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1. High frequency alternating current neurostimulation decreases nocifensive behavior in a disc herniation model of lumbar radiculopathy

   https://doi.org/10.1186/s42234-023-00119-0  

   Dewberry, Lauren Savannah ; Porche, Ken ; Koenig, Travis ; Allen, Kyle D. ; Otto, Kevin J. ( July 2023 , Bioelectronic Medicine)

   The purpose of this study was to evaluate if kilohertz frequency alternating current (KHFAC) stimulation of peripheral nerve could serve as a treatment for lumbar radiculopathy. Prior work shows that KHFAC stimulation can treat sciatica resulting from chronic sciatic nerve constriction. Here, we evaluate if KHFAC stimulation is also beneficial in a more physiologic model of low back pain which mimics nucleus pulposus (NP) impingement of a lumbar dorsal root ganglion (DRG).

   To mimic a lumbar radiculopathy, autologous tail NP was harvested and placed upon the right L5 nerve root and DRG. During the same surgery, a cuff electrode was implanted around the sciatic nerve with wires routed to a headcap for delivery of KHFAC stimulation. Male Lewis rats (3 mo.,n = 18) were separated into 3 groups: NP injury + KHFAC stimulation (n = 7), NP injury + sham cuff (n = 6), and sham injury + sham cuff (n = 5). Prior to surgery and for 2 weeks following surgery, animal tactile sensitivity, gait, and static weight bearing were evaluated.

   KHFAC stimulation of the sciatic nerve decreased behavioral evidence of pain and disability. Without KHFAC stimulation, injured animals had heightened tactile sensitivity compared to baseline (p < 0.05), with tactile allodynia reversed during KHFAC stimulation (p < 0.01). Midfoot flexion during locomotion was decreased after injury but improved with KHFAC stimulation (p < 0.05). Animals also placed more weight on their injured limb when KHFAC stimulation was applied (p < 0.05). Electrophysiology measurements at end point showed decreased, but not blocked, compound nerve action potentials with KHFAC stimulation (p < 0.05).

   KHFAC stimulation decreases hypersensitivity but does not cause additional gait compensations. This supports the idea that KHFAC stimulation applied to a peripheral nerve may be able to treat chronic pain resulting from sciatic nerve root inflammation.

    

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2. Characterization and Miniaturization of Silver-Nanoparticle Microcoil via Aerosol Jet Printing Techniques for Micromagnetic Cochlear Stimulation

   https://doi.org/10.3390/s20216087  

   Sarreal, Ressa Reneth ; Bhatti, Pamela ( November 2020 , Sensors)

   null (Ed.)

   According to the National Institute of Deafness and other Communication Disorders 2012 report, the number of cochlear implant (CI) users is steadily increasing from 324,000 CI users worldwide. The cochlea, located in the inner ear, is a snail-like structure that exhibits a tonotopic geometry where acoustic waves are filtered spatially according to frequency. Throughout the cochlea, there exist hair cells that transduce sensed acoustic waves into an electrical signal that is carried by the auditory nerve to ultimately reach the auditory cortex of the brain. A cochlear implant bridges the gap if non-functional hair cells are present. Conventional CIs directly inject an electrical current into surrounding tissue via an implanted electrode array and exploit the frequency-to-place mapping of the cochlea. However, the current is dispersed in perilymph, a conductive bodily fluid within the cochlea, causing a spread of excitation. Magnetic fields are more impervious to the effects of the cochlear environment due to the material properties of perilymph and surrounding tissue, demonstrating potential to improve precision. As an alternative to conventional CI electrodes, the development and miniaturization of microcoils intended for micromagnetic stimulation of intracochlear neural elements is described. As a step toward realizing a microcoil array sized for cochlear implantation, human-sized coils were prototyped via aerosol jet printing. The batch reproducible aerosol jet printed microcoils have a diameter of 1800 μm, trace width and trace spacing of 112.5 μm, 12 μm thickness, and inductance values of approximately 15.5 nH. Modelling results indicate that the coils have a combined depolarization–hyperpolarization region that spans 1.5 mm and produce a more restrictive spread of activation when compared with conventional CI. 

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3. Asynchronous axonal firing patterns evoked via continuous subthreshold kilohertz stimulation

   https://doi.org/10.1088/1741-2552/acc20f  

   Vargas, Luis ; Musselman, Eric D. ; Grill, Warren M. ; Hu, Xiaogang ( March 2023 , Journal of Neural Engineering)

   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 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.

