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Kersten, R.

Publications and source records attributed to Kersten, R..

7 recordsLinked to original sources

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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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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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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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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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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Myomatrix arrays for high-definition muscle recording

Neurons coordinate their activity to produce an astonishing variety of motor behaviors. Our present understanding of motor control has grown rapidly thanks to new methods for recording and analyzing populations of many individual neurons over time. In contrast, current methods for recording the nervous systems actual motor output - the activation of muscle fibers by motor neurons - typically cannot detect the individual electrical events produced by muscle fibers during natural behaviors and scale poorly across species and muscle groups. Here we present a novel class of electrode devices ("Myomatrix arrays") that record muscle activity at unprecedented resolution across muscles and behaviors. High-density, flexible electrode arrays allow for stable recordings from the muscle fibers activated by a single motor neuron, called a "motor unit", during natural behaviors in many species, including mice, rats, primates, songbirds, frogs, and insects. This technology therefore allows the nervous systems motor output to be monitored in unprecedented detail during complex behaviors across species and muscle morphologies. We anticipate that this technology will allow rapid advances in understanding the neural control of behavior and in identifying pathologies of the motor system.

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Shared internal models for feedforward and feedback control of arm dynamics in non-human primates

Previous work has shown that humans account for and learn novel properties or the arms dynamics, and that such learning causes changes in both the predictive (i.e., feedforward) control of reaching and reflex (i.e., feedback) responses to mechanical perturbations. Here we show that similar observations hold in old-world monkeys (macaca fascicularis). Two monkeys were trained to use an exoskeleton to perform a single-joint elbow reaching and to respond to mechanical perturbations that created pure elbow motion. Both of these tasks engaged robust shoulder muscle activity as required to account for the torques that typically arise at the shoulder when the forearm rotates around the elbow joint (i.e., intersegmental dynamics). We altered these intersegmental arm dynamics by having the monkeys generate the same elbow movements with the shoulder joint either free to rotate, as normal, or fixed by the robotic manipulandum, which eliminates the shoulder torques caused by forearm rotation. After fixing the shoulder joint, we found a systematic reduction in shoulder muscle activity. In addition, after releasing the shoulder joint again, we found evidence of kinematic aftereffects (i.e., reach errors) in the direction predicted if failing to compensate for normal arm dynamics. We also tested whether such learning transfers to feedback responses evoked by mechanical perturbations and found a reduction in shoulder feedback responses, as appropriate for these altered arm intersegmental dynamics. Demonstrating this learning and transfer in non-human primates will allow the investigation of the neural mechanisms involved in feedforward and feedback control of the arms dynamics.

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