1. POWERPOINT PRESENTATION FOR BIOPSYCHOLOGY, 9TH EDITION BY JOHN P.J. PINEL PREPARED BY JEFFREY W. GRIMM WESTERN WASHINGTON UNIVERSITY COPYRIGHT © 2014 PEARSON EDUCATION, INC. ALL RIGHTS RESERVED. This multimedia product and its contents are protected under copyright law. The following are prohibited by law: any public performance or display, including transmission of any image over a network; preparation of any derivative work, including the extraction, in whole or in part, of any images; any rental, lease, or lending of the program.

2. How Your Brain Stores Information Chapter 11 Learning, Memory, and Amnesia Copyright © 2014 Pearson Education, Inc. All rights reserved.

3. Learning Objectives LO1: Describe the case of H.M. Explain how H.M. changed our understanding of memory. LO2: Compare Korsakoff’s amnesia and medial temporal lobe amnesia. LO3: Compare Alzheimer’s amnesia with medial temporal lobe amnesia. LO4: Define anterograde and retrograde amnesia. LO5: Retrograde amnesia provides evidence for memory consolidation. Explain. LO6: Describe the nonmatching-to-sample model of explicit memory. LO7: Summarize the evidence that damage to the medial temporal cortex is largely responsible for object-recognition deficits after medial temporal lobectomy. LO8: Summarize evidence that the hippocampus plays a special role in memory for location. LO9: Discuss the various parts of the brain thought to play a role in memory storage. LO10: Explain LTP and discuss its properties. Copyright © 2014 Pearson Education, Inc. All rights reserved.

4. Amnesic Effects of Bilateral Medial Temporal Lobectomy H.M. was an epileptic who had his temporal lobes removed in 1953. His seizures were dramatically reduced— but so was his long-term memory H.M. experienced both mild retrograde amnesia and severe anterograde amnesia. Copyright © 2014 Pearson Education, Inc. All rights reserved.

5. FIGURE 11.1 Medial temporal lobectomy. The portions of the medial temporal lobes that were removed from H.M.’s brain are illustrated in a view of the inferior surface of the brain. Copyright © 2014 Pearson Education, Inc. All rights reserved.

6. Retrograde (backward-acting): unable to remember the past Anterograde (forward-acting): unable to form new memories While H.M. was unable to form most types of new long-term memories (LTM), his short-term memory (STM) was intact. Amnesic Effects of Bilateral Medial Temporal Lobectomy (Con’t) Copyright © 2014 Pearson Education, Inc. All rights reserved.

7. Formal Assessment of H.M.’s Anterograde Amnesia: Discovery of Unconscious Memories Digit span: H.M. can repeat digits, provided that the time between learning and recall is within the duration of STM. Block-tapping memory-span test: this test demonstrated that H.M.’s amnesia was global—not limited to one sensory modality. Copyright © 2014 Pearson Education, Inc. All rights reserved.

8. Assessing H.M. (Con’t) H.M. improved with practice on sensorimotor tasks (mirror drawing, rotary pursuit) and on a nonsensorimotor task (incomplete pictures)—all without recalling previous practice sessions. H.M. readily learned responses through classical (Pavlovian) conditioning, but had no memory of the conditioning trials. Copyright © 2014 Pearson Education, Inc. All rights reserved.

9. FIGURE 11.2 The learning and retention of the mirrordrawing task by H.M. Despite his good retention of the task, H.M. had no conscious recollection of having performed it before. (Based on Milner, 1965.) Copyright © 2014 Pearson Education, Inc. All rights reserved.

10. Three Major Scientific Contributions of H.M.’s Case Medial temporal lobes are involved in memory. STM, remote memory, and LTM are distinctly separate; H.M. was unable to move memories from STM to LTM, a problem with memory consolidation. Memory may exist but not be recalled—as when H.M. exhibited a skill he did not know he had learned (explicit vs. implicit memories). Copyright © 2014 Pearson Education, Inc. All rights reserved.

11. Explicit vs. Implicit Memories Explicit memories: conscious memories Implicit memories: unconscious memories, as when H.M. showed the benefits of prior experience Repetition priming tests: used to assess implicit memory; performance in identifying word fragments is improved when the words have been seen before. Copyright © 2014 Pearson Education, Inc. All rights reserved.

12. 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. Copyright © 2014 Pearson Education, Inc. All rights reserved.

13. Medial Temporal Lobe Amnesia Not all patients with this form of amnesia are unable to form new explicit long-term memories. Semantic memory (general information) may function normally while episodic memory (events that one has experienced) does not. Medial temporal lobe amnesiacs may have trouble imagining future events. Copyright © 2014 Pearson Education, Inc. All rights reserved.

