1. Functional neuroanatomy bradd@nmr.mgh.harvard.edu Overview of brain anatomy & systems –Localization/networks –Scale in the nervous system –Sensorimotor systems How our brains interact with the external world (loops) –States ‘of mind’ (and body) Specific functional systems –Memory & emotion How our brains use previous experience to modify behavior Vision & attention; language

2. Learning & memory Monday, September 13, 2004

3. Learning & memory “Knowing that” Vs. “Knowing how” Gilbert Ryle, Oxford philosopher of mind, 1949

4. The limbic system: Memory & emotion

5. Medial temporal lobe memory system

6. Courtesy of S. Heckers (J N Trans, 2002)

7. High-resolution MR imaging 7 Tesla ex vivo Courtesy of Jean Augustinack & Bruce Fischl

8. Learning & memory: HM H.M.Control Corkin S, J Nsci, 1997

9. Learning & memory: HM

10. Multiple memory systems

11. Medial temporal atrophy & memory in AD L. deToledo-Morrell, B. Dickerson, et al., Hippocampus, 2000 Left HF volume & verbal memoryRight HF volume & spatial memory

12. Medial temporal lobe atrophy in MCI Dickerson BC, Neurobiol Aging, 2001 Elderly controlsMild AD Hippocampal volume MCI 0.1 0.2 0.3 0.4 0.5 0.6 LRLRLR * * *p<.05

13. Learning & memory What task would you use to show differential hippocampal activation? (When is the hippocampus “off”?)

14. Functional MRI Paradigm Functional MRI Paradigm Scene encoding (block design) ++ +++ Novel Repeated Adapted from C.E. Stern et al., PNAS, 1996 5s40s25s

15. Learning & memory: Novelty Stern CE, PNAS 1996

16. Learning & memory: Events Brewer J, Science 1998; Wagner A, Science 1998

17. Learning & memory: Individual variability in MTL activation Vandenbroucke MWJ, Neuroimage 2004

18. Learning & memory: Individual variability in anatomy Vandenbroucke MWJ, Neuroimage 2004

19. Genetic influences on MTL activation Hariri et al., J Neurosci, 2003Bookheimer et al.,NEJM, 2000 BDNF val/val > val/met APOE 4 > 3

20. Where are memories stored? Vaidya CJ, Neuropsychologia 2002

21. Multiple memory systems

22. Learning & memory: Frontal lobe anatomy

23. Learning & memory: Frontal lobe & episodic memory Brewer J, Science 1998; Wagner A, Science 1998

24. Learning & memory: Working memory Dorsolateral prefrontal cortex: Digit span Delayed match to sample N-back

25. Learning & memory: Working memory D’Esposito M, 2002

26. Learning & memory: Working memory & sleep deprivation Drummond SP, Nature 2004 After full night sleepAfter sleep deprivation N-back task

27. Learning & memory: Striatal anatomy

28. Learning & memory: Striatum & procedural memory Knowlton BJ, Science 1996

29. Learning & memory: Competition between systems Poldrack R, Nature 2001

30. Emotional learning & memory: Amygdala & orbitofrontal cortex Poldrack R, Nature 2001

31. Emotional conditioning is dependent on amygdala, declarative learning on the hippocampus Bechara A, Science 1995

32. Amygdala activation is related to emotional intensity at encoding, and predicts recall Canli T, J Neurosci 2000 Recognition 3 weeks later

33. ‘Unseen’ emotional stimuli activate amygdala & can elicit emotional conditioning Morris JS, Brain 2001

34. Systems for processing facial emotion Adolphs R, Curr Opn Nbiol 2002

35. Learning & memory Binding information processed by the brain for storage and future use