Biology subjects

Pruszynski, J. A.

Publications and source records attributed to Pruszynski, J. A..

At least 19 recordsLinked to original sources

bioRxiv2026

Encoding of bimanual movement directions across the human sensorimotor system

Bimanual coordination requires the control of each hand to account for movements of the other hand. To enable such coordination, it has been hypothesized that the brain has a representation of bimanual movements that supersedes a linear combination of the unimanual movements. To test for such a representation, we mapped the encoding of movement direction during unimanual and bimanual wrist movements in the human brain using functional magnetic resonance imaging (fMRI). For unimanual movements, we found that both the contralateral and ipsilateral movement directions were represented across most cortical motor regions. The representations were similar for mirror-symmetric movements across the hands, revealing an intrinsic (body-centric) code in premotor and parietal regions. For bimanual movements, the neural representations of movement directions could be explained by three components. First, the contralateral movement direction was represented as in the unimanual condition, whereas the representation of the ipsilateral movement direction disappeared. Second, in higher-order regions (rostral premotor and posterior parietal cortex) we found relatively elevated activity when the two movements were directed in unrelated directions. This activity was likely caused by the extra effort to deal with incongruent spatial targets across the hands. Third, and independent of this congruency effect, we found a non-linear interaction between contra- and ipsilateral movement that encoded the specific bimanual movement combination across sensorimotor, premotor, and parietal regions. This representation was suited to facilitate bimanual coordination and learning.

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bioRxiv2026

Reward-driven emergence of auditory pattern encoding in the primate motor system

The ability to anticipate rhythmic patterns is fundamental to human experience, enabling music appreciation, speech comprehension, and dancing in sync to music. How the brain learns to use acoustic information to guide motor behavior remains a key question, with its neural underpinnings and evolutionary origins debated, especially in non-human primates. Reward contingencies improve monkeys ability to synchronize with musical beats with near-human accuracy. However, humans and certain birds spontaneously synchronize with musical beats. Behavioural work in monkeys suggests that the brains reward system can encode rhythmic patterns if sufficiently reinforced, known as the intrinsic reward hypothesis. To investigate the neural mechanism of how the reward gates rhythmic pattern learning, we recorded neural activity from the globus pallidus interna (GPi) of a rhesus macaque during passive listening to auditory patterns. We found that GPis ability to encode auditory patterns in a monkey is shaped by reward association. Specifically, during passive listening (Experiment 1), with reward only at the end of each trial, GPi showed at most a weak response to the auditory tone patterns that was not evident in single neurons or population responses, ruling out spontaneous entrainment of motor activity to auditory patterns. When each tone was simultaneously accompanied by a liquid reward (Experiment 2), GPi showed clear responses to the tone patterns. To test if the tone responses persisted, the reward contingency was subsequently removed (Experiment 3). Strikingly, although the reward was delivered only at the trials end as in Experiment 1, GPi neurons continued to track the occurrence of the tones. Besides GPi, we also recorded single-neuron activity across the primary somatosensory (S1), primary motor (M1), dorsal premotor (PMd), supplementary motor (SMA), pre-supplementary motor (preSMA) cortices, and the medial geniculate body (MGB) of the same animal in experiments 1 and 2. We found that during passive listening (Experiment 1) with a reward only at the end of each trial, primarily the MGB, not motor areas, responded to the auditory tone patterns, ruling out spontaneous entrainment of motor activity to auditory patterns across the primate motor system. When each tone was simultaneously accompanied by a liquid reward (Experiment 2), all areas except S1 showed clear responses to the tone patterns. These findings suggest that while basic sensory processing of tone patterns occurs in the MGB, the GPi exhibits reward-driven encoding of auditory patterns that persists after reward withdrawal. This reorganization of neural responsiveness shows that the capacity for auditory association can be elicited in the motor system through appropriate motivational contexts.

