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