Integrated Control of Predatory Hunting by the Central Nucleus of the Amygdala.

Superior predatory skills led to the evolutionary triumph of jawed vertebrates. However, the mechanisms by which the vertebrate brain controls predation remain largely unknown. Here, we reveal a critical role for the central nucleus of the amygdala in predatory hunting. Both optogenetic and chemogenetic stimulation of central amygdala of mice elicited predatory-like attacks upon both insect and artificial prey. Coordinated control of cervical and mandibular musculatures, which is necessary for accurately positioning lethal bites on prey, was mediated by a central amygdala projection to the reticular formation in the brainstem. In contrast, prey pursuit was mediated by projections to the midbrain periaqueductal gray matter. Targeted lesions to these two pathways separately disrupted biting attacks upon prey versus the initiation of prey pursuit. Our findings delineate a neural network that integrates distinct behavioral modules and suggest that central amygdala neurons instruct predatory hunting across jawed vertebrates.

A universal interface for plug-and-play assembly of stretchable devices.

Stretchable hybrid devices have enabled high-fidelity implantable1-3 and on-skin4-6 monitoring of physiological signals. These devices typically contain soft modules that match the mechanical requirements in humans7,8 and soft robots9,10, rigid modules containing Si-based microelectronics11,12 and protective encapsulation modules13,14. To make such a system mechanically compliant, the interconnects between the modules need to tolerate stress concentration that may limit their stretching and ultimately cause debonding failure15-17. Here, we report a universal interface that can reliably connect soft, rigid and encapsulation modules together to form robust and highly stretchable devices in a plug-and-play manner. The interface, consisting of interpenetrating polymer and metal nanostructures, connects modules by simply pressing without using pastes. Its formation is depicted by a biphasic network growth model. Soft-soft modules joined by this interface achieved 600% and 180% mechanical and electrical stretchability, respectively. Soft and rigid modules can also be electrically connected using the above interface. Encapsulation on soft modules with this interface is strongly adhesive with an interfacial toughness of 0.24 N mm-1. As a proof of concept, we use this interface to assemble stretchable devices for in vivo neuromodulation and on-skin electromyography, with high signal quality and mechanical resistance. We expect such a plug-and-play interface to simplify and accelerate the development of on-skin and implantable stretchable devices.

Actions chains and intention understanding in 3- to 6-year-old children.

In intentional behavior, the final goal of an action is crucial in determining the entire sequence of motor acts. Neurons have been described in the inferior parietal lobule of monkeys, which besides encoding a specific motor act (e.g., grasping), have their discharge modulated by the final goal of the intended action (e.g., grasping-to-eat). Many of these "action-constrained" neurons have mirror properties responding to the observation of the motor act they encode, provided that this is embedded in a specific action. Thanks to this mechanism, the observers have an internal copy of the whole action before its execution and may, in this way, understand the agent's intention. The chained organization of motor acts has been demonstrated in schoolchildren. Here, we examined whether this organization is already present in very young children. To this purpose, we recorded EMG from the mylohyoid (MH) muscle in the children aged 3 to 6 y. The results showed that preschoolers, like older children, possess the chained organization of motor acts in execution. Interestingly, in comparison to older children, they have a delayed ability to use this mechanism to infer others' intentions by observation. Finally, we found a significant negative association between the children's age and the activation of the MH muscle during the grasp-to-eat phase in the observation condition. We, tentatively, interpreted it as a sign of an immature control of motor acts.

Trial of Botulinum Toxin for Isolated or Essential Head Tremor.