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bioRxiv2026

Sensory expectations and prediction error during feedback control in the human brain

External disturbances to the body are better counteracted when their nature can be predicted in advance. Here, we investigated the neural mechanisms through which probabilistic predictions shape feedback responses using functional magnetic resonance imaging (fMRI) in humans. We show that, prior to a mechanical perturbation applied to a finger, the primary motor (M1) and somatosensory (S1) cortices receive a signal that linearly encodes the expected sensory input. When perturbations reach these areas, expectations are combined with the sensory input through a simple additive mechanism, yielding motor commands that reflect a weighted sum of the two signals. At the same time, M1 and S1 receive a prediction error signal encoding the difference between expectations and actual sensory input. This signal is visible in fMRI data in humans and in the local field potentials in non-human primates, but not in M1 or S1 spiking activity.

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bioRxiv2026

High performance sorting of motor unit action potentials with EMUsort

Understanding how neural signals control muscle activity during behavior is a key challenge in motor neuroscience. To this end, recent advances in intramuscular multielectrode arrays have enabled high-quality multichannel recordings of many motor unit action potentials (MUAPs) in freely moving subjects. However, identifying individual MUAP events within multichannel recordings is a significant challenge for existing spike sorting methods, which are typically optimized for identifying action potentials from neurons in the brain. To overcome this challenge, we developed the Enhanced Motor Unit sorter (EMUsort), an extension of Kilosort4 (KS4) that achieves high-performance MUAP spike sorting. We applied EMUsort to high-resolution intramuscular recordings from rat forelimb during locomotion and monkey forelimb during a reaching task. EMUsort improves upon prior methods by addressing key challenges encountered with MUAP datasets, including: 1) long time delays across electrodes due to propagation along muscle fibers, 2) more complex waveform shapes compared to neuronal action potentials, and 3) a high degree of MUAP overlap due to cumulative motor unit recruitment. We compared EMUsort to existing spike sorting methods quantitatively using simulated datasets that closely emulated the rat and monkey datasets we recorded. EMUsort provided median error rate reductions of 67.5% and 49.9% during periods of high motor unit activation for the rat and monkey datasets, respectively. In sum, EMUsort provides a substantial improvement to MUAP spike sorter accuracy, especially during regions of high MUAP overlap, in an easy-to-use software package.

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bioRxiv2025

Sequence preparation is not always associated with a reaction time cost

The extent to which a sequence of movements is prepared before initiating the first movement is a longstanding question in motor neuroscience. The observation that reaction time (RT) increases for longer sequences has been used as evidence of sequence preparation - reflecting the additional demands of preparing multiple movements before initiating a sequential action. However, many processes contribute to RT, making it unclear whether the observed RT increases specifically reflect sequence preparation. For example, with longer sequences, participants face greater ambiguity in selecting their first movement in the sequence. Here, we test how much of the observed RT increases can be explained by the first-target ambiguity when reaching toward spatial targets. In our paradigm, we independently manipulate: (i) the number of future targets displayed, (ii) the number of targets to be acquired, and (iii) the spatial arrangement of the targets. This approach allows us to vary the demands of sequence preparation and first-target ambiguity, thereby enabling a direct assessment of their respective influence on RT. We report that RT increases with additional sequence elements but that this effect is fully explained by the ambiguity in selecting the first reach target. That is, sequence preparation causes no RT increase. In fact, when first-target ambiguity is eliminated, RT is constant across the number of displayed targets even though kinematic analysis reveals that participants have prepared a sequence. Together, these results indicate that preparing multiple reaches to spatial targets does not impose additional temporal costs relative to preparing a single reach.

