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. 2013 Apr;38(5):863-71.
doi: 10.1038/npp.2012.252. Epub 2012 Dec 5.

Using Standardized fMRI Protocols to Identify Patterns of Prefrontal Circuit Dysregulation That Are Common and Specific to Cognitive and Emotional Tasks in Major Depressive Disorder: First Wave Results From the iSPOT-D Study

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Free PMC article

Using Standardized fMRI Protocols to Identify Patterns of Prefrontal Circuit Dysregulation That Are Common and Specific to Cognitive and Emotional Tasks in Major Depressive Disorder: First Wave Results From the iSPOT-D Study

Mayuresh S Korgaonkar et al. Neuropsychopharmacology. .
Free PMC article

Abstract

Functional neuroimaging studies have implicated dysregulation of prefrontal circuits in major depressive disorder (MDD), and these circuits are a viable target for predicting treatment outcomes. However, because of the heterogeneity of tasks and samples used in studies to date, it is unclear whether the central dysfunction is one of prefrontal hyperreactivity or hyporeactivity. We used a standardized battery of tasks and protocols for functional magnetic resonance imaging, to identify the common vs the specific prefrontal circuits engaged by these tasks in the same 30 outpatients with MDD compared with 30 matched, healthy control participants, recruited as part of the International Study to Predict Optimized Treatment in Depression (iSPOT-D). Reflecting cognitive neuroscience theory and established evidence, the battery included cognitive tasks designed to assess functions of selective attention, sustained attention-working memory and response inhibition, and emotion tasks to assess explicit conscious and implicit nonconscious viewing of facial emotion. MDD participants were distinguished by a distinctive biosignature of: hypoactivation of the dorsolateral prefrontal cortex during working memory updating and during conscious negative emotion processing; hyperactivation of the dorsomedial prefrontal cortex during working memory and response inhibition cognitive tasks and hypoactivation of the dorsomedial prefrontal during conscious processing of positive emotion. These results show that the use of standardized tasks in the same participants provides a way to tease out prefrontal circuitry dysfunction related to cognitive and emotional functions, and not to methodological or sample variations. These findings provide the frame of reference for identifying prefrontal biomarker predictors of treatment outcomes in MDD.

Figures

Figure 1
Figure 1
Prefrontal regions (dorsolateral prefrontal cortex (a and b); dorsomedial prefrontal cortex (c and d)) with significant differences between the MDD and control group. Figure shows location of each region of interest and the corresponding plots show the contrast estimates (mean±SE) for each group. R-dLPFC, right dorsolateral prefrontal cortex; ACC, dorsal anterior cingulate cortex.
Figure 2
Figure 2
Scatter plot showing correlation of dmPFC (ACC) activation during working memory (Y-axis) with the right dLPFC activation during conscious processing of negative emotion (X-axis). R-dLPFC, right dorsolateral prefrontal cortex; ACC, dorsal anterior cingulate cortex.

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