Clinically Relevant Functional Neuroanatomy 3: Working Memory and Executive Skills

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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

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From Memory to Executive SkillsThe Anatomy of
Working Memory
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Who invented working memory?

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

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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
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Alan Baddeley
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Episodic Buffer
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Clinical Techniques and Methods

• Verbal
• Memory Span (digits, consonants, words)
• Free Recall
• Short-term forgetting (Peterson/Peterson)
• Memory Probe Techniques
• Prose Recall

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Experimental Techniques and Methods

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

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• 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

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Patricia Goldman-Rakic (1937-2003)
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Goldman-Rakic, 1996
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Wilson, OScalaidhe, Goldman-Rakic, 1993
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A question to think about why would you have
spatially-sensitive neurons in preMOTOR cortex?
Smith Jonides, 1999
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Frontal and parietal neurons are linked
systemically note similar patterns of delay
period response
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Curtis DEsposito, 2003, TICS
DLPFC
VLPFC
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Cohen et al., 1998
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Cohen et al (1998) memory structures active
during delay
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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

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Exec Storage
Storage
Smith Jonides 1999
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Petit, Courtney, Ungerleider, Haxby, 1998
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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

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DEsposito, Postle, and Rypma, 2000
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Curtis DEsposito, 2003 (from Rowe et al, 2000)
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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. 71-13
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Curtis DEsposito, 2003
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• PFCs role in working memory may be as a buffer
  for activated long-term memories

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Anatomy of Executive Skills
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Executive Functions

• Attention and inhibition
• Task management/switching
• Planning
• Monitoring
• Coding representations in WM for time/place of
  appearance
• Response selection

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Frontal Lobe Cortex

• Functional subdivisions
• Lateral (4, 6, 8-10, 43-47)
• 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)

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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
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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) Lesions here produce prominent
anterograde amnesia with confabulation (material
specificity present, but relatively weak)
Tranel, 1992
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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 C) Impaired abstract concept
formation and hypothesis testing D) Defective
planning, motor sequencing E) Defective
cognitive judgement and estimation
Tranel, 1992
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Phineas Gage (1823-1861, accident in 1848)
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Phineas Gages lesion reconstructed (H. Damasio
and R. Frank, 1992)
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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
  information-processors

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General Organization of Frontal
cortical-striatal-pallidal-thalamic-cortical loops
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Blumenfeld, 2002
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Blumenfeld, 2002
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Blumenfeld, 2002
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Dorsolateral Loop

• Critical for executive function
• Damage produces
• Inflexibility
• Planning
• Problem-solving
• Goal-directed behavior

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Orbitofrontal Loop

• Involved in social and emotional functioning
• Damage produces
• Disinhibition
• Hyperactivity
• Emotional lability
• Aggressiveness
• Reduce self-awareness

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Medial Frontal/Cingulate Loop

• Important in behavioral activation/intentional
  disorders
• Damage results in
• Akinetic mutism
• Abulia
• Impairments in spontaneous initiation of behavior

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(Burruss, et. al., Radiology, 2000)
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Motor Activation/Preparation
Heilman, Watson, Valenstein, 2003
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Selective Engagement (Nadeau Crosson, 1997)
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Deco Rolls, Prog Neurobiol, 2005