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Electroencephalograph (EEG) is used in various applications such as diagnosing patients suffering from epilepsy or seizures. Motion artefact is the noise recorded together with the desired biopotential signals. It is mainly introduced by the relative motion between the measurement electrode and the human scalp. Dry electrodes are preferred in long term monitoring because gel is not required, although dry electrodes are more vulnerable to motion artefact. The frequency range of motion artefact overlaps with the frequency range of the EEG. Thus it is difficult to deduct motion artefacts from recorded signals. In imec, a low power wireless headset has been developed for long term EEG acquisition. Since motion artefact introduces significant signal distortion, finding a suitable signal that can help in locating these artefacts is of utmost importance. In order to find the most appropriate signal for the motion artefact detection and possibly also prediction and removal, the relation between EEG, impedance, force and acceleration were investigated. We analysed the influences of external forces, head movements and daily activities on the EEG and electrode-skin impedance magnitude. 11 subjects participated the experiment. Cross correlation coefficient analysis was done to indicate the linear correlations between EEG and impedance, EEG and force, EEG and acceleration, impedance and force, and impedance and acceleration. The results demonstrate that the EEG, the impedance and the force are highly correlated when only external force is applied on the electrodes. However, when body movements are involved the cross correlation is lower due to the non-linearity of the signals. Both positive and negative correlation could be observed between the impedance and the EEG. The relation between the impedance and the EEG varies across the people and due to the motion. In conclusion, impedance is the best candidate for motion artefact detection in EEG compared with force and acceleration.

In order to understand how the different brain systems work, control theory concepts are used to represent the input - output relationships of the structures involved. Perturbations is a common tool to study and analyze a control system. One example of a brain circuitry is the oculomotor system. Although, visual perturbations have been used to perturb the eye no mechanical perturbations have been applied up to now. Mechanics is the only way to evoke an unexpected movement, which is an essential factor to motor control. In this study, a magnetic actuator is designed to be used to apply torques in the rabbit eye. In vitro experiments were conducted in a prototype, which roughly mimics the movement of the eye in the horizontal plane, to test the function of the actuator. Experiments in the rabbit (in vivo) were also performed. In vitro results showed that the conceptual design is sound and the demanded torque of 17 mN mm was achieved. During preliminary in vivo results, clear eye movements were recorded as a result of the actuator's perturbations. The actuator designed enables a series of experiments in the frame of oculomotor control research.

Assessing mechanisms of peripheral reflex control is important for understanding movement disorders after suprapsinal nerve lesions like stroke. In the present study, reflex provocation by ramp and hold rotations (R&H) was combined with Transcranial Magnetic Stimulation (TMS). In four subjects, subthreshold single pulses TMS were applied to the primary motor cortex at carefully timed intervals, while short and long latency EMG responses of the m. flexor carpi radialis were elicited by R&H rotations around the wrist joint. TMS was found to inhibit the long latency response with a maximum inhibition when TMS was calculated to arrive at 45ms after stretch onset in all subjects. Excitation was found at 60 ms in all subjects. An involvement of the primary motor cortex in peripheral reflex loop operation was demonstrated. This involvement may be either exictatory or inhibititory on the stretch reflex.

Endpoint stiffness is known to increase in the direction of instability during learning to accurately execute unstable motor tasks. Reflexes might be present in the time interval used for endpoint stiffness calculations suggesting a possible influence of reflexes on endpoint stiffness measurements. In addition, changes of reflexes during motor learning are still unknown. The purpose of this research was to investigate the separate contributions of intrinsic and reflexive stiffness to the observed change in endpoint stiffness during learning to move the hand in unstable force fields. A divergent (unstable) force field (DF) was applied with a two degrees of freedom manipulator (ARMANDA). Subjects performed 100 point-to-point arm movements in a null field and 300 point-to-point arm movements in the divergent force field holding the manipulator with their right hand. In random (catch) trials a minimum jerk position perturbation was applied in the middle of the movement. Force and EMG responses to the perturbation were used to examine endpoint stiffness and reflexes. Endpoint stiffness is defined as the force response to the imposed perturbation (in the interval 160-200 ms after perturbation onset) divided by the position displacement. Unperturbed trials were analyzed to investigate the decrease of errors (deviations from the straight path between start and target) and changes of co-contraction with motor learning. We found that errors decreased in the first 150 movements in the DF and leveled off from then on. Intrinsic, reflexive and endpoint stiffness were rapidly increased before the 35th DF trial. No significant changes of the stiffness parameters were found after this first learning period. An additional investigation of reflex response timing showed variability in the reflex timing between subjects. Reflexes were seen to influence the endpoint stiffness measurements for some subjects. In case of other subjects reflexes were not present in the time interval used for endpoint stiffness calculation and therefore no reflexive contribution to endpoint stiffness was assumed. In conclusion, our results showed a rapid increase of all stiffness parameters during the early phase of learning and suggest the involvement of other (unknown) mechanisms in the later learning phase. Because of the found variations in reflex response timing, we recommend to always include reflex analysis during endpoint stiffness measurements.

