Abnormal anterior cingulate cortical activity during emotional n-back task performance distinguishes bipolar from unipolar depressed females

Abstract

Background: Depression in the context of bipolar disorder (BDd) is often misdiagnosed as unipolar disorder depression (UDd) leading to poor clinical outcomes for many bipolar sufferers. We examined neural circuitry supporting emotion regulation in females with either BDd or UDd as a first stage toward identifying biomarkers that may differentiate BDd from UDd.

Method: Fifty-seven females aged 18-45 years participated in this study: 23 with UDd, 18 with bipolar disorder type I depression (BDId) and 16 healthy females. During 3-T functional magnetic resonance imaging (fMRI), the participants performed an emotional face n-back (EFNBACK) task, that is an n-back task with high (2-back) and low (0-back) memory load conditions flanked by two positive, negative or neutral face distracters. This paradigm examines executive control with emotional distracters-emotion regulation.

Results: High memory load with neutral face distracters elicited greater bilateral and left dorsal anterior midcingulate cortex (dAMCC) activity in UDd than in healthy and BDId females respectively, and greater bilateral putamen activity in both depressed groups versus healthy females. High memory load with happy face distracters elicited greater left putamen activity in UDd than in healthy females. Psychotropic medication was associated with greater putamen activity to these contrasts in UDd females.

Conclusions: During high memory load with neutral face distracters, elevated dAMCC activity in UDd suggests abnormal recruitment of attentional control circuitry to maintain task performance, whereas elevated putamen activity unrelated to psychotropic medication in BDId females may suggest an attentional bias toward ambiguous neutral face distracters. Differential patterns of functional abnormalities in neural circuitry supporting attentional control during emotion regulation, especially in the dAMCC, is a promising neuroimaging measure to distinguish UDd from BDId in females.

Fig. 1

Illustration of the Emotional Face n-Back (EFNBACK) task. This is an example of the 2-back (high attentional demand) happy-face distracter condition. During the 0-back (low attentional demand) condition, participants must respond to the letter M. ITI, intertribal stimulus interval. (Copyright © 2009 by the American Psychological Association. Reproduced with permission. The official citation that should be used in referencing this material is Ladouceur et al. 2009. The use of APA information does not imply endorsement by the APA.)

Fig. 2

Group differences in the dorsal anterior midcingulate cortex (dAMCC) blood oxygen level-dependent (BOLD) signal during the attentional control of emotion on the 2back: neutral-2back: no face contrast. Females with unipolar disorder depression (UDd) exhibited (a) significantly greater activity in the dAMCC (peak voxel left: −4, −10, 38; voxels=316, right: 4, −10, 40; voxels=264) versus healthy controls during the 2-back neutral-no face distracter condition; and (b) significantly greater activity in the dAMCC (peak voxel left: −4, −10, 28; voxels=53) versus bipolar I depression (BDId) during the 2-back neutral-no face distracter condition. UDd females showed activation whereas healthy females showed deactivation in the bilateral dAMCC and BDId females deactivation in the left dAMCC. Color bars indicate t values of the statistical parametric mapping (SPM).

Fig. 3

Group differences in the putamen BOLD signal during the attentional control of emotion on the 2back:neutral-2back:no face contrast. BDId individuals exhibited significantly greater activity in the putamen (peak voxel left: −26, 12, 2; voxels=85, right: 24, 10, −4; voxels=316) versus healthy controls during the 2-back neutral-no face distracter condition; BDId females showed activation, while healthy females showed deactivation in bilateral putamen. Color bar indicates t values of the statistical parametric mapping (SPM). BDId=Bipolar disorder type I depressed; H=healthy dAMCC=bilateral BA 24 and 32.