Neurophysiology of epidurally evoked spinal cord reflexes in clinically motor-complete posttraumatic spinal cord injury.

Increased use of epidural Spinal Cord Stimulation (eSCS) for the rehabilitation of spinal cord injury (SCI) has highlighted the need for a greater understanding of the properties of reflex circuits in the isolated spinal cord, particularly in response to repetitive stimulation. Here, we investigate the frequency-dependence of modulation of short- and long-latency EMG responses of lower limb muscles in patients with SCI at rest. Single stimuli could evoke short-latency responses as well as long-latency (likely polysynaptic) responses. The short-latency component was enhanced at low frequencies and declined at higher rates. In all muscles, the effects of eSCS were more complex if polysynaptic activity was elicited, making the motor output become an active process expressed either as suppression, tonic or rhythmical activity. The polysynaptic activity threshold is not constant and might vary with different stimulation frequencies, which speaks for its temporal dependency. Polysynaptic components can be observed as direct responses, neuromodulation of monosynaptic responses or driving the muscle activity by themselves, depending on the frequency level. We suggest that the presence of polysynaptic activity could be a potential predictor for appropriate stimulation conditions. This work studies the complex behaviour of spinal circuits deprived of voluntary motor control from the brain and in the absence of any other inputs. This is done by describing the monosynaptic responses, polysynaptic activity, and its interaction through its input-output interaction with sustain stimulation that, unlike single stimuli used to study the reflex pathway, can strongly influence the interneuron circuitry and reveal a broader spectrum of connectivity.

A standalone bioreactor system to deliver compressive load under perfusion flow to hBMSC-seeded 3D chitosan-graphene templates.

The availability of engineered biological tissues holds great potential for both clinical applications and basic research in a life science laboratory. A prototype standalone perfusion/compression bioreactor system was proposed to address the osteogenic commitment of stem cells seeded onboard of 3D chitosan-graphene (CHT/G) templates. Testing involved the coordinated administration of a 1 mL/min medium flow rate together with dynamic compression (1% strain at 1 Hz; applied twice daily for 30 min) for one week. When compared to traditional static culture conditions, the application of perfusion and compression stimuli to human bone marrow stem cells using the 3D CHT/G template scaffold induced a sizable effect. After using the dynamic culture protocol, there was evidence of a larger number of viable cells within the inner core of the scaffold and of enhanced extracellular matrix mineralization. These observations show that our novel device would be suitable for addressing and investigating the osteogenic phenotype commitment of stem cells, for both potential clinical applications and basic research.

Sub-threshold depolarizing pre-pulses can enhance the efficiency of biphasic stimuli in transcutaneous neuromuscular electrical stimulation.

There is multiple evidence in the literature that a sub-threshold pre-pulse, delivered immediately prior to an electrical stimulation pulse, can alter the activation threshold of nerve fibers and motor unit recruitment characteristics. So far, previously published works combined monophasic stimuli with sub-threshold depolarizing pre-pulses (DPPs) with inconsistent findings-in some studies, the DPPs decreased the activation threshold, while in others it was increased. This work aimed to evaluate the effect of DPPs during biphasic transcutaneous electrical stimulation and to study the possible mechanism underlying those differences. Sub-threshold DPPs between 0.5 and 15 ms immediately followed by biphasic or monophasic pulses were administered to the tibial nerve; the electrophysiological muscular responses (motor-wave, M-wave) were monitored via electromyogram (EMG) recording from the soleus muscle. The data show that, under the specific studied conditions, DPPs tend to lower the threshold for nerve fiber activation rather than elevating it. DPPs with the same polarity as the leading phase of biphasic stimuli are more effective to increase the sensitivity. This work assesses for the first time the effect of DPPs on biphasic pulses, which are required to achieve charge-balanced stimulation, and it provides guidance on the effect of polarity and intensity to take full advantage of this feature. Graphical abstract In this work, the effect of sub-threshold depolarizing pre-pulses (DPP) is investigated in a setup with transcutaneous electrical stimulation. We found that, within the tested 0-15 ms DPP duration range, the DPPs administered immediately before biphasic pulses proportionally increase the nerve excitability as visible in the M-waves recorded from the soleus muscle. Interestingly, these findings oppose published results, where DPPs, administered immediately before monophasic stimuli via implanted electrodes, led to decrease of nerve excitability.

