Short-wave Infrared Neural Stimulation Drives Graded Sciatic Nerve Activation Across A Continuum of Wavelengths

Coventry, Brandon S.; Sick, Justin; Talavage, Thomas M.; Stantz, Keith M.; Bartlett, Edward E.

doi:10.1109/embc44109.2020.9176177

Cited by 6 publications

(7 citation statements)

References 27 publications

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“…While many previous INS studies have explored the role of wavelength dependence on INS activation(16, 74, 75), dose-response relationships have largely not been studied. Activation profiles are critical for therapeutic dosing of neuromodulation therapies to titrate efficacious pulses while minimizing patient discomfort from overdriving neurons.…”

Section: Discussionmentioning

confidence: 99%

“…As single unit thalamocortical recordings elicited from INS have largely been unexplored, previous knowledge cannot be adequately constructed into a highly informative prior. However, our previous experience in thalamus and cortical recordings(4–10), the central auditory pathway (11–13), and in INS parameter selection(14, 15) gives prior information on potential variances of firing rate in cortex from thalamic stimulation. As such, we chose moderately informative distributions (see section 3) so as to not unduly influence the posterior and let the observed data fully inform the posterior.…”

Section: Supporting Informationmentioning

confidence: 99%

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Spatially specific, closed-loop infrared thalamocortical deep brain stimulation

Coventry,

Lawlor,

Bagnati

et al. 2023

Preprint

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Deep brain stimulation (DBS) is a powerful clinical tool for the treatment of circuitopathy-related neurological and psychiatric diseases and disorders such as Parkinson’s disease and obsessive-compulsive disorder. Electrically-mediated DBS, however, is limited by the spread of stimulus currents into tissue unrelated to disease course and treatment, potentially causing undesirable patient side effects. In this work, we utilize infrared neural stimulation (INS), an optical neuromodulation technique that uses near to mid-infrared light to drive graded excitatory and inhibitory responses in nerves and neurons, to facilitate an optical and spatially constrained DBS paradigm. INS has been shown to provide spatially constrained responses in cortical neurons and, unlike other optical techniques, does not require genetic modification of the neural target. In this study, we show that INS produces graded, biophysically relevant single-unit responses with robust information transfer in thalamocortical circuits. Importantly, we show that cortical spread of activation from thalamic INS produces more spatially constrained response profiles than conventional electrical stimulation. Owing to observed spatial precision of INS, we used deep reinforcement learning for closed-loop control of thalamocortical circuits, creating real-time representations of stimulus-response dynamics while driving cortical neurons to precise firing patterns. Our data suggest that INS can serve as a targeted and dynamic stimulation paradigm for both open and closed-loop DBS.Significance StatementDespite initial clinical successes, electrical deep brain stimulation (DBS) is fraught with off-target current spillover into tissue outside of therapeutic targets, giving rise to patient side effects and the reduction of therapeutic efficacy. In this study, we validate infrared neural stimulation (INS) as a spatially constrained optical DBS paradigm by quantifying dose-response profiles and robust information transfer through INS driven thalamocortical circuits. We show that INS elicits biophysically relevant responses which are spatially constrained compared to conventional electrical stimulation, potentially reducing off-target side effects. Leveraging the spatial specificity of thalamocortical INS, we used deep reinforcement learning to close the loop on thalamocortical INS and showed the ability to drive subject-specific thalamocortical circuits to target response states in real time.

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Section: Discussionmentioning

confidence: 99%

Section: Supporting Informationmentioning

confidence: 99%

Spatially specific, closed-loop infrared thalamocortical deep brain stimulation

Coventry,

Lawlor,

Bagnati

et al. 2023

Preprint

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“…Infrared neural stimulation (INS) is an optical technique using coherent infrared light to stimulate nerves and neurons without the need for genetic modification of the target or direct contact with tissue that offers spatially constrained activation above electrical stimulation (Wells et al, 2005(Wells et al, , 2005Izzo et al, 2007;Cayce et al, 2011Cayce et al, , 2014Coventry et al, 2020Coventry et al, , 2024. In this study, rats were chronically implanted in A1 with 16 channel planar Utah-style arrays (TDT, Alacua FL) and stimulating optrodes in the medial geniculate body of auditory thalamus (Thor Labs, Newton NJ).…”

Section: Infrared Neural Stimulationmentioning

confidence: 99%

Practical Bayesian Inference in Neuroscience: Or How I Learned To Stop Worrying and Embrace the Distribution

