Objective: To define brain networks modulated by deep brain stimulation (DBS) of the subthalamic nucleus (STN) and correlate connectivity with motor outcomes.

Background: STN DBS is an effective treatment for Parkinson disease (PD), but predictors of clinical response are limited. 15O PET reveals changes in brain activity in DBS without many of the methodological difficulties found in fMRI related to device safety and unpredictable MRI artifact. Regional changes in blood flow during STN DBS have been observed with 15O PET and in some cases correlate with clinical outcomes. A multimodal approach associating blood flow changes during STN DBS and motor outcomes with preoperative functional connectivity (BOLD MRI) may permit improved prediction of clinical response to DBS.

Method: 41 participants with STN DBS had 15O PET in OFF, unilateral dorsal STN stimulation ON, and unilateral ventral STN stimulation ON conditions, and we compared rCBF using paired T-tests. We used a whole-brain approach in addition to an a priori set of regions to identify responses to STN DBS. We used these regions for seed-based correlation in 74 participants with STN DBS and preoperative resting state fcMRI, as well as 300 seeds divided into 17 canonical networks. Connectivity of each PET-defined region to STN and intra-network seeds were correlated to change in UPDRS after DBS.

Results: DBS produced significant changes in 19 regions in the PET analysis. Connectivity of each region to canonical networks using fcMRI revealed that these activations pertained to basal ganglia, thalamic, salience, dorsal sensorimotor, default mode, parietal memory, medial temporal, and frontoparietal networks. Connectivity of left STN to ipsilateral internal globus pallidus strongly correlated with motor outcomes (R = -0.416, p <0.001), with higher connectivity being associated with greater improvement in motor outcomes. Primary motor cortex connectivity to sensorimotor network was the network-level connectivity most correlated with change in motor scores after DBS.

Conclusion: DBS modulates a diverse set of brain regions. These regions not only pertain to networks typically associated with motor activity, e.g. basal ganglia, thalamic, and sensorimotor networks, but also memory, executive and associative functions. Motor outcomes are highly associated with STN connectivity to particular regions modulated by DBS.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/multimodal-pet-and-fcmri-reveals-regional-modulation-by-stn-dbs-correlating-to-motor-outcomes/