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.

The therapeutic alliance has long been recognized as an important component of successful psychotherapy for adults; research has established robust links to outcome. Until recently, however, research on the alliance between youth and their therapists has been sparse. The present review synthesizes the existing findings regarding the youth alliance and utilizes the adult alliance literature and the child and adolescent developmental literatures to suggest future avenues of research. Weak alliance was found to predict premature termination, and strong alliance predicted symptom reduction, with some support for differential effects of the youth-therapist and parent-therapist alliances. In addition, the youth alliance is moderated by several patient and therapist characteristics, including the particular problems of patients and the interpersonal skills of therapists. The field has yet to coalesce around a single definition of the youth alliance, however, making it difficult to assess research results. Adult models of the alliance continue to be used heuristically despite some evidence that the alliance operates differently for youth. Tightening the operational definition of the youth alliance and addressing methodological issues will be essential in future efforts to understand how the alliance develops and what role it may play in the treatment process for youth.

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.

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.

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.

Background: Previous studies indicate that youth with posttraumatic stress disorder (PTSD) have abnormal activation in brain regions important for emotion processing. It is unknown whether symptom improvement is accompanied by normative changes in these regions. This study identified neural changes associated with symptom improvement with the long-term goal of identifying malleable targets for interventions.Methods: A total of 80 functional magnetic resonance imaging (fMRI) scans were collected, including 20 adolescents with PTSD (ages 9-17) and 20 age-and sex-matched healthy control subjects, each scanned before and after a 5-month period. Trauma-focused cognitive behavioral therapy was provided to the PTSD group to ensure improvement in symptoms. Whole brain voxelwise activation and region of interest analyses of facial expression task data were conducted to identify abnormalities in the PTSD group versus HC at baseline (BL), and neural changes correlated with symptom improvement from BL to EOS of study (EOS).Results: At BL, the PTSD group had abnormally elevated activation in the cingulate cortex, hippocampus, amygdala, and medial frontal cortex compared to HC. From BL to EOS, a PTSD symptoms improved an average of 39%. Longitudinal improvement in symptoms of PTSD was associated with decreasing activation in posterior cingulate, mid-cingulate, and hippocampus, while improvement in dissociative symptoms was correlated with decreasing activation in the amygdala.Conclusions: Abnormalities in emotion-processing brain networks in youth with PTSD normalize when symptoms improve, demonstrating neural plasticity of these regions in young patients and the importance of early intervention.

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.

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.