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

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.

Shoulder Apprehension Impacts Large-Scale Functional Brain Networks

“…Our findings of increased functional connectivity in the primary sensory-motor area as well as in the dlPFC, which is consistently involved in the cognitive control of motor behavior, 21 are consistent with a preparation or readiness activation of the motor system in muscular resistance. Moreover, Hamilton et al 22 and Korgaonkar et al 23 propose the dlPFC is involved in the appraisal of negative emotional inputs (appraisal being deregulated in major depressive disorder). In the context of our shoulder apprehension videos, the increase in dlPFC might indicate an increased reappraisal of negative information related to the negative valence of the videos, in addition to its role in modulating pre/motor regions.…”

Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging

“…11 Numerous fMRI studies have revealed that the frontal lobe is associated with motor, perceptual and cognitive functions. [78][79][80][81][82] The CC modulates cognitive processes and information transfer between hemispheres. 83 One DTI study demonstrated that abnormalities in the structural integrity of the anterior genu of the CC may contribute to impairment of interhemispheric connectivity in medication-naive patients with MDD.…”

Effect of Electroconvulsive Therapy on Striatal Morphometry in Major Depressive Disorder

“…Structural alterations in the prefrontal cortex, particularly the anterior cingulate, and subcortical hippocampal, amygdalar, thalamic, and striatal/ pallidal centers are consistently implicated (Drevets et al, 2008;Lorenzetti et al, 2009;Schmaal et al, 2015). Lesion and functional imaging studies show these regions form networks governing mood regulation, reward sensitivity, and emotion (Koenigs and Grafman, 2009;Ochsner et al, 2012;Hamilton et al, 2013;Korgaonkar et al, 2013). Symptoms of depression such as amotivation, anhedonia, apathy, and rumination are linked to functional disturbances in the ventral striatum/ pallidum specifically (Disner et al, 2011;Ochsner et al, 2012;Kuhn et al, 2014).…”