Objective: To test if closed loop Spinal Cord Stimulation (SCS) could be used to restore locomotion in a 6-hydroxydopamine (6-OHDA ) rodent model of Parkinson’s Disease (PD) and to investigate if closed loop stimulation is better than open loop stimulation in alleviating PD symptoms and its neurophysiological correlates.

Background: Spinal cord stimulation has been recently proposed as an alternative therapeutic option for PD patients suffering from gait disorders and postural abnormalities [1,2]. Optimizing stimulation patterns of SCS is necessary for maximizing its therapeutic potential [3]. Closed loop deep brain stimulation (DBS) has shown improvements over traditional DBS in ameliorating symptoms of PD [4,5].

Methods: Rats were implanted with bilateral microelectrode recording arrays in motor cortex (M1) and dorsolateral striatum (DLS), along with bilateral injection cannulae in the dorsolateral striatum. Stimulation electrodes were implanted on the dorsal surface of the spinal cord [6]. One week post surgery, 6-OHDA was injected in the striatum to induce bilateral intrastriatal lesions. Motor activity was recorded as rats explored an open field chamber before and after the lesion along with spiking activity of M1 and DLS neurons and local field potential (LFP) signals. Spinal cord stimulation was administered in a closed loop fashion driven by either M1 or DLS activity. Stimulation was triggered either by 1) M1 or DLS neuron firing within beta (10-25 Hz) oscillatory frequency range or 2) Filtered beta band LFP signal from DLS crossing a baseline threshold.

Results: Bilateral 6-OHDA lesioning in rats resulted in severe akinesia and corresponding increase in corticostriatal beta oscillations. Closed loop SCS increased the magnitude of distance traveled and reduced the amount of time spent in rest by the rats. Improvement in akinesia symptoms was corroborated by a decrease in beta (10-25) Hz corticostriatal oscillations. Improvement of akinesia and reduction of beta oscillations was higher in closed loop mode as compared to open loop mode. Closed loop SCS resulted in 80-90% reduction in stimulation pulses delivered.

Conclusions: Our results show that closed loop SCS triggered by corticostriatal oscillatory activity in rats is effective in ameliorating motor symptoms associated with PD and that stimulation delivered in a closed loop fashion might be more effective than continuous open loop stimulation.

References: [1] Yadav, A. P., & Nicolelis, M. A. (2017). Electrical stimulation of the dorsal columns of the spinal cord for Parkinson’s disease. Movement Disorders. [2] Samotus, O., Parrent, A., & Jog, M. (2018). Spinal cord stimulation therapy for gait dysfunction in advanced Parkinson’s disease patients. Movement Disorders. [3] Yadav, A, Nicolelis, M.A. (2017) A closed loop brain machine interface for Parkinson’s disease using dorsal column electrical stimulation. Society for Neuroscience. [4] Rosin, B., Slovik, M., Mitelman, R., Rivlin-Etzion, M., Haber, S. N., Israel, Z., … & Bergman, H. (2011). Closed-loop deep brain stimulation is superior in ameliorating parkinsonism. Neuron, 72(2), 370-384. [5] Little, S., Pogosyan, A., Neal, S., Zavala, B., Zrinzo, L., Hariz, M., … & Green, A. L. (2013). Adaptive deep brain stimulation in advanced Parkinson disease. Annals of neurology, 74(3), 449-457. [6] Yadav, A. P., Fuentes, R., Zhang, H., Vinholo, T., Wang, C. H., Freire, M. A. M., & Nicolelis, M. A. (2014). Chronic spinal cord electrical stimulation protects against 6-hydroxydopamine lesions. Scientific reports, 4, 3839.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/closed-loop-spinal-cord-stimulation-restores-locomotion-and-desynchronizes-corticostriatal-beta-oscillations/