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Experimental Brain Research

Springer Science and Business Media LLC

Preprints posted in the last 90 days, ranked by how well they match Experimental Brain Research's content profile, based on 46 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.

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Motor learning under mental fatigue: the compensatory role of rest periods

Ruffino, C.; Jacquet, T.; Lepers, R.; Papaxanthis, C.; Truong, C.

2026-03-24 neuroscience 10.64898/2026.03.21.713370 medRxiv
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Mental fatigue is known to impair cognitive and motor performance, but its impact on motor learning remains unclear. This study examined how mental fatigue affects skill acquisition in a sequential finger-tapping task. Twenty-eight participants were assigned to either a mental fatigue group, which completed a thirty-minute Stroop task, or a control group, which watched a documentary of equivalent duration. Both groups then trained on the finger-tapping task across multiple practice blocks with brief rest periods. Overall motor skill improved similarly in both groups. However, mental fatigue altered the pattern of acquisition: participants in the fatigue group showed decreased performance during practice blocks, which was compensated by larger gains during inter-block rest periods. A strong negative correlation was observed between online decrements and offline improvements, indicating that greater declines during practice were associated with larger gains during rest. This study highlights the critical role of rest periods in maintaining learning under cognitively demanding conditions and provides insight into how internal states, such as mental fatigue, can selectively influence the expression of performance without compromising overall learning.

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Competing Effects of Agonist and Antagonist Vibration on the Proprioceptive Sense of Force

Sutton, K. G.; Ryan, O. R.; Pearcey, G.

2026-02-09 neuroscience 10.64898/2026.02.05.704112 medRxiv
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Motor unit (MU) firing is affected by motoneuronal persistent inward currents (PICs), which heavily contribute to gain control of motor output. PICs are highly sensitive to inhibition; for instance, Ia reciprocal inhibition via antagonist muscle vibration drastically reduces discharge rate hysteresis ({Delta}F), an estimate of PIC magnitude. A direct link between sensitivity of PICs to inhibition and voluntary force control, however, has not been established. To determine whether force control is altered with inhibition of PICs, we recorded high-density surface EMG from the tibialis anterior, while 11 participants (5F; 6M) completed and isometric force reproduction task. Tendon vibration was applied to the agonist or antagonist muscle during the first (with visual feedback) or second contraction (without visual feedback) and participants were asked to match percieved effort across contractions, in an attempt to match neural drive to the motor pool. In support of our hypothesis, torque and MU firing rates were reduced when vibration was applied to the antagonist (torque: p < .0001; MU firing rate: p < .0001), but not agonist (torque: p = .9980; MU firing rate: p = .312) muscle tendon in the second contraction, compared to control. Conversely, when vibration was applied during the first contraction, opposite effects were observed. These results suggest that PICs play a role in the proprioceptive sense of force, offering a potential link between PICs and voluntary force control, which may be important for understanding and treatment of motor impairments. KEY POINTSO_LIMotoneuronal persistent inward currents amplify synaptic currents and therefore heavily contribute to motor output, however they are extremely sensitive to Ia reciprocal inhibition induced by muscle tendon vibration. C_LIO_LIWe show that modulation of PICs severely impacts human force sense using an effort-based force reproduction paradigm which enabled us to manipulate combinations of tendon vibration and visual feedback. C_LIO_LIThese findings provide a link between PICs and functional motor output, which may be important for understanding neurological impairments and informing rehabilitation strategies. C_LI

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Stopping and Changing Expected and Unexpected Movements

Weber, S.; Vucak, N.; Salomoni, S. E.; Ross, A. J.; Coleman, E.; Hinder, M. R.

2026-02-18 neuroscience 10.64898/2026.02.16.706101 medRxiv
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The capacity to cancel or adapt planned actions in response to changing environmental demands is essential for navigating our complex world. While past research has shown that an individuals expectations of upcoming movement demands influence the speed of action initiation, the effect this has on subsequent cancellation or adaption of that movement remains unknown. 25 healthy adults completed stop signal tasks and stop change tasks in which biasing cues (e.g., "70% left") accurately indicated the probability that a left, or right button press would be required. As expected, responses that were congruent with the cue were faster than incongruent responses; however, biasing cues had no effect on behavioural or physiological (electromyographical) indices of stopping speed. Stopping latencies were found to be faster in the stop change task than the stop signal task, corroborating other recent work. However, a second experiment (25 healthy adults) which used the same stimuli for both tasks (varying only the instructions), revealed no difference - highlighting the sensitivity of the stop process to stimulus effects, and a common confound in the literature. We also observed that physiological indices of action reprogramming (following a stop) were faster in congruent than incongruent trials. Collectively, these results suggests that preparatory changes that accompany expected movements influence the enaction of movement both prior to, and after stopping, but the stop mechanism itself, remains independent of these preparations. These results inform how action cancellation and adaption are applied in real world environments, where expectations continually interface with our motor plans. HighlightsO_LI* Anticipating a movement increases the speed of its enaction but not subsequent cancellation C_LIO_LI* Expected movements can be reprogrammed more quickly than unexpected movements C_LIO_LI* The latency of action cancellation is highly sensitive to stimulus effects C_LI

