Evidence for deficient modulation of amygdala response by prefrontal cortex in bipolar mania

Abstract

Several studies have implicated the involvement of two major components of emotion regulatory networks, the ventrolateral prefrontal cortex (VLPFC) and amygdala, in the pathophysiology of bipolar disorder. In healthy subjects, the VLPFC has been shown to negatively modulate amygdala response when subjects cognitively evaluate an emotional face by identifying and labeling the emotion it expresses. The current study used such a paradigm to assess whether the strength of this modulation was altered in bipolar subjects when manic. During functional magnetic resonance imaging (fMRI), nine manic subjects with bipolar I disorder and nine healthy subjects either named the emotion shown in a face by identifying one of two words that correctly expressed the emotion (emotion labeling task) or matched the emotion shown in a face to one of two other faces (emotion perception task). The degree to which the VLPFC regulated amygdala response during these tasks was assessed using a psychophysiological interaction (PPI) analysis. Compared with healthy subjects, manic patients had a significantly reduced VLPFC regulation of amygdala response during the emotion labeling task. These findings, taken in context with previous fMRI studies of bipolar mania, suggest that reductions in inhibitory frontal activity in these patients may lead to an increased reactivity of the amygdala.

Frontal lobe hypoactivation in medication-free adults with bipolar II depression during response inhibition

“…Bilateral IFC hypoactivation has previously been reported in subjects with BP I while performing emotion-processing tasks during depression and mania (Foland et al, 2008). The fact that IFC hypoactivation is demonstrated during performance of both response-inhibition and emotion-regulation tasks in BP subjects may not be surprising given the anatomy of this region.…”

Atypical right hemispheric functioning in the euthymic state of bipolar affective disorder

“…Emotional dysregulation in BD has also been linked to atypical functional hemispheric asymmetries as shown by neuroimaging studies (Yurgelun-Todd et al, 2000;Foland et al, 2008;Killgore et al, 2008;Strakowski et al, 2011;Liu et al, 2012) suggesting a deviation from the typical right hemisphere advantage in emotion perception. For example, Killgore et al, (2008) found a decrease in right inferior orbitofrontal activation in BD patients with manic symptoms during passive viewing of a series of black and white fearful facial expressions.…”

Emotional and Motivational Processes in Bipolar Disorder: A Neural Network Perspective

“…Euthymic patients did not show any hyper-activation of the amygdala, which might be attributed to antidepressants [57]. Furthermore, increased activity of the thalamus and the ventral anterior cingulate cortex during mania [55], and increased activity of the dorsolateral prefrontal cortex during depression [56] have been observed. However, as only four studies used this paradigm to investigate bipolar disorder patients, it is difficult to draw any clear and valid conclusions.…”

“…Interestingly, both manic [54,55] and depressed [56] patients showed hypo-activation of the ventrolateral prefrontal cortex during this task, but during euthymia, hyper-activation of the lateral prefrontal cortex was observed, although anticonvulsants showed some normalizing effect [57]. When manic bipolar disorder patients were asked to match facial expressions, they displayed hyper-activation of the amygdala [54,55].…”

“…When manic bipolar disorder patients were asked to match facial expressions, they displayed hyper-activation of the amygdala [54,55]. Euthymic patients did not show any hyper-activation of the amygdala, which might be attributed to antidepressants [57].…”