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bioRxiv2025

Infinite horizon control captures modulation of movement duration in reaching movements

Movement duration, a fundamental aspect of motor control, is often viewed as a pre-programmed parameter requiring dedicated selection mechanisms. An alternative view posits that movement duration emerges from the control policy itself. Here, we demonstrate, using infinite horizon optimal feedback control (IHOFC) and nonlinear limb dynamics that this alternative hypothesis successfully captures diverse aspects of human reaching behavior, including tradeoffs between movement duration and task parameters. Specifically, we reproduced the modulation of movement duration with varying reach distances and accuracy (Fitts law), and extended the infinite horizon framework to include the effect of rewards and biomechanical costs. Furthermore, our model also featured a temporal evolution of feedback responses to perturbations that resembles experimental observations, and naturally accounted for motor decisions observed when participants select one among multiple goals in dynamic environments. Together, these developments show that in many cases, movement duration may not need to be specified a priori, but instead could result from task-dependent control policies. This framework validates a candidate explanation for varied movement durations, which invites to reconsider the nature and strength of evidence for the finite horizon formulation.

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bioRxiv2025

Speed-dependent modulation of tactile edge orientation discrimination

Previous studies investigating edge-orientation discrimination capacity either stimulated an immobilized finger at limited speeds, or did not manipulate movement speed during active exploration. Here we tested the effect of movement speed on edge-orientation discrimination, including very slow and fast speeds. Participants were instructed to move their finger across two pairs of edges while matching their speed to a visual cue. One edge pair was parallel and the other non parallel to varying degrees. Participants were asked to identify the non parallel pair of edges. We report three main findings. First, consistent with previous reports, when they were free to choose their movement speed, participants moved at an average speed of [~]29 mm/s (range: 15-52 mm/s). Second, there was no correlation between a participants natural speed and their edge orientation discrimination capacity. Third, participants got better at edge orientation discrimination at slower than average speeds (5mm/s), and worse at higher than average speeds (90 and 180 mm/s). This change in performance was correlated with their relative change in movement speed. New and NoteworthyHere we demonstrate speed-dependent variation in edge-orientation discrimination during active tactile exploration, with improved performance at very slow speeds. Changes in discrimination capacity as a function of speed are correlated with deviations from a participants natural speed.

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bioRxiv2025

Integration of memory and sensory information in skilled sequence production

Sequential movements rely on two information sources: external sensory cues and internal memory representations. Although often both sources jointly drive sequential behavior, previous research has primarily examined them in isolation. To address this, we trained participants to perform sequences of rapid finger presses in response to numerical cues. Sensory influence was measured by varying the number of visible cues, and memory influence by comparing repeating and random sequences. Early in learning, participants integrated sensory and memory information: repeating sequences were performed more quickly when more cues were visible. After learning, when repeating sequences were predictable with certainty, participants relied solely on memory and ignored sensory cues. However, when this certainty was manipulated by introducing occasional violations within repeating sequences, participants reverted to integrating memory with sensory cues. We propose a computational model that successfully predicted both speed and accuracy of individual presses. Critically, this model relied on the assumption that multiple movements are planned independently of each other. This independence assumption was then validated by examining response patterns to isolated violations in repeating sequences. Finally, we provide evidence into how sequence memories can be flexibly deactivated and reactivated in response to these violations. Together, these results reveal how brain dynamically integrates sensory and memory information to produce sequences of movements.

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bioRxiv2025

Compositional neural dynamics during reaching

The complex mechanics of the arm make the neural control of reaching inherently posture dependent. Because previous reaching studies confound reach direction with final posture, it remains unknown how neural population dynamics in the motor cortex account for arm posture. Here we address this gap with high-density neural recordings and a reaching task in which the same targets serve as start points on some trials and end points on others. We show that neural population dynamics in monkey primary motor cortex and dorsal premotor cortex exhibit a compositional structure with three components that enable posture-dependent control: first, a posture subspace containing fixed points visited whenever the arm is in a specific posture; second, rotational dynamics that transition between these fixed points, systematically organized so that similar rotations produce similar movements while continuously updating the posture representation; third, a condition-independent shift dimension that tracks trial progression across all movements. This compositional structure advances the population-level account of how motor cortical dynamics support skilled reaching.

