Journal of Neurophysiology

The locus coeruleus-norepinephrine (LC-NE) system plays multiple roles in higher brain function that are thought to depend on its mode of activation, which reflects relationships between baseline and evoked activation levels. These relationships are evident in both single-unit LC activity and proposed physiological proxies of LC-NE activity, such as pupil size. Here we used measurements in awake monkeys to show that the baseline-evoked relationships evident within these two different measures are unreliably coupled between them: baseline-evoked relationships of the pupil are not predictive of those in the LC, and vice versa. These results imply that pupil modulations, which can reflect LC-NE activity, should be used with caution to make inferences about "phasic" (moderate baseline, high evoked) and "tonic" (high baseline, low evoked) LC-NE activity modes that are thought to support different forms of information processing in the brain.

We investigated the dimensions of output zones affecting specific combinations of forelimb muscles in the precentral "motor" cortex of macaque monkeys. Single-pulse intracortical microstimulation (S-ICMS) was used to evoke subthreshold effects in multiple wrist and finger muscles. Results indicate that each motor cortex site represents a different combination of muscles. The effects evoked from cortical sites separated by several hundred microns invariably involved different profiles of muscle activity. The muscle fields of remote CM cells were rarely identical, while the fields of neighboring CM cells were often similar. Given the number of unrecorded muscles, we conclude that primate motor cortex is a mosaic of output sites representing forelimb muscles in different combinations.

Learned movements are thought to be represented in both extrinsic and intrinsic coordinate systems. Intrinsic representations have traditionally been characterized using joint-based coordinates, although the relationship between joint movements and muscle activation depends strongly on limb configuration. Consequently, movement directions aligned in joint space may not be aligned in muscle space, but the implications of this mismatch for motor learning have remained largely unexplored. We addressed this question by combining electromyographic (EMG) analysis with a visuomotor adaptation experiment. In Experiment 1, participants performed planar reaching movements in two workspaces separated by a 45{degrees} shoulder rotation while EMG activity was recorded from nine upper-limb muscles. Muscle-pattern similarity analysis revealed that movement directions aligned in joint space were not always aligned in muscle space and that the degree of misalignment varied systematically across movement directions. Based on these results, we predicted that visuomotor adaptation to clockwise (CW) and counterclockwise (CCW) rotations would produce different patterns of motor generalization, contrary to the prediction of conventional joint-space accounts. Experiment 2 confirmed this prediction, revealing a systematic shift between the CW and CCW generalization patterns that was consistent with the muscle-space prediction. These findings suggest that intrinsic representations of learned movements are not fully captured by joint-based coordinates alone and that muscle-based coordinates contribute to motor learning and its generalization. Together, these findings highlight the importance of considering underlying biomechanics when interpreting motor representations using generalization paradigms.

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.

Although muscle spindle sensory signals have been extensively studied, little is known about how and why muscle spindle firing is modulated by the central nervous system during movement. Specialized motor neurons to the muscle spindle, i.e. gamma motor neurons, can profoundly alter spindle firing during behavior, but technological limitations hinder our ability to record gamma motor and muscle spindle sensory signals during most behaviors. We used a biophysical model of a muscle spindle within a muscle-tendon unit to simulate how gamma drive may modulate muscle spindle Ia firing during locomotion. Based on a few available recordings from decerebrate animals, we demonstrate that our model, tuned to passive stretch conditions, can reproduce profound changes in muscle spindle firing in response to identical joint motions in locomotor vs. relaxed stretch conditions. Our model can discover phasic patterns of two types of gamma motor neuron drive based on recorded muscle spindle Ia firing and joint motion. By simulating perturbations, we conclude that: 1) sinusoidal activation of static gamma motor neurons during locomotion, encoding intended movement, modulates muscle spindle signals such that they act as sensorimotor feedback signals based on errors from the intended muscle fascicle length; 2) phasic on/off activation of dynamic gamma motor neurons during locomotion acts as an event detector, heightening muscle spindle Ia responses to discrete perturbations. As such, their muscle-within-muscle structure allows the muscle spindle to act as a highly tunable physical internal model of muscle state to guide movement. Our model supports proposed but as-yet-untested theories of muscle spindle function and offers a framework for extending the testing of muscle spindle function to active, behavioral conditions.

