failure or linguistic insufficiency. McKay and his colleagues have published a number of studies that catalog the grammatical and linguistic anomalies to be found in H.M.'s verbal reports (e.g., MacKay, Burke, & Stewart, 1998; MacKay & James, 2002; MacKay, James, & Hadley, 2008; MacKay, & Johnson, 2013; MacKay, Johnson, & Hadley, 2013), but these studies do not address the significantly disturbed thought processes that appear to underlay these linguistic productions. An extended interview conducted by Marslen-Wilson (1970) offers examples of the jumbled and discontinuous conceptual formulations—as distinct from grammatical or linguistic irregularities—that often characterize H.M.'s verbal productions. At one point in the interview, Marslen-Wilson asked H.M. about the death of President Roosevelt—whose 4 terms of office and death in 1945 occurred 8 years before H.M.'s surgery and —notwithstanding retrograde amnesia—could potentially be recalled by him.

By the end of the interview H.M. claims that Mrs. [Eleanor] Roosevelt and the governor of Michigan were shot and killed along with FDR, suggests that a President Kennedy was shot by a man named Wallace, that General MacArthur was executed (shot) in the war, and adds Stalin, Pat Nixon, and Marilyn Monroe to the list of assassin's victims. The markedly disordered quality of H.M.'s cognition is also apparent in a rarely cited study by Sidman, Stoddard, and Mohr (1968). This article reports the attempt to explore H.M.'s ability to discriminate target stimuli (circles) from distractors (ellipses), in an operant conditioning protocol that used pennies and chimes as positive reinforcers. The task required H.M. to press a lighted display which contained a circular stimulus as opposed to a distractor which contained an ellipse. The vertical to horizontal axis ratio of the ellipse was varied from trial to trial making the task of discrimination more difficult as this value approached that of a circle. H.M. was rewarded with a penny and the sound of chimes every time he successfully discriminated the circle from the elliptical form. The researchers found that H.M. was capable of correctly choosing the circle until the vertical/horizontal axis ratio of the ellipse had the value of .93 (wherein a ratio of 1.00 is a perfect circle). Immediately following this protocol, the researchers asked H.M. to explain the requirements of the just completed task. H.M. Gave the following explanation:

WW: [William Marslen-Wilson] ….…. So .. um .. how did Roosevelt die ? HM: He was… assassinated… in a way….… he died afterwards... uh.. got a bullet-wound and he died. WW: Where was he assassinated, then ? HM: I think of Indiana right off….….... but...uh ... but town I cannot think of... A few lines later in the transcript, after H.M. pauses to light a cigarette: HM: … Well ….… I think of ... right off of .. uh .. the assassination ..... and down in Louisiana. WW: Of who ? HM: Of Roosevelt. WW: Do you know who … who was the … who assassinated him ? HM:….… No, can't say definitely.... but they do know his name ........ um... I thought of ... of Black and then I'm... uh ...... really stopped .. WW: A black person, or the name ‘Black’? HM: No, it started with Black and continued on … more letters ….…... and, but I cannot .. ____(??) ___(??) just what ... and .. the .... what it is ... WW: Blackman ? HM:….…... um ...... that is one of the things I thought of ... is it Blackman or Black- -mere (?) ...... and there ... was the argument I have with that last letter. Approximately 5 minutes later in the interview: WW: …Have you ever heard of somebody called Kennedy? HM: … well ….… Kennedy... uh ... President of the United States ... and ...... well .... think of him as a tall man... thin man. WW: Thin man? HM: Yes ….… and .. don’t remember .. uh .. just .. he held an office before that that was in the government .... also. WW: Yes ….…. Kennedy did? HM: Kennedy did. WW: Do you remember what his first name was? HM: Thought of Robert right off. WW: Uh-huh ….… is he still alive? HM: ….… No, he was assassinated. WW: He was assassinated? HM: He was assassinated. WW: Who … who was? HM: I think Kennedy was assassinated ….…... did I? ..... that’s what .... that ... that’s what I thought of right off. WW Yes. Do you know where he was assassinated? HM:… uh…Some place in Ohio … in the state of Ohio. WW: You don’t remember which town? HM: The town ….… no ....... I believe he was on a train ... and ... was just getting... got on the train and was bidding goodbye to the people ..... the town he was in...and the assassin... shot him.

