Subthalamotomy is effective in alleviating the cardinal features of PD. MRgFUS has become a minimally-invasive tool to perform lesions accurately in deep brain structures.

We assessed STN connectivity with the primary motor cortex (M1) and supplementary motor area (SMA) using multi-direction DWI-MRI in 21 patients (age 55.8±9.5 yo) who underwent unilateral MRgFUS-subthalamotomy. Q-sampling imaging method was used to reconstruct cortico-subthalamic fibers. Lesion-volume was computed by manual segmentation on T1/T2-weighted images. We computed the overlap coefficients between STN connections and each patient’s-specific lesion. Clinical assessments included the MDS-UPDRS-III scale, and specifically, scores for bradykinesia, rigidity and tremor of the treated side in the off-state (24 hours without medication). MRI data was acquired at baseline, 24-hours and 4 months’ post-treatment.

Subthalamic-cortical connectivity at baseline showed the SMA-STN tract within the antero-medial region of motor STN clearly differentiated from the M1-STN tract, which lay postero-laterally, describing in humans what was known from histological (tracer) studies in monkey brains (Nambú et al. J Neurosci 1996).  Change from baseline in MDS-UPDRS-III scores in the treated side was 56.1±27.5 for rigidity, 41.6±26.4 for bradykinesia and 78.4±22.7 for tremor. Impact on M1-STN fibers correlated with rigidity improvement (R=0.65, P<0.001). Lesion of the SMA-STN tract correlated with bradykinesia improvement (R=0.67, P<0.001). No correlation was found for the anti-tremor effect.

Our findings indicate that modulation of white matter tracts directed to M1 and SMA is associated with benefits in specific PD motor features after subthalamotomy. This highlights the importance of integrating brain connectivity to optimize targeting for subthalamotomy.