Memory and its Disorders: The Three Amnesias Russell M. Bauer, Ph.D. University of Florida Human Higher Cortical Function March 24, 2008

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

Where’s the Lesion? Patient presents to you with memory complaints. Where’s the lesion? Answer: Above the cervical vertebrae.

Where’s the Lesion? Patient presents to you with a severe and profound impairment in the ability to remember new information that disables them in everyday life. Where’s the lesion? Answer: In an extended memory system that involves a cortical-subcortical network including the medial temporal lobe, thalamus, basal forebrain, and their interconnections

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

Multiple Forms of Memory Recollection (deliberate, conscious) Familiarity (not deliberate or conscoius)

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) MCI/Early AD

Temporal Lobe Pathology Associated with Herpes Simplex Encephalitis

Patterns of Atrophy in Subtypes of MCI Amnestic-Single Domain (88) Amnestic- Multiple Domain (25) Nonamnestic- Single Domain (25) Nonamnestic- Multiple Domain (7) Whitwell, et al. (2007). Arch Neurol, 64(8),

The Case of Henry M (H.M.)

Bauer, Grande, & Valenstein, 2003

Integrated Circuitry Linking Temporal, Diencephalic, and Basal Forebrain Regions

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

DG CA3 CA1 subic

Classical Trisynaptic Circuit

Bauer, Grande, & Valenstein, 2003

<100 each 2 x 10 3 each

Long-Term Potentiation (LTP)

Delayed Nonmatching to Sample

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

6-8 weeks postsurgery2 years postsurgery

Zola-Morgan & Squire, 1990 Anterior Posterior

Bauer, Grande, & Valenstein, 2003

Zola-Morgan & Squire, 1990

Murray & Richmond, Curr Opin Neurobiol, 2001

Hippocampus Mammillary 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

Figure 3. Anatomy of the MTL region. (a) Approximate locations of the hippocampus (red), the PRc (blue) and the PHc (green) shown on T1- weighted magnetic resonance images. (b) Representation of the anatomical connections among, and the proposed roles of, the hippocampus, PRc and PHc in episodic memory according to the BIC model. The arrow between the PRc and PHc indicates the anatomic connection between the two regions; the PRc receives more inputs from the PHc than vice versa. The connections shown here are based on results from anatomical studies of rats and monkeys. Diana, Yonelinas, and Ranganath, TICS, 2007) Recollection v. Familiarity

Figure 1. Activation of MTL subregions in studies of recollection and/or familiarity. Shown is the percentage of contrasts of each type (recollection, familiarity or associative recognition) in which activation was reported for the hippocampus, the posterior parahippocampal gyrus (PPHG) and the anterior parahippocampal gyrus (APHG). Data are summarized from Tables 1 and 2. Diana, Yonelinas, and Ranganath, TICS, 2007) Recollection v. Familiarity

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

Hippocampus Mammillary 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

Integrated Circuitry Linking Temporal, Diencephalic, and Basal Forebrain Regions

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

Hippocampal Damage: Hypoxic Injury Basal Forebrain Damage due to ACoA Rupture Myers, et al. (2006). Neuropsychologia, 44,

Qualitative Differences between MTL and ACoA patients in conditioned reversal (Myers, et al., 2006) Cheese on right if background is light; on left if dark (reversal = opposite) AcquisitionReversal

Hippocampus Mammillary 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

Hippocampus Mammillary 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 PRPH

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