Memory and its Disorders: The Three Amnesias

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Memory and its Disorders The Three Amnesias

• Russell M. Bauer, Ph.D.
• University of Florida
• Human Higher Cortical Function
• March 24, 2008

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The Three Amnesias
Russell M. Bauer, Ph.D. (DONT BELIEVE HIS LIES)
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Wheres the Lesion?

• Patient presents to you with memory complaints.
• Wheres the lesion?
• Answer Above the cervical vertebrae.

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Wheres 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.
• Wheres 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

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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

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Multiple Forms of Memory
Familiarity (not deliberate or conscoius)
Recollection (deliberate, conscious)
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Integrated Circuitry Linking Temporal,
Diencephalic, and Basal Forebrain Regions
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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

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Temporal Lobe Pathology Associated with Herpes
Simplex Encephalitis
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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.
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The Case of Henry M (H.M.)
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Bauer, Grande, Valenstein, 2003
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Integrated Circuitry Linking Temporal,
Diencephalic, and Basal Forebrain Regions
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Two Limbic Circuits
Anterior Thalamus
Dorsomedial Thalamus
Mamillothalamic Tract
Mammillary Bodies
Cingulate Gyrus
Orbitofrontal
Amygdalofugal pathways
Fornix
Uncus
Hippocampus
Amygdala
Lateral
Medial (Papez)
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CA3
CA1
DG
subic
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Classical Trisynaptic Circuit
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Bauer, Grande, Valenstein, 2003
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2 x 103 each
lt100 each
lt100 each
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Long-Term Potentiation (LTP)
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Delayed Nonmatching to Sample
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Delayed Nonmatching to Sample, multiple trials,
trial-unique objects
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6-8 weeks postsurgery
2 years postsurgery
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Anterior
Posterior
Zola-Morgan Squire, 1990
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Bauer, Grande, Valenstein, 2003
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Zola-Morgan Squire, 1990
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Murray Richmond, Curr Opin Neurobiol, 2001
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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)
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Recollection v. Familiarity
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)
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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)
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Diencephalic Syndromes

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

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Mamillary Body Lesions in a case of Korsakoffs
Disease
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Lesion Profile in a Case of Thalamic Amnesia
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Graff-Radford, et al, 1990
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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)
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Integrated Circuitry Linking Temporal,
Diencephalic, and Basal Forebrain Regions
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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

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Hippocampal Damage Hypoxic Injury
Basal Forebrain Damage due to ACoA Rupture
Myers, et al. (2006). Neuropsychologia, 44,
130-139.
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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
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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)
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(No Transcript)
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Two Limbic Circuits
Anterior Thalamus
Dorsomedial Thalamus
Mamillothalamic Tract
Mammillary Bodies
Cingulate Gyrus
Orbitofrontal
Amygdalofugal pathways
Fornix
Uncus
Hippocampus
Amygdala
PRPH
Lateral
Medial (Papez)
Bauer, Grande, Valenstein, 2003
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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