Targeted Optical Neural Stimulation: A New Era for Personalized Medicine

Abstract

Targeted optical neural stimulation comprises infrared neural stimulation and optogenetics, which affect the nervous system through induced thermal transients and activation of light-sensitive proteins, respectively. The main advantage of this pair of optical tools is high functional selectivity, which conventional electrical stimulation lacks. Over the past 15 years, the mechanism, safety, and feasibility of optical stimulation techniques have undergone continuous investigation and development. When combined with other methods like optical imaging and high-field functional magnetic resonance imaging, the translation of optical stimulation to clinical practice adds high value. We review the theoretical foundations and current state of optical stimulation, with a particular focus on infrared neural stimulation as a potential bridge linking optical stimulation to personalized medicine.

Infrared neuromodulation—a review

“…Damage thresholds were analyzed based on histological hematoxylin & eosin stains, with damage reported in layers 2/3 of the cortex for exposures exceeding 0.6 J cm −2 based on in vitro and in vivo data. This study demonstrated the clinical feasibility of INS for stimulating single cortical nodes and associated sites, highlighting that millimeter selectivity is required for precise activation of neuronal networks [19].…”

“…The damage threshold for human spinal nerve roots was determined at 1.09 J cm −2 (λ = 2.12 µm, 10 s at f = 2 Hz, D = 550 µm) [60]. Overall, it has been suggested that the damage threshold in peripheral nerves is higher than for the cortex in rats and monkeys [19]. However, systematic optical parameter studies combined with acute and long-term thermal damage evaluation, potentially in longitudinal studies, will be important to evaluate INM for personalized medicine.…”

“…In biology and chemistry, light can serve as an external trigger to provide precise control of underlying biochemical processes in diverse manners [16,17]. For light-based neuromodulation approaches [18,19], optogenetic neuromodulation [20][21][22] and photochemical neuromodulation approaches [16] are exciting fields that have revolutionized neuroscience research. Optogenetics offers a pathway to induce precisely timed and cell-specific modulation with the help of light-responsive proteins in cells [23].…”

Two-photon imaging of excitatory and inhibitory neural response to infrared neural stimulation

“…When delivered via 200 μm fiber optic in short pulse trains (0.25 ms, 200 Hz, 0.5 s), this highly focal (submillimeter) optical approach has provided a unique way of functional column-specific stimulation in primate cortex 7 . Thus, the advantages of INS over conventional electrical stimulation include high spatial selectivity, contactless delivery, and importantly for primate and human application, neuromodulation of brain sites without prior opsin expression 8,9 . Furthermore, with this precision of targeted optical fiber stimulation and MRI compatibility, focal INS combined with MRI can be used for in vivo mapping of brain networks in primates [10][11][12] and holds promise for neuromodulation in awake behaving monkeys.…”

Two-photon imaging of GABAergic and non-GABAergic neuronal calcium activity induced by infrared neural stimulation in awake mouse cortex

“…When delivered via 200 μm fiber optic, this highly focal (submillimeter) optical approach has provided a unique way of functional column-specific stimulation in primate cortex [5] . Thus, advantages of INS over conventional electrical stimulation include high spatial-temporal selectivity, contactless delivery, and importantly for primate and human application, neuromodulation of brain sites without prior incorporation of opsins [6] . Furthermore, with this precision of targeted optical fiber stimulation and MRI compatibility, focal INS combined with MRI can be used for in vivo mapping of brain networks in primates [7][8] .…”