Prefrontal and striatal activation during sequence learning in geriatric depression.
BACKGROUND
Frontostriatal dysfunction is a primary hypothesis for the neurocognitive changes of depression in late life. The aim of the present study was to test this hypothesis with the use of functional magnetic resonance imaging (fMRI) tasks that are known to engage the prefrontal and neostriatal cognitive circuits.


METHODS
Twenty-three elderly subjects (mean age, 69.9 years) participated: 11 subjects with a current major depressive episode and 12 nondepressed elderly control subjects. Subjects underwent fMRI while performing a concurrent implicit and explicit sequence learning task. Region of interest (ROI)-based analyses were conducted, focusing on the dorsal anterior cingulate cortex, the dorsolateral prefrontal cortex, and the neostriatum.


RESULTS
As expected, both the control and depressed subjects learned the sequence during both implicit and explicit conditions. During explicit learning, decreased prefrontal activation was found in the depressed subjects, along with increased striatal activation. The increased striatal activity in the depressed subjects was due to increased activity on the trials that violated the sequence. During implicit learning, no significant differences were found between the groups in the identified ROIs.


CONCLUSIONS
The increased striatal activation on trials that violated the sequence demonstrates a greater response to negative feedback for depressed compared with control subjects. Our observations of significant differences in both prefrontal and striatal regions in the depressed elderly subjects relative to elderly control subjects supports the frontostriatal dysfunction hypothesis of late-life depression.
Aizenstein
Howard J
HJ
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. aizen+@pitt.edu
Butters
Meryl A
MA
Figurski
Jennifer L
JL
Stenger
V Andrew
VA
Reynolds
Charles F
CF
Carter
Cameron S
CS
D000368:Aged; D003342:Corpus Striatum / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D003710:Demography; D003866:Depressive Disorder / Q000503:physiopathology*; D005260:Female; D005852:Geriatric Psychiatry / Q000379:methods*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D011930:Reaction Time / Q000502:physiology; D012691:Serial Learning / Q000502:physiology*; D013997:Time Factors
D010100:Oxygen