Optimizing thermal block length during infrared neural inhibition to minimize temperature thresholds

Abstract

Objective. Infrared neural inhibition (INI) is a method of blocking the generation or propagation of neural action potentials through laser heating with wavelengths strongly absorbed by water. Recent work has identified that the distance heated along axons, the block length (BL), modulates the temperature needed for inhibition; however, this relationship has not been characterized. This study explores how BL during INI can be optimized towards minimizing its temperature threshold. Approach. To understand the relationship between BL and the temperature required for INI, excised nerves from Aplysia californica were laser-heated over different lengths of axon during electrical stimulation of compound action potentials. INI was provided by irradiation (λ = 1470 nm) from a custom probe (n = 6 nerves), and subsequent validation was performed by providing heat block using perfused hot media over nerves (n = 5 nerves). Main Results. Two BL regimes were identified. Short BLs (thermal full width at half maximum (tFWHM) = 0.81–1.13 mm) demonstrated that increasing the tFWHM resulted in lower temperature thresholds for INI (p < 0.0125), while longer BLs (tFWHM = 1.13–3.03 mm) showed no significant change between the temperature threshold and tFWHM (p > 0.0125). Validation of this longer regime was performed using perfused hot media over different lengths of nerves. This secondary heating method similarly showed no significant change (p > 0.025) in the temperature threshold (tFWHM = 1.25–4.42 mm). Significance. This work characterized how the temperature threshold for neural heat block varies with BL and identified an optimal BL around tFWHM = 1.13 mm which minimizes both the maximum temperature applied to tissue and the volume of tissue heated during INI. Understanding how to optimally target lengths of nerve to minimize temperature during INI can help inform the design of devices for longitudinal animal studies and human implementation.

High temporal resolution transparent thermoelectric temperature sensors for photothermal effect sensing

“…For example, it would even be possible to measure temperature changes according to a few hundred-ms long pulses of a laser in neural stimulation. 30,31 Despite efforts to develop transparent temperature sensors, such as transparent RTDs and transparent diodes, none of the microsensors were able to directly sense the high-speed photothermal effect. In addition, unlike other temperature sensing devices that are often limited by self-heating, our TE temperature sensor generates output voltage signals by taking the thermal energy as the input and hence avoids the concern of self-heating.…”

Infrared neuromodulation—a review

“…Though the radiant exposure under each fiber was lowered by 38.5%, it is worth noting that the total energy deposition into the nerves was still higher in the two-fiber regime. Additional INI studies in A. californica on optimizing the distance heated along the axon (λ = 1.47 µm, 200 µs pulses for τ = 20 s, f = 200 Hz, 0.09-1.25 mJ/pulse) identified that increasing the exposed axon length (0.81-1.13 mm) led to a lower temperature threshold for INI, whereas for longer lengths (1.13-3.03 mm) no significant changes were noted due to saturation effects [125]. Simulations in the NEURON environment demonstrated similarly that the heating of multiple shorter zones for a cumulative total longer heated length along the axis, reduced the minimum temperature rise required for INI (due to an increase in the potassium currents).…”

Use of an invertebrate animal model (Aplysia californica) to develop novel neural interfaces for neuromodulation

“…These studies were extended by Ford et al (2020Ford et al ( , 2021 showing that one could reduce the IR dose required for thermal inhibition by illuminating a greater length of the nerve, and by Zhuo et al (2021) showing that ion substitution could also reduce the dose of laser light needed for thermal inhibition. Both studies explored the parameter space to determine the change in IR threshold, which required a substantial number of repeated experiments on the same nerve to avoid variation between animals.…”