Abstract Details

Title Identifying a Gait Circuit from Focal Stroke Lesions and Deep Brain Stimulation Connectivity in Parkinson’s Disease

Topic Movement Disorders

Presentation(s) S8 - Neuromodulation in Movement Disorders (2:08 PM-2:16 PM)

Poster/Presentation
Number 002

Background

Gait impairment is present in a wide range of neurological disorders. Identifying the brain circuit responsible for abnormal gait could lead to improved therapies. Lesions disrupting gait can help elucidate this circuit by using a new technique termed lesion network mapping. This approach combines lesion locations with a map of human brain connectivity to localize symptoms to brain circuits.

Objective

To evaluate whether stroke lesion locations disrupting gait and deep brain stimulation (DBS) sites improving gait in Parkinson’s disease (PD) map to a common brain circuit.

Design/Methods First, we derived a circuit connected to lesions associated with gait impairment in 109 stroke patients. Using a large normative connectome database (n=1000), we computed the regions functionally connected to each lesion location. We then identified the connectivity of lesions independently associated with gait impairment using a voxel-wise t-test with permutation analysis (controlling for stroke severity as measured by NIH Stroke Scale score). Next, we assessed the therapeutic relevance of this circuit by comparing it to 94 subthalamic DBS sites in PD patients. We tested whether connectivity of the DBS sites to our lesion-based gait circuit was associated with gait improvement (controlling for PD severity as measured by Unified Parkinson Disease Rating Scale).

Results Connectivity between lesion locations and a network of brain regions including anterior cingulate, midbrain, and pons was significantly associated with gait impairment (p_FWE< 0.05). Connectivity between DBS stimulation sites and this same network was associated with DBS-induced gait improvement (r = 0.41, p< 0.00004). Data-driven gait networks derived from brain lesions and DBS sites showed similar topography (spatial r= 0.7, p=0.025, 1000 permutations).

Conclusions Lesions impairing gait map to a connected brain circuit that shows promise as a therapeutic DBS target in PD.

Authors/Disclosures
Lan Luo, MD (Beth Israel Deaconess Medical Center) PRESENTER	Dr. Luo has received personal compensation in the range of $0-$499 for serving as a Consultant for Destum Partners. Dr. Luo has received personal compensation in the range of $0-$499 for serving as a Consultant for Guidepoint Global. Dr. Luo has received research support from BIDMC/HMS.
	No disclosure on file
	No disclosure on file
Joey Hsu, MD	The institution of Mr. Hsu has received research support from Walter L. Copeland Fund of the Pittsburgh Foundation.
	No disclosure on file
Shan Siddiqi, MD (Washington University in St. Louis)	Dr. Siddiqi has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Magnus Medical. Dr. Siddiqi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Brainsway Ltd. Dr. Siddiqi has stock in Brainsway Ltd. Dr. Siddiqi has stock in Magnus Medical. Dr. Siddiqi has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file
Jens Volkmann, MD (University Hospital of Wuerzburg)	No disclosure on file
Andrea Kuehn	Andrea Kuehn has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medtronic. Andrea Kuehn has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Boston Scientific.
Maurizio Corbetta, MD (Department of Neurology, Washington University School of Medicine)	Dr. Corbetta has nothing to disclose.
Michael D. Fox, MD, PhD (Brigham and Women's Hospital / Harvard Medical School)	Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley.