LAUSR

As we enter the era of precision medicine, and in the absence of reliable disease-specific biomarkers, it is fundamental to identify probes helping characterize in vivo and noninvasively the anatomical–functional organization of the human brain and its relation to motor and nonmotor (dys) functions. New advances in magnetic resonance imaging (MRI) techniques are providing powerful tools for mapping in vivo the complex neural connectivity patterns. The corticobasal ganglia network is characterized by a wide variety of specialized and anatomically interconnected areas, and the rules by which these neural circuits interact are poorly understood, yet to be fully characterized, especially in movement disorders. Despite that many MRI mapping techniques are still under refinement and cannot provide any definitive answers, they have the great potential of improving our understanding of the physiological and aberrant anatomical-functional organization of the human basal ganglia system. In the current issue of the Journal of Magnetic Resonance Imaging, the article by Guo et al attempts to investigate the microstructural changes of limbic and motor pathways and their relations to reveal the potential pathological foundation regarding motor disruption in Parkinson’s disease (PD) by using singleand two-shell diffusion MRI. Probabilistic tractography was used to reconstruct the nigrostriatal, basal ganglia-motor cortex and amygdala-accumbens-pallidum pathways in a total of 94 participants (55 healthy controls [HC] and 39 PD patients). Diffusion tensor imaging (DTI) metrics—fractional anisotropy (FA) and mean diffusivity (MD)—were calculated from single-shell diffusion images. In addition, two-shell diffusion images were fitted to the neurite orientation dispersion and density imaging (NODDI) model in order to generate intracellular volume fraction (Vic) and orientation dispersion index (ODI) maps. They observed that, compared to HCs, PD patients showed increased MD and decreased ODI in the nigrostriatal pathway, which indicated disorganization of this pathway. For the basal ganglia-motor cortex pathway, PD patients exhibited decreased FA and increased ODI, implying axonal degeneration of this tract. It is well known from the literature that axonal degeneration and anatomical connectivity deficits within the motor control pathways occur in PD patients. Taken together, alterations in DTIand NODDI-derived metrics found in the study by Guo et al further reinforce the evidence of microstructural alterations in the motor network, including the nigrostriatal and basal ganglia-motor cortex pathways in PD. In support of these results, the authors found a significant negative correlation between MD in the nigrostriatal pathway and FA in the basal ganglia-motor cortex pathway, thus suggesting a concurrent degeneration of these motor pathways. In addition, PD patients exhibited significantly decreased ODI in the amygdala-accumbens-pallidum pathway, along with a trend of increased FA, likely indicating enhanced coherence in such white matter tracts. Aberrant enhanced coherence of the limbic pathway (ODI) was also significantly positively correlated with the degeneration of the nigrostriatal pathway (MD), thus suggesting a relevant role of the limbic-motor interface in the pathophysiology of PD. Although diffusion MRI and tractography have raised interest in the last decades, some limitations need to be considered. Indeed, these tools present strengths but also weaknesses and intrinsic technical shortcomings. Notwithstanding, they represent valuable resources for further prospective and longitudinal studies with a larger sample size. This could be of crucial importance to longitudinally characterize potential alterations of the limbic and motor networks in different disease stages and to improve the current knowledge of the neuromechanism of motor dysfunction in PD. The last decade has been characterized by an increasing interest in identifying aberrant motor connectivity patterns in PD and in characterizing the limbic-motor interface, which is