An investigation into motor pools and their applicability to a biologically inspired model of ballistic voluntary motor action

This study investigates the properties of motor pools in the human motor control system. The simulations carried out as part of this study used two biologically inspired neuronal models to simulate networks with properties similar to those observed in the human motor system (Burke, 1991). The Synchronous neuronal model developed as part of this study explicitly models the input/output spike train and frequency relationship of each neuron. The motor pool simulations were carried out using the INSIGHT TOO simulation software developed as part of this study. INSIGHT TOO is a flexible neural design tool that allows the visual interactive design of network connectivity and has the power of a node specification language similar to that of BASIC that allows multi-layer, multi-model networks to be simulated. The simulations have shown that the motor pools are capable of reproducing commonly observed physiological properties during normal voluntary reaching movements. As a result of these findings a theoretical model of ballistic voluntary motor action was proposed called the Recruitment Model. The Recruitment model utilises the "recruitment" principle known to exist in motor pools and applies this distributed processing methodology to the higher levels of motor action to explain how complex structures similar to the human skeletal system might be controlled. A simple version of the Recruitment Model is simulated showing an animation of a running "stick man". This simulation demonstrates some of the principles necessary to solve problems relating to synergy formation

Impaired reflex sensitivity cause and effect

When a voluntarily contracting human muscle is stretched its surface reflex electromyographic response has both short-latency (M1) and long-latency (M2) components. The M1 component occurs at a latency compatible with monosynaptic reflex activation. The long-latency component results from stimulation of skin and other subcutaneous receptors. In the initial experiment, using the first dorsal interosseous muscle (FDI) of the hand, the reflex sensitivity in normal human subjects was studied by comparing the various components of the electromyographic response generated by briefly stretching the voluntarily contracting muscle in subjects of various ages. It was found that age-related changes occur in the reflex response of human subjects. Although it is already known that the reflex response in human muscle slows with age, the result of the experiment showed that the size of that reflex response becomes smaller. The evidence suggests an impaired reflex sensitivity in older people which could be reflected in other motor control systems within the body. A detailed investigation was then undertaken to discover the causes of this change. Although the reflex response (M1) was found to alter with age the M2 component did not. This would seem to rule out neuromuscular block (NMB). NMB as a cause of the change was investigated and was found not to occur in the paradigm employed in this investigation. Possible changes in the mechanical properties of muscles and joints were looked for in a series of experiments using an accelerometer. No changes large enough to account for the reflex impairment could be found. In a further series of experiments the effects of fatigue and the effects of training on the electrical response of the FDI were studied. In a final series of experiments the changes with age, in the effects of coffee upon blood pressure were investigated.<p

Understanding motor control in humans to improve rehabilitation robots

Recent reviews highlighted the limited results of robotic rehabilitation and the low quality of evidences in this field. Despite the worldwide presence of several robotic infrastructures, there is still a lack of knowledge about the capabilities of robotic training effect on the neural control of movement. To fill this gap, a step back to motor neuroscience is needed: the understanding how the brain works in the generation of movements, how it adapts to changes and how it acquires new motor skills is fundamental. This is the rationale behind my PhD project and the contents of this thesis: all the studies included in fact examined changes in motor control due to different destabilizing conditions, ranging from external perturbations, to self-generated disturbances, to pathological conditions. Data on healthy and impaired adults have been collected and quantitative and objective information about kinematics, dynamics, performance and learning were obtained for the investigation of motor control and skill learning. Results on subjects with cervical dystonia show how important assessment is: possibly adequate treatments are missing because the physiological and pathological mechanisms underlying sensorimotor control are not routinely addressed in clinical practice. These results showed how sensory function is crucial for motor control. The relevance of proprioception in motor control and learning is evident also in a second study. This study, performed on healthy subjects, showed that stiffness control is associated with worse robustness to external perturbations and worse learning, which can be attributed to the lower sensitiveness while moving or co-activating. On the other hand, we found that the combination of higher reliance on proprioception with \u201cdisturbance training\u201d is able to lead to a better learning and better robustness. This is in line with recent findings showing that variability may facilitate learning and thus can be exploited for sensorimotor recovery. Based on these results, in a third study, we asked participants to use the more robust and efficient strategy in order to investigate the control policies used to reject disturbances. We found that control is non-linear and we associated this non-linearity with intermittent control. As the name says, intermittent control is characterized by open loop intervals, in which movements are not actively controlled. We exploited the intermittent control paradigm for other two modeling studies. In these studies we have shown how robust is this model, evaluating it in two complex situations, the coordination of two joints for postural balance and the coordination of two different balancing tasks. It is an intriguing issue, to be addressed in future studies, to consider how learning affects intermittency and how this can be exploited to enhance learning or recovery. The approach, that can exploit the results of this thesis, is the computational neurorehabilitation, which mathematically models the mechanisms underlying the rehabilitation process, with the aim of optimizing the individual treatment of patients. Integrating models of sensorimotor control during robotic neurorehabilitation, might lead to robots that are fully adaptable to the level of impairment of the patient and able to change their behavior accordingly to the patient\u2019s intention. This is one of the goals for the development of rehabilitation robotics and in particular of Wristbot, our robot for wrist rehabilitation: combining proper assessment and training protocols, based on motor control paradigms, will maximize robotic rehabilitation effects

