Objective: Characterize the changes in oscillatory activity and connectivity in the basal ganglia thalamocortical (BGTC) network after induction of parkinsonian and during therapeutic deep brain stimulation (DBS).

Background: Parkinson’s disease has been associated with enhanced synchronized oscillatory activity in the beta band (8-30 Hz) in the BGTC network. Although previous studies have demonstrated coupling between cortical regions and the STN in the high beta frequency spectrum (20-30 Hz), changes in connectivity with induction of parkinsonism and during therapeutic DBS are poorly understood.

Method: A nonhuman primate was implanted with a 96-channel Utah array in the primary motor cortex (M1) and DBS leads targeting the subthalamic nucleus (STN) and globus pallidus internus (GPi). The animal was rendered moderately parkinsonian by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neural data were simultaneously recorded across M1, STN, and GPi during a resting state (eyes open) in the naïve state, following induction of parkinsonism, and during therapeutic STN DBS. Local field potentials were analyzed to characterize the changes in functional (coherence and phase synchrony) and directed (information-directed transfer function) connectivity.

Results: Parkinsonism was associated with increased M1-STN connectivity across low (8-20 Hz) and high beta bands. Directed connectivity was increased from M1 to STN in the high beta band but decreased from STN to M1 in the low beta band. Changes in M1 to GPi connectivity were centered in the high beta band and were smaller than those in M1 to STN. We also observed a modest increase in connectivity between the STN and GPi. Therapeutic STN DBS decreased M1-STN and STN-GPi connectivity but had minimal impact on M1-GPi connectivity.

Conclusion: Consistent with previous reports coherence was increased across the BGTC network in PD. The directed connectivity change suggests a propagation of high beta oscillatory activity from M1 to the STN via the hyperdirect pathway and is supportive of the hypothesis that exaggerated high beta activity in the hyperdirect pathway can promote synchrony in subcortical structures in the low beta range. Therapeutic STN DBS may shift connectivity profiles in the network by its effect on M1 via hyperdirect and thalamocortical pathways.

References: [1] Oswal, A., Cao, C., Yeh, C. H., Neumann, W. J., Gratwicke, J., Akram, H., … & Litvak, V. (2021). Neural signatures of hyperdirect pathway activity in Parkinson’s disease. Nature communications, 12(1), 5185
[2] Johnson, L. A., Wang, J., Nebeck, S. D., Zhang, J., Johnson, M. D., & Vitek, J. L. (2020). Direct activation of primary motor cortex during subthalamic but not pallidal deep brain stimulation. Journal of Neuroscience, 40(10), 2166-2177.
[3] Xu, W., Russo, G. S., Hashimoto, T., Zhang, J., & Vitek, J. L. (2008). Subthalamic nucleus stimulation modulates thalamic neuronal activity. Journal of Neuroscience, 28(46), 11916-11924

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MDS Abstracts - https://www.mdsabstracts.org/abstract/alterations-in-cortico-basal-ganglia-directed-connectivity-in-parkinsonism-and-during-therapeutic-stn-dbs/