Spatial and temporal variability in response to hybrid electro-optical stimulation

Abstract

Hybrid electro-optical neural stimulation is a novel paradigm combining the advantages of optical and electrical stimulation techniques while reducing their respective limitations. However, in order to fulfill its promise, this technique requires reduced variability and improved reproducibility. Here we used a comparative physiological approach to aid the further development of this technique by identifying the spatial and temporal factors characteristic of hybrid stimulation that may contribute to experimental variability and/or a lack of reproducibility. Using transient pulses of infrared light delivered simultaneously with a bipolar electrical stimulus in either the marine mollusk Aplysia californica buccal nerve or the rat sciatic nerve, we determined the existence of a finite region of excitability with size altered by the strength of the optical stimulus and recruitment dictated by the polarity of the electrical stimulus. Hybrid stimulation radiant exposures yielding 50% probability of firing (RE₅₀) were shown to be negatively correlated with the underlying changes in electrical stimulation threshold over time. In Aplysia, but not in the rat sciatic nerve, increasing optical radiant exposures (J cm⁻²) beyond the RE₅₀ ultimately resulted in inhibition of evoked potentials. Accounting for the sources of variability identified in this study increased the reproducibility of stimulation from 35% to 93% in Aplysia and 23% to 76% in the rat with reduced variability.

Infrared neural stimulation of human spinal nerve rootsin vivo

“…Further, other studies investigating INS have demonstrated that the technique must be optimized for each new application due to different tissue geometries and function. [5][6][7]15,17,22,25,30 Optimization of INS for human applications will be required, but as this study demonstrates, preclinical results will likely translate to clinical application, indicating most optimization can be achieved in preclinical models.…”

Ryanodine and IP3 receptor-mediated calcium signaling play a pivotal role in neurological infrared laser modulation

“…[1][2][3][4][5][6][7][8] Likewise, ∼1.8 μm IR pulse exposure has also been demonstrated to block action potential (AP) generation and propagation. [9][10][11][12][13] While a rapid increase in temperature, due to absorption of the laser radiation, is required to evoke the neural depolarization, and IR stimulation pulses have been shown to produce an acoustic pressure wave, 14-17 the mechanism(s) to stimulate or inhibit an AP is not fully understood. 18 Certain thermal and mechanical mechanisms 17,19 involving ion channels, such as transient receptor potential (TRP) channel activation, 20 plasma membrane poration, 21 and/or membrane potential changes, are suggested as explanations for IR neural stimulation and inhibition, together termed IR neural modulation (INM).…”

Alternating current and infrared produce an onset-free reversible nerve block

“…Previous studies using IR inhibition alone have found that the nerve physiology was unaffected by a similar protocol. 10,11 We also observed that the CAP was of similar size before and after treatment, suggesting that the nerve's physiology was unaffected. Future studies will be necessary to determine if chronic exposure to this treatment has a deleterious effect on nerves.…”

“…Aplysia can be maintained for many hours and have previously been used to define appropriate parameters for optical block in myelinated rat sciatic nerve. 10,11 Animals 300 to 400 g were used, as their nerves are 4 to 7 cm, with a diameter of 0.5 to 1.5 mm, comparable to rat sciatic nerve. Animals were anesthetized with isotonic magnesium chloride.…”

“…9 Studies show that infrared (IR) laser block is fast, reversible, and has high spatial resolution in rat myelinated nerves and in Aplysia unmyelinated nerves. 10,11 We combined KHFAC and optical inhibition using IR lasers [alternating current and infrared (ACIR)] to produce fast and reversible nerve block without an onset response.…”