skip to main content

Title: Asynchronous axonal firing patterns evoked via continuous subthreshold kilohertz stimulation

Objective.Transcutaneous electrical stimulation of peripheral nerves is a common technique to assist or rehabilitate impaired muscle activation. However, conventional stimulation paradigms activate nerve fibers synchronously with action potentials time-locked with stimulation pulses. Such synchronous activation limits fine control of muscle force due to synchronized force twitches. Accordingly, we developed a subthreshold high-frequency stimulation waveform with the goal of activating axons asynchronously.Approach.We evaluated our waveform experimentally and through model simulations. During the experiment, we delivered continuous subthreshold pulses at frequencies of 16.67, 12.5, or 10 kHz transcutaneously to the median and ulnar nerves. We obtained high-density electromyographic (EMG) signals and fingertip forces to quantify the axonal activation patterns. We used a conventional 30 Hz stimulation waveform and the associated voluntary muscle activation for comparison. We modeled stimulation of biophysically realistic myelinated mammalian axons using a simplified volume conductor model to solve for extracellular electric potentials. We compared the firing properties under kHz and conventional 30 Hz stimulation.Main results.EMG activity evoked by kHz stimulation showed high entropy values similar to voluntary EMG activity, indicating asynchronous axon firing activity. In contrast, we observed low entropy values in EMG evoked by conventional 30 Hz stimulation. The muscle forces evoked by kHz stimulation also more » showed more stable force profiles across repeated trials compared with 30 Hz stimulation. Our simulation results provide direct evidence of asynchronous firing patterns across a population of axons in response to kHz frequency stimulation, while 30 Hz stimulation elicited synchronized time-locked responses across the population.Significance.We demonstrate that the continuous subthreshold high-frequency stimulation waveform can elicit asynchronous axon firing patterns, which can lead to finer control of muscle forces.

