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Anxiety is a core human emotion but can become pathologically dysregulated. We used functional magnetic resonance imaging (fMRI) neurofeedback (NF) to noninvasively alter patterns of brain connectivity, as measured by resting-state fMRI, and to reduce contamination anxiety. Activity of a region of the orbitofrontal cortex associated with contamination anxiety was measured in real time and provided to subjects with significant but subclinical anxiety as a NF signal, permitting them to learn to modulate the target brain region. NF altered network connectivity of brain regions involved in anxiety regulation: subjects exhibited reduced resting-state connectivity in limbic circuitry and increased connectivity in the dorsolateral prefrontal cortex. NF has been shown to alter brain connectivity in other contexts, but it has been unclear whether these changes persist; critically, we observed changes in connectivity several days after the completion of NF training, demonstrating that such training can lead to lasting modifications of brain functional architecture. Training also increased subjects' control over contamination anxiety several days after the completion of NF training. Changes in resting-state connectivity in the target orbitofrontal region correlated with these improvements in anxiety. Matched subjects undergoing a sham feedback control task showed neither a reorganization of resting-state functional connectivity nor an improvement in anxiety. These data suggest that NF can enable enhanced control over anxiety by persistently reorganizing relevant brain networks and thus support the potential of NF as a clinically useful therapy.

Orbitofrontal cortex neurofeedback produces lasting changes in contamination anxiety and resting-state connectivity