Journal of Neurophysiology

Motor sequence performance improves during and between brief practice bouts (micro-online and offline gains). We compared both metrics across two groups: one exposed to an implicit motor sequence, and one not. Micro-online gains drove sequence-specific learning and positively correlated with overall skill. However, micro-offline gains were comparable between groups and did not track sequence-specific learning. We conclude that implicit motor sequence learning is driven by micro-online rather than micro-offline gains.

Bimanual coordination is essential for many skilled everyday actions and requires maintaining specific spatiotemporal relationships between the two hands according to task demands. However, the contribution of the primary motor cortices (M1s) to learning such relationships is only partially understood. Conventional bimanual tasks necessarily engage both M1s in controlling the moving hands, making learning-related changes difficult to distinguish from those associated with movement execution. To reduce this effector-related confound, we used a unimanual and bimanual rhythmic coordination paradigm in which participants learned the same novel 90-degree relative-phase relationship by coordinating either hand with a virtual partner and compared these conditions with conventional bimanual practice. In three experiments, performance accuracy and stability improved during practice and improved further after a 6-h retention interval with comparable time-dependent changes across unimanual and bimanual trained groups. In Experiment 2, motor-evoked potentials measured before and after training revealed an overall increase in corticospinal excitability across both M1s under unimanual and bimanual training. In Experiment 3, bidirectional dual-site paired-pulse stimulation revealed effector-dependent changes in interhemispheric inhibition, in which bimanual practice produced no reliable directional modulation, whereas unimanual practice produced asymmetric changes that depended on the trained hand. Neither corticospinal excitability nor interhemispheric inhibition showed a consistent relationship with behavioral improvement. Together, these findings demonstrate comparable behavioral learning of a novel spatiotemporal coordination relationship across bimanual and unimanual contexts, while showing that behavioral improvement is not straightforwardly reflected in M1 neurophysiological changes. Causal intervention studies are therefore needed to determine whether and when M1 contributes directly to acquisition of novel coordination relationships.

The control of visually guided bimanual movements is thought to represent a compromise between the drive for synchrony that characterizes many bimanual movements and the competing demands that characterize the constituent unimanual movements. As a result, while visually guided bimanual movements are found to be ostensibly synchronized, they also demonstrate subtle asynchronies. Here, we conducted a fine-grained analysis of bimanual reaching movements focusing on their relative synchrony as movements unfold and the relationship with gaze behavior. Our novel analysis revealed that participants frequently shifted their gaze laterally several times during bimanual reaches and that these gaze shifts were systematically associated with changes in the speed ratio of the two limbs. More specifically, we observed a strong association between gaze shifts and the speed ratio shifting toward the limb on the attended side. This pattern of behavior was seen regardless of hand dominance and target difficulty, suggesting that it may reflect a common visuomotor strategy during bimanual reaching.

Although growing evidence indicates that decision-making and movement control are tightly coordinated, the functional significance of this coordination remains poorly understood. In particular, it is unclear whether changes in the animals arousal are sufficient to reorganize decision-action coordination in a manner that preserves behavioral efficiency. To address this question, we pharmacologically slowed behavior in rhesus monkeys performing a reaching-based foraging task while leaving task demands unchanged. Under this internal perturbation, prolonged decisions were initially associated with shorter movement durations, revealing a compensatory coordination that reduced the additional temporal cost of slower deliberation. As animals progressively adapted across sessions, decision durations decreased, reward rates increased, and compensatory coordination became less prevalent, giving way to patterns of decision-movement co-regulation. This observation suggests that compensatory adjustments are recruited transiently during adaptation rather than representing a constitutive mode of behavioral control. These findings provide causal evidence that an internally-induced slowing of decision-making is sufficient to reorganize the temporal relationship between decisions and movements. More broadly, they support the view that decision-making and movement execution are regulated as complementary components of a unified adaptive control process that flexibly adjusts the temporal organization of behavior in response to changes in internal state, thereby contributing to the maintenance of efficient reward acquisition.