BACKGROUND: Local injections of botulinum toxin type A have been used to treat essential head tremor but have not been extensively studied in randomized trials. METHODS: In a multicenter, double-blind, randomized trial, we assigned, in a 1:1 ratio, adult patients with essential or isolated head tremor to receive botulinum toxin type A or placebo. Botulinum toxin or placebo was injected under electromyographic guidance into each splenius capitis muscle on the day of randomization (day 0) and during week 12. The primary outcome was improvement by at least 2 points on the Clinical Global Impression of Change (CGI) scale at week 6 after the second injection (week 18 after randomization). The CGI scale was used to record the patient's assessment of the degree of improvement or worsening of head tremor since baseline; scores range from 3 (very much improved) to -3 (very much worse). Secondary outcomes included changes in tremor characteristics from baseline to weeks 6, 12, and 24. RESULTS: A total of 120 patients were enrolled; 3 patients were excluded during screening, and 117 patients were randomly assigned to receive botulinum toxin (62 patients) or placebo (55 patients) and were included in the intention-to-treat analysis. Twelve patients in the botulinum toxin group and 2 patients in the placebo group did not receive injections during week 12. The primary outcome - improvement by at least 2 points on the CGI scale at week 18 - was met by 31% of the patients in the botulinum toxin group as compared with 9% of those in the placebo group (relative risk, 3.37; 95% confidence interval, 1.35 to 8.42; P = 0.009). Analyses of secondary outcomes at 6 and 12 weeks but not at 24 weeks were generally supportive of the primary-outcome analysis. Adverse events occurred in approximately half the patients in the botulinum toxin group and included head and neck pain, posterior cervical weakness, and dysphagia. CONCLUSIONS: Injection of botulinum toxin into each splenius capitis muscle on day 0 and during week 12 was more effective than placebo in reducing the severity of isolated or essential head tremor at 18 weeks but not at 24 weeks, when the effects of injection might be expected to wane, and was associated with adverse events. (Funded by the French Ministry of Health; Btx-HT ClinicalTrials.gov number, NCT02555982.).

Patterns of spinal sensory-motor connectivity prescribed by a dorsoventral positional template.

Sensory-motor circuits in the spinal cord are constructed with a fine specificity that coordinates motor behavior, but the mechanisms that direct sensory connections with their motor neuron partners remain unclear. The dorsoventral settling position of motor pools in the spinal cord is known to match the distal-to-proximal position of their muscle targets in the limb, but the significance of invariant motor neuron positioning is unknown. An analysis of sensory-motor connectivity patterns in FoxP1 mutant mice, where motor neuron position has been scrambled, shows that the final pattern of sensory-motor connections is initiated by the projection of sensory axons to discrete dorsoventral domains of the spinal cord without regard for motor neuron subtype or, indeed, the presence of motor neurons. By implication, the clustering and dorsoventral settling position of motor neuron pools serve as a determinant of the pattern of sensory input specificity and thus motor coordination.

Human Cervical Epidural Spinal Electrogram Topographically Maps Distinct Volitional Movements.

Little is known about the electrophysiologic activity of the intact human spinal cord during volitional movement. We analyzed epidural spinal recordings from a total of five human subjects of both sexes during a variety of upper extremity movements and found that these spinal epidural electrograms contain spectral information distinguishing periods of movement, rest, and sensation. Cervical epidural electrograms also contained spectral changes time-locked with movement. We found that these changes were primarily associated with increased power in the theta (4-8 Hz) band and feature increased theta phase to gamma amplitude coupling, and this increase in theta power can be used to topographically map distinct upper extremity movements onto the cervical spinal cord in accordance with established myotome maps of the upper extremity. Our findings have implications for the development of neurostimulation protocols and devices focused on motor rehabilitation for the upper extremity, and the approach presented here may facilitate spatiotemporal mapping of naturalistic movements.

Erroneous Compensation for Long-Latency Feedback Delays as Origin of Essential Tremor.

Essential tremor (ET), a movement disorder characterized by involuntary oscillations of the limbs during movement, remains to date not well understood. It has been recently suggested that the tremor originates from impaired delay compensation, affecting movement representation and online control. Here we tested this hypothesis directly with 24 ET patients (14 female; 10 male) and 28 neurologically intact (NI) human volunteers (17 female; 11 male) in an upper limb postural perturbation task. After maintaining their hand in a visual target, participants experienced perturbations of unpredictable direction and magnitude and were instructed to counter the perturbation and steer their hand back to the starting position. In comparison with NI volunteers, ET patients' early muscular responses (short and long-latency responses, 20-50 and 50-100 ms, respectively) were preserved or even slightly increased. However, they exhibited perturbation-dependent deficits when stopping and stabilizing their hand in the final target supporting the hypothesis that the tremor was generated by the feedback controller. We show in a computational model that errors in delay compensation accumulating over time produced the same small increase in initial feedback response followed by oscillations that scaled with the perturbation magnitude as observed in ET population. Our experimental results therefore validate the computational hypothesis that inaccurate delay compensation in long-latency pathways could be the origin of the tremor.

The Volitional Control of Individual Motor Units Is Constrained within Low-Dimensional Neural Manifolds by Common Inputs.

