In Upper Motor Neuron Lesion (UMNL) following stroke, patients can experience increased joint impedance, resisting joint rotation and hindering functional movement. This heightened impedance in UMNL is driven by both exaggerated reflexes and increased intrinsic muscle activation through co-contraction, hypertonus, or synergies. The simultaneous presence of these mechanisms complicates clinical distinction, especially given their theorised interplay, where increased intrinsic activation would further heighten reflex responses. Separate quantification of this intrinsic and reflexive impedance and their interaction, can aid in further investigation of the pathophysiology of post-stroke joint impairment and its treatment.

This work presents the investigation of an Open Loop System Identification (OL-SID) protocol, to perform this separate quantification of intrinsic and reflexive impedance for the elbow joint. Perturbation experiments were performed with 16 healthy subjects, using multisine positional perturbations and measuring the elbow torque response. An impedance model consisting of both intrinsic and reflexive parameters was fit to the estimated frequency response function (FRF), relating perturbation angle to joint torque. It was assessed how background muscle activation, as well as the frequency and velocity of the perturbation signal, influenced the modelled intrinsic stiffness, intrinsic damping, and reflex velocity-gain.

For this, three different biceps muscle activation levels were requested from the participants in different trials; 0%, 10%, and 30% of Maximum Voluntary Contraction (MVC), as confirmed by online EMG measurements. Participants were requested to not actively resist perturbations, but only to comply with the requested biceps activation level. Furthermore, three rotational multisine perturbations with a max. amplitude of 2 degrees were applied; Wide Bandwidth - High Velocity, Narrow Bandwidth - Low Velocity, and Wide Bandwidth - Low Velocity. Cross-combination of biceps activation levels and perturbation signal resulted in 9 impedance quantifications per participant.

Increased biceps activation resulted in a significant increase of intrinsic stiffness, intrinsic damping, and the reflex-gain. This confirmed the expected relationship between muscle activation and intrinsic impedance, as well as the theorised relation between intrinsic activation and the reflex response. Unexpectedly, differences in used perturbation bandwidth or velocity showed no clear influence on identified reflex gain. This contradicts findings of reflex suppression during high-bandwidth force perturbations in tasks that require resisting these perturbations, as well as during high-velocity binary or unidirectional joint stretches. This discrepancy shows that joint system identification results are highly dependent on perturbation type and subject task, emphasising the need to align the experimental design with the clinical question at hand.

Despite some shortcomings regarding low coherence of the estimated FRFs, and necessary further research on perturbation signal properties and their effect on the reflex response, the results of this study are promising. The observed trends in fitted parameters with increased activation levels in line with physiological expectations, indicate the ability of this technique to validly identify reflexive and intrinsic joint impedance. This distinction is highly valuable for advancing investigation of the pathophysiology and clinical presentation of UMNL post-stroke, in the pursuit of adequate treatment for different patients.

Background
Spasticity is a condition that affects patients who have sustained an upper motor neuron lesion. Such lesions include for example cerebral palsy (CP), of which 35% is affected by spasticity, and stroke, of which 90% is affected by spasticity. Pharmacological therapy often involves the prescription of oral baclofen. However, due to the difficulty of medication in crossing the blood-brain barrier, high dosages of oral baclofen are required to achieve the desired therapeutic effect, which in turn leads to an increase of the incidence of negative side-effects. For patients with severe spasticity, the intrathecal baclofen (ITB) pump is indicated for more effective drug delivery. To monitor the efficacy of the treatment and quantify the level of spasticity, the Modified Ashworth Scale (MAS) is employed. Nevertheless, the moderate inter- and intra-rater reliability indicates that the subjectivity of the approach represents a potential limitation. Therefore, a more objective approach is required. Surface electromyography (sEMG) can measure direct muscle activity and is an objective and non-invasive approach. Yet, there is no research available on sEMG measurements to assess the change in muscle activity as a result of ITB treatment.

Objective
The primary objective of this exploratory study is to assess the effect of intrathecal baclofen on lower limb muscle activity using sEMG. The secondary objectives are assessing the correlation between the sEMG feature values and MAS scores, and between the sEMG feature values and Patient's Global Impression of Change (PGIC) scores.

Method
sEMG measurements were performed during standard assessment of the MAS on patients receiving an ITB single shot trial (SS) and/or pump implantation. The following features were analyzed: (1) Root Mean Square (RMS), (2) Peak Amplitude Value (PAV), (3) Median Frequency, and (4) Co-Contraction (CCR). A comparative analysis was conducted to assess the change in mean feature value of each individual muscle between pre- and post-treatment for the purpose of study aim 1. The Spearman's rank correlation coefficient was calculated in order to assess the relationship between changes in feature values and changes in MAS scores. Furthermore, the Spearman's rank correlation coefficient was calculated to assess the relationship between the changes in most effective feature and the PGIC scores.

