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Does Vestibular Motion Perception Correlate with Axonal Pathways Stimulated by Subthalamic Deep Brain Stimulation in Parkinson’s Disease?

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Abstract

Perception of our linear motion — heading — is critical for postural control, gait, and locomotion, and it is impaired in Parkinson’s disease (PD). Deep brain stimulation (DBS) has variable effects on vestibular heading perception, depending on the location of the electrodes within the subthalamic nucleus (STN). Here, we aimed to find the anatomical correlates of heading perception in PD. Fourteen PD participants with bilateral STN DBS performed a two-alternative forced-choice discrimination task where a motion platform delivered translational forward movements with a heading angle varying between 0 and 30° to the left or to the right with respect to the straight-ahead direction. Using psychometric curves, we derived the heading discrimination threshold angle of each patient from the response data. We created patient-specific DBS models and calculated the percentages of stimulated axonal pathways that are anatomically adjacent to the STN and known to play a major role in vestibular information processing. We performed correlation analyses to investigate the extent of these white matter tracts’ involvement in heading perception. Significant positive correlations were identified between improved heading discrimination for rightward heading and the percentage of activated streamlines of the contralateral hyperdirect, pallido-subthalamic, and subthalamo-pallidal pathways. The hyperdirect pathways are thought to provide top-down control over STN connections to the cerebellum. In addition, STN may also antidromically activate collaterals of hyperdirect pathway that projects to the precerebellar pontine nuclei. In select cases, there was strong activation of the cerebello-thalamic projections, but it was not consistently present in all participants. Large volumetric overlap between the volume of tissue activation and the STN in the left hemisphere positively impacted rightward heading perception. Altogether, the results suggest heavy involvement of basal ganglia cerebellar network in STN-induced modulation of vestibular heading perception in PD.

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Acknowledgements

The authors thank Sarah Ozinga, PhD, Palak Gupta, and Mark Walker, MD, for their support.

Funding

This study is funded by grants from US Department of Veterans Affairs Merit Review 5 I01 CX002086-03 (Shaikh), The American Academy of Neurology (Shaikh), American Parkinson’s Disease Association George C Cotzias Memorial Fellowship (Shaikh), Dystonia Medical Research Foundation Research (Shaikh), and philanthropic funds to the Department of Neurology at University Hospitals (The Allan Woll Fund and The Fox Fund). Shaikh also has Penni and Steven Weinberg Chair in Brain Health.

The research was supported by American Academy of Neurology Career Award, George C Cotzias Memorial Fellowship and Department of VA I01 CX002086.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA

    Sinem Balta Beylergil, Angela M. Noecker, Cameron C. McIntyre & Aasef G. Shaikh

  2. National VA Parkinson Consortium Center, Neurology Service, Daroff-Dell’Osso Ocular Motility and Vestibular Laboratory, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA

    Sinem Balta Beylergil & Aasef G. Shaikh

  3. Department of Neurology, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH, 44110, USA

    Camilla Kilbane & Aasef G. Shaikh

  4. Movement Disorders Center, Neurological Institute, University Hospitals, Cleveland, OH, USA

    Camilla Kilbane & Aasef G. Shaikh

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  1. Sinem Balta Beylergil
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  2. Angela M. Noecker
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  3. Camilla Kilbane
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  4. Cameron C. McIntyre
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Contributions

AS, SB: conceptualized the project, collected data, analyzed data, wrote the manuscript, and edited the manuscript. CM, AN: analyzed data and edited the manuscript. CK: collected data and edited the manuscript.

Corresponding author

Correspondence to Aasef G. Shaikh.

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Institutional internal review board at University Hospitals Cleveland Medical Center and Cleveland VA Medical Center has approved the study protocol. The participants signed informed consent before participation in the study.

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The authors declare no competing interests.

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Beylergil, S.B., Noecker, A.M., Kilbane, C. et al. Does Vestibular Motion Perception Correlate with Axonal Pathways Stimulated by Subthalamic Deep Brain Stimulation in Parkinson’s Disease?. Cerebellum 23, 554–569 (2024). https://doi.org/10.1007/s12311-023-01576-8

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