Infrared neural stimulation of primary visual cortex in non-human primates

Abstract

Infrared neural stimulation (INS) is an alternative neurostimulation modality that uses pulsed infrared light to evoke spatially precise neural activity that does not require direct contact with neural tissue. With these advantages INS has the potential to increase our understanding of specific neural pathways and impact current diagnostic and therapeutic clinical applications. In order to develop this technique, we investigate the feasibility of INS (λ = 1.875 μm, fiber diameter = 100–400 μm) to activate and modulate neural activity in primary visual cortex (V1) of Macaque monkeys. Infrared neural stimulation was found to evoke localized neural responses as evidenced by both electrophysiology and intrinsic signal optical imaging (OIS). Single unit recordings acquired during INS indicated statistically significant increases in neuron firing rates that demonstrate INS evoked excitatory neural activity. Consistent with this, INS stimulation led to focal intensity-dependent reflectance changes recorded with OIS. We also asked whether INS is capable of stimulating functionally specific domains in visual cortex and of modulating visually evoked activity in visual cortex. We found that application of INS via 100 μm or 200 μm fiber optics produced enhancement of visually evoked OIS response confined to the eye column where INS was applied and relative suppression of the other eye column. Stimulating the cortex with a 400 μm fiber, exceeding the ocular dominance width, led to relative suppression, consistent with involvement of inhibitory surrounds. This study is the first to demonstrate that INS can be used to either enhance or diminish visual cortical response and that this can be done in a functional domain specific manner. INS thus holds great potential for use as a safe, non-contact, focally specific brain stimulation technology in primate brains.

Thermal Transients Excite Neurons through Universal Intramembrane Mechanoelectrical Effects

“…This study explored the effects of temperature changes on membrane capacitance and its associated currents in a joint attempt to clarify the experimental results of a key recent study [16] and to pave the way towards predictive modeling of INS [2][3][4][5][6][7][8][9][10][11][12][13][14][15] and other thermal neurostimulation techniques [18][19][20], which could potentially facilitate the development of more advanced and multimodal methods for neural circuit control. Another key motivation to pursue this problem came from our noting the very similar temperature-related capacitance rates of change observed in very different model systems [ Fig.…”

“…Both approaches also offer the long-term prospect of remotely affecting aberrant localized neural circuits that underlie many neurological diseases. A multitude of INS-related studies explored the ability of short-wave infrared (IR) pulses to stimulate neural structures including peripheral [3,4] and cranial nerves [5][6][7][8][9][10], retinal and cortical neurons [10][11][12], as well as cardiomyocytes [13,14]. It is stipulated that the INS phenomenon is mediated by temperature transients induced by IR absorption [15][16][17]; such transients can alternatively be induced using other forms of photoabsorption [18][19][20], or potentially by any other physical form of thermal neurostimulation that can be driven rapidly enough [21,22].…”

Optical stimulation enables paced electrophysiological studies in embryonic hearts

“…These include the time and cost required to perform genetic manipulations, the potential that the added ion channels may alter the electrical properties of the cells, the decreased responsiveness to light with repeated stimulation [38], and the likelihood of triggering an action potential when the light-sensitive channels are exposed to the optical mapping excitation light due to overlap of the excitation spectra [39,40] and much lower power requirements necessary for exciting the channels [41]. Infrared stimulation does have the potential to damage tissue if too much heat is deposited, but previously published results suggest that infrared stimulation can be used without damage [24][25][26][27][28][29][30][33][34][35]. Similarly, in this study, no functional damage was observed, as the pacing threshold did not increase over the course of an experiment.…”

“…Infrared stimulation was first developed in nerves [24] and has been used to stimulate a variety of nerves and neurons [25][26][27][28][29][30], vestibular hair cells [31], and isolated myocytes [32] using multimode fibers. Additionally, we have recently demonstrated the use of infrared stimulation to optically pace whole intact embryonic [33] and adult hearts [34].…”

“…Second, since optical pacing works through a heat deposition mechanism, no areas of potentially damaging high charge densities are generated. While heat can damage tissue, previous studies indicate that the stimulation threshold is below the thermal damage threshold [24][25][26][27][28][29][30][33][34][35]. Third, optical pacing does not inject current, avoiding the electrical artifact created by electrode pacing.…”