Chapter 8 - Learning Memory PDF

Chapter 11 Learning, Memory, and Amnesia How Your Brain Stores Information Africa Studio/Shutterstock Chapter Overview and Learning Objectives Amnesic Effects of LO 11.1 Describ...

Chapter 11 Learning, Memory, and Amnesia How Your Brain Stores Information Africa Studio/Shutterstock Chapter Overview and Learning Objectives Amnesic Effects of LO 11.1 Describe five specific memory tests that were used to assess Bilateral Medial Temporal H.M.’s anterograde amnesia. Lobectomy LO 11.2 Describe three major scientific contributions of H.M.’s case. LO 11.3 Discuss what research on medial temporal lobe amnesias has taught us about learning and memory. LO 11.4 Describe the difference between semantic and episodic memories. LO 11.5 Discuss two pieces of evidence that support the notion that selective hippocampal dysfunction can cause medial temporal lobe amnesia. 287 M11_PINE1933_11_GE_C11.indd 287 22/01/2021 11:19  288 Chapter 11 Amnesias of Korsakoff’s LO 11.6 Describe the etiology and symptoms of the amnesia of Syndrome and Korsakoff’s syndrome. Alzheimer’s Disease LO 11.7 Describe the symptoms of Alzheimer’s disease that have been associated with amnesia. Amnesia after Traumatic LO 11.8 Summarize the effects of a closed-head traumatic brain injury Brain Injury: Evidence for (TBI) on memory. Consolidation LO 11.9 Describe the classic view of memory consolidation and some of the evidence it rests upon. Contrast that with current thinking about memory consolidation. Evolving Perspective of the LO 11.10 Describe the delayed nonmatching-to-sample tests for monkeys Role of the Hippocampus in and rats. Memory LO 11.11 Describe the neuroanatomical basis for the object-recognition deficits that result from bilateral medial temporal lobectomy. Neurons of the Medial LO 11.12 Describe hippocampal place cells and entorhinal grid cells and Temporal Lobes and the relationship between these two cell types. Memory LO 11.13 Explain what a concept cell is and describe the key properties of concept cells with reference to the experimental evidence. LO 11.14 Explain what an engram cell is and describe how these cells were identified using optogenetics. Where Are Memories LO 11.15 For each of the following brain structures, describe the type(s) Stored? of memory they have been implicated in: inferotemporal cortex, amygdala, prefrontal cortex, cerebellum, and striatum. Cellular Mechanisms of LO 11.16 Describe the phenomenon known as long-term potentiation Learning and Memory (LTP) and provide evidence for its role in learning and memory. LO 11.17 Describe the mechanisms underlying the induction of LTP. LO 11.18 Describe four findings that have emerged from the study of the maintenance and expression phases of LTP. LO 11.19 Define long-term depression (LTD) and metaplasticity. LO 11.20 Describe two sorts of neuroplastic changes that occur outside the synapse that may play a role in learning and memory. Conclusion: Biopsychology LO 11.21 Define infantile amnesia and describe two experiments that of Memory and You investigated whether infantile amnesia extends to implicit memories. LO 11.22 Discuss the findings on the efficacy of smart drugs. LO 11.23 Explain what the case of R.M. tells us about the relationship between posttraumatic amnesia and episodic memory. M11_PINE1933_11_GE_C11.indd 288 22/01/2021 11:19  Learning, Memory, and Amnesia 289 Learning and memory are two ways of thinking about the Figure 11.1 Medial temporal lobectomy. The portions same thing: Both are neuroplastic processes; they deal with of the medial temporal lobes removed from H.M.’s brain are the ability of the brain to change its functioning in response illustrated in a view of the inferior surface of the brain. to experience. Learning deals with how experience changes Frontal the brain, and memory deals with how these changes are lobe stored and subsequently reactivated. Without the ability to learn and remember, we would experience every moment Olfactory as if waking from a lifelong sleep—each person would bulb be a stranger, each act a new challenge, and each word incomprehensible. Temporal lobe This chapter focuses on the roles played by various brain structures in the processes of learning and memory. Our knowledge of these roles has come to a great extent from the study of neuropsychological patients with brain- Optic damage-produced amnesia (any pathological loss of chiasm memory) and from research on animal models of the same memory problems. Mammillary body Amnesic Effects of Bilateral Medial Temporal Tissue typically excised in medial temporal lobectomy Lobectomy Ironically, the person who contributed more than any other major part of one, is removed from the brain; a lobotomy is an to our understanding of the neuropsychology of memory operation in which a lobe, or a major part of one, is separated from the rest of the brain by a large cut but is not removed.) was not a neuropsychologist. In fact, although he collabo- In several respects, H.M.’s bilateral medial temporal lobec- rated on dozens of studies of memory, he had no formal tomy was an unqualified success. His generalized seizures research training and not a single degree to his name. He were all but eliminated, and the incidence of focal seizures was was H.M., a man who in 1953, at the age of 27, had the reduced to one or two per day, even though the level of his anti- medial portions of his temporal lobes removed for the treat- convulsant medication was substantially reduced. Furthermore, ment of a severe case of epilepsy. Just as the Rosetta Stone H.M. entered surgery a reasonably well-adjusted individual with provided archaeologists with important clues to the mean- normal perceptual and motor abilities and normal intelligence, ing of Egyptian hieroglyphics, H.M.’s memory deficits were and he left it in nearly the same condition. Be that as it may, instrumental in the achievement of our current understand- H.M. was the last patient to receive a bilateral medial temporal ing of the neural bases of memory. lobectomy—because of its devastating amnesic effects. In assessing the amnesic effects of brain surgery, it is usual to administer tests of the patient’s ability to remember things learned before the surgery and tests of the patient’s ability to remember things learned after the surgery. Deficits on The Case of H.M., the Man Who the former tests lead to a diagnosis of retrograde (backward- Changed the Study of Memory acting) amnesia; those on the latter tests lead to a diagnosis of anterograde (forward-acting) amnesia. If a patient is During the 11 years preceding his surgery, H.M. suffered an found to have anterograde amnesia, the next step is usually average of one generalized seizure each week and many focal to determine whether the difficulty in storing new memories seizures each day, despite massive doses of anticonvulsant influences short-term memory (storage of new information for medication. Electroencephalography suggested that H.M.’s sei- brief periods of time while a person attends to it), long-term zures arose from foci in the medial portions of both his left and memory (storage of new information once the person stops right temporal lobes. Because the removal of one medial tempo- attending to it), or both. ral lobe had proved to be an effective treatment for patients with Like his intellectual abilities, H.M.’s memory for events a unilateral temporal lobe focus, the decision was made to per- predating his surgery remained largely intact. Although he had form a bilateral medial temporal lobectomy—the removal a mild retrograde amnesia for those events that occurred in of the medial portions of both temporal lobes, including most the 2 years before his surgery, his memory for more remote of the hippocampus, amygdala, and