Prediction of forelimb muscle activities and movement phases using corticospinal signals in the rat

The targeted population for this project is primarily patients with high level spinal cord injury (SCI) and individuals with motor neuron diseases (MND). In both SCI and MND cases motor control is interrupted due to lack of communication between the brain and the musculature, although both sides are otherwise functional. The approach in this project is to use neural engineering techniques to restore the motor function that was lost because of an injury or disease. Brain-computer interfaces (BCIs) attempt to extract the volitional signals from the cortex when the brain\u27s normal outputs to the musculoskeletal system are impaired. However, BCIs that depend on the cortical activities suffer from two main impediments that are intrinsic to the BCI approach itself; firstly, under-sampling of the volitional information due to limited number of recording channels, and secondly, the long-term instability of the neuronal firings that make it difficult to track movement parameters, such as hand kinematics. As an alternative approach, a spinal cord computer interface (SCCI) can address both obstacles by providing means to access neural signals from a relatively smaller yet denser implant area in order to extract low-level movement parameters, such as muscle electromyography (EMG) signals, for prolonged signal stability. Since the descending fibers of the spinal cord influence the lower motor neurons that directly innervate the skeletal muscles, decoding the information in these fibers can provide a way to establish a robust relationship between the neural control signals and the output parameter, that is the EMG signal. The axons carrying the cortical information through the spinal cord are tightly bundled together in the descending tracts that eventually synapse with the inter-neurons and alpha motor neurons located in the spinal grey matter. The corticospinal tract (CST) is one of the descending tracts that carry the forelimb volitional information. In this study, the CST signals are recorded in rats that are implanted with custom-designed flexible multi-electrode arrays (MEAs). The power spectral density of the CST signals during the movement is notably higher than those observed during resting and anesthesia. The average inter-channel coherences up to 1.5 kHz are significantly higher for reach-to-pull task compared to face grooming and resting states, suggesting the presence of volitional information in the recorded CST signals. The results show that the CST signals can be segregated into two or three different classes using the forelimb movement components as guidance criteria with 97% and 71% accuracies, respectively. Predictions with correlation coefficients as high as 0.81 for the biceps EMG are achieved in individual sessions, although the average prediction accuracies vary considerably among rats. These results support the feasibility of an EMG-based Spinal Cord Computer Interface for patients with high level of paralysis

Sensorimotor content of multi-unit activity in the paramedian lobule of the cerebellum

Based on Center for Disease Control and Prevention report 2016, around 39.5 million people in the United States suffer from motor disabilities. These disabilities are due to traumatic conditions like traumatic brain injury (TBI), neurological diseases such as amyotrophic lateral sclerosis (ALS), or congenital conditions. One of the approaches for restoring the lost motor function is to extract the volitional information from the central nervous system (CNS) and control a mechanical device that can replace the function of a paralyzed limb through systems called Brain-Computer Interfaces (BCI). One of the major challenges being faced in BCIs and also in general neural recording field is the limitations of the microelectrodes. In this study, as the first aim, a custom-made micro-electrode array (MEA) using carbon fibers is developed. After ex vivo testing, they are implanted into the paramedian lobule (PML) of the rat cerebellum to record the multi-unit activity from its cortex. Following animal termination, tissue samples are examined with histological techniques for the assessment of tissue damage caused by the electrodes. Another challenge in the BCI field is extracting the control information regarding the intended motor function from the CNS. The way the cerebellar cortex encodes sensorimotor information and contributes to motor coordination has been a topic of discussion for decades. Recent studies have revealed high correlations between Purkinje cell simple spikes and the forelimb kinematics in experimental animals. However, tracking single spike activity in long-term implants with multi-channel electrodes has well-known challenges. Therefore, as the second aim of this study, the correlation of multi-unit neural signals from the paramedian lobule (PML) of the cerebellar cortex to the forelimb muscle activities (EMG) in rats during behavior was investigated. Linear regression is performed to predict the EMG signal envelopes using the cerebellar activity for various time shifts of the data (±10, ±50, ±100, and ±200 ms) to determine if the neural signals are primarily motor or sensory. The highest correlations (~0.6 on average) between neural and EMG envelopes are observed when the EMG signals are either shifted only about ±10 ms or not shifted at all with respect to the neural signals. There were however still correlations above the chance level for larger shifts in time. The results suggest that PML cortex contains both motor and sensory information in relation to the forelimb activity, and also that the extraction of motor information is feasible from multi-unit neural recordings from the cerebellar cortex. Increased prediction success was observed in reaching and retrieval phases compared to grasping phase when predictions were tested on three phases of the behavior separately. When EMG and neural signal envelopes were clustered, they showed patterns of surges of activity in all three phases. The neural signals showed higher activity in the reaching phase. The 300-1000Hz components of neural signals contributed to the predictions more than the other frequency bands. The results of this study supports the feasibility of a BCI based on MUA extracted from the cerebellar cortex using MEAs

