Functional neuroimaging of major depressive disorder: a meta-analysis and new integration of base line activation and neural response data

Abstract

Objective: Functional neuroimaging investigations of major depressive disorder can advance both the neural theory and treatment of this debilitating illness. Inconsistency of neuroimaging findings and the use of region-of-interest approaches have hindered the development of a comprehensive, empirically informed neural model of major depression. In this context, the authors sought to identify reliable anomalies in baseline neural activity and neural response to affective stimuli in major depressive disorder.

Method: The authors applied voxel-wise, whole-brain meta-analysis to neuroimaging investigations comparing depressed to healthy comparison groups with respect to baseline neural activity or neural response to positively and/or negatively valenced stimuli.

Results: Relative to healthy subjects, those with major depression had reliably higher baseline activity, bilaterally, in the pulvinar nucleus. The analysis of neural response studies using negative stimuli showed greater response in the amygdala, insula, and dorsal anterior cingulate cortex and lower response in the dorsal striatum and dorsolateral prefrontal cortex in individuals with major depressive disorder than in healthy subjects.

Conclusions: The meta-analytic results support an elegant and neuroanatomically viable model of the salience of negative information in major depressive disorder. In this proposed model, high baseline pulvinar activity in depression first potentiates responding of the brain's salience network to negative information; next, and owing potentially to low striatal dopamine levels in depression, this viscerally charged information fails to propagate up the cortical-striatal-pallidalthalamic circuit to the dorsolateral prefrontal cortex for contextual processing and reappraisal.

FIGURE 1.. Statistical Map of Reliable Results From Meta-Analytic Synthesis Showing Differences in Baseline Regional Cerebral Blood Flow Between Persons With Major Depressive disorder and Healthy Comparison Subjects^a

^a Presented data were smoothed by using cubic interpolation.

FIGURE 2.. Statistical Map of Reliable Results From Meta-Analytic Synthesis Showing Brain Structures With different Responses^a to Negative Stimuli Between Persons With Major depressive disorder and Healthy Comparison Subjects^b

^a As assessed with functional magnetic resonance imaging. ^b Presented data were smoothed by using cubic interpolation.

FIGURE 3.. Neural Model of Biased Responding to Negative Information in Major Depressive disorder^a

^a Part A: high pulvinar activation at baseline potentiates responding in the amygdala, dorsal anterior cingulate cortex, and insula; mutual excitation among these components of the salience network and connectivity from them back to the pulvinar may sustain their activation. Part B: possibly because of low striatal dopamine levels in major depressive disorder, signals from the dorsal anterior cingulate cortex and amygdala fail to propagate up the ascending cortical­striatal­pallidal­thalamic circuit, resulting in diminished responses to negative stimuli in the dorsal striatum and dorsolateral prefrontal cortex.