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We hypothesized that the communication between the insula (part of the limbic system) and sensorimotor cortex in PD is altered and hemispheric asymmetric. Furthermore, that this asymmetry relates to non\u2010motor symptoms, and specifically, that apathy\u2010related asymmetry is unique to PD. To test these hypotheses, we used a novel multivariate time\u2010frequency analysis method applied to resting\u2010state functional magnetic resonance imaging (MRI) data of 28 controls and 25 participants with PD measured in their OFF medication state. The analysis infers directionality of coupling, that is, afferent or efferent, among four anatomical regions, thus defining directed pathways of information flow, which enables the extension of symmetry measures to include directionality. A major right asymmetry reduction of the dorsal\u2010posterior insula efferent and a slight bilateral increase of insula afferent pathways were observed in participants with PD versus controls. Between\u2010group pathways that correlated with mild cognitive impairments combined the central\u2010executive and default\u2010mode networks through the right insula. Apathy\u2010correlated pathways of the posterior insula in participants with PD versus controls exhibited reduced right efferent and increased left afferent. Because apathy scores were comparable between the groups and effects of the other motor and non\u2010motor symptoms were statistically removed by the analysis, the differences in apathy\u2010correlated pathways were suggested as unique to PD. These pathways could be predictors in the pre\u2010symptomatic phase in patients with apathy.<\/jats:p>","DOI":"10.1111\/ejn.15432","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T13:00:50Z","timestamp":1630069250000},"page":"6267-6280","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Asymmetry of the insula\u2010sensorimotor circuit in Parkinson's disease"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-7808","authenticated-orcid":false,"given":"Gadi","family":"Goelman","sequence":"first","affiliation":[{"name":"Department of Neurology, Hadassah Hebrew University Medical Center The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4341-330X","authenticated-orcid":false,"given":"Rotem","family":"Dan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hadassah Hebrew University Medical Center The Hebrew University of Jerusalem  Jerusalem Israel"},{"name":"Edmond and Lily Safra Center for Brain Sciences (ELSC) The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filip","family":"R\u016f\u017ei\u010dka","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital Charles University  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ondrej","family":"Bezdicek","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital Charles University  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Jech","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital Charles University  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)62678-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23895"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.08.008"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","unstructured":"Beck A. 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