adjacent cortex (see events (e.g., for the events of his childhood) was reasonably Figure 11.1). (A lobectomy is an operation in which a lobe, or a normal. M11_PINE1933_11_GE_C11.indd 289 22/01/2021 11:19  290 Chapter 11 H.M.’s short-term anterograde memory also remained BLOCK-TAPPING TEST. H.M. had global amnesia— normal: For example, his digit span, the classic test of short- amnesia for information presented in all sensory modalities. term memory (see Chapter 5), was six digits (see Wickelgren, Milner (1971) demonstrated that H.M.’s amnesia was not 1968)—this means that if a list of six digits was read to him, restricted to verbal material by assessing his performance he could usually repeat the list correctly, but he would have on the block-tapping test. An array of 9 blocks was spread difficulty repeating longer lists. out on a board in front of H.M., and he was asked to watch In contrast, H.M. had an almost total inability to form new the neuropsychologist touch a sequence of them and then long-term memories: Once he stopped thinking about a new experience, it was lost forever. In effect, H.M. became sus- to repeat the same sequence of touches. Whereas a typical pended in time on that day in 1953 when he regained his health person has a block-tapping span of 6, H.M. could not learn but lost his future. His family moved shortly after his surgery, to correctly touch a sequence of 6 blocks—even when the but he was never able to remember his new address or where same sequence was repeated 12 times. commonly used items were kept in his new residence. He never MIRROR-DRAWING TEST. The first indication that H.M.’s learned to recognize people (e.g., doctors and nurses) who he anterograde amnesia did not involve all long-term memories did not meet until after his surgery, and he read the same maga- zines over and over without finding them familiar. If you met H.M. came from the results of a mirror-drawing test (see Milner, at a party he could chat quite normally until he was distracted 1965). H.M.’s task was to draw a line within the boundaries (e.g., by the phone); then he would not remember you, the of a star-shaped target by watching his hand in a mirror. conversation, or where he was. It was as if he was continually H.M. was asked to trace the star 10 times on each of 3 con- regaining consciousness. secutive days, and the number of times he went outside the boundaries on each trial was recorded. As Figure 11.2 shows, Figure 11.2 The learning and retention of the mirror- drawing task by H.M. Despite his good retention of the task, H.M. had no conscious recollection of having performed it Formal Assessment of H.M.’s before. Anterograde Amnesia: Discovery of Unconscious Memories LO 11.1 Describe five specific memory tests that were used to assess H.M.’s anterograde amnesia. In order to characterize H.M.’s anterograde memory prob- lems, researchers began by measuring his performance on objective tests of various kinds of memory. This subsection describes five tests that were used to assess H.M.’s long- term memory. The results of the first two tests documented H.M.’s severe deficits in long-term memory, whereas the results of the last three indicated that H.M.’s brain was capable of storing long-term memories but that H.M. had no conscious awareness of those memories. This finding changed the way biopsychologists think about the brain and memory. DIGIT-SPAN 1 1 TEST. H.M.’s inability to form certain long-term memories was objectively illustrated by his per- Errors by H.M. on Each Trial Number of Mirror-Drawing 30 formance on the digit-span + 1 test, a classic test of verbal Day 1 Day 2 Day 3 long-term memory. H.M. was asked to repeat 5 digits that were read to him at 1-second intervals. He repeated the 20 sequence correctly. On the next trial, the same 5 digits were presented in the same sequence with 1 new digit added on 10 the end. This same 6-digit sequence was presented a few times until he got it right, and then another digit was added to the end of it, and so on. After 25 trials, H.M. had not 2 4 6 8 10 2 4 6 8 10 2 4 6 8 10 managed to repeat the 8-digit-sequence. Most people can Trials Based on Milner, B. 1965. Memory disturbances after bilateral hippocampal correctly repeat about 15 digits after 25 trials of the digit- lesions. In P. Milner & S. Glickman (Eds.), Cognitive Processes and the Brain span + 1 test (see Drachman & Arbit, 1966). (pp. 104–105). Princeton, NJ: D. Van Nostrand. M11_PINE1933_11_GE_C11.indd 290 22/01/2021 11:19  Learning, Memory, and Amnesia 291 H.M.’s performance improved over the 3 days, which indi- (Woodruff-Pak, 1993). A tone was sounded just before a puff cates retention of the task. However, despite his improved of air was administered to his eye; these trials were repeated performance, H.M. could not recall ever having completed until the tone alone elicited an eye blink. Two years later, the task before. H.M. retained this conditioned response almost perfectly, although he had no conscious recollection of the training. INCOMPLETE-PICTURES TEST. The discovery that H.M. was capable of forming long-term memories for mir- ror drawing suggested that sensorimotor tasks were the Three Major Scientific Contributions one exception to his inability to form long-term memories. However, this view was challenged by the demonstration of H.M.’s Case that H.M. could also form new long-term memories for the LO 11.2 Describe three major scientific contributions incomplete-pictures test—a non­sensorimotor test of mem- of H.M.’s case. ory that employs five sets of fragmented drawings. Each H.M.’s case is a story of personal tragedy, but his contri- set contains drawings of the same 20 objects, but the sets butions to the study of the neural basis of memory were differ in their degree of completeness: Set 1 contains the immense. The following three contributions proved to be most fragmented drawings, and set 5 contains the complete particularly influential. drawings. The subject is asked to identify the 20 objects First, by showing that the medial temporal lobes play from the most fragmented set (set 1); then, those objects an especially important role in memory, H.M.’s case chal- that go unrecognized are presented in their set 2 versions, lenged the then prevalent view that memory functions and so on, until all 20 items have been identified. Figure 11.3 are diffusely and equivalently distributed throughout the illustrates the performance of H.M. on this test and his brain. In so doing, H.M.’s case renewed efforts to relate improved performance 1 hour later (Milner et al., 1968). individual brain structures to specific mnemonic (memory- Despite his improved performance, H.M. could not recall related) processes; in particular, H.M.’s case spawned a previously performing the task. massive research effort aimed at clarifying the mnemonic PAVLOVIAN CONDITIONING. H.M. learned an eye- functions of the hippocampus and other medial temporal blink Pavlovian conditioning task, albeit at a slower rate lobe structures. Figure 11.3 Two items from the incomplete-pictures test. H.M.’s memory for the 20 items on the test was indicated by his ability to recognize the more fragmented versions of them when he was retested. Nevertheless, he had no conscious awareness of having previously seen the items. Set 1 Set 2 Set 3 Set 4 Set 5 14 Initial test Retest 12 Errors by H.M. on each set of the incomplete-pictures test 10 8 1 hour 6 4 2 0 Set 1 Set 2 Set 3 Set 4 Set 1 Set 2 Set 3 M11_PINE1933_11_GE_C11.indd 291 22/01/2021 11:19  292 Chapter 11 Second, the discovery that bilateral medial temporal Tests that assess implicit memory are called repetition lobectomy abolished H.M.’s ability to form certain kinds of priming tests. The incomplete-pictures test and mirror- long-term memories without