{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:29:53Z","timestamp":1790692193254,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T00:00:00Z","timestamp":1642118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p>Generalized Anxiety Disorder (GAD) is a highly prevalent yet poorly understood chronic mental disorder. Previous studies have associated GAD with excessive activation of the right dorsolateral prefrontal cortex (DLPFC). This study aimed to investigate the effect of low-frequency repetitive transcranial magnetic stimulation (repetitive TMS, rTMS) targeting the right DLPFC on clinical symptoms and TMS-evoked time-varying brain network connectivity in patients with GAD. Eleven patients with GAD received 1 Hz rTMS treatment targeting the right DLPFC for 10 days. The severity of the clinical symptoms was evaluated using the Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD) at baseline, right after treatment, and at the one-month follow-up. Co-registration of single-pulse TMS (targeting the right DLPFC) and electroencephalography (TMS-EEG) was performed pre- and post-treatment in these patients and 11 healthy controls. Time-varying brain network connectivity was analyzed using the adaptive directed transfer function. The scores of HAMA and HAMD significantly decreased after low-frequency rTMS treatment, and these improvements in ratings remained at the one-month follow-up. Analyses of the time-varying EEG network in the healthy controls showed a continuous weakened connection information outflow in the left frontal and mid-temporal regions. Compared with the healthy controls, the patients with GAD showed weakened connection information outflow in the left frontal pole and the posterior temporal pole at baseline. After 10-day rTMS treatment, the network patterns showed weakened connection information outflow in the left frontal and temporal regions. The time-varying EEG network changes induced by TMS perturbation targeting right DLPFC in patients with GAD were characterized by insufficient information outflow in the left frontal and temporal regions. Low-frequency rTMS targeting the right DLPFC reversed these abnormalities and improved the clinical symptoms of GAD.<\/jats:p>","DOI":"10.3389\/fpsyt.2021.779201","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T05:47:46Z","timestamp":1642139266000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Repetitive Transcranial Magnetic Stimulation Modulates Frontal and Temporal Time-Varying EEG Network in Generalized Anxiety Disorder: A Pilot Study"],"prefix":"10.3389","volume":"12","author":[{"given":"Penghui","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningning","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wensi","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1001\/archpsyc.62.6.593","article-title":"Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication","volume":"62","author":"Kessler","year":"2005","journal-title":"Arch Gen Psychiatry."},{"key":"B2","doi-asserted-by":"publisher","first-page":"611","DOI":"10.3238\/arztebl.2018.0611","article-title":"The diagnosis and treatment of anxiety disorders","volume":"155","author":"Str\u00f6hle","year":"2018","journal-title":"Dtsch Arztebl Int."},{"key":"B3","doi-asserted-by":"publisher","first-page":"ITC49","DOI":"10.7326\/AITC201904020","article-title":"Generalized anxiety disorder","volume":"170","author":"DeMartini","year":"2019","journal-title":"Ann Intern Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s11920-017-0779-5","article-title":"Anxiety disorders and temperament-an update review","volume":"19","author":"Kampman","year":"2017","journal-title":"Curr Psychiatry Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1080\/15622970802465807","article-title":"World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders\u2014first revision","volume":"9","author":"Bandelow","year":"2008","journal-title":"World J Biol Psychiatry."},{"key":"B6","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1080\/00029157.2018.1458594","article-title":"Cognitive behavioral therapy, mindfulness, and hypnosis as treatment methods for generalized anxiety disorder","volume":"61","author":"Daitch","year":"2018","journal-title":"Am J Clin Hypn."},{"key":"B7","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/S0140-6736(18)31793-8","article-title":"Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis","volume":"393","author":"Slee","year":"2019","journal-title":"Lancet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1517\/14656566.2013.759559","article-title":"New approaches to the pharmacological management of generalized anxiety disorder","volume":"14","author":"Buoli","year":"2013","journal-title":"Expert Opin Pharmacother."