Emotional response inhibition in bipolar disorder: a functional magnetic resonance imaging study of trait- and state-related abnormalities

Abstract

Background: Impaired response inhibition and poor impulse control are hallmarks of the manic phase of bipolar disorder but are also present during depressive and, to a lesser degree, euthymic periods. The neural mechanisms underlying these impairments are poorly understood, including how mechanisms are related to bipolar trait or state effects.

Methods: One-hundred four unmedicated participants with bipolar mania (BM) (n = 30), bipolar depression (BD) (n = 30), bipolar euthymia (BE) (n = 14), and healthy control subjects (n = 30) underwent functional magnetic resonance imaging during emotional and nonemotional go/no-go tasks. The go/no-go task requires participants to press a button for go stimuli, while inhibiting the response to no-go trials. In separate blocks, participants inhibited the response to happy faces, sad faces, or letters.

Results: The BE group had higher insula activity during happy face inhibition and greater activity in left inferior frontal gyrus during sad face inhibition, demonstrating bipolar trait effects. Relative to the BE group, BD and BM groups demonstrated lower insula activity during inhibition of happy faces, though the depressed sample had lower activity than manic patients. The BD and BM groups had a greater response to inhibiting sad faces in emotion processing and regulation regions, including putamen, insula, and lateral prefrontal cortex. The manic group also had higher activity in insula and putamen during neutral letter inhibition.

Conclusions: These results suggest distinct trait- and state-related neural abnormalities during response inhibition in bipolar disorder, with implications for future research and treatment.

Figure 1

Functional magnetic resonance imaging paradigm. Examples of presented instructions and stimuli for (A) letter go and (B) sad no-go blocks. The paradigm for the entire run is shown below (C).

Figure 2

Group activation during response inhibition. Significant activity within healthy control (HC), bipolar depressed (BD), bipolar manic (BM), and bipolar euthymic (BE) groups is depicted. For HC, BD, and BM groups, voxels significant at p < .005 and within clusters of at least 76 voxels to correct for multiple comparisons (p < .05) are depicted. Due to smaller size of BE group, individual voxel threshold is lowered to p < .01 for graphical purposes.

Figure 3

Group activation differences during inhibition of happy faces (happy no-go – sad go) (A), inhibition of sad faces (sad no-go – happy go) (B), and sad inhibition vs/happy inhibition ([sad no-go – happy go] – [happy no-go – sad go]) (C). Depicted voxels demonstrate a main effect of diagnosis at p < .01, with cluster-size thresholds correcting for multiple comparisons (p < .05). Boxplots represent mean activation of all voxels within the cluster. BD, bipolar depressed; BE, bipolar euthymic; BM, bipolar manic; HC, healthy control group; IFG, inferior frontal gyrus.