Results
A total of twelve patients were included in the study, diagnosed with a variety of conditions including spinal cord injury (SCI), multiple sclerosis (MS), traumatic brain injury (TBI) and CP. Following ITB treatment, the RMS demonstrated a statistically significant decrease for three out of eight muscles: the left semitendinosus (p = 0.020), the right rectus femoris (p = 0.025) and the right tibialis anterior (p = 0.002). The PAV presented a decrease in 3-8 out of 10 patients following SS baclofen treatment. The changes in median frequency exhibited considerable variability between patients following ITB treatment. The CCR decreased in six out of ten patients for the left leg following SS baclofen treatment. A significant correlation was observed between the change in MAS scores and change in RMS in the medial gastrocnemius (p = 0.027) and the change in median frequency in the semitendinosus (p = 0.002). A low correlation was observed between the change in RMS and the PGIC score.

Conclusion
In conclusion, this study demonstrates the potential of sEMG features, such as RMS, in assessing the impact of ITB treatment on muscle activity. Future work could validate these findings by increasing the sample size and improving certain methodological aspects.

Introduction: In the Pediatric Intensive Care Unit (PICU), maintaining stable cerebral blood flow (CBF) is essential incirtically ill children, as fluctuations can lead to severe neurological complications. Cerebral autoregulation (CA) ensures stable CBF despite changes in systemic blood pressure. Traditional methods such as intracranial pressure (ICP) monitoring and transcranial Doppler (TCD) provide indirect assessments of CA and are often invasive or limited in continuous monitoring. Near-infrared spectroscopy (NIRS) offers a more non-invasive alternative by continuously measuring cerebral oxygenation. By correlating cerebral regional oxygen saturation (CrSO2) with, though invasive, mean arterial pressure (MAP), the cerebral oximetry index (COx) can be calculated, quantifying the brain’s autoregulatory efficiency. This allows clinicians to determine the optimal MAP (MAPopt) per individual, where CA is most effective, which could improve patient outcomes by maintaining stable cerebral perfusion.
Objective: This thesis aims to evaluate COx, derived from (CrSO2) and MAP, to identify the MAPopt in pediatric patients undergoing surgery for congenital diaphragmatic hernia (CDH) or esophageal atresia (EA). Additionally, it examines differences in CA across pre-, intra-, and postoperative phases, providing insights into how surgery affects CA.
Method: Left and right CrSO2 and MAP signals, pre-, intra-, and post-operatively, were retrospectively analyzed to assess CA using the COx. Data preprocessing involved the removal of artifacts, normalization, and signal alignment. COx was calculated as the moving Pearson correlation of CrSO2 with MAP over time
using a 5 minute sliding window with a one minute stepsize. Impaired CA was defined as a COx cut-off value ≥ 0.3, defining a correlation between the MAP and CrSO2. The MAPopt was identified as the MAP associated with the lowest COx values, representing the most effective CA. The optimal MAP range was calculated per patient.
Results: CA was interpreted to be most compromised during the intraoperative phase, with elevated COx values in both CDH and EA patient groups. The MAPopt was successfully determined in most cases, showing variability across operative states, with lower values observed intraoperatively. The percentage of time with COx above the cut-off of 0.3 was highest during surgery, especially for EA patients. No remarkable differences were found between the left and right CrSO2 signals.
Conclusion: The study demonstrates the feasibility of using NIRS-derived COx to determine MAPopt in neonates undergoing CDH or EA surgery. These findings highlight the potential for individualized MAP targets
to optimize cerebral perfusion, especially during critical surgical interventions.

This study investigates ”How does the modulation of the Soleus H-reflex vary across different levels of isometric voluntary contractions?” The hypothesis that the Soleus H-reflex amplitude follows a biphasic response, with an initial increase at lower contraction levels, followed by a plateau or decrease at higher levels of contractions. To test this, ten healthy subjects were recruited to perform isometric voluntary contractions at different levels of maximal voluntary contraction (MVC) (0%, 20%, 40%, 60%, and 80% MVC). The H-reflex peak-to-peak amplitude was measured and normalized as a percentage of the maximum M-wave (H/Mmax). The data were analyzed using a repeated measures ANOVA to assess the effect of MVC level on the Soleus H-reflex amplitude, followed by pairwise comparisons to identify significant differences between contraction levels. A repeated measures ANOVA revealed a significant effect of MVC level on Soleus H-reflex amplitude (H/Mmax) (F(4,32) = 4.82, p < 0.05). Pairwise comparisons showed a significant increase in H-reflex amplitude between 0% and 20% MVC (p = 0.013), while no significant differences were observed between higher contraction levels (20%, 40%, 60%, and 80% MVC). This pattern is indicative of the biphasic hypothesis, suggesting that the reflex amplitude significantly increases initially but plateaus as contraction intensity increases. These findings suggest that the initial increase and subsequent plateau in reflex amplitude may be influenced by changes in spinal excitability and inhibitory mechanisms as contraction intensity increases.

