PTSD Psychotherapy Outcome Predicted by Brain Activation During Emotional Reactivity and Regulation

Abstract

Objective Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but many patients will not respond. Brain functions governing treatment outcome are not well characterized. Here, we examined brain systems relevant to emotional reactivity and regulation, constructs thought to be central to PTSD and exposure therapy effects, to identify the functional traits of individuals most likely to benefit from treatment. Methods Individuals with PTSD underwent functional magnetic resonance imaging (fMRI) while completing three tasks assessing emotional reactivity and regulation. Participants were then randomized to immediate prolonged exposure treatment (N=36) or waitlist (N=30). A random subset of treatment-randomized individuals (N=17) underwent single-pulse transcranial magnetic stimulation (TMS) concurrent with fMRI to examine if predictive activation patterns reflect causal influence within circuits. Linear mixed effects modeling in line with the intent-to-treat principle was used to examine how baseline brain function moderated the treatment effect on PTSD symptoms. Results Individuals with larger treatment-related symptom reductions (compared to waitlist) showed at baseline: 1) greater dorsal prefrontal activation and 2) less left amygdala activation, both during emotion reactivity; 3) better inhibition of the left amygdala induced by single TMS pulses to the right dorsolateral prefrontal cortex; and 4) greater ventromedial prefrontal activation during emotional conflict regulation. Reappraisal-related activation was not a significant moderator of the treatment effect. Conclusions Capacity to benefit from prolonged exposure for PTSD is gated by the degree to which prefrontal resources are spontaneously engaged when superficially processing threat and adaptively mitigating emotional interference, but not when deliberately reducing negative emotionality.

Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man

“…Although the invasiveness of DBS is likely to mean that such treatments would be reserved for only the most intractable of cases, the use of TMS has been steadily increasing as a therapeutic tool in psychiatry. The mechanisms by which TMS might exert its effects to mediate symptom improvement in PTSD remain unclear; however, the concurrent combination of TMS with electroencephalography (EEG) or fMRI is becoming a powerful technology for identifying pathological changes in brain functional network connectivity and predicting the efficacy of the treatment 161,162 . The hope of using more targeted methodologies to modulate circuits remains.…”

Exposure-based therapy changes amygdala and hippocampus resting-state functional connectivity in patients with posttraumatic stress disorder

“…While considered an essential step in understanding the neural substrates of PE, the use of a waiting list as a control group can only provide a partial answer to the effects of PE on rsFC. As suggested by the Fonzo et al (2017), it remains unclear whether the observed post-treatment functional changes reflected a normalization of neural abnormalities or compensatory neural adaptations.…”

“…Psychotherapy research in posttraumatic stress disorder (PTSD) has recently begun using neuroimaging methods to assess structural (Helpman, Papini, et al, 2016) and functional (Fonzo, Goodkind, Oathes, Zaiko, Harvey, Peng, Weiss, Thompson, Zack, Lindley, et al, 2017; Helpman, Marin, et al, 2016) neural alterations of evidence-based treatments. Prolonged Exposure (PE) therapy is a relatively brief, highly structured, exposure-based treatment, considered to be effective in treating PTSD (Bradley, Greene, Russ, Dutra, & Westen, 2005).…”

Trauma Memory Processing in Posttraumatic Stress Disorder Psychotherapy: A Unifying Framework

“…However, another recent study did not find evidence of EN and DMN coactivation and inhibition of SN emotional reactivity; instead, the authors reported increased anterior prefrontal cortex activation only in a cognitive reappraisal task, not in emotional reactivity or conflict tasks, and only following prolonged exposure TMP, not for waitlist controls. This was associated with a reduction in hyperarousal symptoms but not reexperiencing or avoidance symptoms, as well as improved psychological well‐being (Fonzo et al., ). Moreover, TMP was associated with increased connectivity by the EN with the SN, leading to a reduction in the intensity of arousal and emotional reactivity (Fonzo et al., ).…”

“…This was associated with a reduction in hyperarousal symptoms but not reexperiencing or avoidance symptoms, as well as improved psychological well‐being (Fonzo et al., ). Moreover, TMP was associated with increased connectivity by the EN with the SN, leading to a reduction in the intensity of arousal and emotional reactivity (Fonzo et al., ). The anterior prefrontal cortex is involved simultaneously in attention to the external environment and internal processing and potentially serves a coordinating function for cognitive reappraisal and emotion regulation activities undertaken by the EN and DMN.…”