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. The Three Amnesias. Russell M. Bauer, Ph.D. (DON’T BELIEVE HIS LIES). Where’s the Lesion?. Patient presents to you with memory complaints.

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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


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

Familiarity

(not deliberate or conscoius)

Recollection

(deliberate, conscious)


IntegratedCircuitry 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


IntegratedCircuitry Linking Temporal, Diencephalic, and Basal Forebrain Regions


Two Limbic Circuits

Anterior Thalamus

Dorsomedial Thalamus

Mamillothalamic Tract

Mammillary Bodies

Cingulate Gyrus

Orbitofrontal

Amygdalofugal pathways

Fornix

Uncus

Hippocampus

Amygdala

Lateral

Medial (Papez)


CA3

CA1

DG

subic


Classical Trisynaptic Circuit


Bauer, Grande, & Valenstein, 2003


2 x 103 each

<100 each

<100 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


Anterior Posterior

Zola-Morgan & Squire, 1990


Bauer, Grande, & Valenstein, 2003


Zola-Morgan & Squire, 1990


Murray & Richmond, Curr Opin Neurobiol, 2001


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)


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)


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.

Recollection v. Familiarity

Diana, Yonelinas, and Ranganath, TICS, 2007)


Diencephalic Syndromes

  • Korsakoff Syndromeassociated 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

PRPH

Lateral

Medial (Papez)


IntegratedCircuitry 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


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)


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


Key Points

  • Extended memory systemincluding hippocampus, amygdala, and basal forebrain

  • We (basically) understand anatomy, now we need to understand computation

  • Notion ofdistinct subtypes of amnesia generally less favorablenow than 10 years ago

  • Certain structures are‘wired’ for associational processing; these structures are reciprocally connected to cortical processors


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