Transcript Clinically Relevant Functional Neuroanatomy

Clinically Relevant Functional
Neuroanatomy IV:
Neuroanatomy of Memory
Russell M. Bauer, Ph.D.
University of Florida
AACN 5th Annual Conference
June 8, 2007
Multiple Forms of Memory
“Core” Features of Amnesia
1. anterograde amnesia: defect in new
learning
2. retrograde amnesia/remote memory
disturbance: defect in retrieving old
memories
3. spared memory abilities: attention
span, psychometric intelligence, and
‘nondeclarative’ forms of memory are
generally spared
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
Clinically Relevant Dimensions of
Human Memory Performance
Immediate-recent-remote
Encoding-storage-retrieval
Material, modality specificity
Tests vs. processes
Encoding
• Definition: process of transforming to-be
remembered in formation into memorable and
retrievable form
– Encoding I: bringing information-processing
capacity to bear on stimuli
– Encoding II: ability to use the results of E-1
mnemonically
• Relevance: levels-of-processing accounts of
memory (memory as by-product of information
processing)
• Clinical manifestation: poor immediate
(superspan) recall
Consolidation/Storage
• definition: process of making new
memories permanent
• basis: anatomic and physiological changes at
cellular level; hippocampal system important
• when? during study-test interval
• duration: hours? days? years?
• clinical symptom: delayed memory <<
immediate memory (forgetting)
Performance on a test of memory for news stories. From Squire &
Bayley, Curr Opin Neurobiol, 2007, 17, 185-196.
Retrieval
• definition: process of locating, selecting,
and activating a memory representation
• basis: re-enactment of pattern of excitation
occurring at encoding
• when? at point of test
• clinical symptom: recall << recognition
(also true of shallow encoding), inconsistent
errors
Medial Temporal Syndromes
• Anoxic-hypoxic syndromes
– cardiac arrest
– CO poisoning
• Amnesia associated with ECT
• CNS Infections (Herpes)
• MTS and complex-partial epilepsy
(material-specific)
• Early AD
Temporal Lobe Pathology Associated
with Herpes Simplex Encephalitis
FLAIR (Fluid Attenuated Inversion Recovery) in
Medial Temporal Sclerosis
Hippocampus in ischemia
Hippocampus in Alzheimer’s Disease
The Case of
Henry M (H.M.)
Bauer, Grande, & Valenstein, 2003
Integrated Circuitry Linking Temporal,
Diencephalic, and Basal Forebrain Regions
Two Limbic Circuits
Anterior
Thalamus
Cingulate
Gyrus
Dorsomedial
Thalamus
Mamillothalamic
Tract
Mammilary
Bodies
Fornix
Hippocampus
Medial (Papez)
Orbitofrontal
Amygdalofugal
pathways
Uncus
Amygdala
Lateral
CA3
CA1
DG
subic
Bauer, Grande, & Valenstein, 2003
Delayed Nonmatching to Sample
Delayed Nonmatching to Sample, multiple
trials, trial-unique objects
6-8 weeks postsurgery
2 years postsurgery
Bauer, Grande, &
Valenstein, 2003
Zola-Morgan & Squire, 1990
Zola-Morgan & Squire, 1990
Murray &
Richmond, Curr
Opin Neurobiol,
2001
-perirhinal cortex
obviously
important in
memory, but also
has many
additional
connections
Two Limbic Circuits and the
Two-system theory of amnesia
Anterior
Thalamus
Cingulate
Gyrus
Dorsomedial
Thalamus
Mamillothalamic
Tract
Mammilary
Bodies
Orbitofrontal
Amygdalofugal
pathways
Fornix
Uncus
Hippocampus
Amygdala
PRPH
Medial (Papez)
Lateral
Hippocampus is
important in specific
types of relational
memory (e.g.,
transitive inference)
Morris Water Maze
Morris Water Maze
Lesioned
rats
Sham
operated
rats
(Eichenbaum, et al, 1990)
Time to
Target
Aged
rats
Young
rats
(Gallagher, et al, 1993)
Leutgeb, et al., Curr Opin Neurobiol, 2005, 15, 738-746.
Hippocampus v. Entorhinal Cortex Lesions and
“Reference” vs. “Working” Memory MWM
“Reference Memory (H<ECo)
“Working Memory (H=Eco=Sub<Sham)
Galani, et al., Behav Brain Res, 1998, 96, 1-12.
Two Limbic Circuits and the
Two-system theory of amnesia
Anterior
Thalamus
Cingulate
Gyrus
Dorsomedial
Thalamus
Mamillothalamic
Tract
Mammilary
Bodies
Orbitofrontal
Amygdalofugal
pathways
Fornix
Uncus
Hippocampus
Amygdala
PRPH
Medial (Papez)
Lateral
Integrated Circuitry Linking Temporal,
Diencephalic, and Basal Forebrain Regions
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
MRI in paramedian
thalamic stroke
Lövblad, et al (1997)
Neuroradiology, 39, 693-698.
Mammillary body (a),
medial thalamic
(arrows in B,C) and
fornix (arrowheads in
B) damage in a case of
Alcholic Korsakoff
syndrome. D shows
resolution of signal
changes after 5 months
of abstinence.
Caolo, et al (2005).
Brain, 128, 1584-98.
