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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


Memory and its disorders the three amnesias

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


Memory and its disorders the three amnesias

Multiple Forms of Memory

Familiarity

(not deliberate or conscoius)

Recollection

(deliberate, conscious)


Memory and its disorders the three amnesias

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


Memory and its disorders the three amnesias

Temporal Lobe Pathology Associated

with Herpes Simplex Encephalitis


Memory and its disorders the three amnesias

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.




Memory and its disorders the three amnesias

IntegratedCircuitry Linking Temporal, Diencephalic, and Basal Forebrain Regions


Memory and its disorders the three amnesias

Two Limbic Circuits

Anterior Thalamus

Dorsomedial Thalamus

Mamillothalamic Tract

Mammillary Bodies

Cingulate Gyrus

Orbitofrontal

Amygdalofugal pathways

Fornix

Uncus

Hippocampus

Amygdala

Lateral

Medial (Papez)


Memory and its disorders the three amnesias

CA3

CA1

DG

subic




Memory and its disorders the three amnesias

2 x 103 each

<100 each

<100 each





Memory and its disorders the three amnesias

6-8 weeks postsurgery objects

2 years postsurgery


Memory and its disorders the three amnesias

Anterior Posterior objects

Zola-Morgan & Squire, 1990




Memory and its disorders the three amnesias

Murray & Richmond, objectsCurr Opin Neurobiol, 2001


Memory and its disorders the three amnesias

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)


Memory and its disorders the three amnesias

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)


Memory and its disorders the three amnesias

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


Memory and its disorders the three amnesias

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


Memory and its disorders the three amnesias

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.


Memory and its disorders the three amnesias

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.


Memory and its disorders the three amnesias

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)


Memory and its disorders the three amnesias

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


Memory and its disorders the three amnesias

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.


Memory and its disorders the three amnesias

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


Memory and its disorders the three amnesias

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)


Memory and its disorders the three amnesias

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