Transcript Clinically Relevant Functional Neuroanatomy

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 D’Esposito
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

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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
Patricia Goldman-Rakic (1937-2003)
Goldman-Rakic, 1996
Wilson, O’Scalaidhe,
& 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, D’Esposito)
– 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
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
PFC’s role in
working
memory may
be as a buffer
for activated
long-term
memories
Anatomy of
Executive Skills
Executive Functions
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•
•
•
•
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: Broca’s 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 (material specificity
present, but relatively weak)
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
Tranel, 1992
E) Defective cognitive judgement and
estimation
Phineas Gage
(1823-1861, accident in 1848)
Phineas Gage’s 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 information-processors
General Organization of Frontal corticalstriatal-pallidal-thalamic-cortical 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
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).
Selective Engagement
(Nadeau & Crosson, 1997)
Deco & Rolls, Prog Neurobiol, 2005