{"doi":"10.1016/j.brs.2025.04.012","title":"Accelerated iTBS-Induced changes in resting-state functional connectivity correspond with cognitive improvement in amnestic MCI","abstract":"BACKGROUND: Published results of our Phase I safety and feasibility trial of accelerated intermittent theta burst stimulation (a-iTBS) in mild cognitive impairment (MCI) due to Alzheimer's disease showed a large effect-size improvement in cognition. OBJECTIVE: Further demonstrate target engagement by identifying whether changes in local and network-level functional connectivity relate to the observed cognitive improvement. METHODS: Eighteen patients with MCI received 3-day a-iTBS (8 sessions/day) to the left dorsolateral prefrontal cortex at Beam F3 (14,400 total pulses) and completed MRI and cognitive testing at pre- and post-treatment. Based on electric field models, we selected 3 stimulated target regions of interest (ROIs) which belonged to the frontoparietal (FPN), default mode (DMN), and ventral attention (VAT) networks (3 target networks). Metrics of resting-state functional connectivity were computed at the ROI level (within-network degree: number of connections) and network level (segregation: strength of connectivity within-network relative to other networks). We correlated changes in cognition and connectivity of the target ROIs and networks; off-target ROI (primary visual) and networks served as negative controls. RESULTS: Improvements in cognition were associated with connectivity changes in the target ROIs and networks, but not in off-target negative controls. Positive associations were observed for degree of the l-DMN and segregation of target networks overall, with significant effects for DMN and VAT. CONCLUSION: Cognitive improvement following a-iTBS in MCI may be attributable to local and network-level reconfigurations in functional connectivity. These findings will inform larger trials designed to further evaluate the neural mechanisms of a-iTBS for cognition in MCI.","journal":"Brain stimulation","year":2025,"id":520982,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9593,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":815192,"name":"Sara A. Nolin","orcid":"0000-0001-7107-1891","position":1,"is_corresponding":false},{"id":628712,"name":"Andrew A. Chen","orcid":"0000-0002-5027-6422","position":2,"is_corresponding":false},{"id":289790,"name":"Kevin A. Caulfield","orcid":"0000-0001-8268-4204","position":3,"is_corresponding":false},{"id":328906,"name":"James W. Lopez","orcid":"0000-0003-0761-1560","position":4,"is_corresponding":false},{"id":1245012,"name":"Katrina Rbeiz","orcid":"0000-0003-3312-9137","position":5,"is_corresponding":false},{"id":328907,"name":"Holly H Fleischmann","orcid":"0000-0003-3501-8027","position":6,"is_corresponding":false},{"id":1152107,"name":"Olivia Horn","orcid":"0009-0004-7826-0571","position":7,"is_corresponding":false},{"id":1245476,"name":"Katrina S. Madden","orcid":null,"position":8,"is_corresponding":false},{"id":1101249,"name":"Michael U. Antonucci","orcid":"0000-0003-4392-3465","position":9,"is_corresponding":false},{"id":490578,"name":"Gonzalo J. Revuelta","orcid":"0000-0003-3917-8634","position":10,"is_corresponding":false},{"id":258809,"name":"Lisa M. McTeague","orcid":"0000-0003-4475-9425","position":11,"is_corresponding":false},{"id":391287,"name":"Andreana Benitez","orcid":"0000-0002-8294-7809","position":12,"is_corresponding":false},{"id":1245011,"name":"Stephanie Aghamoosa","orcid":"0000-0002-9365-4884","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T02:49:32.958846Z","pmid":"40252967","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":[]}