Galvanic vestibular stimulation (GVS) alters the firing rates of vestibular afferents and consequently provokes the illusion of movement. In standing balance GVS is used to assess the contribution of the vestibular system, where it has been shown to elicit coherent responses in lower extremity muscles involved in maintaining balance. However, to date no information exists regarding the influence of GVS on neck muscles or head-neck stabilization. This study aims to test the hypothesis that GVS can be used as a technique to investigate the vestibular contribution to head and neck stabilization. Sinusoidal stimuli of 0.5 – 2 mA within the bandwidth of 0.4 – 5.2 Hz were used as GVS signals and applied to eleven healthy subjects using a bilateral bipolar configuration. Subjects were blindfolded and stimulated while seated on and restrained to a chair. Measurements of natural sway (without stimulation) were included as control trials. Displacements of head and torso were recorded using a motion capture system. System identification techniques were used to identify the relationship between the input (GVS) and the output (motion) of the head and neck. The results show significant coherence between GVS and the head-neck kinematics and modulation of these responses was observed across frequency and not amplitude, demonstrating the linear range of the vestibular feedback. Furthermore, the vestibular origin of the responses was demonstrated using non-vestibular stimulation tests. EMG measurements were used to characterize the relationship between the vestibular input and muscle activities in neck. Based on the findings of this study we propose that using GVS with system identification techniques provides a viable approach to quantify small motions (~ 0.1 mm) in neck and understand motion control of the head-neck.

Corticomuscular communication during wrist motor tasks was investigated in this study. EEG signals from the sensorimotor cortex and EMG data from the reflexive carpi radialis and extensor carpi radialis muscles were recorded from five healthy subjects while performing visual-motor force tasks, with and without perturbation on the wrist. Different continuous perturbation signals with different frequency content (multisines), as well as perturbation resulting in rapid angular displacements of the wrist were applied to study the existence of synchronization on corticomuscular communication, as well as the possible trancortical contribution to the late reflexes on the muscle. Corticomuscular, perturbation- EEG and perturbation - EMG coherences were calculated for all tasks. Three out of five subjects did show high coherence results in beta band when applying multisine perturbation and decreased in base task and in tasks with rapid angular displacements of the wrist, implying an Ia afferent contribution from muscle spindles to beta EEG. The connection of the perturbation to the brain and the muscles is considered non-linear due to high corticomuscular coherence found in harmonics of the excited frequencies. Current source density was applied on frequencies with high corticomuscular coherence. Contralateral supplementary motor cortex is more likely to cause corticomuscular communication at high frequencies of the beta band. Moreover, proprioceptive-evoked potentials were calculated from tasks with continuous rapid angular displacements of the wrist. The basal ganglia is more likely to be involved in the generation of early proprioceptive-evoked activity.

