Progressive supranuclear palsy (PSP) is an atypical Parkinsonian syndrome characterized initially by falls and eye movement impairment. This multimodal imaging study aimed at eliciting structural and functional disease-specific brain alterations. T1-weighted and resting-state functional MRI were applied in multi-centric cohorts of PSP and matched healthy controls. Midbrain, cerebellum, and cerebellar peduncles showed severely low gray/white matter volume, whereas thinner cortical gray matter was observed in cingulate cortex, medial and temporal gyri, and insula. Eigenvector centrality analyses revealed regionally specific alterations. Multivariate pattern recognition classified patients correctly based on gray and white matter segmentations with up to 98 % accuracy. Highest accuracies were obtained when restricting feature selection to the midbrain. Eigenvector centrality indices yielded an accuracy around 70 % in this comparison; however, this result did not reach significance. In sum, the study reveals multimodal, widespread brain changes in addition to the well-known midbrain atrophy in PSP. Alterations in brain structure seem to be superior to eigenvector centrality parameters, in particular for prediction with machine learning approaches.

Clinic of Cognitive Neurology University of Leipzig Germany

Department of Neurology Charles University 1st Faculty of Medicine and General University Hospital Prague Czech Republic

Department of Neurology Martin Luther University Halle Wittenberg Halle Germany

Department of Neurology Saarland University Germany

Department of Neurology University of Ulm Ulm Germany

Division of Physiotherapy Department of Neurobiology Care Sciences and Society Karolinska Institutet Stockholm Sweden

German Center for Neurodegenerative Diseases Göttingen Germany

Max Planck Institute for Human Cognitive and Brain Sciences Leipzig Germany

University Medical Center Göttingen Germany

Women's Health and Allied Health Professionals Theme Medical Unit Occupational Therapy and Physiotherapy Karolinska University Hospital Stockholm Sweden

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