Numerous applications in neuroscience research and neural prosthetics, such as electrocorticogram (ECoG) recording and retinal prosthesis, involve electrical interactions with soft excitable tissues ...using a surface recording and/or stimulation approach. These applications require an interface that is capable of setting up high-throughput communications between the electrical circuit and the excitable tissue and that can dynamically conform to the shape of the soft tissue. Being a compliant material with mechanical impedance close to that of soft tissues, polydimethylsiloxane (PDMS) offers excellent potential as a substrate material for such neural interfaces. This paper describes an integrated technology for fabrication of PDMS-based stretchable microelectrode arrays (MEAs). Specifically, as an integral part of the fabrication process, a stretchable MEA is directly fabricated with a rigid substrate, such as a thin printed circuit board (PCB), through an innovative bonding technology-via-bonding-for integrated packaging. This integrated strategy overcomes the conventional challenge of high-density packaging for this type of stretchable electronics. Combined with a high-density interconnect technology developed previously, this stretchable MEA technology facilitates a high-resolution, high-density integrated system solution for neural and muscular surface interfacing. In this paper, this PDMS-based integrated stretchable MEA (isMEA) technology is demonstrated by an example design that packages a stretchable MEA with a small PCB. The resulting isMEA is assessed for its biocompatibility, surface conformability, electrode impedance spectrum, and capability to record muscle fiber activity when applied epimysially.
Current methods of evaluating essential tremor (ET) either rely on subjective ratings or use limited tremor metrics (i.e., severity/amplitude and frequency). In this study, we explored performance ...metrics from Fitts' law tasks that replicate and expand existing tremor metrics, to enable low-cost, home-based tremor quantification and analyze the cursor movements of individuals using a 3D mouse while performing a collection of drawing tasks. We analyzed the 3D mouse cursor movements of 11 patients with ET and three controls, on three computer-based tasks-a spiral navigation (SPN) task, a rectangular track navigation (RTN) task, and multi-directional tapping/clicking (MDT)-with several performance metrics (i.e., outside area (OA), throughput (TP in Fitts' law), path efficiency (PE), and completion time (CT). Using an accelerometer and scores from the Essential Tremor Rating Assessment Scale (TETRAS), we correlated the proposed performance metrics with the baseline tremor metrics and found that the OA of the SPN and RTN tasks were strongly correlated with baseline tremor severity (R 2 = 0.57, and R 2 = 0.83). We also found that the TP in the MDT tasks were strongly correlated with tremor frequency (R 2 = 0.70). In addition, as the OA of the SPN and RTN tasks was correlated with tremor severity and frequency, it may represent an independent metric that increases the dimensionality of the characterization of an individual's tremor. Thus, this pilot study of the analysis of those with ET-associated tremor performing Fitts' law tasks demonstrates the feasibility of introducing a new tremor metric that can be expanded for repeatable multi-dimensional data analyses.
High‐density stretchable electronics are achieved using multilayer interconnects on an elastomeric substrate. Two major challenges associated with stretchable electronics—increasing integration ...density and improving electrical bonding—have been addressed by our innovative multilayer via‐bonding technology. The resulting multichip‐module architecture provides an elastic, high‐density solution for numerous potential applications.
High‐resolution, high‐density gold interconnects are effectively patterned on an elastomeric substrate. A 3 cm cable of ten gold wires with 10 μm width and 20 μm pitch is achieved, successfully ...demonstrating density increases of more than one order of magnitude from previously established work. Many applications in the fields of stretchable electronics and conformable neural interfaces will benefit from these fabrication developments.