The neuromusculoskeletal model of this study was built to better understand the mechanisms behind negative position and velocity feedback gains as identified in human postural control (Van der Helm et al.,2002). Specifically, causes were sought which could explain: a) why Reflex Sympathetic Dystrophy (RSD) patients with tonic dystonia are unable to set negative gains (Schouten et al., 2003) when optimal posture control dictates these gains as desirable (Schouten et al.,2001; De Vlugt et al., 2001), and b) how these patients are still able to modulate the gains, although restricted to positive values (Schouten et al., 2003). The model is an integration of a biological realistic neural network based on Bashor (1998) with a 1-degree of freedom musculoskeletal model derived from human shoulder studies (Stroeve, 1999; Van der Helm et al., 2002; Schouten et al., 2003). Muscle proprioceptors obtained from comparative studies (Prochazka and Gorassini, 1998a,b) provide the neural network with feedback information from the musculoskeletal model. It has been suggested that the inability to set negative gains is due to neurotransmitter deficiencies in inhibiting synapses in the spinal neural network (Van Hilten et al., 2000; Jankowska and Hammar, 2002). Two synaptic connections were selected for possible disfunctioning: 1) the synapse which presynaptically inhibits the monosynaptic stretch reflex synapse, and 2) the synapse connecting the inhibitory interneuron to the motoneuron. A lack of presynaptic inhibition of the first resulted in an overly dominant monosynaptic stretch reflex with high, positive feedback gains. Disabling the second prevented several major proprioceptive feedback paths from providing the motoneurons with with negative stimulation, making the setting of negative feedback gains next to impossible. It was concluded that: a) both synapses play an important role in obtaining negative feedback gains and that disfunctioning of these synapses could account for the previously unexplainable feedback gain quantification results for healthy subjects and RSD patients, and b) a disabled synapse, other than the one presynaptically inhibiting the monosynaptic stretch reflex synapse, still allows for limited feedback gain modulation.

Parkinsonʼ’s disease (PD) is a progressive neurodegenerative disorder characterized by reduced movement. Postural instability and gait dysfunction (PIGD) is one of the more debilitating symptoms of PD due to its effect on activities of daily life and increased risk for falls. In later stages of the disease, cognitive impairment affects executive functioning and working memory. Although, most activities in daily living require both motor and cognitive functioning like cycling (motor) while holding a conversation (cognitive). Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to reduce motor deficits in advanced Parkinsonʼ’s disease patients. However, the effectiveness of STN DBS on postural instability is less pronounced. It has been shown that bilateral STN DBS results in cognitive declines under dual-‐‑task conditions using an upper extremity task and these declines compromise motor function. The aim of this study was to asses the effectiveness of STN DBS on cognitive-‐‑motor performance during a lower extremity task. 15 advanced PD patients, of which seven presented PIGD symptoms, were tested under single-‐‑ and dual-‐‑task conditions. All patients were bilaterally implanted with STN DBS and had stable parameters as determined through typical clinical programming for at least 6 moths prior to study enrollment. Patients were assessed off anti-‐‑parkinsonian medication under two DBS settings; Off DBS and On DBS. In each condition, patients performed a working memory task (n-‐‑back) and a postural stability task (quiet standing). During the dual task, patients performed the working memory and postural stability tasks simultaneously. DBS was effective in improving Unified Parkinsonʼ’s disease Rating Scale III scores relative to no stimulation. Cognitive functioning showed no difference between the two DBS conditions. Patients with PIGD symptoms were significantly less stable than patients with no PIGD symptoms for both On and Off DBS conditions. These data show that with the paradigm used in this study, PIGD symptoms continue to be refractory to DBS. Postural stability as assessed by quietly standing on a force platform may not have been challenging enough to evoke cognitive declines.

In movement control cortical signals are integrated with afferent feedback from reflexes. Disturbed integration is suggested to underlie many movement disorders. Cortical and afferent signals can integrate in the spinal cord and at supraspinal centres, though the exact location and mechanism of integration are unknown yet. The goal of this study is to assess the cortical involvement during the stretch reflex response. Mechanically induced stretches of the muscle flexor carpi radialis where combined with subthreshold transcranial magnetic stimulation (TMS, 97% of active motor threshold) at interstimulus intervals ranging from 35 to 80 ms. Muscle response was measured using high-density electromyography (EMG), providing additional spatial muscle activation patterns. Magnitude of resulting EMG reflex activity, i.e. short (M1, 20-50 ms) and long (M2, 55-100 ms) latency reflex responses were compared to stretch-only trials. Subthreshold TMS was found to significantly increase the stretch evoked EMG response (p < 0.001) when TMS pulses were timed to arrive at the muscle in the time window of the M2 response. Absence of facilitation of the spinally mediated M1 response indicates that integration of cortical and afferent feedback signals in M2 occurs at a supraspinal level. Spatial muscle activation patterns of suprathreshold TMS were consistent over trials, while spatial patterns due to stretch reflexes were less consistent. Spatial patterns of combined trials are therefore not conclusive about the mechanism of integration.

