RT Journal Article SR Electronic T1 Real-time functional connectivity-based neurofeedback of amygdala-frontal pathways reduces anxiety JF bioRxiv FD Cold Spring Harbor Laboratory SP 308924 DO 10.1101/308924 A1 Zhiying Zhao A1 Shuxia Yao A1 Keshuang Li A1 Cornelia Sindermann A1 Feng Zhou A1 Weihua Zhao A1 Jianfu Li A1 Michael Lührs A1 Rainer Goebel A1 Keith M. Kendrick A1 Benjamin Becker YR 2018 UL http://biorxiv.org/content/early/2018/04/28/308924.abstract AB Deficient emotion regulation and exaggerated anxiety represent a major transdiagnostic psychopathological marker. On the neural level these deficits have been closely linked to impaired, yet treatment-sensitive, prefrontal regulatory control over the amygdala. Gaining direct control over these pathways could therefore provide an innovative and promising strategy to regulate exaggerated anxiety. To this end the current proof-of-concept study evaluated the feasibility, functional relevance and maintenance of a novel connectivity-informed real-time fMRI neurofeedback training. In a randomized within-subject sham-controlled design high anxious subjects (n = 26) underwent real-time fMRI-guided training to enhance connectivity between the ventrolateral prefrontal cortex (vlPFC) and the amygdala (target pathway) during threat exposure. Maintenance of regulatory control was assessed after three days and in the absence of feedback. Training-induced changes in functional connectivity of the target pathway and anxiety ratings served as primary outcomes. Training of the target, yet not the sham-control, pathway significantly increased amygdala-vlPFC connectivity and decreased subjective anxiety levels. On the individual level stronger connectivity increases were significantly associated with anxiety reduction. At follow-up, volitional control over the target pathway and decreased anxiety level were maintained in the absence of feedback. The present results demonstrate for the first time that successful self-regulation of amygdala-prefrontal top-down regulatory circuits may represent a novel strategy to control anxiety. As such, the present findings underscore both the critical contribution of amygdala-prefrontal circuits to emotion regulation and the therapeutic potential of connectivity-informed real-time neurofeedback.