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High-Frequency Stimulation for Parkinson’s Disease and Effects on Pathways in Basal Ganglia Network Model

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Abstract

Deep brain stimulation of nuclei in the basal ganglia has been recognized as the most effective neurosurgical therapy for hypokinesia in patients with Parkinson’s disease; however, the mechanism underlying its curative effect remains unknown. In addition, the known effects of the two major pathways of the basal ganglia on the thalamus can offer information on optimal targets for further exploration and research. To simulate high-frequency stimulation to the different targets in Parkinson’s disease, a cortico-basal-thalamic network model was constructed based on the biological principles of anatomical structures and utilization of conductance-based models. Taking three different nucleus regions as targets, we simulated and analyzed the diversity of different stimulus durations and periods, along with stimulus efficacy, for the three targets. Then, by adopting different stimulus magnitudes that acted on the three targets, a comparative analysis of the effects of different stimulus magnitudes and targets for the treatment of Parkinson’s disease was performed. To identify the optimal target, different effects of the two major pathways on the thalamus were calculated. The calculation results show that the cortico-basal-thalamic network is reliable, and through the use of feasible models, high-frequency stimulation of the three targets can improve the pathological thalamic rhythmicity. It is shown that the direct pathway excites the thalamus, while the indirect pathway plays a regulatory role in the thalamus.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China under Grant 11572127 and 11172103.

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Authors and Affiliations

  1. School of Mathematics, South China University of Technology, Guangzhou, 510640, China

    Xiaofang Jiang, Shenquan Liu & Bo Lu

  2. Biomedical Engineering Center, Beijing University of Technology, Beijing, 100022, China

    Yanjun Zeng

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  1. Xiaofang Jiang
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  2. Shenquan Liu
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Corresponding author

Correspondence to Shenquan Liu.

Appendix

Appendix

Here, we describe the direct and indirect pathways internal synaptic connection strengths and external stimuli.

In the direct pathway, synaptic connection strengths are g N(PY→D1)  = 0.02196, g A(PY→D1)  = 1.134, g G(D1→GPi)  = 26.265, g N(DA→D1)  = 0.0488, g A(DA→D1)  = 0.252, and g G(GPi→TH)  = 0.85 μS. External stimuli are I S(DA)  = 0.3 and I S(GPi)  = −3.74 nA. In the indirect pathway, the internal connection strengths are g N(PY→D2)  = 0.03172, g A(PY→D2)  = 0.1638, g N(PY→STN)  = 10.5, g A(PY→STN)  = 3.15, g G(DA→D2)  = 0.34, g G(D2→GPe)  = 0.425, g G(GPe→STN)  = 8.5, g N(STN→GPi)  = 0.0122, g A(STN→GPi)  = 0.063, and g G(GPi→TH)  = 0.425 μS. The external stimuli are I S(DA)  = 0.3, I S(GPe)  = −1.5, and I S(GPi)  = −4.0 nA. For g syn(x→y) , syn indicates the type of synapse and (N, A, G = NMDA, AMPA, GABA), x → y indicates that neuron y was affected by synapses that came from neuron x. I S(X) indicates that neuron X incurred an external stimulus.

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Jiang, X., Liu, S., Lu, B. et al. High-Frequency Stimulation for Parkinson’s Disease and Effects on Pathways in Basal Ganglia Network Model. J. Med. Biol. Eng. 36, 704–717 (2016). https://doi.org/10.1007/s40846-016-0170-8

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  • DOI: https://doi.org/10.1007/s40846-016-0170-8

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