The long-latency reflex (LLR), the fastest feedback response that recruits supraspinal pathways, is an important model for understanding how descending motor pathways shape rapid corrective responses in humans. While the corticospinal tracts contribution to the LLR has been well established, that of the reticulospinal tract, the other major descending motor pathway, remains purely speculative. To address this online contribution to the generation of the LLR, we used loud acoustic stimulation (LAS), which can strongly engage brainstem circuits including the pontomedullary reticular formation. By delivering LAS at nine timings (0-80 ms in 10-ms steps) relative to perturbation onset, we tested whether LAS selectively facilitates the LLR but not the short-latency reflex (SLR), and whether the facilitated epoch shifts systematically with LAS timing. In twelve healthy participants, elbow extension perturbations were applied to evoke stretch reflexes in the biceps brachii muscle. LAS produced significant supralinear facilitation in the LLR but not in the SLR. Moreover, at LAS timings of 50 ms or more after perturbation onset, LLR facilitation shifted progressively later with LAS, remaining at an approximately fixed delay of 30 ms after LAS onset. This fixed delay indicates that LAS-evoked descending input from the same origin facilitates the ongoing LLR. Together with the lack of significant SLR facilitation, this temporal pattern supports an online reticulospinal contribution to the human LLR, alongside the established corticospinal contribution. This approach provides a new, non-invasive means to investigate the physiological role of the reticulospinal tract in human motor control. Key PointsO_LIThe long-latency reflex is a rapid muscle response to sudden stretch. Unlike faster spinal reflexes, it is shaped by commands descending from the brain and adjusts to the task. C_LIO_LIThough the corticospinal tract is known to shape this reflex, whether the reticulospinal tract also contributes to the reflex has not been tested in humans. C_LIO_LIWe stretched the arm and, at various delays, played a loud sound that engages the brainstem origin of the reticulospinal tract. The sound significantly enhanced the long-latency reflex, whereas no significant enhancement was detected in the faster spinal reflex. C_LIO_LIWhen the sound came 50 milliseconds or more after the stretch, the enhancement followed the sound at a stable delay, indicating that sound-evoked descending signals interacted with the ongoing reflex response. C_LIO_LIThese findings support a real-time contribution of the reticulospinal tract to the human long-latency reflex and provide a non-invasive way to study this pathway. C_LI

Implicit sequence learning is commonly inferred from changes in motor performance, although anticipatory gaze behavior may provide complementary information about emerging perceptual sequence knowledge. We tracked anticipatory gaze and response time on every trial of a reach-grasp-and-move sequence-learning task to examine when individual differences became detectable in each measure. Between-participant differences became detectable earlier in anticipatory gaze than in response time, with this ordering preserved in 95.5% of participant-level bootstrap resamples. Across the repeated sequence, anticipatory gaze became increasingly frequent, and most participants showed faster responses on anticipatory-gaze trials. Exploratory analyses further indicated that participants differed in the trial-to-trial persistence of anticipatory gaze, but these gaze characteristics were not reliably associated with sequence-specific motor learning expressed at the end of the session. Together, these findings show that anticipatory gaze and motor performance provide related but non-redundant information about implicit sequence learning where individual differences in perceptual knowledge may be detectable before corresponding differences are apparent in behavioral performance.

Preventing object slippage requires the central nervous system to control and coordinate the muscle groups while adapting to the variations in the slip characteristics. Our study investigates how slip characteristics, such as slip direction, slip distance, and slip speed, affect the modulation of muscle synergies as a manifestation of object slippage. Our results reveal that there are shared synergies existing in the upward and downward slip emulation, and that these shared synergies are dependent on slip characteristics. However, there were no specific synergies found to exist in the upward and downward slip conditions. Our results also indicate the existence of combined synergies, as the motor modules in the upward slip direction were found to have shared synergies with multiple motor modules in the downward slip direction. We also observed that the number of shared synergies varied depending on the slip distance and slip speed. Together, these findings suggest that the CNS flexibly reconfigures a limited set of muscle synergies to accommodate varying slip dynamics, balancing control stability with adaptability.