disrupting his performance on drawing task are two examples, but repetition priming tests tests of short-term memory or his remote memory (memory that involve memory for words are more common. First, the for experiences in the distant past) supported the theory that participants are asked to examine a list of words; they are there are different modes of storage for short-term, long- not asked to learn or remember anything. Later, they are term, and remote memory. H.M.’s specific problem appeared shown a series of fragments (e.g., _ O B _ _ E R) of words to be a difficulty in memory consolidation (the translation from the original list and are simply asked to complete of short-term memories into long-term memories). them. Controls who have seen the original words perform Third, H.M.’s case was the first to reveal that an amne- well. Surprisingly, participants with amnesia often perform sic patient might claim no recollection of a previous expe- equally well, even though they have no explicit memory of rience while demonstrating memory for it by improved seeing the original list. (By the way, the correct answer to performance (e.g., on the mirror-drawing and incomplete- the repetition priming example is “lobster.”) pictures tests). This discovery led to the creation of two The discovery that there are two memory systems— distinct categories of long-term memories: Conscious long- explicit and implicit—raises an important question: Why term memories became known as explicit memories, and do we have two parallel memory systems, one conscious long-term memories demonstrated by improved test per- (explicit) and one unconscious (implicit)? Presumably, the formance without conscious awareness became known as implicit system was the first to evolve because it is more implicit memories. As you will soon learn, this distinction simple (it does not involve consciousness), so the question is of general relevance: Many people with amnesia lose their is actually this: What is the advantage in having a second, ability to form explicit memories while maintaining their conscious system? ability to form implicit memories. Two experiments, one with amnesic patients (Reber, Knowlton, & Squire, 1996) and one with amnesic monkeys Journal Prompt 11.1 with medial temporal lobe lesions (Buckley & Gaffan, 1998), suggest that the answer is “flexibility.” In both experiments, Suppose one of your patients shows preserved ability to play the violin but has no recollection of what they had the amnesic subjects learned an implicit learning task as for lunch. How would you use implicit memory to help well as control subjects did; however, if they were asked to your patient learn new things, and will they be aware use their implicit knowledge in a different way or in a differ- that they have gained this new knowledge? ent context, they failed miserably. Presumably, the evolution of explicit memory systems provided for the flexible use of H.M. died in 2008. Before his death, H.M. donated his information. brain to science, and his brain was sliced a few years after his death. Images of those brain slices are now archived Semantic and Episodic Memories online, where anyone can view them: H.M. continues to LO 11.4 Describe the difference between semantic and contribute to science, long after his death. H.M.’s real name episodic memories. was Henry Molaison. H.M. was able to form very few new explicit memories. Medial Temporal Lobe Amnesia However, most people with medial temporal lobe amnesia display memory deficits that are less complete. The study LO 11.3 Discuss what research on medial temporal of these amnesics has found that explicit memories fall into lobe amnesias has taught us about learning two categories and that many of these amnesics tend to have and memory. far greater difficulties with one category than the other. Neuropsychological patients with a profile of mnemonic Explicit long-term memories come in two varieties: deficits similar to those of H.M., with preserved intellectual semantic and episodic (see Squire et al., 2015). Semantic functioning, and with evidence of medial temporal lobe dam- memories are explicit memories for general facts or infor- age are said to suffer from medial temporal lobe amnesia. mation; episodic memories are explicit memories for Research on medial temporal lobe amnesia has shown specific moments (i.e., episodes) in one’s life (see Rugg & that H.M.’s difficulty in forming explicit long-term memories Vilberg, 2013). People with medial temporal lobe amnesia while retaining the ability to form implicit long-term memories have particular difficulty with episodic memories. In other of the same experiences is not unique to him. This problem has words, they have difficulty remembering specific events proved to be a symptom of medial temporal lobe amnesia, as from their lives, even though their memory for general well as many other amnesic disorders. As a result, the assess- information is often normal. Although they can’t remember ment of implicit long-term memories now plays an important having breakfast with an old friend in the morning, or going role in the study of human memory (see Reber, 2013). to a new movie in the afternoon, they often remember a M11_PINE1933_11_GE_C11.indd 292 22/01/2021 11:19  Learning, Memory, and Amnesia 293 language they learned, world events, and the sorts of things become very effective at providing semantic answers to learned at school. episodic questions. The following paraphrased exchange Endel Tulving has been a major force in research on the illustrates why neuropsychologists have difficulty spotting semantic-episodic dichotomy (Tulving, 2002). Following is a episodic memory problems. description of Tulving’s patient K.C. Episodic memory (also called autobiographical memory) has been likened to traveling back in time mentally and experiencing one’s past. The Case of the Clever Neuropsychologist: Spotting The Case of K.C., the Man Who Episodic Memory Deficits Can’t Time Travel Neuropsychologist: I understand that you were a teacher. Patient: That’s right, I taught history. K.C. had a motorcycle accident in 1981. He suffered diffuse Neuropsychologist: You must have given some good lectures brain damage, including damage to the medial temporal lobes. in your time. Can you recall one of them that stands out? Despite severe amnesia, K.C.’s other cognitive abilities remain Patient: Sure. I have given thousands of lectures. I especially remarkably normal. His general intelligence and use of language liked Greek history. are normal; he has no difficulty concentrating; he plays the Neuropsychologist: Was there any particular lecture that organ, chess, and various card games; and his reasoning abili- stood out—perhaps because it was very good or because ties are good. His knowledge of mathematics, history, science, something funny happened? geography, and other school subjects is good. Patient: Oh, yes. Many stand out. My students liked my Similarly, K.C. has good retention of many of the facts of lectures—at least some of them—and sometimes I was his early life. He knows his birth date, where he lived as a youth, quite funny. where his parents’ summer cottage was located, the names Neuropsychologist: But is there one—just one—that you of schools he attended, the makes and colors of cars that he remember? And can you tell me something about it? has owned. Patient: Oh yes, no problem. I didn’t understand what Still, in the midst of these normal memories, K.C. has you wanted. I can remember giving lectures and all my severe amnesia for personal experiences. He cannot recall students were there watching and smiling. a single personal event for more than a minute or two. This Neuropsychologist: But can you describe a lecture where inability to recall any