Clinically Relevant Functional Neuroanatomy 2: Neuroanatomy of Memory Russell M. Bauer, Ph.D. University of Florida, USA Vivian Smith Summer Institute 23 June, 2006

Russell M. Bauer, Ph.D. (DON’T BELIEVE HIS LIES) The Three Amnesias Russell M. Bauer, Ph.D. (DON’T BELIEVE HIS LIES)

Multiple Forms of Memory

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

Integrated Circuitry Linking Temporal, Diencephalic, and Basal Forebrain Regions

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

Temporal Lobe Pathology Associated with Herpes Simplex Encephalitis

The Case of Henry M (H.M.)

Bauer, Grande, & Valenstein, 2003

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

CA3 CA1 DG subic

Bauer, Grande, & Valenstein, 2003

Delayed Nonmatching to Sample

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

6-8 weeks postsurgery 2 years postsurgery

Anterior Posterior Zola-Morgan & Squire, 1990

Bauer, Grande, & Valenstein, 2003

Zola-Morgan & Squire, 1990

Murray & Richmond, Curr Opin Neurobiol, 2001 -perirhinal cortex obviously important in memory, but also apparently important in fine-grained visual discrimination

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

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

Mamillary Body Lesions in a case of Korsakoff’s Disease

Lesion Profile in a Case of Thalamic Amnesia

Graff-Radford, et al, 1990

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

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

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

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

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

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)

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

Key Points Extended memory system including hippocampus, amygdala, and basal forebrain 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; these structures are reciprocally connected to cortical processors