The vestibular system consists of peripheral end organs that provide the brain with temporally precise information about head position in space required for motor coordination and postural stability. Irregular vestibular afferents of the inner ear are particularly sensitive to rapid changes in acceleration, or jerk, which is necessary for making quick, corrective movements and postural adjustments. Vestibular short-latency evoked potentials (VsEPs) are waveforms that provide a measure of synchronous irregular afferent activity originating from peripheral (early peaks) and central (later peaks) vestibular pathways. These VsEPs are elicited by head jerk stimuli, commonly used preclinically. Previous studies have shown that early VsEP waves are dependent upon jerks of an adequate intensity, number, and duration. However, less is known about jerk characteristics necessary for generation of reliable VsEP signals centrally (later peaks). The present study examines the precise temporal dynamics of peripheral and central vestibular centers across a broad range of mechanical vestibular load in rats. We found differential changes in synchrony and timing driven by jerk repetition, intensity, and duration between early and late VsEP waves representing distinct anatomical components of the vestibular circuit. Our results suggest that central components are uniquely sensitive to jerk duration, intensity, and repetition, indicating a disconnect between peripheral and central neuronal recruitment, adaptive plasticity, and time-frequency dynamics. This work provides a foundation for using VsEP to assess jerk-induced physiological vestibular dysfunction and to understand how central relays differentially adapt to variations of mechanical vestibular stress compared with the precise, high-fidelity transmission observed in the periphery.

In mirror reversed (MR) learning, the magnitude and direction of the visuomotor distortion varies with target location. To date, implicit (i.e., unconscious) processes have not been implicated in learning to reach with an MR distortion, even when the distortion is small in magnitude. Across two experiments, we examined whether explicit processes (i.e., motor and perceptual awareness of reaching strategies) are engaged when learning to reach with a small (20{degrees}) MR distortion and whether this learning generalizes to novel targets. Learning to reach with an MR distortion was compared to learning to reach with a small visuomotor rotation (VR), in which cursor feedback was rotated 20{degrees} relative to hand motion at each target. Participants in the MR group engaged both motor and perceptual awareness and learning to reach with the MR distortion generalized to novel targets. Participants in the VR group also learned to reach with the VR distortion but they did not engage either motor or perceptual awareness and there was no evidence of generalization. Reaction times were longer for the MR group compared to the VR group, consistent with engagement of explicit processes. Together, these findings suggest that learning to reach with an MR distortion is supported by motor and perceptual awareness that generalize to novel targets.

Standing balance relies on the continuous detection of body motion across a wide range of amplitudes and frequencies. According to Weber's law, sensory discrimination should degrade in proportion to stimulus amplitude, yet vestibular self-motion perception deviates from this prediction. Whether this deviation extends to the vestibular control of posture remains unknown. To test this hypothesis, we delivered amplitude-increasing electrical vestibular stimulation (EVS, 0-2 mA) at four frequencies (0.1, 0.2, 0.5, and 1 Hz) to 10 healthy young adults, and quantified balance discrimination thresholds (DTs) from the gain and inter-trial variability of the lateral ground reaction force, using signal detection theory. Balance control DTs increased sublinearly with EVS amplitude at all frequencies, deviating from Weber's law. Both balance-correcting response gain and variability accounted for this deviation: gain decreased more slowly than the strictly inverse relationship that would have alone produced strict adherence to Weber's law, while variability exhibited an initial increase followed by saturation at higher EVS amplitudes, a signal-dependent structure necessary to reproduce the observed DT pattern. EVS frequency modulated the shape of this deviation but affected neither overall DT nor the signal-to-noise ratio of the balance-correcting response, which instead remained similar across frequencies. This study revealed a particular property of postural control discrimination by extending the psychophysical and neural deviations from Weber's law previously reported for vestibular perception. Overall, these results provide a better understanding of the balance control discrimination process and provide potential additional assessment criteria for vestibular impairments.

Movements are systematically affected by the recent motor history. These history effects may be induced either by reused motor plans or from lingering tuning of the previous movements' execution. We dissociated planning and execution using four experimental manipulations across two complementary motor paradigms. We isolated planning by preventing execution with stop signals and mechanical blocks, and execution by moving participants' hand passively using a robot manipulandum. History effects emerged in feedforward movement aspects - reaction time and early movement kinematics - following isolated planning. In contrast, they were absent or markedly reduced for isolated execution. History effects emerged also in late movement aspect that involves sensory feedback during execution - movement accuracy and precision - but only when movements were both planned and executed. Feedforward effects generalized across hands, whereas feedback effects were effector specific. Thus, prior motor planning and execution make distinct and complementary contributions in shaping future motor behavior.

