{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:50:38Z","timestamp":1790283038912,"version":"4.1.0"},"reference-count":32,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Depressive symptoms in patients with Parkinson disease (PD) are common and burdensome. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC-L) is effective but time intensive, limiting practicality.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the antidepressant efficacy and neurofunctional effects of the ultra-brief intermittent theta-burst stimulation (iTBS) protocol for patients with PD depression (PD-D) compared with active HF-rTMS and sham stimulation.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This triple-arm, randomized, sham-controlled single-center clinical trial was conducted at Xinhua Hospital, Shanghai Jiao Tong University School of Medicine in China from August 1, 2024, to January 31, 2025. Patients with PD aged 50 to 80 years with 24-item Hamilton Depression Rating Scale (HAMD-24) scores of 8 to 20 were randomized 1:1:1 to iTBS, HF-rTMS, or sham iTBS. Outcomes were assessed at baseline, week 1, week 2, and week 6. Data analysis was finalized in February 2026.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Ten daily sessions over 2 weeks: active iTBS (3 minutes and 20 seconds), active HF-rTMS (20 minutes), or sham iTBS.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was the HAMD-24 score at week 2. Secondary outcomes included anxiety (measured by the 14-item Hamilton Anxiety Rating Scale [HAMA-14]), motor symptoms (measured by the Movement Disorder Society\u2013Unified Parkinson Disease Rating Scale), quality of life (measured by the 8-item Parkinson\u2019s Disease Questionnaire [PDQ-8]), and prefrontal hemodynamics (measured using functional near-infrared spectroscopy). Primary analysis followed the principle of intention to treat.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 54 randomized participants (mean [SD] age, 70.1 [5.3] years; 29 men [53.7%]), 50 (92.6%) completed the trial. Linear mixed-effects models revealed a significant group\u2009\u00d7\u2009time interaction for the HAMD-24 (\n F<\/jats:italic>\n 6,145<\/jats:sub>\n \u2009=\u20094.84;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). At week 2, both active interventions were superior to sham (HAMD-24 score mean difference: iTBS, \u22124.97 [95% CI, \u22127.71 to \u22122.23];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001; and HF-rTMS, \u22125.73 [95% CI, \u22128.95 to \u22122.51];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). Effects persisted at week 6 (HAMD-24 score mean difference: iTBS vs sham, \u22126.05 [95% CI, \u22129.26 to \u22122.83];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001; and HF-rTMS vs sham, \u22125.57 [95% CI, \u22129.36 to \u22121.78];\n P<\/jats:italic>\n \u2009=\u2009.002), with no between-group differences. Both interventions improved PDQ-8 scores at week 2 (mean difference: iTBS vs sham, \u22122.33 [95% CI, \u22123.33 to \u22121.33];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001; and HF-rTMS vs sham, \u22122.43 [95% CI, \u22124.60 to \u22120.26];\n P<\/jats:italic>\n \u2009=\u2009.02). iTBS also alleviated anxiety (mean difference: HAMA-14 score vs sham, \u22124.04 [95% CI, \u22127.73 to \u22120.35;\n P<\/jats:italic>\n \u2009=\u2009.03). Active stimulations increased DLPFC-L activation (estimated adjusted difference: iTBS vs sham, 151.18 [95% CI, 51.24-251.11];\n P<\/jats:italic>\n \u2009=\u2009.004; and HF-rTMS vs sham, 173.26 [95% CI, 71.92-274.60];\n P<\/jats:italic>\n \u2009=\u2009.001) and reduced time in low-efficiency connectivity states (iTBS: median change, \u22120.12 [IQR, \u22120.29 to 0.02]; false discovery rate\u2013corrected\n P<\/jats:italic>\n \u2009=\u2009.045; and HF-rTMS: \u22120.12 [IQR, \u22120.32 to 0]; false discovery rate\u2013corrected\n P<\/jats:italic>\n \u2009=\u2009.02).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this randomized clinical trial of patients with PD-D, the ultra-brief iTBS achieved antidepressant efficacy comparable with that of standard HF-rTMS while markedly reducing treatment time, supporting its use as a pragmatic therapy for PD-D. This study suggests the promise of symptom-stratified neuromodulation for personalized treatment protocols.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n Chinese Clinical Trial Registry Identifier:\n ChiCTR2100044421<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.13580","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:30:35Z","timestamp":1779291035000},"page":"e2613580","source":"Crossref","is-referenced-by-count":3,"title":["Intermittent Theta-Burst Stimulation for Depressive Symptoms in Parkinson Disease"],"prefix":"10.1001","volume":"9","author":[{"given":"Miaomiao","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Neurology, Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Yangpu District, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjie","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Nursing, Huashan Hospital Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Yangpu District, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Yangpu District, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pain Medicine, Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Yangpu District, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wenzhou Central