14. Effects of Cerebral Ischemia on the Hippocampus and Memory R.B. suffered damage to just one part of the hippocampus (CA1 pyramidal cell layer) and developed amnesia. R.B.’s case suggests that hippocampal damage alone can produce amnesia. H.M.’s damage and amnesia were more severe than R.B.’s. Copyright © 2014 Pearson Education, Inc. All rights reserved.

15. FIGURE 11.4 The major components of the hippocampus: CA1, CA2, CA3, and CA4 subfields and the dentate gyrus. R.B.’s brain damage appeared to be restricted largely to the pyramidal cell layer of the CA1 subfield. (CA stands for cornu ammonis, another name for hippocampus.) Copyright © 2014 Pearson Education, Inc. All rights reserved.

16. Amnesia of Korsakoff’s Syndrome Korsakoff’s syndrome is most commonly seen in severe alcoholics (or others with a thiamine deficiency). It is characterized by amnesia, confusion, personality changes, and physical problems. Damage in the Medial Diencephalon: Medial Thalamus + Medial Hypothalamus Copyright © 2014 Pearson Education, Inc. All rights reserved.

17. Amnesia of Korsakoff’s Syndrome (Con’t) Amnesia experienced by Korsakoff’s sufferers is comparable to medial temporal lobe amnesia in the early stages. Anterograde amnesia for episodic memories Differs in Later Stages Severe retrograde amnesia develops. Differs in that It Is Progressive, Complicating Its Study Copyright © 2014 Pearson Education, Inc. All rights reserved.

18. What Damage Causes the Amnesia Seen in Korsakoff’s? Hypothalamic Mammillary Bodies? No: Korsakoff’s amnesia is seen in cases without such damage. Thalamic Mediodorsal Nuclei? Possibly: damage is seen here when there is no mammillary bodies damage. The cause of amnesia is not likely to be damage to a single diencephalic structure. Copyright © 2014 Pearson Education, Inc. All rights reserved.

19. Amnesia of Alzheimer’s Disease (AD) AD begins with slight loss of memory and progresses to dementia. General Deficits in Predementia AD Major anterograde and retrograde amnesia in explicit memory tests Deficits in STM and some types of implicit memory: verbal and perceptual Implicit sensorimotor memory is intact. Copyright © 2014 Pearson Education, Inc. All rights reserved.

20. What Damage Causes the Amnesia Seen in AD? Decreased Acetylcholine Due to basal forebrain degeneration Basal forebrain strokes can cause amnesia and attentional deficits, which may be mistaken for memory deficits. The medial temporal lobe and prefrontal cortex are also involved. Damage is diffuse. The resulting amnesia is likely a consequence of acetylcholine depletion and brain damage. Copyright © 2014 Pearson Education, Inc. All rights reserved.

21. Amnesia after Concussion: Evidence for Consolidation Posttraumatic amnesia: concussions may cause retrograde amnesia for the period before the blow and some anterograde amnesia after. The same is seen with comas, with the severity of the amnesia correlated with the duration of the coma. The period of anterograde amnesia suggests a temporary failure of memory consolidation. Copyright © 2014 Pearson Education, Inc. All rights reserved.

22. Gradients of Retrograde Amnesia and Memory Consolidation Concussions disrupt consolidation (storage) of recent memories. Hebb’s theory is that memories are stored in the short term by neural activity. Interference with this activity prevents memory consolidation. Examples: Blows to the head (i.e., concussion) ECS (electronconvulsive shock) Long gradients of retrograde amnesia are inconsistent with consolidation theory. Copyright © 2014 Pearson Education, Inc. All rights reserved.

23. FIGURE 11.5 The retrograde amnesia and anterograde amnesia associated with a concussion-producing blow to the head. Copyright © 2014 Pearson Education, Inc. All rights reserved.

24. The Hippocampus and Consolidation H.M. has some retrograde amnesia. Perhaps the hippocampus stores memories temporarily (standard consolidation theory). Consistent with the temporally graded retrograde amnesia seen in experimental animals with temporal lobe lesions Or perhaps the hippocampus stores memories permanently, but they become “stronger” over time. Copyright © 2014 Pearson Education, Inc. All rights reserved.

25. Reconsolidation Each time a memory is retrieved from LTM, it is temporarily held in STM. Memory in STM is susceptible to post- traumatic amnesia until it is reconsolidated. Anisomycin, a protein synthesis inhibitor, prevents reconsolidation of conditioned fear in rats if applied directly to the amygdalae. Not all kinds of memories are subject to reconsolidation. Copyright © 2014 Pearson Education, Inc. All rights reserved.

26. Neuroanatomy of Object- Recognition Memory Early animal models of amnesia involved implicit memory and assumed the hippocampus was key. In the 1970s, monkeys with bilateral medial temporal lobectomies showed LTM deficits in explicit memory: the delayed nonmatching-to- sample test. As with H.M., performance was normal when memory needed to be held for only a few seconds (within the duration of STM). Copyright © 2014 Pearson Education, Inc. All rights reserved.

