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The objectives of this study were to investigate whether apathy and depression in de novo parkinsonian patients are related to structural alterations and how structural abnormalities relate to serotonergic or dopaminergic dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We compared the morphological and microstructural architecture in gray matter using voxel\u2010based morphometry and diffusion tensor imaging coupled with white matter tract\u2010based spatial statistics in a multimodal imaging case\u2010control study enrolling 14 apathetic and 13 nonapathetic patients with de novo Parkinson's disease and 15 age\u2010matched healthy controls, paired with PET imaging of the presynaptic dopaminergic and serotonergic systems.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>De novo parkinsonian patients with apathy had bilateral microstructural alterations in the medial corticostriatal limbic system, exhibiting decreased fractional anisotropy and increased mean diffusivity in the anterior striatum and pregenual anterior cingulate cortex in conjunction with serotonergic dysfunction. Furthermore, microstructural alterations extended to the medial frontal cortex, the subgenual anterior cingulate cortex and subcallosal gyrus, the medial thalamus, and the caudal midbrain, suggesting disruption of long\u2010range nondopaminergic projections originating in the brainstem, in addition to microstructural alterations in callosal interhemispheric connections and frontostriatal association tracts early in the disease course. In addition, microstructural abnormalities related to depressive symptoms in apathetic and nonapathetic patients revealed a distinct, mainly right\u2010sided limbic subnetwork involving limbic and frontal association tracts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Early limbic microstructural alterations specifically related to apathy and depression emphasize the role of early disruption of ascending nondopaminergic projections and related corticocortical and corticosubcortical networks which underpin the variable expression of nonmotor and neuropsychiatric symptoms in Parkinson's disease. \u00a9 2019 International Parkinson and Movement Disorder Society<\/jats:p>\n                  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Movement Disorders Unit, Neurology Department  Grenoble France"},{"name":"Univ Grenoble Alpes, Inserm U1216, Neurosciences, GIN  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9on","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Univ Lyon, Institut des Sciences Cognitives Marc Jeannerod, CNRS  UMR 5229 Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8792-8586","authenticated-orcid":false,"given":"V\u00e9ronique","family":"Sgambato","sequence":"additional","affiliation":[{"name":"Univ Lyon, Institut des Sciences Cognitives Marc Jeannerod, CNRS  UMR 5229 Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Broussolle","sequence":"additional","affiliation":[{"name":"Univ Lyon, Institut des Sciences Cognitives Marc Jeannerod, CNRS  UMR 5229 Bron France"},{"name":"Hospices Civils de Lyon, H\u00f4pital Neurologique Pierre 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