Fears Worth Testing Out: A Systematic Review of the Neural Mechanisms of Treatment Outcome for Anxiety-Related Disorders

Abstract

With the advent of human neuroimaging, researchers were drawn to the idea that by better understanding the human brain, more effective mental health interventions could be developed. It has been more than 20 years since the first functional magnetic resonance imaging (fMRI) studies were conducted to examine changes in brain activation with anxiety-related treatments and more than 60 studies have since been published in this vein. For the current review, we conduct a systematic review of this literature, focusing on adult studies using task-based fMRI to measure brain activation changes with pharmacologic or psychotherapy interventions for phobia, social anxiety disorder, panic disorder, generalized anxiety disorder, posttraumatic stress disorder, and obsessive-compulsive disorder. Neuroscientific theories of anxiety-related disorders and their treatment have focused on prefrontal-insula-amygdala networks. Treatment-related decreases in amygdala and/or anterior insula activation were identified as the most consistent finding across disorders, with the most consistent results reported for specific phobia. Directionality of change and specific regions implicated in the prefrontal cortex were inconsistent across studies. The potential importance for probing other networks and processes as mechanisms of anxiety treatment was recognized, such as striatal regions underlying inhibitory learning or reward responsivity. Future treatment-fMRI research related to anxiety disorders would benefit from larger sample sizes, use of more nuanced computational approaches, and increased focus on replication. There is continued promise that fMRI research will enhance our understanding of how treatments work and inform the evolution of more effective or personalized mental health treatment.

Keywords: Amygdala; Anxiety disorders; Cognitive-behavioral therapy; Exposure therapy; Functional MRI; Insula; OCD; PTSD; Pharmacotherapy; Prefrontal cortex; SSRI; Striatum.