Biology subjects

Glowacki, E. D.

Publications and source records attributed to Glowacki, E. D..

6 recordsLinked to original sources

bioRxiv2026

Phasic Neural Stimulation via Frequency-Modulated Kilohertz Signals: An Alternative to Amplitude Modulation

Kilohertz-frequency (kHz) electrical stimulation (1-100 kHz) is emerging as a powerful tool in both invasive and non-invasive neurostimulation applications, including functional electrical stimulation, spinal cord stimulation, and non-invasive brain stimulation. Most commonly these paradigms rely on amplitude modulation (AM-kHz)--achieved via burst or sinusoidal modulation--to produce phasic neural activation. Here, we propose, and validate, an alternative: frequency-modulated kilohertz stimulation (FM-kHz). This approach leverages the distinct strength-frequency dependence of kHz signals, whereby higher carrier frequencies are less efficient in depolarizing neurons than lower frequencies. By sweeping between sub- and suprathreshold frequencies, at a constant amplitude, FM-kHz generates a phasic neural activation envelope analogous to AM-kHz, without requiring amplitude modulation. Using both computational modelling and experimental data from Locusta migratoria (N5 nerve) and the human median nerve, we demonstrate that FM-kHz stimulation: 1. Produces reliable phasic evoked responses at the FM frequency; 2. Enables two degrees of control over stimulation--via FM frequency and frequency deviation. Across models tested, FM-kHz thresholds followed the same increasing strength-frequency relationship as AM-kHz, with FM-kHz requiring modestly higher thresholds at the upper end of the tested frequency range. These findings position FM-kHz as a viable and potentially advantageous alternative to AM-kHz strategies for future neuromodulation devices, and conceptually ground strength-frequency dependence as the key parameter in interpreting the effects of kHz electrical stimulation.

neuroscience↗

bioRxiv2024

There is no Biophysical Distinction between Temporal Interference Stimulation and Direct kHz Stimulation for Actuation of Peripheral Nerves

Temporal interference stimulation (TIS) has attracted increasing attention as a promising noninvasive electrical stimulation method. Despite positive results and optimistic expectations, the TIS field has been beset by misunderstandings concerning its mechanism of action and efficacy in safely targeting deep neural structures. Various studies posit that TIS exploits the low-frequency "beat" frequency produced by interference of multiple kHz carriers to essentially deliver low-frequency stimulation at the intersection of the carriers, thereby circumventing limitations associated with tissue impedance and depth penetration. Due to the documented electrophysiological effects of kHz-range stimuli, such a picture is an oversimplification, and at present a critical open question for TIS is how much stimulation thresholds practically differ for amplitude-modulated versus unmodulated kHz stimuli. This paper presents experimental evidence supporting the conclusion that TIS is driven by the kHz carrier itself, and that amplitude modulation frequency has little relatively effect on thresholds. We test TIS and different modulated/unmodulated kHz waveforms on peripheral nerve targets in an invertebrate model (Locusta migratoria), and on sensory and motor stimulation in human subjects. We find that modulated (TIS) and unmodulated sine carrier frequencies in the range 0.5 - 12.5 kHz in humans, and further up to 100 kHz in locusts, demonstrate overlapping strength-frequency (s-f) dependence across all stimulation types. Since all stimulation waveforms are governed by the same s-f curve, this implicates a common underlying biophysical mechanism. This equivalence challenges the notion that the TIS modulated "envelope" frequency can uniquely facilitate neural engagement via other mechanisms. We test amplitude-modulation frequency (AMF) dependence, confirming the resonance effect predicted by kHz rectification theory, and we evaluate the regions of tonic (unmodulated) and phasic (amplitude-modulated) stimulation regions inherent when using TIS. Our results help to resolve the mechanistic debate, at least for suprathreshold TIS. We explain how the findings can be extrapolated to subthreshold stimulation, and further suggest possible advantages of using 2-electrode amplitude-modulated kHz waveforms over the multielectrode TIS configurations.

neuroscience↗

bioRxiv2023

Obstructive Sleep Apnea Improves with Non-invasive Hypoglossal Nerve Stimulation using Temporal Interference

BackgroundPeripheral nerve stimulation is used in both clinical and fundamental research for therapy and exploration. At present, non-invasive peripheral nerve stimulation still lacks the penetration depth to reach deep nerve targets and the stimulation focality to offer selectivity. It is therefore rarely employed as the primary selected nerve stimulation method. We have previously demonstrated that a new stimulation technique, temporal interference stimulation, can overcome depth and focality issues. MethodsHere, we implement a novel form of temporal interference, bilateral temporal interference stimulation, for bilateral hypoglossal nerve stimulation in rodents and humans. Pairs of electrodes are placed alongside both hypoglossal nerves to stimulate them synchronously and thus decrease the stimulation amplitude required to activate hypoglossal-nerve controlled tongue movement. ResultsComparing bilateral temporal interference stimulation with unilateral temporal interference stimulation, we show that it can elicit the same behavioral and electrophysiological responses at a reduced stimulation amplitude. Traditional transcutaneous stimulation evokes no response with equivalent amplitudes of stimulation. ConclusionsDuring first in-man studies, temporal interference stimulation was found to be well-tolerated, and to clinically reduce apnea-hypopnea events in a subgroup of female patients with obstructive sleep apnea. These results suggest a high clinical potential for the use of temporal interference in the treatment of obstructive sleep apnea and other diseases as a safe, effective, and patient-friendly approach. Trial registrationThe protocol was conducted with the agreement of the International Conference on Harmonisation Good Clinical Practice (ICH GCP), applicable United States Code of Federal Regulations (CFR) and followed the approved BRANY IRB File # 22-02-636-1279.

