Attenuation of Frontostriatal Connectivity During Reward Processing Predicts Response to Psychotherapy in Major Depressive Disorder

Abstract

There are few reliable predictors of response to antidepressant treatments. In the present investigation, we examined pretreatment functional brain connectivity during reward processing as a potential predictor of response to Behavioral Activation Treatment for Depression (BATD), a validated psychotherapy that promotes engagement with rewarding stimuli and reduces avoidance behaviors. Thirty-three outpatients with major depressive disorder (MDD) and 20 matched controls completed two runs of the monetary incentive delay task during functional magnetic resonance imaging after which participants with MDD received up to 15 sessions of BATD. Seed-based generalized psychophysiological interaction analyses focused on task-based connectivity across task runs, as well as the attenuation of connectivity from the first to the second run of the task. The average change in Beck Depression Inventory-II scores due to treatment was 10.54 points, a clinically meaningful response. Groups differed in seed-based functional connectivity among multiple frontostriatal regions. Hierarchical linear modeling revealed that improved treatment response to BATD was predicted by greater connectivity between the left putamen and paracingulate gyrus during reward anticipation. In addition, MDD participants with greater attenuation of connectivity between several frontostriatal seeds, and midline subcallosal cortex and left paracingulate gyrus demonstrated improved response to BATD. These findings indicate that pretreatment frontostriatal functional connectivity during reward processing is predictive of response to a psychotherapy modality that promotes improving approach-related behaviors in MDD. Furthermore, connectivity attenuation among reward-processing regions may be a particularly powerful endophenotypic predictor of response to BATD in MDD.

Figures

Figure 1

Group differences in task-dependent connectivity attenuation (run 1>run 2) during the anticipation and outcome phases of the MID task. Relative to the control group, the MDD group showed greater connectivity attenuation (run 1>run 2) with clusters in the orbitofrontal cortex and subcallosal cortex and (a) the left striatum seed during reward anticipation, (b) the right striatum seed during reward anticipation, and (c) the right striatum seed during reward outcomes. Note that across all three contrast maps, clusters are within the orbitofrontal cortex and subcallosal cortex. A full color version of this figure is available at the Neuropsychopharmacology journal online.

Figure 2

Within the MDD group, greater global connectivity between the left caudate (seed) and right paracingulate gyrus (BA 24/32) during reward anticipation predicted greater improvement in BDI total scores over the course of BATD treatment. The plot is a graphical illustration of the significant interaction between pretreatment connectivity 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 brain connectivity variability. The brain image indicates the seed region above and the connecting cluster beneath. The bar graph illustrates connectivity estimates. A full color version of this figure is available at the Neuropsychopharmacology journal online.

Figure 3

Within the MDD group, less connectivity attenuation between the right putamen (seed) and right orbitofrontal cortex/temporal pole (BA 47) during reward anticipation predicted greater improvement in BDI total scores over the course of BATD treatment. The plot is a graphical illustration of the significant interaction between pretreatment connectivity 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 brain connectivity variability. The brain image indicates the seed region above and the connecting cluster beneath. The bar graph illustrates connectivity estimates. A full color version of this figure is available at the Neuropsychopharmacology journal online.

Figure 4

Within the MDD group, greater connectivity attenuation between the left nucleus accumbens (seed) and paracingulate gyrus (BA 32) during reward outcomes predicted greater improvement in BDI total scores over the course of BATD treatment. Findings between the left putamen (seed) and subcallosal cortex (BA 11) during reward anticipation and the right frontal medial cortex (seed) and paracingulate gyrus (BA 32) during reward anticipation followed the same pattern. A full color version of this figure is available at the Neuropsychopharmacology journal online.