An electrophysiological and morphometric study of the effect of different methods of surgical repair in motor and mixed nerve: a comparison of the repair of the facial nerve and the median nerve in a large animal

The outcome of peripheral nerve injuries has been poorly documented. This is due to the heterogeneity of the injuries, the variety of surgeons from different surgical specialities performing the repairs and a lack of objective follow up. Anecdotal reports have suggested that injuries to purely motor nerves have a better outcome than those affecting mixed nerves.This aims of this work were to document the natural history of nerve injuries and their repair under controlled conditions in order to ascertain the outcome of different types of nerve injury and to compare the outcome of the same injuries in motor nerves and mixed nerves. A further objective was to determine which investigations would be useful in the assessment and follow up of peripheral nerve injuries both as predictors of outcome and in clinical practice.The sheep model was selected as its peripheral nerves are a similar size, and behave in a similar manner to, human peripheral nerves. A set of six standardised nerve injuries (normal control, neurapraxia, axonotmesis, neurotmesis and suture repair, neurotmesis and entubulation, and nerve graft) was created in both the facial (motor) nerve and the median (mixed) nerve. The function of the nerves and their target muscles was assessed using nerve conduction studies (maximum conduction velocity, distribution of conduction velocities, refractory period), single-fibre electromyography (jitter), target muscle tension and mass, and nerve fibre morphometry.In the carefully controlled conditions of the experiments, for both nerves the transection injuries had a poorer outcome than the non-transection injuries. This effect was more marked in the median nerve than in the facial nerve suggesting that the type of nerve affected the outcome of injury. Maximum conduction velocity was determined to be the most useful test for use in the clinical management of nerve injuries. Distribution of conduction velocities, a nerve conduction test based on collision theory, may be too sensitive to be of use in the management of mechanical nerve injury but may have a valuable role in the assessment of more subtle conditions such as neuropathies and Bell's palsy. Nerve fibre morphometry discriminated between the different injuries and remains a useful tool in a research setting

Learning Contrast-Invariant Cancellation of Redundant Signals in Neural Systems

Cancellation of redundant information is a highly desirable feature of sensory systems, since it would potentially lead to a more efficient detection of novel information. However, biologically plausible mechanisms responsible for such selective cancellation, and especially those robust to realistic variations in the intensity of the redundant signals, are mostly unknown. In this work, we study, via in vivo experimental recordings and computational models, the behavior of a cerebellar-like circuit in the weakly electric fish which is known to perform cancellation of redundant stimuli. We experimentally observe contrast invariance in the cancellation of spatially and temporally redundant stimuli in such a system. Our model, which incorporates heterogeneously-delayed feedback, bursting dynamics and burst-induced STDP, is in agreement with our in vivo observations. In addition, the model gives insight on the activity of granule cells and parallel fibers involved in the feedback pathway, and provides a strong prediction on the parallel fiber potentiation time scale. Finally, our model predicts the existence of an optimal learning contrast around 15% contrast levels, which are commonly experienced by interacting fish

Cholinergic signalling pathways in the superficial layers of the human bladder; comparing health, detrusor overactivity and the effect of Botulinum Toxin Type A