episodes (events) at which he was pres- something happened that never happened in any other ent covers his entire life. Despite these serious memory prob- lecture? Perhaps something funny or disturbing. lems, K.C. has no difficulty having a conversation, and his Patient: That’s hard. memory problems are far less obvious to others than one Neuropsychologist: Before I go, I have some news for you that would expect. Basically, he does quite well using only his I think you will like. I understand that you are a hockey fan semantic memory. and follow the Toronto Maple Leafs. K.C. understands the concept of time but he cannot “time Patient: Jeez, you guys know everything. travel” into either the past or the future. He cannot imagine future Neuropsychologist: Last night was a great night for Toronto. events any better than he can recall his past: He can’t imagine They beat New York 6–0. Do you think that you can what he will be doing for the rest of the day, the week, or his life. remember that score for me? I will ask you about it a bit later. Patient: That’s great news. I will have no problem remembering that. [Neuropsychologist leaves the room and returns an hour later.] Vargha-Khadem and colleagues (1997) followed the mat- Neuropsychologist: I asked you to remember something the uration of three patients with medial temporal lobe amnesia last time we chatted. Do you remember it? who experienced bilateral medial temporal lobe damage Patient: I don’t think so. I seem to have forgotten. It must have been a long time ago. early in life. Remarkably, although they could remember few Neuropsychologist: That’s strange. Do you remember anything of the experiences they had during their daily lives (episodic specific about our last meeting, or even when it was? memory), they progressed through mainstream schools and Patient: Yes, I think we chatted about my memory. acquired reasonable levels of language ability and factual Neuropsychologist: I understand that you are a Toronto Maple knowledge (semantic memory). However, despite their Leafs fan. Are they a good team? ­academic success, their episodic memory did not improve Patient: Yes, they are very good. I used to go to every game (de Haan et al., 2006). with my father when I was a kid. They had great players; It is difficult to spot episodic memory deficits, even they were fast skaters and worked very hard. Did you when the deficits are extreme. This occurs in part because know that they beat the New York Rangers 6–0? Now neuropsychologists usually have no way of knowing the that’s good. true events of a patient’s life and in part because the patients M11_PINE1933_11_GE_C11.indd 293 22/01/2021 11:19  294 Chapter 11 Effects of Global Cerebral Figure 11.4 The major components of the hippocampus: Ischemia on the Hippocampus CA1, CA2, CA3, and CA4 subfields and the dentate gyrus. R.B.’s brain damage appeared to be restricted largely to and Memory the pyramidal cell layer of the CA1 subfield. (CA stands for “cornu ammonis,” another name for hippocampus.) LO 11.5 Discuss two pieces of evidence that support the notion that selective hippocampal dysfunction can cause medial temporal lobe amnesia. Patients who have experienced global cerebral ischemia— that is, have experienced an interruption of blood supply to their entire brain—often suffer from medial temporal lobe amnesia. R.B. is one such individual (Zola-Morgan, Squire, & Amaral, 1986). The Case of R.B., Product of a Bungled Operation At the age of 52, R.B. underwent cardiac bypass surgery. The surgery was bungled, and, as a consequence, R.B. suffered brain damage. The pump that was circulating R.B.’s blood to his body while his heart was disconnected broke down, and it was several minutes before a replacement arrived from another part of the hospital. R.B. lived, but the resulting ischemic brain damage left him amnesic. Although R.B.’s amnesia was not as severe as H.M.’s, it was comparable in many aspects. R.B. died in 1983, and a detailed postmortem examination of his brain was carried out with the permission of his family. Obvious brain dam- age was restricted largely to the pyramidal cell layer of just one part of the hippocampus—the CA1 subfield (see Figure 11.4). Pyramidal cell layer R.B.’s case suggested that hippocampal damage Dentate gyrus by itself can produce medial temporal lobe amnesia. CA1 Subfield However, in such cases of cerebral ischemia, it is difficult CA2 Subfield Hippocampus to rule out the possibility of subtle dysfunction to other CA3 Subfield areas of the brain. CA4 Subfield Arguably, the strongest evidence that selective hippo- campal damage can cause medial temporal lobe amnesia comes from cases of transient global amnesia. Transient global amnesia is defined by its sudden onset in the absence The sudden onset of transient global amnesias suggests of any obvious cause in otherwise normal adults. As in they are caused by stroke; however, until recently no brain other cases of medial temporal lobe amnesia, there is severe pathology could be linked to the disorder. But, in recent anterograde amnesia and moderate retrograde amnesia for years, investigators have identified abnormalities in the explicit episodic memories (see Arena & Rabinstein, 2015; CA1 subfield of the hippocampus (see Arena & Rabinstein, Bartsch & Butler, 2013). However, in the case of transient 2015; Bartsch & Butler, 2013). The time course of these global amnesia, the amnesia is transient, typically lasting abnormalities—they are not usually apparent for several only 4 to 6 hours. Imagine the distress of the otherwise- hours after the beginning of the attack and have usually healthy people who suddenly develop the symptoms of cleared up 10 days later—are suggestive of ischemia- medial temporal lobe amnesia. induced damage (see Hunter, 2011). M11_PINE1933_11_GE_C11.indd 294 22/01/2021 11:19  Learning, Memory, and Amnesia 295 amnesia, associated with damage to the medial diencepha- Amnesias of Korsakoff’s lon). Although his memory deficits were conventional, their cause was not (Teuber, Milner, & Vaughan, 1968). Syndrome and Alzheimer’s The Up-Your-Nose Case of N.A. Disease N.A. joined the U.S. Air Force after a year of college, serving as The preceding module focused on amnesias associated with a radar technician until his accident. On the fateful day, N.A.’s different sorts of brain dysfunction that both occur over a roommate was playing with a fencing foil behind N.A.’s chair. N.A. relatively brief period of time and are localized to specific turned unexpectedly and was stabbed up the right nostril. The brain areas. This module considers the amnesias associated foil punctured the cribriform plate (the thin bone around the base with two syndromes that involve both a much slower pro- of the frontal lobes), taking an upward course into N.A.’s brain. gression of brain dysfunction and dysfunction that is more When tested a few weeks after his accident, N.A. was diffuse: Korsakoff’s syndrome and Alzheimer’s disease. unable to recall any significant personal, national, or interna- tional events that had occurred in the 2 years preceding his accident. However, when retested 3 years later, his retrograde Amnesia of Korsakoff’s Syndrome amnesia had decreased in duration, covering only those events LO 11.6 Describe the etiology and symptoms of the that occurred in the 2 weeks before the accident. N.A.’s recall of day-to-day events that occurred after the amnesia of Korsakoff’s syndrome. accident was extremely poor. On initial testing, he could not As you learned in Chapter 1, Korsakoff’s syndrome is a remember what he ate for breakfast, people whom he had disorder of memory that is most common in people who recently met, or visits from his family. However, unpredictably have consumed large amounts of alcohol; the