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Multiple Forms of Memory “Core” Features of Amnesia anterograde amnesia: defect in new learning retrograde amnesia/remote memory disturbance: defect in retrieving old memories spared memory abilities: attention span, psychometric intelligence, and ‘nondeclarative’ forms of memory are generally spared 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 Clinically Relevant Dimensions of Human Memory Performance Immediate-recent-remote Encoding-storage-retrieval Material, modality specificity Tests vs. processes 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 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 Integrated Circuitry Linking Temporal, Diencephalic, and Basal Forebrain Regions Two Limbic Circuits Anterior Thalamus Cingulate Gyrus Dorsomedial Thalamus Mamillothalamic Tract Mammilary Bodies Fornix Hippocampus Medial (Papez) Orbitofrontal Amygdalofugal pathways Uncus Amygdala Lateral CA3 CA1 DG subic Delayed Nonmatching to Sample Delayed Nonmatching to Sample, multiple trials, trial-unique objects 6-8 weeks postsurgery 2 years postsurgery Zola-Morgan & Squire, 1990 Bauer, Grande, & Valenstein, 2003 Zola-Morgan & Squire, 1990 Two Limbic Circuits and the Two-system theory of amnesia Anterior Thalamus Cingulate Gyrus Dorsomedial Thalamus Mamillothalamic Tract Mammilary Bodies Orbitofrontal Amygdalofugal pathways Fornix Uncus Hippocampus Amygdala PRPH Medial (Papez) Lateral 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 Graff-Radford, et al, 1990 Two Limbic Circuits and the Two-system theory of amnesia Anterior Thalamus Cingulate Gyrus Dorsomedial Thalamus Mamillothalamic Tract Mammilary Bodies Fornix Hippocampus Medial (Papez) Orbitofrontal Amygdalofugal pathways Uncus Amygdala Lateral Two Potential Lesion Scenarios in Diencephalic Amnesia 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 Basal Forebrain Anatomy Two Limbic Circuits Anterior Thalamus Cingulate Gyrus Dorsomedial Thalamus Mamillothalamic Tract Mammilary Bodies Fornix Hippocampus Medial (Papez) Orbitofrontal Amygdalofugal pathways Uncus Amygdala Lateral Two Potential Lesion Scenarios in Basal Forebrain Amnesia Two Limbic Circuits Anterior Thalamus Cingulate Gyrus Dorsomedial Thalamus Mamillothalamic Tract Mammilary Bodies Fornix Hippocampus Medial (Papez) Orbitofrontal Amygdalofugal pathways Uncus Amygdala Lateral Bauer, Grande, & Valenstein, 2003 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