Memory and its Disorders: The Three Amnesias
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Transcript of Memory and its Disorders: The Three Amnesias
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 MemoryMultiple 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), 1130-1138.
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<100 each
2 x 103 each
Long-Term Potentiation (LTP)
Delayed Nonmatching to Sample
Delayed Nonmatching to Sample, multiple trials, trial-unique objects
6-8 weeks postsurgery 2 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 theTwo-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, 130-139.
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)
Acquisition Reversal
Hippocampus
Mammillary Bodies
Anterior Thalamus
Cingulate Gyrus
Fornix
Mamillothalamic Tract
Amygdala
Dorsomedial Thalamus
Orbitofrontal
Uncus
Two Limbic Circuits and theTwo-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