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Proximo-distal muscle modulation as a function of hand orientation in a reach-and-grasp task

Chambellant, F.; Hilt, P.; Cronin, N.; Thomas, E.

2026-03-30 neuroscience 10.64898/2026.03.27.714710 medRxiv
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The aim of this study was to improve our understanding of muscle contractions in the arm as a function of hand orientation for grasp. While there have been several reports on arm kinematics for reach and grasp movements, little has been done at the muscular level. To this end, we analyzed the modulation of shoulder, elbow and hand muscles for a reach and grasp task involving a target in either horizontal or vertical orientation. We hypothesized that unlike what has been observed for kinematics, at the muscular level we would see less correlation between the three muscle groups. A decoding approach with Machine Learning revealed adaptation patterns that were not visible using classical methods. Reach-and-grasp has traditionally been treated as being made of two components - the reach and the grasp components. Our dynamic decoding approach revealed a more complex picture with very different dynamics in the shoulder and elbow muscle groups during reach. All muscle groups showed peak capacity for predicting hand orientation before the start of grasp and followed the ubiquitous proximo-distal organization. The patterns of muscular modulation for hand orientation were strongly perturbed by the eyes closed and slow movement conditions, potentially decreasing the available degrees of freedom for adaptation.

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No evidence for an effect of M1 cTBS on schema-mediated motor sequence learning

Reverberi, S.; Cuypers, K.; King, B. R.; Albouy, G.

2026-03-16 neuroscience 10.64898/2026.03.12.711304 medRxiv
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The availability of a pre-existing cognitive-motor schema accelerates the learning of novel motor information. The encoding of a novel schema-compatible, compared to-incompatible, motor sequence was recently shown to be supported by the left primary motor cortex (M1). However, causal evidence for the role of M1 in schema-mediated motor learning is currently lacking. In the current study, we aimed to address this knowledge gap by transiently disrupting M1 using inhibitory continuous theta burst stimulation (cTBS). Forty-eight young healthy participants learned a bimanual motor sequence task (cognitive-motor schema). Twenty-four hours later, they learned a novel sequence whose ordinal schematic structure was compatible with that learned on the previous day. To provide causal evidence for a role of M1 on such schema-mediated motor learning, we applied either cTBS or sham stimulation to the left M1 immediately prior to encoding the schema-compatible novel sequence. Electromyography results showed no evidence for an effect of left M1 cTBS on corticospinal excitability as measured with motor-evoked potentials. Similarly, behavioral results indicated no significant effect of cTBS on subsequent schema-mediated motor sequence learning. Altogether, the present data do not provide evidence for a causal role of the left M1 in schema-mediated motor sequence learning.

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Reward Reduces Motor Fatigability by Increasing Movement Vigour

Imhof, J.; Heimhofer, C.; Baechinger, M.; Meissner, S. N.; Ramsey, R.; Wenderoth, N.

2026-03-26 neuroscience 10.64898/2026.03.24.713707 medRxiv
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Reward can enhance motor performance. However, its potential to counteract motor fatigability, a reduction in motor performance during sustained movements, remains underinvestigated. This could be particularly relevant in neurological conditions such as multiple sclerosis, where increased motor fatigability is a prominent symptom. One form of motor fatigability is motor slowing, a decline in movement speed over time evoked by fast, repetitive movements. In this study, we investigated whether the possibility to earn reward attenuates motor slowing, and examined associated changes in muscle activity and pupil size, a putative marker of physical effort. Participants performed a wrist tapping task at maximal voluntary speed with or without the possibility of earning a reward. We found that wrist tapping induced motor slowing and that slowing was significantly reduced by reward. Over time, tapping became more costly as indicated by higher muscle activity and coactivation per tap. This was accompanied by a sustained pupil dilation, which could not solely be explained by tapping speed. These findings suggest that, rather than restoring efficient motor control, reward attenuates motor slowing by allowing participants to access a performance reserve and invest more resources into the task, reflected by increased muscle activation per tap and sustained pupil dilation.

