Tolerability and feasibility of at-home remotely supervised transcranial direct current stimulation (RS-tDCS): Single-center evidence from 6,779 sessions.

INTRODUCTION: The ability to deploy transcranial direct current stimulation (tDCS) at home is a key usability advantage to support scaling for pivotal clinical trials. We have established a home-based tDCS protocol for use in clinical trials termed remotely supervised (RS)-tDCS. OBJECTIVE: To report the tolerability and feasibility of tDCS sessions completed to date using RS-tDCS in clinical trials. METHODS: We analyzed tolerability (i.e., adverse events, AEs) reported in six Class I/II/III trials using RS-tDCS to study symptom outcomes over 10 to 60 daily applications. Across the six clinical trials, 308 participants (18-78 years old) completed an average of 23 sessions for a total of 6779 RS-tDCS administrations. The majority of participants were diagnosed with multiple sclerosis, and open-label trials included those diagnosed with a range of other conditions (e.g., Parkinson's disease, post-stroke aphasia, traumatic brain injury, cerebellar ataxia), with minimum-to-severe neurologic disability. Clinical trial feasibility (i.e., treatment fidelity and blinding integrity) was examined using two Class I randomized controlled trials (RCTs). RESULTS: No serious AEs occurred. Across administrations, three sessions (0.04%) were aborted due to discomfort, but no participant discontinued due to tolerability. The AEs most commonly reported by participants were tingling (68%), itching (41%) and warmth sensation (42%) at the electrode site, and these were equally reported in active and sham tDCS conditions. The two Class I RCTs resulted in rapid enrollment, high fidelity to treatment completion, and blinding integrity. CONCLUSIONS: At-home RS-tDCS is tolerable, including when used over extended periods of time. Home-based RS-tDCS is feasible and can enable Class I tDCS clinical trial designs.

Cerebral metabolic rate of oxygen (CMRO2) changes measured with simultaneous tDCS-MRI in healthy adults.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a safe and well-tolerated noninvasive technique used for cortical excitability modulation. tDCS has been extensively investigated for its clinical applications; however further understanding of its underlying in-vivo physiological mechanisms remains a fundamental focus of current research. OBJECTIVES: We investigated the simultaneous effects of tDCS on cerebral blood flow (CBF), venous blood oxygenation (Yv) and cerebral metabolic rate of oxygen (CMRO2) using simultaneous MRI in healthy adults to provide a reference frame for its neurobiological mechanisms. METHODS: Twenty-three healthy participants (age = 35.6 ± 15.0 years old, 10 males) completed a simultaneous tDCS-MRI session in a 3 T scanner fitted with a 64-channels head coil. A MR-compatible tDCS device was used to acquire CBF, Yv and CMRO2 at three time points: pre-, during- and post- 15 minutes of 2.0 mA tDCS on left anodal dorsolateral prefrontal cortex. RESULTS: During tDCS, CBF significantly increased (57.10 ± 8.33 mL/100g/min) from baseline (53.67 ± 7.75 mL/100g/min; p < 0.0001) and remained elevated in post-tDCS (56.79 ± 8.70 mL/100g/min). Venous blood oxygenation levels measured in pre-tDCS (60.71 ± 4.12 %) did not significantly change across the three timepoints. The resulting CMRO2 significantly increased by 5.9 % during-tDCS (175.68 ± 30.78 µmol/100g/min) compared to pre-tDCS (165.84 ± 25.32 µmol/100g/min; p = 0.0015), maintaining increased levels in post-tDCS (176.86 ± 28.58 µmol/100g/min). CONCLUSIONS: tDCS has immediate effects on neuronal excitability, as measured by increased cerebral blood supply and oxygen consumption supporting increased neuronal firing. These findings provide a standard range of CBF and CMRO2 changes due to tDCS in healthy adults that may be incorporated in clinical studies to evaluate its therapeutic potential.