Psychological Medicine

Original Articles

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

M. A. Bertoccia1 c1, G. M. Bebkoa1, B. C. Mullina1, S. A. Langeneckera2, C. D. Ladouceura1, J. R. C. Almeidaa1 and M. L. Phillipsa1a3

a1 Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

a2 Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA

a3 Department of Psychological Medicine, Cardiff University, Cardiff, UK


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.

(Received June 21 2011)

(Revised August 31 2011)

(Accepted September 15 2011)

(Online publication November 21 2011)


c1 Address for correspondence: M. A. Bertocci, Ph.D., Western Psychiatric Institute and Clinic, Loeffler Building, room 205, 121 Meyran Avenue, Pittsburgh, PA 15213, USA. (Email:


These data were presented as a poster at the Society of Biological Psychiatry Conference, San Francisco, 2011.