    

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4. Comparative analysis of Dipodomys species indicates that kangaroo rat hindlimb anatomy is adapted for rapid evasive leaping

   https://doi.org/10.1111/joa.13567  

   Freymiller, Grace A. ; Whitford, Malachi D. ; Schwaner, M. Janneke ; McGowan, Craig P. ; Higham, Timothy E. ; Clark, Rulon W. ( October 2021 , Journal of Anatomy)

   Body size is a key factor that influences antipredator behavior. For animals that rely on jumping to escape from predators, there is a theoretical trade‐off between jump distance and acceleration as body size changes at both the inter‐ and intraspecific levels. Assuming geometric similarity, acceleration will decrease with increasing body size due to a smaller increase in muscle cross‐sectional area than body mass. Smaller animals will likely have a similar jump distance as larger animals due to their shorter limbs and faster accelerations. Therefore, in order to maintain acceleration in a jump across different body sizes, hind limbs must be disproportionately bigger for larger animals. We explored this prediction using four species of kangaroo rats (Dipodomysspp.), a genus of bipedal rodent with similar morphology across a range of body sizes (40–150 g). Kangaroo rat jump performance was measured by simulating snake strikes to free‐ranging individuals. Additionally, morphological measurements of hind limb muscles and segment lengths were obtained from thawed frozen specimens. Overall, jump acceleration was constant across body sizes and jump distance increased with increasing size. Additionally, kangaroo rat hind limb muscle mass and cross‐sectional area scaled with positive allometry. Ankle extensor tendon cross‐sectional area also scaled with positive allometry. Hind limb segment length scaled isometrically, with the exception of the metatarsals, which scaled with negative allometry. Overall, these findings support the hypothesis that kangaroo rat hind limbs are built to maintain jump acceleration rather than jump distance. Selective pressure from single‐strike predators, such as snakes and owls, likely drives this relationship.

    

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5. Artifact propagation in electrocorticography stimulation

   Lim, J. ; Wang, P.T. ; Shaw, S.J. ; Armacost, M. ; Gong, H. ; Liu, C.Y. ; Heydari, P. ; Do, A.H. ; Nenadic, Z. ( May 2018 , Seventh International BCI Meeting, Abstract Book)

   Introduction:Current brain-computer interfaces (BCIs) primarily rely on visual feedback. However, visual feedback may not be sufficient for applications such as movement restoration, where somatosensory feedback plays a crucial role. For electrocorticography (ECoG)-based BCIs, somatosensory feedback can be elicited by cortical surface electro-stimulation [1]. However, simultaneous cortical stimulation and recording is challenging due to stimulation artifacts. Depending on the orientation of stimulating electrodes, their distance to the recording site, and the stimulation intensity, these artifacts may overwhelm the neural signals of interest and saturate the recording bioamplifiers, making it impossible to recover the underlying information [2]. To understand how these factors affect artifact propagation, we performed a preliminary characterization of ECoG signals during cortical stimulation.Materials/Methods/ResultsECoG electrodes were implanted in a 39-year old epilepsy patient as shown in Fig. 1. Pairs of adjacent electrodes were stimulated as a part of language cortical mapping. For each stimulating pair, a charge-balanced biphasic square pulse train of current at 50 Hz was delivered for five seconds at 2, 4, 6, 8 and 10 mA. ECoG signals were recorded at 512 Hz. The signals were then high-pass filtered (≥1.5 Hz, zero phase), and the 5-second stimulation epochs were segmented. Within each epoch, artifact-induced peaks were detected for each electrode, except the stimulating pair, where signals were clipped due to amplifier saturation. These peaks were phase-locked across electrodes and were 20 ms apart, thus matching the pulse train frequency. The response was characterized by calculating the median peak within the 5-second epochs. Fig. 1 shows a representative response of the right temporal grid (RTG), with the stimulation channel at RTG electrodes 14 and 15. It also shows a hypothetical amplifier saturation contour of an implantable, bi-directional, ECoG-based BCI prototype [2], assuming the supply voltage of 2.2 V and a gain of 66 dB. Finally, we quantify the worstcase scenario by calculating the largest distance between the saturation contour and the midpoint of each stimulating channel.Discussion:Our results indicate that artifact propagation follows a dipole potential distribution with the extent of the saturation region (the interior of the white contour) proportional to the stimulation amplitude. In general, the artifacts propagated farthest when a 10 mA current was applied with the saturation regions extending from 17 to 32 mm away from the midpoint of the dipole. Consistent with the electric dipole model, this maximum spread happened along the direction of the dipole moment. An exception occurred at stimulation channel RTG11-16, for which an additional saturation contour emerged away from the dipole contour (not shown), extending the saturation region to 41 mm. Also, the worst-case scenario was observed at 6 mA stimulation amplitude. This departure could be a sign of a nonlinear, switch-like behavior, wherein additional conduction pathways could become engaged in response to sufficiently high stimulation.Significance:While ECoG stimulation is routinely performed in the clinical setting, quantitative studies of the resulting signals are lacking. Our preliminary study demonstrates that stimulation artifacts largely obey dipole distributions, suggesting that the dipole model could be used to predict artifact propagation. Further studies are necessary to ascertain whether these results hold across other subjects and combinations of stimulation/recording grids. Once completed, these studies will reveal practical design constraints for future implantable bi-directional ECoG-based BCIs. These include parameters such as the distances between and relative orientations of the stimulating and recording electrodes, the choice of the stimulating electrodes, the optimal placement of the reference electrode, and the maximum stimulation amplitude. These findings would also have important implications for the design of custom, low-power bioamplifiers for implantable bi-directional ECoG-based BCIs.References:[1] Hiremath, S. V., et al. "Human perception of electrical stimulation on the surface of somatosensory cortex." PloS one 12.5 (2017): e0176020.[2] Rouse, A. G., et al. "A chronic generalized bi-directional brain-machine interface." Journal of Neural Engineering 8.3 (2011): 036018 

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