Biology subjects

Hardesty, R. L.

Publications and source records attributed to Hardesty, R. L..

8 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

Bidirectional locomotion induces unilateral limb adaptations

Humans can acquire and maintain motor skills throughout their lives through motor learning. Motor learning and skill acquisition are essential for rehabilitation following neurological disease or injury. Adaptation, the initial stage of motor learning, involves short-term changes in motor performance in response to a new demand in the persons environment. Repeated adaptation can improve skill performance and result in long-term skill retention. Locomotor adaptation is extensively studied using split-belt treadmill paradigms. In this study we explored whether bidirectional walking (BDW) on a split-belt treadmill can induce short-term gait adaptations. Twelve healthy volunteers participated in our single session, starting with 2 minutes of normal walking (NW), followed by four 5-minute blocks of BDW with a 1-minute passive rest in between blocks, and ending with another 2-minute of NW. We recorded body kinematics and ground reaction forces throughout the experiment. Participants quickly adapted to BDW with both legs showing decreased step lengths. However, only the backward-walking leg exhibited aftereffects upon returning to NW, indicating short-term adaptation. Notable kinematic changes were observed, particularly in hip extension and pelvis tilt, though these varied among participants. Our findings suggest that BDW induces unilateral adaptations despite bilateral changes in gait, offering new insights into locomotor control and spinal CPG organization. Key PointsO_LILocomotor adaptation extensively studied using split-belt treadmill paradigms with asymmetric belt speeds. C_LIO_LIThis study examined whether bidirectional walking, i.e. walking with each leg stepping in opposite directions, would induce short-term adaptations in spatiotemporal characteristics of gait. C_LIO_LIVolunteers performed bidirectional walking with bilateral changes in step length. C_LIO_LIDespite equal but opposite belt speeds, volunteers exhibited a unilateral aftereffect of decreased step length in the leg which performed backwards stepping during bidirectional walking. C_LI

neuroscience↗

bioRxiv2022

Variability and Impact of Musculoskeletal Modeling Parameters for the Human Elbow

Musculoskeletal modeling has significant potential as a translational and clinical research tool for examining neuromuscular injuries and disorders. However its adoption has been limited due, in part, to the difficulty of measuring the subject-specific physiological measures that define model parameters. These measurements may require substantial time and expensive methods, such as MRI, to determine the parameters of a model and thus ensure its accuracy. We used a Monte Carlo simulation to examine the impact of parameter variability on the ill-defined, inverse approximation of muscle activity. We first amalgamated previously published measurements of the physiological characteristics of the upper/lower arm and the biceps/triceps muscles. We then used the observed distributions of these measurements to set physiologically plausible boundaries on uniform distributions and then generated perturbed parameter sets. We computed the root mean squared error (RMSE) between muscle activity patterns generated by the perturbed model parameters to those generated by the original parameters. Regression models were fit to the RMSE of the approximated muscle activity patterns to determine the sensitivity of the simulation results to variation in each parameter. We found that variation in parameters associated with muscle physiology had the most effect on RMSE, suggesting that these parameters may require subject-specific scaling, whereas parameters associated with skeletal bodies had less effect, and might be safely approximated by their population means.

bioengineering↗

bioRxiv2019

Distinct Proximal and Distal Corticospinal Signals Embed Limb Dynamics Through the Modulation of Stiffness

How the neural motor system recruits muscles to support the arm against gravity is a matter of active debate. It is unknown how the neural motor system compensates for the changing gravity-related joint moments either when holding a steady-state posture or during movement between postural steady states, e.g., during reaching. Here we used single-pulse transcranial magnetic stimulation to compare the roles that the human primary motor cortex plays in the muscle recruitment to compensate for gravity. We hypothesized that the motor cortex contributes to muscle recruitment to both maintain posture and to compensate for changes in gravitational passive joint moments during movement. To test this hypothesis, we used visual targets in virtual reality to instruct five postures and three movements with or against gravity. We then measured the amplitude and gain of motor evoked potentials in multiple muscles of the arm at several phases of the reaching motion and during posture maintenance. Stimulation below the resting motor threshold, calibrated to the biceps muscle, caused motor evoked potentials in all muscles during all postural and reaching tasks. The amplitude of motor evoked potentials was proportional to the motoneuronal excitability measured as muscle activity. The coefficient of proportionality was positively correlated with the postural component of muscle moment during posture and movement. Altogether our results support the hypothesis. The observed contribution of the motor cortex to the recruitment of multiple antagonistic muscles suggests a whole-limb strategy for overcoming passive gravity-related moments with both active muscle moments and muscle co-activation that modulates limb impedance. New & NoteworthyMaintaining static posture and producing motion appear to be contradictory tasks for the nervous system. In contrast to this seeming dichotomy, our results show that the motorcortical control signals play the same role in both tasks when it is framed in biomechanical terms, i.e., muscle contractions needed to compensate for gravity.

neuroscience↗

bioRxiv2017

The Nonlinear Relationship Between Sensory And Motor Primitives During Reaching Movements

The stabilizing role of sensory feedback in relation to realistic 3-dimensional movement dynamics remains poorly understood. The objective of this study was to quantify how primary afferent activity contributes to shaping muscle activity patterns during reaching movements. To achieve this objective, we designed a virtual reality task that guided healthy human subjects through a set of planar reaching movements with controlled kinematic and dynamic conditions that minimized inter-subject variability. Next, we integrated human upper-limb models of musculoskeletal dynamics and proprioception to analyze motion and major muscle activation patterns during these tasks. We recorded electromyographic and motion-capture data and used the integrated model to simulate joint kinematics, joint torques due to muscle contractions, muscle length changes, and simulated primary afferent feedback. The parameters of the primary afferent model were altered systematically to evaluate the effect of fusimotor drive. The experimental and simulated data were analyzed with hierarchical clustering. We found that the muscle activity patterns contained flexible task-dependent groups that consisted of co-activating agonistic and antagonistic muscles that changed with the dynamics of the task. The activity of muscles spanning only the shoulder generally grouped into a proximal cluster, while the muscles spanning the wrist grouped into a distal cluster. The bifunctional muscle spanning the shoulder and elbow were flexibly grouped with either proximal or distal cluster based on the dynamical requirements of the task. The composition and activation of these groups reflected the relative contribution of active and passive forces to each motion. In contrast, the simulated primary afferent feedback was most related to joint kinematics rather than dynamics, even though the primary afferent models had nonlinear dynamical components and variable fusimotor drive. Simulated physiological changes to the fusimotor drive were not sufficient to reproduce the dynamical features in muscle activity pattern. Altogether, these results suggest that sensory feedback signals are in a different domain from that of muscle activation signals. This indicates that to solve the neuromechanical problem, the central nervous system controls limb dynamics through task-dependent co-activation of muscles and non-linear modulation of monosynaptic primary afferent feedback. New & NoteworthyHere we answered the fundamental question in sensorimotor transformation of how primary afferent signals can contribute to the compensation for limb dynamics evident in muscle activity. We combined computational and experimental approaches to create a new experimental paradigm that challenges the nervous system with passive limb dynamics that either assists or resists the desired movement. We found that the active dynamical features present in muscle activity are unlikely to arise from direct feedback from primary afferents.

neuroscience↗