Repeated Sessions of Transcranial Direct Current Stimulation on Adolescents With Autism Spectrum Disorder: Study Protocol for a Randomized, Double-Blind, and Sham-Controlled Clinical Trial

Abstract

Background: Social–emotional difficulties are a core symptom of autism spectrum disorder (ASD). Accordingly, individuals with ASD have problems with social cognition such as recognizing emotions from other peoples' faces. Various results from functional magnetic resonance imaging and electroencephalography studies as well as eye-tracking data reveal a neurophysiological basis of these deficits by linking them to abnormal brain activity. Thus, an intervention targeting the neural origin of ASD impairments seems warranted. A safe method able to influence neural activity is transcranial direct current stimulation (tDCS). This non-invasive brain stimulation method has already demonstrated promising results in several neuropsychiatric disorders in adults and children. The aim of this project is to investigate the effects of tDCS on ASD symptoms and their neural correlates in children and adolescents with ASD.Method: This study is designed as a double-blind, randomized, and sham-controlled trial with a target sample size of 20 male participants (aged 12–17 years) diagnosed with ASD. Before randomization, the participants will be stratified into comorbid depression, comorbid ADHS/conduct disorder, or no-comorbidity groups. The intervention phase comprises 10 sessions of anodal or sham tDCS applied over the left prefrontal cortex within 2 consecutive weeks. To engage the targeted brain regions, participants will perform a social cognition training during the stimulation. TDCS-induced effects on ASD symptoms and involved neural circuits will be investigated through psychological, neurophysiological, imaging, and behavioral data at pre- and post-measurements. Tolerability will be evaluated using a standardized questionnaire. Follow-up assessments 1 and 6 months after the intervention will examine long-lasting effects.Discussion: The results of this study will provide insights into the changeability of social impairments in ASD by investigating social and emotional abilities on different modalities following repeated sessions of anodal tDCS with an intra-simulation training. Furthermore, this trial will elucidate the tolerability and the potential of tDCS as a new treatment approach for ASD in adolescents.Clinical Trial Registration: The study is ongoing and has been registered in the German Registry of Clinical Trials (DRKS00017505) on 02/07/2019.

Brain Stimulation for Emotion Regulation in Adolescents With Psychiatric Disorders: Study Protocol for a Clinical-Transdiagnostical, Randomized, Triple-Blinded and Sham-Controlled Neurotherapeutic Trial

“…Single-subject analysis of the fMRI data will be conducted using the general linear model (GLM) as implemented in SPM12. The conditions will be modeled as previously described for the eSTROOP ( 120 ), e-nBACK ( 124 ) and the ERT [similar to ( 123 )]. Image-derived movement estimates and surrogates of physiological artifacts (heartbeat, breathing) will be used as covariates and regressed out.…”

“…After the stimulus and a short baseline of 1 s, the subjects have to select the target emotion out of six options. Stimulus-response pairs are interleaved with a jittered baseline of 5–10 s. The duration of the task strongly depends on the response times of the subjects but was ~10 min in previous investigations ( 123 ).…”

Individual brain regulation as learned via neurofeedback is related to affective changes in adolescents with autism spectrum disorder

“…A particular family of treatment approaches based on a system-and network-level understanding of ASD includes the application of non-invasive neuromodulation techniques [4]. Among these, transcranial direct current [5][6][7] and magnetic stimulation [8][9][10] have been more widely explored in the past. In contrast, neurofeedback (NF) is a neuromodulatory intervention without external stimulation.…”

Individual brain regulation as learned via neurofeedback is related to affective changes in adolescents with autism spectrum disorder

“…A particular family of treatment approaches based on a system- and network-level understanding of ASD comprises the application of non-invasive neuromodulation techniques (Khaleghi, Zarafshan, Vand, & Mohammadi, 2020). Especially transcranial direct current (Amatachaya et al, 2014; Amatachaya et al, 2015; Prillinger et al, 2021) and magnetic stimulation (Anninos, Chatzimichael, Adamopoulos, Kotini, & Tsagas, 2016; Doruk Camsari, Kirkovski, & Croarkin, 2018; Panerai et al, 2014) have been explored in the past. In contrast, neurofeedback (NF) is a neuromodulatory intervention without external stimulation.…”

“…A particular family of treatment approaches based on a system- and network-level understanding of ASD comprises the application of non-invasive neuromodulation techniques (4). Especially transcranial direct current (5-7) and magnetic stimulation (8-10) have been explored in the past. In contrast, neurofeedback (NF) is a neuromodulatory intervention without external stimulation.…”