The implementation of low-dimensional movement control by the central nervous system has been debated for decades. In this study, we investigated the dimensionality of the control signals received by spinal motor neurons when controlling either the ankle or knee joint torque. We first identified the low-dimensional latent factors underlying motor unit activity during torque-matched isometric contractions in male participants. Subsequently, we evaluated the extent to which motor units could be independently controlled. To this aim, we used an online control paradigm in which participants received the corresponding motor unit firing rates as visual feedback. We identified two main latent factors, regardless of the muscle group (vastus lateralis-medialis and gastrocnemius lateralis-medialis). The motor units of the gastrocnemius lateralis could be controlled largely independently from those of the gastrocnemius medialis during ankle plantarflexion. This dissociation of motor unit activity imposed similar behavior to the motor units that were not displayed in the feedback. Conversely, it was not possible to dissociate the activity of the motor units between the vastus lateralis and medialis muscles during the knee extension tasks. These results demonstrate that the number of latent factors estimated from linear dimensionality reduction algorithms does not necessarily reflect the dimensionality of volitional control of motor units. Overall, individual motor units were never controlled independently of all others but rather belonged to synergistic groups. Together, these findings provide evidence for a low-dimensional control of motor units constrained by common inputs, with notable differences between muscle groups.

Hand-Jaw Coordination as Mice Handle Food Is Organized around Intrinsic Structure-Function Relationships.

Rodent jaws evolved structurally to support dual functionality, for either biting or chewing food. Rodent hands also function dually during food handling, for actively manipulating or statically holding food. How are these oral and manual functions coordinated? We combined electrophysiological recording of muscle activity and kilohertz kinematic tracking to analyze masseter and hand actions as mice of both sexes handled food. Masseter activity was organized into two modes synchronized to hand movement modes. In holding/chewing mode, mastication occurred as rhythmic (∼5 Hz) masseter activity while the hands held food below the mouth. In oromanual/ingestion mode, bites occurred as lower-amplitude aperiodic masseter events that were precisely timed to follow regrips (by ∼200 ms). Thus, jaw and hand movements are flexibly coordinated during food handling: uncoupled in holding/chewing mode and tightly coordinated in oromanual/ingestion mode as regrip-bite sequences. Key features of this coordination were captured in a simple model of hierarchically orchestrated mode-switching and intramode action sequencing. We serendipitously detected an additional masseter-related action, tooth sharpening, identified as bouts of higher-frequency (∼13 Hz) rhythmic masseter activity, which was accompanied by eye displacement, including rhythmic proptosis, attributable to masseter contractions. Collectively, the findings demonstrate how a natural, complex, and goal-oriented activity is organized as an assemblage of distinct modes and complex actions, adapted for the divisions of function arising from anatomical structure. These results reveal intricate, high-speed coordination of disparate effectors and show how natural forms of dexterity can serve as a model for understanding the behavioral neurobiology of multi-body-part coordination.

Thoracoabdominal Wall Motion-Guided Biofeedback Treatment of Abdominal Distention: A Randomized Placebo-Controlled Trial.

BACKGROUND & AIMS: Abdominal distention results from abdominophrenic dyssynergia (ie, diaphragmatic contraction and abdominal wall relaxation) in patients with disorders of gut-brain interaction. This study aimed to validate a simple biofeedback procedure, guided by abdominothoracic wall motion, for treating abdominal distention. METHODS: In this randomized, parallel, placebo-controlled trial, 42 consecutive patients (36 women and 6 men; ages 17-64 years) with meal-triggered visible abdominal distention were recruited. Recordings of abdominal and thoracic wall motion were obtained using inductance plethysmography via adaptable belts. The signal was shown to patients in the biofeedback group, who were taught to mobilize the diaphragm. In contrast, the signal was not shown to the patients in the placebo group, who were given a placebo capsule. Three sessions were performed over a 4-week intervention period, with instructions to perform exercises (biofeedback group) or to take placebo 3 times per day (control group) at home. Outcomes were assessed through response to an offending meal (changes in abdominothoracic electromyographic activity and girth) and clinical symptoms measured using daily scales for 7 days. RESULTS: Patients in the biofeedback group (n = 19) learned to correct abdominophrenic dyssynergia triggered by the offending meal (intercostal activity decreased by a mean ± SE of 82% ± 10%, anterior wall activity increased by a mean ± SE of 97% ± 6%, and increase in girth was a mean ± SE of 108% ± 4% smaller) and experienced improved clinical symptoms (abdominal distention scores decreased by a mean ± SE of 66% ± 5%). These effects were not observed in the placebo group (all, P < .002). CONCLUSIONS: Abdominothoracic wall movements serve as an effective biofeedback signal for correcting abdominophrenic dyssynergia and abdominal distention in patients with disorders of gut-brain interaction. ClincialTrials.gov, Number: NCT04043208.

