{"doi":"10.1016/j.brs.2021.02.013","title":"Accelerated neuromodulation therapy for Obsessive-Compulsive Disorder","abstract":"An accelerated course of modified continuous theta-burst stimulation (cTBSmod) shows potential as a treatment for neurological conditions like spatial neglect symptoms in patients with right-hemispheric stroke [[1]Cazzoli D. Muri R.M. Schumacher R. et al.Theta burst stimulation reduces disability during the activities of daily living in spatial neglect.Brain. 2012; 135: 3426-3439Crossref PubMed Scopus (109) Google Scholar]; however, its potential in other neuropsychiatric disorders remains unknown. Patients with obsessive-compulsive disorder (OCD) are in particular need of novel therapeutic interventions, since they usually experience considerable residual symptoms despite treatment. OCD symptoms are associated with cortico-striatal circuit hyperactivation, right orbitofrontal cortex hyperactivation, and increased functional connectivity between the orbitofrontal cortex and the striatum [[2]Ursu S. Carter C.S. An initial investigation of the orbitofrontal cortex hyperactivity in obsessive-compulsive disorder: exaggerated representations of anticipated aversive events?.Neuropsychologia. 2009; 47: 2145-2148Crossref PubMed Scopus (33) Google Scholar,[3]Ahmari S.E. Dougherty D.D. Dissecting ocd circuits: from animal models to targeted treatments.Depress Anxiety. 2015; 32: 550-562Crossref PubMed Scopus (61) Google Scholar]. This cortico-striatal hyperactivity normalizes following successful treatment [[4]Dunlop K. Woodside B. Olmsted M. et al.Reductions in cortico-striatal hyperconnectivity accompany successful treatment of obsessive-compulsive disorder with dorsomedial prefrontal rTMS.Neuropsychopharmacology. 2016; 41: 1395-1403Crossref PubMed Scopus (64) Google Scholar]. To test whether an accelerated course of cTBSmod could induce rapid clinical responses in other populations, we conducted an open-label trial of accelerated cTBSmod protocol targeting this frontal-striatal circuit and assessed symptom reduction in seven OCD patients. Using modified cTBS parameters, we delivered multiple cTBSmod sessions daily. We added individualized functional connectivity magnetic resonance imaging (fcMRI)-guided targeting to optimally target the frontal-striatal circuit and delivered high-dose stimulation, based on evidence suggesting standard once-daily, 6-week transcranial magnetic stimulation (TMS) protocols may be under-dosing [[5]Cole E.J. Stimpson K.H. Bentzley B.S. et al.Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression.Am J Psychiatr. 2020; 177: 716-726Crossref PubMed Scopus (45) Google Scholar]. We used a variant of the spaced delivery, high-dose, individualized fcMRI-guided targeting method previously applied in treatment-resistant depression [[5]Cole E.J. Stimpson K.H. Bentzley B.S. et al.Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression.Am J Psychiatr. 2020; 177: 716-726Crossref PubMed Scopus (45) Google Scholar]. Since altered activation in front-striatal circuits—probed by tasks that require resolution of conflict [[6]Marsh R. Tau G.Z. Wang Z. et al.Reward-based spatial learning in unmedicated adults with obsessive-compulsive disorder.Am J Psychiatr. 2015; 172: 383-392Crossref PubMed Scopus (31) Google Scholar,[7]Pagliaccio D. Middleton R. Hezel D. et al.Task-based fMRI predicts response and remission to exposure therapy in obsessive-compulsive disorder.Proc Natl Acad Sci U S A. 2019; 116: 20346-20353Crossref PubMed Scopus (7) Google Scholar] and inhibitory control [[8]Norman L.J. Taylor S.F. Liu Y. et al.Error processing and inhibitory control in obsessive-compulsive disorder: a meta-analysis using statistical parametric maps.Biol Psychiatr. 2019; 85: 713-725Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar]—suggests brain regions implicated in cognitive control may be linked to OCD, we explored brain activation before and after treatment probed by a task that requires inhibitory cognitive control (Go/No-Go) [[9]Tozzi L. Goldstei","journal":"Brain stimulation","year":2021,"id":162307,"datarank":2.397727592608571,"base_score":3.8918202981106265,"endowment":3.8918202981106265,"self_citation_contribution":0.5837730447165941,"citation_network_contribution":1.8139545478919765,"self_endowment_contribution":0.5837730447165941,"citer_contribution":1.8139545478919765,"corpus_percentile":null,"corpus_rank":null,"citation_count":48,"citer_count":44,"citers_with_citation_signal":33,"citers_with_endowment":33,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9595,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03404609"]},"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":678845,"name":"Keith Sudheimer","orcid":"0000-0002-9909-0063","position":1,"is_corresponding":false},{"id":95858,"name":"Eleanor Cole","orcid":"0000-0002-8477-7508","position":2,"is_corresponding":false},{"id":275886,"name":"Andrea Varias","orcid":"0000-0002-9868-0088","position":3,"is_corresponding":false},{"id":397625,"name":"Andrea Goldstein‐Piekarski","orcid":"0000-0001-6382-4312","position":4,"is_corresponding":false},{"id":409587,"name":"Patrick Stetz","orcid":"0000-0002-9511-4849","position":5,"is_corresponding":false},{"id":678846,"name":"Anthony Lombardi","orcid":"0000-0001-5211-9378","position":6,"is_corresponding":false},{"id":275889,"name":"Maria Filippou-Frye","orcid":"0000-0001-5516-0384","position":7,"is_corresponding":false},{"id":678847,"name":"Peter van Roessel","orcid":"0000-0002-9477-604X","position":8,"is_corresponding":false},{"id":678848,"name":"Kelley Anderson","orcid":"0009-0007-4598-3687","position":9,"is_corresponding":false},{"id":51251,"name":"Elizabeth A. McCarthy","orcid":"0000-0001-7321-9319","position":10,"is_corresponding":false},{"id":678849,"name":"Brianna Wright","orcid":"0000-0003-4284-1644","position":11,"is_corresponding":false},{"id":678850,"name":"Thasveen Sandhu","orcid":"0000-0001-9341-6547","position":12,"is_corresponding":false},{"id":679527,"name":"Sindu Menon","orcid":null,"position":13,"is_corresponding":false},{"id":263618,"name":"Booil Jo","orcid":"0000-0001-8855-147X","position":14,"is_corresponding":false},{"id":678851,"name":"Lorrin Koran","orcid":"0000-0003-0092-3721","position":15,"is_corresponding":false},{"id":326861,"name":"Leanne M. Williams","orcid":"0000-0001-9987-7360","position":16,"is_corresponding":false},{"id":275891,"name":"Carolyn I. 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