Subgenual Cingulum Microstructure Supports Control of Emotional Conflict.

Paul A Keedwell,Amie N Doidge,Natalia Lawrence,Andrew D Lawrence,Marcel Meyer,Derek K Jones

doi:10.1093/cercor/bhw030

Abstract

Major depressive disorder (MDD) is associated with specific difficulties in attentional disengagement from negatively valenced material. Diffusion MRI studies have demonstrated altered white matter microstructure in the subgenual cingulum bundle (CB) in individuals with MDD, though the functional significance of these alterations has not been examined formally. This study explored whether individual differences in selective attention to negatively valenced stimuli are related to interindividual differences in subgenual CB microstructure. Forty-six individuals (21 with remitted MDD, 25 never depressed) completed an emotional Stroop task, using happy and angry distractor faces overlaid by pleasant or unpleasant target words and a control gender-based Stroop task. CBs were reconstructed in 38 individuals using diffusion-weighted imaging and tractography, and mean fractional anisotropy (FA) computed for the subgenual, retrosplenial, and parahippocampal subdivisions. No significant correlations were found between FA and performance in the control gender-based Stroop task in any CB region. However, the degree of interference produced by angry face distractors on time to identify pleasant words (emotional conflict) correlated selectively with FA in the subgenual CB (r = −0.53; P = 0.01). Higher FA was associated with reduced interference, irrespective of a diagnosis of MDD, suggesting that subgenual CB microstructure is functionally relevant for regulating attentional bias toward negative interpersonal stimuli.

Highlights

Network models for mental illness propose that genetic and environmental risk factors produce alterations in corticolimbic circuit function that induce susceptibility to psychopathology (Drevets et al 2008; Kim et al 2011; Buckholtz and MeyerLindenberg 2012)
RD and no history of MDD (ND) groups were well matched for age and estimated verbal IQ; the groups were still matched on these parameters for the final sample (N = 34) used for the analyses pertaining to fractional anisotropy (FA) in cingulum bundle (CB)
Between Group Comparisons of Stroop Effects For the emotional Stroop task, there was a significant congruency × group interaction (F1, 41 = 5.86, P = 0.02, η2 = 0.13). When this interaction was plotted, it was apparent that RD individuals performed better on incongruent word-face trials than ND individuals (t(41) = 2.18, P = 0.04, 95% CI 4.03; 104.21, Hedges’ gs = 0.66), with no significant difference emerging between these groups for congruent trials (t(41) = 1.51, P = 0.14, 95% CI −9.02; 63.01, Hedges’ gs = 0.45)

Summary

Introduction

Network models for mental illness propose that genetic and environmental risk factors produce alterations in corticolimbic circuit function that induce susceptibility to psychopathology (Drevets et al 2008; Kim et al 2011; Buckholtz and MeyerLindenberg 2012). Risk for depression has been linked to altered functioning of a neural circuit encompassing the amygdala and regions of the ventral-rostral ( pregenual– subgenual) anterior cingulate cortex (ACC) (Pezawas et al 2005; Holmes et al 2012). The cingulum bundle (CB) is a major white matter pathway linking cortical regions implicated in cognitive control with limbic regions involved in emotion (Heilbronner and Haber 2014). It extends through frontal, parietal, and temporal cortices, connecting the cingulate cortex with proximal and distal cortical. The subgenual CB links ventral and rostral ACC with the amygdala (Heilbronner and Haber 2014) and may be uniquely placed to play an integrative role in emotion–cognition interactions

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Conclusion