disorder is he would sometimes recall specific experiences of no particular largely attributable to the brain dysfunction associated with significance. Although his ability to remember new experiences the thiamine deficiency that often accompanies heavy alco- has improved somewhat since he was first tested, he has not hol consumption (see Scalzo et al., 2015). In its advanced been able to function well enough to gain employment. An MRI of N.A.’s brain was taken in the late 1980s (Squire et al., stages, it is characterized by a variety of sensory and motor 1989). It revealed extensive medial diencephalic damage, including problems, extreme confusion, personality changes, and a damage to the mediodorsal nuclei and mammillary bodies. risk of death from liver, gastrointestinal, or heart disorders. Postmortem examination typically reveals lesions to the medial diencephalon (the medial-thalamus and the medial- hypothalamus) and diffuse damage to several other brain Journal Prompt 11.2 structures, most notably the neocortex, hippocampus, and How have case studies played an important role in the cerebellum (see Fama, Pitel, & Sullivan, 2012; Kril & Harper, study of memory? 2012; Savage, Hall, & Resende, 2012). The amnesia of Korsakoff’s syndrome is similar to medial temporal lobe amnesia in some respects. For example, dur- Amnesia of Alzheimer’s Disease ing the early stages of the disorder, anterograde amnesia for explicit episodic memories is the most prominent symptom. LO 11.7 Describe the symptoms of Alzheimer’s disease However, as the disorder progresses, retrograde amnesia, that have been associated with amnesia. which can eventually extend back into childhood, also devel- Alzheimer’s disease is another major cause of amnesia. ops. Deficits in implicit memory depend on the particular test The first sign of Alzheimer’s disease is often a mild dete- used, but in general they are less severe than those in explicit rioration of memory. However, the disorder is progressive: memory (see Oudman et al., 2011; Van Tilborg et al., 2011). Eventually, dementia develops and becomes so severe that Because the brain damage associated with Korsakoff’s the patient is incapable of even simple activities (e.g., eat- syndrome is diffuse, it has been difficult to identify which ing, speaking, recognizing a spouse, or bladder control). part of it is specifically responsible for the amnesia. Still, Alzheimer’s disease is terminal. much attention has focused on one pair of medial dience- Efforts to understand the neural basis of Alzheimer’s phalic nuclei: the mediodorsal nuclei of the thalamus; this amnesia have focused on predementia Alzheimer’s patients is because there is almost always damage to these nuclei in (Alzheimer’s patients who have yet to develop dementia). Korsakoff patients. However, it is unlikely that the memory The memory deficits of these patients are more general deficits of Korsakoff patients are attributable to the damage than those associated with medial temporal lobe damage, of any single structure. medial diencephalic damage, or Korsakoff’s syndrome. In N.A. is a particularly well-known patient with medial addition to major anterograde and retrograde deficits in diencephalic amnesia (amnesia, such as Korsakoff tests of explicit memory, predementia Alzheimer’s patients M11_PINE1933_11_GE_C11.indd 295 22/01/2021 11:19  296 Chapter 11 often display deficits in short- Figure 11.5 The retrograde amnesia and anterograde amnesia associated with a term memory and in some types closed-head traumatic brain injury (TBI). of implicit memory: Their implicit memory for verbal and percep- tual material is often deficient, whereas their implicit memory for 1 A blow to the head produces coma. sensorimotor learning is not (see Postle, Corkin, & Growdon, 1996). 2 When the victim regains consciousness, there is a period of confusion. 3 The level of acetylcholine When the period of is greatly reduced in the brains confusion ends, the victim of Alzheimer ’s patients. This has retrograde amnesia for events that occurred during the reduction results from the degen- period just before the blow and eration of the basal forebrain BLOW anterograde amnesia for events (a midline area located just TO that occurred during the period above the hypothalamus; see HEAD of confusion. Figure 11.16), which is the brain’s main source of acetylcholine. Normal Retro- Confusion Normal Cognitive grade Coma and Anterograde Cognitive This finding, coupled with the Function Amnesia Amnesia Function finding that strokes in the basal TIME TIME TIME forebrain area can cause amne- sia, led to the view that acetyl- choline depletion is the cause of Craig Durling/ZUMA Wire/Alamy Live News Alzheimer’s amnesia. Although acetylcholine depletion resulting from dam- tested at all. Testing usually reveals that the patient has perma- age to the basal forebrain may contribute to Alzheimer’s nent retrograde amnesia for the events that led up to the blow amnesia, it is clearly not the only factor. The brain damage and permanent anterograde amnesia for many of the events associated with Alzheimer’s disease is extremely diffuse, that occurred during the subsequent period of confusion. involving many areas including the medial temporal lobes The anterograde memory deficits that follow a closed- and the prefrontal cortex, which play major roles in memory head TBI are often quite puzzling to the friends and rela- (see Braskie & Thompson, 2013). tives who have talked to the patient during the period of confusion—for example, during a hospital visit. The patient may seem reasonably lucid at the time, because short-term memory is normal, but later may have no recollection what- Amnesia after Traumatic soever of the conversation. Brain Injury: Evidence for Figure 11.5 summarizes the effects of a closed-head TBI on memory. Note that the duration of the period of confusion Consolidation and anterograde amnesia is typically longer than that of the coma, which is typically longer than the period of retrograde Closed-head traumatic brain injuries (TBIs) (brain injuries amnesia. More severe blows to the head tend to produce lon- produced by blows to the head that do not penetrate ger comas, longer periods of confusion, and longer periods of the skull; see Chapter 10) are the most common cause of amnesia. Not illustrated in Figure 11.5 are islands of memory— amnesia. The amnesia following a closed-head TBI is called surviving memories for isolated events that occurred during posttraumatic amnesia. periods for which other memories have been wiped out. Posttraumatic Amnesia Gradients of Retrograde Amnesia LO 11.8 Summarize the effects of a closed-head and Memory Consolidation traumatic brain injury (TBI) on memory. LO 11.9 Describe the classic view of memory consolidation and some of the evidence it The coma (pathological state of unconsciousness) following a rests upon. Contrast that with current thinking severe blow to the head usually lasts a few seconds or minutes, about memory consolidation. but in severe cases it can last weeks. Once the patient regains consciousness, he or she experiences a period of confusion. Gradients of retrograde amnesia after closed-head TBI seem Victims of closed-head TBIs are typically not tested by a neu- to provide evidence for memory consolidation. The fact that ropsychologist until after the period of confusion—if they are closed-head TBIs preferentially disrupt recent memories M11_PINE1933_11_GE_C11.indd 296 22/01/2021 11:19  Learning, Memory, and Amnesia 297 suggests that the storage of older memories Figure 11.6 Demonstration of a long gradient of ECS-produced has been strengthened (i.e., consolidated). ­retrograde amnesia. A series of five electroconvulsive shocks produced The classic theory of memory consolida- ­retrograde