Prefrontal hyperactivation during working memory task in untreated individuals with major depressive disorder

Abstract

The prefrontal cortex, a part of the limbic-thalamic-cortical network, participates in regulation of mood, cognition and behavior and has been implicated in the pathophysiology of major depressive disorder (MDD). Many neuropsychological studies demonstrate impairment of working memory in patients with MDD. However, there are few functional neuroimaging studies of MDD patients during working memory processing, and most of the available ones included medicated patients or patients with both MDD and bipolar disorder. We used functional magnetic resonance imaging (fMRI) to measure prefrontal cortex function during working memory processing in untreated depressed patients with MDD. Fifteen untreated individuals with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition recurrent MDD (mean age7s.d. = 34.3711.5 years) and 15 healthy comparison subjects (37.7712.1 years) matched for age, sex and race were studied using a GE/Elscint 2T MR system. An echo-planar MRI sequence was used to acquire 24 axial slices. The n-back task (0-back, 1-back and 2-back) was used to elicit frontal cortex activation. Data were analyzed with a multiple regression analysis using the FSL-FEAT software. MDD patients showed significantly greater left dorsolateral cortex activation during the n-back task compared to the healthy controls (P < 0.01), although task performance was similar in the two groups. Furthermore, the patients showed significant anterior cingulate cortex activation during the task, but the comparison subjects did not (P < 0.01). This study provides in vivo imaging evidence of abnormal frontolimbic circuit function during working memory processing in individuals with MDD.

Prefrontal mechanisms for executive control over emotional distraction are altered in major depression

“…Decreased activation was observed in response to targets overall collapsing the target subtypes in bilateral MFG, indicating the task importance in influencing fMRI results in MDD. Two recent studies in medication-free MDD patients revealed increased prefrontal activation during effortful cognitive tasks compared to the controls (Matsuo et al, 2006, Wagner et al, 2006. Although antidepressant medication use may influence the fMRI findings in MDD (Mayberg et al, 2000, Davidson et al, 2003, Fu et al, 2004, task differences may also greatly contribute to the discrepancy in findings across studies as evident by our current study (discrepancy of activation in the MFG to overall targets and target subtypes).…”

Prefrontal cortex, cognitive control, and the registration of decision costs

“…One such disorder, clinical depression, has indeed been associated with increased task-evoked LPFC activity (45,46). Outside the context of psychopathology, however, the motive to minimize internal decision costs might serve a beneficial purpose, guiding behavior toward maximally efficient tasks and strategies.…”

Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

“…Although the CVLT is associated with hippocampal volume (Banos et al, 2004;Tischler et al, 2006) and frontal function (Baldo et al, 2002), the relationship between ACC function and memory processing measured by CLVT is unclear. Therefore, other neurocognitive tasks that activate ACC function (Gehring and Willoughby, 2002;Matsuo et al, 2007) are warranted to determine whether the BDNFVal66Met polymorphism participates in working memory processing related to ACC function in BD patients.…”