Spatial extent of cochlear infrared neural stimulation determined by tone-on-light masking.
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ABSTRACT: Artificial neural stimulation is widely used in clinic, rehabilitation, and research. One of the limitations of electrical stimulation is the current spread in tissue. Recently, pulsed mid-infrared laser stimulation of nerves has been investigated as an alternative stimulation method. The likely benefits of infrared neural stimulation (INS) include spatial selectivity of stimulation, noncontact mode of operation, and the lack of stimulation artifact in simultaneous electrical recordings. The hypothesis for this study is that INS of the cochlear spiral ganglion at low pulse energy is as spatially selective as low-level tonal stimulation of the cochlea. Spatial selectivity was measured using a masking method. An optical pulse with fixed optical parameters was delivered through a 200-μm diameter optical fiber. An acoustic tone, variable in frequency and level, was presented simultaneously with the optical pulse. Tone-on-light masking in gerbils revealed tuning curves with best frequencies between 5.3 and 11.4 kHz. The width of the tone-on-light tuning curves was similar to the width of tone-on-tone tuning curves. The results indicate that the spatial area of INS in the gerbil cochlea is similar to the cochlear area excited by a low level acoustic tone, showing promising results for future use of INS in implantable cochlear prostheses.
Project description:Acoustic therapy in tinnitus treatment is poorly characterized, and efficacy assessment depends on subjective descriptions. Narrow-band noise, notched sound, and white noise have positive therapeutic effects on monotonous tinnitus. Considering the tonotopic characteristics of the auditory system and the spectral characteristics of these three masking sounds, the activation pattern of the auditory cortex and the mechanism of inhibiting tinnitus may be different. This study aimed to compare the activation patterns of three spectrally different masking noises and study the correlation between the masking effects and variational amplitude of oxygenated hemoglobin (HbO) in the corresponding cortical regions. We also assessed near-infrared spectroscopy brain function imaging (NIRS) as an objective assessment tool in acoustic therapy. Patients with persistent non-pulsatile tinnitus and control volunteers without tinnitus were enrolled in this study. The subjects were seated in a sound-proof room, with two optode arrays covering the bilateral temporal lobe. Auditory stimuli were presented; stimulation sequences followed the block design: different noises appeared randomly and repeated in five cycles. Tinnitus match and residual inhibition were performed in the tinnitus group. The data analyses were conducted using the NIRS_SPM toolbox. The group analysis results showed that the narrow-band noise caused a marginally significant decrease in HbO signal in the Brodmann 21 region (BA21), while white noise caused a significant increase in HbO signal in BA21. Notched sound did not cause significant changes in the HbO signal in the temporal cortex. And none of the three masking noises caused significant changes in the HbR signal in the temporal cortex. The depth of residual inhibition induced by the narrow-band noise and white noise significantly correlated with ?HbO in the region of interest (ROI). However, neither the depth nor duration of the residual inhibition induced by notched sound correlated with the ?HbO. Thus, NIRS showed three cortical activation patterns induced by three different masking noises, and correlations between residual inhibition effects and change of HbO amplitude were found. NIRS could therefore be applied in objective assessment of acoustic therapy.
Project description:Infrared neural stimulation (INS) has been proposed as an alternative method to electrical stimulation because of its spatial selective stimulation. Independent of the mechanism for INS, to translate the method into a device it is important to determine the energy for stimulation required at the target structure. Custom-designed, flat and angle polished fibers, were used to deliver the photons. By rotating the angle polished fibers, the orientation of the radiation beam in the cochlea could be changed. INS-evoked compound action potentials and single unit responses in the central nucleus of the inferior colliculus (ICC) were recorded. X-ray computed tomography was used to determine the orientation of the optical fiber. Maximum responses were observed when the radiation beam was directed towards the spiral ganglion neurons (SGNs), whereas little responses were seen when the beam was directed towards the basilar membrane. The radiant exposure required at the SGNs to evoke compound action potentials (CAPs) or ICC responses was on average 18.9 ± 12.2 or 10.3 ± 4.9 mJ/cm(2), respectively. For cochlear INS it has been debated whether the radiation directly stimulates the SGNs or evokes a photoacoustic effect. The results support the view that a direct interaction between neurons and radiation dominates the response to INS.