amnesia for television shows that played for only one season tion is Hebb’s theory. He argued that memo- in the 3 years before the shocks; however, the shocks did not produce ries of experiences are stored in the short amnesia for one-season shows that had played prior to that. term by neural activity reverberating (circu- (percent of TV show titles correctly recognized) lating) in closed circuits (see Hanslmayr, Test given after ECS Staresina, & Bowman, 2016). These reverber- 70 Test given before ECS ating patterns of neural activity are suscep- tible to disruption—for example, by a blow to the head—but eventually they induce Retrograde Amnesia 60 structural changes in the involved synapses, Memory which provide stable long-term storage. Electroconvulsive shock seemed to pro- vide a controlled method of studying mem- 50 ory consolidation. Electroconvulsive shock (ECS) is an intense, brief, diffuse, seizure- inducing current that is administered to the 40 brain through large electrodes attached to the scalp. The rationale for using ECS to study memory consolidation was that by disrupting neural activity, ECS would erase from storage 1–3 4–5 6–7 8–9 10–17 years years years years years only those memories that had not yet been converted to structural synaptic changes; the (number of years before ECS that one-season TV shows played) length of the period of retrograde amnesia Duration of Learning–ECS Interval produced by an ECS would thus provide an Based on Squire, L. R., Slater, P. C., & Chace, P. M. (1975). Retrograde amnesia: Temporal gradient in very long term memory following electroconvulsive therapy. Science, 187, 77–79. estimate of the amount of time needed for memory consolidation. Karni, & Born, 2015; Dudai & Morris, 2013). In other words, Many studies have employed ECS to study the duration the evidence indicates that lasting memories become more of consolidation. Some studies have been conducted on human and more resistant to disruption throughout a person’s life. patients receiving ECS for the treatment of depression; others Each time a memory is activated, it is updated and linked to have been conducted with laboratory animals. Since the 1950s, additional memories (see Sandrini, Cohen, & Censor, 2015). hundreds of studies have examined ECS-produced gradients These additional links increase the memory’s resistance to of retrograde amnesia in order to estimate the duration of disruption by cerebral trauma, such as concussion or ECS. memory consolidation. Hebb’s theory implies that memory consolidation is relatively brief, a few seconds or minutes, HIPPOCAMPUS AND CONSOLIDATION. The case about as long as specific patterns of reverberatory neural of H.M. provided evidence of memory consolidation, and it activity could conceivably maintain a memory. However, seemed to suggest that the hippocampus played a special role many studies found evidence for much longer gradients. in it. To account for the fact that the bilateral medial temporal The classic study of Squire, Slater, and Chace (1975) is lobectomy disrupted only those retrograde memories acquired an example of a study that found a long gradient of ECS- in the few years before H.M.’s surgery, Scoville and Milner (1957) produced retrograde amnesia. They measured the memory suggested that memories are temporarily stored in the hippo- of a group of ECS-treated patients for television shows that campus until they can be transferred to a more stable cortical had played for only one season in different years prior to their storage system. This theory has become known as the standard electroconvulsive therapy. They tested each patient twice on consolidation theory or dual-trace theory (see Clark & Maguire, different forms of the test: once before they received a series 2016; Dudai, Karni, & Born 2015; Moscovitch et al., 2016). of five electroconvulsive shocks and once after. The differ- Today, there are few adherents to standard consolidation ence between the before- and after-scores served as an esti- theory. As you have just read, temporally graded retrograde mate of memory loss for the events of each year. Figure 11.6 amnesia is a feature of many forms of human amnesia (e.g., illustrates that five electroconvulsive shocks disrupted the Alzheimer’s amnesia, Korsakoff’s amnesia); consequently, it retention of television shows that had played in the 3 years seems unlikely that the hippocampus plays a special role in prior to treatment but not those that had played earlier. consolidation. It appears that when a conscious experience The current view of memory consolidation is that it occurs, it is rapidly and sparsely encoded in a distributed fash- continues for a very long time if not indefinitely (see Dudai, ion throughout the hippocampus and other involved structures. M11_PINE1933_11_GE_C11.indd 297 22/01/2021 11:19  298 Chapter 11 According to Moscovitch and colleagues (e.g., Nadel memory is retrieved from long-term storage, it is tempo- and Moscovitch, 1997; Winocur and Moscovitch, 2011), rarily held in labile (changeable or unstable) short-term retained memories become progressively more resistant to memory, where it is once again susceptible to posttraumatic disruption by hippocampal dysfunction because each time a amnesia until it is reconsolidated. similar experience occurs or the original memory is recalled, Interest in the process of reconsolidation originated a new engram (a change in the brain that stores a memory) is with several studies in the 1960s, but then faded until a key established and linked to the original engram. With the addi- study by Nader, Schafe, and LeDoux (2000) rekindled it. tion of each new engram, aspects of the original memory are These researchers infused the protein-synthesis inhibitor progressively transformed into a semantic memory whose anisomycin into the amygdalae of rats shortly after the rats storage is less dependent on the hippocampus and more had been required to recall a fear-conditioning trial. The dependent on cortical structures (see Clarke & Maguire, infusion produced retrograde amnesia for the fear condi- 2016; Moscovitch et al., 2016). This makes the memory easier tioning, even though the original conditioning trial had to recall and the original engram more difficult to disrupt. occurred many days before. Most research on reconsolida- tion has involved fear conditioning, but some evidence sug- RECONSOLIDATION. One theoretical construct that has gests that it may be a general phenomenon in the nervous attracted significant attention is reconsolidation (see Bonin system (see Bonin & De Koninck, 2015). & De Koninck, 2015). The hypothesis is that each time a Scan Your Brain This chapter is about to move from discussion of human 5. _______ amnesia refers to the loss of memories that memory disorders to consideration of animal models of human took place before the brain injury. memory disorders. Are you ready? Scan your brain to assess 6. _______ depletion resulting from damage to the basal your knowledge of human memory disorders by filling in the forebrain may contribute to Alzheimer’s amnesia. blanks in the following sentences. The correct answers are 7. Memory consolidation is studied using _______ shock, provided at the end of the exercise. Before proceeding, review which induces seizures using large electrodes. the material related to your errors and omissions. 8. Each time a memory is recalled or a similar experience occurs, a new _______ is formed, making that memory 1. Improved test performance without conscious more difficult to forget. ­ wareness, as in the case of H.M.’s mirror-drawing task, a exemplifies long-term memories which became known as 9. Amnesia caused by a nonpenetrative head injury is _______ memories. called _______. 