{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:48:59Z","timestamp":1789688939910,"version":"4.0.1"},"reference-count":40,"publisher":"BMJ","issue":"11","funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19H01091"],"award-info":[{"award-number":["19H01091"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K21770"],"award-info":[{"award-number":["20K21770"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21H03308"],"award-info":[{"award-number":["21H03308"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K19745"],"award-info":[{"award-number":["21K19745"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22H04788"],"award-info":[{"award-number":["22H04788"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23H00459"],"award-info":[{"award-number":["23H00459"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Gait disturbance lowers activities of daily living in patients with Parkinson\u2019s disease (PD) and related disorders. However, the effectiveness of pharmacological, surgical and rehabilitative treatments is limited. We recently developed a novel neuromodulation approach using gait-combined closed-loop transcranial electrical stimulation (tES) for healthy volunteers and patients who are post-stroke, and achieved significant entrainment of gait rhythm and an increase in gait speed. Here, we tested the efficacy of this intervention in patients with Parkinsonian gait disturbances.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty-three patients were randomly assigned to a real intervention group using gait-combined closed-loop oscillatory tES over the cerebellum at the frequency of individualised comfortable gait rhythm, and to a sham control group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ten intervention sessions were completed for all patients and showed that the gait speed (<jats:italic>F<\/jats:italic><jats:sub>(1, 21)<\/jats:sub>=13.0, p=0.002) and stride length (<jats:italic>F<\/jats:italic><jats:sub>(1, 21)<\/jats:sub>=8.9, p=0.007) were significantly increased after tES, but not after sham stimulation. Moreover, gait symmetry measured by swing phase time (<jats:italic>F<\/jats:italic><jats:sub>(1, 21)<\/jats:sub>=11.9, p=0.002) and subjective feelings about freezing (<jats:italic>F<\/jats:italic><jats:sub>(1, 21)<\/jats:sub>=14.9, p=0.001) were significantly improved during gait.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings showed that gait-combined closed-loop tES over the cerebellum improved Parkinsonian gait disturbances, possibly through the modulation of brain networks generating gait rhythms. This new non-pharmacological and non-invasive intervention could be a breakthrough in restoring gait function in patients with PD and related disorders.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2022-329966","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T17:25:15Z","timestamp":1686331515000},"page":"938-944","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Gait-combined closed-loop brain stimulation can improve walking dynamics in Parkinsonian gait disturbances: a randomised-control trial"],"prefix":"10.1136","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9284-0247","authenticated-orcid":false,"given":"Ippei","family":"Nojima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuya","family":"Horiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kento","family":"Sahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Koganemaru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satona","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiminori","family":"Aoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Matsukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumie","family":"Ono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7787-4855","authenticated-orcid":false,"given":"Tatsuya","family":"Mima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshino","family":"Ueki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,6,9]]},"reference":[{"key":"2023101202051495000_94.11.938.1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa019"},{"key":"2023101202051495000_94.11.938.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.252"},{"key":"2023101202051495000_94.11.938.3","doi-asserted-by":"crossref","unstructured":"Beretta VS , Concei\u00e7\u00e3o NR , N\u00f3brega-Sousa P , et al . Transcranial direct current stimulation combined with physical or cognitive training in people with Parkinson\u2019s disease: a systematic review. J Neuroeng Rehabil 2020;17:74. doi:10.1186\/s12984-020-00701-6","DOI":"10.1186\/s12984-020-00701-6"},{"key":"2023101202051495000_94.11.938.4","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.parkreldis.2019.02.029","article-title":"Effects of non-invasive brain stimulation on freezing of gait in parkinsonism: a systematic review with meta-analysis","volume":"64","author":"Kim","year":"2019","journal-title":"Parkinsonism Relat Disord"},{"key":"2023101202051495000_94.11.938.5","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3109\/17518423.2015.1131755","article-title":"Transcranial direct current stimulation associated with gait training in Parkinson\u2019s disease: a pilot randomized clinical trial","volume":"20","author":"Costa-Ribeiro","year":"2017","journal-title":"Dev Neurorehabil"},{"key":"2023101202051495000_94.11.938.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.05.016"},{"key":"2023101202051495000_94.11.938.7","doi-asserted-by":"crossref","unstructured":"Koganemaru S , Mikami Y , Maezawa H , et al . Anodal transcranial patterned stimulation of the motor cortex during gait can induce activity-dependent corticospinal plasticity to alter human gait. PLoS One 2018;13:e0208691. doi:10.1371\/journal.pone.0208691","DOI":"10.1371\/journal.pone.0208691"},{"key":"2023101202051495000_94.11.938.8","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.1161\/STROKEAHA.119.025354","article-title":"Gait-synchronized rhythmic brain stimulation improves poststroke gait disturbance: a pilot study","volume":"50","author":"Koganemaru","year":"2019","journal-title":"Stroke"},{"key":"2023101202051495000_94.11.938.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.01.019"},{"key":"2023101202051495000_94.11.938.10","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1999.82.1.290"},{"key":"2023101202051495000_94.11.938.