Bhattacharjee Sagarika, Sivakumar Palanimuthu T, Venkatasubramanian Ganesan, Bharath Rose Dawn, Oishi Kenichi, Rapp Brenda, Desmond John E, Chen S H Annabel, Sathyaprabha T N, Udupa Kaviraja, Kashyap Rajan
Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bengaluru, India.
Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, India.
JAMA Netw Open. 2025 Aug 1;8(8):e2526148. doi: 10.1001/jamanetworkopen.2025.26148.
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.
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.
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.
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]).
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.
经颅直流电刺激（tDCS）正逐渐成为一种用于神经精神疾病和认知增强的居家干预方法。然而，其有效性受到个体差异的限制，因为固定剂量方案未能考虑到影响电流传递至目标区域及治疗效果的解剖学差异。虽然计算模型支持个体化给药以提高一致性，但实验验证仍然有限。
比较固定剂量与个体化剂量tDCS的行为和神经生理结果。
设计、场所和参与者：这项采用参与者内、双盲、交叉设计的比较有效性研究于2024年1月1日至3月31日在印度国家心理健康和神经科学研究所进行。成年参与者（年龄21 - 35岁）以平衡顺序接受3次tDCS治疗（固定剂量、个体化剂量和假刺激）。使用定制的模拟工具箱计算个体化剂量。
在快速命名任务期间使用反应时间测量行为表现。使用刺激前后记录的运动诱发电位（MEP）评估神经生理效应。采用线性混合效应模型进行统计分析。
纳入了16名以右手为主、会说英语和达罗毗荼语的双语者（平均[标准差]年龄，23.1[3.9]岁；8名女性[50%]）。与固定剂量tDCS相比，个体化剂量tDCS与假刺激相比反应时间改善显著更大（估计边际均值[标准差]：刺激前，753.0[41.1]毫秒；刺激后，619.0[41.1]毫秒；变化[Δ] = 133.6毫秒；标准误，10.2毫秒；z评分比，13.09）（刺激前，694.0[41.1]毫秒；刺激后，680.0[41.1]毫秒；Δ = 14.6毫秒；标准误，10.1毫秒；z评分比，1.45）。个体化剂量刺激的变异性较低（变异系数，固定剂量为0.39，个体化剂量为 -1.14）。按性别分层分析显示，女性在固定刺激（Δ = 58.0毫秒；P = 0.003）和个体化刺激（Δ = 113.8毫秒；P < 0.001）下均有改善，而男性仅在个体化tDCS下有改善（Δ = 153.4毫秒；P < 0.001）。7名参与者（5名男性和2名女性）通过个体化给药从不 responders 转变为 responders。对于MEP，个体化剂量tDCS与假刺激相比刺激后振幅增加更大（β[标准误]，0.91[0.23]），尽管固定剂量tDCS刺激后振幅较小，但具有显著性（β[标准误]，0.56[0.23]；P = 0.02）且显示出更高的百分比变化（β[标准误]，144.26%[55.74%]；P = 0.01）以及变异性降低（变异系数，固定剂量为1.12，个体化剂量为 -0.79）。
在这项比较有效性研究中，剂量控制的tDCS与一致的行为和神经生理改善相关，突出了其在神经精神疾病治疗中的转化重要性。
