Frontal and Limbic Activation During Inhibitory Control Predicts Treatment Response in Major Depressive Disorder
Received 7 June 2006; received in revised form 21 February 2007; accepted 21 February 2007. published online 22 June 2007.
Background
Inhibitory control or regulatory difficulties have been explored in major depressive disorder (MDD) but typically in the context of affectively salient information. Inhibitory control is addressed specifically by using a task devoid of affectively-laden stimuli, to disentangle the effects of altered affect and altered inhibitory processes in MDD.
Methods
Twenty MDD and 22 control volunteer participants matched by age and gender completed a contextual inhibitory control task, the Parametric Go/No-go (PGNG) task during functional magnetic resonance imaging. The PGNG includes three levels of difficulty, a typical continuous performance task and two progressively more difficult versions including Go/No-go hit and rejection trials. After this test, 15 of 20 MDD patients completed a full 10-week treatment with s-citalopram.
Results
There was a significant interaction among response time (control subjects better), hits (control subjects better), and rejections (patients better). The MDD participants had greater activation compared with the control group in frontal and anterior temporal areas during correct rejections (inhibition). Activation during successful inhibitory events in bilateral inferior frontal and left amygdala, insula, and nucleus accumbens and during unsuccessful inhibition (commission errors) in rostral anterior cingulate predicted post-treatment improvement in depression symptoms.
Conclusions
The imaging findings suggest that in MDD subjects, greater neural activation in frontal, limbic, and temporal regions during correct rejection of lures is necessary to achieve behavioral performance equivalent to control subjects. Greater activation in similar regions was further predictive of better treatment response in MDD.
aDepartment of Psychiatry, University of Michigan Medical Center, Ann Arbor, Michigan
bMolecular & Behavioral Neuroscience Institute, Ann Arbor, Michigan
cDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
Address reprint requests to Scott A Langenecker, Ph.D., Department of Psychiatry, University of Michigan Medical Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109
ABSTRACT