Biology subjects

Wolpaw, J. R.

Publications and source records attributed to Wolpaw, J. R..

7 recordsLinked to original sources

bioRxiv2026

Test-Retest Reliability of Motor Evoked Potentials Across Eight Bilateral Lower-Limb Muscles

Objectives: Transcranial magnetic stimulation (TMS) is widely used to probe corticospinal excitability by eliciting motor evoked potential (MEP)s in targeted muscles, with MEP characteristics such as magnitude and latency reflecting the physiological state of the pathways being stimulated. Although numerous studies have examined MEP reliability in upper extremity muscles, less is known about the reliability of this measurement across the lower extremity. We hypothesized that inter-session, test-retest reliability of MEPs recorded simultaneously from multiple lower-limb muscles, from a single TMS location, would differ by muscle, stimulation intensity, and quantification method. Materials and Methods: Ten healthy participants (5 males, 5 females) completed three TMS sessions separated by atleast one week. At each session, the stimulation hotspot was identified using a five-location virtual grid anchored at the vertex, with electromyography (EMG) recorded from all eight muscles of interest at each grid location; the grid location producing the largest and most consistent MEPs in the tibialis anterior (TA), the primary target muscle, was selected as the stimulation site and held constant across all three sessions. MEPs were then recorded bilaterally from the TA, soleus, rectus femoris, and biceps femoris muscles at two stimulation intensities (110% and 120% resting motor threshold (RMT)). MEP size was quantified using mean rectified magnitude and peak-to-peak amplitude, and inter-session reliability was assessed using intraclass correlation coefficients (ICC). Bland-Altman analysis was used to characterize the range of measurement variability across all eight muscles. Results: MEP size differed across sessions, and reliability varied by muscle, intensity, and quantification method. The highest reliability was observed in the right TA, the muscle used to establish the stimulation hotspot, using mean rectified magnitude at 120% RMT. Reliability was comparatively lower in the seven non-target muscles recorded from the same fixed stimulation site, indicating that MEP consistency was not uniform across the lower-limb musculature. Conclusions: MEP reliability in the lower extremity depends heavily on the muscle, stimulation intensity, and quantification method used, and is highest in the muscle for which the stimulation site was optimized. These findings support the interpretation that coil positioning targeted to a specific muscle yields more consistent responses in that muscle than in others recorded from the same fixed site, and underscore the importance of careful muscle selection and hotspot optimization when designing TMS protocols for longitudinal or clinical lower-limb research.

neuroscience↗

bioRxiv2026

Neuromuscular Basis of Kinematic Adaptations During Bidirectional Walking

1BackgroundHuman locomotion is a highly adaptive motor skill that adjusts to new environmental demands through learning. Split-belt treadmill paradigms have advanced our understanding of gait adaptation. Most studies have examined gait when the belts move at different speeds in the same direction. We are studying muscle activation patterns during an asymmetric gait, when the treadmill belts move at equal speed in opposite directions, i.e., bidirectional walking (BDW). MethodsTwelve healthy volunteers performed a single session on a split-belt treadmill. We simultaneously collected ground reaction forces via treadmill force plates, joint kinematics via motion capture, and surface electromyography (EMG) from bilateral soleus (SOL) and tibialis anterior (TA) muscles. Participants started with 2 min of forward walking (FW), followed with four 5-min blocks of BDW separated by 1-min standing rest intervals, and finished the session with 2 min of FW (washout). ResultsAll participants successfully completed the protocol. We analyzed EMG signals for temporal activation patterns (rhythm generation) and amplitude characteristics (pattern formation). EMG recordings revealed antiphasic activation of SOL and TA muscles bilaterally throughout all trials. During BDW, the backward-moving legs TA showed prolonged activation patterns that persisted during washout FW, suggesting retention of adaptive changes. Burst-to-cycle duration ratios showed transient changes during early adaptation but remained relatively stable across conditions, demonstrating robust rhythm generation despite adaptive modulation of activation patterns during BDW. DiscussionThese findings demonstrate that BDW induces asymmetric adjustments in muscle activation patterns. Rhythm generation (timing) did not significantly differ between BDW and FW. However, we did observe changes in pattern formation (i.e., EMG profiles) during FW pre- and post-BDW training. Burst-to-cycle duration ratios, as a measure of rhythm generation, showed changes during early adaptation, particularly the increase in right SOL and right TA during block 1, though these changes did not reach statistical significance and largely returned to baseline during washout. The underlying pattern formation structure, was maintained across all conditions, with selective amplitude modulations rather than fundamental reorganization of activation patterns. The substantial temporal adjustments in the backward-moving legs SOL and phase shifts in TA provide the neuromuscular mechanism driving the bilateral step-length reduction, altered inter-limb phasing, and asymmetric double stance timing. These results extend our understanding of locomotor control by suggesting how the central nervous system (CNS) dynamically recalibrates muscle timing and amplitude to maintain satisfactory locomotion under new environmental demands.