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Transcranial Direct Current Stimulation enhances long-term retention after 5 days of lower-limb motor skill learning

Kvistad, A. L.; Jespersen, L.; Bjoerndal, J. R.; Christiansen, L.; Karabanov, A. N.; Lundbye-Jensen, J.

2026-02-12 neuroscience 10.64898/2026.02.11.705269 medRxiv
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Transcranial direct current stimulation (tDCS) holds the potential to affect behavior by modulating ongoing neural activity, and tDCS paired with hand motor practice can enhance motor learning. While augmenting the behavioral benefits of motor practice is relevant for neurorehabilitation following central and peripheral lesions to the motor system, as well as in sports, the short- and long-term effects of tDCS targeting the mesial motor cortex (M1-Leg) during lower-limb motor skill practice remain unexplored. We tested whether five days of anodal tDCS over M1-Leg during training of a sequential visuomotor tracking task improves within- and between-session learning and one-week retention. Participants were randomized to skill practice with active tDCS, skill practice with sham stimulation, or volume-matched non-skilled ankle movements with sham stimulation. Changes in corticospinal excitability accompanying skill and nonskill motor practice with real and sham tDCS, were assessed as motor evoked potential amplitudes recorded from the tibialis anterior muscle at rest. Compared to non-skill practice, motor skill practice yielded robust sequence-specific performance gains, which were transferred to the untrained leg and persisted for at least one week after practice ended. Concurrent tDCS did not increase learning within or between training sessions, but it did lead to improved one-week retention compared to sham stimulation. Corticospinal excitability did not increase after practice and was unaffected by tDCS. These findings suggest that combining lower-limb motor skill practice with tDCS over M1-Leg can strengthen retention of skill learning without measurable changes in resting corticospinal excitability. This is relevant for motor practice scheduling in neurorehabilitation. Key pointsO_LITranscranial direct current stimulation (tDCS) is a weak electrical brain stimulation that may boost learning when paired with motor practice; however, its effects during lower-limb skill training are not well known. C_LIO_LIWe tested whether stimulation over the leg area of the motor cortex during 5 days of ankle skill training improves learning, consolidation, and delayed retention. C_LIO_LIAnkle skill training produced clear sequence-specific improvements that transferred to the untrained leg and were still present 1 week later. C_LIO_LIStimulation did not increase short-term learning, but it did improve 1-week retention compared to sham stimulation. C_LIO_LICorticospinal excitability assessed based on motor evoked potentials elicited by transcranial magnetic stimulation did not change with motor training or stimulation, suggesting that the observed positive effect of tDCS on delayed retention may arise from other brain network processes relevant to long-term motor learning and memory. C_LI

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Neuromuscular Basis of Kinematic Adaptations During Bidirectional Walking

Mojtabavi, H.; Ajdari, A.; Rueda-Parra, S.; Gemoets, D. E.; Wolpaw, J. R.; Hardesty, R. L.

2026-02-14 neuroscience 10.64898/2026.02.11.705376 medRxiv
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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.

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Neural mechanisms underlying leg muscle responses during cervical transcutaneous spinal cord stimulation

Phelps, N.; Keesey, R. E.; Hawthorn, R.; Atkinson, C.; Seanez, I.

2026-02-09 neuroscience 10.64898/2026.02.06.702847 medRxiv
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Transcutaneous spinal cord stimulation (tSCS) of the cervical spinal cord has been thought to modulate lumbar networks, leading to the hypothesis that leg muscle recruitment may occur via recruitment of long-range spinal connections between cervical and lumbar circuits. To directly test this hypothesis, we compared arm and leg muscle responses elicited in unimpaired participants (N = 12) by cervical tSCS with the anodes placed over the iliac crests, with the anodes placed over the clavicles, and with lumbar tSCS as a control for leg muscle recruitment via the posterior root-muscle reflex. The idea of tSCS targeting cervico-lumbar connectivity would suggest that cervical stimulation could evoke responses in leg muscles. However, in our experiments, leg responses via cervical tSCS were only observed when the anodes were placed over the iliac crests, but not over the clavicles. These leg muscle responses had shorter latencies than those with lumbar tSCS and showed minimal post-activation depression, indicating efferent rather than afferent recruitment. Therefore, changes in leg muscle excitability by cervical-iliac tSCS previously attributed to descending cervical circuits could instead be explained by direct recruitment of efferent fibers near the iliac anodes. These findings suggest that cervical tSCS alone does not engage leg muscle motoneurons via long-range spinal or bidirectional pathways. Therefore, our study highlights the need to carefully consider electrode configuration when interpreting cervical tSCS mechanisms and additional or unexpected rehabilitative effects that extend caudally from the cervical spinal cord.