Interception of moving objects requires the nervous system to compensate for sensory delays and uncertainty, yet how behavior is controlled remains debated. Key questions concern whether predictive processes play any role at all and, if so, whether they rely on simple motion extrapolation or incorporate internalized physical priors, such as gravity. Another open question is whether observers adopt a single control strategy or flexibly switch between predictive and reactive control - or between different predictive strategies - depending on task demands. To address these questions, we developed a virtual interception task in which participants intercepted moving targets under systematically varied conditions. We manipulated gravity (1g vs. 0g), visual availability (occluded vs. non-occluded), target velocity, and the initial spatial configuration of the ball and paddle (same vs. opposite side). Results indicate that interception is supported by predictive mechanisms across conditions. Behavioral patterns during occluded 0g trials suggest that participants extrapolate target motion using expectations consistent with gravity. Target velocity, visual occlusion, and task geometry modulated movement strategies, indicating that predictive control is flexibly adapted to task demands. These findings support the view that interception relies on predictive internal models incorporating structured physical priors while revealing flexible, context-dependent adaptations to sensory and task constraints.

The human sensorimotor system is remarkably effective at automatically parsing total movement error into its constituent parts, the error component due to a perturbation, or externally-generated error (EGE), versus the error component due to motor noise, or internally-generated error (IGE). Participants robustly, and implicitly, adapt to minuscule (2{degrees}) EGEs in the form of randomized visuomotor rotations while ignoring identically-sized errors caused by IGE. This error parsing, and its associated perceptual processes, directly contrasts previous work showing that humans must observe rotations that are > 1.5x the standard deviations of their motor variability, or [≥] 4{degrees}, before explicitly reporting their presence. While the combined results suggest a dissociation between perception for action--which allows for precise and automatic error parsing--and perception for conscious detection, this must be inferred across studies using different methodologies. Here, we combined a within-subjects study design and computational modeling to shed light on the principles underlying implicit adaptation to a perturbation and explicit perturbation detection. Neuro-typical adults participated in two experiments consisting of pseudo-randomized rotations during reaches to a single target, with one session requiring explicit reports after each reach of whether a perturbation was detected. Participants demonstrated a clear dissociation between implicit responses to a perturbation and explicit detection, with robust adaptation to 1{degrees} EGEs, but an inability to reliably report the presence of an EGE until it reached [~] 4{degrees}. For the adaptation task, a model that assumes the participant compares proprioceptive and visual cues to detect a perturbation and corrects for a proportion of this error best fit the data. For signal-detection, a Bayesian causal-inference model in which sensory cues are optimally integrated with a prior on their cause best fit those data. These results indicate that implicit adaptation is dissociated from explicit perturbation detection and the sensorimotor system applies distinct computational strategies to these behaviors.

Certain features of everyday motor skills become automatic while others remain controlled. Here we use a novel keyboard typing task to investigate whether motor automaticity depends on the frequency of naturally learned motor sequences. Participants type five-letter strings that vary in their word and bigram (two-letter sequence) frequency in natural language, allowing us to examine the influence of prior exposure without laboratory training. Novel pseudo word strings are tested as well. We find greater sequence frequency in natural language is associated with faster inter-keypress intervals and lower temporal variability within the sequence. In contrast, latencies to initiate a sequence are slower for novel pseudo-word strings but are otherwise insensitive to natural word frequency. We also find individual differences in inter-keypress speed and variability are robust across frequency levels but are unrelated to conventional measures of typing skill. Our method establishes keyboard typing as a scalable, ethologically valid framework for probing features of a naturally acquired human motor skill. This research will help extend laboratory-based studies of motor sequence learning and sets the stage for future investigations of linguo-motor processes. Moreover, our findings demonstrate which features within naturally acquired motor sequences become automatic and that typing proficiency is not determined solely by automaticity.

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.

