Defining focal brain stimulation targets for PTSD using neuroimaging

• Authors: Sanne van Rooij, Emory University; Lauren M Sippel, U.S. Department of Veterans Affairs; William McDonald, Emory University; Paul E Holtzheimer, U.S. Department of Veterans Affairs
• Journal Title: DEPRESSION AND ANXIETY
• Volume: Volume 38, Number 7
• Publisher: WILEY | 2021-07-01, Pages 768-785
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/da.23159
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: Social Sciences; Science & Technology; Life Sciences & Biomedicine; Psychology, Clinical; Psychiatry; Psychology; functional connectivity; functional magnetic resonance imaging; neuromodulation; posttraumatic stress disorder; predictors; treatment; POSTTRAUMATIC-STRESS-DISORDER; TRANSCRANIAL MAGNETIC STIMULATION; SMALLER HIPPOCAMPAL VOLUME; COGNITIVE-BEHAVIORAL THERAPY; TREATMENT RESPONSE; AMYGDALA RESPONSE; PREFRONTAL CORTEX; FEAR EXTINCTION; ACTIVATION; DEPRESSION

Abstract

Introduction: Focal brain stimulation has potential as a treatment for posttraumatic stress disorder (PTSD). In this review, we aim to inform selection of focal brain stimulation targets for treating PTSD by examining studies of the functional neuroanatomy of PTSD and treatment response. We first briefly review data on brain stimulation interventions for PTSD. Although published data suggest good efficacy overall, the neurobiological rationale for each stimulation target is not always clear. Methods: Therefore, we assess pre- and post-treatment (predominantly psychotherapy) functional neuroimaging studies in PTSD to determine which brain changes seem critical to treatment response. Results of these studies are presented within a previously proposed functional neural systems model of PTSD. Results: While not completely consistent, research suggests that downregulating the fear learning and threat and salience detection circuits (i.e., amygdala, dorsal anterior cingulate cortex and insula) and upregulating the emotion regulation and executive function and contextual processing circuits (i.e., prefrontal cortical regions and hippocampus) may mediate PTSD treatment response. Conclusion: This literature review provides some justification for current focal brain stimulation targets. However, the examination of treatment effects on neural networks is limited, and studies that include the stimulation targets are lacking. Further, additional targets, such as the cingulate, medial prefrontal cortex, and inferior parietal lobe, may also be worth investigation, especially when considering how to achieve network level changes. Additional research combining PTSD treatment with functional neuroimaging will help move the field forward by identifying and validating novel targets, providing better rationale for specific treatment parameters and personalizing treatment for PTSD.