Amygdala and Insula Connectivity Changes Following Psychotherapy for Posttraumatic Stress Disorder: A Randomized Clinical Trial.

BACKGROUND: Exposure-based psychotherapy is a first-line treatment for posttraumatic stress disorder (PTSD), but its mechanisms are poorly understood. Functional brain connectivity is a promising metric for identifying treatment mechanisms and biosignatures of therapeutic response. To this end, we assessed amygdala and insula treatment-related connectivity changes and their relationship to PTSD symptom improvements. METHODS: Individuals with a primary PTSD diagnosis (N = 66) participated in a randomized clinical trial of prolonged exposure therapy (n = 36) versus treatment waiting list (n = 30). Task-free functional magnetic resonance imaging was completed prior to randomization and 1 month following cessation of treatment/waiting list. Whole-brain blood oxygenation level-dependent responses were acquired. Intrinsic connectivity was assessed by subregion in the amygdala and insula, limbic structures key to the disorder pathophysiology. Dynamic causal modeling assessed evidence for effective connectivity changes in select nodes informed by intrinsic connectivity findings. RESULTS: The amygdala and insula displayed widespread patterns of primarily subregion-uniform intrinsic connectivity change, including increased connectivity between the amygdala and insula; increased connectivity of both regions with the ventral prefrontal cortex and frontopolar and sensory cortices; and decreased connectivity of both regions with the left frontoparietal nodes of the executive control network. Larger decreases in amygdala-frontal connectivity and insula-parietal connectivity were associated with larger PTSD symptom reductions. Dynamic causal modeling evidence suggested that treatment decreased left frontal inhibition of the left amygdala, and larger decreases were associated with larger symptom reductions. CONCLUSIONS: PTSD psychotherapy adaptively attenuates functional interactions between frontoparietal and limbic brain circuitry at rest, which may reflect a potential mechanism or biosignature of recovery.

Selective Effects of Psychotherapy on Frontopolar Cortical Function in PTSD.

OBJECTIVE: Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but a comprehensive, emotion-focused perspective on how psychotherapy affects brain function is lacking. The authors assessed changes in brain function after prolonged exposure therapy across three emotional reactivity and regulation paradigms. METHOD: Individuals with PTSD underwent functional MRI (fMRI) at rest and while completing three tasks assessing emotional reactivity and regulation. Individuals were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30) and underwent a second scan approximately 4 weeks after 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 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 after treatment. Concurrent transcranial magnetic stimulation and fMRI in healthy participants demonstrated that 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 frontopolar connectivity with ventromedial regions during emotion regulation is enhanced by psychotherapy and that the frontopolar cortex exerts downstream influence on ventromedial regions in healthy individuals, these findings inform a novel conceptualization of how psychotherapy works, and they identify a promising target for stimulation-based therapeutics.

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

OBJECTIVE: Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but many patients do not respond. Brain functions governing treatment outcome are not well characterized. The authors examined brain systems relevant to emotional reactivity and regulation, constructs that are thought to be central to PTSD and exposure therapy effects, to identify the functional traits of individuals most likely to benefit from treatment. METHOD: Individuals with PTSD underwent functional MRI (fMRI) while completing three tasks assessing emotional reactivity and regulation. Participants were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30). A random subset of the prolonged exposure group (N=17) underwent single-pulse transcranial magnetic stimulation (TMS) concurrent with fMRI to examine whether 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 effect of treatment on PTSD symptoms. RESULTS: At baseline, individuals with larger treatment-related symptom reductions (compared with the waiting list condition) demonstrated 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/ventral striatal activation during emotional conflict regulation. Reappraisal-related activation was not a significant moderator of the treatment effect. CONCLUSIONS: Capacity to benefit from prolonged exposure in 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.

Attachment history as a moderator of the alliance outcome relationship in adolescents.

The role of the alliance in predicting treatment outcome is robust and long established. However, much less attention has been paid to mechanisms of change, including moderators, particularly for youth. This study examined the moderating role of pretreatment adolescent-caregiver attachment and its impact on the working alliance-treatment outcome relationship. One hundred adolescents and young adults with primary substance dependence disorders were treated at a residential facility, with a cognitive-behavioral emphasis. The working alliance and clinical symptoms were measured at regular intervals throughout treatment. A moderator hypothesis was tested using a path analytic approach. Findings suggested that attachment to the primary caregiver moderated the impact of the working alliance on treatment outcome, such that for youth with the poorest attachment history, working alliance had a stronger relationship with outcome. Conversely, for those with the strongest attachment histories, alliance was not a significant predictor of symptom reduction. This finding may help elucidate alliance-related mechanisms of change, lending support for theories of corrective emotional experience as one function of the working alliance in youth psychotherapy.

Conducting research and collaborating with researchers: the experience of clinicians in a residential treatment center.

This paper describes the experience of clinicians in conducting research and collaborating with academic researchers. As part of clinical routine of a residential program for adolescent substance abusers, empirical data have been collected to assess client's needs before and after treatment, improve clinical practice, and identify barriers to change. Some of the challenges faced and the benefits learned in conducting these studies are presented. In addition to highlighting the convergence of research interests between clinicians and academicians, the conclusion offers general recommendations to foster these partnerships and solidify the scientific-practitioner model.

Helpful and hindering events in psychotherapy: a practice research network study.

This paper presents the findings of a psychotherapy process study conducted within the Pennsylvania Psychological Association Practice Research Network (PPA-PRN). The investigation was the product of a long-term collaborative effort, both in terms of the study design and implementation, between experienced clinicians of various theoretical orientations and full-time psychotherapy researchers. Based on a relatively large sample of clients seen in independent practice settings, close to 1,500 therapeutic events (described by clients and therapists as being particularly helpful or hindering) were collected. These events were coded by three independent observers using a therapy content analysis system. Among the findings, both clients and therapists perceived the fostering of self-awareness as being particularly helpful. The results also point to the importance of paying careful attention to the therapeutic alliance and other significant interpersonal relationships. The merits and difficulties of conducting scientifically rigorous and clinically relevant studies in naturalistic contexts are also discussed.