Dusan Hirjak, Philipp A. Thomann, Robert C. Wolf, Katharina M. Kubera, Caspar Goch, Jan Hering, Klaus H. Maier‐Hein

Neurological soft signs (NSS) are core features of psychiatric disorders with significant neurodevelopmental origin. However, it is unclear whether NSS correlates are associated with neuropathological processes underlying the disease or if they are confounded by medication. Given that NSS are also present in healthy persons (HP), investigating HP could reveal NSS correlates, which are not biased by disease-specific processes or drug treatment. Therefore, we used a combination of diffusion MRI analysis tools to provide a framework of specific white matter (WM) microstructure variations underlying NSS in HP. NSS of 59 HP were examined on the Heidelberg Scale and related to diffusion associated metrics. Using tract-based spatial statistics (TBSS), we studied WM variations in fractional anisotropy (FA) as well as radial (RD), axial (AD), and mean diffusivity (MD). Using graph analytics (clustering coefficient-CC, local betweenness centrality -BC), we then explored DTI-derived structural network variations in regions identified by previous MRI studies on NSS. NSS scores were negatively associated with RD, AD and MD in corpus callosum, brainstem and cerebellum (P < 0.05, corr.). NSS scores were negatively associated with CC and BC of the pallidum, the superior parietal gyrus, the precentral sulcus, the insula, and the cingulate gyrus (P < 0.05, uncorr.). The present study supports the notion that WM microstructure variations in subcortical and cortical sensorimotor regions contribute to NSS expression in young HP. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.