2. Explicit long-term memory is broadly divided in two main 10. Most research on reconsolidation has involved _______ categories: episodic and _______. conditioning using rats. 3. Ischemia in the _______ could result in transient global (10) fear. amnesia. (7) electroconvulsive, (8) engram, (9) posttraumatic amnesia (PTA), 4. Amnesia due to Korsakoff’s syndrome is typically (4) medial diencephalon, (5) Anterograde, (6) Acetylcholine, associated with large lesions to the _______. Scan Your Brain answers: (1) implicit, (2) semantic, (3) hippocampus, humans, a major effort has been made to develop animal Evolving Perspective of the models of human brain-damage-produced amnesia. The first reports of H.M.’s case in the 1950s triggered a Role of the Hippocampus massive effort to develop an animal model of his disorder in Memory so that it could be subjected to experimental analysis. In its early years, this effort was a dismal failure; lesions of medial As interesting and informative as the study of patients with temporal lobe structures did not produce severe anterograde amnesia can be, it has major limitations. Many important amnesia in rats, monkeys, or other nonhuman species. questions about the neural bases of amnesia can be answered In retrospect, there were two reasons for the initial only by controlled experiments. For example, in order to difficulty in developing an animal model of medial tem- identify the particular structures of the brain that partici- poral lobe amnesia. First, it was not initially apparent that pate in various kinds of memory, it is necessary to make H.M.’s anterograde amnesia did not extend to all kinds of precise lesions in various structures and to control what and long-term memory—that is, it was specific to explicit long- when the subjects learn and how and when their retention term memories—and most animal memory tests widely is tested. Because such experiments are not feasible with used in the 1950s and 1960s were tests of implicit memory M11_PINE1933_11_GE_C11.indd 298 22/01/2021 11:19  306 Chapter 11 Although it is not yet clear how concept cells contribute to the storage of memories, it is clear that they play a role, and their discovery is a major step forward (see De Falco Where Are Memories et al., 2016). Stored? In the mid-20th century, when modern biopsychology Engram Cells began, there was a major push to identify the areas in the LO 11.14 Explain what an engram cell is and describe brain where memories are stored. The search was largely how these cells were identified using championed by Karl Lashley, who wrote a famous review optogenetics. paper, In Search of the Engram, in which he described his fruitless efforts. Lashley and many who subsequently took As you learned in Chapter 5, one new approach in the tool- up the search used the lesion method. If a particular struc- kit available to biopsychologists is optogenetics. If you recall, ture were the storage site for all memories of a particular in optogenetics, neuroscientists insert an opsin gene into type, then destruction of that structure should eliminate particular neurons, after which they can then use light to all memories of that type that were acquired prior to the either hyperpolarize or depolarize those neurons. In recent lesion. No brain structure has shown this result: Lesions of years, this tool has been used extensively in studies of learn- particular structures tend to produce either no retrograde ing and memory in mice (see Goshen, 2014). One line of amnesia at all or retrograde amnesia for only the experi- research has been particularly interesting because it can ences that occurred in the days or weeks just before the shed light on the location of the neurons that maintain an surgery. These findings have led to two major conclusions: engram: so-called engram cells (see Josselyn, Köhler, and (1) Memories are stored diffusely in the brain and thus can Frankland, 2015; Tonegawa, Morrissey, & Kitamura, 2018). survive destruction of any single structure; and (2) memo- Engram cells are neurons that undergo a persistent change ries become more resistant to disruption over time. as the result of experience such that when they are subse- So far, this chapter has focused on four neural structures quently activated or inhibited, the retrieval of the original that appear to play some role in the storage of memories: (1) experience is triggered or suppressed, respectively (see Bliss The hippocampus and (2) the medial temporal cortex play et al., 2018; Tonegawa, Morrissey, & Kitamura, 2018). roles in episodic memory; and (3) the mediodorsal nucleus The identification of an engram cell via optogenetics is of the thalamus and (4) the basal forebrain have been impli- typically a two-stage process. In the first stage, the tagging cated in the memory deficits of Korsakoff’s and Alzheimer’s stage, the neurons that are active during the learning task are diseases, respectively. In this module, we take a brief look induced to express opsins while an animal engages in a partic- at five other areas of the brain that have been implicated in ular learning task. In the second stage, the manipulate stage, the memory: inferotemporal cortex, amygdala, prefrontal cor- previously active neurons are now either inhibited or excited tex, cerebellum, and striatum. See Figure 11.16. by using light to influence the activity of the opsin-tagged neurons (see Josselyn, Köhler, & Frankland, 2015; Redondo et al., 2014; Ryan et al., 2015; Takeuchi & Morris, 2014). Five Brain Areas Implicated in In essence, researchers are now able to observe, sup- Memory press, or activate engram cells in different parts of the nervous system. For example, researchers have been able LO 11.15 For each of the following brain structures, to reverse depressive-like behavior in mice by optogeneti- describe the type(s) of memory they have cally reactivating hippocampal cells that had previously been implicated in: inferotemporal cortex, been active during the encoding of a positive experience amygdala, prefrontal cortex, cerebellum, and (Ramirez et al., 2015). Moreover, researchers have shown striatum. that in mouse models of Alzheimer’s disease, activating engram cells leads to the retrieval of memories that are oth- INFEROTEMPORAL CORTEX. Numerous electrophysi- erwise inaccessible—suggesting that the memory deficits of ological recording and functional brain-imaging studies of Alzheimer’s disease are retrieval deficits rather than encod- memory have led to the same important conclusion: Areas ing deficits (see Roy et al., 2016; Shrestha & Klann, 2016). of the brain that are active during the retention of an expe- rience tend to be the same ones active during the original experience. This has focused attention on the mnemonic functions of the sensory and motor areas of the brain. In Journal Prompt 11.4 particular, attention has focused on inferotemporal cortex Do you think that optogenetics might have clinical impli- (cortex of the inferior temporal cortex), which has complex cations for humans sometime in the future? If so, what do you think such interventions might look like? visual functions—see Lehky and Tanaka (2016); Naya and Suzuki (2011); Suzuki (2010). M11_PINE1933_11_GE_C11.indd 306 22/01/2021 11:19  Learning, Memory, and Amnesia 307 Bussey and Saksida (2005) have argued Figure 11.16 The structures of the brain that have been shown to play a that the inferotemporal cortex, in concert role in memory. Because it would have blocked the view of other structures, with adjacent perirhinal cortex (see Miyas- the striatum is not included. (See Figure 3.27 on page 93.) hita, 2019; Suzuki & Naya, 2014), plays an important role in storing memories of visual input. In support of this view, Naya, Basal Mediodorsal Yoshida, and Miyashita (2001) recorded the forebrain