27. FIGURE 11.7 Performance of a delayed nonmatching-to-sample trial. Copyright © 2014 Pearson Education, Inc. All rights reserved.

28. Delayed Nonmatching-to- Sample Test for Rats Aspiration is used to lesion the hippocampus in monkeys, resulting in additional cortical damage. Extraneous damage is limited in rats due to the lesion methods used. Bilateral damage to rat hippocampus, amygdala, and rhinal cortex produces the same deficits seen in monkeys with hippocampal lesions. Copyright © 2014 Pearson Education, Inc. All rights reserved.

29. Neuroanatomical Basis of the Object-Recognition Deficits Resulting from Medial Temporal Lobectomy Bilateral removal of the rhinal cortex consistently results in object-recognition deficits. Bilateral removal of the hippocampus produces no or moderate effects on object recognition. Bilateral removal of the amygdala has no effect on object recognition. Copyright © 2014 Pearson Education, Inc. All rights reserved.

30. FIGURE 11.9 The three major structures of the medial temporal lobe, illustrated in the monkey brain: the hippocampus, the amygdala, and the rhinal cortex. Copyright © 2014 Pearson Education, Inc. All rights reserved.

31. A Paradox Complete removal of the hippocampus results in a moderate deficit in object recognition, but small lesions of the hippocampus (from ischemias) lead to a severe deficit. How can this be? Copyright © 2014 Pearson Education, Inc. All rights reserved.

32. A Hypothesis Ischemia-induced hyperactivity of CA1 pyramidal cells damages neurons outside of the hippocampus. Extrahippocampal damage is not readily detectable. Extrahippocampal damage is largely responsible for ischemia-induced object recognition deficits. Evidence? Copyright © 2014 Pearson Education, Inc. All rights reserved.

33. A Hypothesis (Con’t) Ischemia-induced hyperactivity leads to extrahippocampal damage that explains ischemia-induced object-recognition deficits. Bilateral hippocampectomy prevents ischemia-induced deficits. Also supported by functional brain-imaging studies Copyright © 2014 Pearson Education, Inc. All rights reserved.

34. Hippocampus and Memory for Spatial Location The rhinal cortex plays an important role in object recognition. The hippocampus plays a key role in memory for spatial location. Hippocampectomy produces deficits in Morris maze and radial arm maze performance. Many hippocampal cells are place cells, responding when a subject is in a particular place (and to other cues). Grid cells are also found in hippocampus and the entorhinal cortex. Copyright © 2014 Pearson Education, Inc. All rights reserved.

35. Comparative Studies of the Hippocampus Food-caching birds: caching and retrieving is needed for hippocampal growth. Primate studies are inconsistent; place cells and grid cells are less prevalent. Place cells respond to where the subject is looking rather than where the subject is located. Perhaps discrepancies are due to different testing paradigms (navigating the environment vs. locating on a computer screen). Copyright © 2014 Pearson Education, Inc. All rights reserved.

36. Theories of Hippocampal Function Cognitive map theory: the hippocampus constructs and stores allocentric maps of the world. This theory has been challenged. The firing of place cells sometimes depends on other behaviors. Hippocampal damage sometimes impairs behavior without a spatial component. Evidence for “concept” cells in human temporal lobe Respond to particular individuals or related individuals (e.g., Jennifer Aniston but also Lisa Kudrow) The hippocampus is large and complex, and its component substructures need to be evaluated in more detail. Copyright © 2014 Pearson Education, Inc. All rights reserved.

37. Where Are Memories Stored? Each memory is stored diffusely throughout the brain structures that were involved in its formation. Some structures have particular roles in storage of memories. Hippocampus: spatial location Perirhinal cortex: object recognition Mediodorsal nucleus: Korsakoff’s symptoms Basal forebrain: Alzheimer’s symptoms Copyright © 2014 Pearson Education, Inc. All rights reserved.

38. Where Are Memories Stored? (Con’t) Damage to a variety of structures results in memory deficits. Inferotemporal Cortex Visual perception of objects Changes in activity seen with visual recall Amygdala Emotional learning Lesions of the amygdalae disrupt fear learning. Copyright © 2014 Pearson Education, Inc. All rights reserved.

39. Where Are Memories Stored? (Con’t) Prefrontal Cortex Temporal order of events and working memory Tasks involving a series of responses Different parts of the prefrontal cortex may mediate different types of working memory. Some evidence from functional brain imaging studies Copyright © 2014 Pearson Education, Inc. All rights reserved.

40. Where Are Memories Stored? (Con’t) Cerebellum and Striatum Cerebellum Stores memories of sensorimotor skills Striatum Habit formation Copyright © 2014 Pearson Education, Inc. All rights reserved.

