Machine learning-optimized non-invasive brain stimulation and treatment response classification for major depression

Background/ObjectivesTranscranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention that shows promise as a potential treatment for depression. However, the clinical efficacy of tDCS varies, possibly due to individual differences in head anatomy affecting tDCS dosage. While functional changes in brain activity are more commonly reported in major depressive disorder (MDD), some studies suggest that subtle macroscopic structural differences, such as cortical thickness or brain volume reductions, may occur in MDD and could influence tDCS electric field (E-field) distributions. Therefore, accounting for individual anatomical differences may provide a pathway to optimize functional gains in MDD by formulating personalized tDCS dosage.MethodsTo address the dosing variability of tDCS, we examined a subsample of sixteen active-tDCS participants' data from the larger ELECT clinical trial (NCT01894815). With this dataset, individualized neuroimaging-derived computational models of tDCS current were generated for (1) classifying treatment response, (2) elucidating essential stimulation features associated with treatment response, and (3) computing a personalized dose of tDCS to maximize the likelihood of treatment response in MDD.ResultsIn the ELECT trial, tDCS was superior to placebo (3.2 points [95% CI, 0.7 to 5.5; P = 0.01]). Our algorithm achieved over 90% overall accuracy in classifying treatment responders from the active-tDCS group (AUC = 0.90, F1 = 0.92, MCC = 0.79). Computed precision doses also achieved an average response likelihood of 99.981% and decreased dosing variability by 91.9%.ConclusionThese findings support our previously developed precision-dosing method for a new application in psychiatry by optimizing the statistical likelihood of tDCS treatment response in MDD.