Optimization of Interphase Intervals to Enhance the Evoked Muscular Responses of Transcutaneous Neuromuscular Electrical Stimulation.

Neuromuscular electrical stimulation (NMES) is a widely used technique for clinical diagnostic, treatment, and research. Normally, it applies charge-balanced biphasic pulses, which several publications have reported to be less efficient than monophasic pulses. A good alternative is the use of interphase intervals (IPI) on biphasic pulses that allows to achieve similar responses than those evoked by monophasic stimulation. This study analyzes the enhancing mechanism of the IPI and provides guidelines on how to optimize the IPI in order to reduce secondary effects such as the electrode corrosion. The tibial nerve was excited by NMES biphasic pulses with different IPI durations and polarities. Then, the elicited responses were recorded on the soleus muscle via electromyography. When cathodic-first pulses were applied, the responses increased proportionally to the IPI until the duration of 250 µs, where the increase saturated at 30% of the original amplitude. The responses evoked during anodic-first were 6% to 30% smaller than those evoked during cathodic-first pulses and continuously increased until the IPI duration of 2500 µs, where the responses reached an increase of around 30%. The results suggest that when a cathodic-first pulse is used, the IPI could be optimized (based on the setup geometry) to allow the action potentials to travel out of the hyperpolarization zone induced by the anodic phase. When anodic-first stimuli are applied, the IPI duration allows the fiber to recover from an apparent insensitive state induced by the anodic phase. The use of IPI is a viable option to improve the efficiency of actual stimulation systems, since only small modifications are required to significantly reduce the electrical charge required and boost the stimulation efficiency.

Comparison of Twitch Responses During Current- or Voltage-Controlled Transcutaneous Neuromuscular Electrical Stimulation.

Neuromuscular electrical stimulation (NMES) is an established method for functional restoration of muscle function, rehabilitation, and diagnostics. In this work, NMES was applied with surface electrodes placed on the anterior thigh to identify the main differences between current-controlled (CC) and voltage-controlled (VC) modes. Measurements of the evoked knee extension force and the myoelectric signal of quadriceps and hamstrings were taken during stimulation with different amplitudes, pulse widths, and stimulation techniques. The stimulation pulses were rectangular and symmetric biphasic for both stimulation modes. The electrode-tissue impedance influences the differences between CC and VC stimulation. The main difference is that for CC stimulation, variation of pulse width and amplitude influences the amount of nerve depolarization, whereas VC stimulation is only dependent on amplitude variations for pulse widths longer than 150 µs. An important remark is that these findings are strongly dependent on the characteristics of the electrode-skin interface. In our case, we used large stimulation electrodes placed on the anterior thigh, which cause higher capacitive effects. The controllability, voltage compliance, and charge characteristics of each stimulation technique should be considered during the stimulators design. For applications that require the activation of a large amount of nerve fibers, VC is a more suitable option. In contrast, if the application requires a high controllability, then CC should be chosen prior to VC.

Dynamic impedance model of the skin-electrode interface for transcutaneous electrical stimulation.

Transcutaneous electrical stimulation can depolarize nerve or muscle cells applying impulses through electrodes attached on the skin. For these applications, the electrode-skin impedance is an important factor which influences effectiveness. Various models describe the interface using constant or current-depending resistive-capacitive equivalent circuit. Here, we develop a dynamic impedance model valid for a wide range stimulation intensities. The model considers electroporation and charge-dependent effects to describe the impedance variation, which allows to describe high-charge pulses. The parameters were adjusted based on rectangular, biphasic stimulation pulses generated by a stimulator, providing optionally current or voltage-controlled impulses, and applied through electrodes of different sizes. Both control methods deliver a different electrical field to the tissue, which is constant throughout the impulse duration for current-controlled mode or have a very current peak for voltage-controlled. The results show a predominant dependence in the current intensity in the case of both stimulation techniques that allows to keep a simple model. A verification simulation using the proposed dynamic model shows coefficient of determination of around 0.99 in both stimulation types. The presented method for fitting electrode-skin impedance can be simple extended to other stimulation waveforms and electrode configuration. Therefore, it can be embedded in optimization algorithms for designing electrical stimulation applications even for pulses with high charges and high current spikes.