Yogi A. Patel

Differential fiber-specific block of nerve conduction in mammalian peripheral nerves using kilohertz electrical stimulation

Kilohertz electrical stimulation (KES) has been shown to induce repeatable and reversible nerve conduction block in animal models. In this study, we characterized the ability of KES stimuli to selectively block specific components of stimulated nerve activity using in vivo preparations of the rat sciatic and vagus nerves. KES stimuli in the frequency range of 5-70 kHz and amplitudes of 0.1-3.0 mA were applied. Compound action potentials were evoked using either electrical or sensory stimulation, and block of components was assessed through direct nerve recordings and muscle force measurements. Distinct observable components of the compound action potential had unique conduction block thresholds as a function of frequency of KES. The fast component, which includes motor activity, had a monotonically increasing block threshold as a function of the KES frequency. The slow component, which includes sensory activity, showed a nonmonotonic block threshold relationship with increasing KES frequency. The distinct trends with frequency of the two components enabled selective block of one component with an appropriate choice of frequency and amplitude. These trends in threshold of the two components were similar when studying electrical stimulation and responses of the sciatic nerve, electrical stimulation and responses of the vagus nerve, and sensorimotor stimulation and responses of the sciatic nerve. This differential blocking effect of KES on specific fibers can extend the applications of KES conduction block to selective block and stimulation of neural signals for neuromodulation as well as selective control of neural circuits underlying sensorimotor function.

Kilohertz frequency nerve block enhances anti-inflammatory effects of vagus nerve stimulation

Efferent activation of the cervical vagus nerve (cVN) dampens systemic inflammatory processes, potentially modulating a wide-range of inflammatory pathological conditions. In contrast, afferent cVN activation amplifies systemic inflammatory processes, leading to activation of the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system through the greater splanchnic nerve (GSN), and elevation of pro-inflammatory cytokines. Ideally, to clinically implement anti-inflammatory therapy via cervical vagus nerve stimulation (cVNS) one should selectively activate the efferent pathway. Unfortunately, current implementations, in animal and clinical investigations, activate both afferent and efferent pathways. We paired cVNS with kilohertz electrical stimulation (KES) nerve block to preferentially activate efferent pathways while blocking afferent pathways. Selective efferent cVNS enhanced the anti-inflammatory effects of cVNS. Our results demonstrate that: (i) afferent, but not efferent, cVNS synchronously activates the GSN in a dose-dependent manner; (ii) efferent cVNS enabled by complete afferent KES nerve block enhances the anti-inflammatory benefits of cVNS; and (iii) incomplete afferent KES nerve block exacerbates systemic inflammation. Overall, these data demonstrate the utility of paired efferent cVNS and afferent KES nerve block for achieving selective efferent cVNS, specifically as it relates to neuromodulation of systemic inflammation.

Hard real-time closed-loop electrophysiology with the Real-Time eXperiment Interface (RTXI)

The ability to experimentally perturb biological systems has traditionally been limited to static pre-programmed or operator-controlled protocols. In contrast, real-time control allows dynamic probing of biological systems with perturbations that are computed on-the-fly during experimentation. Real-time control applications for biological research are available; however, these systems are costly and often restrict the flexibility and customization of experimental protocols. The Real-Time eXperiment Interface (RTXI) is an open source software platform for achieving hard real-time data acquisition and closed-loop control in biological experiments while retaining the flexibility needed for experimental settings. RTXI has enabled users to implement complex custom closed-loop protocols in single cell, cell network, animal, and human electrophysiology studies. RTXI is also used as a free and open source, customizable electrophysiology platform in open-loop studies requiring online data acquisition, processing, and visualization. RTXI is easy to install, can be used with an extensive range of external experimentation and data acquisition hardware, and includes standard modules for implementing common electrophysiology protocols.

