Objective: We aim to investigate how structural connectivity of the brain affects gait freezing after globus pallidus internus (GPi) deep brain stimulation (DBS).

Background: Freezing of gait (FOG) is one of the most disabling symptoms in Parkinson’s disease (PD), increasing the risk of fracture and frequent falls. The symptoms of FOG improve after DBS only in some patients. A hypothesis suggested that several white matter structures and axonal modulation affect heterogeneity of treatment response.

Method: In this study, we investigated patients with PD who underwent GPi DBS at Asan Medical Center. We included patients who had magnetic resonance images preoperatively. We evaluated the Unified Parkinson’s Disease Rating Scale (UPDRS) before and after levodopa medication and/or stimulation. Structural connectivity was analyzed from diffusion tensor images using probabilistic tractography. First, we compared the brain connectivity of the patients who had FOG (FOG group) and patients who did not have FOG (no-FOG group) preoperatively. Second, we selected the patients who had FOG 1 year after DBS at medication off and stimulation off state. We compared the brain connectivity of the patients whose FOG improve after stimulation (DBS-responsive FOG), and those of the patients whose FOG did not improve after stimulation (DBS-unresponsive FOG).

Results: The study population included 77 patients with PD. We found no statistical differences in age and sex between the FOG group (n=56) and the no-FOG group (21) (Median age 60.0 vs 63.0, P=0.23). The connectivity between limbic or basal ganglia and motor/premotor cortex was found in the FOG group compared with the no-FOG group (all P<0.01). One year after the operation, the DBS-responsive FOG group showed higher connectivity between GPi and orbitofrontal cortex, and between GPi and red nucleus than the DBS-unresponsive FOG group (all P<0.01). On the other hand, the DBS-unresponsive FOG group had higher connectivity between structures involved in the sensory system including visual cortex, rostral inferior temporal cortex, somatosensory cortex, and basal ganglia than the DBS-responsive FOG group (all P<0.01).

Conclusion: We found that differential stimulation response to FOG was associated with individual brain structural connectivity. Patients with FOG who have higher connectivity between GPi and other cortical regions would benefit from GPi DBS.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/structural-connectivity-affecting-freezing-of-gait-after-globus-pallidus-internus-deep-brain-stimulation-in-parkinsons-disease/