Hospital,Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Yangpu District, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Yangpu District, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Yangpu District, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenguo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Yangpu District, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Yangpu District, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"issue":"10","key":"zoi260399r1","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1136\/jnnp-2023-333007","article-title":"Neuroanatomical and prognostic associations of depression in Parkinson\u2019s disease.","volume":"95","author":"Badenoch","year":"2024","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"4","key":"zoi260399r2","doi-asserted-by":"publisher","first-page":"277","DOI":"10.2174\/1570159X17666191016094857","article-title":"Drug choices and advancements for managing depression in Parkinson\u2019s disease.","volume":"18","author":"Assogna","year":"2020","journal-title":"Curr Neuropharmacol"},{"issue":"12","key":"zoi260399r3","doi-asserted-by":"publisher","first-page":"4323","DOI":"10.1007\/s10072-023-06891-w","article-title":"Exploring depression in Alzheimer\u2019s disease: an Italian Delphi Consensus on phenomenology, diagnosis, and management.","volume":"44","author":"Padovani","year":"2023","journal-title":"Neurol Sci"},{"issue":"1","key":"zoi260399r4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1177\/08919887241254471","article-title":"Greater apathy associated with selective serotonin reuptake inhibitor use in Parkinson\u2019s disease.","volume":"38","author":"Schade","year":"2025","journal-title":"J Geriatr Psychiatry Neurol"},{"issue":"14","key":"zoi260399r5","doi-asserted-by":"publisher","first-page":"2311","DOI":"10.1002\/mds.23270","article-title":"The impact of left prefrontal repetitive transcranial magnetic stimulation on depression in Parkinson\u2019s disease: a randomized, double-blind, placebo-controlled study.","volume":"25","author":"Pal","year":"2010","journal-title":"Mov Disord"},{"issue":"7","key":"zoi260399r6","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1007\/s00415-016-8160-x","article-title":"Effect of high-frequency repetitive transcranial magnetic stimulation on major depressive disorder in patients with Parkinson\u2019s disease.","volume":"263","author":"Shin","year":"2016","journal-title":"J Neurol"},{"issue":"2","key":"zoi260399r7","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.clinph.2019.11.002","article-title":"Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014-2018).","volume":"131","author":"Lefaucheur","year":"2020","journal-title":"Clin Neurophysiol"},{"issue":"3","key":"zoi260399r8","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.brs.2016.01.006","article-title":"Ten years of theta burst stimulation in humans: established knowledge, unknowns and prospects.","volume":"9","author":"Suppa","year":"2016","journal-title":"Brain Stimul"},{"key":"zoi260399r9","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2023.1244289","article-title":"Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review.","volume":"14","author":"Lan","year":"2023","journal-title":"Front Psychiatry"},{"issue":"1","key":"zoi260399r10","doi-asserted-by":"publisher","first-page":"3700","DOI":"10.1038\/s41598-019-40273-7","article-title":"Differential role of prefrontal, temporal and parietal cortices in verbal and figural fluency: implications for the supramodal contribution of executive functions.","volume":"9","author":"Ghanavati","year":"2019","journal-title":"Sci Rep"},{"key":"zoi260399r11","doi-asserted-by":"publisher","journal-title":"Mov Disord","DOI":"10.1002\/mds.26424"},{"issue":"2","key":"zoi260399r12","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/j.jad.2013.04.028","article-title":"Severity classification on the Hamilton Depression Rating Scale.","volume":"150","author":"Zimmerman","year":"2013","journal-title":"J Affect Disord"},{"issue":"2","key":"zoi260399r13","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/0165-1781(85)90057-5","article-title":"The Modified Hamilton Rating Scale for Depression: reliability and validity.","volume":"14","author":"Miller","year":"1985","journal-title":"Psychiatry Res"},{"issue":"2","key":"zoi260399r14","doi-asserted-by":"publisher","first-page":"132","DOI":"10.35772\/ghm.2023.01043","article-title":"Decreased resting-state functional connectivity and brain network abnormalities in the prefrontal cortex of elderly patients with Parkinson\u2019s disease accompanied by depressive symptoms.","volume":"6","author":"Tian","year":"2024","journal-title":"Glob Health Med"},{"key":"zoi260399r15","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1142741","article-title":"Pattern of prefrontal cortical activation and network revealed by task-based and resting-state fNIRS in Parkinson\u2019s disease\u2019s patients with overactive bladder symptoms.","volume":"17","author":"Hou","year":"2023","journal-title":"Front Neurosci"},{"key":"zoi260399r16","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1109\/TNSRE.2023.3242263","article-title":"An fNIRS-based dynamic functional connectivity analysis method to signify functional neurodegeneration of Parkinson\u2019s disease.","volume":"31","author":"Lu","year":"2023","journal-title":"IEEE Trans Neural Syst