High-density EEG characterization of brain responses to auditory rhythmic stimuli during wakefulness and NREM sleep

ABSTRACT Auditory rhythmic sensory stimulation modulates brain oscillations by increasing phase‐locking to the temporal structure of the stimuli and by increasing the power of specific frequency bands, resulting in Auditory Steady State Responses (ASSR). The ASSR is altered in different diseases of the central nervous system such as schizophrenia. However, in order to use the ASSR as biological markers for disease states, it needs to be understood how different vigilance states and underlying brain activity affect the ASSR. Here, we compared the effects of auditory rhythmic stimuli on EEG brain activity during wake and NREM sleep, investigated the influence of the presence of dominant sleep rhythms on the ASSR, and delineated the topographical distribution of these modulations. Participants (14 healthy males, 20‐33 years) completed on the same day a 60 min nap session and two 30 min wakefulness sessions (before and after the nap). During these sessions, amplitude modulated (AM) white noise auditory stimuli at different frequencies were applied. High‐density EEG was continuously recorded and time‐frequency analyses were performed to assess ASSR during wakefulness and NREM periods. Our analysis revealed that depending on the electrode location, stimulation frequency applied and window/frequencies analysed the ASSR was significantly modulated by sleep pressure (before and after sleep), vigilance state (wake vs. NREM sleep), and the presence of slow wave activity and sleep spindles. Furthermore, AM stimuli increased spindle activity during NREM sleep but not during wakefulness. Thus, (1) electrode location, sleep history, vigilance state and ongoing brain activity needs to be carefully considered when investigating ASSR and (2) auditory rhythmic stimuli during sleep might represent a powerful tool to boost sleep spindles. HighlightsAuditory brain responses are affected by vigilance state.The presence of sleep spindles and slow waves modulates auditory brain responses.The observed effects depend on stimuli type, electrode location, and window analyzed.Auditory stimuli at 14‐ and 40 Hz can induce sleep spindles during NREM sleep.

Microneedle cuff electrodes for extrafascicular peripheral nerve interfacing

OBJECTIVE The work presented here describes a new tool for peripheral nerve interfacing, called the microneedle cuff (μN-cuff) electrode. APPROACH μN arrays are designed and integrated into cuff electrodes for penetrating superficial tissues while remaining non-invasive to delicate axonal tracts. MAIN RESULTS In acute testing, the presence of 75 μm height μNs decreased the electrode-tissue interface impedance by 0.34 kΩ, resulting in a 0.9 mA reduction in functional stimulation thresholds and increased the signal-to-noise ratio by 9.1 dB compared to standard (needle-less) nerve cuff electrodes. Preliminary acute characterization suggests that μN-cuff electrodes provide the stability and ease of use of standard cuff electrodes while enhancing electrical interfacing characteristics. SIGNIFICANCE The ability to stimulate, block, and record peripheral nerve activity with greater specificity, resolution, and fidelity can enable more precise spatiotemporal control and measurement of neural circuits.Objective. The work presented here describes a new tool for peripheral nerve interfacing, called the microneedle cuff (μN-cuff) electrode. Approach. μN arrays are designed and integrated into cuff electrodes for penetrating superficial tissues while remaining non-invasive to delicate axonal tracts. Main results. In acute testing, the presence of 75 μm height μNs decreased the electrode-tissue interface impedance by 0.34 kΩ, resulting in a 0.9 mA reduction in functional stimulation thresholds and increased the signal-to-noise ratio by 9.1 dB compared to standard (needle-less) nerve cuff electrodes. Preliminary acute characterization suggests that μN-cuff electrodes provide the stability and ease of use of standard cuff electrodes while enhancing electrical interfacing characteristics. Significance. The ability to stimulate, block, and record peripheral nerve activity with greater specificity, resolution, and fidelity can enable more precise spatiotemporal control and measurement of neural circuits.

Corrigendum: Kilohertz frequency nerve block enhances anti-inflammatory effects of vagus nerve stimulation

This corrects the article DOI: 10.1038/srep39810.