Distinguishing reflex from non-reflex responses elicited by transcutaneous spinal stimulation targeting the lumbosacral cord in healthy individuals.

Transcutaneous spinal stimulation (TSS) studies rely on the depolarization of afferent fibers to provide input to the spinal cord; however, this has not been routinely ascertained. Thus, we aimed to characterize the types of responses evoked by TSS and establish paired-pulse ratio cutoffs that distinguish posterior root reflexes, evoked by stimulation of afferent nerve fibers, from motor responses, evoked by stimulation of efferent nerve fibers. Twelve neurologically intact participants (six women) underwent unipolar TSS (cathode over T11-12 spinal processes, anode paraumbilically) while resting supine. In six participants, unipolar TSS was repeated 2-3 months later and also compared to a bipolar TSS configuration (cathode 2.5 cm below T11-12, anode 5 cm above cathode). EMG signals were recorded from 16 leg muscles. A paired-pulse paradigm was applied at interstimulus intervals (ISIs) of 25, 50, 100, 200, and 400 ms. Responses were categorized by three assessors into reflexes, motor responses, or their combination (mixed responses) based on the visual presence/absence of paired-pulse suppression across ISIs. The paired-pulse ratio that best discriminated between response types was derived for each ISI. These cutoffs were validated by repeating unipolar TSS 2-3 months later and with bipolar TSS. Unipolar TSS evoked only reflexes (90%) and mixed responses (10%), which were mainly recorded in the quadriceps muscles (25-42%). Paired-pulse ratios of 0.51 (25-ms ISI) and 0.47 (50-ms ISI) best distinguished reflexes from mixed responses (100% sensitivity, > 99.2% specificity). These cutoffs performed well in the repeated unipolar TSS session (100% sensitivity, > 89% specificity). Bipolar TSS exclusively elicited reflexes which were all correctly classified. These results can be utilized in future studies to ensure that the input to the spinal cord originates from the depolarization of large afferents. This knowledge can be applied to improve the design of future neurophysiological studies and increase the fidelity of neuromodulation interventions.

Selective Tibial Neurotomy Outcomes for Spastic Equinovarus Foot: Patient Expectations and Functional Assessment.

BACKGROUND: Spastic equinovarus foot (SEF) is a common dysfunctional foot posture after stroke that impairs balance and mobility. Selective tibial neurotomy (STN) is a simple but underutilized surgical option that can effectively address critical aspects of SEF and thereby provide enduring quality of life gains. There are few studies that examine both functional outcomes and patient satisfaction with this treatment option. OBJECTIVE: To elucidate the patient goals that motivated their decision to undergo the procedure and compare subjective and objective changes in balance and functional mobility as a consequence of surgery. METHODS: Thirteen patients with problematic SEF who had previously failed conservative measures were treated with STN. Preoperative and postoperative (on average 6 months) assessments evaluated gait quality and functional mobility. In addition, a custom survey was conducted to investigate patient perspectives on STN intervention. RESULTS: The survey showed that participants who opted for STN were dissatisfied with their previous spasticity management. The most common preoperative expectation for STN treatment was to improve walking, followed by improving balance, brace comfort, pain, and tone. Postoperatively, participants rated the improvement in their expectations and were, on average, 71 on a 100-point scale, indicating high satisfaction. The gait quality, assessed with the Gait Intervention and Assessment Tool, improved significantly between preoperative and postoperative assessment (M = -4.1, P = .01) with a higher average difference in stance of -3.3 than in swing -0.5. Improvement in both gait endurance (M = 36 m, P = .01) and self-selected gait speed (M = .12 m/s, P = .03) was statistically significant. Finally, static balance (M = 5.0, P = .03) and dynamic balance (M = 3.5, P = .02) were also significantly improved. CONCLUSION: STN improved gait quality and functional mobility and was associated with high satisfaction in patients with SEF.

Neuromodulation with transcutaneous spinal stimulation reveals different groups of motor profiles during robot-guided stepping in humans with incomplete spinal cord injury.

Neuromodulation via spinal stimulation has been investigated for improving motor function and reducing spasticity after spinal cord injury (SCI) in humans. Despite the reported heterogeneity of outcomes, few investigations have attempted to discern commonalities among individual responses to neuromodulation, especially the impact of stimulation frequencies. Here, we examined how exposure to continuous lumbosacral transcutaneous spinal stimulation (TSS) across a range of frequencies affects robotic torques and EMG patterns during stepping in a robotic gait orthosis on a motorized treadmill. We studied nine chronic motor-incomplete SCI individuals (8/1 AIS-C/D, 8 men) during robot-guided stepping with body-weight support without and with TSS applied at random frequencies between 1 and up to 100 Hz at a constant, individually selected stimulation intensity below the common motor threshold for posterior root reflexes. The hip and knee robotic torques needed to maintain the predefined stepping trajectory and EMG in eight bilateral leg muscles were recorded. We calculated the standardized mean difference between the stimulation conditions grouped into frequency bins and the no stimulation condition to determine changes in the normalized torques and the average EMG envelopes. We found heterogeneous changes in robotic torques across individuals. Agglomerative clustering of robotic torques identified four groups wherein the patterns of changes differed in magnitude and direction depending mainly on the stimulation frequency and stance/swing phase. On one end of the spectrum, the changes in robotic torques were greater with increasing stimulation frequencies (four participants), which coincided with a decrease in EMG, mainly due to the reduction of clonogenic motor output in the lower leg muscles. On the other end, we found an inverted u-shape change in torque over the mid-frequency range along with an increase in EMG, reflecting the augmentation of gait-related physiological (two participants) or pathophysiological (one participant) output. We conclude that TSS during robot-guided stepping reveals different frequency-dependent motor profiles among individuals with chronic motor incomplete SCI. This suggests the need for a better understanding and characterization of motor control profiles in SCI when applying TSS as a therapeutic intervention for improving gait.

