Connectomic Guided DBS for Parkinson's Disease

Patients with Parkinson's disease (PD) can suffer from significant disability due to tremors, rigidity, bradykinesia, or motor fluctuations, in addition to non-motor symptoms of the disease. Deep brain stimulation (DBS) is the main surgical approach approved by the US Food and Drug Administration (FDA) for the treatment of medication-refractory PD. Despite recent advances, the selection of DBS parameters is based on trial-and-error experimentation by specialists over the course of months. Better understanding of the optimal network targets for symptomatic control would allow for therapy improvement and simplify the DBS programming process, increase efficiency, and possibly increase access to care.

Most studies of structural connectivity in PD have focused on the analysis of the subthalamic nucleus (STN). Previous studies analyzing structural connectivity of STN DBS have shown that specific motor symptoms benefit from the activation of different networks. Several tracts such as the cerebellothalamic tract (CBT), pallidothalamic (PT) and corticospinal tract (CST) course through the STN and might be relevant for DBS targeting. For patients with essential tremor, stimulation of the CBT might provide better tremor control, but studies in PD are lacking.

The investigators will use connectomic models to better understand the mechanistic qualities of axonal pathways in the STN in Parkinson's disease and address the need for phenotype driven stimulation in PD. Estimating targeted axonal pathways by using connectomic models may guide personalized decision-making and targeting of DBS. It has the potential to improve clinical outcomes and reduce the number of visits needed for DBS optimization.

The study involves the extraction of data collected during routine clinical care, and data collected during the intervention study.

Data collected during routine clinical care includes:

• Demographic characteristics: age, gender, ethnicity, race.
• Clinical characteristics: disease duration, Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) prior to DBS implementation, levodopa equivalent daily dose of medications.
• Imaging data: DBS lead location, stimulation model activation pathway, recruitment curves, percent of each pathway activated with clinical DBS settings

Inclusion criteria

• Age 18 or older
• Diagnosed with Parkinson's disease and has previously been implanted with bilateral subthalamic nucleus deep brain stimulation (DBS)
• Received DBS at least three months prior to the time of the study to allow for optimization of usual clinical care
• With at least mild tremor on a pre-operatory MDS-UPDRS clinical scale as defined by at least 2 out of 4 resting tremor grading on MDS-UPDRS on at least one extremity

Exclusion criteria

• Not having a post-operative head CT with 1mm or smaller axial slices at least 1 week after initial lead implantation.
• Patients who received DBS less than three months prior to the start of the study