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bioRxiv2025

Developing a model of temporomandibular disorder in the common marmoset using nerve growth factor

Developing an animal model that more closely represents the human multidimensional pain experience is an important step towards addressing the current chronic pain crisis. The common marmoset has potential as this model species given its biological, neurological and phylogenetic similarity to humans. Here, we developed a model of myofascial temporomandibular disorder (TMD) in the marmoset by injecting nerve growth factor (NGF) into the superficial masseter. Following injection, animals showed reduced mechanical withdrawal thresholds at 5 g and 10 g doses of NGF and changes in circadian rhythm and feeding initiation following injection of 10 g of NGF. Animals did not show evidence of jaw dysfunction, masticatory alterations, or grimace during novel behavioural assays. The model is transient, with pain resolution occurring approximately 7 days after onset, which allows for repeated testing on the same animal. This same NGF-TMD model has been previously validated in rodents and humans and presents an opportunity for forward and reverse translation to examine mechanisms, develop relevant pain assessment tools, and ultimately test novel treatments for TMD and other musculoskeletal pain conditions. New & NoteworthyWe developed a long-lasting but transient ([~]7 days) model of myofascial temporomandibular disorder pain in marmosets. Mechanical hypersensitivity and changes to circadian activity and spontaneous eating behaviours were observed. There was no evidence of jaw dysfunction, altered food preference or changes in grimace. The NGF-TMD model can be translated to the marmoset with the potential for investigating mechanisms and novel interventions for TMD.

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bioRxiv2025

A paradigm to study the learning of muscle activity patterns outside of the natural repertoire

The acquisition of novel muscle activity patterns is a key aspect of motor skill learning which can be seen at play, for example, when beginner musicians learn new guitar or piano chords. To study this process, here we introduce a new paradigm that requires quick and synchronous flexion and extension of multiple fingers. First, participants practiced all the 242 possible combinations of isometric finger flexion and extension around the metacarpophalangeal joint (i.e., chords). We found that some chords were initially extremely challenging, but participants could eventually achieve them with practice, showing that the initial difficulty did not reflect hard biomechanical constraints imposed by the interaction of tendons and ligaments. In a second experiment we found that chord learning was largely chord-specific and did not generalize to untrained chords. Finally, we explored which factors make some chords more difficult than others. Difficulty was well predicted by the muscle activity pattern required by that chord. Interestingly, difficulty related to how similar chords muscle activity patterns are to the muscle activity patterns required by everyday hand use, and to the overall size of the muscle activity. Together, our results suggest that the new paradigm introduced in this work may provide a valuable tool to study the neural processes underlying the acquisition of novel muscle activity patterns in the human motor system.

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bioRxiv2024

Motor sequence learning involves better prediction of the next action andoptimization of movement trajectories

Learning new sequential movements is a fundamental skill for many animals. Although the behavioral manifestations of sequence learning are clear, the underlying mechanisms remain poorly understood. Motor sequence learning may arise from three distinct processes: (1) improved execution of individual movements independent of their sequential context; (2) enhanced anticipation of "what" movement should be executed next, enabling faster initiation; and (3) the development of motoric sequence-specific representations that encode "how" movements should be optimally performed within a sequence. However, many existing paradigms conflate the "what" and "how" components of learning, as participants often acquire both the sequence content (what to do) and its execution (how to do it). This overlap obscures the distinct contributions of each mechanism to motor sequence learning. In this study, we disentangled these mechanisms using a continuous reaching task. Performance in trained sequences was compared to random sequences to rule out improvements attributable solely to isolated movement execution. By also varying how many upcoming targets were visible we assessed the role of anticipation in learning. When participants could only see one future target, improvements were mostly due to them learning which target would come next. When they could see four future targets, participants immediately demonstrated fast movement times and increased movement smoothness, surpassing late-stage performance in the one target condition. Crucially, even with full visibility of future targets, participants showed further sequence-specific learning caused by a continuous optimization of movement trajectories. Follow-up experiments revealed that the learned sequence representations were effector-specific and encoded contextual information of four movements or longer. Our paradigm enables a clear dissociation between the "what" and "how" components of motor sequence learning and provides compelling evidence for the development of effector-specific sequence representations that guide optimal movement execution.

