Research ArticlePsychiatry

Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder

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Science Translational Medicine  03 Apr 2019:
Vol. 11, Issue 486, eaal3236
DOI: 10.1126/scitranslmed.aal3236

PTSD’s secrets hidden in a VAN

Post-traumatic stress disorder (PTSD) is a severe psychiatric illness. Psychotherapy is the only effective treatment for PTSD but only works in a portion of patients. Etkin and colleagues now report a neuroimaging and behavioral signature in a subgroup of PTSD patients who failed to respond to psychotherapy. This signature was associated with impairments in fMRI connectivity in the brain’s ventral attention network and a deficit on a word list learning task. Use of noninvasive brain stimulation in combination with neuroimaging identified a brain location in which network connectivity correlated with the effects of stimulation. This work may help to define a target for future noninvasive brain stimulation approaches for treating patients with PTSD who are refractory to psychotherapy.


A mechanistic understanding of the pathology of psychiatric disorders has been hampered by extensive heterogeneity in biology, symptoms, and behavior within diagnostic categories that are defined subjectively. We investigated whether leveraging individual differences in information-processing impairments in patients with post-traumatic stress disorder (PTSD) could reveal phenotypes within the disorder. We found that a subgroup of patients with PTSD from two independent cohorts displayed both aberrant functional connectivity within the ventral attention network (VAN) as revealed by functional magnetic resonance imaging (fMRI) neuroimaging and impaired verbal memory on a word list learning task. This combined phenotype was not associated with differences in symptoms or comorbidities, but nonetheless could be used to predict a poor response to psychotherapy, the best-validated treatment for PTSD. Using concurrent focal noninvasive transcranial magnetic stimulation and electroencephalography, we then identified alterations in neural signal flow in the VAN that were evoked by direct stimulation of that network. These alterations were associated with individual differences in functional fMRI connectivity within the VAN. Our findings define specific neurobiological mechanisms in a subgroup of patients with PTSD that could contribute to the poor response to psychotherapy.

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