« less
; ; ;
Publication Date:
Journal Name:
Journal of Neural Engineering
Page Range or eLocation-ID:
Article No. 026015
IOP Publishing
Sponsoring Org:
National Science Foundation
More Like this
  1. Neuromuscular electrical stimulation (NMES) targeting the muscle belly is commonly used to restore muscle strength in individuals with neurological disorders. However, early onset of muscle fatigue is a major limiting factor. Transcutaneous nerve stimulation (TNS) can delay muscle fatigue compared with traditional NMES techniques. However, the recruitment of Ia afferent fibers has not be specifically targeted to maximize muscle activation through the reflex pathway, which can lead to more orderly recruitment of motor units, further delaying fatigue. This preliminary study assessed the distribution of M-wave and H-reflex of intrinsic and extrinsic finger muscles. TNS was delivered using an electrode array placed along the medial side of the upper arm. Selective electrode pairs targeted the median and ulnar nerves innervating the finger flexors. High-density electromyography (HD EMG) was utilized to quantify the spatial distribution of the elicited activation of finger intrinsic and extrinsic muscles along the hand and forearm. The spatial patterns were characterized through isolation of the M-wave and H-reflex across various stimulation levels and EMG channels. Our preliminary results showed that, by altering the stimulation amplitude, distinct M-wave and H-reflex responses were evoked across EMG channels. In addition, distinct stimulation locations appeared to result in varied levels of reflexmore »recruitment. Our findings indicate that it is possible to adjust stimulation parameters to maximize reflex activation, which can potentially facilitate physiological recruitment order of motoneurons.« less
  2. Abstract Objective . Neural prosthetics often use intracortical microstimulation (ICMS) for sensory restoration. To restore natural and functional feedback, we must first understand how stimulation parameters influence the recruitment of neural populations. ICMS waveform asymmetry modulates the spatial activation of neurons around an electrode at 10 Hz; however, it is unclear how asymmetry may differentially modulate population activity at frequencies typically employed in the clinic (e.g. 100 Hz). We hypothesized that stimulation waveform asymmetry would differentially modulate preferential activation of certain neural populations, and the differential population activity would be frequency-dependent. Approach . We quantified how asymmetric stimulation waveforms delivered at 10 or 100 Hz for 30 s modulated spatiotemporal activity of cortical layer II/III pyramidal neurons using in vivo two-photon and mesoscale calcium imaging in anesthetized mice. Asymmetry is defined in terms of the ratio of the duration of the leading phase to the duration of the return phase of charge-balanced cathodal- and anodal-first waveforms (i.e. longer leading phase relative to return has larger asymmetry). Main results . Neurons within 40–60 µ m of the electrode display stable stimulation-induced activity indicative of direct activation, which was independent of waveform asymmetry. The stability of 72% of activated neurons and themore »preferential activation of 20%–90% of neurons depended on waveform asymmetry. Additionally, this asymmetry-dependent activation of different neural populations was associated with differential progression of population activity. Specifically, neural activity tended to increase over time during 10 Hz stimulation for some waveforms, whereas activity remained at the same level throughout stimulation for other waveforms. During 100 Hz stimulation, neural activity decreased over time for all waveforms, but decreased more for the waveforms that resulted in increasing neural activity during 10 Hz stimulation. Significance. These data demonstrate that at frequencies commonly used for sensory restoration, stimulation waveform alters the pattern of activation of different but overlapping populations of excitatory neurons. The impact of these waveform specific responses on the activation of different subtypes of neurons as well as sensory perception merits further investigation.« less
  3. A reliable neural-machine interface is essential for humans to intuitively interact with advanced robotic hands in an unconstrained environment. Existing neural decoding approaches utilize either discrete hand gesture-based pattern recognition or continuous force decoding with one finger at a time. We developed a neural decoding technique that allowed continuous and concurrent prediction of forces of different fingers based on spinal motoneuron firing information. High-density skin-surface electromyogram (HD-EMG) signals of finger extensor muscle were recorded, while human participants produced isometric flexion forces in a dexterous manner (i.e. produced varying forces using either a single finger or multiple fingers concurrently). Motoneuron firing information was extracted from the EMG signals using a blind source separation technique, and each identified neuron was further classified to be associated with a given finger. The forces of individual fingers were then predicted concurrently by utilizing the corresponding motoneuron pool firing frequency of individual fingers. Compared with conventional approaches, our technique led to better prediction performances, i.e. a higher correlation ([Formula: see text] versus [Formula: see text]), a lower prediction error ([Formula: see text]% MVC versus [Formula: see text]% MVC), and a higher accuracy in finger state (rest/active) prediction ([Formula: see text]% versus [Formula: see text]%). Our decodingmore »method demonstrated the possibility of classifying motoneurons for different fingers, which significantly alleviated the cross-talk issue of EMG recordings from neighboring hand muscles, and allowed the decoding of finger forces individually and concurrently. The outcomes offered a robust neural-machine interface that could allow users to intuitively control robotic hands in a dexterous manner.« less
  4. Background: Myoelectric-based decoding has gained popularity in upper-limb neural-machine interfaces. Motor unit (MU) firings decomposed from surface electromyographic (EMG) signals can represent motor intent, but EMG properties at different arm configurations can change due to electrode shift and differing neuromuscular states. This study investigated whether isometric fingertip force estimation using MU firings is robust to forearm rotations from a neutral to either a fully pronated or supinated posture. Methods: We extracted MU information from high-density EMG of the extensor digitorum communis in two ways: (1) Decomposed EMG in all three postures (MU-AllPost); and (2) Decomposed EMG in neutral posture (MU-Neu), and extracted MUs (separation matrix) were applied to other postures. Populational MU firing frequency estimated forces scaled to subjects’ maximum voluntary contraction (MVC) using a regression analysis. The results were compared with the conventional EMG-amplitude method. Results: We found largely similar root-mean-square errors (RMSE) for the two MU-methods, indicating that MU decomposition was robust to postural differences. MU-methods demonstrated lower RMSE in the ring (EMG = 6.23, MU-AllPost = 5.72, MU-Neu = 5.64 %MVC) and pinky (EMG = 6.12, MU-AllPost = 4.95, MU-Neu = 5.36 %MVC) fingers, with mixed results in the middle finger (EMG = 5.47, MU-AllPost = 5.52,more »MU-Neu = 6.19% MVC). Conclusion: Our results suggest that MU firings can be extracted reliably with little influence from forearm posture, highlighting its potential as an alternative decoding scheme for robust and continuous control of assistive devices.« less
  5. Abstract

    Objective: The objective of this study was to investigate the effects of micromagnetic stimuli strength and frequency from the Magnetic Pen (MagPen) on the rat right sciatic nerve. The nerve’s response would be measured by recording muscle activity and movement of the right hind limb. Approach: The MagPen was custom-built such that it can be held over the sciatic nerve in a stable manner. Rat leg muscle twitches were captured on video and movements were extracted using image processing algorithms. EMG recordings were also used to measure muscle activity. Main results: The MagPen prototype when driven by alternating current, generates time-varying magnetic field which as per Faraday’s Law of Electromagnetic Induction, induces an electric field for neuromodulation. The orientation dependent spatial contour maps for the induced electric field from the MagPen prototype has been numerically simulated. Furthermore, in this in vivo work on µMS, a dose-response relationship has been reported by experimentally studying how the varying amplitude (Range: 25 mVp-p through 6 Vp-p) and frequency (Range: 100 Hz through 5 kHz) of the MagPen stimuli alters the hind limb movement. The primary highlight of this dose-response relationship is that at a higher frequency of the µMS stimuli, significantly smallermore »amplitudes can trigger hind limb muscle twitch. This frequency-dependent activation can be justified following directly from the Faraday’s Law as the magnitude of the induced electric field is directly proportional to frequency. Significance: This work reports that µMS can successfully activate the sciatic nerve in a dose-dependent manner. The MagPen probe, unlike electrodes, does not have a direct electrochemical interface with tissues rendering it much safer than an electrode. Magnetic fields create more precise activation than electrodes because they induce smaller volumes of activation. Finally, unique features of µMS such as orientation dependence, directionality and spatial selectivity have been demonstrated.

    « less