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bioRxiv2024

Sensory expectations shape neural population dynamics in motor circuits

The neural basis of movement preparation has been extensively studied during self-initiated actions where motor cortical activity during preparation shows a lawful relationship to the parameters of the subsequent action1,2. However, movements are regularly triggered and constantly corrected based on sensory inputs caused by disturbances to the body or environment. Since such disturbances are often predictable and since preparing for disturbances would make movements better, we hypothesized that expectations about sensory inputs also influence preparatory activity in motor circuits. Here we show that when humans and monkeys are probabilistically cued about the direction of a future mechanical perturbation, they incorporate sensory expectations into their movement preparation and improve their corrective responses. Using high-density neural recordings, we establish that sensory expectations are widespread across the brain, including the motor cortical areas involved in preparing self-initiated actions. The geometry of these preparatory signals in the neural population state is simple, scaling directly with the probability of each perturbation direction. After perturbation onset, a condition-independent perturbation signal shifts the neural state leading to rapid responses that initially reflect sensory expectations. Based on neural networks coupled to a biomechanical model of the arm3, we show that this neural geometry emerges through training, but only when the incoming sensory information indicating perturbation direction coincides with - or is preceded by - a condition-independent signal indicating that a perturbation has occurred. Thus, motor circuit dynamics are shaped by future sensory inputs, providing clear empirical support for the idea that movement is governed by the sophisticated manipulation of sensory feedback4.

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bioRxiv2024

String-pulling by the common marmoset

Coordinated hand movements used to grasp and manipulate objects are crucial for many daily activities, such as tying shoelaces or opening jars. Recently, the string-pulling task - which involves cyclically reaching, grasping and pulling a string - has been used to study coordinated hand movements in rodents and humans. Here we characterize how adult common marmosets perform the string-pulling task and describe changes in performance across the lifespan. Marmosets (n=15, 7 female) performed a string-pulling task for a food reward using an instrumented apparatus attached to their home-cage. Movement kinematics were acquired using markerless video tracking and we assessed individual hand movements and bimanual coordination using standard metrics. Marmosets oriented their gaze towards the string above their hands and readily performed the task regardless of sex or age. The task required very little training and animals routinely engaged in multiple pulling trials per session despite not being under water or food control. All marmosets showed consistent pulling speed and similar hand movements regardless of age. Adult marmosets exhibited a clear hand effect, performing straighter and faster movements with their right hand despite showing idiosyncratic hand preference according to a traditional food retrieval assay. Hand effects were also evident for younger animals but seemed attenuated in the older animals. In terms of bimanual coordination, all adult marmosets demonstrated an alternating movement pattern for vertical hand positions. Two younger and two older marmosets exhibited idiosyncratic coordination patterns even after substantial experience. In general, younger and older animals exhibited higher variability in bimanual coordination than did adults.

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bioRxiv2024

Single-shot detection of microscale tactile features

Tactile detection of very small features requires relative motion between the fingertip and a surface. The specific movement strategies that people use may be critical to maximize detection ability but little is known about the movement strategies people employ to support such detection. Here, human participants actively scanned a fingertip across a pair of silica wafers to detect which of the two contained a microscale feature (2, 6, and 10 m height and 525 m diameter). We constrained fingertip movement to ensure that participants would always contact the feature and would only contact the feature once. These procedures encouraged participants to use strategies that optimized detection rather than search and thus allowed us to more directly link movement strategies to detection. We also investigated the effects of fingertip movement direction and the finger used on detection. We found that participants were able to consistently detect microscale features as small as 2 m on the basis of a single contact event. The contact forces that participants used were substantially higher than those observed in previous studies focused on tactile search or geometric feature extraction. Scanning speeds were slower than those found during tactile search but faster than those reported during geometric feature extraction. Taken in conjunction with the associations between detection and finger used as well as scan direction, our results suggest that control and consistency of fingertip movement may be a primary consideration for movement strategies that optimize tactile detection.

