{"doi":"10.1016/j.brs.2021.06.014","title":"Transcranial alternating current stimulation for the treatment of obsessive-compulsive disorder?","abstract":"We read with great interest the recent report by Reinhart and colleagues on their transcranial alternating current stimulation (tACS) study that targeted orbitofrontal cortex for the modulation of reward-learning and obsessive-compulsive behaviors [[1]Grover S. et al.High-frequency neuromodulation improves obsessive–compulsive behavior.Nat Med. 2021; 27: 232-238Google Scholar]. In a series of two elegant studies, linked by a computational model of reward-learning, the authors first show a selective impairment in optimal behavioral choices in a monetary reinforcement learning task in which participants learn the unequal rewards associated with different stimuli and accordingly adjust their choice behavior. This effect was only found for individualized beta-gamma tACS but not for alpha- or sham-tACS, suggesting that the effect of stimulation is frequency-specific and not a general electric effect. Furthermore, the authors report specificity with regards to task condition, as only the reward and not the punishment trials showed impairment by beta-gamma tACS. In the second experiment, a double-blind, active-sham-controlled study of beta-gamma versus alpha-tACS was performed with “non-clinical” participants who exhibited obsessive-compulsive behaviors as measured by OCI-R. The authors recruited participants with a wide-range of symptoms, which enabled analysis of baseline beta-gamma activity during reward-learning as a function of OCD symptom severity. Building on an emerging literature of tACS clinical trials in psychiatry [2Alexander M.L. et al.Double-blind, randomized pilot clinical trial targeting alpha oscillations with transcranial alternating current stimulation (tACS) for the treatment of major depressive disorder (MDD).Transl Psychiatry. 2019; 9: 106Crossref PubMed Scopus (54) Google Scholar, 3Ahn S. et al.Targeting reduced neural oscillations in patients with schizophrenia by transcranial alternating current stimulation.Neuroimage. 2019; 186: 126-136Crossref PubMed Scopus (48) Google Scholar, 4Mellin J.M. et al.Randomized trial of transcranial alternating current stimulation for treatment of auditory hallucinations in schizophrenia.Eur Psychiatr. 2018; 51: 25-33Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar], a five-day paradigm was used with follow-up visits up to 3 months. Beta-gamma tACS outperformed alpha-tACS in terms of symptom improvements, leading the authors to propose that such an intervention could be investigated in future clinical trials for the treatment of OCD. This study raises several interesting questions that are important to be considered for this nascent field of non-invasive brain stimulation for the treatment of psychiatric disorders. First, the authors use a cutting-edge strategy of identifying their individually targeted neural oscillations by recording EEG during the task, extracting individual peak frequency, and adjusting the stimulation frequency [[5]Riddle J. McFerren A. Frohlich F. Causal role of cross-frequency coupling in distinct components of cognitive control.Prog Neurobiol. 2021; 102033Google Scholar,[6]Reinhart R.M. Nguyen J.A. Working memory revived in older adults by synchronizing rhythmic brain circuits.Nat Neurosci. 2019; 22: 820-827Crossref PubMed Scopus (145) Google Scholar]. Such frequency-matching is particularly important in the context of tACS where the mechanism of action (described in dynamical systems terms as the so-called Arnold tongue) requires frequency tuning for achieving entrainment of neural oscillations [[7]Ali M.M. Sellers K.K. Fröhlich F. Transcranial alternating current stimulation modulates large-scale cortical network activity by network resonance.J Neurosci. 2013; 33: 11262-11275Crossref PubMed Scopus (254) Google Scholar,[8]Huang W.A. Stitt I.M. Negahbani E. Passey D.J. Ahn S. Davey M. Dannhauer M. Doan T.T. Hoover A.C. Peterchev A.V. Radtke-Schuller S. Fröhlich F. Transcranial alternating current stimulation entrains alpha oscillations","journal":"Brain stimulation","year":2021,"id":204383,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9611,"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":236458,"name":"Justin Riddle","orcid":"0000-0003-2251-3643","position":1,"is_corresponding":false},{"id":400115,"name":"Jonathan S. Abramowitz","orcid":"0000-0002-1721-8060","position":2,"is_corresponding":false},{"id":395860,"name":"Flavio Frӧhlich","orcid":"0000-0002-3724-5621","position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:51:26.121843Z","pmid":"34192553","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":[]}