neuroscience↗

bioRxiv2025

Characterization of cutaneous reflexes elicited from saphenous nerve stimulation

Phantom limb pain (PLP) is a chronic neuropathic condition that affects amputees. Cutaneous reflexes (CRs), mediated by spinal interneuronal circuits, represent a potential pathway linking non-nociceptive input to nociceptive modulation that could be targeted with neuromodulatory techniques such as operant conditioning. The objective of this study was to develop and validate a novel method for eliciting CRs from proximal muscles via saphenous nerve stimulation to enable future applications in individuals with PLP. We recruited 14 healthy adults and elicited CRs in the rectus femoris muscle via transcutaneous stimulation of the saphenous nerve at multiple stimulation intensities below their pain thresholds. We evaluated the consistency and reliability of CR response latencies and magnitudes, comparing the symmetry between the bilaterally (e.g. right and left legs). We found that CRs could be reliably elicited 50-100ms post-stimulus using saphenous stimulation and that responses were reliable at stimulation intensities below pain thresholds. Furthermore, we found the CR responses were relatively symmetrical in our healthy adult population. This study is the first of its kind to show that proximal (vs distal) CRs could be consistently elicited through the saphenous nerve stimulation. These findings imply that proximal CRs may be a feasible target for neuromodulatory interventions such as operant conditioning paradigms in the future.

neuroscience↗

bioRxiv2025

Soleus H-reflex size versus stimulation rate in the presence of background muscle activity: A methodological study

IntroductionHoffmann reflex (HR) operant conditioning has emerged as an important intervention in neurorehabilitation. During conditioning, the HR is elicited at low rates ([~]0.2 Hz) to avoid the initial reduction in HR size that can occur over repeated stimulation, i.e., rate-dependent depression (RDD), thereby maintaining reflex size. This study investigated the impact of higher stimulation rates on HR size, where a stable, low-level, background electromyographic (EMG) signal is maintained over 225 conditioning trials in each of 30 sessions. A higher rate could shorten session length and/or number. MethodsFifteen healthy participants maintained low background soleus EMG (5-18 {micro}V, [~]1-3% of the maximum stimulation evoked direct muscle (M-wave) EMG response (Mmax) while standing. Soleus HR and M-wave recruitment curves were obtained at rates of 0.2, 1, and 2 Hz, from which Mmax and Hmax were calculated. Seventy-five HR trials (HRT) were collected for each stimulation rate at a target M-wave size ([~]10-20% of Mmax). ResultsThere was no evidence of RDD at higher stimulation rates. In addition, the mean HR over trials was reliable across participants and rates. The Intraclass Correlation Coefficient (ICC) was 0.965 (95%CI:0.915, 0.987). DiscussionThis study shows that H-reflex conditioning might be performed at rates up to 2 Hz with no RDD and with consistent HR values. A faster rate could increase the number of conditioning trials per session, reduce session duration, and/or reduce the number of sessions. It could thereby accelerate the conditioning process and make the process less demanding for participants. SupportNIH Grant P41 EB018783 (Wolpaw), NYS Spinal Cord Injury Research Board C37714GG (Gupta) and C38338GG (Wolpaw), VA SPiRE NCT05880251(Brangaccio), Stratton Veterans Affairs Medical Center.

neuroscience↗

bioRxiv2024

Soleus H-Reflex Up-Conditioning during Sciatic Nerve Regeneration in Rats Improves Recovery of Locomotion

