106 research outputs found

    Neurological Disease Diagnosis and Treatment via Precise Robotic Intervention

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    This work focuses on the development and application of mechatronic systems for measurement, diagnosis and treatment of acute and chronic neurological conditions. The development of an automated tendon reflex stimulation device, as well as analysis and classification methods for both automated and manual stimulus delivery will provide the groundwork for improvements to both diagnosis and treatment of neurological injuries. In a similar vein, development of a variable resonance actuator for Magnetic Resonance Elastography imaging enables tissue property measurement of the intervertebral discs, hopefully providing an early marker and better understanding of degeneration. In addition to MRI based spinal tissue property measurements, an MRI guided high precision robot is developed for direct injection into the spinal cord, along with an accompanying image guided control scheme. The novel parallel plane mechanism enables control of 4 degrees of freedom, while the linear piezoelectric actuators in a direct drive configuration enables superior accuracy. Taken together, these robotic device developments constitute contributions to the field of precision medical robotics with applications to physiological understanding of the human body.Ph.D

    Cardiac activity impacts cortical motor excitability

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    Human cognition and action can be influenced by internal bodily processes such as heartbeats. For instance, somatosensory perception is impaired both during the systolic phase of the cardiac cycle and when heartbeats evoke stronger cortical responses. Here, we test whether these cardiac effects originate from overall changes in cortical excitability. Cortical and corticospinal excitability were assessed using electroencephalographic and electromyographic responses to transcranial magnetic stimulation while concurrently monitoring cardiac activity with electrocardiography. Cortical and corticospinal excitability were found to be highest during systole and following stronger cortical responses to heartbeats. Furthermore, in a motor task, hand-muscle activity and the associated desynchronization of sensorimotor oscillations were stronger during systole. These results suggest that systolic cardiac signals have a facilitatory effect on motor excitability – in contrast to sensory attenuation that was previously reported for somatosensory perception. Thus, distinct time windows may exist across the cardiac cycle that either optimize perception or action

    Reorganisation of sensorimotor function in children with brain disease

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    Introduction: In this study, paradigms were developed for the investigation of sensorimotor function in children using functional MRI (fMRI), somatosensory evoked potential (SEP) recordings and behavioural measures. These techniques were applied both to normal controls subjects and to children with brain disease. A major aim was to investigate the remarkable recovery of function that can take place following brain injury sustained early in life. Methods: Three fMRI paradigms were developed, namely active movement of the hand, passive flexion/extension movement of the fingers and median nerve stimulation. In addition, SEPs of functional cortical responses to stimulation of the median nerve were recorded at high temporal resolution. Finally, the extent of residual or recovered sensory and motor hand function was assessed using behavioural tests, including grip strength and double simultaneous stimulation. In one set of investigations, all three techniques were applied to children following hemispherectomy or children following vascular damage to the middle cerebral artery territory, to examine the pattern of residual sensorimotor function following brain injury. In a second study, fMRI was carried out in pre-surgical paediatric patients for mapping of the sensorimotor cortex in preparation for surgical resection of lesions in the vicinity of this cortical region. Results and Discussion: fMRI was successful in locating the hand cortical sensorimotor area in 11 out of 12 paediatric patients pre-operatively, and was of value to the neurosurgeon in helping to delineate the boundaries of subsequent cortical resection. In patients following stroke and hemispherectomy, a combination of fMRI, SEP and behavioural techniques provided evidence for inter-hemispheric reorganisation of sensorimotor function through ipsilateral sensorimotor pathways, and also suggested an increase in the involvement of ipsilateral secondary sensorimotor areas. The data also indicate that cortical sensorimotor reorganisation and functional recovery can be seen in patient both with congenital disease and with late-onset acquired disease, suggesting that factors additional to age at injury may influence the degree of residual function resulting from cerebral reorganisation. Informed consent was obtained for all patients and controls, and the study was approved by the Great Ormond Street Hospital for Children/Institute of Child Health Research Ethics Committee

    Central nervous system physiology

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    This is the second chapter of the series on the use of clinical neurophysiology for the study of movement disorders. It focusses on methods that can be used to probe neural circuits in brain and spinal cord. These include use of spinal and supraspinal reflexes to probe the integrity of transmission in specific pathways; transcranial methods of brain stimulation such as transcranial magnetic stimulation and transcranial direct current stimulation, which activate or modulate (respectively) the activity of populations of central neurones; EEG methods, both in conjunction with brain stimulation or with behavioural measures that record the activity of populations of central neurones; and pure behavioural measures that allow us to build conceptual models of motor control. The methods are discussed mainly in relation to work on healthy individuals. Later chapters will focus specifically on changes caused by pathology

    Intracortical microstimulation of human somatosensory cortex as a source of cutaneous feedback