This study describes a method for the identification of Time-Varying joint admittance. The method transforms the time signals into a time--frequency representation using the wavelet transform, from which the Time--Varying frequency response function (TV--FRF) is estimated, and the model parameters are derived. Analysis of the performance of the developed method is established by simulation of the human arm. The study showed that increasing the observation time, increase the confidence regions of the estimate. The study showed that smoothing is needed, but it comes with a trade-off between precision and response time. Increasing the time smoothing increases the precision but decreases the response time. The developed method showed promising results by estimating the properties of the simulated model, giving the bases for a posterior study using experimental data.

Galvanic vestibular stimulation (GVS) alters the firing rates of vestibular afferents and consequently provokes the illusion of movement. In standing balance GVS is used to assess the contribution of the vestibular system, where it has been shown to elicit coherent responses in lower extremity muscles involved in maintaining balance. However, to date no information exists regarding the influence of GVS on neck muscles or head-neck stabilization. This study aims to test the hypothesis that GVS can be used as a technique to investigate the vestibular contribution to head and neck stabilization. Sinusoidal stimuli of 0.5 – 2 mA within the bandwidth of 0.4 – 5.2 Hz were used as GVS signals and applied to eleven healthy subjects using a bilateral bipolar configuration. Subjects were blindfolded and stimulated while seated on and restrained to a chair. Measurements of natural sway (without stimulation) were included as control trials. Displacements of head and torso were recorded using a motion capture system. System identification techniques were used to identify the relationship between the input (GVS) and the output (motion) of the head and neck. The results show significant coherence between GVS and the head-neck kinematics and modulation of these responses was observed across frequency and not amplitude, demonstrating the linear range of the vestibular feedback. Furthermore, the vestibular origin of the responses was demonstrated using non-vestibular stimulation tests. EMG measurements were used to characterize the relationship between the vestibular input and muscle activities in neck. Based on the findings of this study we propose that using GVS with system identification techniques provides a viable approach to quantify small motions (~ 0.1 mm) in neck and understand motion control of the head-neck.

Tremor, characterized by involuntary and rhythmical movements, is the most common movement disorder. Tremors can have peripheral and central oscillatory components which properly assessed and separated may improve diagnostics. An MR-safe haptic wrist manipulator enables simultaneous measurement of proprioceptive reflexes (peripheral components) and brain activations (central components) through fMRI. For such a MR-safe manipulator, this study determined the design criteria, created the design and presented its prototype. The prototype is divided into an MR-safe and MR-unsafe part. The hydraulic MR-safe vane motor (end effector) and optical sensors in the MR-environment are connected to the MR-unsafe part in the control room via hydraulic tubes and optical fibers. As a result, the fMRI quality is ensured and the manipulator is suited for safe use in any MR-environment. During a test in an MR-scanner (AMC, Amsterdam) no distortions in the MR-image or sensor signal were observed. The vane motor has a range of motion of 134° with a designed torque delivery of 8 Nm at a 3 bar pressure difference. The achieved accuracy for the torque sensor is ±2% full scale (F.S. = 14.3 Nm) and for the absolute position sensor ±1% full scale (F.S. = 70=1.22 rad). The prototype vane motor had some leakage along the axis, this prevented the use of pre-pressure and consequently reduced the bandwidth and maximum torque. However the maximum achieved torque of 1.5 Nm was still enough to met the requirement of 1.2 Nm. A PI controller was used to control the system, however this controller could not cope with the inherent non-linearities of hydraulics over the intended bandwidth (20 Hz). Despite the fact that the controller was not optimal, typical responses were obtained with impedance FRFs of two inertial loads. For future research it is recommended to remedy the axis leakage and implement a model-based controller. The open-loop FRF of the commanded velocity to the measured vane velocity was determined to characterize the system. Even with leakage and without pre-pressure, the measured bandwidth (-3 dB) was approximately 5 Hz and the -180° phase is passed at 7 Hz. Although the bandwidth does not fulfill the requirement for proprioceptive reflex identification it does allow for various motor control experiments. With the recommendations carried out, it is expected that the next prototype will be suited for proprioceptive reflex identification during fMRI.

