Parkinsonism Is Associated with Altered SMA-Basal Ganglia Structural and Functional Connectivity in Frontotemporal Degeneration

Background: Patients with frontotemporal degeneration (FTD) often manifest parkinsonism, which likely results from cortical and subcortical degeneration of brain structures involved in motor control. We used a multimodal magnetic resonance imaging (MRI) approach to investigate possible structural and/or functional alterations in FTD patients with and without parkinsonism (Park+ and Park-). Methods: Thirty FTD patients (12 Park+, 18 Park-) and 30 healthy controls were enrolled and underwent 3T MRI scanning. MRI analyses included: (1) surface-based morphometry; (2) basal ganglia and thalamic volumetry; (3) diffusion-based probabilistic tractography of fiber tracts connecting the supplementary motor area (SMA) and primary motor cortex (M1) to the putamen, globus pallidus, and thalamus; and (4) resting-state functional connectivity (RSFC) between the aforementioned regions. Results: Patients in Park+ and Park- groups showed comparable patterns of cortical thinning in frontotemporal regions and reduced thalamic volume with respect to controls. Only Park+ patients showed reduced putaminal volume and reduced fractional anisotropy of the fibers connecting the SMA to the globus pallidus, putamen, and thalamus, with respect to controls. Park+ patients also showed decreased RSFC between the SMA and putamen with respect to both Park- patients and controls. Conclusions: The present findings support the hypothesis that FTD patients with parkinsonism are characterized by neurodegenerative processes in specific corticobasal ganglia-thalamocortical motor loops.

Automated summary

This study used multimodal magnetic resonance imaging to investigate the relationship between parkinsonism and brain structure and function in patients with frontotemporal degeneration (FTD). The results showed that patients with and without parkinsonism exhibited similar patterns of cortical thinning and reduced thalamic volume, but only patients with parkinsonism showed reduced putaminal volume and decreased connectivity between the supplementary motor area and putamen. These findings suggest that FTD patients with parkinsonism have specific neurodegenerative processes in the corticobasal ganglia-thalamocortical motor loops.