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Stimulus prior and reward probability differentially affect response bias in perceptual decision making

Koss, C.; Blanke, J.-H.; de la Cuesta-Ferrer, L.; Jakel, F.; Stuttgen, M. C.

2026-02-17 animal behavior and cognition 10.64898/2026.02.16.706079 medRxiv
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Signal detection theory posits that subjects in two-stimulus, two-choice discrimination tasks decide by comparing random samples of an evidence variable to a static decision criterion. While the core assumptions of the theory have received ample experimental support, it has become evident that the decision criterion is not static but subject to trial-by-trial fluctuations and can be influenced by experimental manipulations. The mechanisms governing the trial-by-trial criterion changes are however not well understood. Here, we report results from five experiments in which we subjected rats to a two-stimulus, two-choice auditory discrimination task. In the first three experiments, we investigated the effects of stimulus presentation ratios and reward ratios and provide clear evidence that the effects of changing reward ratios are more pronounced than those of stimulus presentation ratios. A model-based analysis revealed that this effect was due to more than tenfold higher learning rates when reward ratios were manipulated. In two separate experiments, we investigated the effect of reward density (i.e., global reward rate) on criterion learning but failed to find consistent effects. A systematic comparison of three different trial-by-trial criterion learning models based on detection theory, the matching law, and reinforcement learning showed that no model was able to capture the differential effects of stimulus presentation and reward ratios. We conclude that subjects explicitly represent either prior stimulus probabilities or entire stimulus distributions, and accordingly future models need to represent these factors as well.

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The central motor command, but not the muscle afferent feedback, is necessary to perceive effort

Pageaux, B.; Bergevin, M.; Angius, L.; Mangin, T.; Lepers, R.; Marcora, S.

2026-02-07 neuroscience 10.64898/2026.02.04.703832 medRxiv
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Two theoretical models are proposed on the signal processed by the brain to generate the perception of effort (PE): the corollary discharge model and the afferent feedback model. To test the validity of these models, we used electromyostimulation to manipulate the magnitude of the central motor command during voluntary (high motor command), evoked (no motor command) and combined (low motor command) contractions at similar torque outputs. As electromyostimulation evokes sensory volleys to the central nervous system, it was used to evoke muscle contractions and to stimulate afferent feedback. We hypothesized that PE would reflect the magnitude of the central motor command and that evoked muscle contractions in the absence of central motor command would not elicit any PE. Twenty participants (n=10 experienced and n=10 novice with electromyostimulation) volunteered in this study. Participants reported their PE after isometric (10% and 20% MVC) and dynamic (5% and 20% MVC) voluntary, evoked, and combined contractions. For the same torque, participants reported no PE during evoked contractions, but all reported PE during voluntary contractions. Experienced but not novice participants reported lower PE during the combined than during voluntary contractions. This study questions the validity of the afferent feedback model and highlights the key role of motor command-related signals in PE generation. However, results from the novice participants during the combined contractions suggest that other factors such as inhibitory control may affect PE. Future studies should investigate the relationship between the central motor command and PE during physical tasks at various levels of complexity.

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The tilt board task as an internally valid practice-transfer paradigm for stabilometer balance assessments

Mahdaviani, K.; Tremblay, L.; Novak, A.; Mansfield, A.