Temperature influences neuronal and circuit output and extreme temperatures can disrupt neuronal performance. Acclimation invokes a form of neuronal plasticity that we call robustness tuning, that preserves nervous system performance during seasonal alterations in environmental conditions. The stomatogastric nervous system (STNS) of the American lobster, Homarus americanus, produces stereotyped rhythmic motor patterns that are maintained over a range of acute temperature changes, but lost under more extreme conditions. In the wild, H. americanus experience water temperatures from [~]2{degrees}C to 25{degrees}C during the course of a year. We acclimated lobsters to 18{degrees}C versus 4{degrees}C for [~]3 weeks, and found that the pyloric rhythm from warm-acclimated animals maintained its characteristic properties over an extended temperature range, when compared to those recorded from cold-acclimated animals. There were acclimation and temperature dependent differences in the responses of pyloric neurons to the neuropeptide, Crustacean Cardioactive Peptide (CCAP). Computational models suggest that pyloric neuron morphology and neuromodulator conductance distribution play a role in robustness tuning, the reversible changes that allow animals to repeatedly adapt to seasonal change.

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

Skilled control of visually-guided reaching is fundamental for many daily activities. Visual information about hand and target position are used for movement planning and online corrections through rapid visuomotor feedback responses. Such feedback control is generally believed to implicate a single error signal, representing a difference vector between hand and target position. Here, we directly assess whether shared or independent systems serve visually-guided feedback control. We tested whether feedback gains can be independently modulated by hand/cursor and target motion through manipulating the task-relevance of each signal during goal-directed reaching. Our results demonstrate that the gains of visuomotor feedback responses to perturbed hand and target motion can be set independently of one another, at the same time, as a function of task-relevance. By dissociating feedback control of cursor and target signals, our findings support the existence of two independent visuomotor feedback pathways, revealing a more flexible neural architecture for goal-directed action.

Tactile sensitivity is reduced during limb movement, a phenomenon known as somatosensory gating. Here, across two experiments, we ask whether gating is driven by motor prediction or by motor execution. In a Go/NoGo paradigm, in which participants planned movements in every trial but on rare trials had to withhold them. Since previous work indicated that predictions about movement kinematics influence gating also during passive movements, we also tested a mechanical arm transport in a passive Go/NoGo paradigm. Perceived intensity was attenuated exclusively on Go trials, in both active and passive movements, and was indistinguishable from baseline on NoGo trials. However, discrimination precision was selectively degraded in Active NoGo trials when a movement was planned and then withheld. In Experiment 2, vibro-tactile probes delivered before movement onset already showed the same bias as probes delivered during movement, in both active and passive conditions, while precision remained unchanged. Our data demonstrates that the sensorimotor system predictively establishes tactile precision before movement onset. Such a mechanism might contribute to active texture exploration by separating tactile signals from the sensory signals arising through the self-produced movement.

It has been demonstrated that people who stutter exhibit atypical motor control not only in speech tasks but also movements in the non-speech effector system, such as finger or arm motion. Notably, studies have reported that people who stutter show limited sensorimotor adaptation (i.e., updating subsequent movements in response to sensory errors) in both speech auditory-motor (i.e., updating speech movements in response to altered auditory feedback) and upper limb visuo-motor (i.e., updating arm movements in response to altered visual feedback) tasks. Given that speech auditory-motor adaptation is mostly if not entirely implicit (i.e., participants are unaware of the learning), it is thought that people who stutter have limited implicit adaptation in the speech effector system. It remains unclear however, whether such limited implicit learning also extends to upper limb visuomotor adaptation. Here, we examined implicit visuomotor learning in adults who stutter through the means of arm reaching adaptation to clamped visual feedback which provides a cursor that is fixed in direction (8{degrees} counterclockwise from targets) regardless of the participants actual hand location. All participants gradually adjusted their reach angle towards the clockwise direction, adapting in response to clamped feedback, but adults who stutter showed less adaptation compared to adults who do not stutter. In addition, computational modeling suggests that this implicit adaptation difficulties in stuttering individuals may reflect reduced error sensitivity. Together, our findings suggest that implicit sensorimotor learning difficulties in adults who stutter may generalize across multiple effector systems, providing important implications for understanding sensorimotor mechanisms underlying stuttering. Significance statementBy employing the clamped visual feedback paradigm during arm reaching movements, we demonstrated that adults who stutter showed less implicit visuomotor adaptation compared to adults who do not stutter. This study provides the first evidence that implicit sensorimotor adaptation limitations in developmental stuttering generalize across multiple effector systems. Our findings not only add to a growing body of evidence that stuttering is associated with domain-general sensorimotor difficulties but also point to specific underlying processes that may lead to stuttering.