Project description:Can direct stimulation of primate V1 substitute for a visual stimulus and mimic its perceptual effect? To address this question, we developed an optical-genetic toolkit to 'read' neural population responses using widefield calcium imaging, while simultaneously using optogenetics to 'write' neural responses into V1 of behaving macaques. We focused on the phenomenon of visual masking, where detection of a dim target is significantly reduced by a co-localized medium-brightness mask (Cornsweet and Pinsker, 1965; Whittle and Swanston, 1974). Using our toolkit, we tested whether V1 optogenetic stimulation can recapitulate the perceptual masking effect of a visual mask. We find that, similar to a visual mask, low-power optostimulation can significantly reduce visual detection sensitivity, that a sublinear interaction between visual- and optogenetic-evoked V1 responses could account for this perceptual effect, and that these neural and behavioral effects are spatially selective. Our toolkit and results open the door for further exploration of perceptual substitutions by direct stimulation of sensory cortex.
Project description:Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients ([Formula: see text]) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and [Formula: see text]. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at [Formula: see text] and a [Formula: see text] safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans.
Project description:Over the past decade, optical methods have emerged for modulating brain functions as an alternative to electrical stimulation. Among various optical techniques, infrared neural stimulation has been effective via a thermal mechanism enabling focused and noninvasive stimulation without any genetic manipulation, but it results in bulk heating of neural tissue. Recently, it has been shown that neural cells can be activated more efficiently by pulsed near-infrared (NIR) light delivered to gold nanorods (GNRs) near the neural cells. Despite its potential, however, the biophysical mechanism underlying this GNR-enhanced NIR stimulation has not been clearly explained yet. Here, we propose an integrative and quantitative model to elucidate the mechanism by modeling heat generated from interaction between NIR light and GNRs, the temperature-dependent ion channels (transient receptor potential vanilloid 1; TRPV1) in the neuronal membrane, and a heat-induced capacitive current through the membrane. Our results show that NIR pulses induce abrupt temperature elevation near the neuronal membrane and lead to both the TRPV1-channel and capacitive currents. Both current sources synergistically increase the membrane potential and elicit an action potential, and which mechanism is dominant depends on conditions such as the laser pulse duration and TRPV1 channel density. Although the TRPV1 mechanism dominates in most cases we tested, the capacitive current makes a larger contribution when a very short laser pulse is illuminated on neural cells with relatively low TRPV1 channel densities.
Project description:The mechanisms by which noninvasive vagal nerve stimulation (nVNS) affect central and peripheral neural circuits that subserve pain and autonomic physiology are not clear, and thus remain an area of intense investigation. Effects of nVNS vs sham stimulation on subject responses to five noxious thermal stimuli (applied to left lower extremity), were measured in 30 healthy subjects (n = 15 sham and n = 15 nVNS), with fMRI and physiological galvanic skin response (GSR). With repeated noxious thermal stimuli a group × time analysis showed a significantly (p < .001) decreased response with nVNS in bilateral primary and secondary somatosensory cortices (SI and SII), left dorsoposterior insular cortex, bilateral paracentral lobule, bilateral medial dorsal thalamus, right anterior cingulate cortex, and right orbitofrontal cortex. A group × time × GSR analysis showed a significantly decreased response in the nVNS group (p < .0005) bilaterally in SI, lower and mid medullary brainstem, and inferior occipital cortex. Finally, nVNS treatment showed decreased activity in pronociceptive brainstem nuclei (e.g. the reticular nucleus and rostral ventromedial medulla) and key autonomic integration nuclei (e.g. the rostroventrolateral medulla, nucleus ambiguous, and dorsal motor nucleus of the vagus nerve). In aggregate, noninvasive vagal nerve stimulation reduced the physiological response to noxious thermal stimuli and impacted neural circuits important for pain processing and autonomic output.
