Targeting the prefrontal-supplementary motor network in obsessive-compulsive disorder with intensified electrical stimulation in two dosages: a randomized, controlled trial.

Obsessive-compulsive disorder (OCD) is associated with a high disease burden, and treatment options are limited. We used intensified electrical stimulation in two dosages to target a main circuitry associated with the pathophysiology of OCD, left dorsolateral prefrontal cortex (l-DLPFC), and pre-supplementary motor area (pre-SMA) and assessed clinical outcomes, neuropsychological performance, and brain physiology. In a double-blind, randomized controlled trial, thirty-nine patients with OCD were randomly assigned to three groups of sham, 2-mA, or 1-mA transcranial direct current stimulation (tDCS) targeting the l-DLPFC (F3) and pre-SMA (FC2) with anodal and cathodal stimulation respectively. The treatment included 10 sessions of 20-minute stimulation delivered twice per day with 20-min between-session intervals. Outcome measures were reduction in OCD symptoms, anxiety, and depressive states, performance on a neuropsychological test battery (response inhibition, working memory, attention), oscillatory brain activities, and functional connectivity. All outcome measures except EEG were examined at pre-intervention, post-intervention, and 1-month follow-up times. The 2-mA protocol significantly reduced OCD symptoms, anxiety, and depression states and improved quality of life after the intervention up to 1-month follow-up compared to the sham group, while the 1-mA protocol reduced OCD symptoms only in the follow-up and depressive state immediately after and 1-month following the intervention. Both protocols partially improved response inhibition, and the 2-mA protocol reduced attention bias to OCD-related stimuli and improved reaction time in working memory performance. Both protocols increased alpha oscillatory power, and the 2-mA protocol decreased delta power as well. Both protocols increased connectivity in higher frequency bands at frontal-central areas compared to the sham. Modulation of the prefrontal-supplementary motor network with intensified tDCS ameliorates OCD clinical symptoms and results in beneficial cognitive effects. The 2-mA intensified stimulation resulted in larger symptom reduction and improved more converging outcome variables related to therapeutic efficacy. These results support applying the intensified prefrontal-SMA tDCS in larger trials.

A systematic review of randomized controlled trials on efficacy and safety of transcranial direct current stimulation in major neurodevelopmental disorders: ADHD, autism, and dyslexia.

OBJECTIVE: Among the target groups in child and adolescent psychiatry, transcranial direct current stimulation (tDCS) has been more applied in neurodevelopmental disorders specifically, attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and dyslexia. This systematic review aims to provide the latest update on published randomized-controlled trials applying tDCS in these disorders for evaluating its efficacy and safety. METHODS: Based on a pre-registered protocol (PROSPERO: CRD42022321430) and using the PRISMA approach, a literature search identified 35 randomized controlled trials investigating the effects of tDCS on children and adolescents with ADHD (n = 17), ASD (n = 11), and dyslexia (n = 7). RESULTS: In ADHD, prefrontal anodal tDCS is reported more effective compared to stimulation of the right inferior frontal gyrus. Similarly in ASD, prefrontal anodal tDCS was found effective for improving behavioral problems. In dyslexia, stimulating temporoparietal regions was the most common and effective protocol. In ASD and dyslexia, all tDCS studies found an improvement in at least one of the outcome variables while 64.7% of studies (11 of 17) in ADHD found a similar effect. About 88% of all tDCS studies with a multi-session design in 3 disorders (16 of 18) reported a significant improvement in one or all outcome variables after the intervention. Randomized, double-blind, controlled trials consisted of around 70.5%, 36.3%, and 57.1% of tDCS studies in ADHD, ASD, and dyslexia, respectively. tDCS was found safe with no reported serious side effects in 6587 sessions conducted on 745 children and adolescents across 35 studies. CONCLUSION: tDCS was found safe and partially effective. For evaluation of clinical utility, larger randomized controlled trials with a double-blind design and follow-up measurements are required. Titration studies that systematically evaluate different stimulation intensities, duration, and electrode placement are lacking.

Consolidation of motor sequence learning eliminates susceptibility of SMAproper to TMS: a combined rTMS and cTBS study.

Earlier research suggested that after 210 practice trials, the supplementary motor area (SMA) is involved in executing all responses of familiar 6-key sequences in a discrete sequence production (DSP) task (Verwey, Lammens, and van Honk, 2002). This was indicated by slowing of each response 20 and 25 min after the SMA had been stimulated for 20 min using repetitive transcranial magnetic stimulation (rTMS). The present study used a similar approach to assess the effects of TMS to the more posterior SMAproper at the end of practice and also 24 h later. As expected stimulation of SMAproper with 20 min of 1 Hz rTMS and 40 s of continuous theta burst stimulation (cTBS) immediately after practice slowed sequence execution relative to a sham TMS condition, but stimulation on the day following practice did not cause slowing. This indicates that offline consolidation makes learning robust against stimulation of SMAproper. Execution of all responses in the sequence was disrupted 0, 20, and 40 min after rTMS, but after cTBS, this occurred only after 40 min. The results suggest that it is implicit sequence knowledge that is processed by the SMAproper and that consolidates.