NeuroMotion: Open-source platform with neuromechanical and deep network modules to generate surface EMG signals during voluntary movement.

Neuromechanical studies investigate how the nervous system interacts with the musculoskeletal (MSK) system to generate volitional movements. Such studies have been supported by simulation models that provide insights into variables that cannot be measured experimentally and allow a large number of conditions to be tested before the experimental analysis. However, current simulation models of electromyography (EMG), a core physiological signal in neuromechanical analyses, remain either limited in accuracy and conditions or are computationally heavy to apply. Here, we provide a computational platform to enable future work to overcome these limitations by presenting NeuroMotion, an open-source simulator that can modularly test a variety of approaches to the full-spectrum synthesis of EMG signals during voluntary movements. We demonstrate NeuroMotion using three sample modules. The first module is an upper-limb MSK model with OpenSim API to estimate the muscle fibre lengths and muscle activations during movements. The second module is BioMime, a deep neural network-based EMG generator that receives nonstationary physiological parameter inputs, like the afore-estimated muscle fibre lengths, and efficiently outputs motor unit action potentials (MUAPs). The third module is a motor unit pool model that transforms the muscle activations into discharge timings of motor units. The discharge timings are convolved with the output of BioMime to simulate EMG signals during the movement. We first show how MUAP waveforms change during different levels of physiological parameter variations and different movements. We then show that the synthetic EMG signals during two-degree-of-freedom hand and wrist movements can be used to augment experimental data for regressing joint angles. Ridge regressors trained on the synthetic dataset were directly used to predict joint angles from experimental data. In this way, NeuroMotion was able to generate full-spectrum EMG for the first use-case of human forearm electrophysiology during voluntary hand, wrist, and forearm movements. All intermediate variables are available, which allows the user to study cause-effect relationships in the complex neuromechanical system, fast iterate algorithms before collecting experimental data, and validate algorithms that estimate non-measurable parameters in experiments. We expect this modular platform will enable validation of generative EMG models, complement experimental approaches and empower neuromechanical research.

De novo sensorimotor learning through reuse of movement components.

From tying one's shoelaces to driving a car, complex skills involving the coordination of multiple muscles are common in everyday life; yet relatively little is known about how these skills are learned. Recent studies have shown that new sensorimotor skills involving re-mapping familiar body movements to unfamiliar outputs cannot be learned by adjusting pre-existing controllers, and that new task-specific controllers must instead be learned "de novo". To date, however, few studies have investigated de novo learning in scenarios requiring continuous and coordinated control of relatively unpractised body movements. In this study, we used a myoelectric interface to investigate how a novel controller is learned when the task involves an unpractised combination of relatively untrained continuous muscle contractions. Over five sessions on five consecutive days, participants learned to trace a series of trajectories using a computer cursor controlled by the activation of two muscles. The timing of the generated cursor trajectory and its shape relative to the target improved for conditions trained with post-trial visual feedback. Improvements in timing transferred to all untrained conditions, but improvements in shape transferred less robustly to untrained conditions requiring the trained order of muscle activation. All muscle outputs in the final session could already be generated during the first session, suggesting that participants learned the new task by improving the selection of existing motor commands. These results suggest that the novel controllers acquired during de novo learning can, in some circumstances, be constructed from components of existing controllers.

Precise cortical contributions to sensorimotor feedback control during reactive balance.