nucleus responses of neurons in inferotemporal cor- Prefrontal tex and perirhinal cortex while monkeys cortex learned the relation between the two items in pairs of visual images. When a pair was presented, responses were first recorded in inferotemporal neurons and then in perirhi- nal neurons; however, when the monkeys were required to recall that pair, activity was recorded in perirhinal neurons before infero- temporal neurons. Naya and colleagues con- cluded that this reversed pattern of activity reflected the retrieval of visual memories from inferotemporal cortex. AMYGDALA. The amygdala is thought to Amygdala play a special role in memory for the emo- tional significance of experiences (see Herry Medial & Johansen, 2014; Paz & Pare, 2013). Rats temporal cortex with amygdalar lesions, unlike intact rats, do not respond with fear to a neutral stimulus Inferotemporal Hippocampus Cerebellum that has previously been followed by electric cortex foot shock (see Maren, 2015; Nader, 2015). Also, Bechara and colleagues (1995) reported the case of a neuropsychological patient with and retrograde deficits in memory for the temporal order bilateral damage to the amygdala who could not acquire of events, even when they can remember the events conditioned autonomic startle responses to various visual themselves. They also display deficits in working memory or auditory stimuli but had good explicit memory for the (the ability to maintain relevant memories while a task training. However, there is little evidence that the amygdala is being completed)—see D’Esposito and Postle (2015); stores memories; it appears to be involved in strengthen- Constantinidis & Klingberg (2016). As a result of these two ing emotionally significant memories stored in other struc- deficits, patients with prefrontal cortex damage often have tures (Do-Monte, Quiñones-Laracuente, & Quirk, 2015; difficulty performing tasks that involve a series of responses Likhtik & Paz, 2015). The amygdala might be the reason (see Colvin, Dunbar, & Grafman, 2001). why emotion-provoking events are remembered better than neutral events (see Dunsmoor et al., 2015; McGaugh, 2015; Yonelinas & Ritchey, 2015). Journal Prompt 11.5 The study of the anatomy of memory has come a long PREFRONTAL CORTEX. Patients with damage to the pre- way since H.M.’s misfortune. What kind of advances do frontal cortex (the area of frontal cortex anterior to motor you think will be made in the next decade? cortex) are not grossly amnesic; they often display no defi- cits at all on conventional tests of memory. This lack of reli- able memory deficits in patients with prefrontal damage The prefrontal cortex is a large structure that is com- may in part result from the fact that different parts of the posed of many anatomically distinct areas that have dif- prefrontal cortex play different roles in memory and that ferent connections and, presumably, different functions. patients with damage to different areas of prefrontal cortex Functional brain-imaging studies are finding that specific are often combined for analysis. complex patterns of prefrontal activity are associated with Be that as it may, two episodic memory abilities are various memory functions. Some regions of prefrontal cor- often lost by patients with large prefrontal lesions. Patients tex seem to perform fundamental cognitive processes (e.g., with large prefrontal lesions often display both anterograde attention and task management) during working memory M11_PINE1933_11_GE_C11.indd 307 22/01/2021 11:19  308 Chapter 11 tasks, and other regions of prefrontal cortex participate in (see Freeman, 2015). In this paradigm, a tone (conditional other memory processes (e.g., Lehky & Tanaka, 2016; Morici, stimulus) is sounded just before a puff of air (unconditional Bekinschtein, & Weisstaub, 2015). For example, recent stud- stimulus) is delivered to the eye. After several trials, the tone ies in laboratory animals have highlighted an important comes to elicit an eye blink. The convergence of evidence role for hippocampal–prefrontal connections in episodic from stimulation, recording, and lesion studies suggests memory (see Barker et al., 2017; Eichenbaum, 2017). that the effects of this conditioning are stored in the form of changes in the way that cerebellar neurons respond to the The Case of the Cook Who tone (see De Zeeuw & Ten Brinke, 2015; Freeman, 2015). Couldn’t The striatum is thought to store memories for consis- tent relationships between stimuli and responses—the type The story of one patient with prefrontal cortex damage is very of memories that develop incrementally over many trials well known because she was the sister of Wilder Penfield, the (see Graybiel & Grafton, 2015). Sometimes this striatum- famous Montreal neurosurgeon (Penfield & Evans, 1935). Before based form of learning is referred to as habit-formation (see her brain damage, she had been an excellent cook; and after- O’Tousa & Grahame, 2014). ward, she still remembered her favorite recipes and how to Although few would disagree that the cerebellum and perform each individual cooking technique. However, she was the striatum play a role in sensorimotor memory, there is incapable of preparing even simple meals because she could growing evidence that these structures also play a role in not carry out the various steps in proper sequence. certain types of memory with no obvious motor component. For example, Knowlton, Mangels, and Squire (1996) found CEREBELLUM AND STRIATUM. Just as explicit memo- that Parkinson’s patients with striatal damage could not ries of experiences are presumed to be stored in the cir- solve a probabilistic discrimination problem. The problem cuits of the brain that mediated their original perception, was a computer “weather forecasting” game, and the task implicit memories of sensorimotor learning are presumed to was to correctly predict the weather by pressing one of two be stored in sensorimotor circuits (see Graybiel & Grafton, keys, rain or shine. The patients based their predictions on 2015). Most research on the neural mechanisms of memory stimulus cards presented on the screen—each card had a dif- for sensorimotor tasks has focused on two structures: the ferent probability of leading to sunshine, which the patients cerebellum and the striatum. had to learn and remember. The Parkinson’s patients did The cerebellum is thought to participate in the storage of not improve over 50 trials, although they displayed normal memories of learned sensorimotor skills through its various explicit (conscious) memory for the training episodes. In con- neuroplastic mechanisms (see Gao, van Beugen, & De Zeeuw, trast, amnesic patients with medial temporal lobe or medial 2012). Its role in the Pavlovian conditioning of the eye-blink diencephalic damage displayed marked improvement in response of rabbits has been most intensively investigated performance but had no explicit memory of their training. Scan Your Brain The preceding modules of this chapter have dealt with the gross 5. Neurons in the hippocampus that respond only when neuroanatomy of memory—with the cells and structures of the the subject is in specific locations are called _______. brain that are involved in various aspects. Before you proceed to 6. _______ neurons are very selective and ­invariant. the next module, which deals with the synaptic mechanisms of This means that they respond to concepts and learning and memory, test your knowledge by filling in the blanks ideas ­exclusively, which is why they are also called in the following sentences. The correct answers are provided at concept cells. the end of the exercise. Before proceeding, review the material 7. The _______ has been known for its role in Pavlovian related to your errors and omissions. conditio