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. 2014 Jun;44(8):1639-51.
doi: 10.1017/S003329171300202X. Epub 2013 Aug 12.

Fronto-limbic-striatal dysfunction in pediatric and adult patients with bipolar disorder: impact of face emotion and attentional demands

M A Brotman  1 , W-L Tseng  1 , A K Olsavsky  2 , S J Fromm  1 , E J Muhrer  1 , J G Rutenberg  1 , C M Deveney  1 , N E Adleman  1 , C A Zarate  3 , D S Pine  1 , E Leibenluft  1
Affiliations

Fronto-limbic-striatal dysfunction in pediatric and adult patients with bipolar disorder: impact of face emotion and attentional demands

M A Brotman et al. Psychol Med. 2014 Jun.

Abstract

Background: Research in bipolar disorder (BD) implicates fronto-limbic-striatal dysfunction during face emotion processing but it is unknown how such dysfunction varies by task demands, face emotion and patient age.

Method: During functional magnetic resonance imaging (fMRI), 181 participants, including 62 BD (36 children and 26 adults) and 119 healthy comparison (HC) subjects (57 children and 62 adults), engaged in constrained and unconstrained processing of emotional (angry, fearful, happy) and non-emotional (neutral) faces. During constrained processing, subjects answered questions focusing their attention on the face; this was processed either implicitly (nose width rating) or explicitly (hostility; subjective fear ratings). Unconstrained processing consisted of passive viewing.

Results: Pediatric BD rated neutral faces as more hostile than did other groups. In BD patients, family-wise error (FWE)-corrected region of interest (ROI) analyses revealed dysfunction in the amygdala, inferior frontal gyrus (IFG), anterior cingulate cortex (ACC) and putamen. Patients with BD showed amygdala hyperactivation during explicit processing (hostility ratings) of fearful faces and passive viewing of angry and neutral faces but IFG hypoactivation during implicit processing of neutral and happy faces. In the ACC and striatum, the direction of dysfunction varied by task demand: BD demonstrated hyperactivation during unconstrained processing of angry or neutral faces but hypoactivation during constrained processing (implicit or explicit) of angry, neutral or happy faces.

Conclusions: Findings suggest amygdala hyperactivation in BD while processing negatively valenced and neutral faces, regardless of attentional condition, and BD IFG hypoactivation during implicit processing. In the cognitive control circuit involving the ACC and putamen, BD neural dysfunction was sensitive to task demands.

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Conflict of interest statement

Declaration of Interest

Dr Olsavsky’s research was made possible through the Clinical Research Training Program, a public–private partnership supported jointly by the NIH and Pfizer Inc. (through a grant to the Foundation for NIH from Pfizer Inc.). Dr Zarate is listed as a co-inventor on a patent application for the use of ketamine in major depression. Dr Zarate has assigned his rights in the patent to the US government but will share a percentage of any royalties that may be received by the government. All other authors have no conflicts to disclose.

Figures

Fig. 1
Fig. 1
Left amygdala hyperactivity during explicit (hostility) ratings of fearful faces and passive viewing of angry faces in patients with bipolar disorder (BD) and healthy comparisons (HC).
Fig. 2
Fig. 2
Right anterior cingulate cortex (ACC) activation during angry faces: hypoactivity during implicit (nose width) ratings but hyperactivity during passive viewing in patients with bipolar disorder (BD) and healthy comparisons (HC).
Fig. 3
Fig. 3
Right inferior frontal gyrus (IFG) hypoactivation during implicit (nose width) ratings of happy and neutral faces in patients with bipolar disorder (BD) and healthy comparisons (HC).
See this image and copyright information in PMC

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