Past studies using transcranial magnetic stimulation have shown larger motor-evoked potentials when people observe someone lifting a heavy object than when they observe someone lifting a light one. This means that observers may engage their own motor system in proportion to the perceived effort. However, the different responses during the observation of light and heavy objects may have been influenced by predictable trial sequences within blocked presentation, making it unclear whether corticospinal excitability reflects online processing of kinematics or is affected by top-down expectations. In this Registered Report, 57 right-handed participants passively observed videos of a precision grip and lift of heavy and light objects while receiving a single-pulse TMS to the left primary motor cortex during the lift phase of the movement. Motor-evoked potentials were recorded from the right first dorsal interosseous muscle. The study compared two main observation contexts: a predictable trial sequence in which repeated videos of the same lifts were presented in a blocked order, and an unpredictable one in which videos were presented semi-randomly and participants could rely only on kinematic cues to perceive the weight of the lifted object. In both conditions, the same videos of lifts of equivalent-looking heavy and light objects were used and only the order of presentation differed. Contrary to our predictions, in the blocked (predictable) condition, there was no significant difference in MEPs elicited by light and heavy lifts. In the unpredictable condition, participants showed greater corticospinal excitability during the observation of the light lifts compared to the heavy lifts. This suggests that in the absence of predictable information, the corticospinal system was sensitive to the observed kinematics, but contrary to previous findings, its excitability varied inversely with the object weight.

Background: Detecting environmental regularities is a sophisticated cognitive skill, but its neural basis remains unclear. We tested whether corticospinal excitability tracks stimulus predictability, prediction errors, and task progression while the participants played the Goalkeeper Game. Methods: Sixteen right-handed males (24.4 +/- 6.8 years) saved penalty kicks using index, middle, or ring fingers (left, center, right). Kick sequences were generated by a context tree model, in which contexts represent the minimum recent history required to predict the next event. Participants completed 1,200 trials (6 blocks x 200 trials each). Transcranial magnetic stimulation (TMS) delivered 400 ms before the go signal elicited motor evoked potentials (MEPs) in the first dorsal interosseous (FDI) and flexor digitorum superficialis (FDS) muscles during blocks 2, 4, and 6. Contexts were classified as unpredictable (1, 10) or predictable (2, 20, 00); prediction errors were defined for non-deterministic transitions after context 1. Log-MEPs were analyzed using mixed-effects models. Results: In FDI, a Predictability x Previous-Error x Block interaction emerged (F(2,8997)=6.89, p=.001), confined to the final block. Predictability increased MEP amplitudes after successful transitions (+6.3%; p=0.006) but decreased MEP amplitudes after failed transitions (-7.0%; p=0.007). For FDS, unpredictable trials elicited larger MEPs (+7.2%; p=0.002), and MEPs increased from block 2 to 6 (+16.8%; p=0.003). Conclusions: FDS MEP responses were broadly associated with uncertainty and task progression, whereas FDI MEP responses showed context-specific, error-dependent modulation after extended exposure, suggesting fine-grained predictive coding in goal-executing effectors.

The sodium leak channel NALCN regulates resting membrane potential and spontaneous firing in neurons and can be modulated by G-protein coupled receptors (GPCRs). Whether metabotropic glutamate receptors (mGluRs) modulate NALCN is unknown and would represent a novel mechanism through which glutamate could affect neuronal excitability. Here we examine NALCN function and modulation by mGluRs in cerebellar unipolar brush cells (UBCs) in mouse brain slices. Activation of group II mGluRs inhibited the NALCN current through a G protein-dependent mechanism, as the effect was abolished by intracellular GDP-{beta}-S and by NALCN deletion. The OFF UBC subtype that is inhibited by glutamate had a larger NALCN current than the ON UBC subtype that is excited by glutamate. OFF UBCs also had a tonic NALCN current that was absent in ON UBCs. Genetic deletion of NALCN converted the regular spontaneous firing pattern of OFF UBCs, to an irregular pattern similar to that of ON UBCs, suggesting that a tonic NALCN current may be a general mechanism to promote regular firing. Additionally, we identify the presence of group III mGluRs in OFF UBCs and GABA-B receptors in ON UBCs and show that neither inhibit NALCN, demonstrating that different GPCRs engage distinct downstream ion channels. These findings identify a previously unrecognized form of glutamatergic synaptic inhibition that is selectively initiated by group II mGluRs, but not other Gi/o-coupled GPCRs, within the same neurons.

