Dissociable cortico-striatal connectivity abnormalities in major depression in response to monetary gains and penalties

Abstract

Background Individuals with major depressive disorder (MDD) are characterized by maladaptive responses to both positive and negative outcomes, which have been linked to localized abnormal activations in cortical and striatal brain regions. However, the exact neural circuitry implicated in such abnormalities remains largely unexplored. Methods In this study 26 unmedicated adults with MDD and 29 matched healthy controls completed a monetary incentive delay task during functional magnetic resonance imaging (fMRI). Psycho-physiological interaction (PPI) analyses probed group differences in connectivity separately in response to positive and negative outcomes (i.e., monetary gains and penalties). Results Relative to controls, MDD subjects displayed decreased connectivity between the caudate and dorsal anterior cingulate cortex (dACC) in response to monetary gains, yet increased connectivity between the caudate and a different, more rostral, dACC sub-region in response to monetary penalties. Moreover, exploratory analyses of 14 MDD patients who completed a 12-week, double-blind, placebo-controlled clinical trial after the baseline fMRI scans indicated that a more normative pattern of cortico-striatal connectivity pre-treatment was associated with more symptoms improvement 12 weeks later. Conclusions These results identify the caudate as a region with dissociable incentive-dependent dACC connectivity abnormalities in MDD, and provide initial evidence that cortico-striatal circuitry may play a role in MDD treatment response. Given the role of cortico-striatal circuitry in encoding action-outcome contingencies, such dysregulated connectivity may relate to the prominent disruptions in goal-directed behavior that characterize MDD.

Effect of Electroconvulsive Therapy on Striatal Morphometry in Major Depressive Disorder

“…Functional imaging studies demonstrate depressionrelated hyporesponsivity in striatal areas (Epstein et al, 2006;Smoski et al, 2009) and disturbances in fronto-striatal connectivity (Furman et al, 2011). Deficits in brain activation and functional connectivity in basal ganglia substructures are suggested to normalize with different antidepressant treatments (Stoy et al, 2012;Admon et al, 2015). In ECT-treated patients, we recently showed a hyperconnectivity between the ventral striatum and ventral default-mode network, while simultaneously demonstrating hypoconnectivity with the anterior default-mode network, patterns that were modulated by ECT (Leaver et al, 2015).…”

Dopaminergic Enhancement of Striatal Response to Reward in Major Depression

“…Previous studies with this task revealed reduced striatal activation and functional connectivity in depressed versus healthy adults during anticipation and receipt of monetary reward (7, 26), making it well-suited for the present study (supplementary methods). …”

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment

“…MDD patients generally exhibit reduced sensitivity to reward; this cognitive blunting is reflected by reduced ventral CSTC loop activation in the orbitofrontal cortex, anterior cingulate and ventral striatum to reward and loss receipt/anticipation (Smoski et al, 2011; Chantiluke et al, 2012; Schiller et al, 2013; Admon et al, 2015; Manelis et al, 2016). …”

“…Connectivity between the putamen, caudate and cingulate during a monetary incentive delay task has been shown to predict response to psychotherapy (Admon et al, 2015; Walsh et al, 2016). High baseline ACC and low striatal activity were also shown to be predictive of improvement on antidepressants in a recent meta-analysis of 15 studies (Fu et al, 2013).…”