Surface electromyography (EMG) studies have demonstrated anticipatory muscle activation prior to predictable voluntary actions. However, the mechanism through which this preparation is expressed, whether through motor-unit recruitment or discharge-rate modulation, remains to be elucidated. We employed surface decomposition EMG to quantify motor-unit behavior prior to self-paced rapid isometric elbow-flexion force pulses. Twelve healthy young men were instructed to generate elbow-flexion pulse force at 30%, 40%, and 50% of the maximal voluntary contraction (MVC) at a self-selected time. Motor-unit activity was decomposed from the biceps brachii and triceps brachii muscles, and the normalized active motor-unit number and mean discharge rate were analyzed prior to pulse onset. In the agonist, the pre-pulse increase mean discharge rate exhibited a higher value than the change in detected motor-unit count, particularly at the 40% and 50% MVC targets. The discharge-rate increase scaled with the target force, with a heightened response observed in high-threshold as compared to low-threshold motor units. Antagonist recordings with sufficient decomposition yield exhibited a similar discharge-rate-dominant pattern; however, these data were available from a smaller sample size. Present findings suggest that discharge-rate modulation is a primary motor-unit-level feature of anticipatory preparation for rapid isometric force production.

ObjectiveAging is associated with changes in cortical excitability and altered responsiveness to benzodiazepines, but the effects of benzodiazepine challenge on motor cortical paired-pulse physiology in older adults remain incompletely understood. We examined whether intravenous midazolam differentially modulates corticospinal excitability and short-interval paired-pulse transcranial magnetic stimulation (TMS) responses in younger and older adults. MethodsFifteen younger adults (18-35 years) and fifteen older adults (50-69 years) underwent single-pulse and paired-pulse TMS of the left primary motor cortex at baseline and during intravenous midazolam administration. Single-pulse motor evoked potential (MEP) amplitude was used to assess corticospinal excitability. Short-interval paired-pulse responses were quantified as the ratio of conditioned to unconditioned MEP amplitude. ResultsAt baseline, younger adults showed greater corticospinal excitability than older adults, reflected by larger single-pulse MEP amplitudes (adjusted p = 0.04). Younger adults demonstrated paired-pulse inhibition at baseline, reflected by a conditioned/unconditioned MEP ratio below 1.0 (ratio = 0.73; adjusted p < 0.01), whereas older adults did not show inhibition and instead had a mean ratio above 1.0 (ratio = 1.25). Midazolam reduced single-pulse MEP amplitudes in both groups. During midazolam administration, paired-pulse inhibition was no longer observed in younger adults, and older adults continued to show no evidence of inhibition. ConclusionsYounger and older adults differed in baseline corticospinal excitability and in short-interval paired-pulse TMS responses. Intravenous midazolam reduced corticospinal excitability and altered paired-pulse response patterns, eliminating baseline paired-pulse inhibition in younger adults while producing little measurable change in older adults. These findings suggest that aging may modify the net motor cortical response to benzodiazepine challenge. The results should be interpreted in relation to the paired-pulse stimulation parameters used and support further studies using complementary approaches to characterize age-related differences in inhibitory and facilitatory motor cortical circuits.