},{"key":"B9","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1017\/S1461145710001434","article-title":"Evidence-based pharmacological treatment of generalized anxiety disorder","volume":"14","author":"Baldwin","year":"2011","journal-title":"Int J Neuropsychopharmacol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.1284","article-title":"Transcranial magnetic stimulation in anxiety and trauma-related disorders: a systematic review and meta-analysis","author":"Cirillo","year":"2019","journal-title":"Brain Behav."},{"key":"B11","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1177\/1039856217748249","article-title":"Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists","volume":"26","author":"Taylor","year":"2018","journal-title":"Australas Psychiatry"},{"key":"B12","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1109\/TBCAS.2020.2981012","article-title":"Equipment for repetitive transcranial magnetic stimulation","volume":"14","author":"Pernia","year":"2020","journal-title":"IEEE Trans Biomed Circuits Syst."},{"key":"B13","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1097\/WNP.0000000000000098","article-title":"Neuroimaging effects of 1 Hz right temporoparietal rTMS on normal auditory processing: implications for clinical hallucination treatment paradigms","volume":"31","author":"Tracy","year":"2014","journal-title":"J Clin Neurophysiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.neulet.2014.06.003","article-title":"The effects of 3 weeks of rTMS treatment on P200 amplitude in patients with depression","volume":"577","author":"Choi","year":"2014","journal-title":"Neurosci Lett."},{"key":"B15","doi-asserted-by":"publisher","first-page":"351","DOI":"10.3389\/fpsyt.2019.00351","article-title":"Three weeks of rTMS treatment maintains clinical improvement but not electrophysiological changes in patients with depression: a 6-week follow-up pilot study","volume":"10","author":"Choi","year":"2019","journal-title":"Front Psychiatry."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.09.008","article-title":"The use of repetitive transcranial magnetic stimulation for stroke rehabilitation: a systematic review","volume":"27","author":"Dion\u00edsio","year":"2018","journal-title":"J Stroke Cerebrovasc Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1192\/bjp.2019.75","article-title":"Repetitive transcranial magnetic stimulation in non-treatment-resistant depression","volume":"215","author":"Kiebs","year":"2019","journal-title":"Br J Psychiatry."},{"key":"B18","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.psychres.2018.08.013","article-title":"Repetitive transcranial magnetic stimulation in the treatment of eating disorders: a review of safety and efficacy","volume":"269","author":"Rachid","year":"2018","journal-title":"Psychiatry Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1016\/j.clinthera.2020.05.016","article-title":"Review of transcranial magnetic stimulation in epilepsy","volume":"42","author":"Tsuboyama","year":"2020","journal-title":"Clin Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/j.jad.2018.12.102","article-title":"High-frequency repetitive transcranial magnetic stimulation (rTMS) improves neurocognitive function in bipolar disorder","volume":"246","author":"Yang","year":"2019","journal-title":"J Affect Disord."},{"key":"B21","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.clinph.2019.01.001","article-title":"Clinical utility and prospective of TMS-EEG","volume":"130","author":"Tremblay","year":"2019","journal-title":"Clin Neurophysiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.neurol.2015.11.004","article-title":"Transcranial magnetic stimulation (TMS) coupled with electroencephalography (EEG): biomarker of the future","volume":"172","author":"Kimiskidis","year":"2016","journal-title":"Rev Neurol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/j.clinph.2019.02.004","article-title":"The new era of TMS-EEG: Moving towards the clinical practice","volume":"130","author":"Koch","year":"2019","journal-title":"Clin Neurophysiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.sleep.2019.01.007","article-title":"Repetitive transcranial magnetic stimulation (rTMS) modulates time-varying electroencephalography (EEG) network in primary insomnia patients: a TMS-EEG study","volume":"56","author":"Song","year":"2019","journal-title":"Sleep Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"22","DOI":"10.3389\/fninf.2019.00022","article-title":"Transcranial magnetic stimulation to the middle frontal gyrus during attention modes induced dynamic module reconfiguration in brain networks","volume":"13","author":"Song","year":"2019","journal-title":"Front Neuroinform."