1. Clinically Relevant Functional Neuroanatomy IV: Neuroanatomy of Memory Russell M. Bauer, Ph.D. University of Florida AACN 5 th Annual Conference June 8, 2007

2. Anatomy of Memory Russell M. Bauer, Ph.D. (DON’T BELIEVE HIS LIES)

6. Multiple Forms of Memory

7. “Core” Features of Amnesia 1.anterograde amnesia: defect in new learning 2.retrograde amnesia/remote memory disturbance: defect in retrieving old memories 3.spared memory abilities: attention span, psychometric intelligence, and ‘nondeclarative’ forms of memory are generally spared

8. The Human Amnesic Syndrome Impaired new learning (anterograde amnesia), exacerbated by increasing retention delay Impaired recollection of events learned prior to onset of amnesia (retrograde amnesia), often in temporally graded fashion Not limited to one sensory modality or type of material Normal IQ, attention span, “nondeclarative” forms of memory

9. Clinically Relevant Dimensions of Human Memory Performance Immediate-recent-remote Encoding-storage-retrieval Material, modality specificity Tests vs. processes

10. Encoding Definition: process of transforming to-be remembered in formation into memorable and retrievable form –Encoding I: bringing information-processing capacity to bear on stimuli –Encoding II: ability to use the results of E-1 mnemonically Relevance: levels-of-processing accounts of memory (memory as by-product of information processing) Clinical manifestation: poor immediate (superspan) recall

11. Consolidation/Storage definition: process of making new memories permanent basis: anatomic and physiological changes at cellular level; hippocampal system important when? during study-test interval duration: hours? days? years? clinical symptom: delayed memory << immediate memory (forgetting)

12. Performance on a test of memory for news stories. From Squire & Bayley, Curr Opin Neurobiol, 2007, 17, 185-196.

13. Retrieval definition: process of locating, selecting, and activating a memory representation basis: re-enactment of pattern of excitation occurring at encoding when? at point of test clinical symptom: recall << recognition (also true of shallow encoding), inconsistent errors

15. Medial Temporal Syndromes Anoxic-hypoxic syndromes –cardiac arrest –CO poisoning Amnesia associated with ECT CNS Infections (Herpes) MTS and complex-partial epilepsy (material-specific) Early AD

16. Temporal Lobe Pathology Associated with Herpes Simplex Encephalitis

17. FLAIR (Fluid Attenuated Inversion Recovery) in Medial Temporal Sclerosis

18. Hippocampus in ischemia

19. Hippocampus in Alzheimer’s Disease

20. The Case of Henry M (H.M.)

24. Bauer, Grande, & Valenstein, 2003

25. Integrated Circuitry Linking Temporal, Diencephalic, and Basal Forebrain Regions

26. Hippocampus Mammilary Bodies Anterior Thalamus Cingulate Gyrus Fornix Mamillothalamic Tract Amygdala Dorsomedial Thalamus Orbitofrontal Uncus Two Limbic Circuits Medial (Papez) Lateral Amygdalofugal pathways

28. DG CA3 CA1 subic

29. Bauer, Grande, & Valenstein, 2003

31. Delayed Nonmatching to Sample

32. Delayed Nonmatching to Sample, multiple trials, trial-unique objects

33. 6-8 weeks postsurgery2 years postsurgery

36. Bauer, Grande, & Valenstein, 2003

37. Zola-Morgan & Squire, 1990

39. Murray & Richmond, Curr Opin Neurobiol, 2001 -perirhinal cortex obviously important in memory, but also has many additional connections

40. Hippocampus Mammilary Bodies Anterior Thalamus Cingulate Gyrus Fornix Mamillothalamic Tract Amygdala Dorsomedial Thalamus Orbitofrontal Uncus Two Limbic Circuits and the Two-system theory of amnesia Medial (Papez) Lateral Amygdalofugal pathways PRPH

43. Hippocampus is important in specific types of relational memory (e.g., transitive inference)

45. Morris Water Maze

46. Lesioned rats Sham operated rats Morris Water Maze (Eichenbaum, et al, 1990) (Gallagher, et al, 1993) Time to Target Aged rats Young rats

47. Leutgeb, et al., Curr Opin Neurobiol, 2005, 15, 738-746.

48. Galani, et al., Behav Brain Res, 1998, 96, 1-12. Hippocampus v. Entorhinal Cortex Lesions and “Reference” vs. “Working” Memory MWM “ Reference Memory (H<ECo) “ Working Memory (H=Eco=Sub<Sham)

49. Hippocampus Mammilary Bodies Anterior Thalamus Cingulate Gyrus Fornix Mamillothalamic Tract Amygdala Dorsomedial Thalamus Orbitofrontal Uncus Two Limbic Circuits and the Two-system theory of amnesia Medial (Papez) Lateral Amygdalofugal pathways PRPH

50. Integrated Circuitry Linking Temporal, Diencephalic, and Basal Forebrain Regions

51. Diencephalic Syndromes Korsakoff Syndrome associated with ETOH abuse or malabsorption –prominent encoding deficits –role of frontal pathology Vascular disease Thalamic trauma

52. Mamillary Body Lesions in a case of Korsakoff’s Disease

54. MRI in paramedian thalamic stroke Lövblad, et al (1997) Neuroradiology, 39, 693-698.

55. Caolo, et al (2005). Brain, 128, 1584-98. Mammillary body (a), medial thalamic (arrows in B,C) and fornix (arrowheads in B) damage in a case of Alcholic Korsakoff syndrome. D shows resolution of signal changes after 5 months of abstinence.

