Resting state fMRI reveals increased subthalamic nucleus-motor cortex connectivity in Parkinson's disease

Parkinson's disease (PD) is associated with abnormal hypersynchronicity in basal ganglia-thalamo-cortical loops. The clinical effectiveness of subthalamic nucleus (STN) high frequency stimulation indicates a crucial role of this nucleus within the affected motor networks in PD. Here we investigate alterations in the functional connectivity (FC) profile of the STN using resting state BOLD correlations on a voxel-by-voxel basis in functional magnetic resonance imaging (fMRI). We compared early stage PD patients (n=31) during the medication-off state with healthy controls (n=44). The analysis revealed increased FC between the STN and cortical motor areas (BA 4 and 6) in PD patients in accordance with electrophysiological studies. Moreover, FC analysis of the primary motor cortex (M1) hand area revealed that the FC increase was primarily found in the STN area within the basal ganglia. These findings are in good agreement with recent experimental data, suggesting that an increased STN-motor cortex synchronicity mediated via the so called hyperdirect motor cortex-subthalamic pathway might play a fundamental role in the pathophysiology of PD. An additional subgroup analysis was performed according to the presence (n=16) or absence (n=15) of tremor in patients. Compared to healthy controls tremor patients showed increased STN FC specifically in the hand area of M1 and the primary sensory cortex. In non-tremor patients, increased FC values were also found between the STN and midline cortical motor areas including the SMA. Taken together our results underline the importance of the STN as a key node for the modulation of BG-cortical motor network activity in PD patients.