Time precise closed-loop protocols for non-invasive infrared laser neural stimulation
Alicia Garrido-Peña¹,Pablo Sanchez-Martin¹, Irene Elices¹, Rafael. Levi¹, Francisco B. Rodriguez¹, Javier Castilla², Jesus Tornero², Pablo Varona¹
1. Grupo de Neurocomputación Biológica, Departamento de Ingeniería Informática, Escuela Politecnica Superior, Universidad Autónoma de Madrid, Madrid, Spain
2. Center for Clinical Neuroscience, Hospital los Madroños, Brunete, Spain
*Email: alicia.garrido@uam.es
Introduction
In the context of the increasing interest in noninvasive neural stimulation techniques, infrared (IR) laser has shown its potential to achieve an effective and spatially localized stimulation. In our recent publication [1], we demonstrated that it is possible to modulate neural dynamics with a Continuous-Wave (CW) Near IR laser in terms of firing rate and spike waveform. We analyzed the biophysical cause of this effect in a computational model, observing a combined alteration of ionic channels and significant action of temperature change. We also assessed the illumination effect at different stages of the action potential generation with a closed-loop protocol. Here we extend these results and stimulation protocols.
Methods
We used a CW-IR laser focused with a micromanipulator in the ganglia of Lymnaea stagnalis and Carcius maenas, while recording membrane potential intracellularly. For the closed-loop protocols, we employed the RTXI software [2], designing algorithms in modules for spike, and burst prediction, target-driven stimulation and neuronal digital-twin experiments built with conductance-based models. The laser was triggered based on the ongoing activity with a precise electro-optical shutter (range of µs). Our software is open-source and available atgithub.com/GNB-UAM.
Results
We show the effectiveness of laser stimulation with high spatial resolution (by the nature of this technique) and temporal precision (by our real-time closed-loop protocols and an electro-optical shutter) on two different neural systems. For both cases, sustained CW laser illumination accelerates neural activity. We also report on the efficacy of activity-dependent illumination with a time-precise shutter. We extend our spike prediction algorithms to neural bursting activity and a target-driven stimulation. To leverage this closed-loop neurotechnology, we present a biohybrid circuit where a model neuron acts as a digital twin of the recorded cell. This enables real-time automatic decision-making based on the model tested response.
Discussion
CW-IR laser illumination is a novel noninvasive neurotechnology with high temporal and spatial resolution. CW-IR laser effectively modulated neural activity in two different neural systems with distinct closed-loop protocols. These protocols employ a library for time-precise stimulation adaptable to different neural dynamics (e.g. tonic spiking or bursting activity) and different target goals (a specific firing rate, burst duration...). The digital-twin model also enables online adjustment by the combined modification of the stimulation parameters and the simulated neuron. Exploiting the advantages of closed-loop stimulation and real-time tools, expands the possibilities of this neurotechnology to novel research and clinical applications.
AcknowledgementsWork funded by PID2024-155923NB-I00, CPP2023-010818, PID2023-149669NB-I00 and PID2021-122347NB-I00.
References[1] Garrido-Peña, A., Sanchez-Martin, P., Reyes-Sanchez, M., Levi, R., Rodriguez, F. B., Castilla, J., Tornero, J., & Varona, P. (2024). Modulation of neuronal dynamics by sustained and activity-dependent continuous-wave near-infrared laser stimulation. Neurophotonics, 11(2), 024308.doi.org/10.1117/1.NPh.11.2.024308
[2] Patel, Y. A., George, A., Dorval, A. D., White, J. A., Christini, D. J., & Butera, R. J. (2017). Hard real-time closed-loop electrophysiology with the Real-Time eXperiment Interface (RTXI). PLOS Computational Biology, 13(5), e1005430.doi.org/10.1371/journal.pcbi.1005430