neuroscience↗

bioRxiv2022

Photo-electrochemical Stimulation of Neurons With Organic Donor-Acceptor Heterojunctions

Recent advancements in light-responsive materials enabled the development of devices to artificially activate tissue with light, and show great potential for use in different types of therapy. Photo-stimulation based on organic semiconductors has recently attracted interest due to their unique set of properties such as biocompatibility, better mechanical match with human tissue, and strong absorption of light in the visible spectrum. Here we show the development of solution processed organic heterojunctions that are able to control the activity of primary neurons in vitro with light. The p-type polymer semiconductor PDCBT and the n-type polymer semiconductor ITIC (also known as non-fullerene acceptor) are simply spin coated on glass substrates forming a bilayer p-n junction with high photo-sensitivity in aqueous electrolytes. Photo-electrochemical measurements reveal that high photo-voltage and photo-current is produced, as a result of a charge transfer between the polymers and oxygen in the electrolyte. The biocompatibility of the proposed materials is addressed with live/dead assays on both primary mouse cortical neurons and human cell lines that are cultured on their surface. We have found that light of low intensity (i.e. 40 mW/cm2) is absorbed, and converted into a cue that triggers action potential on primary cortical neurons directly cultured on glass/PDCBT/ITIC interfaces as proven by patch clamp measurements. The activation of neurons is most likely due to photochemical reactions at the polymer/electrolyte interface that result in hydrogen peroxide, which might lead to modulation of specific ion channels on neurons membrane. Photo-thermal effects are excluded with controlled patch clamp measurements on neurons cultured on plain glass and on photoresist thin films. The profound advantages of low intensity light stimulation, simplified fabrication, and wireless operation pave the way for the integration of these interfaces in multiplex bioelectronic devices for the development of novel light therapy concepts and powerful neuroscience research tools.

bioengineering↗

bioRxiv2021

Noninvasive Stimulation of Peripheral Nerves using Temporally-Interfering Electrical Fields

Electrical stimulation of peripheral nerves is a cornerstone of bioelectronic medicine. Effective ways to accomplish peripheral nerve stimulation noninvasively without surgically implanted devices is enabling for fundamental research and clinical translation. Here we demonstrate how relatively high frequency sine-wave carriers (3 kHz) emitted by two pairs of cutaneous electrodes can temporally interfere at deep peripheral nerve targets. The effective stimulation frequency is equal to the offset frequency (0.5 - 4 Hz) between the two carriers. We validate this principle of temporal interference nerve stimulation (TINS) in vivo using the murine sciatic nerve model. Effective actuation is delivered at significantly lower current amplitudes than standard transcutaneous electrical stimulation. Further, we demonstrate how flexible and conformable on-skin multielectrode arrays can facilitate precise alignment of TINS onto a nerve. Our method is simple, relying on repurposing of existing clinically-approved hardware. TINS opens the possibility of precise noninvasive stimulation with depth and efficiency previously impossible with transcutaneous techniques.

neuroscience↗

bioRxiv2020

A chronic photocapacitor implant for noninvasive neurostimulation with deep red light

Implantable clinical neuroelectronic devices are limited by a lack of reliable, safe, and minimally invasive methods to wirelessly modulate neural tissue. Here, we address this challenge by using organic electrolytic photocapacitors (OEPCs) to perform chronic peripheral nerve stimulation via transduction of tissue-penetrating deep-red light into electrical signals. The operating principle of the OEPC relies on efficient charge generation by nanoscale organic semiconductors comprising nontoxic commercial pigments. OEPCs integrated on an ultrathin cuff are implanted, and light impulses at wavelengths in the tissue transparency window are used to stimulate from outside of the body. Typical stimulation parameters involve irradiation with pulses of 50-1000 s length (638 or 660 nm), capable of actuating the implant about 10 mm below the skin. We detail how to benchmark performance parameters of OEPCs first ex vivo, and in vivo using a rat sciatic nerve. Incorporation of a microfabricated zip-tie mechanism enabled stable, long-term nerve implantation of OEPC devices in rats, with sustained ability to non-invasively mediate neurostimulation over 100 days. OEPC devices introduce a high performance, ultralow volume (0.1 mm3), biocompatible approach to wireless neuromodulation, with potential applicability to an array of clinical bioelectronics.

neuroscience↗