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B01: Neurobehavioral effects of repetitive prefrontal transcranial direct current stimulation (tDCS) on pathological aggression

TDCS will be used as an interventional tool to decrease aggression. Using a simultaneous tDCS – fMRI approach, the project aims to enhance cognitive control by repeated prefrontal brain stimulation, investigating its effect on aggression. In addition to gauging tDCS responsivity, identifying the role of individual factors such as genetic profiles in aggression will be a particular focus of this project. By examining brain activity at multiple time points (e.g., before, during multiple stimulation sessions and after tDCS), it will add to the understanding of mechanisms underlying neural tDCS effects and help to identify individual factors that predict responsiveness to the stimulation. To determine the therapeutic potential, we will include psychiatric patients with substance use problems, a group of criminal, violent offenders, and healthy matched controls.

Contributors


Andreas Reif

Andreas Reif is a German Psychiatrist, who received his training at the University Hospital Würzburg, where he also did his residency and later on became Vice Chair. In 2014, he took over the position of Chair of the Department of Psychiatry, Psychosomatic Medicine and Psychotherapy at the University Medical Center Frankfurt, where he is also full professor. ARs clinical and research interests include affective disorders (TRD, bipolar disorder, suicidality) and adult ADHD; his research is translational in nature and revolves around the ideas of precision psychiatry, i.e. identifying the best therapy at the exact time for a given individual patient. He has published more than 650 original papers and reviews, also in the most prestigious journals such a the New England Journal of Medicine, Lancet and Science, and has an h² index of 97. He is an internationally renowned speaker and active in several learned societies, especially the German Psychiatric Association (DGPPN), where he is an executive board member, as well as ECNP, where he is president elect. Also, he is involved in several clinical guidelines and outreach programs.

Carmen Weidler

Carmen Weidler is a neuroscientist whose research primarily focuses on the neural underpinnings of aggressive and impulsive behavior. Her work explores the effects of brain stimulation techniques, such as transcranial direct current stimulation (tDCS), on behavioral and neural correlates of aggression and impulsivity in violent criminal offenders, patients with mental disorders, and healthy individuals. The primary aim of her research is to achieve a better understanding of the individual and methodological factors that enhance the efficacy of tDCS.

Publications


A mechanism-based group psychotherapy approach to aggressive behavior (MAAP) in borderline personality disorder: a multicenter randomized controlled clinical trial

High levels of trait anger and aggressive behavior are common and problematic phenomena in patients with borderline personality disorder (BPD). In BPD, patterns of reactive aggression often lead to functional impairment affecting important areas of life. Despite the high burden on individuals and their social environment, there are no specific, cost-effective treatments to reduce aggression in BPD. In previous studies, we and others have been able to infer specific biobehavioral mechanisms underlying patterns of reactive aggression in BPD that can be used as potential treatment targets. To address this, we developed a mechanism-based anti-aggression psychotherapy (MAAP) for the group setting that specifically targets the biobehavioral mechanisms underlying outward-directed aggression in BPD. A previously conducted proof-of-concept study had suggested beneficial effects for this neglected group of patients. In this multicenter, confirmatory, randomized-controlled-clinical-trial, MAAP, which consists of multifaceted, evidence-based treatment elements adapted from other sophisticated treatment programs such as Dialectical Behavior Therapy and Mentalization-Based Treatment, is tested for efficacy against a non-specific supportive psychotherapy (NSSP) program focusing on non-specific general factors of psychotherapy at seven different sites in Germany. Both treatment arms, based on one individual and 13 group therapeutic sessions (1.5 h per session, twice a week), are delivered over a period of 7–10 weeks. A total of N = 186 patients will be recruited, half of whom will be cluster-randomized to MAAP. Outcomes are assessed at baseline, immediately, and 4, 12, 20, and 24 weeks post-treatment using ecological momentary assessment, clinical interviews, questionnaires, and online tasks. If proven superior, MAAP can be incorporated into standard psychiatric care, filling a critical gap in the current therapeutic landscape by offering a structured, cost-effective, and evidence-based treatment that directly targets the biobehavioral mechanisms underlying reactive aggression in BPD. By potentially improving clinical outcomes and reducing the burden of reactive aggression in BPD, MAAP could be beneficial for both individuals and their social environments. The study’s large, multicenter design enhances the generalizability of the results, making them more relevant for broader clinical applications.

Targeting aggression with prefrontal high-definition transcranial direct current stimulation

Heightened aggression is associated with behavioural and neural deficits in inhibitory control. Transcranial direct current stimulation (tDCS) shows promise in facilitating inhibitory control and reducing aggression. However, the mixed effects and widespread electric fields of tDCS warrant more precise stimulation methods. High-definition tDCS (HD-tDCS) may enhance focality to target the right inferior frontal gyrus (rIFG), a key region in inhibitory control. In a double-blind and sham-controlled study, we investigated behavioral and neural differences between anodal and sham HD-tDCS in a subsequent Taylor Aggression Paradigm (TAP). Anodal HD-tDCS was applied at 1.5 mA for 20 min over the rIFG. Reference electrodes were located at TP8, PZ, FC3, and FP1. 41 healthy male participants were randomly assigned to either anodal (19) or sham (22) HD-tDCS and completed the TAP during functional magnetic resonance imaging. Anodal HD-tDCS did not directly reduce aggression; however, the stimulation weakened the effect of provocation on aggressive behaviour. Imaging results indicated that anodal HD-tDCS was associated with a positive provocation-related increase of bilateral parietal lobule (IPL) activation. Taken together, behavioural and neuroimaging findings suggest that anodal rIFG stimulation may engage the inhibitory control network as reflected in reduced responsiveness to provocation and increased activation during provocation.