Post-stroke gait impairment is associated with altered muscle coordination. Understanding how functional muscle coordination contributes to joint control is essential for clarifying the mechanisms of gait impairment after stroke. Functional muscle network approaches quantify how muscle interactions contribute to joint kinematics. We investigated how gait-related functional muscle networks are reorganized after stroke and how this reorganization relates to motor impairment and gait dysfunction. Thirty-five participants with subacute stroke and 25 healthy controls underwent gait analysis using surface electromyography and lower-limb kinematics. We quantified functionally similar (redundant information), complementary (synergistic information), and independent (unique information) muscle interactions underlying joint kinematics. Participants with stroke exhibited greater redundant information and lower independent information than healthy controls. Stroke-specific functional muscle network modules emerged through merging modules observed in healthy controls. Stroke-specific module activation was also associated with motor impairment and gait performance. Overall, these findings identify a shift toward more redundant muscle coordination and stroke-specific reorganization of functional network modules, providing new insights into post-stroke gait dysfunction.

We explored the role of proprioceptive feedback from Ia afferents in intra-muscle synergies stabilizing muscle force with the help of muscle vibration, which is known to increase presynaptic inhibition of those afferents to alpha-motoneurons. Healthy young adults performed an accurate three-finger force production task by pressing with the index, middle and ring fingers of the dominant (right) hand. This was done without vibration and with vibration applied to the extrinsic finger flexors, extensors, both muscles, the palm, or biceps brachii. High-density electromyography was used to identify motor units in both finger flexors and extensors. The raster plots of motor units were converted into firing frequency functions and then subjected to principal component analysis to extract stable motor unit groups (MU-modes). The uncontrolled manifold (UCM) analysis was used to quantify the variance components affecting and not affecting force, and the synergy index in the MU-mode space. Contrary to our expectations, the synergy index did not drop under any vibration condition and showed an increase during vibration applied simultaneously to both flexor and extensor muscles. This was primarily associated with a drop in the component of variance affecting the force magnitude. The results speak against an important role of monosynaptic Ia-afferent projections to alpha-motoneurons in the formation of intra-muscle synergies. They suggest that muscle vibration can play the role of a noisy signal decreasing performance-affecting variance via stochastic resonance effects.

Learning to reach with a visuomotor distortion has been shown to influence subsequent reaches with the same distortion and with a new distortion. Here, we examined whether learning to reach with a small 20{degrees} mirror reversed distortion leads to faster re-learning of the same distortion (i.e., demonstrates savings) and whether learning to reach with a mirror reversed distortion influences subsequent reaches with a 20{degrees} visuomotor rotation distortion. Thirty participants first learned to reach with the mirror reversed distortion. Following washout trials with aligned cursor feedback, 15 participants reached again with the mirror reversed distortion (MR-MR group), while the 15 other participants reached with a visuomotor rotation distortion (MR-VMR group). An additional twenty participants only reached with the visuomotor rotation distortion (VMR-only group). Implicit (unconscious) and explicit (conscious strategy) contributions to learning were assessed using the process dissociation procedure. Evidence of savings was evident in the MR-MR group, such that participants demonstrated reduced hand angles when re-introduced to the mirror reversed distortion. This savings was driven by explicit processes, consistent with the rapid retrieval of previously acquired task solutions. Additionally, learning to reach with the mirror reversed distortion interfered with learning to reach with the visuomotor rotation distortion, such that the MR-VMR group demonstrated increased reach variability and longer reaction times when reaching with the visuomotor rotation distortion compared to the VMR-only group. Reduced implicit contributions were also evident in the MR-VMR group compared to the VMR-only group. Together, results indicate that learning to reach with a mirror reversed distortion promotes savings and influences learning to reach with a visuomotor rotation distortion through engagement of explicit processes.