Rehabil Eng"},{"issue":"10","key":"zoi260399r17","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1007\/s10072-015-2345-4","article-title":"Repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression in Parkinson disease: a meta-analysis of randomized controlled clinical trials.","volume":"36","author":"Xie","year":"2015","journal-title":"Neurol Sci"},{"key":"zoi260399r18","doi-asserted-by":"publisher","first-page":"273","DOI":"10.2147\/NDT.S156695","article-title":"Effectiveness of high-frequency repetitive transcranial magnetic stimulation in patients with depression and Parkinson\u2019s disease: a meta-analysis of randomized, controlled clinical trials.","volume":"14","author":"Qin","year":"2018","journal-title":"Neuropsychiatr Dis Treat"},{"key":"zoi260399r19","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2024.115361","article-title":"Four weeks standard vs. one week accelerated intermittent theta burst stimulation for the treatment of depression\u2014a retrospective analysis.","volume":"479","author":"Dragon","year":"2025","journal-title":"Behav Brain Res"},{"issue":"10131","key":"zoi260399r20","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1016\/S0140-6736(18)30295-2","article-title":"Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial.","volume":"391","author":"Blumberger","year":"2018","journal-title":"Lancet"},{"issue":"3","key":"zoi260399r21","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/j.brs.2022.05.011","article-title":"Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: a randomized controlled trial (THETA-DEP).","volume":"15","author":"Bulteau","year":"2022","journal-title":"Brain Stimul"},{"key":"zoi260399r22","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2024.120596","article-title":"Neural response during prefrontal theta burst stimulation: interleaved TMS-fMRI of full iTBS protocols.","volume":"291","author":"Chang","year":"2024","journal-title":"Neuroimage"},{"issue":"5","key":"zoi260399r23","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1002\/hbm.25740","article-title":"Critical role of rhythms in prefrontal transcranial magnetic stimulation for depression: a randomized sham-controlled study.","volume":"43","author":"Tsai","year":"2022","journal-title":"Hum Brain Mapp"},{"issue":"11","key":"zoi260399r24","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.3390\/cells12111525","article-title":"Intermittent theta burst stimulation improves motor and behavioral dysfunction through modulation of NMDA receptor subunit composition in experimental model of Parkinson\u2019s disease.","volume":"12","author":"Zeljkovic Jovanovic","year":"2023","journal-title":"Cells"},{"issue":"12","key":"zoi260399r25","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1038\/s41562-021-01161-1","article-title":"Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease.","volume":"5","author":"Siddiqi","year":"2021","journal-title":"Nat Hum Behav"},{"issue":"41","key":"zoi260399r26","doi-asserted-by":"publisher","first-page":"E4367","DOI":"10.1073\/pnas.1405003111","article-title":"Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases.","volume":"111","author":"Fox","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"zoi260399r27","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.biopsych.2019.07.023","article-title":"A human depression circuit derived from focal brain lesions.","volume":"86","author":"Padmanabhan","year":"2019","journal-title":"Biol Psychiatry"},{"issue":"8","key":"zoi260399r28","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1176\/appi.ajp.2019.19070720","article-title":"Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression.","volume":"177","author":"Cole","year":"2020","journal-title":"Am J Psychiatry"},{"issue":"6","key":"zoi260399r29","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/j.biopsych.2023.11.011","article-title":"Targeting symptom-specific networks with transcranial magnetic stimulation.","volume":"95","author":"Siddiqi","year":"2024","journal-title":"Biol Psychiatry"},{"issue":"5","key":"zoi260399r30","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1176\/appi.ajp.2019.19090915","article-title":"Distinct symptom-specific treatment targets for circuit-based neuromodulation.","volume":"177","author":"Siddiqi","year":"2020","journal-title":"Am J Psychiatry"},{"issue":"19","key":"zoi260399r31","doi-asserted-by":"publisher","first-page":"6124","DOI":"10.1523\/JNEUROSCI.0728-09.2009","article-title":"Dose-dependent inverted U-shaped effect of dopamine (D2-like) receptor activation on focal and nonfocal plasticity in humans.","volume":"29","author":"Monte-Silva","year":"2009","journal-title":"J Neurosci"},{"issue":"pt 18","key":"zoi260399r32","doi-asserted-by":"publisher","first-page":"3415","DOI":"10.1113\/jphysiol.2010.190181","article-title":"Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity.","volume":"588","author":"Monte-Silva","year":"2010","journal-title":"J Physiol"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2849167\/hou_2026_oi_260399_1778598211.78137.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:30:36Z","timestamp":1779291036000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2849167"}},"subtitle":["A Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":32,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2026.13580","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]}}}