Effects of tDCS during inhibitory control training on performance and PTSD, aggression and anxiety symptoms: a randomized-controlled trial in a military sample

Abstract

Background Post-traumatic stress disorder (PTSD), anxiety, and impulsive aggression are linked to transdiagnostic neurocognitive deficits. This includes impaired inhibitory control over inappropriate responses. Prior studies showed that inhibitory control can be improved by modulating the right inferior frontal gyrus (IFG) with transcranial direct current stimulation (tDCS) in combination with inhibitory control training. However, its clinical potential remains unclear. We therefore aimed to replicate a tDCS-enhanced inhibitory control training in a clinical sample and test whether this reduces stress-related mental health symptoms. Methods In a preregistered double-blind randomized-controlled trial, 100 active-duty military personnel and post-active veterans with PTSD, anxiety, or impulsive aggression symptoms underwent a 5-session intervention where a stop-signal response inhibition training was combined with anodal tDCS over the right IFG for 20 min at 1.25 mA. Inhibitory control was evaluated with the emotional go/no-go task and implicit association test. Stress-related symptoms were assessed by self-report at baseline, post-intervention, and after 3-months and 1-year follow-ups. Results Active relative to sham tDCS neither influenced performance during inhibitory control training nor on assessment tasks, and did also not significantly influence self-reported symptoms of PTSD, anxiety, impulsive aggression, or depression at post-assessment or follow-up. Conclusions Our results do not support the idea that anodal tDCS over the right IFG at 1.25 mA enhances response inhibition training in a clinical sample, or that this tDCS-training combination can reduce stress-related symptoms. Applying different tDCS parameters or combining tDCS with more challenging tasks might provide better conditions to modulate cognitive functioning and stress-related symptoms.

Right inferior frontal gyrus and ventromedial prefrontal activation during response inhibition is implicated in the development of PTSD symptoms

“…Similar findings were shown during an intrusive memory suppression task with trauma-exposed civilians, where PTSD- individuals showed reduced IFG-parahippocampal functional connectivity but not PTSD+ individuals, supporting a potential disruption of the regulation signal that helps to control activation of unwanted memories in individuals with PTSD (Mary et al, 2020 ). Importantly, there is evidence that rIFG activation and connectivity with other fear-related brain regions can improve with trauma-focused treatment (Rousseau et al, 2019 ) and may improve emotion and fear regulation when targeted using transcranial direct current stimulation (tDCS) (Herrmann, Beier, Simons, & Polak, 2016 ), although findings are mixed (Smits, Geuze, Schutter, van Honk, & Gladwin, 2021 ). A recent resilience model of PTSD has been suggested whereby post-trauma biomarkers of cognitive control, specifically dorsolateral PFC structural integrity, promotes resilience (Roeckner, Oliver, Lebois, van Rooij, & Stevens, 2021 ).…”

Neuromodulation Treatments of Pathological Anxiety in Anxiety Disorders, Stressor-Related Disorders, and Major Depressive Disorder: A Dimensional Systematic Review and Meta-Analysis

“…Detailed evaluation of the risk of bias is reported in Supplementary Table 1. The majority of studies were considered at high risk of bias, both for the studies included for primary outcome analysis ( studies applied and reported appropriate randomization (48,50,52,57,63,66). Overall, according to the GRADE guidelines (39), evidence from this study was considered of moderate quality.…”

“…First despite performing an extensive search of literature databases and applying PRISMA recommendations, a limited number of studies were included, with relatively small sample sizes [except for two studies measuring disorder-specific symptoms; (63,66)]. Second, the primary outcome of the meta-analysis (generic anxiety scales results) was the explicit primary outcome in only 5/19 of the studies included.…”

Non‐invasive neuromodulation can reduce aggressive behaviors in humans: A critical perspective

“…Furthermore, many studies have enrolled male participants only, making it impossible to investigate potential gender effects [88,90,94,96]. Further methodological limitations concern the single tDCS sessions and absence of follow-up measures [30,33,39,41,46,48,52,88]; indeed, given that the literature focuses on the acute effects of the stimulation (i.e., immediately after the stimulation), no evidence is available for the long-term effects.…”

“…Smits et al [90] found a null effect of tDCS on aggressiveness. Authors recruited a military sample with PTSD or impulsive aggression and performed a‐tDCS stimulation over the right Inferior Frontal Gyrus (IFG) coupled with inhibitory control training.…”