{"doi":"10.1016/j.brs.2022.09.014","title":"A replication study of NMDA receptor agonism sufficiency to enhance 10-Hz rTMS-induced motor cortex plasticity","abstract":"Clinical applications of repetitive transcranial magnetic stimulation (rTMS) have advanced without complete understanding of its mechanisms of action. Pharmacology can help unravel the neuronal-level actions of rTMS in humans by blocking or targeting molecular mechanisms and examining the impact on neurophysiology measures such as motor-evoked potentials (MEPs). However, such studies are scarce and underpowered, necessitating replication studies to confirm these foundational findings (reviewed in Refs. [[1]Ziemann U. et al.TMS and drugs revisited 2014.Clin Neurophysiol. 2015; 126: 1847-1868Crossref PubMed Scopus (399) Google Scholar,[2]Brown J.C. Higgins E.S. George M.S. Synaptic plasticity 101: the story of the AMPA receptor for the brain stimulation practitioner. Neuromodulation, 2021Google Scholar]). We sought to replicate our own experiment, which found a significant effect of n-methyl-d-aspartate (NMDA) receptor agonism on rTMS-induced plasticity, despite only 10 subjects and effect size of only 0.3 (Power = 0.42). We therefore sought to test the reproducibility of our previously low-powered study while retesting the role of the NMDA receptor in 10-Hz rTMS [[3]Brown J.C. et al.NMDA receptor partial agonist, d-cycloserine, enhances 10 Hz rTMS-induced motor plasticity, suggesting long-term potentiation (LTP) as underlying mechanism.Brain Stimul. 2020; 13: 530-532Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar]. We hypothesized that 10-Hz rTMS strengthens affected networks by reinforcing synaptic connections through long-term potentiation (LTP), based on animal studies and our previous findings [[4]Brown J.C. et al.NMDA-receptor agonist reveals LTP-like properties of 10-Hz rTMS in the human motor cortex.Brain Stimul. 2021; 14: 619-621Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar,[5]Vlachos A. et al.Repetitive magnetic stimulation induces functional and structural plasticity of excitatory postsynapses in mouse organotypic hippocampal slice cultures.J Neurosci. 2012; 32: 17514-17523Crossref PubMed Scopus (136) Google Scholar]. We therefore predicted that a single dose of DCS, relative to placebo, would enhance the magnitude of MEPs otherwise potentiated by 20 minutes of 10-Hz rTMS. We used similar methods to the study performed at the Medical University of South Carolina (MUSC) [[3]Brown J.C. et al.NMDA receptor partial agonist, d-cycloserine, enhances 10 Hz rTMS-induced motor plasticity, suggesting long-term potentiation (LTP) as underlying mechanism.Brain Stimul. 2020; 13: 530-532Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar] by again recruiting ten healthy right-handed, non-smoking adults (6 female) from 21 to 39 years old (28 ± 6.0) into a randomized, double-blind, crossover study approved by the Butler Hospital Institutional Review Board. All participants provided informed consent prior to any research procedures, and we excluded those with brain disorders, or who were actively taking neuropsychotropic medications. We randomly assigned participants to a single dose of either 100 mg d-cycloserine or identical microcrystalline cellulose capsules (Tidewater pharmacy, Mt. Pleasant, SC) in a blinded random manner over two separate visits, at least 1-week apart (Fig. 1A). A PowerMAG EEG100 power unit and PMD70-pCool Coil (Mag&More, Germany) were used to stimulate the left motor cortex “hotspot”. MEPs were recorded from the right first dorsal interosseous (FDI) muscle with surface electromyography (EMG) electrodes (Cardinal Health, USA). The raw signal was amplified and filtered by CED 1902 and 1401 microprocessors and analyzed with Signal software (Cambridge Electronic Devices, UK). Pulses were kept within 0.5 mm of target with neuronavigation performed with a Brainsight 2 System (Rogue Research, Quebec, Canada). Approximately 60 minutes following drug administration, we measured baseline assessments including: resting motor threshold (rMT), one bin of 40 single-pulses","journal":"Brain stimulation","year":2022,"id":256827,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9613,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":906160,"name":"Megan Vigne","orcid":"0000-0002-0590-0986","position":1,"is_corresponding":false},{"id":282467,"name":"Richard N. 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Brown","orcid":"0000-0003-0887-2746","position":5,"is_corresponding":false},{"id":906159,"name":"Jamie Kweon","orcid":"0009-0009-3157-1555","position":0,"is_corresponding":true}],"reference_count":14,"raw_metadata":null,"created_at":"2026-07-19T00:25:25.728895Z","pmid":"36180040","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":[]}