Increased left prefrontal activation in patients with unipolar depression: An event-related, parametric, performance-controlled fMRI study

Background: Executive deficits associated with frontal lobe dysfunction are prominent in depression. We applied a newly developed WM task to investigate the neural correlates of executive processes with functional magnetic resonance imaging (fMRI) at comparable performance levels analyzing correct trials only. Methods: We studied 12 partially remitted, medicated inpatients meeting DSM-IV criteria for major depressive disorder and 17 healthy controls. We used a parametric version of a delayed match-to-sample WM task requiring manipulation of verbal material during a delay period in an event-related fMRI design. Results: Depressed patients were generally slower and load-dependently less accurate than healthy controls. Patients showed significantly more activation of left dorsolateral prefrontal cortex with highest cognitive load. Additionally, they showed higher activation in ventromedial prefrontal cortex during the control condition. Limitations: The fact that patients were taking different antidepressant drugs could limit the explanatory power of the present results. Conclusions: Increased lateral prefrontal activation despite comparably successful performance - when only correct trials were analyzed - in patients with depression can be interpreted as evidence for compensatory recruitment of prefrontal cortical resources. (c) 2006 Elsevier B.V. All rights reserved.