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    The field of brain computer interfaces (BCI) has been making rapid advances in decoding brain activity into control signals capable of operating neural prosthetic devices, such as dexterous robotic arms and computer cursors. Potential users of neural prostheses, including people with amputations or spinal cord injuries, retain intact brain function that can be decoded using BCIs. Recent work has demonstrated simultaneous control over up to 10 degrees-of-freedom, but the current paradigms lack a component crucial to normal motor control: somatosensory feedback. Currently, BCIs are controlled using visual feedback alone, which is important for many reaching movement and identifying target locations. However, as the actuators controlled by BCIs become more complex and include devices approximating the performance of human limbs, visual feedback becomes especially limiting, as it cannot convey information used during object manipulation, such as grip force. The objective of this work is to provide real-time, cutaneous, somatosensory feedback to users of dexterous prosthetic limbs under BCI control by applying intracortical microstimulation (ICMS) to primary somatosensory cortex (S1). Long-term microstimulation of the cortex with microelectrode arrays had never been attempted in a human prior to this work, and while this work is ultimately motivated by efforts to improve BCIs, this general approach also enables INTRACORTICAL MICROSTIMULATION OF HUMAN PRIMARY SOMATOSENSORY CORTEX AS A SOURCE OF CUTANEOUS FEEDBACK Sharlene Nicole Flesher, PhD University of Pittsburgh, 2017 v unprecedented access to the human cortex enabling investigations of more basic scientific issues surrounding cutaneous perception, its conscious components, and its role in motor planning and control. To this end, two microelectrode arrays were placed in human somatosensory cortex of a human participant. I first characterized qualities of sensations evoked via ICMS, such as percept location, modality, intensity and size, over a two-year study period. The sensations were found to be focal to a single digit, and increased in intensity linearly with pulse train amplitude, which suggests that ICMS will be a suitable means of relaying locations of object contact with single-digit precision, and a range of grasp forces can be relayed for each location. Additionally, I found these qualities to be stable over a two-year period, suggesting that delivering ICMS was not damaging the electrode-tissue interface. ICMS was then used as a real-time feedback source during BCI control of a robotic limb during tasks ranging from simple force-matching tasks to functional reach, grasp and carry tasks. Finally, we examined the relationship between pulse train parameters and conscious perception of sensations, an endeavor that until now could not have been undertaken. These results demonstrate that ICMS is a suitable means of relaying somatosensory feedback to BCI users. Adding somatosensory feedback to BCI users has the potential to improve embodiment and control of the devices, bringing this technology closer to restoring upper limb function

    Multisite Repetitive Transcranial Magnetic Stimulation: Safety, Feasibility, Tolerability, and Electro-Neurophysiology

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    The thesis investigated the potential clinical application and measurement of multisite priming repetitive transcranial magnetic stimulation (rTMS) protocols. The findings showed that multisite rTMS protocols are safe and tolerable. Furthermore, the neuro-modulatory effects of rTMS are highly variable but can be characterised using multi-modal techniques

    The clinical spectrum and pathophysiology of neuropathic tremor

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    This thesis describes a series of studies involving patients with neuropathies and healthy controls. In the studies of disease, two groups were recruited: patients with inflammatory neuropathies and those with hereditary neuropathies. Each group was separated into those with and those without tremor and compared with healthy controls. Clinical assessments and neurophysiological tests were employed to correlate cerebellar function with tremor. The final study of healthy participants investigated the effect of transcranial direct current stimulation (TDCS) on the cerebellum during finger tapping. 1) Tremor was most common in IgM paraproteinaemic neuropathies, also occurring in 58% of those with chronic inflammatory demyelinating polyradiculoneuropathy and 56% of those with multifocal motor neuropathy with conduction block (MMNCB). Tremor was generally refractory to treatment and contributed to disability in some patients. Although tremor severity correlated with F wave latency, it was insufficient to distinguish those with, from those without tremor. 2) Impaired eyeblink classical conditioning and paired associative stimulation in patients with inflammatory neuropathy and tremor differentiated them from neuropathy patients without tremor and healthy controls, strongly suggesting impairment of cerebellar function is linked to the production of tremor in these patients. 3) The prevalence study in CMT1A patients revealed tremor in 21% and in 42% of those it caused impairment. Eyeblink conditioning, visuomotor adaptation and electro-oculography were no different between tremulous and non-tremulous patients and healthy controls. This argues against a prominent role for an abnormal cerebellum in tremor generation in the patients studied. Rather, they suggest an enhancement of the central neurogenic component of physiological tremor as a possible mechanism. 4) TDCS of the lateral cerebellum and its effect on paced finger tapping was examined. There was no effect on accuracy or variability of the intertap interval, providing no support for a direct role of the cerebellum in event based timing

    On sensorimotor function and the relationship between proprioception and motor learning