Primate Motor Cortex: Individual and Ensemble Neuron-Muscle Output Relationships

The specific aims of this study were to: 1) investigate the encoding of forelimb muscle activity timing and magnitude by corticomotoneuronal (CM) cells, 2) test the stability of primary motor cortex (M1) output to forelimb muscles under different task conditions, and 3) characterize input/output relationships associated with different intracortical microstimulation (ICMS) methods. Neuronal recording and stimulating methods were used in combination with electromyographic (EMG) recording of 24 forelimb muscles to investigate questions related to M1 control of forelimb muscles. Target muscles of CM neurons were identified by the presence of post-spike facilitation (PSpF) in spike-triggered averages (SpTA) of EMG activity. Post-stimulus output effects were obtained with three different ICMS methods; stimulus-triggered averaging (StTA) of EMG activity, repetitive short duration ICMS (RS-ICMS) and repetitive long duration ICMS (RL-ICMS). Our results demonstrate that CM cells exhibit strong and consistent coactivation with their target muscles. Further, the summed activity of populations of identified CM cells was a better predictor of the common muscle's EMG activity than individual neurons. Our data support the view that M1 output encodes muscle activation related parameters. Regarding stability, we found that output effects in StTAs of EMG activity are remarkably stable and largely independent of changes in joint angle, or limb posture. This further validates the use of StTA for mapping and other studies of cortical motor output. RL-ICMS evoked EMG activity was also stable in sign, strength and distribution independent of starting position of the hand. Our data support a model in which RL-ICMS produces sustained co-activation of multiple agonist and antagonist muscles which then generates joint movements according to the length-tension properties of the muscles until an equilibrium position is achieved. Further, RL-ICMS evoked EMG activity did not sum with the existing level of activity; rather the stimulus forced a new EMG level that was independent of existing voluntary background. Our results further show that post-stimulus output effects on muscle activity obtained with StTA and RS-ICMS closely resemble one another. However, RL-ICMS produces effects that can deviate substantially from those observed with StTA

Cortico-spinal modularity in the parieto-frontal system: a new perspective on action control

: Classical neurophysiology suggests that the motor cortex (MI) has a unique role in action control. In contrast, this review presents evidence for multiple parieto-frontal spinal command modules that can bypass MI. Five observations support this modular perspective: (i) the statistics of cortical connectivity demonstrate functionally-related clusters of cortical areas, defining functional modules in the premotor, cingulate, and parietal cortices; (ii) different corticospinal pathways originate from the above areas, each with a distinct range of conduction velocities; (iii) the activation time of each module varies depending on task, and different modules can be activated simultaneously; (iv) a modular architecture with direct motor output is faster and less metabolically expensive than an architecture that relies on MI, given the slow connections between MI and other cortical areas; (v) lesions of the areas composing parieto-frontal modules have different effects from lesions of MI. Here we provide examples of six cortico-spinal modules and functions they subserve: module 1) arm reaching, tool use and object construction; module 2) spatial navigation and locomotion; module 3) grasping and observation of hand and mouth actions; module 4) action initiation, motor sequences, time encoding; module 5) conditional motor association and learning, action plan switching and action inhibition; module 6) planning defensive actions. These modules can serve as a library of tools to be recombined when faced with novel tasks, and MI might serve as a recombinatory hub. In conclusion, the availability of locally-stored information and multiple outflow paths supports the physiological plausibility of the proposed modular perspective

Neuroprosthetic Technologies to Evaluate and Train Leg Motor Control in Neurologically Impaired Individuals