Introduction: Muscarinic receptors have been identified both in the suburothelium and urothelium of the human bladder. It has been proposed that increased release of Acetylcholine (ACh) from the urothelial and suburothelial nerves may act on suburothelial and detrusor muscarinic receptors, resulting in detrusor overactivity (DO). Neuropeptide Y (NPY) is a cholinergic co-transmitter. Botulinum neurotoxin type A (BoNT/A) is known to act by blocking the release of ACh. We compared expression of M1, M2, M3 receptors, NPY and SNAP-25 in patients with DO, controls and following successful treatment with BoNT/A. Methods: Flexible cystoscopy bladder biopsies were obtained from 36 patients with DO at baseline, four and sixteen weeks after successful BoNT/A treatment, together with 9 asymptomatic controls. Specimens were immunostained using specific antibodies to the above mentioned antigens. Immunoreactivity (IR) were quantified with image analysis. Results: Reduced levels of M1 IR were noted in DO patients compared to controls. Following BoNT/A, there were increases and „normalisation‟ of M1 IR with similar changes in the urothelium. Significant similar post-BoNT/A increases were seen in M2 IR. Decreased M3 IR was observed at baseline DO compared to controls, with significant increases only in the urothelium following BoNT/A. SNAP-25 IR showed no changes. NPY IR increased in DO, with a decreasing trend following BoNT/A. Inverse IR correlations were found with frequency and urgency. Conclusions: Reduced levels of suburothelial muscarinic receptors in DO are in accordance with previous RT-PCR findings, showing reduced mRNA levels in overactive bladders. NPY IR is increased and may illustrate upregulated cholinergic transmission with DO, similar to ATP. SNAP-25 IR demonstrates the presence of BoNT/A sensitive neurones within the suburothelium. Post-BoNT/A changes in suburothelial muscarinic receptors and NPY appear compensatory to the reduced release of ACh, supporting a neuroplastic effect of BoNT/A on bladder afferent pathways as part of its mechanism of action

Aspects of Respiratory Heat Transfer in Asthma

During the winter some asthma suffers are incapable of exertion without provoking bronchoconstriction. The rate of respiratory heat exchange (RHER) is proposed as a stimulus of exercise induced asthma. A respiratory test was required to determine heat loss sensitivity. A pumped cold air supply was developed (-2

The use of pupillometry, serology, ethnicity and imaging in the diagnosis of optic neuritis

‘Acute isolated optic neuritis' may be the first manifestation of both Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO). Twenty percent of patients with MS in western Europe present with optic neuritis as their first relapse (Mcdonald & Compston, 2006). NMO has been recently found to be more common amongst the Caucasian population of northern Europe than previously believed (Asgari et al, 2011). Patients with NMO may experience a long temporal delay after acute isolated optic neuritis before another relapse occurs, which can help to confirm the diagnosis (Wingerchuk et al, 2007). In such cases an episode of optic neuritis caused by NMO may be indistinguishable from optic neuritis caused by MS. This thesis explores differences in the manifestation of optic neuritis caused by MS and that caused by NMO and evaluates four ways in which the two aetiologies may be identified from one another: pupillometry, serum glial fibrillary acidic protein analysis, ethnic background considerations and MRI findings in the context of the visual pathways. The thesis begins by assessing the potential role of pupillometry in the diagnosis of optic nerve disease; eventually investigating its potential in discriminating between MS related optic neuritis and NMO related optic neuritis. The results of the first part of the thesis indicate the usefulness of pupillometry in patients with optic neuritis who show poor recovery, when tested in a chronic setting. Three further ways of differentiating optic neuritis caused by MS and NMO in an acute setting are then pursued. First, the measurement of serum Glial Fibrillary Acidic protein (GFAP) is shown to be a useful potential indicator of the presence of NMO. Second, the ethnic background of a patient is found to correlate with the risk of NMO. Third, the Magnetic Resonance (MR) image of the visual pathway of patients with optic neuritis from the two aetiologies is found to differ with regard to the lesion extent and the lesion site. The four investigative approaches tested in this thesis (pupillometry, serology testing for GFAP, assessment of ethnic background and MR image) can be combined to offer a patient with isolated optic neuritis of unknown cause a likelihood of suffering from NMO. The latter three methods may be used to assess the risk of NMO in a patient presenting acutely with optic neuritis in the absence of any other sign of underlying disease, and may allow for the appropriate management of this condition