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Objective Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but a comprehensive, emotion-focused perspective on how psychotherapy impacts brain function is lacking. Here, we assess changes in brain function following prolonged exposure therapy across three emotional reactivity and regulation paradigms. Methods Individuals with PTSD underwent functional magnetic resonance imaging (fMRI) at rest and while completing three tasks assessing emotional reactivity and regulation. Individuals were then randomized to prolonged exposure treatment (N=36) or waitlist (N=30) and underwent a second scan approximately four weeks following the last treatment session or a comparable waiting period, respectively. Results Treatment-specific changes were observed only during cognitive reappraisal of negative images. Psychotherapy increased lateral frontopolar cortex activity and its connectivity with the ventromedial prefrontal cortex/ventral striatum. Greater increases in frontopolar activation were associated with improvement in hyperarousal symptoms and psychological well-being. The frontopolar cortex also displayed a greater variety of temporal resting state signal pattern changes following treatment. Using concurrent transcranial magnetic stimulation and fMRI in healthy participants, we demonstrate the lateral frontopolar cortex exerts downstream influence on the ventromedial prefrontal cortex/ventral striatum. Conclusions Changes in frontopolar function during deliberate regulation of negative affect is one key mechanism of adaptive psychotherapeutic change in PTSD. Given that: a) frontopolar connectivity with ventromedial regions during emotion regulation is enhanced by psychotherapy; and b) frontopolar cortex exerts downstream influence on ventromedial regions in healthy individuals, these findings inform a novel conceptualization of how psychotherapy works and identify a promising target for stimulation-based therapeutics.

BackgroundBoth major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are characterized by alterations in intrinsic functional connectivity. Here we investigated changes in intrinsic functional connectivity across these disorders as a function of cognitive behavioral therapy (CBT), an effective treatment in both disorders.Methods53 unmedicated right-handed participants were included in a longitudinal study. Patients were diagnosed with PTSD (n = 18) and MDD (n = 17) with a structured diagnostic interview and treated with 12 sessions of manualized CBT over a 12-week period. Patients received an MRI scan (Siemens 3 T Trio) before and after treatment. Longitudinal functional principal components analysis (LFPCA) was performed on functional connectivity of the bilateral amygdala with the fronto-parietal network. A matched healthy control group (n = 18) was also scanned twice for comparison.ResultsLFPCA identified four eigenimages or principal components (PCs) that contributed significantly to the longitudinal change in connectivity. The second PC differentiated CBT-treated patients from controls in having significantly increased connectivity of the amygdala with the fronto-parietal network following CBT.LimitationsAnalysis of CBT-induced amygdala connectivity changes was restricted to the a priori determined fronto-parietal network. Future studies are needed to determine the generalizability of these findings, given the small and predominantly female sample.ConclusionWe found evidence for the hypothesis that CBT treatment is associated with changes in connectivity between the amygdala and the fronto-parietal network. CBT may work by strengthening connections between the amygdala and brain regions that are involved in cognitive control, potentially providing enhanced top-down control of affective processes that are dysregulated in both MDD and PTSD.

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Many individuals in need of mental health services do not currently receive care. Scalable programs are needed to reduce the burden of mental illness among those without access to existing providers. Digital interventions present an avenue for increasing the reach of mental health services. These interventions often rely on paraprofessionals, or coaches, to support the treatment. Although existing programs hold immense promise, providers must ensure that treatments are delivered with high fidelity and adherence to the treatment model. In this paper, we first highlight the tension between the scalability and fidelity of mental health services. We then describe the design and implementation of a peer-to-peer coach training program to support a digital mental health intervention for undergraduate students within a university setting. We specifically note strategies for emphasizing fidelity within our scalable framework, including principles of learning theory and competency-based supervision. Finally, we discuss future applications of this work, including the potential adaptability of our model for use within other contexts.