2026-03-05 neuroscience 10.64898/2026.03.03.709278 medRxiv
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Practice-transfer paradigms are central to motor learning research, yet dynamic balance lacks standardized, internally valid practice-transfer task pairings. This study evaluated whether a mediolateral tilt board can serve as a valid transfer task for stabilometer-based balance assessment. Sixteen healthy young adults (20-35 years) completed a single session consisting of two 40-second trials on a mediolateral stabilometer and two 40-second trials on a mediolateral tilt board. Participants aimed to keep each platform horizontal during each trial. Performance outcomes were derived from platform deviation angle. Neuromuscular outcomes were derived from surface EMG of bilateral gluteus medius, vastus lateralis, and vastus medialis, including muscle synergy structure, bilateral co-activation index, RMS amplitude of muscle activation, and strategy ratios (hip-to-knee and asymmetry metrics). Between-task associations were assessed using Spearman correlations. Cross-task muscle synergy similarity was high (mean cosine similarity = 0.915 {+/-} 0.044) and close to within-task trial-to-trial similarity, indicating preserved modular coordination across devices. Performance metrics were moderately to strongly correlated between tasks (RMS deviation angle: {rho} = 0.621, p = 0.0089; time-in-balance: {rho} = 0.668, p = 0.0036). EMG-derived strategy metrics also correlated significantly across tasks, including bilateral co-activation ({rho} = 0.688, p = 0.0023), hip-to-knee ratio ({rho} = 0.765, p = 0.0003), hip asymmetry ratio ({rho} = 0.688, p=0.0023), and knee asymmetry ratio ({rho} = 0.679, p = 0.0028). In contrast, EMG RMS amplitude did not correlate across tasks ({rho} = -0.044, p = 0.873), suggesting task-specific gain of activation magnitude. Stabilometer and tilt board tasks shared a similar coordination structure and showed a high correlation in balance performance and neuromuscular strategy, supporting the tilt board as an internally valid transfer task for stabilometer-based dynamic balance paradigms. Similarity of tasks appears strongest at the level of modular control and strategy organization, with device-specific gain scaling of activation amplitude.

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Effects of lumbar disc injury and nociception on trunk motor control during rat locomotion

Xiao, F.; Noort, W.; Han, J.; van Dieën, J. H.; Maas, H.

2026-03-26 neuroscience 10.64898/2026.03.24.713869 medRxiv
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Intervertebral disc (IVD) injury is a major cause of low-back pain and can lead to structural deficits and mechanical instability. When the IVD is compromised, neuromuscular compensation by paraspinal muscles, such as the multifidus (MF) and longissimus (ML), is critical for maintaining spine stability. However, it is unknown how IVD injury and its interaction with nociception affect neuromuscular control. This study assessed the effects of IVD injury and additional muscle-derived nociception on trunk motor control during locomotion in a rat model. IVD injury was induced via needle puncture at L4/L5. One week later, hypertonic saline was injected into the lumbar MF to induce nociception. Trunk and pelvic kinematics, bilateral EMG activity of MF and ML were recorded during treadmill locomotion at baseline, one week after IVD injury, and immediately following hypertonic saline injection. Trunk and pelvic kinematics and bilateral muscle activation patterns remained largely consistent across conditions. No significant changes were found in stride duration, pelvic, lumbar and spine angle changes, variability, or movement asymmetry. MF activation was bilaterally synchronized, whereas ML showed left-right alternating activation patterns. Following IVD injury, right MF mean activation and EMG variability increased significantly compared to baseline. When muscle-derived nociception was added in the unstable spine (IVD injury) condition, left MF minimum amplitude was significantly reduced, and instability-related increases in right MF mean activation and variability were attenuated, but not fully reversed. These findings suggest that IVD injury, alone or in combination with muscle-derived nociception, elicits localized neuromuscular adaptations without disrupting the global locomotor patterns.

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Visual Context Influences Lateral Balance While Walking on Winding Paths

Render, A. C.; Singh, T.; Cusumano, J. P.; Dingwell, J. B.

2026-01-21 neuroscience 10.64898/2026.01.18.700184 medRxiv
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Effectively navigating daily environments necessitates achieving adaptability while maintaining stability. This requires integrating sensory feedback, primarily from the visual system, to maintain balance and maneuverability as we walk. This study examined the impact of visual information salience on lateral balance and stepping. Twenty-eight healthy adults (16F/12M; 26.16{+/-}4.23 years) participated. Participants walked along each of two virtual paths (Straight vs. Winding), having each of two path color contrasts (High vs. Low), in each of two environments with differing visual richness (Rich vs. Sparse). We quantified stepping errors as the percentage of steps landing outside designated path boundaries. We computed means () and standard deviations ({sigma}) of the minimum mediolateral margins of stability (MoSL), and we computed lateral Probability of Instability (PoIL) to assess participants risk of taking unstable (MoSL < 0) steps. On Straight paths, participants made more stepping errors on Low (vs. High) contrast paths for both environments, and exhibited decreased{sigma} (MoSL) in Sparse (vs. Rich) environments on paths of both visual contrasts. On Winding paths, participants made the most stepping errors on Low Contrast paths in Sparse environments. They walked with smaller (MoSL) and exhibited higher PoIL on Low Contrast paths in both environments, and they exhibited higher PoIL in Sparse environments on paths of both visual contrasts. The effects of diminished visual information were far more pronounced on Winding paths (vs. Straight), hindering performance and balance maintenance, as these conditions challenged both mechanical and sensory mechanisms underlying balance control.