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    Research continues to explore the mechanisms that mediate successful motor control. Behaviourally-relevant modulation of muscle commands is dependent on sensory signals. Proprioception -- the sense of body position -- is one signal likely to be crucial for motor learning. The present thesis explores the relationship between human proprioception and motor learning. First we investigated changes to sensory function during the adaptation of arm movements to novel forces. Subjects adapted movements in the presence of directional loads over the course of learning. Psychophysical estimates of perceived hand position showed that motor learning resulted in sensed hand position becoming \emph{biased} in the direction of the experienced load. This biasing of perception occurred for four different perturbation directions and remained even after washout movements. Therefore, motor learning can result in systematic changes to proprioceptive function. In a second experiment we investigated proprioceptive changes after subjects learned highly accurate movements to targets. Subjects demonstrated improved acuity of the hand\u27s position following this type of motor learning. Interestingly, improved acuity did not generalize to the entire workspace but was instead restricted to local positions within the region of the workspace where motor learning occurred. These results provide evidence that altered sensory function from motor learning may also include sensory acuity improvements. Subsequently the duration of acuity improvements was assessed. Improved acuity of hand position was observed immediately after motor learning and 24h later, but was not reliably different from baseline at 1h or 4h. Persistent sensory change may thus be similar to retention of motor learning and may involve a sleep-dependent component. In the fourth study we investigated the ability of proprioceptive training to improve motor learning. Subjects had to match the position and speed of desired trajectories. At regular intervals during motor motor learning, subjects were presented with the desired trajectory either only visually, or with both vision and and passive proprioceptive movement through the desired trajectory using a robot. Subjects who received proprioceptive guidance indeed performed better in matching both velocity and position of desired movements, suggesting a role for passive proprioceptive training in improving motor learning

    An investigation into central nervous system involvement in distal symmetrical diabetic neuropathy in type 1 diabetes mellitus.

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    Diabetes is a leading cause of peripheral neuropathy. It is the main initiating factor for foot ulceration and amputation resulting in considerable morbidity and remarkable consumption of scarce medical resources. Relatively little is known about the pathophysiology underlying DPN. Research into DPN has focused mainly on the peripheral nervous system (PNS) with central nervous system (CNS) involvement relatively overlooked. The studies undertaken have been designed to investigate CNS involvement in DPN. 1. Before embarking on spinal cord studies, I reviewed and modified the techniques employed in the pilot study to improve the precision and accuracy of cord cross sectional area measurements. These modifications were patiented to quality control studies, which are reported in Chapter 2. 2. I performed in-vivo cross-sectional magnetic resonance imaging of the cervical spine and reported evidence of spinal cord shrinkage (atrophy) in Painless DPN (Chapter 3). This study showed spinal cord atrophy to be an early phenomenon, present even in subclinical DPN. As the spinal cord is the caudal portion of the CNS, its involvement made us question whether the brain too may be involved. 3. Using MR spectroscopy I examined thalamic involvement in Painless DPN (Chapter 4). This deep brain nucleus is considered the gateway to all somatosensory information entering the brain, and responsible for modulation of sensory information prior to presentation to the cerebral cortex. I demonstrated thalamic biochemical abnormalities consistent with possible neuronal dysfunction in patients with Painless DPN. 4. The demonstration of thalamic neuronal dysfunction in DPN suggests that CNS involvement is not limited to the spinal cord but other important areas, responsible for somatosensory perception, may also be involved. Although the pathogenesis of thalamic involvement is unknown, it is likely that both vascular and metabolic factors that have been implicated in the pathogenesis of DPN are involved. In Chapter 4, I examined the possible role of metabolic factors in the pathogenesis of thalamic neuronal dysfunction in DPN. Using MR spectroscopy, I demonstrated a significant elevation in thalamic glutamine/glutamate in patients with diabetes. Glutamate is the most abundant excitatory neurotransmitter and implicated in various models of neuronal cell death. Astrocytes, which play an important role in glutamate/glutamine metabolism, were impaired in the thalamus of diabetic patients in this study. The combination of elevated glutamate and impaired thalamic astrocytes may provide a pathophysiological explanation for thalamic dysfunction in DPN. 5. In Chapter 5, an alternative hypothesis for thalamic neuronal dysfunction in DPN was tested. Using dynamic contrast enhanced MR perfusion imaging, I demonstrated that Painful DPN is associated with unique thalamic perfusion abnormalities. Intriguingly, these abnormalities were present in patients with Painful but not Painless DPN. 6. Finally, in Chapter 6, I conducted a randomised, double blind and placebo-control trial (RCT) comparing the efficacy and tolerability of sativex, a cannabis based medicinal extract (CBME), with placebo in the symptomatic treatment of painful DPN. This is the first ever RCT using a CBME in painful DPN. We report no significant difference in the primary outcome measure due to a massive placebo effect and that depression is a potential major confounder in such clinical trials
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