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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

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
Where’s the Lesion?

  • Patient presents to you with memory complaints.

  • Where’s the lesion?

  • Answer: Above the cervical vertebrae.


Where s the lesion1
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
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
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.




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




2 x 103 each

<100 each

<100 each





6-8 weeks postsurgery objects

2 years postsurgery


Anterior Posterior objects

Zola-Morgan & Squire, 1990




Murray & Richmond, objectsCurr Opin Neurobiol, 2001


Two Limbic Circuits and the objects

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 objects

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
Diencephalic Syndromes 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.

  • Korsakoff Syndromeassociated with ETOH abuse or malabsorption

    • prominent encoding deficits

    • role of frontal pathology

  • Vascular disease

  • Thalamic trauma


Mamillary Body Lesions in a case 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.

of Korsakoff’s Disease


Lesion Profile in a Case of Thalamic Amnesia 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.


Graff-Radford, et al, 1990 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.


Two Limbic Circuits and the 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.

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)


Integrated 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. Circuitry Linking Temporal, Diencephalic, and Basal Forebrain Regions


Basal forebrain syndromes
Basal Forebrain Syndromes 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.

  • 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 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.

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 conditioned reversal (Myers, et al., 2006)

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 conditioned reversal (Myers, et al., 2006)

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
Key Points conditioned reversal (Myers, et al., 2006)

  • 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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