56. Lesion Profile in a Case of Thalamic Amnesia

57. Graff-Radford, et al (1990). Brain, 113, 1-25. Anterior thalamic lesions affecting the MTT and VAF pathways produce persistent amnesia, posterior lesions do not

60. Hippocampus Mammilary Bodies Anterior Thalamus Cingulate Gyrus Fornix Mamillothalamic Tract Amygdala Dorsomedial Thalamus Orbitofrontal Uncus Two Limbic Circuits and the Two-system theory of amnesia Medial (Papez) Lateral Amygdalofugal pathways

61. Integrated Circuitry Linking Temporal, Diencephalic, and Basal Forebrain Regions

62. Basal Forebrain Syndromes Anterior Communicating Artery (ACoA) infarctions –prominent anterograde, variable retrograde amnesia –prominent confabulation –frontal extension of lesions Basal forebrain and cholinergic projections to hippocampus

64. Myers, et al. (2006) Myers, DeLuca, Hopkins, & Gluck (2006), Neuropsychologia, 44, 130-139.

65. Myers, et al. (2006)

66. Reversal H<AcoA Learning AcoA<H Myers, et al. (2006)

69. Hippocampus Mammilary Bodies Anterior Thalamus Cingulate Gyrus Fornix Mamillothalamic Tract Amygdala Dorsomedial Thalamus Orbitofrontal Uncus Two Limbic Circuits Medial (Papez) Lateral Amygdalofugal pathways

71. Hippocampus Mammilary Bodies Anterior Thalamus Cingulate Gyrus Fornix Mamillothalamic Tract Amygdala Dorsomedial Thalamus Orbitofrontal Uncus Two Limbic Circuits Medial (Papez) Lateral Amygdalofugal pathways Bauer, Grande, & Valenstein, 2003

72. Frontal Contributions to Memory Working Memory Selective Engagement Cognitive contributions –Strategy development –Retrieval support/intention –Metamemory

73. Miller, G. A., Galanter, E. & Pribram, K. H. (1960). Plans and the structure of behavior. New York: Holt, Rinehart & Winston. G.A. Miller E. Galanter K.H. Pribram

74. Alan Baddeley

75. Episodic Buffer

76. Working memory and associative memory may be distinguished using the delayed response task When PFC-lesioned monkey must remember which well is baited from trial to trial, performance is poor When PFC-lesioned monkey must remember which symbol is baited from trial to trial, performance is good

77. Patricia Goldman-Rakic (1937-2003)

82. Smith & Jonides, 1999 A question to think about: why would you have spatially- sensitive neurons in pre- MOTOR cortex?

83. Curtis & D’Esposito, 2003, TICS DLPFC VLPFC

84. Two views about specificity in WM Domain-specificity (Goldman-Rakic, Ungerleider, Courtney) –Ventral prefrontal: object working memory –Dorsal prefrontal: spatial working memory Process-specificity (Petrides, D’Esposito) –Ventral prefrontal: sequential organization and storage –Dorsal prefrontal: executive control and monitoring

86. Smith & Jonides 1999 Storage Exec + Storage

87. D’Esposito, Postle, and Rypma, 2000

88. Curtis & D’Esposito, 2003 (from Rowe et al, 2000)

89. D’Esposito, M., Zarahn, E., Balard, D., Shin, R.K., and Lease, J. (1998) Functional MRI studies of spatial and nonspatial working memory. Cogn. Brain Res. 7:1-13

90. Curtis & D’Esposito, 2003

91. Selective Engagement “Activation” or “bringing online” of a cortical processor needed to perform a cognitive task Dependent on complex reciprocal connections among regions in frontal lobe, basal ganglia, thalamus, and ascending activation centers Important for memory retrieval

92. General Organization of Frontal cortical- striatal-pallidal-thalamic-cortical loops

93. Motor Activation/Preparation Heilman, Watson, & Valenstein, 2003

95. Key Points Extended memory system including hippocampus, amygdala, and basal forebrain (and their connections) We (basically) understand anatomy, now we need to understand computation Notion of distinct subtypes of amnesia generally less favorable now than 10 years ago Certain structures are ‘wired’ for associational processing through intrinsic and corticocortical connections; these structures appear important in establishing distributed network connections supporting memory Cortical-subcortical interactions appear critical for selectively activating and engaging specific cortical processors needed for performance of specific tasks