Clinically Relevant Functional Neuroanatomy: Memory and ...

Clinically Relevant Functional Neuroanatomy: Memory and ...

Clinically Relevant Functional Neuroanatomy 3: Working Memory and Executive Skills Russell M. Bauer, Ph.D. University of Florida, USA Vivian Smith Summer

Institute 28 June, 2006 From Memory to Executive Skills: The Anatomy of Working Memory

Who invented working memory? a. b. c. d.

e. Mark DEsposito Alan Baddeley Monte Buchsbaum Patricia Goldman-Rakic William James

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 Clinical Techniques and Methods Verbal Memory Span (digits, consonants, words)

Free Recall Short-term forgetting (Peterson/Peterson) Memory Probe Techniques Prose Recall Experimental Techniques

and Methods Spatial delayed response Oculomotor delayed response Delayed matching-to-sample Attentional set-shifting N-back

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 (19372003) Goldman-Rakic, Wilson, OScalaidhe, &

Goldman-Rakic, 1993 A question to think about: why would you have

spatiallysensitive neurons in preMOTOR cortex? Smith & Jonides,

1999 Frontal and parietal neurons are linked systemically note similar patterns of delay period response

Cohen et al., 1998 Cohen et al (1998); memory structures active during delay

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, DEsposito) Ventral prefrontal: sequential organization and storage Dorsal prefrontal: executive control and monitoring Storage

Exec + Storage Smith & Jonides 1999

Petit, Courtney, Ungerleider, & Haxby, 1998 Medial Wall Activity in WM Primary activity in Pre-SMA and Caudal AC Extensive connections with DLPFC Pre-SMA: response selection and

output preparation Caudal AC: attention for action, response selection DEsposito, Postle, and Rypma, 2000 Curtis & DEsposito, 2003 (from Rowe et al, 2000)

DEsposito, 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 & DEsposito, 2003 PFCs role in

working memory may be as a buffer for activated long-term memories

Anatomy of Executive Skills Executive Functions Attention and inhibition Task management/switching

Planning Monitoring Coding representations in WM for time/place of appearance Response selection Frontal Lobe Cortex

Functional subdivisions: Lateral (4, 6, 8-10, 4347) Medial (6, 8-12, 24, 25, 32, 22) Inferior (11-15, 25, 47)

Another division: Motor (4) Premotor (6, 8, 43, 44, 45) Prefrontal (9-15, 46, 47) Neuropsychological

Manifestations of Frontal Lesions I Frontal Operculum (44,45,47) A) Left: Brocas aphasia B) Right: expressive aprosodia Superior Mesial (mesial 6, 24) A) Left: akinetic mutism

B) Right: akinetic mutism Bilateral lesions of mesial SMA (6) and anterior cingulate (24) produce more severe form of akinetic mutism Tranel, 1992

Neuropsychological Manifestations of Frontal Lobe Lesions II Inferior Mesial Region A) Orbital Region (10, 11) Lesions in this region

produce disinhibition, altered social conduct, acquired sociopathy, and other disturbances due to impairment in fronto-limbic relationships B) Basal Forebrain

(posterior extension of inferior mesial region, including diagonal band of Broca, nucleus accumbens, septal nuclei, substantia innominata)

Tranel, 1992 Lesions here produce prominent anterograde amnesia with confabulation Neuropsychological

Manifestations of Frontal Lobe Lesions III Lateral Prefrontal Region (8,9,46) Lesions in this region produce impairment in a variety of executive skills that cut across

domains. Some degree of material-specificity is present, but relatively weak. A) Fluency: impaired verbal fluency (left) or design fluency (right) B) Memory impairments:

defective recency judgment, metamemory defects, difficulties in memory monitoring Tranel, 1992 C) Impaired abstract concept

formation and hypothesis testing Phineas Gage (1823-1861, accident in 1848) Phineas Gages lesion reconstructed (H. Damasio and R. Frank, 1992)

Keys to Understanding Frontal Lobe Function Realize that it is as far away from the external world as any cortical region Appreciate patterns of connectivity (you can tell a lot about someone by

getting to know their friends) Appreciate inhibitory/excitatory (modulatory) aspects in addition to idea of specialized informationprocessors General Organization of Frontal cortical-striatal-pallidal-thalamiccortical loops

Blumenfeld, 2002 Blumenfeld, 2002 Blumenfeld, 2002

Dorsolateral Loop Critical for executive function Damage produces Inflexibility Planning Problem-solving

Goal-directed behavior Orbitofrontal Loop Involved in social and emotional functioning

Damage produces:

Disinhibition Hyperactivity Emotional lability Aggressiveness Reduce selfawareness Medial Frontal/Cingulate

Loop Important in behavioral activation/intentional disorders Damage results in Akinetic mutism

Abulia Impairments in spontaneous initiation of behavior (Burruss, et. al., Radiology, 2000)

Motor Activation/Preparation Heilman, Watson, & Valenstein, 2003 Selective Engagement and Disengagement of Cortex

Thalamus A E G Cortex


I H Nucleus Reticularis Excitatory cortical projections to the thalamus (A) course through the nucleus

reticularis (NR) synapsing on inhibitory thalamic interneurons (B), reticulo-thalamic neurons (C), and providingarborizing collaterals (D). The direct cortical projection to the thalamic interneuron (B) results in the inhibition ofthalamo-cortical projection (E). This inhibition of thalamo-cortical projections results in the disengagement (inhibition) of select cortical areas. Thereticulo-thalamic neuron (C) synapses on, and inhibits, a thalamic interneuron (F), resulting in excitation of thethalamo-cortical neuron (G). This excitation of thethalamo-cortical projection results in theengagement of select cortical areas. The collateral (D) synapses on, and inhibits, a reticulo-thalamic neuron (H) which synapses on a thalamic

interneuron (I). The thalamic interneuron (I) inhibits thethalamo-cortical neuron (J) resulting in thedisengagement of select cortical areas. = Glutamatergic (excitatory) = GABA-ergic (inhibitory) Dashed lines represent inhibited neuron (neuron unable to exert its influence on downstream neuron).

Selective Engagement (Nadeau & Crosson, 1997) Deco & Rolls, Prog Neurobiol, 2005

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