Serial dependence, whereby current perception is systematically biased toward the most recent sensory experience, has been demonstrated across multiple sensory modalities. However, whether serial dependence occurs during active haptic perception remains unknown. Moreover, because haptic perception of object geometry depends on hand movements for sensory acquisition (i.e., active touch), it remains unclear whether serial dependence, if any, originates from perceptual processing, movement, or both. Here, we investigated whether active haptic perception exhibits attractive serial dependence using a newly developed haptic device that let participants explore virtual slopes of different heights. Participants reported perceived slope heights, and we recorded their kinematics. Perceptual judgments were systematically attracted toward the most recently experienced slope, demonstrating serial dependence during active haptic perception. By contrast, none of the kinematic parameters exhibited corresponding serial dependence. These findings show that serial dependence extends to the somatosensory perceptual domain and suggest that the observed perceptual bias was not mediated by systematic changes in hand movements.

Pupillometry is commonly used to assess workload and fatigue, but its interpretation in applied, continuous-control tasks remains unclear because pupil responses are strongly shaped by task context and often lack a theory-guided interpretive basis. The Compensatory Control Model and Locus Coeruleus-Norepinephrine system offer complementary frameworks for interpreting pupil dynamics in relation to regulatory effort and engagement under sustained cognitive demand. We aimed to examine how tonic and phasic pupil dynamics reflect compensatory regulation following sustained cognitive demand, and how these dynamics relate to subsequent performance during continuous motor control. Participants completed two sessions consisting of a low- versus high- demand working-memory task followed by a joystick-based continuous motor-control task. Linear mixed-effects models tested demand effects on pupil dynamics and behavior and evaluated trial- level pupil-performance associations. Prior high demand produced small and specific changes in motor-control performance. Task-evoked pupil response showed effects of engagement dependent on prior demand and small associations with movement timing and accuracy. Our results show that pupil dynamics sensitively reflect sustained cognitive demand, but their trial-level predictive value for subsequent continuous motor performance is limited.

Emerging evidence suggests that cortical activity is organized in traveling waves that coordinate neural activity across space and time. How anesthesia alters these waves remains underexplored. We recently showed that cortical activity undergoes spontaneous state transitions at steady-state anesthetic concentrations including a paradoxical state exhibiting awake-like spectral properties during deep anesthesia. Here, we investigated traveling wave dynamics across spontaneous cortical states using hemispheric electrocorticography in rats anesthetized with desflurane at inhaled concentrations of 6, 4, 2, and 0%. Compared with the awake state, delta-band traveling waves in cortical states predominantly associated with 4-6% desflurane were more frequent and exhibited more stereotyped propagation patterns, characterized by a greater prevalence of planar waves and a corresponding reduction in source/sink wave patterns. The occurrence rate and pattern complexity of theta- and gamma-band waves remained largely unchanged, whereas the propagation direction of planar waves became more variable. Feedforward-feedback organization was also altered: compared with the awake state, the feedback-dominance of theta-band diminished, and the feed-forward dominance of gamma-band was attenuated. Despite occurring predominantly in deep anesthesia associated with behavioral unresponsiveness, traveling-wave dynamics of the paradoxical state exhibited partial, frequency-dependent shifts toward those observed in the awake state. These findings demonstrate that spontaneous cortical states under anesthesia are associated with frequency-dependent reorganization of cortical traveling waves and identify the paradoxical state as a distinct dynamical regime of deep anesthesia. Significance StatementAnesthesia is commonly thought to alter cortical dynamics progressively with increasing anesthetic depth, yet cortical activity can transition spontaneously between distinct states even at constant anesthetic concentrations. Here, we show that cortical states spectrally derived from the electrocorticogram of rats are associated with distinct frequency-specific organization of cortical traveling waves, revealing spatiotemporal dynamics beyond conventional spectral measures. Notably, a paradoxical state, occurred predominantly in deep anesthesia associated with behavioral unresponsiveness, exhibited traveling-wave dynamics that approached those observed during wakefulness. These findings demonstrate that cortical traveling-wave organization changes dynamically with brain state rather than anesthetic concentration alone. They suggest that structured cortical dynamics can emerge during deep anesthesia, providing new insights into large-scale cortical dynamics associated with anesthetic modulation of consciousness.