Learning, memory & amnesia

1. Learning, memory & amnesia Chapter 11

2. The case of H.M. • Intractable epilepsy • one generalized convulsion each week • Several partial convulsions each day • 1953 surgery: Bilateral medial temporal lobectomy • temporal pole • amygdala • entorhinal cortex • hippocampus

3. Corkin et al. (1997)

4. Corkin et al. (1997)

5. Effects of Bilateral Medial Temporal Lobectomy • Convulsions were dramatically reduced • IQ increased from 104 to 118 • Short-term memory (STM) intact • Temporally-graded retrograde amnesia • Severe anterograde amnesia

6. Amnesia • 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, his STM was intact

7. Mirror-drawing task H.M.’s performance improved over 3 days (10 trials/day) despite the fact that he could not consciously remember the task on days 2 and 3.

8. Rotary-Pursuit Test H.M.’s performance improved over 9 daily practice sessions; again, with no recognition of the experience

9. Explicit vs Implicit Memories • Explicit memories – conscious memories • Implicit memories – unconscious memories Repetition priming tests were developed to assess implicit memory performance;

10. Incomplete pictures test

11. Implications of H.M.’s amnesia • Medial temporal lobes are involved in memory formation. • STM and LTM are dissociable – H.M. is unable to consolidate certain kinds of explicit memory. • the fact that he could form some memories suggests that there are multiple memory systems in the brain.

12. Medial Temporal Lobe Amnesia • Not all patients with this form of amnesia are unable form new explicit long-term memories, as was the case with H.M. Two kinds of explicit memory: Semantic memory (general information) may function normally while episodic memory (events that one has experienced) does not – they are able to learn facts, but do not remember doing so (the episode when it occurred)

13. Vargha-Khadem et al., (1997) • Studied three children that had bilateral temporal lobe damage early in life. • Like H.M., the children could not form episodic memory, however they did acquire reasonable levels of factual knowledge and language ability in mainstream school.

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 was more severe than R.B.’s

16. Object-Recognition Memory • Early animal models of amnesia involved implicit memory and assumed the hippocampus was key • 1970’s – monkeys with bilateral medial temporal lobectomies showed LTM deficits in 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)

17. Delayed nonmatching-to-sample task pretend you’re the monkey Sample stimulus touch it and get a yummy treat

18. 10 min delay during which other sample stimuli are presented

19. Choice phase: pick the image that is new Another yummy treat Darn, no food

20. Testing object-recognition memory

21. Medial temporal lobe (MTL)

22. Delayed non-match to sample results

23. The Mumby Box

24. Object recognition in rats

25. Comparison of lesions in monkeys and rats

26. Neuroanatomy of object recognition • Bilateral removal of the rhinal cortex consistently results in object-recognition deficits. • Bilateral removal of the hippocampus produces moderate deficits or none at all. • Bilateral removal of the amygdala has no effect on object-recognition.

27. Is the hippocampus involved in object recognition memory? • The Case of R.B. suggests that the lesions of the CA1 region of the hippocampus (due to ischemia) can produce severe memory deficits • Ischemia in animal models also produces deficits in object recognition • Yet deficits in object recognition are only moderate to non-existent in other animal lesion models • Why?

28. Mumby et al. (1996) • Bilateral hippocampectomy actually blocks the damage produced by ischemia! Explanation: • Ischemia causes hippocampal neurons to release glutamate, which produces damage outside of the hippocampus (particularly in rhinal cortex), although standard histological techniques do not show the damage follow-up functional imaging studies have confirmed the dysfunction.

29. The Hippocampus • 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 (Chapter 5) • Many hippocampal cells are place cells – responding when a subject is in a particular place

30. Theories of Hippocampal Function • O’Keefe & Nadel (1978) Cognitive map theory – constructs and stores allocentric maps of the world • Rudy & Sutherland (1992) Configural association theory – involved in retaining the behavioral significance of combinations of stimuli • Brown & Aggleton (1999) is involved in recognizing the spatial arrangements of objects

31. Synaptic Mechanisms of Learning and Memory • What is happening within the brain structures involved in memory? • Hebb – changes in synaptic efficiency are the basis of LTM • Long-term potentiation (LTP) – synapses are effectively made stronger by repeated stimulation

32. Long Term Potentiation (LTP)

33. Cross-section of the NMDA receptor complex