The role of the cortex in shaping automatic whole-body motor behaviors such as walking and balance is poorly understood. Gait and balance are typically mediated through subcortical circuits, with the cortex becoming engaged as needed on an individual basis by task difficulty and complexity. However, we lack a mechanistic understanding of how increased cortical contribution to whole-body movements shapes motor output. Here we use reactive balance recovery as a paradigm to identify relationships between hierarchical control mechanisms and their engagement across balance tasks of increasing difficulty in young adults. We hypothesize that parallel sensorimotor feedback loops engaging subcortical and cortical circuits contribute to balance-correcting muscle activity, and that the involvement of cortical circuits increases with balance challenge. We decomposed balance-correcting muscle activity based on hypothesized subcortically- and cortically-mediated feedback components driven by similar sensory information, but with different loop delays. The initial balance-correcting muscle activity was engaged at all levels of balance difficulty. Its onset latency was consistent with subcortical sensorimotor loops observed in the lower limb. An even later, presumed, cortically-mediated burst of muscle activity became additionally engaged as balance task difficulty increased, at latencies consistent with longer transcortical sensorimotor loops. We further demonstrate that evoked cortical activity in central midline areas measured using electroencephalography (EEG) can be explained by a similar sensory transformation as muscle activity but at a delay consistent with its role in a transcortical loop driving later cortical contributions to balance-correcting muscle activity. These results demonstrate that a neuromechanical model of muscle activity can be used to infer cortical contributions to muscle activity without recording brain activity. Our model may provide a useful framework for evaluating changes in cortical contributions to balance that are associated with falls in older adults and in neurological disorders such as Parkinson's disease.

Combined translational and rotational perturbations of standing balance reveal contributions of reduced reciprocal inhibition to balance impairments in children with cerebral palsy.

Balance impairments are common in cerebral palsy. When balance is perturbed by backward support surface translations, children with cerebral palsy have increased co-activation of the plantar flexors and tibialis anterior muscle as compared to typically developing children. However, it is unclear whether increased muscle co-activation is a compensation strategy to improve balance control or is a consequence of reduced reciprocal inhibition. During translational perturbations, increased joint stiffness due to co-activation might aid balance control by resisting movement of the body with respect to the feet. In contrast, during rotational perturbations, increased joint stiffness will hinder balance control as it couples body to platform rotation. Therefore, we expect increased muscle co-activation in response to rotational perturbations if co-activation is caused by reduced reciprocal inhibition but not if it is merely a compensation strategy. We perturbed standing balance by combined backward translational and toe-up rotational perturbations in 20 children with cerebral palsy and 20 typically developing children. Perturbations induced forward followed by backward movement of the center of mass. We evaluated reactive muscle activity and the relation between center of mass movement and reactive muscle activity using a linear feedback model based on center of mass kinematics. In typically developing children, perturbations induced plantar flexor balance correcting muscle activity followed by tibialis anterior balance correcting muscle activity, which was driven by center of mass movement. In children with cerebral palsy, the switch from plantar flexor to tibialis anterior activity was less pronounced than in typically developing children due to increased muscle co-activation of the plantar flexors and tibialis anterior throughout the response. Our results thus suggest that a reduction in reciprocal inhibition causes muscle co-activation in reactive standing balance in children with cerebral palsy.

Insights into muscle metabolic energetics: Modelling muscle-tendon mechanics and metabolic rates during walking across speeds.

The metabolic energy rate of individual muscles is impossible to measure without invasive procedures. Prior studies have produced models to predict metabolic rates based on experimental observations of isolated muscle contraction from various species. Such models can provide reliable predictions of metabolic rates in humans if muscle properties and control are accurately modeled. This study aimed to examine how muscle-tendon model individualization and metabolic energy models influenced estimation of muscle-tendon states and time-series metabolic rates, to evaluate the agreement with empirical data, and to provide predictions of the metabolic rate of muscle groups and gait phases across walking speeds. Three-dimensional musculoskeletal simulations with prescribed kinematics and dynamics were performed. An optimal control formulation was used to compute muscle-tendon states with four levels of individualization, ranging from a scaled generic model and muscle controls based on minimal activations, inclusion of calibrated muscle passive forces, personalization of Achilles and quadriceps tendon stiffnesses, to finally informing muscle controls with electromyography. We computed metabolic rates based on existing models. Simulations with calibrated passive forces and personalized tendon stiffness most accurately estimate muscle excitations and fiber lengths. Interestingly, the inclusion of electromyography did not improve our estimates. The whole-body average metabolic cost was better estimated with a subset of metabolic energy models. We estimated metabolic rate peaks near early stance, pre-swing, and initial swing at all walking speeds. Plantarflexors accounted for the highest cost among muscle groups at the preferred speed and were similar to the cost of hip adductors and abductors combined. Also, the swing phase accounted for slightly more than one-quarter of the total cost in a gait cycle, and its relative cost decreased with walking speed. Our prediction might inform the design of assistive devices and rehabilitation treatment. The code and experimental data are available online.