Blindness imposes constraints on the acquisition of environmental sensory information. To mitigate those constraints, some blind people employ active echolocation, a technique in which self-generated tongue "clicks" produce informative reflections from surrounding surfaces. Practitioners typically produce multiple clicks that guide, and are in turn shaped by, goal-relevant action. What perceptual information is gained in the echoacoustic signal from each click, and how does it inform motor behavior during task performance? To explore these poorly understood dynamics, here we recorded head movements and clicking behavior of an early-blind expert echolocation practitioner who localized and oriented toward a target object positioned at a 1 m distance and random azimuth in the frontal hemifield. Three additional participants, including a blind self-reported echolocator, were unable to perform the task better than chance level. Performance clearly benefited from available echoacoustic information: The larger target was localized with an average absolute angular error of 9.5{degrees} in 9.3 s, vs. 24.6{degrees} in 23.2 s for the smaller target. In a passive control condition prohibiting clicks altogether, no significant convergence on the target was observed, confirming the necessity of active sampling. Clicks were emitted somewhat more rapidly and intensely for small targets, but within-trial emission rate and head kinematics (left-to-right reversals) remained relatively invariant. Angular convergence toward the target was consistent with an exponential decay profile, though only weakly distinguishable from a linear trend for small targets. Pooled across trials within each condition, clicks were unimodally distributed about the target azimuth, suggesting an intensity-maximization strategy. In sum, clicking behavior and target size (therefore sonar strength) strongly influenced the rate and precision of orientation convergence toward the target, suggesting that dynamic interactions between motor-driven head movements, click production, and the resulting echoacoustic feedback accumulate goal-relevant evidence across multiple samples. Together, these results illustrate naturalistic sensorimotor dependencies underlying auditory active sensing in the absence of vision.

Multiple learning signals can shape motor output, including reward and punishment (via value-based reinforcement learning) and sensorimotor error (via motor adaptation). However, it is unclear if action values, learned via reinforcement learning, interact with error-based motor learning. Here, we asked if the learned value of competing motor goals influences how the motor system learns from sensorimotor errors linked to those goals. We designed a paradigm that required participants (N = 85) to learn about the value associated with different movement targets prior to undergoing implicit visuomotor adaptation at or nearby those same targets. We observed two classes of related effects: repulsion and suppression. When adaptation brought the limb toward targets associated with low-value, learning was attenuated compared to when adaptation brought the limb away from targets associated with low-value, indicating a "repelling" effect of low-value actions. Moreover, adaptation was suppressed in all directions when low-value targets were themselves the goal of movement. These findings were asymmetric with respect to valence: we did not observe comparable attraction effects when adaptation brought the limb toward targets associated with high-value, nor did we see overall enhancement of adaptation when targets associated with high-value acted as movement goals. Additional analyses and experiments demonstrated that these effects did not reflect generic biases and were driven by relative rather than absolute goal values. Repulsion and suppression effects were tied to movement directions rather than the targets themselves. These results point to a novel interaction between reinforcement learning and motor memory -- a kind of "instrumental-motor transfer." Significance StatementIn order to ensure our motor behavior yields our desired outcomes, we must not only learn which actions lead to which outcomes (via reinforcement learning) but also how to precisely execute those actions to achieve the desired outcome (by calibrating our actions via implicit motor adaptation. While it is clear that reinforcement learning and motor adaptation operate at different levels of an action selection hierarchy, it is unclear if they interact. Knowing if and how these processes interact is critical for understanding the fundamental algorithms and various neural circuits underlying real-world motor behavior. Here, we show a novel interaction between the two processes where implicit adaptation is suppressed when adaptation would bring the hand toward a previously punished movement goal.

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.

Motor outputs vary even in response to identical sensory inputs, yet the origin of this variability within the sensorimotor pathway remains unresolved. Here, we evaluate how variability in sensory representations can explain behavioural fluctuations in a reflexive oculomotor task. We used Neuropixels probes to record neuronal activity in area MT of marmosets during ocular following responses and applied partial least squares regression to extract the shared variance between population activity and eye movements. Stimulus-evoked activity reliably predicted trial-by-trial variability in open-loop eye velocity. Additionally, closed-loop analyses revealed trial-by-trial correspondence between eye movements and subsequent neural responses. These results demonstrate that variability in sensory neural populations contributes to motor variability, supporting the claim that sensory noise is propagated through the sensorimotor pathway. Surprisingly, however, traditional models trained to only capture neural variability across trials poorly predicted behavioural variations, suggesting that only a subset of sensory representations is accessible to the motor system.