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Oculomotor dance learning task: Implications for audio-visual cued spatial learning

Petrovski, M.; Beheiry, S.; Das, U. U.; Rooprai, S.; Karimi, A.; Simon, J. R.; Bar, R. J.; DeSouza, J. F.

2026-01-26 neuroscience 10.64898/2026.01.23.701340 medRxiv
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Learning dance of a motor sequence involves the coordination of both oculomotor and manual motor systems through the practiced repetition of a fixed sequence of actions, resulting in automatized execution of movement through habit learning. This study aims to address whether a sequence-based learning paradigm centered on the visual-motor system can feasibly be measured while listening to music (Bar and DeSouza 2016). It aims to develop a new visual-motor-based learning paradigm with music, potentially promoting neuroplasticity and creating new interventional tools, building upon prior research that shows behavioural and putative neural changes following dance-based neurorehabilitation in people with Parkinson's disease (Bearss et al. 2024). Eye movements of 10 participants (8 female, 2 male) were tracked using the Eyelink 1000 Plus system during a 68-second eye-dance sequence. The experiment consisted of a learning phase, where participants observed the sequence five times with 30-second breaks, and a performance phase, where they performed the sequence five times from memory on a grey screen without visual cues. Music was incorporated into both phases to aid memorization of the 4 spatial locations. After each performance, the participant was shown a visual reinforcer and asked for their thoughts on how well they executed the dance. A visual reinforcer flashes one of three different colours: red, yellow, or green. Each colour corresponds to how many steps in the dance a participant performed correctly, with key points being: under one third, between one to two thirds, and over two thirds of total steps correct. Participants were scored based on timing of the steps as well for exact (1.00), good (0.66), slightly off (0.33) or missed (0) steps. Data was analyzed using R4.3.1, MATLAB, and Experiment Builder: Data Viewer software. Results showed a significant improvement in performance accuracy between the first session (g1; M = 40%, SD = 7.2%) and the last session (g5; M = 69.7%, SD = 22.8%). A repeated-measures ANOVA revealed a significant main effect of session on performance accuracy, F(4, 36) = 6.99, p < 0.001, 2G = 0.26, indicating that accuracy significantly improved over sessions. Post-hoc Bonferroni comparisons showed that accuracy in later sessions was significantly higher than earlier sessions, suggesting a defined learning curve and consolidation of performance pattern across repeated practice. Similarly, there was significant improvement in timing accuracy between the first session g1; M = 0.29, SD = 0.06) and the fifth session (g5; M = 0.46, SD = 0.12). A repeated-measures ANOVA revealed a significant main effect of session on timing precision, F(4, 36) = 11.67, p < 0.001, 2G = 0.25, indicating significant improvements in temporal control and coordination over sessions. Post-hoc Bonferroni comparisons showed that timing precision significantly improved between early and late sessions (e.g, g1-g4, p <0.01; g1-g5, p < 0.001), suggesting a defined learning curve and increase in precision across repeated practice. These findings suggest that visual-motor-based interventions have the potential to enhance motor and non-motor symptoms like depression and anxiety for neurodegenerative diseases such as Parkinson's Disorder (PD). The results provide a foundation for developing targeted therapies that integrate learning paradigms to improve functional outcomes, warranting further exploration of their long-term efficacy.

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Voluntary wheel running provides pain relief but transiently exacerbates gait impairments in male and female mice with unilateral osteoarthritis

Florea, R.; Hestehave, S.; Andreoli, L.; Wright, A.; Geranton, S.