Distinct neuronal circuits mediate cortical hyperexcitability in amyotrophic lateral sclerosis.

Cortical hyperexcitability is an important pathophysiological mechanism in amyotrophic lateral sclerosis (ALS), reflecting a complex interaction of inhibitory and facilitatory interneuronal processes that evolves in the degenerating brain. The advances in physiological techniques have made it possible to interrogate progressive changes in the motor cortex. Specifically, the direction of transcranial magnetic stimulation (TMS) stimulus within the primary motor cortex can be utilized to influence descending corticospinal volleys and to thereby provide information about distinct interneuronal circuits. Cortical motor function and cognition was assessed in 29 ALS patients with results compared to healthy volunteers. Cortical dysfunction was assessed using threshold-tracking TMS to explore alterations in short interval intracortical inhibition (SICI), short interval intracortical facilitation (SICF), the index of excitation and stimulus response curves using a figure-of-eight coil with the coil oriented relative to the primary motor cortex in a posterior-anterior, lateral-medial and anterior-posterior direction. Mean SICI, between interstimulus interval of 1-7 ms, was significantly reduced in ALS patients compared to healthy controls when assessed with the coil oriented in posterior-anterior (P = 0.044) and lateral-medial (P = 0.005) but not the anterior-posterior (P = 0.08) directions. A significant correlation between mean SICI oriented in a posterior-anterior direction and the total Edinburgh Cognitive and Behavioural ALS Screen score (Rho = 0.389, P = 0.037) was evident. In addition, the mean SICF, between interstimulus interval 1-5 ms, was significantly increased in ALS patients when recorded with TMS coil oriented in posterior-anterior (P = 0.035) and lateral-medial (P < 0.001) directions. In contrast, SICF recorded with TMS coil oriented in the anterior-posterior direction was comparable between ALS and controls (P = 0.482). The index of excitation was significantly increased in ALS patients when recorded with the TMS coil oriented in posterior-anterior (P = 0.041) and lateral-medial (P = 0.003) directions. In ALS patients, a significant increase in the stimulus response curve gradient was evident compared to controls when recorded with TMS coil oriented in posterior-anterior (P < 0.001), lateral-medial (P < 0.001) and anterior-posterior (P = 0.002) directions. The present study has established that dysfunction of distinct interneuronal circuits mediates the development of cortical hyperexcitability in ALS. Specifically, complex interplay between inhibitory circuits and facilitatory interneuronal populations, that are preferentially activated by stimulation in posterior-to-anterior or lateral-to-medial directions, promotes cortical hyperexcitability in ALS. Mechanisms that underlie dysfunction of these specific cortical neuronal circuits will enhance understanding of the pathophysiological processes in ALS, with the potential to uncover focussed therapeutic targets.

A direct spinal cord-computer interface enables the control of the paralysed hand in spinal cord injury.

Paralysis of the muscles controlling the hand dramatically limits the quality of life for individuals living with spinal cord injury (SCI). Here, with a non-invasive neural interface, we demonstrate that eight motor complete SCI individuals (C5-C6) are still able to task-modulate in real-time the activity of populations of spinal motor neurons with residual neural pathways. In all SCI participants tested, we identified groups of motor units under voluntary control that encoded various hand movements. The motor unit discharges were mapped into more than 10 degrees of freedom, ranging from grasping to individual hand-digit flexion and extension. We then mapped the neural dynamics into a real-time controlled virtual hand. The SCI participants were able to match the cue hand posture by proportionally controlling four degrees of freedom (opening and closing the hand and index flexion/extension). These results demonstrate that wearable muscle sensors provide access to spared motor neurons that are fully under voluntary control in complete cervical SCI individuals. This non-invasive neural interface allows the investigation of motor neuron changes after the injury and has the potential to promote movement restoration when integrated with assistive devices.

Dopamine and deep brain stimulation accelerate the neural dynamics of volitional action in Parkinson's disease.

