ABERRANT FUNCTIONAL ABERRANT FUNCTIONAL CONNECTIVITY OF DL PFC CONNECTIVITY OF DL PFC
AND CINGULATE NETWORKS AND CINGULATE NETWORKS IN PATIENTS WITH MDD IN PATIENTS WITH MDD
DURING WORKING MEMORY DURING WORKING MEMORY PROCESSINGPROCESSING
ABERRANT FUNCTIONAL ABERRANT FUNCTIONAL CONNECTIVITY OF DL PFC CONNECTIVITY OF DL PFC
AND CINGULATE NETWORKS AND CINGULATE NETWORKS IN PATIENTS WITH MDD IN PATIENTS WITH MDD
DURING WORKING MEMORY DURING WORKING MEMORY PROCESSINGPROCESSING
By Sharleen YuanBy Sharleen Yuan
Special Topics-Affective DisordersSpecial Topics-Affective Disorders
10.2.0910.2.09
Depression affects 5% of the total population
www.cdc.gov/nchs
Depression Symptoms (more than 2 weeks)
• 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
• 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
H S G
H S G
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