2026-03-02 animal behavior and cognition 10.64898/2026.02.27.708530 medRxiv
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ObjectivePhysical activity is a first-line therapeutic intervention for managing osteoarthritis-related pain and functional impairment. However, the growing literature questions the long-term relevance of exercise-induced improvements in patients, while pre-clinical research evidence base is limited by reliance on stressful, forced exercise paradigms which do not reflect voluntary engagement. Here, we aimed to investigate the effects of voluntary wheel running on the pain experience in mice with joint pain. DesignWe investigated the impact of free access to a running wheel on sensory, functional and affective outcomes following unilateral intra-articular injection of monoiodoacetate in single-housed male and female C57Bl/6J mice. ResultsMonoiodoacetate injection transiently reduced running activity in both sexes; however, females rapidly resumed and sustained high activity levels over a two-month period, while males showed a progressive decline in running distance. Active males and females showed improvements in the monoiodoacetate-induced hindpaw secondary mechanical hypersensitivity. Moreover, mechanical thresholds positively correlated with the distance ran after injury, suggesting a functional relationship between exercise and secondary pain relief. However, access to a wheel temporarily exacerbated several monoiodoacetate-induced gait impairments in both sexes. Finally, while there were no obvious effects of running on anxio-depressive-like behaviours or cognitive functioning, exercise significantly impacted stress-induced faecal output and phenotypic regulation of body weight. ConclusionsOur findings suggest that persistent loading of an injured knee joint may compromise functional outcomes independently of pain relief away from the joint, underscoring a critical consideration for exercise-based therapeutic strategies in osteoarthritis.

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Altering sensory cues for spatial navigation does not impose a dual-task effect on gait and balance

Beech, S.; McCracken, M. K.; Geisler, C.; Dibble, L. E.; Hansen, C. R.; Creem-Regehr, S. H.; Fino, P. C.

2026-03-18 physiology 10.64898/2026.03.16.712118 medRxiv
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Walking is an attentionally demanding process that draws from a limited pool of attentional resources. Dual-task assessments, where individuals perform a cognitive task while walking, often reveal changes in gait and balance due to competing attentional demands. As cognitive task difficulty increases, the attentional resources necessary to complete the task also increase, leading to greater interference with gait and balance. However, these interactions are typically examined using contrived lab-based tasks, leaving it unclear how the cognitive processes engaged during real-world movement impact walking. In the present study, we investigated whether increasing the attentional demand of spatial navigation, a cognitive process intrinsically linked to movement, interferes with gait and balance. Healthy adults completed an ambulatory virtual reality homing task in which they walked through a virtual environment and navigated to previously visited locations while wearing ankle and lumbar trackers. We increased the attentional demand of navigation by removing sensory cues during this homing phase: full cues, visual cues only, or self-motion cues only. Navigation performance declined as sensory cues were removed, but we observed no corresponding changes in their spatiotemporal gait and balance metrics. These results show that, in healthy adults, increasing the attentional demand of spatial navigation does not interfere with gait and balance during real-world movement. This finding suggests that locomotor control may be robust to navigation-related cognitive demands. Further research is needed to determine why navigation did not interfere with mobility and to clarify the relationship between these two interconnected processes.

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Spinal Mechanisms in Post-Activation Potentiation: Facilitation of Presynaptic Inhibition Contrasts H-Reflex Amplitude Reduction

Kalc, M.; Holobar, A.; Kramberger, M.; Murks, N.; Skarabot, J.

2026-01-20 neuroscience 10.64898/2026.01.16.699288 medRxiv
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This study investigated the spinal neural mechanisms underlying post-activation potentiation in ten healthy young males (21.9 {+/-} 4.8 years). Participants performed a 10-second maximal isometric plantarflexion, after which we measured twitch torque and assessed spinal excitability using the soleus H-reflex, D1 presynaptic inhibition and heteronymous Ia facilitation (HF). High-density surface EMG was decomposed to track single motor unit responses. The conditioning contraction increased twitch torque by 12.2 Nm (p < 0.001) immediately and returning to baseline within nine minutes. This mechanical potentiation was accompanied by a 29% reduction in H-reflex amplitude (p < 0.001), which recovered within three minutes. Paradoxically, neurophysiological indices of presynaptic inhibition, D1 and HF were significantly increased (D1: p<0.017; HF: p<0.001), resulting in spinal facilitation. Single MU analysis revealed increased discharge probability, particularly in higher-threshold units indicating overall spinal facilitation. These results demonstrate that post-activation potentiation involves a complex dissociation: H-reflex pathway inhibition along with facilitation of presynaptic spinal mechanisms. This paradox can be explained by either post-activation depression (caused by depletion of neurotransmitter at the Ia-motoneuron synapse) or muscle thixotropy, a contraction history-dependent decrease in muscle spindle sensitivity, which reduces the efficacy of the Ia afferent volley independently of spinal inhibitory mechanisms. Our findings highlight a dissociation between spinal presynaptic facilitation and the decreased H-reflex, underscoring the need for future studies to explicitly test the roles of post-activation depression and muscle thixotropy during post-activation potentiation. New & NoteworthyThis study provides evidence that post-activation potentiation reduces the soleus H-reflex amplitude while concurrently facilitating presynaptic spinal mechanisms. By combining global EMG and single motor unit analyses extracted from high-density surface EMG, we reveal a dissociation between spinal disinhibition and reflex depression. These findings suggest that acute post-contraction reflex suppression might be mediated by mechanisms other than presynaptic inhibition, potentially involving post-activation depression spinal mechanisms or changes in muscle spindle sensitivity.

