Transcript Sharleen Yuan

ABERRANT FUNCTIONAL
CONNECTIVITY OF DL PFC
AND CINGULATE NETWORKS
IN PATIENTS WITH MDD
DURING WORKING MEMORY
PROCESSING
By Sharleen Yuan
Special Topics-Affective Disorders
10.2.09
Depression affects 5%
of the total population
www.cdc.gov/nchs
Depression Symptoms
(more than 2 weeks)
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Agitation, restlessness, and
irritability
Dramatic change in appetite,
often with weight gain or loss
Extreme difficulty
concentrating
Fatigue and lack of energy
Feelings of hopelessness and
helplessness
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Feelings of worthlessness,
self-hate, and inappropriate
guilt
Inactivity and withdrawal
from usual activities, a loss of
interest or pleasure in
activities that were once
enjoyed (such as sex)
Thoughts of death or suicide
Trouble sleeping or excessive
sleeping
“THE HOURS”
Depression research has focused
on monoamine transmission
Different mechanisms and systems
are now being examined
• Genetics
• BDNF
• HPA axis
– Stress
• Structural changes
• Abnormal brain activation
– DLPFC activation (main focus)
PFC anatomy and orientation
Image: Caltech/Todd Hare
ACC anatomy and
orientation
PFC: What does it do?
• Weighs consequences of future
actions
– Plans and organizes those action
– Integration of motor and sensory
information
• Executive functions
– Planning and regulating behavior
– Problem solver!
PFC: What else does it
do?
• Concerned with sequencing of
behavior over time
– ST “working” memory
• DLPFC: Densely interconnected
association regions
– Projects to numerous cortical and
subcortical regions
People with MDD had an
increase in left DLPFC
activation
Matsuo, K. et al. (2007). Molecular
Psychiatry, Vol 12.
Depression and DLPFC
• DLPFC-striatum-thalamus circuit and
frontolimbic-subcoritcal circuit
– Involved in control of cognitive and
executive function (DLPFC primary
center)
– Debate b/twn hypoactivity and
hyperactivity (more now showing
hyperactivity)
Depression and DLPFC
• Hyperactivity of the DLPFC
– Seen also in schizophrenia
– Could be due to DA abnormalities
• DA important in modulating prefrontal
activation dur working memory
• Underlie issue of abnormal function of
frontolimbic network in frontolimbic circuit
Depression and DLPFC
• Why is there hyperactivity?
– Could be a compensatory mechanism 
increase WM-related activation is
needed
– But also found abnormalities in the ACC
Depression and ACC
• Anterior cingulate cortex
– Contributes to executive functions
• Attention, inhibition, cognitive conflicts
– Key role in emotional expression, affect
regulation, and cognitive processing
– Significant activation in MDD
Depression and ACC
• Activated during low cognitive
demand or neutral baseline
• Is activation due to the cognitive
task or reflect an aberrant TID?
• Functional connectivity and
relationship of lateral PFC and ACC
not determined
Hypothesis
• In MDD patients:
– Abberant functional connectivity
pattern in DLPFC  increased TIA
– Aberrant functional connectivity
pattern in the ACC  decreased TID
Methods
• 8 males, 6 females with MDD
– DSM-IV diagnosed w/o any other Axis I
disorder
– Pts treated w/ AD (different types)
• Psychopathology rated through the
BPRS, the HAMD-21, and the CGI
• 7 males, 7 females in Control grp
Methods
HSG
HSG
r
Results
Results
Results
Discussion
• Two main findings:
– 1. connectivity abnormalities in the
DLPF/parietal network ( + correlation w
the delay period of WM task)
– 2. connectivity abnormalities in the
VLPF/cingulate network
Discussion
• Increased DLPFC suggests a
compensatory recruitment
• Increasing cognitive demand requires
greater recruitment to maintain task
performance
Discussion
• Increased ACC contributes to a
failure of deactivation in MDD
patients
• MDD patients with more deactivation
of ACC showed greater clinical
improvement increased activation
cld represent a neg prognostic
regarding clinical recovery
EPIC