Project description:Analysis and control of neural circuitry requires the ability to selectively activate or inhibit neurons. Previous work showed that infrared laser light selectively excited neural activity in endogenous unmyelinated and myelinated axons. However, inhibition of neuronal firing with infrared light was only observed in limited cases, is not well understood and was not precisely controlled. Using an experimentally tractable unmyelinated preparation for detailed investigation and a myelinated preparation for validation, we report that it is possible to selectively and transiently inhibit electrically-initiated axonal activation, as well as to both block or enhance the propagation of action potentials of specific motor neurons. Thus, in addition to previously shown excitation, we demonstrate an optical method of suppressing components of the nervous system with functional spatiotemporal precision. We believe this technique is well-suited for non-invasive investigations of diverse excitable tissues and may ultimately be applied for treating neurological disorders.
Project description:Significance: We present a new optical method for modulating cortical activity in multiple locations and across multiple time points with high spatial and temporal precision. Our method uses infrared light and does not require dyes or transgenic modifications. It is compatible with a number of other stimulation and recording techniques. Aim: Infrared neural stimulation (INS) has been largely confined to single point stimuli. In this study, we expand upon this approach and develop a rapidly switched fiber array capable of generation of stimulus patterns. Our prototype is capable of stimulating at nine separate locations but is easily scalable. Approach: Our device is made of commercially available components: a solid-state infrared laser, a piezoelectric fiber coupled optical switch, and 200-μm diameter optical fibers. We validate it using intrinsic optical signal imaging of INS responses in macaque and squirrel monkey sensory cortical areas. Results: We demonstrate that our switched array can consistently generate responses in primate cortex, consistent with earlier single channel INS investigations. Conclusions: Our device can successfully target the cortical surface, either at one specific region or multiple points spread out across different areas. It is compatible with a host of other imaging and stimulation modalities.
Project description:Brain is one of the most temperature sensitive organs. Besides the fundamental role of temperature in cellular metabolism, thermal response of neuronal populations is also significant during the evolution of various neurodegenerative diseases. For such critical environmental factor, thorough mapping of cellular response to variations in temperature is desired in the living brain. So far, limited efforts have been made to create complex devices that are able to modulate temperature, and concurrently record multiple features of the stimulated region. In our work, the in vivo application of a multimodal photonic neural probe is demonstrated. Optical, thermal, and electrophysiological functions are monolithically integrated in a single device. The system facilitates spatial and temporal control of temperature distribution at high precision in the deep brain tissue through an embedded infrared waveguide, while it provides recording of the artefact-free electrical response of individual cells at multiple locations along the probe shaft. Spatial distribution of the optically induced temperature changes is evaluated through in vitro measurements and a validated multi-physical model. The operation of the multimodal microdevice is demonstrated in the rat neocortex and in the hippocampus to increase or suppress firing rate of stimulated neurons in a reversible manner using continuous wave infrared light (λ = 1550 nm). Our approach is envisioned to be a promising candidate as an advanced experimental toolset to reveal thermally evoked responses in the deep neural tissue.
Project description:In surgical procedures where the risk of accidental nerve damage is prevalent, surgeons commonly use electrical stimulation (ES) during intraoperative nerve monitoring (IONM) to assess a nerve's functional integrity. ES, however, is subject to off-target stimulation and stimulation artifacts disguising the true functionality of the specific target and complicating interpretation. Lacking a stimulation artifact and having a higher degree of spatial specificity, infrared neural stimulation (INS) has the potential to improve upon clinical ES for IONM. Here, we present a direct comparison between clinical ES and INS for IONM performance in an in vivo rat model. The sensitivity of INS surpasses that of ES in detecting partial forms of damage while maintaining a comparable specificity and sensitivity to more complete forms. Without loss in performance, INS is readily compatible with existing clinical nerve monitoring systems. These findings underscore the clinical potential of INS to improve IONM and surgical outcomes.