Sustained anterior cingulate cortex activation during reward processing predicts response to psychotherapy in major depressive disorder

Abstract

Background: The purpose of the present investigation was to evaluate whether pre-treatment neural activation in response to rewards is a predictor of clinical response to Behavioral Activation Therapy for Depression (BATD), an empirically validated psychotherapy that decreases depressive symptoms by increasing engagement with rewarding stimuli and reducing avoidance behaviors.

Methods: Participants were 33 outpatients with major depressive disorder (MDD) and 20 matched controls. We examined group differences in activation, and the capacity to sustain activation, across task runs using functional magnetic resonance imaging (fMRI) and the monetary incentive delay (MID) task. Hierarchical linear modeling was used to investigate whether pre-treatment neural responses predicted change in depressive symptoms over the course of BATD treatment.

Result: MDD and Control groups differed in sustained activation during reward outcomes in the right nucleus accumbens, such that the MDD group experienced a significant decrease in activation in this region from the first to second task run relative to controls. Pretreatment anhedonia severity and pretreatment task-related reaction times were predictive of response to treatment. Furthermore, sustained activation in the anterior cingulate cortex during reward outcomes predicted response to psychotherapy; patients with greater sustained activation in this region were more responsive to BATD treatment.

Limitation: The current study only included a single treatment condition, thus it unknown whether these predictors of treatment response are specific to BATD or psychotherapy in general.

Conclusion: Findings add to the growing body of literature suggesting that the capacity to sustain neural responses to rewards may be a critical endophenotype of MDD.

Keywords: Anhedonia; Functional magnetic resonance imaging; Major depressive disorder; Nucleus accumbens; Psychotherapy; Reward.

Copyright © 2016 Elsevier B.V. All rights reserved.

Figures

Fig. 1

Left: ROIs from Harvard-Oxford subcortical and cortical structural probabilistic atlases. a) Nucleus accumbens: light blue; b) caudate: red; c) putamen: green; d) frontal medial cortex: purple; e) orbitofrontal cortex: dark blue; f) anterior cingulate cortex: yellow. Right: The monetary incentive delay (MID) task presents a cue indicating whether money can be won, followed by an anticipatory phase, then a target, and feedback indicating whether or not money was won. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Within the MDD group, higher levels anhedonia, measured by the BDI anhedonia subscale, at pretreatment predicted greater improvement in BDI total scores over the course of BATD treatment. The plot is a graphical illustration of the significant interaction between pre-treatment anhedonia and time predicting change in BDI scores from the HLM models. The lines represent the expectation for change in an individual who is one SD below the mean and one SD above the mean. Note the lines are model-based estimates and do not represent averages but rather ranges of anhedonia variability.

Fig. 3

3a: Average reaction times during the MID task, separated by group (MDD, Control), run (run 1, run 2), and trial type (rewarded, unrewarded). 3b: Within the MDD group, greater change in reaction times during reward trials (i.e., faster response at run 2) at pretreatment predicted greater reductions in BDI total scores and anhedonia scores (not shown) over the course of BATD treatment. The plot is a graphical illustration of the significant interaction between pre-treatment depression and time predicting change in BDI scores from the HLM models. The lines represent the expectation for change in an individual who is one SD below the mean and one SD above the mean. Note the lines are model-based estimates and do not represent averages but rather ranges of RT variability.

Fig. 4

Signal intensity in the right nucleus accumbens (NAcc) during reward outcomes averaged by groups and task runs. The Group (MDD, Control) × Run (run 1, run 2) interaction term in this region was significant, p<.04, as was the effect of Run in the MDD group alone, p<.03.

Fig. 5

a: Signal intensity in the left ACC during reward outcomes averaged by groups and task runs. The Group (MDD, Control) × Run (run 1, run 2) interaction term in this region was not significant, but the effect of Run in the MDD group alone was significant, p<.005. b: Within the MDD group, decreased left ACC activation from run 1 to run 2 during reward outcomes predicted change in BDI total scores.