Analysis of modulation of motor, cognitive and affective brain networks combining advanced MRI techniques with directional deep brain stimulation in Parkinson’s disease

Subthalamic Deep Brain Stimulation (STN-DBS) provides marked amelioration of quality of life in Parkinson’s disease (PD) patients.1 However, <10% of patients are considered eligible for DBS with many factors affecting the optimal outcome.2 Based on conventional MRI and CT data we estimated the anatomical distribution of the area modulated by DBS on patients’ basal nuclei and expected white matter tracts based on brain atlases. Within such an approximation, we were able to predict beneficial effects of DBS and some motor side effects. Against these preliminary data, we hypothesize that advanced MRI acquisitions will allow a detailed characterization of discrete cortico-basal circuits modulated by STN-DBS. This might allow to predict DBS effects on motor, cognitive, and behavioral symptoms, and to shape, at a single subject level, selective stimulation paradigms in the framework of personalized medicine. We plan to test our central hypothesis by pursuing two specific aims: 1) To identify at a group-level areas of the STN and surrounding fibers associated with structural and functional networks related to main motor and nonmotor symptoms. Interactions between volumes of tissue activated (VTA - an estimation of the tissue surrounding electrodes modulated by DBS -) and structurally and functionally connected networks investigated by diffusion and resting-state functional MRI data will be tested to predict desired and side effects of DBS. 2) To confirm at a single patient-level the usefulness of quantitative MRI to inform the best setting-up of DBS to modulate networks related to individual clinical features, with the final goal of improving clinical outcome and minimizing side effects. Methods: In this prospective interventional study, 25 consecutive PD patients undergoing STN- DBS with implant of directional leads will be enrolled, acquiring presurgical structural and functional quantitative MRI data at 3T to be coregistered with postoperative CT scans. ‘Lead-DBS’ software will be used for electrode localization and modelling of VTA.3,4 Patients will be evaluated before surgery (T0), early after surgery during the stimulation parameter setting (T1), and after 6 months of chronic stimulation (T2), assessing rigidity, tremor, bradykinesia, gait, depression, anxiety, apathy, impulse control disorder, verbal fluency, working memory, frontal-executive functions and stimulation-related side effects by means of validated scales and wearable motion sensors. VTA will be used to identify the DBS local effects as well as effects on remote structural and functional networks, and their clinical correlates with the different stimulation parameters tested at T1(acute effects) and the final stimulation paradigm maintained from T1 to T2 (chronic effects). The project findings will help to clarify the pathophysiology of PD motor and nonmotor symptoms, providing new treatment opportunities by DBS.