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Evidence for Impaired Homeostatic Regulation of Plasticity after Spinal Cord Injury

Chowdhury, N. S.; Cheng, D.; Nikolin, S.; Quide, Y.; Hesam-Shariati, N.; Gustin, S. M.

2026-03-30 neurology 10.64898/2026.03.24.26349041 medRxiv
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Background: Spinal cord injury (SCI) is associated with widespread reorganisation of cortical sensorimotor circuits. Persistent complications such as spasticity and neuropathic pain suggest that homeostatic plasticity, which normally helps stabilise and constrain activity-dependent changes in sensorimotor circuits, may be disrupted after SCI. Homeostatic plasticity can be probed using repeated blocks of transcranial direct current stimulation (tDCS); in healthy individuals, two closely spaced excitatory blocks typically leads to an inhibitory response, reflected as a reduction in corticomotor excitability. Objective: To determine whether individuals with SCI show reduced homeostatic suppression of corticospinal excitability in response to repeated anodal tDCS, compared with healthy controls. Methods: Twenty adults with thoracic or below SCI and 20 healthy controls completed three counterbalanced sessions. Each session comprised two 10-minute blocks of 2 mA tDCS separated by 5 minutes, with the second block always being anodal tDCS over left primary motor cortex. The first block was either anodal, cathodal, or sham tDCS, yielding 3 condition types: anodal-anodal, cathodal-anodal, and sham-anodal. To assess corticomotor excitability, transcranial magnetic stimulation-evoked motor evoked potentials (MEPs) were elicited at baseline, after priming, and every 5 minutes for 60 minutes after the second block. The primary outcome was percent change in MEP amplitude from baseline. Results: In the anodal-anodal condition, the SCI group showed greater facilitation than controls over 0-30 minutes (estimate = 83.09, 95% CI 49.75 to 116.43, p < 0.001), suggestive of a weaker homeostatic response. The cathodal-anodal condition led to a significant overall facilitatory effect with no between-group difference, while the sham-anodal condition showed no change in MEP amplitude relative to baseline. Within the SCI group, exploratory subgroup analysis suggests that those with neuropathic pain and a traumatic injury showed greater facilitation in the anodal-anodal condition than those without these features, indicative of a weaker homeostatic response. Conclusions: SCI is associated with impairment in the homeostatic regulation of corticomotor excitability following repeated excitatory brain stimulation. Disrupted plasticity stabilisation may be relevant to persistent symptoms such as neuropathic pain.

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Visual Strategies During a Cooperative Mechanically Coupled Bilateral Task

Burgardt, R. T.; Hawe, R. L.

2026-02-03 neuroscience 10.64898/2026.01.31.703066 medRxiv
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A subset of bilateral tasks requires one arm to perform a stabilizing role while the other completes a movement, such as slicing a loaf of bread. Visual attention during bilateral tasks has previously been examined with bilateral reaching tasks, demonstrating that visual attention switches between the two target locations. The goal of this study was to characterize visual attention during a cooperative mechanically coupled bilateral "stabilizing and reach" task to determine how visual attention is divided between the two limbs when one limb plays a stabilizing role. Twenty-six healthy young adults completed a robotic task in which the hands were coupled with a haptic spring. Participants were instructed to keep one hand stationary in a target while they reached for a target with the other hand, thus stretching the spring and applying a force to both arms. We found that individuals primarily fixated their gaze on the reaching target, only fixating on the stabilizing target for approximately 10% of the reaching time. Longer fixations on the reaching target were associated with faster reaching times, while longer fixations on the stabilizing target were associated with slower reaching times. While the performance of the stabilizing hand differed between the dominant and non-dominant limbs, visual strategies did not vary based on which hand was stabilizing. These results demonstrate that unlike bilateral reaching tasks in which the eyes frequently saccade between the two targets, visual guidance is primarily used for the reaching hand while minimal overt visual attention is directed to the stabilizing hand.