Spinal cord injury (SCI) disrupts many essential sensorimotor and autonomic functions. Consequently, individuals with SCI can face decades with permanent disabilities. Advances in clinical management have decreased morbidity, but no clinical trial has yet demonstrated the efficacy of a repair strategy. In the past decade, Courtine lab has developed neurotechnologies that restored volitional control of locomotion in animal models of SCI. The intervention acts over two-time windows. In the short-term, the delivery of epidural electrical stimulation (EES) targeting the posterior lumbar roots with timing that mimics the natural activation of the spinal cord enables stepping in otherwise paralyzed rats. In the long-term, this targeted EES with intensive robot-assisted overground training triggers a reorganization of descending pathways that reestablished voluntary control of the paralyzed legs, even without EES. These results in animal models encouraged the transfer of these technologies and concepts to clinical applications. My contribution to this translational research program forms the core of my thesis. The first section presents a software that I developed in order to enable a comprehensive yet semi-automated analysis of kinematics and muscle activity underlying locomotor functions in humans. This toolbox allows to evaluate gait features of people with neuromotor deficits, quantify locomotor performance compared to healthy people or to monitor changes in different experimental conditions or over the time course of interventions, and automatically generate comprehensive gait reports directly understandable by scientists and clinicians. The second section introduces a paradigm shift in robotic postural assistance: the gravity-assist. We demonstrated the detrimental impact of high levels of body weight support on gravity-dependent interactions during standing and walking. We developed a gravity-assist algorithm that fine-tunes the forward and upward body weight support to reestablish these interactions based on each patientâs residual capacities. We validated the personalized gravity-assist in 30 individuals with SCI or stroke. Compared to other conditions of support, the gravity-assist enabled all the patients to improve their locomotion performance. This platform establishes refined conditions to empower and train overground locomotion in a safe yet ecological environment. The third section reports the development of targeted EES in patients with chronic SCI, and the impact of an intensive 5-month rehabilitation with gravity-assist and targeted EES on the recovery of motor functions. The key findings can be summarized as follows: We established procedures to configure targeted EES that immediately enabled voluntary control of weak or paralyzed muscles; Targeted EES boosts the residual supraspinal inputs to the lumbar spinal cord, enabling all the patients to adapt their gait to specific tasks; Locomotor performance improved during the rehabilitation; All the patients regained voluntary control over previously paralyzed muscles without EES. These combined results establish the proof-of-concept on the therapeutic potential of targeted EES and intensive, robot-assisted rehabilitation to restore locomotion after SCI. Together with similar results obtained in the US in patients with severe SCI, our findings are establishing a pathway towards the development of a viable treatment to support motor functions and improve recovery after SCI

Programming the cerebellum

It is argued that large-scale neural network simulations of cerebellar cortex and nuclei, based on realistic compartmental models of me major cell populations, are necessary before the problem of motor learning in the cerebellum can be solved, [HOUK et al.; SIMPSON et al.

Epidemiology of Injury in English Women's Super league Football: A Cohort Study

INTRODUCTION: The epidemiology of injury in male professional football has been well documented (Ekstrand, Hägglund, & Waldén, 2011) and used as a basis to understand injury trends for a number of years. The prevalence and incidence of injuries occurring in womens super league football is unknown. The aim of this study is to estimate the prevalence and incidence of injury in an English Super League Women’s Football squad. METHODS: Following ethical approval from Leeds Beckett University, players (n = 25) signed to a Women’s Super League Football club provided written informed consent to complete a self-administered injury survey. Measures of exposure, injury and performance over a 12-month period was gathered. Participants were classified as injured if they reported a football injury that required medical attention or withdrawal from participation for one day or more. Injuries were categorised as either traumatic or overuse and whether the injury was a new injury and/or re-injury of the same anatomical site RESULTS: 43 injuries, including re-injury were reported by the 25 participants providing a clinical incidence of 1.72 injuries per player. Total incidence of injury was 10.8/1000 h (95% CI: 7.5 to 14.03). Participants were at higher risk of injury during a match compared with training (32.4 (95% CI: 15.6 to 48.4) vs 8.0 (95% CI: 5.0 to 10.85)/1000 hours, p 28 days) of which there were three non-contact anterior cruciate ligament (ACL) injuries. The epidemiological incidence proportion was 0.80 (95% CI: 0.64 to 0.95) and the average probability that any player on this team will sustain at least one injury was 80.0% (95% CI: 64.3% to 95.6%) CONCLUSION: This is the first report capturing exposure and injury incidence by anatomical site from a cohort of English players and is comparable to that found in Europe (6.3/1000 h (95% CI 5.4 to 7.36) Larruskain et al 2017). The number of ACL injuries highlights a potential injury burden for a squad of this size. Multi-site prospective investigations into the incidence and prevalence of injury in women’s football are require