Neural basis of negative future mental imagery-based simulation in the bipolar disorder spectrum

Objectives Dysfunctional mental imagery-based simulations of emotional future events (episodic future simulation) - can contribute to emotional dysregulation in the bipolar disorder spectrum (BPDS). For example, vividly imaging social encounters having a disastrous outcome can trigger low mood. However, episodic future simulation may be perceptually modified to reduce their emotional intensity, which may in turn reduce BPDS mood instability. This study investigates the neural bases of perceptual and emotional characteristics of negative episodic future simulation in BPDS, and of perceptually manipulating such imagery. Methods Euthymic participants with BPDS (N=20) and healthy controls (HC, N=17) underwent an fMRI scan whilst generating, then perceptually modifying, negative episodic future imagery, and during rest. Results Negative episodic future imagery were rated as significantly more real and unpleasant in the BPDS compared to HC group. Critically, perceptual manipulation of such imagery reduced ratings in the BPDS group to HC levels. Whole-brain analyses of task-based neural activity revealed greater activation in networks including right frontal pole, middle and inferior frontal gyrus and insula during episodic future simulation in BPSD versus HC. BPDS participants showed greater intrinsic resting state functional connectivity within the default mode network than HC participants. Conclusions Findingss: uggest dysfunctional episodic future simulation circuitry across default mode network, fronto-parietal and fronto-insular areas may represent a neural mechanism via which mental imagery amplifies emotion in BPDS. Perceptual modifications to dampen such imagery successfully abolished subjective and neural differences between groups, indicating promise as an intervention tool targeting mood instability.