H.M.: Well let's see. Something would flash up there and the idea was to pick out one of those squares and to point it toward dark. To tip it—to hit it with my finger tip and to match up. Each time the two matched a penny would drop in. E: Each time the two matched? H.M.: The two matched. E: Uh-huh. What was on them? H.M.: X E: X was on them? H.M.: Yeah. … [a few minutes later] E: What were you pointing to – what were you pressing over there? H.M.: Well, one of these would light up and get one of them matched and every time one would match, of course, a penny would drop in. E: What did the one that matched look like? H.M. Cross. E: A cross. Uh-huh. A plus sign? H.M.: Uh-huh. E: Or a multiplication sign? H.M. Well, you'd say, uh, it wouldn't be multiplication – addition.

3.1. Discussion Despite H.M.'s demonstrated ability to discriminate circles from ellipses, he was completely unable to accurately describe the task after 32 separate experimental trials. His references to the presence of an “X” or a “cross” (later referred to as a “plus sign”), to the need to “point it toward dark” and to the principle of “matching” different squares are clearly indicative of a disordered cognitive process, as opposed to some form of linguistic insufficiency. It should be stressed that these questions were asked immediately after the completion of the task, and so 138


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those with Capgras delusion, isolated frontal lobe pathology, or schizophrenia. Moreover, in some amnesics, such as those with WernickeKorsakoffs syndrome, confabulation may occur only in the early stages of disorder, after which a relatively pure, confabulation-free amnestic condition persists (Gilboa & Moscovitch, 2002; Hirstein, 2005; Johnson, 1991; Moscovitch, 1995). While confabulation is most typically described as involving aberrations of autobiographical memory, confabulations of semantic memory have been documented as well (Gilboa & Moscovitch, 2002; Hirstein, 2005; Moscovitch, 1995). The statements produced by H.M in the Marslen-Wilson interview, such as the false assertions of assassination of numerous public figures, refer to historical events that cannot be classified as part of H.M.'s personal autobiographical experience; they are thus something closer to confabulations and conflations of semantic-level information. H.M.'s verbal responses as reported in Sidman et al. (1968) offer another exception to conventionally accepted categories of confabulation. While confabulation is typically understood to involve some aberration of long-term memory, the confabulatory responses reported there occur immediately after H.M.'s experience with the experimental protocol (see above), and thus represent confabulations within the span of short term or working memory, a phenomena which appears to be previously unreported in a non-psychotic or delusion patient. Another interesting and atypical element of H.M.’s confabulation is the tentativeness of his statements. One might say that there is a “dithering” quality to his response to questions. Confabulators are more typically reported as being confident in their statements, even when the contradictory or improbable nature of these statements is pointed out (Gilboa & Moscovitch, 2002; Hirstein, 2005; Johnson, 1991; Moscovitch, 1995). The tentative nature of H.M.’s responses may be a consequence of the failure of a frontally-based response filtering mechanism, as per Shimamura’s dynamic filtering theory, or Johnson’s reality monitoring theory; he thus experiences the multiple response alternatives that occur to him as confusing, and has difficulty choosing between them—hence the tentativeness. It is not clear why this sense of conflict between response choices should be present in H.M., but absent in the majority of other confabulators who cases have been reported. Notwithstanding these category violations, H.M.'s verbal productions seem to be most parsimoniously understood as variants of confabulations; moreover these aberrations may be best explained as failures, based in putative frontal lobe insufficiency, to inhibit, filter, or monitor competing responses as they present to working memory. The language H.M. uses in prefacing his responses to questions seems to signify a retrieval process which is passively experienced, as opposed to an intentionally initiated process. He almost never states that he positively and clearly remembers a given event; instead he qualifies his responses with phrases like “right away I thought of”, as opposed to “I do remember” (as in the Marslen-Wilson interview excerpted above). Moreover, H.M.'s oft-reported use of the phrase “I'm having an argument with myself” (e.g. Corkin, 2013, Dittrich, 2016) in attempting to respond to questions can be taken as an indication of his difficulty in evaluating the appropriateness or accuracy of competing response alternatives, as would be consistent with the filtering or reality monitoring models of confabulation (Hirstein, 2005, Johnson, 1991; Shimamura, 1995, 2000).