Lesion Profile in a Case of Thalamic Amnesia
Anterior thalamic
lesions affecting the
MTT and VAF
pathways produce
persistent amnesia,
posterior lesions do
not
Graff-Radford, et al
(1990). Brain, 113, 1-25.
Two Limbic Circuits and the
Two-system theory of amnesia
Anterior
Thalamus
Cingulate
Gyrus
Dorsomedial
Thalamus
Mamillothalamic
Tract
Mammilary
Bodies
Fornix
Hippocampus
Medial (Papez)
Orbitofrontal
Amygdalofugal
pathways
Uncus
Amygdala
Lateral
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
Myers, DeLuca, Hopkins, & Gluck (2006),
44, 130-139.
Myers,Neuropsychologia,
et al. (2006)
Myers, et al. (2006)
Learning
AcoA<H
Reversal
H<AcoA
Myers, et al. (2006)
Myers, et al. (2006)
Two Limbic Circuits
Anterior
Thalamus
Cingulate
Gyrus
Dorsomedial
Thalamus
Mamillothalamic
Tract
Mammilary
Bodies
Fornix
Hippocampus
Medial (Papez)
Orbitofrontal
Amygdalofugal
pathways
Uncus
Amygdala
Lateral
Two Limbic Circuits
Anterior
Thalamus
Cingulate
Gyrus
Dorsomedial
Thalamus
Mamillothalamic
Tract
Mammilary
Bodies
Fornix
Hippocampus
Medial (Papez)
Orbitofrontal
Amygdalofugal
pathways
Uncus
Amygdala
Lateral
Bauer, Grande, & Valenstein, 2003
Frontal Contributions to Memory
• Working Memory
• Selective Engagement
• Cognitive contributions
– Strategy development
– Retrieval support/intention
– Metamemory
G.A. Miller
E. Galanter
Miller, G. A., Galanter, E. & Pribram, K. H.
(1960). Plans and the structure of behavior.
New York: Holt, Rinehart & Winston.
K.H. Pribram
Alan Baddeley
Episodic
Buffer



Working memory and
associative memory may be
distinguished using the
delayed response task
When PFC-lesioned monkey
must remember which well
is baited from trial to trial,
performance is poor
When PFC-lesioned monkey
must remember which
symbol is baited from trial
to trial, performance is
good
Patricia Goldman-Rakic (1937-2003)
A question to
think about:
why would you
have spatiallysensitive
neurons in preMOTOR cortex?
Smith &
Jonides, 1999
Two views about specificity in WM
• Domain-specificity (Goldman-Rakic,
Ungerleider, Courtney)
– Ventral prefrontal: object working memory
– Dorsal prefrontal: spatial working memory
• Process-specificity (Petrides, D’Esposito)
– Ventral prefrontal: sequential organization and
storage
– Dorsal prefrontal: executive control and monitoring
Storage
Exec
+
Storage
Smith & Jonides 1999
D’Esposito, Postle, and Rypma, 2000
Curtis & D’Esposito, 2003 (from Rowe et al, 2000)
D’Esposito, M., Zarahn, E., Balard, D., Shin, R.K., and Lease, J. (1998) Functional MRI studies of spatial and nonspatial working
memory. Cogn. Brain Res. 7:1-13
Curtis & D’Esposito, 2003
Selective Engagement
• “Activation” or “bringing online” of a
cortical processor needed to perform a
cognitive task
• Dependent on complex reciprocal
connections among regions in frontal lobe,
basal ganglia, thalamus, and ascending
activation centers
• Important for memory retrieval
General Organization of Frontal corticalstriatal-pallidal-thalamic-cortical loops
Motor Activation/Preparation
Heilman, Watson, & Valenstein, 2003
Selective Engagement and Disengagement of Cortex
Thalamus
A
E
G
Cortex
B
F
C
D
J
I
H
Nucleus Reticularis
Excitatory cortical projections to the thalamus (A) course through the nucleusreticularis (NR) sy napsing on inhibitory thalamic
interneurons (B), reticulo-thalamic neurons (C), and prov iding arborizing collaterals (D). The direct cortical projection to the thalamic
interneuron (B) results in the inhibition of thalamo-cortical projection (E). This inhibition of thalamo-cortical projections results in the
disengagement (inhibition) of select cortical areas. The reticulo-thalamic neuron (C) sy napses on, and inhibits, a thalamic interneuron
(F), resulting in excitation of thethalamo-cortical neuron (G). This excitation of thethalamo-cortical projection results in the engagement
of select cortical areas. The collateral (D) sy napses on, and inhibits, areticulo-thalamic neuron (H) which sy napses on a thalamic
interneuron (I). The thalamic interneuron (I) inhibits the thalamo-cortical neuron (J) resulting in the disengagement of select cortical
areas.
= Glutamatergic (excitatory )
= GABA-ergic (inhibitory )
Dashed lines represent inhibited neuron (neuron unable to exert it ’s inf luence on downstream neuron).
Key Points
• Extended memory system including hippocampus,
amygdala, and basal forebrain (and their connections)
• 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
through intrinsic and corticocortical connections; these
structures appear important in establishing distributed
network connections supporting memory
• Cortical-subcortical interactions appear critical for
selectively activating and engaging specific cortical
processors needed for performance of specific tasks