The cutaneus trunci muscle (CTM) reflex produces a skin "shrug" in response to pinch on a rat's back through a three-part neural circuit:
) A-fiber and C-fiber afferents in segmental dorsal cutaneous ...nerves (DCNs) from lumbar to cervical levels,
) ascending propriospinal interneurons, and
) the CTM motoneuron pool located at the cervicothoracic junction. We recorded neurograms from a CTM nerve branch in response to electrical stimulation. The pulse trains were delivered at multiple DCNs (T
-L
), on both sides of the midline, at two stimulus strengths (0.5 or 5 mA, to activate Aδ fibers or Aδ and C fibers, respectively) and four stimulation frequencies (1, 2, 5, or 10 Hz) for 20 s. We quantified both the temporal dynamics (i.e., latency, sensitization, habituation, and frequency dependence) and the spatial dynamics (spinal level) of the reflex. The evoked responses were time-windowed into Early, Mid, Late, and Ongoing phases, of which the Mid phase, between the Early (Aδ fiber mediated) and Late (C fiber mediated) phases, has not been previously identified. All phases of the response varied with stimulus strength, frequency, history, and DCN level/side stimulated. In addition, we observed nociceptive characteristics like C fiber-mediated sensitization (wind-up) and habituation. Finally, the range of latencies in the ipsilateral responses were not very large rostrocaudally, suggesting a myelinated neural path within the ipsilateral spinal cord for at least the A fiber-mediated Early-phase response. Overall, these results demonstrate that the CTM reflex shares the temporal dynamics in other nociceptive reflexes and exhibits spatial (segmental and lateral) dynamics not seen in those reflexes.
We have physiologically studied an intersegmental reflex exploring detailed temporal, stimulus strength-based, stimulation history-dependent, lateral and segmental quantification of the reflex responses to cutaneous nociceptive stimulations. We found several physiological features in this reflex pathway, e.g., wind-up, latency changes, and somatotopic differences. These physiological observations allow us to understand how the anatomy of this reflex may be organized. We have also identified a new phase of this reflex, termed the "mid" response.
Objective: Currently available treatments for kinetic tremor can cause intolerable side effects or be highly invasive and expensive. Even though several studies have shown the positive effects of ...external feedback (i.e., electrical stimulation) for suppressing tremor, such approaches have not been fully integrated into wearable real-time feedback systems. Method: We have developed a wireless wearable stimulation system that analyzes upper limb tremor using a three-axis accelerometer and that modulates/attenuates tremor using peripheral-nerve electrical stimulation with adjustable stimulation parameters and a real-time tremor detection algorithm. We outfitted nine subjects with tremor with a wearable system and a set of surface electrodes placed on the skin overlying the radial nerve and tested the effects of stimulation with nine combinations of parameters for open- and closed-loop stimulation on tremor. To quantify the effects of the stimulation, we measured tremor movements, and analyzed the dominant tremor frequency and tremor power. Results:Baseline tremor power gradually decreased over the course of 18 stimulation trials. During the last trial, compared with the control trial, the reduction rate of tremor power was 42.17 ± 3.09%. The dominant tremor frequency could be modulated more efficiently by phase-locked closed-loop stimulation. The tremor power was equally reduced by open- and closed-loop stimulation. Conclusion: Peripheral nerve stimulation significantly affects tremor, and stimulation parameters need to be optimized to modulate tremor metrics. Clinical Impact: This preliminary study lays the foundation for future studies that will evaluate the efficacy of the proposed closed-loop peripheral nerve stimulation method in a larger group of patients with kinetic tremor.
Cutaneous sensory feedback from the paw pads plays an important role in regulating body balance, especially in challenging environments like ladder or slope walking. Here, we investigated the ...contribution of cutaneous sensory feedback from the paw pads to balance control in cats stepping on a split-belt treadmill. Forepaws and hindpaws were anesthetized unilaterally using lidocaine injections. We evaluated body balance in intact and compromised cutaneous feedback conditions during split-belt locomotion with belt-speed ratios of 0.5, 1.0, 1.5 and 2.0. Measures of body balance included step width, relative duration of limb support phases, lateral bias of center of mass (CoM) and margins of static and dynamic stability. In the intact condition, static and dynamic balance declined with increasing belt-speed ratio as a result of a lateral shift of the CoM toward the borders of support on the slower moving belt. Anesthesia of the ipsilateral paws improved locomotor balance with increasing belt-speed ratios by reversing the CoM shift, decreasing the relative duration of the two-limb support phase, increasing the duration of four- or three-limb support phases, and increasing the hindlimb step width and static stability. We observed no changes in most balance measures in anesthetized conditions during tied-belt locomotion at 0.4 m s
CoM lateral displacements closely resembled those of the inverted pendulum and of human walking. We propose that unilaterally compromised cutaneous feedback from the paw pads is compensated for by improving lateral balance and by shifting the body toward the anesthetized paws to increase tactile sensation during the stance phase.