H.M.'s inability to provide an accurate account cannot be viewed as a consequence of long-term memory failure, nor can it be ascribed to an acute post-operative confusional condition, since this evaluation was published 15 years post-operatively. The Marslen-Wilson interview sheds further light on H.M.'s cognitive deficiencies. H.M. inappropriately generalizes the historical fact of the assassination of John F. Kennedy, and possibly also of his brother Robert Kennedy to other figures of note. In the course of the same interview, H.M. makes reference to Sputnik (the pioneering cold war era Soviet satellite), but mislabels it as a “rocket-bomb”, asserts that Dewey succeeded Eisenhower as president, misidentifies a photograph of the Beatles as the Rolling Stones (a band that he claims plays “jive music”) and with some correction and prompting, eventually produces the name of the Beatles while looking at their photograph. That H.M. should have any knowledge of the Kennedy assassinations, Sputnik, the Rolling Stones, the Beatles and other such historicities is indeed remarkable, given that all of these developments occurred years after his surgery. Indeed, Corkin (2013) remarked that he has “no business” knowing these things. An intriguing possibility is that this residual capability of forming declarative memories for post-surgical historical events can be explained by the fact that H.M.’s hippocampus was incompletely resected by his surgery, as confirmed by post mortem examination conducted by Jacopo Annese and colleagues (Annese et al., 2014). There is a larger point to be made, however, regarding H.M.'s general cognitive integrity. In the interview, H.M. blithely offers incongruous assertions concerning the assassination deaths of Franklin and Eleanor Roosevelt, General MacArthur, Pat Nixon, Stalin, and Marilyn Monroe. He provides rapidly changing assertions as to the circumstances of these events: H.M. explains first that Roosevelt was shot in Indiana—moments later in Louisiana—and still later, in Michigan along with his wife and the governor. Robert Kennedy was assassinated in Ohio, on the back of a train as he was addressing a crowd, and later in Alabama, but also in Reno, Nevada along with a “general” and Pat Nixon. Stalin was assassinated “on the border of Russia”, possibly by a Swedish national, MacArthur was shot in a revenge killing in Michigan, or in a parade in Tokyo, and Marilyn Monroe was also shot in a revenge killing in the Midwest by a jealous wife. These peculiar conflations of historical fact are not simple failures of long-term memory, as would be the case in “pure” anterograde amnesia. The mental process involved seems to reflect an inability to appropriately inhibit, or filter out, incorrect response alternatives as they happen to present themselves to H.M.’s working memory. Shimamura (1995, 2000) has outlined a dynamic filtering theory, in which he proposes that a primary function of the prefrontal cortex is to selectively gate or filter competing response alternatives as a function of information processing control. This model bears similarity to Marcia Johnson's proposal of a reality monitoring theory, which likewise points to the importance of executive prefrontal operations in evaluating candidate ideations (Johnson, 1991). H.M.'s behaviors as described above seem to reflect a failure of this filtering or monitoring mechanism, and as such may be understood to be examples of a type of confabulation. The term confabulation is most frequently used to refer to the involuntary or unintended telling of verbal untruths. Moscovitch and colleagues have described it as “honest lying” (Gilboa & Moscovitch, 2002; Moscovitch, 1995). Despite the production of an untruth, there is an absence of intent to deceive, and a lack of awareness on the part of the speaker that the verbal production is not true. Confabulation has long been associated with memory impairment; the mnemonic conceptualization attributes confabulation to the attempt to fill in the gaps in faulty and incomplete memories generated by amnesic or memory impaired patients (Gilboa & Moscovitch, 2002; Hirstein, 2005; Johnson, 1991; Moscovitch, 1995). This model is challenged by the fact that confabulation has been documented in some patient populations who do not suffer from impaired memory, such as

4. Conclusion This paper reviews previously published accounts of significant disturbances in the behavior of the well-known amnesic patient H.M. which cannot be reasonably ascribed to failures of long-term memory. Previously, these anomalous behaviors have been explained as consequences of the amygdalar damage that was a collateral result of the bilateral resection of his hippocampal formation, or owing to the cerebellar atrophy presumably caused by decades of treatment with the anti-convulsant Dilantin (e.g., Augustinak et al., 2014; Corkin, 2013; 139


