Dissociable patterns of abnormal frontal cortical activation during anticipation of an uncertain reward or loss in bipolar versus major depression

Abstract

Objectives: Recent research has found abnormalities in reward-related neural activation in bipolar disorder (BD), during both manic and euthymic phases. However, reward-related neural activation in currently depressed individuals with BD and that in currently depressed individuals with major depressive disorder (MDD) have yet to be directly compared. Here, we studied these groups, examining the neural activation elicited during a guessing task in fronto-striatal regions identified by previous studies.

Methods: We evaluated neural activation during a reward task using fMRI in two groups of depressed individuals, one with bipolar I disorder (BD-I) (n = 23) and one with MDD (n = 40), with similar levels of illness severity, and a group of healthy individuals (n = 37).

Results: Reward expectancy-related activation in the anterior cingulate cortex was observed in the healthy individuals, but was significantly reduced in depressed patients (BD-I and MDD together). Anticipation-related activation was increased in the left ventrolateral prefrontal cortex in the BD-I depressed group compared with the other two groups. There were no significant differences in prediction error-related activation in the ventral striatum across the three groups.

Conclusions: The findings extend previous research which has identified dysfunction within the ventrolateral prefrontal cortex in BD, and show that abnormally elevated activity in this region during anticipation of either reward or loss may distinguish depressed individuals with BD-I from those with MDD. Altered activation of the anterior cingulate cortex during reward expectancy characterizes both types of depression. These findings have important implications for identifying both common and distinct properties of the neural circuitry underlying BD-I and MDD.

Keywords: anticipation; bipolar disorder; functional magnetic resonance imaging; mood disorders; prediction error; prefrontal cortex; reward; ventral striatum.

Fig. 1

Diagram describing the sequence of events in a given trial. The paradigm consists of 24 trials: 12 are reward-expectation trials, in which the arrow points upward and the possible outcomes are a win (six trials) or no change (six trials); the remaining 12 are loss-expectation trials, in which the arrow points downward, and the possible outcomes are a loss (six trials) or no change (six trials). Reward and outcome expectancy regressors are coupled to the onset of the arrow stimulus, while the outcome and prediction error regressors are coupled to the presentation of the number and the feedback (one sec total). ITI = inter-trial interval; MRI = magnetic resonance imaging.

Fig. 2

Main effect of reward expectancy in each of the three groups [top left = healthy individuals; top right = individuals with major depressive disorder (MDD); bottom left = individuals with bipolar disorder (BD); bottom right = controls versus patients; colored bars above the images reflect T statistic scale] thresholded at p < 0.005 uncorrected. The inset plot represents the parameter estimates obtained from the anterior cingulate cortex (ACC) region [8-mm sphere centered at: x = 2, y = 28, z = 30 for each group]. Error bars represent standard error of the mean.

Fig. 3

Main effect of anticipation per se in all three groups [top left = healthy individuals; top right = individuals with major depressive disorder (MDD); bottom left = individuals with bipolar disorder (BD); bottom right = BD versus non-BD; colored bars above the images reflect T statistic scale] thresholded at p < 0.005 uncorrected (z = 5). The inset plot represents the parameter estimates obtained from the left ventrolateral prefrontal cortex (VLPFC) region [8-mm sphere centered at: x = –43, y = 30, z = –11 for each group]. Error bars represent standard error of the mean.

Fig. 4

Main effect of prediction error activation in all three groups [top = healthy individuals; middle = individuals with major depressive disorder (MDD); bottom = individuals with bipolar disorder]. Regional brain activation (left) thresholded at p < 0.005 uncorrected. The inset displays data extracted from the ventral striatum for each group: top graph = all participants in each group; bottom graph = groups stratified by antipsychotic (AP) medications. Error bars represent standard error of the mean.