In many everyday activities such as steering a bicycle, unpredictable mechanical disturbances trigger quick involuntary and situation-specific reactions via neural loops generally referred to as reflexes. Research investigating reflexes via transient perturbations elicit muscle activations typically observed as two distinct responses in an electromyography with the short-latency response M1 viewed as stereotyped and task-independent and the long-latency response M2 seen as task-dependent. In contrast, task-dependency of short-latency pathways (specifically velocity and force feedback) was demonstrated by studies using continuous perturbations and system identification techniques to separate reflex from voluntary contributions. This study addressed the opposing experimental findings by isolating reflex contributions in the human wrist joint using both the transient and the continuous approach simultaneously in conditions where reflex modulation is expected. Subjects (n = 11) held a manipulator handle which applied mechanical perturbations and imposed a virtual mechanical environment to the wrist. Increasing damping of the environment and reduced continuous perturbation bandwidth in a "maintain position" task (PT) decreased the subject’s mechanical joint admittance, increased excitatory velocity and force feedback obtained from a neuromuscular model, increased M2 but did not affect M1. Instructing subjects to "maintain force" increased the joint admittance, decreased M2 and counterproductive to the task increased M1 with respect to the PT. Results from this study indicate that the continuous approach does not condition M1 and that the reflexive feedback from short-latency pathways obtained via the presented neuromuscular model does not directly map to the M1 elicited by transient perturbations.

The goal of this study was to assess if the superposition principle is valid in head-neck stabilization during combined torso perturbations and continuous galvanic vestibular stimulation. Nine seated subjects were perturbed in lateral direction on a motion platform while GVS was simultaneously applied. Both the mechanical and galvanic input signals consisted of multisine signals and were designed to be mathematically uncorrelated. For the motion perturbations, two direction and two amplitude variations were included. The GVS signal was applied in a bilateral bipolar configuration at 4 mA. During trials subjects had their eyes closed and were asked to perform a natural stabilization task. Displacements of the head, torso and platform were recorded using a motion capture system. System identification techniques were used to identify the relationship between respectively inputs GVS and torso motion and output head motion. Results show that it is feasible to apply low-level torso perturbations together with continuous galvanic stimulation in studying the head-neck system as high coherencies and consistent behavior are found for the transfer functions from mechanical and galvanic inputs to head motion over all subjects. It is concluded that superposition principle does not hold as gain, phase and coherence modulations were found with the addition of GVS.

Complex Regional Pain Syndrome (CRPS) is a disabling syndrome associated with sensory (e.g., burning pain, allodynia, hyperalgesia), autonomic (e.g., edema, skin color and temperature changes), and motor impairments (e.g., tremor, myoclonus, dystonia). Approximately 25% of the patients with CRPS develop fixed dystonia which is characterized by abnormal sustained muscle contractions and abnormal postures. No definitive pathophysiology of CRPS and related dystonia exists. Neurophysiological studies have found evidence of impaired inhibition at the spinal cord and motor cortex. In this thesis, a computational neuromuscular model has been developed to explain the movement disorder fixed dystonia through disturbed proprioceptive reflexes. To validate the model, methods have been developed to quantify proprioceptive reflexes in vivo during postural control of patients with fixed dystonia. The prime goal of this thesis is to gain insight into the pathophysiology of fixed dystonia and develop a diagnostic protocol. Although the mechanisms behind fixed dystonia are still elusive, the evidence implicating involvement of aberrant muscle force feedback is compelling. Aberrant muscle force feedback successfully mimicked dystonia in the neuromuscular model while experiments demonstrated involvement of muscle force feedback in fixed dystonia.