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bioRxiv2024

Spike frequency adaptation in primate lateral prefrontal cortex neurons results from interplay between intrinsic properties and circuit dynamics

Recordings of cortical neurons isolated from brain slices and dissociated from their networks, display intrinsic spike frequency adaptation (I-SFA) to a constant current input. Interestingly, extracellular recordings in behaving subjects also show extrinsic-SFA (E-SFA) in response to sustained visual stimulation. Because neurons are isolated from brain networks in slice recordings, it is challenging to infer how I-SFA contributes to E-SFA in interconnected brains during behavior. To investigate this, we recorded responses of macaque lateral prefrontal cortex neurons in vivo during a visually guided saccade task and in acute brain slices in vitro. Broad spiking (BS) putative pyramidal cells and narrow spiking (NS) putative inhibitory interneurons exhibited E-SFA in vivo. In acute brain slices, both cell types displayed I-SFA though their magnitudes differed. To investigate how in vitro I-SFA contributes to in vivo E-SFA, we developed a data-driven hybrid circuit model in which local NS neurons are driven by BS input. We observed that model NS cell responses show longer SFA than observed in vivo. Introducing inhibition of NS cells to the model circuit removed this discrepancy. Our results indicate that both I-SFA and inhibitory circuit dynamics contribute to E-SFA in LPFC neurons. They highlight the contribution of single neuron and network dependent computations to neural activity underlying behavior.

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bioRxiv2024

Repetition effects reveal the sub-sequence representation of actions

When a movement sequence is repeated, the second execution is faster than the first. This demonstrates that the brain retains some trace of the just-executed sequence, the earliest form of sequence memory. Currently, it is unclear whether this memory trace is represented at the level of (a) transitions between movements, (b) chunks of multiple movements, or (c) the entire sequence. To answer this question, we instructed human participants to generate sequences of 11 finger presses in a delayed response paradigm. From one trial to the next, segments of variable length (1, 2, 4, 6, 11) could be repeated from the previous trial. We observed that repetition benefits appeared when a segment of 4 consecutive finger presses or longer was repeated from the previous trial. This suggests that the benefit of repetition is not merely the sum of improvements in individual transitions, nor does it require the entire sequence to be repeated. The repetition benefit was small for the first transition of a repeated segment and increased with additional repetitions. This suggests that the memory supporting the repetition effect is mainly activated when a series of past movements matches the memory trace. Planned future movements had less of an effect on the repetition effect. Our results provide insight into the structure of the earliest memory traces for motor sequences. Significance StatementMany motor skills involve concatenating single movements into complex sequences. Already after a single execution of a sequence, humans retain a memory trace that accelerates the execution of the sequence if it is repeated in the next trial. Our results show a repetition benefit even when only a small portion of movements from the previous trial is repeated, suggesting that full sequence repetition is not necessary. Detailed analyses indicate that the memory trace is activated when the last 2-3 movements match the current execution. Our work, therefore, sheds light on the structure of the earliest sequence memory and will interest researchers studying motor skill learning and the neural basis of movement control.

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bioRxiv2024

Parallel feedback processing for voluntary control: knowledge of spinal feedback in motor cortex

How hierarchical feedback pathways coordinate goal-directed motor corrections remains unknown. We show that systematic increases in spinal reflex responses to applied loads lead to a reciprocal reduction in the neural response in primary motor cortex. We use a neural network model to highlight how knowledge on lower-level feedback processing (i.e. spinal reflexes) can be embedded into a network to generate goal-directed corrections through parallel feedback pathways.

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