Propulsion power is an important metric in wheelchair racing. For a flat surface, it can be estimated from the sum of friction power and kinetic power. Usually, to determine friction power, the rolling and air drag coefficient first need to be determined with coast-down tests or other time-consuming methods. The aim of this paper was to investigate whether friction power could be estimated from Inertial Measurement Unit (IMU) data during wheelchair propulsion without the need for previously determining these coefficients. Two approaches were investigated using the kinematic data of a wheelchair athlete measured by a wheel, frame and trunk IMU. Firstly, an approach was used that considers the recovery phase of the propulsion cycle to be a coast-down period. Secondly, a machine-learning approach (Random Forest Regressor) was implemented. Coast-down tests were used to calculate a reference power with which the results from the two approaches could be compared. Results indicate that the machine-learning approach is more promising than the recovery phase analysis. However, whether the current machine-learning model can predict friction power for unseen subjects and surfaces should still be determined with inter-subject validation. Otherwise, it is recommended that a machine-learning model is trained for multiple subjects and a variation in conditions affecting friction force (surface, tyre pressure, wind, slope) to achieve a more robust model.

People can learn voluntary regulation of certain brain rhythms with help of real-time feedback through a brain-computer interface. Modulation of brain rhythms associated with movement, also known as sensorimotor rhythms (SMR), has shown to alter excitability of the spinal cord. This may indicate a potential role of the SMR in reflex modulation. Until now, no study has assessed the effect of SMR modulation in the mechanically induced stretch reflex. Additionally, inconsistencies in electroencephalography processing for extraction of human intent lead to contradictory results in SMR modulation abilities. In this report, a paradigm is suggested in which people are asked to navigate a virtual cursor to a target with their SMR activity. Once they reach adequate control, mechanical perturbations are applied to their wrist to measure reflex responses. This report summarizes the development and validation of the protocol. Five participants took part in the experiment, four of which successfully acquired control over their SMR. Furthermore, results from one subject suggest that with sufficient modulation of the SMR, changes can be seen in the strength of the stretch reflex. This protocol can be used to further investigate the role of the SMR in reflex modulation, which is useful in the context of rehabilitation of reflex abnormalities. 

Introduction Traumatic brain injury (TBI) is a leading cause of childhood morbidity, disability and mortality worldwide. In the treatment of TBI, neuromonitoring is essential to prevent secondary neurological damage. However, the use of neuromonitoring and specifically therapeutic targets is currently limited evidence-based.
Objective The primary objective is to implement suitable neuromonitoring parameters into a novel bedside dashboard for paediatric TBI patients. In addition, basic insights into neuromonitoring parameters between different outcome groups are provided.
Methods Intracranial pressure (ICP), cumulative ICP (ICP_cum), cerebral perfusion pressure (CPP), pressure reactivity index (PRx), wavelet transform PRx, optimal CPP (CPP_opt), partial pressure of arterial oxygen (P_aO₂), partial pressure of arterial carbon dioxide (P_aCO₂), end tidal CO2 (etCO₂), temperature and sodium levels were implemented into a dashboard. The parameters (except wPRx) were retrospectively analysed in TBI patients admitted to the paediatric intensive care unit (PICU) of the Erasmus MC- Sophia. Patients were divided into a good (GO) or bad (BO) outcome group. Per outcome group, the mean and 95 % confidence interval or the median and interquartile range of parameters were calculated.
Results A total of 35 patients (24 GO, 11 BO) were included. Significant differences between GO and BO were observed in median PRx (-0.06 [-0.13 – 0.01] vs. 0.17 [-0.05 – 0.39]), median percentage outside of the CPP_opt (curve) range (15 % [4 – 26] vs. 30 % [26 – 34]), ICP_cum distributions (12.0 mmHg [8.0 – 16.0] vs. 12.0 mmHg [8.5 – 15.5]) and mean sodium levels (146.4 mmol/L (144.5 – 148.3) vs. 151.2 mmol/L (148.6 – 153.8)).
Conclusion In a retrospective analysis, PRx, CPP_opt (curve) and ICP_cum showed potential to improve prognostication for paediatric TBI and to determine therapeutic targets. Based on our results, we recommend implementing MAP, ICP, ICP_cum, CPP alongside CPP_opt (curve), and sodium levels in a future neuromonitoring dashboard.

