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Brain. 2018 Nov 1;141(11):3211-3232. doi: 10.1093/brain/awy252.

Brain structural alterations are distributed following functional, anatomic and genetic connectivity.

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GCS-fMRI, Koelliker Hospital and Department of Psychology, University of Turin, Turin, Italy.
FOCUS Lab, Department of Psychology, University of Turin, Turin, Italy.
Stroke Unit, Azienda Socio Sanitaria Territoriale Spedali Civili, Spedali Civili Hospital, Brescia, Italy.
Centre for Neurodegenerative Disorders, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Department of Neuroscience, University of Turin, Turin, Italy.
Research Imaging Institute, University of Texas Health Science Center at San Antonio, Texas, USA.
South Texas Veterans Health Care System, San Antonio, Texas, USA.


The pathological brain is characterized by distributed morphological or structural alterations in the grey matter, which tend to follow identifiable network-like patterns. We analysed the patterns formed by these alterations (increased and decreased grey matter values detected with the voxel-based morphometry technique) conducting an extensive transdiagnostic search of voxel-based morphometry studies in a large variety of brain disorders. We devised an innovative method to construct the networks formed by the structurally co-altered brain areas, which can be considered as pathological structural co-alteration patterns, and to compare these patterns with three associated types of connectivity profiles (functional, anatomical, and genetic). Our study provides transdiagnostical evidence that structural co-alterations are influenced by connectivity constraints rather than being randomly distributed. Analyses show that although all the three types of connectivity taken together can account for and predict with good statistical accuracy, the shape and temporal development of the co-alteration patterns, functional connectivity offers the better account of the structural co-alteration, followed by anatomic and genetic connectivity. These results shed new light on the possible mechanisms at the root of neuropathological processes and open exciting prospects in the quest for a better understanding of brain disorders.

[Available on 2019-11-01]

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