Coventry,

Bartlett

2023

Preprint

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Typical statistical practices in biological sciences have been increasingly called into question due to difficulties in replication of an increasing number of studies, much of which is confounded by the relative difficulty of null significance hypothesis testing designs and interpretation of p-values. Bayesian inference, representing a fundamentally different approach to hypothesis testing, is receiving renewed interest as a potential alternative or complement to traditional null significance hypothesis testing due to its ease of interpretation and explicit declarations of prior assumptions. Bayesian models are more mathematically complex than equivalent frequentist approaches, which have historically limited applications to simplified analysis cases. However, the advent of probability distribution sampling tools with exponential increases in computational power now allows for quick and robust inference under any distribution of data. Here we present a practical tutorial on the use of Bayesian inference in the context of neuroscientific studies. We first start with an intuitive discussion of Bayes’ rule and inference followed by the formulation of Bayesian-based regression and ANOVA models using data from a variety of neuroscientific studies. We show how Bayesian inference leads to easily interpretable analysis of data while providing an open-source toolbox to facilitate the use of Bayesian tools.Significance StatementBayesian inference has received renewed interest as an alternative to null-significance hypothesis testing for its interpretability, ability to encapsulate prior knowledge into current inference, and robust model comparison paradigms. Despite this renewed interest, discussions of Bayesian inference are often obfuscated by undue mathematical complexity and misunderstandings underlying the Bayesian inference process. In this article, we aim to empower neuroscientists to adopt Bayesian statistical inference by providing a practical methodological walkthrough using single and multi-unit recordings from the rodent auditory circuit accompanied by a well-documented and user-friendly toolkit containing regression and ANOVA statistical models commonly encountered in neuroscience.

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“…However, Coventry et al showed evidence of evoked CNAPs at 700-800 nm using very short pulses of 10 ns, i.e. in the regime of both thermal and stress confinement [77]. In this regard, neural activation may have different mechanisms at the cell membrane depending on whether the thermal or pressure confinement regime is prevailing.…”

Section: • Shapiro Et Al Obtained Experimental Evidencementioning

confidence: 99%

“…(a) In-vivo experiments in: humans [60], rats [36, 43, 44, 48-50, 53, 55], gerbils [40, 41, 45-47, 52, 54] and quails [76]. (b) Ex-vivo experiments in: rats [77], lobsters [37], aplysia [55], rabbits [78], bullfrog [79] and murine [80]. (c) In-vitro experiments in: hippocampal and cortical neurons from rat [81,82], untransfected HEK-293 T cells, X. laevis oocytes and artificial lipid bilayers [67].…”

Section: Introductionmentioning

confidence: 99%

Infrared neurostimulation in ex-vivo rat sciatic nerve using 1470 nm wavelength

Cury¹,

Perre²,

Smets³

et al. 2021

J. Neural Eng.

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Objective. To design and implement a setup for ex-vivo optical stimulation for exploring the effect of several key parameters (optical power and pulse duration), activation features (threshold, spatial selectivity) and recovery characteristics (repeated stimuli) in peripheral nerves. Approach. A nerve chamber allowing ex-vivo electrical and optical stimulation was designed and built. A 1470 nm light source was chosen to stimulate the nerve. A photodiode module was implemented for synchronization of the electrical and optical channels. Main results. Compound neural action potentials (CNAPs) were successfully generated with infrared light pulses of 200–2000 µs duration and power in the range of 3–10 W. These parameters determine a radiant exposure for stimulation in the range 1.59–4.78 J cm−2. Recruitment curves were obtained by increasing durations at a constant power level. Neural activation threshold is reached at a mean radiant exposure of 3.16 ± 0.68 J cm−2 and mean pulse energy of 3.79 ± 0.72 mJ. Repetition rates of 2–10 Hz have been explored. In eight out of ten sciatic nerves (SNs), repeated light stimuli induced a sensitization effect in that the CNAP amplitude progressively grows, representing an increasing number of recruited fibres. In two out of ten SNs, CNAPs were composed of a succession of peaks corresponding to different conduction velocities. Significance. The reported sensitization effect could shed light on the mechanism underlying infrared neurostimulation. Our results suggest that, in sharp contrast with electrical stimuli, optical pulses could recruit slow fibres early on. This more physiological order of recruitment opens the perspective for specific neuromodulation of fibre population who remained poorly accessible until now. Short high-power light pulses at wavelengths below 1.5 µm offer interesting perspectives for neurostimulation.

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Short-wave Infrared Neural Stimulation Drives Graded Sciatic Nerve Activation Across A Continuum of Wavelengths

Cited by 6 publications

References 27 publications

Spatially specific, closed-loop infrared thalamocortical deep brain stimulation

Spatially specific, closed-loop infrared thalamocortical deep brain stimulation

Practical Bayesian Inference in Neuroscience: Or How I Learned To Stop Worrying and Embrace the Distribution

Infrared neurostimulation in ex-vivo rat sciatic nerve using 1470 nm wavelength

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