Objective: An approach to characterize the neural response to electrical brain stimulation with spatiotemporal precision in mice.

Background: Electrical brain stimulation is a clinically accessible tool that is used to treat movement disorders including Essential Tremor, Parkinson’s Disease, and dystonia. Despite its clinical success, how electrical stimulation precisely modulates neural activity remains poorly understood. Insights into how electrical stimulation and its many parameters affect neural activity have been gleaned from clinical responses and off-target side effects in patients implanted with deep brain stimulating (DBS) electrodes. However, optimizing DBS settings in the clinic to achieve maximal therapeutic efficacy while minimizing side effects is burdensome for patients and clinicians. Predicting the neural response to stimulation and its many parameters can help efficiently explore parameter spaces. The neural response to stimulation has previously been difficult to record given the technical challenges of simultaneous recording and stimulating.

Method: Three high-density electrophysiological recording probes (Neuropixels) are implanted orthogonal to a multi-channel linear stimulating electrode in mice. This approach allows simultaneous sampling of 100s of neurons near the stimulating source with spatial and temporal resolution. The neural response to varying clinically relevant parameters including amplitude, pulse-width, polarity, and frequency are obtained.

Results: We have developed and validated a novel approach to capturing the previously intractable neural response to electrical stimulation. We characterize single unit and local field potential responses as a function of distance from stimulation to varying parameters. Preliminary findings validate that neural activation is a function of distance and current delivered. Neural substrate (e.g., somas, axons, and dendrites) heterogeneity influences patterns of activation to different stimulation parameters. High amplitude single pulses elicit early excitation for 20-30 ms followed by nearly 200 ms of inhibition. Polarity (bipolar, cathodal, anodal) recruits distinct neural populations.

Conclusion: We developed a basic science approach to interrogate the neural response to electrical stimulation with varying parameters. These findings can be leveraged to explore parameter spaces more efficiently in DBS and improve therapeutic efficacy.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/characterizing-the-neural-response-to-electrical-brain-stimulation-with-spatiotemporal-precision-in-mice/