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(97)00381-9"},{"key":"2023101202051495000_94.11.938.12","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1093\/brain\/122.7.1271","article-title":"Mechanisms underlying gait disturbance in Parkinson\u2019s disease: a single photon emission computed tomography study","volume":"122 (Pt 7)","author":"Hanakawa","year":"1999","journal-title":"Brain"},{"key":"2023101202051495000_94.11.938.13","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.5.965"},{"key":"2023101202051495000_94.11.938.14","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31827f0fd1"},{"key":"2023101202051495000_94.11.938.15","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.47.1.1"},{"key":"2023101202051495000_94.11.938.16","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000324625.00404.15"},{"key":"2023101202051495000_94.11.938.17","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.neures.2019.11.001","article-title":"Gait-synchronized oscillatory brain stimulation modulates common neural drives to ankle muscles in patients after stroke: a pilot study","volume":"156","author":"Kitatani","year":"2020","journal-title":"Neurosci Res"},{"key":"2023101202051495000_94.11.938.18","doi-asserted-by":"crossref","first-page":"4791","DOI":"10.1111\/ejn.14919","article-title":"Gait-combined transcranial alternating current stimulation modulates cortical control of muscle activities during gait","volume":"52","author":"Kitatani","year":"2020","journal-title":"Eur J Neurosci"},{"key":"2023101202051495000_94.11.938.19","doi-asserted-by":"publisher","DOI":"10.1177\/1545968314552528"},{"key":"2023101202051495000_94.11.938.20","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5867-12.2013"},{"key":"2023101202051495000_94.11.938.21","doi-asserted-by":"crossref","unstructured":"Reato D , Rahman A , Bikson M , et al . Effects of weak transcranial alternating current stimulation on brain activity-a review of known mechanisms from animal studies. Front Hum Neurosci 2013;7:687. doi:10.3389\/fnhum.2013.00687","DOI":"10.3389\/fnhum.2013.00687"},{"key":"2023101202051495000_94.11.938.22","doi-asserted-by":"crossref","unstructured":"\u017divanovi\u0107 M , Bjeki\u0107 J , Konstantinovi\u0107 U , et al . Effects of online parietal transcranial electric stimulation on associative memory: a direct comparison between tDCS, Theta tACS, and Theta-oscillatory tDCS. Sci Rep 2022;12:14091. doi:10.1038\/s41598-022-18376-5","DOI":"10.1038\/s41598-022-18376-5"},{"key":"2023101202051495000_94.11.938.23","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.1007\/s00429-016-1355-1","article-title":"Effects of cerebellar transcranial alternating current stimulation on motor cortex excitability and motor function","volume":"222","author":"Naro","year":"2017","journal-title":"Brain Struct Funct"},{"key":"2023101202051495000_94.11.938.24","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-0102(98)00006-6"},{"key":"2023101202051495000_94.11.938.25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000496107"},{"key":"2023101202051495000_94.11.938.26","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws360"},{"key":"2023101202051495000_94.11.938.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.03.050"},{"key":"2023101202051495000_94.11.938.28","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.neures.2020.01.002","article-title":"Oscillotherapeutics - time-targeted interventions in epilepsy and beyond","volume":"152","author":"Takeuchi","year":"2020","journal-title":"Neurosci Res"},{"key":"2023101202051495000_94.11.938.29","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa450"},{"key":"2023101202051495000_94.11.938.30","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.brs.2017.11.015","article-title":"Effects of cerebellar Neuromodulation in movement disorders: a systematic review","volume":"11","author":"Fran\u00e7a","year":"2018","journal-title":"Brain Stimul"},{"key":"2023101202051495000_94.11.938.31","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/brain\/awz314","article-title":"Freezing of gait: understanding the complexity of an enigmatic phenomenon","volume":"143","author":"Weiss","year":"2020","journal-title":"Brain"},{"key":"2023101202051495000_94.11.938.32","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-016-8174-4"},{"key":"2023101202051495000_94.11.938.33","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.20815"},{"key":"2023101202051495000_94.11.938.34","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30403-9"},{"key":"2023101202051495000_94.11.938.35","doi-asserted-by":"crossref","unstructured":"Ferrucci R , Bocci T , Cortese F , et al . Cerebellar transcranial direct current stimulation in neurological disease. Cerebellum Ataxias 2016;3:16. doi:10.1186\/s40673-016-0054-2","DOI":"10.1186\/s40673-016-0054-2"},{"key":"2023101202051495000_94.11.938.36","doi-asserted-by":"publisher","DOI":"10.1177\/0269215514534277"},{"key":"2023101202051495000_94.11.938.37","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/mds.26561","article-title":"Mild cognitive impairment in Parkinson\u2019s disease is improved by transcranial direct current stimulation combined with physical therapy","volume":"31","author":"Manenti","year":"2016","journal-title":"Mov Disord"},{"key":"2023101202051495000_94.11.938.38","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-015-0737-x"},{"key":"2023101202051495000_94.11.938.39","doi-asserted-by":"crossref","first-page":"96","DOI":"10.3390\/brainsci10020096","article-title":"Cerebellar transcranial direct current stimulation in people with Parkinson\u2019s disease: a pilot study","volume":"10","author":"Workman","year":"2020","journal-title":"Brain Sciences"},{"key":"2023101202051495000_94.11.938.40","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20692"}],"container-title":["Journal of Neurology, Neurosurgery &amp; Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jnnp-2022-329966","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T09:08:10Z","timestamp":1697101690000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnnp.bmj.com\/lookup\/doi\/10.1136\/jnnp-2022-329966"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,9]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,10,12]]},"published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1136\/jnnp-2022-329966"],"URL":"https:\/\/doi.org\/10.1136\/jnnp-2022-329966","relation":{},"ISSN":["0022-3050","1468-330X"],"issn-type":[{"value":"0022-3050","type":"print"},{"value":"1468-330X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,9]]}}}