Clinically Relevant Functional Neuroanatomy
IV: Neuroanatomy of Memory
Russell M. Bauer, Ph.D.University of Florida
AACN 5th Annual ConferenceJune 8, 2007
Anatomy of Memory
Russell M. Bauer, Ph.D. (DON’T BELIEVE HIS LIES)
Multiple Forms of MemoryMultiple 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-remoteEncoding-storage-retrieval
Material, modality specificityTests 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
Hippocampus
Mammilary Bodies
Anterior Thalamus
Cingulate Gyrus
Fornix
Mamillothalamic Tract
Amygdala
Dorsomedial Thalamus
Orbitofrontal
Uncus
Two Limbic Circuits
Medial (Papez) Lateral
Amygdalofugal pathways
DG
CA3
CA1
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
Hippocampus
Mammilary Bodies
Anterior Thalamus
Cingulate Gyrus
Fornix
Mamillothalamic Tract
Amygdala
Dorsomedial Thalamus
Orbitofrontal
Uncus
Two Limbic Circuits and the Two-system theory of amnesia
Medial (Papez) Lateral
Amygdalofugal pathways
PRPH
Hippocampus is important in specific types of relational memory (e.g., transitive inference)
Morris Water Maze
Lesioned rats
Sham operated rats
Morris Water Maze
(Eichenbaum, et al, 1990)
(Gallagher, et al, 1993)
Time to Target
Aged rats
Young rats
Leutgeb, et al., Curr Opin Neurobiol, 2005, 15, 738-746.
Galani, et al., Behav Brain Res, 1998, 96, 1-12.
Hippocampus v. Entorhinal Cortex Lesions and “Reference” vs. “Working” Memory MWM
“Reference Memory (H<ECo) “Working Memory (H=Eco=Sub<Sham)
Hippocampus
Mammilary Bodies
Anterior Thalamus
Cingulate Gyrus
Fornix
Mamillothalamic Tract
Amygdala
Dorsomedial Thalamus
Orbitofrontal
Uncus
Two Limbic Circuits and the Two-system theory of amnesia
Medial (Papez) Lateral
Amygdalofugal pathways
PRPH
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.
Caolo, et al (2005). Brain, 128, 1584-98.
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.
Lesion Profile in a Case of Thalamic Amnesia
Graff-Radford, et al (1990). Brain, 113, 1-25.
Anterior thalamic lesions affecting the MTT and VAF pathways produce persistent amnesia, posterior lesions do not
Hippocampus
Mammilary Bodies
Anterior Thalamus
Cingulate Gyrus
Fornix
Mamillothalamic Tract
Amygdala
Dorsomedial Thalamus
Orbitofrontal
Uncus
Two Limbic Circuits and theTwo-system theory of amnesia
Medial (Papez) Lateral
Amygdalofugal pathways
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, et al. (2006)
Myers, DeLuca, Hopkins, & Gluck (2006), Neuropsychologia, 44, 130-139.
Myers, et al. (2006)
Reversal
H<AcoA
Learning
AcoA<H
Myers, et al. (2006)Myers, et al. (2006)
Hippocampus
Mammilary Bodies
Anterior Thalamus
Cingulate Gyrus
Fornix
Mamillothalamic Tract
Amygdala
Dorsomedial Thalamus
Orbitofrontal
Uncus
Two Limbic Circuits
Medial (Papez) Lateral
Amygdalofugal pathways
Hippocampus
Mammilary Bodies
Anterior Thalamus
Cingulate Gyrus
Fornix
Mamillothalamic Tract
Amygdala
Dorsomedial Thalamus
Orbitofrontal
Uncus
Two Limbic Circuits
Medial (Papez) Lateral
Amygdalofugal pathways
Bauer, Grande, & Valenstein, 2003
Frontal Contributions to Memory
• Working Memory
• Selective Engagement
• Cognitive contributions– Strategy development– Retrieval support/intention– Metamemory
Miller, G. A., Galanter, E. & Pribram, K. H. (1960). Plans and the structure of behavior. New York: Holt, Rinehart & Winston.
G.A. Miller
E. Galanter
K.H. Pribram
Alan Baddeley
EpisodicBuffer
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)
Smith & Jonides, 1999
A question to think about: why would you have spatially-sensitive neurons in pre-MOTOR cortex?
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
Smith & Jonides 1999
Storage Exec
+
Storage
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 General Organization of Frontal cortical-striatal-pallidal-thalamic-cortical-striatal-pallidal-thalamic-
cortical loopscortical loops
Motor Activation/Preparation
Heilman, Watson, & Valenstein, 2003
Cortex
Thalamus
Nucleus Reticularis
Selective Engagement and Disengagement of Cortex
Excitatory cortical projections to the thalamus (A) course through the nucleus reticularis (NR) synapsing on inhibitory thalamicinterneurons (B), reticulo-thalamic neurons (C), and providing arborizing collaterals (D). The direct cortical projection to the thalamicinterneuron (B) results in the inhibition of thalamo-cortical projection (E). This inhibition of thalamo-cortical projections results in thedisengagement (inhibition) of select cortical areas. The reticulo-thalamic neuron (C) synapses on, and inhibits, a thalamic interneuron(F), resulting in excitation of the thalamo-cortical neuron (G). This excitation of the thalamo-cortical projection results in the engagementof select cortical areas. The collateral (D) synapses on, and inhibits, a reticulo-thalamic neuron (H) which synapses on a thalamicinterneuron (I). The thalamic interneuron (I) inhibits the thalamo-cortical neuron (J) resulting in the disengagement of select corticalareas.
= Glutamatergic (excitatory) = GABA-ergic (inhibitory)
Dashed lines represent inhibited neuron (neuron unable to exert it’s influence on downstream neuron).
A
J
C
B
G F
E
HI
D
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