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approximately 5 min. The article notes that H.M. had his first petit mal seizure at age 10 and first grand mal seizure at 16, and that Scoville performed the mid temporal lobe resection on H.M. in September of 1953. Thus H.M.’s neurosurgery occurred fully 17 years since his first petit mal seizure, and 11 years following his first major epileptic episode, a time interval which should provide ample opportunity to observe and record significant deterioration of cognitive functions. Scoville and Milner’s article, however, gives no clinical information regarding H.M.’s pre-operative condition. Dittrich (2016) reports that no record of Scoville’s first interview/evaluation with H.M. is extant; notes describing the subsequent pre-operative meetings do not make mention of any significant cognitive dysfunction, outside of some memory difficulties, and, of course, the persistent and increasingly severe seizures. While mild to moderate memory dysfunction in individuals who suffer from seizure disorder has been well documented, there is no firmly established or consensually agreed upon connection to chronic frontal lobe dysfunction (e.g., Kolb & Whishaw, 1985; Sutula, Hagen, & Pitkänen, 2003, Vingerhoets, 2006). Given the number of years between H.M.’s initial seizure episodes and his neurosurgery, it would seem that cognitive dysfunctions as serious as those detailed above would have been noticed and documented in his clinical record. Moreover, it is unlikely that his condition can be ascribed to long-term anti-convulsant use. As mentioned above, cerebellar atrophy is a known concomitant of long term anti-convulsant use, but there appears to be no widely acknowledged or accepted causative connection to the type of cognitive deficiencies displayed by H.M., which are argued here to be rooted in frontal lobe dysfunction. Scoville and Milner (1957) do note that H.M.’s pre-operative condition rendered him unable to continue his employment as a “motor winder” at the Ace Electric Motors firm, but cite the increasing intensity and severity of his seizures as the reason for his cessation of employment. What is definitely clear is that H.M.'s overall pattern of cognitive and behavioral disturbances do not resemble those of other mid-temporal lobe amnesics. Most relevant to this argument, mid-temporal lobe amnesics do not confabulate (Hirstein, 2005, citing Parkin, 1984; Moscovitch & Melo, 1997). Moreover, they show longer response latencies and provide more deliberative self-corrections in answering questions than amnesic patients with frontal lobe pathologies, and have been shown to be less likely than normal controls to generate false memories on a task designed specifically to produce them (Hirstein, 2005, citing Mercer, Wapner, Gardner, & Benson, 1977; Schacter, Verfaellie, & Pradere, 1996). The glib, off hand, self-contradictory, rapidly shifting, and seemingly impulsive manner in which H.M. has been documented to supply false memories and confabulations is clearly anomalous with respect to isolated mid-temporal lobe amnesia, offering instead a pattern of behaviors suggestive of an overlay of frontal lobe pathology.

Milner et al., 1968). This paper argues that these explanations do not offer a complete or satisfying accounting for the types of behavior H.M. has been reported to display. For example, the claim that H.M.'s disturbances of basic autonomic promptings associated with hunger, thirst, sex drive and the experience of pain can be explained by his amygdalar resection is contradicted by comparison to the patient S.M., whose bilateral amygdalar atrophy produces no such set of conditions. Moreover, there appears to be no published account of a patient with circumscribed amygdalar pathology whose condition resembles that of H.M. in any respect. Moreover, a body of evidence exists connecting frontal lobe pathology with autonomic and nocioceptive disturbances. Depending upon the precise location and extent of a given lesion, damage to prefrontal areas has been associated with disturbances of appetite, thirst, motivation, initiative, pain perception, and emotionality, as well as functions more typically categorized as involving executive cognitive functioning (see Szczepanski & Knight, 2014 for a recent review). In addition to the autonomic and nocioceptive anomalies detailed above, H.M.'s verbal productions offer evidence of cognitive disturbances that cannot be accounted for by simple impairment of longterm memory. This paper argues that these productions are best understood as examples of confabulation. While the phenomena of confabulation is complex, having engendered many theories and categorical parsings, a convergence of opinion has emerged regarding the centrality of prefrontal cortical dysfunction as a prime neural substrate underlying the condition (e.g., Gilboa & Moscovitch, 2002; Hirstein, 2005; Johnson, 1991; Moscovitch, 1995). This point is relevant to the case of H.M., given the detection by Jacopo Annese’s Brain Observatory team, of damage to H.M.’s left pre frontal cortex (specifically the left lateral orbital gyrus), as well as some localized damage to frontal white matter (as distinct from more widely spread age-related white matter deterioration). These lesions were uncovered initially through post-mortem block imaging and shortly after via histological examination (Annese et al., 2014). The authors note that these lesions can be plausibly ascribed to damage incurred during the mid-temporal resection, given the particular surgical approach which involved the physical lifting of the frontal lobes in order to access the interior mid-temporal region (see Fig. 1). This paper makes the argument that the anomalous behaviors exhibited by H.M., as reviewed above, are parsimoniously attributed to some manner of frontal lobe dysfunction, whether owing to the specific prefrontal cortical lesion and/or white matter disruption as reported by Annese, or to some interaction of known or as yet undiscovered pathologies relevant to frontally-mediated executive control. An alternative view concerning these anomalous behaviors is that they may be a direct consequence of neurological damage accrued through his long-standing seizure disorder, and that this set of cognitive dysfunctions existed pre-operatively. The seminal Scoville and Milner study (1957) reported H.M.’s early clinical history as such: he was knocked down by a bicycle at age 9 and was unconscious for

Fig. 1. Left image: T1 weighted MRI of H.M.’s brain showing site of left frontal lesion, indicated by area in rectangle. Center image: histological visualization of lesion site stained for myelinated fibers. Right image: same tissue stained to resolve cell bodies. Images from https://www.thebrainobservatory.org/project-hm.

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