From Immediate Impact to Enduring Change: A Transcriptomic Comparison of tDCS’s Temporal Effects and Its Long-Term Equivalence with TMS

Transcranial Direct Current Stimulation (tDCS) and Transcranial Magnetic Stimulation (TMS) are neuromodulatory techniques with therapeutic potential for similar disorders; however, their molecular effects require further elucidation, and whether both strategies work in similar biological pathways is unknown. Thus, determining whether these effects are unique or shared across techniques is essential for optimizing their therapeutic applications. We investigated the long-term effects of tDCS by generating a novel transcriptomic dataset and comparing it to immediate tDCS effects and long-term TMS effects using publicly available data. Transcriptomics data were generated using nanopore sequencing on parietal cortices below the stimulation electrode of C57BL/6 mice that underwent repetitive anodal tDCS (200 µA) for 20 min over 5 consecutive days. Bioinformatics analyses were conducted on this dataset in conjunction with publicly available datasets on immediate tDCS and long-term TMS effects. Repetitive tDCS induces long-term alterations in protein translation, mitochondrial function, and cellular respiration, while TMS primarily affects calcium-mediated signaling, suggesting distinct neuromodulatory and molecular mechanisms. These findings demonstrate that tDCS and TMS elicit lasting but distinct molecular changes, highlighting technique-specific neuromodulatory effects relevant to their therapeutic applications.