(1) Background: Non-invasive neuromodulation is a promising alternative to medication or deep-brain stimulation treatment for Parkinson's Disease or essential tremor. In previous work, we developed ...and tested a wearable system that modulates tremor via the non-invasive, electrical stimulation of peripheral nerves. In this article, we examine the proper range and the effects of various stimulation parameters for phase-locked stimulation. (2) Methods: We recruited nine participants with essential tremor. The subjects performed a bean-transfer task that mimics an eating activity to elicit kinetic tremor while using the wearable stimulation system. We examined the effects of stimulation with a fixed duty cycle, at different stimulation amplitudes and frequencies. The epochs of stimulation were locked to one of four phase positions of ongoing tremor, as measured with an accelerometer. We analyzed stimulation-evoked changes of the frequency and amplitude of tremor. (3) Results: We found that the higher tremor amplitude group experienced a higher rate of tremor power reduction (up to 65%) with a higher amplitude of stimulation when the stimulation was applied at the ±peak of tremor phase. (4) Conclusions: The stimulation parameter can be adjusted to optimize tremor reduction, and this study lays the foundation for future large-scale parameter optimization experiments for personalized peripheral nerve stimulation.
Electrical stimulation to segmental dorsal cutaneous nerves (DCNs) activates a nociceptive sensorimotor reflex and the same afferent stimulation also evokes blood pressure (BP) and heart rate (HR) ...responses in rats. To investigate the relationship between those cardiovascular responses and the activation of nociceptive afferents, we analyzed BP and HR responses to electrical stimulations at each DCN from T6 to L1 at 0.5 mA to activate A-fiber alone or 5 mA to activate both A- and C-fibers at different frequencies. Evoked cardiovascular responses showed a decrease and then an increase in BP and an increase and then a plateau in HR. Segmentally, both cardiovascular responses tended to be larger when evoked from the more rostral DCNs. Stimulation frequency had a larger effect on cardiovascular responses than the rostrocaudal level of the DCN input. Stimulation strength showed a large effect on BP changes dependent on C-fibers whereas HR changes were dependent on A-fibers. Additional A-fiber activation by stimulating up to 4 adjacent DCNs concurrently, but only at 0.5 mA, affected HR but not BP. These data support that cutaneous nociceptive afferent subtypes preferentially contribute to different cardiovascular responses, A-fibers to HR and C-fibers to BP, with temporal (stimulation frequency) and spatial (rostrocaudal level) dynamics.
We have developed a stretchable microneedle electrode array (sMEA) to stimulate and measure the electrical activity of muscle across multiple sites. The technology provides the signal fidelity and ...spatial resolution of intramuscular electrodes across a large area of tissue. Our sMEA is composed of a polydimethylsiloxane (PDMS) substrate, conductive-PDMS traces, and stainless-steel penetrating electrodes. The traces and microneedles maintain a resistance of less than 10 kQ when stretched up to a ~63% tensile strain, which allows for the full range of physiological motion of feline muscle. The device and its constituent materials are cytocompatible for at least 28 days in vivo. When implanted in vivo, the device measures electromyographic (EMG)activitywith clear compound motor unit action potentials. The sMEA also maintains a stable connection with moving muscle while electrically stimulating the tissue. This technology has direct application to wearable sensors, neuroprostheses, and electrophysiological studies of animals and humans.
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