Personalized Transcranial Direct Current Stimulation for Behavioral and Neurophysiologic Outcomes.

Importance: Transcranial direct current stimulation (tDCS) is emerging as a home-based intervention for neuropsychiatric conditions and cognitive enhancement. However, its effectiveness is limited by interindividual variability, as fixed-dose protocols have failed to account for anatomic differences influencing current delivery to targeted regions and treatment outcome. While computational modeling supports individualized dosing to improve consistency, experimental validation remains limited.

Objective: To compare the behavioral and neurophysiologic outcomes of fixed-dose vs individualized-dose tDCS.

Design, Setting, And Participants: This comparative effectiveness study using a within-participant, double-masked, crossover design was conducted from January 1, to March 31, 2024, at the National Institute of Mental Health and Neurosciences in India. Adult participants (aged 21-35 years) received 3 sessions of tDCS (fixed-dose, individualized-dose, and sham stimulation) in counterbalanced order. Individualized doses were calculated using a custom-built simulation toolbox.

Main Outcomes And Measures: Behavioral performance was measured using reaction time during a rapid naming task. Neurophysiologic effects were assessed using motor-evoked potentials (MEPs) recorded before and after stimulation. Linear mixed-effects models were used for the statistical analysis.

Results: Sixteen right-hand-dominant, bilingual English-Dravidian speakers (mean [SD] age, 23.1 [3.9] years; 8 female [50%]) were included. Individualized-dose tDCS associated with significantly greater reaction time improvement over sham (estimated marginal mean [SD]: before, 753.0 [41.1] ms; after, 619.0 [41.1] ms; change [Δ] = 133.6 ms; SE, 10.2 ms; z score ratio, 13.09) compared with fixed-dose tDCS (before, 694.0 [41.1] ms; after, 680.0 [41.1] ms; Δ = 14.6 ms; SE, 10.1 ms; z score ratio, 1.45). Variability was lower with individualized-dose stimulation (coefficient of variation, -1.14 vs 0.39 fixed vs individualized dose, respectively). Sex-stratified analyses showed that women had improvements with both fixed (Δ = 58.0 ms; P = .003) and individualized (Δ = 113.8 ms; P < .001) stimulation, while men had improvement only with individualized tDCS (Δ = 153.4 ms; P < .001). Seven participants (5 men and 2 women) converted from nonresponders to responders with individualized dosing. For MEPs, individualized-dose tDCS showed greater poststimulation amplitude increases over sham (β [SE], 0.91 [0.23]), although fixed-dose tDCS poststimulation amplitude was smaller, but significant (β [SE], 0.56 [0.23]; P = .02) and showed a higher percentage change (β [SE], 144.26% [55.74%]; P = .01) and reduced variability (coefficient of variation, -0.79 vs 1.12 [fixed]).

Conclusions And Relevance: In this comparative effectiveness study, dose-controlled tDCS was associated with consistent behavioral and neurophysiologic improvement, highlighting its translational importance in the treatment of neuropsychiatric disorders.