Operant conditioning of the spinal stretch reflex or its electrical analog, the H-reflex, induces plasticity in the brain and spinal cord that increases (up-conditioning) or decreases (down-conditioning) the reflex elicited by primary afferent input to the spinal motoneuron. In rats in which the sciatic nerve is transected and repaired, soleus (SOL) H-reflex up-conditioning during regeneration strengthens primary afferent reinnervation of SOL motoneurons and improves recovery of the SOL H-reflex. This suggests that H-reflex up-conditioning could improve functional recovery after nerve injury and repair. To explore this possibility, we examined the impact of SOL H-reflex up- or down-conditioning during sciatic regeneration on recovery of locomotor symmetry. Sprague-Dawley rats were implanted with EMG electrodes in right SOL and a stimulating cuff on right posterior tibial nerve. After control data collection, right sciatic nerve was transected and repaired. Control EMG and H-reflex data collection continued for 20 more days. The rat was then exposed for 100 days to either: continued control data collection; SOL H-reflex up-conditioning; or SOL H-reflex down-conditioning. Locomotor EMG, H-reflex, and kinematics were assessed before nerve transection and 120 days after transection. H-reflex up-conditioning improved H-reflex recovery and also restored right/left step symmetry. H-reflex down-conditioning did not worsen H-reflex recovery or right/left step asymmetry. These results suggest that H-reflex up-conditioning might enhance functional recovery after nerve injury in humans. They also confirm previous results indicating that compensatory plasticity prevents inappropriate H-reflex conditioning (i.e., down-conditioning) from further impairing function.

neuroscience↗

bioRxiv2021

Revealing the Physiological Origin of Event-Related Potentials using Electrocorticography in Humans

The scientific and clinical value of event-related potentials (ERPs) depends on understanding the contributions to them of three possible mechanisms: (1) additivity of time-locked voltage changes; (2) phase resetting of ongoing oscillations; (3) asymmetrical oscillatory activity. Their relative contributions are currently uncertain. This study uses analysis of human electrocorticographic activity to quantify the origins of movement-related potentials (MRPs) and auditory evoked potentials (AEPs). The results show that MRPs are generated primarily by endogenous additivity (88%). In contrast, P1 and N1 components of AEPs are generated almost entirely by exogenous phase reset (93%). Oscillatory asymmetry contributes very little. By clarifying ERP mechanisms, these results enable creation of ERP models; and they enhance the value of ERPs for understanding the genesis of normal and abnormal auditory or sensorimotor behaviors.

neuroscience↗

bioRxiv2020

Targeting Neuroplasticity to Improve Motor Recovery after Stroke

After neurological injury, people develop abnormal patterns of neural activity that limit motor recovery. Traditional rehabilitation, which concentrates on practicing impaired skills, is seldom fully effective. New targeted neuroplasticity (TNP) protocols interact with the CNS to induce beneficial plasticity in key sites and thereby enable wider beneficial plasticity. They can complement traditional therapy and enhance recovery. However, their development and validation is difficult because many different TNP protocols are conceivable, and evaluating even one of them is lengthy, laborious, and expensive. Computational models can address this problem by triaging numerous candidate protocols rapidly and effectively. Animal and human empirical testing can then concentrate on the most promising ones. Here we simulate a neural network of corticospinal neurons that control motoneurons eliciting unilateral finger extension. We use this network to (1) study the mechanisms and patterns of cortical reorganization after a stroke, and (2) identify and parameterize a TNP protocol that improves recovery of extension force. After a simulated stroke, standard training produced abnormal bilateral cortical activation and suboptimal force recovery. To enhance recovery, we interdigitated standard trials with trials in which the teaching signal came from a targeted population of sub-optimized neurons. Targeting neurons in secondary motor areas on 5-20% of the total trials restored lateralized cortical activation and improved recovery of extension force. The results illuminate mechanisms underlying suboptimal cortical activity post-stroke; they enable identification and parameterization of the most promising TNP protocols. By providing initial guidance, computational models could facilitate and accelerate realization of new therapies that improve motor recovery.

neuroscience↗