1. 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

2. Depression affects 5% of the total population www.cdc.gov/nchs

3. 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

4. “THE HOURS”

5. Depression research has focused on monoamine transmission

6. Different mechanisms and systems are now being examined Genetics BDNF HPA axis –Stress Structural changes Abnormal brain activation –DLPFC activation (main focus)

7. PFC anatomy and orientation Image: Caltech/Todd Hare

8. ACC anatomy and orientation

9. 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!

10. 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

11. People with MDD had an increase in left DLPFC activation Matsuo, K. et al. (2007). Molecular Psychiatry, Vol 12.

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)

13. 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

14. 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

15. 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

16. 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

17. Hypothesis In MDD patients: –Abberant functional connectivity pattern in DLPFC  increased TIA –Aberrant functional connectivity pattern in the ACC  decreased TID

18. 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

19. Methods

20. H S G

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24. Results

27. 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

28. Discussion Increased DLPFC suggests a compensatory recruitment Increasing cognitive demand requires greater recruitment to maintain task performance

29. 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

30. EPIC