The ability to initiate volitional action is fundamental to human behaviour. Loss of dopaminergic neurons in Parkinson's disease is associated with impaired action initiation, also termed akinesia. Both dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown. An important question is whether dopamine and DBS facilitate de novo build-up of neural dynamics for motor execution or accelerate existing cortical movement initiation signals through shared modulatory circuit effects. Answering these questions can provide the foundation for new closed-loop neurotherapies with adaptive DBS, but the objectification of neural processing delays prior to performance of volitional action remains a significant challenge. To overcome this challenge, we studied readiness potentials and trained brain signal decoders on invasive neurophysiology signals in 25 DBS patients (12 female) with Parkinson's disease during performance of self-initiated movements. Combined sensorimotor cortex electrocorticography and subthalamic local field potential recordings were performed OFF therapy (n = 22), ON dopaminergic medication (n = 18) and on subthalamic deep brain stimulation (n = 8). This allowed us to compare their therapeutic effects on neural latencies between the earliest cortical representation of movement intention as decoded by linear discriminant analysis classifiers and onset of muscle activation recorded with electromyography. In the hypodopaminergic OFF state, we observed long latencies between motor intention and motor execution for readiness potentials and machine learning classifications. Both, dopamine and DBS significantly shortened these latencies, hinting towards a shared therapeutic mechanism for alleviation of akinesia. To investigate this further, we analysed directional cortico-subthalamic oscillatory communication with multivariate granger causality. Strikingly, we found that both therapies independently shifted cortico-subthalamic oscillatory information flow from antikinetic beta (13-35 Hz) to prokinetic theta (4-10 Hz) rhythms, which was correlated with latencies in motor execution. Our study reveals a shared brain network modulation pattern of dopamine and DBS that may underlie the acceleration of neural dynamics for augmentation of movement initiation in Parkinson's disease. Instead of producing or increasing preparatory brain signals, both therapies modulate oscillatory communication. These insights provide a link between the pathophysiology of akinesia and its' therapeutic alleviation with oscillatory network changes in other non-motor and motor domains, e.g. related to hyperkinesia or effort and reward perception. In the future, our study may inspire the development of clinical brain computer interfaces based on brain signal decoders to provide temporally precise support for action initiation in patients with brain disorders.

Low blood concentration of alcohol enhances activity related to stopping failure in the right inferior frontal cortex.

This study investigated the effects of low doses of alcohol, which are acceptable for driving a car, on inhibitory control and neural processing using the stop-signal task (SST) in 17 healthy right-handed social drinkers. The study employed simultaneous functional magnetic resonance imaging and electromyography (EMG) recordings to assess behavioral and neural responses under conditions of low-dose alcohol (breath-alcohol concentration of 0.15 mg/L) and placebo. The results demonstrated that even a small amount of alcohol consumption prolonged Go reaction times in the SST and modified stopping behavior, as evidenced by a decrease in the frequency and magnitude of partial response EMG that did not result in button pressing during successful inhibitory control. Furthermore, alcohol intake enhanced neural activity during failed inhibitory responses in the right inferior frontal cortex, suggesting its potential role in behavioral adaptation following stop-signal failure. These findings suggest that even low levels of alcohol consumption within legal driving limits can greatly impact both the cognitive performance and brain activity involved in inhibiting responses. This research provides important evidence on the neurobehavioral effects of low-dose alcohol consumption, with implications for understanding the biological basis of impaired motor control and decision-making and potentially informing legal guidelines on alcohol consumption.

Corticocortical and corticomuscular connectivity dynamics in standing posture: electroencephalography study.

Cortical mechanism is necessary for human standing control. Previous research has demonstrated that cortical oscillations and corticospinal excitability respond flexibly to postural demands. However, it is unclear how corticocortical and corticomuscular connectivity changes dynamically during standing with spontaneous postural sway and over time. This study investigated the dynamics of sway- and time-varying connectivity using electroencephalography and electromyography. Electroencephalography and electromyography were recorded in sitting position and 3 standing postures with varying base-of-support: normal standing, one-leg standing, and standing on a piece of wood. For sway-varying connectivity, corticomuscular connectivity was calculated based on the timing of peak velocity in anteroposterior sway. For time-varying connectivity, corticocortical connectivity was measured using the sliding-window approach. This study found that corticomuscular connectivity was strengthened at the peak velocity of postural sway in the γ- and ß-frequency bands. For time-varying corticocortical connectivity, the θ-connectivity in all time-epoch was classified into 7 clusters including posture-relevant component. In one of the 7 clusters, strong connectivity pairs were concentrated in the mid-central region, and the proportion of epochs under narrow-base standing conditions was significantly higher, indicating a functional role for posture balance. These findings shed light on the connectivity dynamics and cortical oscillation that govern standing balance.