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Neurosci."],"abstract":"<jats:p>The aim of the current resting-state functional magnetic resonance imaging (fMRI) study was to investigate the potential mechanism of schizophrenia through the posterior\u2013anterior cerebrum imbalance in methylazoxymethanol acetate (MAM) rats and to evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as an early-stage intervention. The rats were divided into four groups: the MAM-sham group, vehicle-sham group, MAM-rTMS group, and vehicle-rTMS group. The rTMS treatment was targeted in the visual cortex (VC) in adolescent rats. Granger Causality Analysis (GCA) was used to evaluate the effective connectivity between regions of interest. Results demonstrated a critical right VC\u2013nucleus accumbens (Acb)\u2013orbitofrontal cortex (OFC) pathway in MAM rats; significant differences of effective connectivity (EC) were found between MAM-sham and vehicle-sham groups (from Acb shell to OFC: <jats:italic>t<\/jats:italic> = \u22122.553, <jats:italic>p<\/jats:italic> = 0.021), MAM-rTMS and MAM-sham groups (from VC to Acb core: <jats:italic>t<\/jats:italic> = \u22122.206, <jats:italic>p<\/jats:italic> = 0.043; from Acb core to OFC: <jats:italic>t<\/jats:italic> = 4.861, <jats:italic>p<\/jats:italic> &amp;lt; 0.001; from Acb shell to OFC: <jats:italic>t<\/jats:italic> = 4.025, <jats:italic>p<\/jats:italic> = 0.001), and MAM-rTMS and vehicle-rTMS groups (from VC to Acb core: <jats:italic>t<\/jats:italic> = \u22122.482, <jats:italic>p<\/jats:italic> = 0.025; from VC to Acb shell: <jats:italic>t<\/jats:italic> = \u22122.872, <jats:italic>p<\/jats:italic> = 0.012; from Acb core to OFC: <jats:italic>t<\/jats:italic> = 4.066, <jats:italic>p<\/jats:italic> = 0.001; from Acb shell to OFC: <jats:italic>t<\/jats:italic> = 3.458, <jats:italic>p<\/jats:italic> = 0.004) in the right hemisphere. Results of the early-stage rTMS intervention revealed that right nucleus accumbens played the role as a central hub, and VC was a potentially novel rTMS target region during adolescent schizophrenia. Moreover, the EC of right nucleus accumbens shell and orbitofrontal cortex was demonstrated to be a potential biomarker. To our knowledge, this was the first resting-state fMRI study using GCA to assess the deficits of a visual-reward neural pathway and the effectiveness of rTMS treatment in MAM rats. More randomized controlled trials in both animal models and schizophrenia patients are needed to further elucidate the disease characteristics.<\/jats:p>","DOI":"10.3389\/fnins.2021.652715","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T06:38:57Z","timestamp":1621579137000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Early-Stage Repetitive Transcranial Magnetic Stimulation Altered Posterior\u2013Anterior Cerebrum Effective Connectivity in Methylazoxymethanol Acetate Rats"],"prefix":"10.3389","volume":"15","author":[{"given":"Huiling","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dandan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaning","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyu","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengfei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanbo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinfeng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xizhe","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"53","DOI":"10.9758\/cpn.2013.11.2.53","article-title":"Use of repetitive transcranial magnetic stimulation for treatment in psychiatry.","volume":"11","author":"Aleman","year":"2013","journal-title":"Clin. 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