1. Prepared by Jeffrey W. Grimm Western Washington University
PowerPoint Presentation for Biopsychology, 8th Edition by John P.J. Pinel
Prepared by Jeffrey W. Grimm
Western Washington University
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2. How Your Brain Stores Information
Chapter 11
Learning, Memory, and Amnesia
How Your Brain Stores Information
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3. Amnesic Effects of Bilateral Medial Temporal Lobectomy
H.M. – an epileptic who had his temporal lobes removed in 1953
His seizures were dramatically reduced but so was his long-term memory
Mild retrograde amnesia and severe anterograde amnesia
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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.
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5. Amnesic Effects of Bilateral Medial Temporal Lobectomy Continued
Retrograde (backward-acting) – unable to remember the past
Anterograde (forward-acting) – unable to form new memories
While H.M. is unable to form most types of new long-term memories (LTM), his short-term memory (STM) is intact
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Formal Assessment of H.M.’s Anterograde Amnesia: Discovery of Unconscious Memories
Digit span – H.M. can repeat digits provided 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
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7. Assessing H.M. Continued
H.M. improves with practice on sensorimotor tasks (mirror-drawing, rotary-pursuit) and on a nonsensorimotor task (incomplete-pictures) – without recalling previous practice sessions
H.M. readily “learns” responses through classical (Pavlovian) conditioning, but has no memory of conditioning trials
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8. 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. is unable to move memories from STM to LTM, a problem with memory consolidation
Memory may exist but not be recalled – as when H.M. exhibits a skill he does not know he has learned (explicit vs. implicit memories)
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9. Explicit vs. Implicit Memories
Explicit memories: conscious memories
Implicit memories: unconscious memories, as when H.M. shows 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
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FIGURE 11.4 Two items from the incomplete-pictures test.
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11. 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
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12. 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
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FIGURE 11.5 The major components of the hippocampus: CA1, CA2, CA3, and CA4 subfields and the dentate gyrus.
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14. Amnesia of Korsakoff’s Syndrome
Most commonly seen in severe alcoholics (or others with a thiamine deficiency)
Characterized by amnesia, confusion, personality changes, and physical problems
Damage in the medial diencephalon: medial thalamus + medial hypothalamus
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15. Amnesia of Korsakoff’s Syndrome Continued
Amnesia 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
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16. 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
Cause of amnesia is not likely to be damage to a single diencephalic structure
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17. Amnesia of Alzheimer’s Disease (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
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18. 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
Medial temporal lobe and prefrontal cortex also involved
Damage is diffuse
resulting amnesia is likely a consequence of acetylcholine depletion and brain damage
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19. 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
Period of anterograde amnesia suggests a temporary failure of memory consolidation
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20. Gradients of Retrograde Amnesia and Memory Consolidation
Concussions disrupt consolidation (storage) of recent memories
Hebb’s theory – 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
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21. 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
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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
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23. Neuroanatomy of Object-Recognition Memory
Early animal models of amnesia involved implicit memory and assumed the hippocampus was key
1970s – monkeys with bilateral medial temporal lobectomies show LTM deficits in explicit memory, the delayed nonmatching-to-sample test
Like H.M., performance was normal when memory needed to be held for only a few seconds (within the duration of STM)
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FIGURE 11.9 The correct performance of a delayed nonmatching-to-sample trial. (Based on Mishkin & Appenzeller, 1987.)
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25. Delayed Nonmatching-to-Sample Test for Rats
Aspiration used to lesion the hippocampus in monkeys – resulting in additional cortical damage
Extraneous damage is limited in rats due to lesion methods used
Bilateral damage to rat hippocampus, amygdala, and rhinal cortex produces the same deficits seen in monkeys with hippocampal lesions
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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
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FIGURE The three major structures of the medial temporal lobe, illustrated in the monkey brain: the hippocampus, the amygdala, and the rhinal cortex.
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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?
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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?
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30. A Hypothesis Continued
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
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31. Hippocampus and Memory for Spatial Location
Rhinal cortex plays an important role in object recognition
Hippocampus plays a key role in memory for spatial location
Hippocampectomy produces deficits on Morris maze and radial arm maze
Many hippocampal cells are place cells, responding when a subject is in a particular place and to other cues
Grid cells also found in hippocampus and entorhinal cortex
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32. Comparative Studies of the Hippocampus
Food-caching birds: caching and retrieving is needed for hippocampal growth
Primate studies are inconsistent: no place cells
Perhaps discrepancies due to different testing paradigms (navigating the environment vs. locating on a computer screen)
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33. Theories of Hippocampal Function
Cognitive map theory: hippocampus constructs and stores allocentric maps of the world
Theory has been challenged
Firing of place cells sometimes depends on other behaviors
Hippocampal damage sometimes impairs behavior without a spatial component
The hippocampus is large and complex and its component substructures need to be evaluated in more detail
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34. 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 symptomos
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35. Where Are Memories Stored? Continued
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
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36. Where Are Memories Stored? Continued
Prefrontal cortex
Temporal order of events and working memory
Tasks involving a series of responses
Different part of prefrontal cortex may mediate different types of working memory
Some evidence from functional brain imaging studies
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37. Where Are Memories Stored? Continued
Cerebellum and striatum
Cerebellum
Stores memories of sensorimotor skills
Striatum
Habit formation
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38. 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
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39. 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
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40. 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
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FIGURE 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.)
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42. LTP as a Neural Mechanism of Learning and Memory Continued
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)
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43. 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
Ca2+ channels do not open fully unless both conditions are met
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44. Induction of LTP: Learning Continued
Ca2+ 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
Ca2+ influx may activate protein kinases that induces changes causing LTP
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45. 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) also involved in LTP
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46. Maintenance and Expression of LTP: Storage and Recall Continued
How are presynaptic and postsynaptic changes coordinated?
Nitric oxide synthesized in postsynaptic neurons in response to Ca2+ influx may diffuse back to presynaptic neurons
Structural changes are now a well-established consequence of LTP
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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
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Infantile Amnesia
Explicit and implicit memory can be demonstrated in normal, intact subjects
Skin conductance responses (implicit memory) 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
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49. Smart Drugs: Do They Work?
Smart drugs are substances thought to improve memory
Limited research has shown that no purported nootropic has memory-enhancing effects in normal people
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50. Posttraumatic Amnesia and Episodic Memory
May occur following head trauma
Patient may have difficulty with episodic memory
Might include amnesia for details of their personal life
Might also include anterograde amnesia
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