41. FIGURE 11.16 The structures of the brain that have been shown to play a role in memory. Because it would have blocked the view of other structures, the striatum is not included. (See FIGURE 3.28 on page 71.) Copyright © 2014 Pearson Education, Inc. All rights reserved.

42. Synaptic Mechanisms of Learning and Memory Molecular Events that Appear to Underlie Learning and Memory Hebb Changes in synaptic efficiency are the basis of LTM. Long-term potentiation (LTP) Synapses are effectively made stronger by repeated stimulation. Copyright © 2014 Pearson Education, Inc. All rights reserved.

43. Long-Term Potentiation (LTP) LTP is consistent with the synaptic changes hypothesized by Hebb. LTP can last for many weeks. LTP only occurs if presynaptic firing is followed by postsynaptic firing. Hebb’s Postulate for Learning Co-occurrence of firings in pre- and postsynaptic neurons necessary for learning and memory Copyright © 2014 Pearson Education, Inc. All rights reserved.

44. LTP as a Neural Mechanism of Learning and Memory Elicited by High-Frequency Electrical Stimulation of Presynaptic Neuron; Mimics Normal Neural Activity LTP effects are greatest in brain areas involved in learning and memory. Learning can produce LTP-like changes. Drugs that impact learning often have parallel effects on LTP. Copyright © 2014 Pearson Education, Inc. All rights reserved.

45. FIGURE 11.18 Long-term Potentiation in the granule cell layer of the rat hippocampal dentate gyrus. (Traces courtesy of Michael Corcoran, Department of Psychology, University of Saskatchewan.) Copyright © 2014 Pearson Education, Inc. All rights reserved.

46. LTP as a Neural Mechanism of Learning and Memory (Con’t) Much indirect evidence supports a role for LTP in learning and memory. LTP can be viewed as a three-part process. Induction (learning) Maintenance (memory) Expression (recall) Copyright © 2014 Pearson Education, Inc. All rights reserved.

47. Induction of LTP: Learning Most Commonly Studied Where NMDA Glutamate Receptors Are Prominent NMDA receptors do not respond maximally unless glutamate binds and the neuron is already partially depolarized. Ca 2+ channels do not open fully unless both conditions are met. Copyright © 2014 Pearson Education, Inc. All rights reserved.

48. Induction of LTP: Learning (Con’t) Ca 2+ influx only occurs if there is the co- occurrence that is needed for LTP, leading to the binding of glutamate at an NMDA receptor that is already depolarized. Ca 2+ influx may activate protein kinases that induce changes, causing LTP. Copyright © 2014 Pearson Education, Inc. All rights reserved.

49. FIGURE 11.19 The induction of NMDA-receptor–mediated LTP. Copyright © 2014 Pearson Education, Inc. All rights reserved.

50. Maintenance and Expression of LTP: Storage and Recall Pre- and Postsynaptic Changes LTP is only seen in synapses where it was induced. Protein synthesis (structural changes) underlies long-term changes. LTP begins in the postsynaptic neuron, which signals the presynaptic neuron. Astrocytes (not just neurons) are also involved in LTP. Copyright © 2014 Pearson Education, Inc. All rights reserved.

51. Maintenance and Expression of LTP: Storage and Recall (Con’t) How are presynaptic and postsynaptic changes coordinated? Nitric oxide synthesized in postsynaptic neurons in response to Ca 2+ influx may diffuse back to presynaptic neurons. Structural changes are now a well- established consequence of LTP. Copyright © 2014 Pearson Education, Inc. All rights reserved.

52. Variability of LTP Most LTP research has focused on NMDA- receptor–mediated LTP in the hippocampus, but LTP is mediated by different mechanisms elsewhere. LTD (long-term depression) also exists. Much of LTP and the neural basis of memory is still a mystery, despite many research discoveries. Copyright © 2014 Pearson Education, Inc. All rights reserved.

53. Infantile Amnesia Explicit and implicit memory can be demonstrated in normal, intact subjects. Skin conductance responses (implicit memory) were elicited by pictures of preschool classmates, whether they were explicitly recognized or not. Modern incomplete-pictures test: previously seen pictures were recognized sooner (implicit memory) than new pictures, whether the old pictures were explicitly recognized or not. Copyright © 2014 Pearson Education, Inc. All rights reserved.

54. Smart Drugs: Do They Work? Smart drugs (nootropics) are substances thought to improve memory. Limited research has shown that no purported nootropic has memory- enhancing effects in normal people. Copyright © 2014 Pearson Education, Inc. All rights reserved.

55. Posttraumatic Amnesia and Episodic Memory May Occur Following Head Trauma Patients may have difficulty with episodic memory. Might include amnesia for details of their personal lives Might also include anterograde amnesia Copyright © 2014 Pearson Education, Inc. All rights reserved.