},{"key":"B26","doi-asserted-by":"publisher","first-page":"20611","DOI":"10.18632\/aging.103946","article-title":"Repetitive transcranial magnetic stimulation of the cerebellum improves ataxia and cerebello-fronto plasticity in multiple system atrophy: a randomized, double-blind, sham-controlled and TMS-EEG study","volume":"12","author":"Song","year":"2020","journal-title":"Aging."},{"key":"B27","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1111\/j.1749-6632.2012.06751.x","article-title":"Functional imaging studies of emotion regulation: a synthetic review and evolving model of the cognitive control of emotion","volume":"1251","author":"Ochsner","year":"2012","journal-title":"Ann N Y Acad Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.neuroimage.2011.05.073","article-title":"Fear is only as deep as the mind allows: a coordinate-based meta-analysis of neuroimaging studies on the regulation of negative affect","volume":"58","author":"Diekhof","year":"2011","journal-title":"Neuroimage."},{"key":"B29","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.jagp.2014.05.003","article-title":"Emotion reactivity and regulation in late-life generalized anxiety disorder: functional connectivity at baseline and post-treatment","volume":"23","author":"Andreescu","year":"2015","journal-title":"Am J Geriatr Psychiatry."},{"key":"B30","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/j.2044-8341.1959.tb00467.x","article-title":"The assessment of anxiety states by rating","volume":"32","author":"Hamilton","year":"1959","journal-title":"Br J Med Psychol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1136\/jnnp.23.1.56","article-title":"A rating scale for depression","volume":"23","author":"Hamilton","year":"1960","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B32","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3389\/fncom.2017.00077","article-title":"Time-varying networks of inter-ictal discharging reveal epileptogenic zone","author":"Zhang","year":"2017","journal-title":"Front Comput Neurosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1109\/10.668741","article-title":"Adaptive AR modeling of nonstationary time series by means of Kalman filtering","volume":"45","author":"Arnold","year":"1998","journal-title":"IEEE Transac Biomed Eng."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.4088\/JCP.v69n0708","article-title":"A preliminary study of fMRI-guided rTMS in the treatment of generalized anxiety disorder","volume":"69","author":"Bystritsky","year":"2008","journal-title":"J Clin Psychiatry."},{"key":"B35","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1192\/bjp.bp.115.168203","article-title":"Repetitive transcranial magnetic stimulation for generalised anxiety disorder: a pilot randomised, double-blind, sham-controlled trial","volume":"209","author":"Diefenbach","year":"2016","journal-title":"Br J Psychiatry."},{"key":"B36","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1037\/0021-843X.106.3.376","article-title":"Patterns of regional brain activity differentiate types of anxiety","volume":"106","author":"Heller","year":"1997","journal-title":"J Abnorm Psychol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-981-32-9705-0_1","article-title":"Task MRI-based functional brain network of anxiety","volume":"1191","author":"Lai","year":"2020","journal-title":"Adv Exp Med Biol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.bandc.2007.08.002","article-title":"Alteration of expected hemispheric asymmetries: valence and arousal effects in neuropsychological models of emotion","volume":"66","author":"Alfano","year":"2008","journal-title":"Brain Cogn."},{"key":"B39","doi-asserted-by":"publisher","first-page":"4048916","DOI":"10.1155\/2020\/4048916","article-title":"Altered default mode network and salience network functional connectivity in patients with generalized anxiety disorders: an ICA-based resting-state fMRI study","volume":"2020","author":"Xiong","year":"2020","journal-title":"Evid Based Complement Alternat Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"553","DOI":"10.3389\/fnhum.2016.00553","article-title":"Goal directed worry rules are associated with distinct patterns of amygdala functional connectivity and vagal modulation during perseverative cognition","volume":"10","author":"Meeten","year":"2016","journal-title":"Front Hum Neurosci."}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2021.779201\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T05:47:49Z","timestamp":1642139269000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2021.779201\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,14]]},"references-count":40,"alternative-id":["10.3389\/fpsyt.2021.779201"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2021.779201","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,14]]},"article-number":"779201"}}