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Neural correlates of anger expression in patients with PTSD.

ABSTRACT: Anger is a common and debilitating symptom of post-traumatic stress disorder (PTSD). Although studies have identified brain circuits underlying anger experience and expression in healthy individuals, how these circuits interact with trauma remains unclear. Here, we performed the first study examining the neural correlates of anger in patients with PTSD. Using a data-driven approach with resting-state fMRI, we identified two prefrontal regions whose overall functional connectivity was inversely associated with anger: the left anterior middle frontal gyrus (aMFG) and the right orbitofrontal cortex (OFC). We then used concurrent TMS-EEG to target the left aMFG parcel previously identified through fMRI, measuring its cortical excitability and causal connectivity to downstream areas. We found that low-anger PTSD patients exhibited enhanced excitability in the left aMFG and enhanced causal connectivity between this region and visual areas. Together, our results suggest that left aMFG activity may confer protection against the development of anger, and therefore may be an intriguing target for circuit-based interventions for anger in PTSD.

SUBMITTER: Eshel N

PROVIDER: S-EPMC8280145 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Neural correlates of anger expression in patients with PTSD.

Eshel Neir N Maron-Katz Adi A Wu Wei W Abu-Amara Duna D Marmar Charles R CR Etkin Amit A

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20210126 9

Anger is a common and debilitating symptom of post-traumatic stress disorder (PTSD). Although studies have identified brain circuits underlying anger experience and expression in healthy individuals, how these circuits interact with trauma remains unclear. Here, we performed the first study examining the neural correlates of anger in patients with PTSD. Using a data-driven approach with resting-state fMRI, we identified two prefrontal regions whose overall functional connectivity was inversely a ...[more]

PMID: 33500557

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Project description:Studies have examined sex differences in emotion processing in health and illness. However, it remains unclear how these neural processes may relate to individual differences in affective traits. We addressed this issue with a dataset of 970 subjects (508 women) curated from the Human Connectome Project. Participants were assessed with the NIH Toolbox Emotion Measures and fMRI while identifying negative facial emotion and neutral shape targets in alternating blocks. Imaging data were analyzed with published routines and the results were reported at a corrected threshold. Men scored similarly in Anger- but lower in Fear-Affect, as compared to women. Men as compared with women engaged the occipital-temporal visual cortex, retrosplenial cortex (RSC), and both anterior and posterior cingulate cortex to a greater extent during face versus shape identification. Women relative to men engaged higher activation of bilateral middle frontal cortex. In regional brain responses to face versus shape identification, men relative to women showed more significant modulations by both Anger- and Fear- Affect traits. The left RSC and right RSC/precuneus each demonstrated activities during face vs. shape identification in negative correlation with Anger- and Fear- Affect scores in men only. Anger affect was positively correlated with prolonged RT in identifying face vs. shape target in men but not women. In contrast, women relative to men showed higher Fear-Affect score and higher activation in the right middle frontal cortex, which was more strongly correlated with prolonged RT during face vs. shape identification. Together, men and women with higher Fear-Affect demonstrated lower accuracy in identifying negative facial emotion versus neutral shape target, a relationship mediated by activity of the RSC. These findings add to the literature of sex and trait individual differences in emotion processing and may help research of sex-shared and sex-specific behavioral and neural markers of emotional disorders.

Project description:BackgroundNeural alterations related to treatment outcome in patients with both post-traumatic stress disorder (PTSD) and comorbid personality disorder are unknown. Here we describe the protocol for a neuroimaging study of treatment of patients with PTSD and comorbid borderline (BPD) or cluster C (CPD) personality disorder traits. Our specific aims are to 1) investigate treatment-induced neural alterations, 2) predict treatment outcome using structural and functional magnetic resonance imaging (MRI) and 3) study neural alterations associated with BPD and CPD in PTSD patients. We hypothesize that 1) all treatment conditions are associated with normalization of limbic and prefrontal brain activity and hyperconnectivity in resting-state brain networks, with additional normalization of task-related activation in emotion regulation brain areas in the patients who receive trauma-focused therapy and personality disorder treatment; 2) Baseline task-related activation, together with structural brain measures and clinical variables predict treatment outcome; 3) dysfunction in task-related activation and resting-state connectivity of emotion regulation areas is comparable in PTSD patients with BPD or CPD, with a hypoconnected central executive network in patients with PTSD+BPD.MethodsWe aim to include pre- and post-treatment 3 T-MRI scans in 40 patients with PTSD and (sub) clinical comorbid BPD or CPD. With an expected attrition rate of 50%, at least 80 patients will be scanned before treatment. MRI scans for 30 matched healthy controls will additionally be acquired. Patients with PTSD and BPD were randomized to either EMDR-only or EMDR combined with Dialectical Behaviour Therapy. Patients with PTSD and CPD were randomized to Imaginary Rescripting (ImRs) or to ImRs combined with Schema Focused Therapy. The scan protocol consists of a T1-weighted structural scan, resting state fMRI, task-based fMRI during an emotional face task and multi-shell diffusion weighted images. For data analysis, multivariate mixed-models, regression analyses and machine learning models will be used.DiscussionThis study is one of the first to use neuroimaging measures to predict and better understand treatment response in patients with PTSD and comorbid personality disorders. A heterogeneous, naturalistic sample will be included, ensuring generalizability to a broad group of treatment seeking PTSD patients.Trial registrationClinical Trials, NCT03833453 & NCT03833531 . Retrospectively registered, February 2019.

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Neural correlates of anger expression in patients with PTSD.

Publications

Neural correlates of anger expression in patients with PTSD.

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