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.

Prefrontal hypoactivation during working memory in bipolar II depression

“…An fMRI study of bipolar I depression explored blood oxygenation level-dependent (BOLD) response during a 2-back working memory task and found that medicated depressed subjects with bipolar I disorder exhibited increased left DLPFC activation compared with healthy subjects (Deckersbach et al 2008). An increased activation pattern has also been found in studies in predominantly medicated unipolar depressed subjects (Fitzgerald et al 2008; Bertocci et al 2012) in which performance on n-back tasks is associated with increased anterior cingulate response, which could represent compensatory activation. However, Townsend et al (2010), found that, relative to healthy comparison subjects, medicated subjects with bipolar I depression exhibited decreased activation in the right DLPFC and the posterior parietal cortex [Brodmann area (BA) 40] during a working memory task.…”

Neural Correlates of Emotional Distractibility in Bipolar Disorder Patients, Unaffected Relatives, and Individuals With Hypomanic Personality

“…In a previous study (15), we applied an emotional go/no-go task, which yielded behavioral distraction effects in the emotional compared with the neutral condition, but no behavioral alterations in bipolar disorder, although activation was increased in frontal and limbic regions. Similar activation increases without behavioral effects were found in working memory tasks with sad mood induction (16) and face distractor stimuli (17). Critically, these studies could not clarify whether the observed hyperactivations reflect altered processing of the cognitive tasks (e.g., as a compensatory effect) or simply aberrant emotional processing.…”

Amplitude of low-frequency fluctuations in first-episode, drug-naïve depressive patients: A 5-year retrospective study

“…A meta-analysis [11] found that MDD showed overreactive salience network (amygdala, dorsal anterior cingulate cortex, and insula) and low response of dorsolateral prefrontal cortex and dorsal striatum to negative information. In addition, different brain activation patterns have been observed by directly comparing activations BD and MDD during performing a series of tasks (e.g., executive function [12,13], facial expressions [14–16], and reward [17]). However, the findings of these studies vary from the tasks performed by participants, posing a challenge to compare data obtained from different cognitive studies.…”