Influence of Spine Curvature on the Efficacy of Transcutaneous Lumbar Spinal Cord Stimulation.

Transcutaneous spinal cord stimulation is a non-invasive method for neuromodulation of sensorimotor function. Its main mechanism of action results from the activation of afferent fibers in the posterior roots-the same structures as targeted by epidural stimulation. Here, we investigated the influence of sagittal spine alignment on the capacity of the surface-electrode-based stimulation to activate these neural structures. We evaluated electromyographic responses evoked in the lower limbs of ten healthy individuals during extension, flexion, and neutral alignment of the thoracolumbar spine. To control for position-specific effects, stimulation in these spine alignment conditions was performed in four different body positions. In comparison to neutral and extended spine alignment, flexion of the spine resulted in a strong reduction of the response amplitudes. There was no such effect on tibial-nerve evoked H reflexes. Further, there was a reduction of post-activation depression of the responses to transcutaneous spinal cord stimulation evoked in spinal flexion. Thus, afferent fibers were reliably activated with neutral and extended spine alignment. Spinal flexion, however, reduced the capacity of the stimulation to activate afferent fibers and led to the co-activation of motor fibers in the anterior roots. This change of action was due to biophysical rather than neurophysiological influences. We recommend applying transcutaneous spinal cord stimulation in body positions that allow individuals to maintain a neutral or extended spine.

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.

Bipolar transcutaneous spinal stimulation evokes short-latency reflex responses in human lower limbs alike standard unipolar electrode configuration.

Noninvasive electrical stimulation targeting the posterior lumbosacral roots has been applied recently in reflexes studies and as a neuromodulation intervention for modifying spinal cord circuitry after an injury. Here, we characterized short-latency responses evoked by four bipolar electrode configurations placed longitudinally over the spinal column at different vertebral levels from L1 to T9. They were compared with the responses evoked by the standard unipolar (aka monopolar) electrode configuration (cathode at T11/12, anode over the abdominal wall). Short-latency responses were recorded in the rectus femoris, medial hamstrings, tibialis anterior, and soleus muscles, bilaterally, in 11 neurologically intact participants. The response recruitment characteristics (maximal amplitude, motor threshold) and amplitude-matched onset latencies and paired-pulse suppression (35-ms interstimulus interval) were assessed with 1-ms current-controlled pulses at intensities up to 100 mA. The results showed that short-latency responses can be elicited with all bipolar electrode configurations. However, only with the cathode at T11/12 and the anode 10 cm cranially (∼T9), the maximum response amplitudes were statistical equivalent (P < 0.05) in the medial hamstrings, tibialis anterior, and soleus but not the rectus femoris, whereas motor thresholds were not significantly different across all muscles. The onset latency and paired-pulse suppression were also not significantly different across the tested electrode configurations, thereby confirming the reflex nature of the bipolar short-latency responses. We conclude that the bipolar configuration (cathode T11/12, anode ∼T9) produces reflex responses that are ostensibly similar to those evoked by the standard unipolar configuration. This provides an alternative approach for neuromodulation intervention.NEW & NOTEWORTHY Transcutaneous spinal stimulation with the identified bipolar electrode configuration may offer several advantages for neuromodulation interventions over commonly used unipolar configurations: there are no associated abdominal contractions, which improves the participant's comfort; additional dermatomes are not stimulated as when the anode is over the abdominal wall or iliac crest, which may have unwanted effects; and, due to a more localized electrical field, the bipolar configuration offers the possibility of targeting cord segments more selectively.

Transcutaneous Spinal Cord Stimulation Induces Temporary Attenuation of Spasticity in Individuals with Spinal Cord Injury.

Epidural spinal cord stimulation (SCS) is currently regarded as a breakthrough procedure for enabling movement after spinal cord injury (SCI), yet one of its original applications was for spinal spasticity. An emergent method that activates similar target neural structures non-invasively is transcutaneous SCS. Its clinical value for spasticity control would depend on inducing carry-over effects, because the surface-electrode-based approach cannot be applied chronically. We evaluated single-session effects of transcutaneous lumbar SCS in 12 individuals with SCI by a test-battery approach, before, immediately after and 2 h after intervention. Stimulation was applied for 30 min at 50 Hz with an intensity sub-threshold for eliciting reflexes in lower extremity muscles. The tests included evaluations of stretch-induced spasticity (Modified Ashworth Scale [MAS] sum score, pendulum test, electromyography-based evaluation of tonic stretch reflexes), clonus, cutaneous-input-evoked spasms, and the timed 10 m walk test. Across participants, the MAS sum score, clonus, and spasms were significantly reduced immediately after SCS, and all spasticity measures were improved 2 h post-intervention, with large effect sizes and including clinically meaningful improvements. The effect on walking speed varied across individuals. We further conducted a single-case multi-session study over 6 weeks to explore the applicability of transcutaneous SCS as a home-based therapy. Self-application of the intervention was successful; weekly evaluations suggested progressively improving therapeutic effects during the active period and carry-over effects for 7 days. Our results suggest that transcutaneous SCS can be a viable non-pharmacological option for managing spasticity, likely working through enhancing pre- and post-synaptic spinal inhibitory mechanisms, and may additionally serve to identify responders to treatments with epidural SCS.