{"doi":"10.1016/j.brs.2021.05.015","title":"Differing dose details and controlling confounding covariates in modulating motor cortex excitability by transcranial direct current stimulation","abstract":"We appreciate the recent letter [[1]Bland N.S. Is two decades of tDCS work wrong? Commentary on Ahn and Frohlich.Brain Stimul: Basic, Transl, Clin Resear Neuromodul. 2021; 14: 438-439Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar] that commented on our study of modulating motor cortex excitability by transcranial direct current stimulation (tDCS) [[2]Ahn S. Fröhlich F. Pinging the brain with transcranial magnetic stimulation reveals cortical reactivity in time and space.Brain Stimul. 2021; 14: 304-315Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar]. The main point of the letter was that our reported modulation of motor evoked potentials (MEPs) by tDCS was more consistent and thus had a larger effect size than previously reported results in the literature. We agree with the author that our results are much clearer than the ones from previous studies in the field and that the standard mean difference calculated for pairwise comparisons substantially exceeds what has been previously reported. Yet, there are several underappreciated aspects that can easily explain this difference in findings. First and foremost, one fallacy that the field has yet to fully grapple with is the idea that tDCS is a monolithic entity, leading sometimes to absurd questions such as ‘Does tDCS work?” Even tDCS applied to the motor cortex can take many different forms and numerous experimental details, often neither controlled for nor reported in published analyses, that do likely matter. One aspect that has gotten lost in the debate is that we on purpose used a higher current density than the vast majority of tDCS summarized in a recent meta-analysis [[3]Dissanayaka T. et al.Does transcranial electrical stimulation enhance corticospinal excitability of the motor cortex in healthy individuals? A systematic review and meta-analysis.Eur J Neurosci. 2017; 46: 1968-1990Crossref PubMed Scopus (32) Google Scholar]: we used 2 mA stimulation current with 25cm2 electrode surface area (for example only 15% employed 2mA stimulation, 12% used same or smaller electrode size, and 0% of studies used 2mA and same or smaller electrodes). This discrepancy questions whether the comparison of our results to the meta-analysis results is appropriate and illustrates the principle that stronger perturbations can reduce heterogeneity but not necessarily raw magnitude of an effect. Furthermore, the resulting electric field and thus the perturbation to neural activity is sufficiently weak for tDCS that the “stimulation dose” concept makes only limited sense since the effect of stimulation is likely mostly determined by endogenous brain activity patterns that are often neither measured nor analyzed. Yet, the field has become enamored with electric field simulations that can be helpful but are often misunderstood. Knowing the strength of the electric field (or at least having a reasonably accurate estimate from a physics simulation) may have little to do with which neurons (where in the brain) change their activity in response to stimulation. Likely more important, given the small change in membrane voltage caused by tDCS, is the state of neuron in terms of how close to firing threshold it is. While indeed our publication did not show significant correlations between the effect of tDCS and the simulated electric fields, we found significant correlations between oscillatory dynamics (pre-stimulus mu rhythms) and the response to tDCS both in terms of MEPs and transcranial magnetic stimulation (TMS) evoked potentials (TEPs). In addition, anodal tDCS increased and cathodal tDCS decreased the pre-stimulus mu rhythm oscillatory power, respectively. In other words, our report directly supports the model in which endog enous state trumps simulated electric field strength as a predictor of the response to TMS. Second, we appreciate the statistical considerations provided by Bland [[1]Bland N.S. Is two decades of tDCS work wrong? Commentary on Ahn and Frohli","journal":"Brain stimulation","year":2021,"id":224936,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":510082,"name":"Sangtae Ahn","orcid":"0000-0001-9487-5649","position":1,"is_corresponding":false},{"id":395860,"name":"Flavio Frӧhlich","orcid":"0000-0002-3724-5621","position":0,"is_corresponding":true}],"reference_count":3,"raw_metadata":null,"created_at":"2026-07-18T23:54:22.889584Z","pmid":"34118495","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}