Background: Complex regional pain syndrome (CRPS) is a clinical disorder characterized by continuous, disproportionate pain and sensory, vasomotor, sudomotor and motor trophic changes. CRPS patients have a heterogeneous clinical picture caused by multiple underlying pathophysiology mechanisms including inflammation, vasomotor disturbances and central nervous system (CNS) dysregulation. Spinal cord stimulation (SCS) is believed to target multiple CRPS mechanisms by stimulating the dorsal column in the spinal cord. Closed-loop SCS is a recently developed form of SCS in which the stimulation intensity adapts to the patient's position, continuously stimulating the same amount of fibers in the dorsal column. This constant perceived stimulation intensity may benefit CRPS patients who are generally hypersensitive.

Objectives: To better understand the effects SCS has on the CRPS mechanisms, my research focuses on quantifying changes in vasomotor disturbances due to conventional SCS treatment using thermographic image analysis. In addition, exploratory analysis is performed in patients treated with closed-loop SCS to evaluate its effects on CRPS mechanisms.

Method: Various histogram features indicating temperature intensity were selected based on histogram distributions of the thermographic images. These features were then extracted from the affected and unaffected extremities of each image. The histogram features of patients with and without vasomotor improvement were compared based on the change in differences between affected and unaffected extremities after 3 months of SCS. The change between improved or not improved was then determined for different characteristics of the patients, such as affected extremity and CRPS type. It was hypothesized that with improved vasomotor symptoms, the affected and unaffected extremities would become more similar and thus the difference would become smaller.
For evaluation of the effects of closed-loop SCS on CPRS mechanisms, measurements were conducted before implantation and up to 6 months of follow-up. Measurements include thermographic images, CRPS severity score (CSS), Condition Pain Modulation (CPM), Temporal Summation (TS) and determination of sIL-2R levels using blood samples. In addition, conventional SCS was compared to closed-loop SCS, with patients randomized to receive both settings during the follow-up for two months.

Results: The following histogram features were selected: mean, median, minimum, maximum, peak, skewness, kurtosis, and quartile range. Based on 28 patients, for patients with improved vasomotor symptoms a decrease in difference was observed for histogram features mean, median, minimum, peak and quartile range. Furthermore, statistically significant differences were found in patients with vasomotor symptoms at baseline compared to patients without vasomotor symptoms for the mean (p=0.026), median (p=0.046), minimum (p=0.008), and quartile range (p=0.016). For patients with a cold CRPS type, statistically significant different feature values were observed between patients with and without vasomotor improvement in maximum (p=0.024), peak (p=0.016), and quartile range (p=0.027), with a decrease of histogram feature values. No statistically significant differences were found between the affected upper or lower extremities...

Reflex mechanisms are an efficient method humans use to deal with mechanical disturbances in daily life. In the muscle we see two reflexes, the M1 reflex and the M2 reflex. The M2 reflex is cortically modulated and is affected by intention
and habituation. A lot of research has been conducted on understanding the M2 reflexes, their origin and the factors influencing these reflexes. Less research, however, has been done to understand the cortical contribution of these M2 reflexes and what affects the muscle stretch evoked potentials. This research investigates the relationship between the stretch evoked potential and the corresponding M2 reflexes. We investigate the effects of the traditional ’Resist’ and ’Let Go’ tasks with a wrist manipulator on the evoked potential and M2 reflex, as well as the effect of longer periods between perturbations. This research showed that between the ’Let Go’ and ’Resist’ tasks, no difference in evoked potentials were present. There was a difference in the late M2 reflex however. The evoked potential was affected by the time between perturbations. A higher time between perturbations elicited a higher cortical response at the motor cortex as well as a higher M2 reflex. This result suggests that besides the task goal, the habituation and time between perturbation can be a significant factor at both the muscle as well as cortical levels. These results facilitate more elaborate research where the effect of these factors is investigated during voluntary movements.

Resting-state functional magnetic resonance imaging (rs-fMRI) is one of the promising non-invasive technology that helps in the detection of neurodegenerative and neurological disorders, localisation of the different areas of the brain and understanding the connectivity between them. It involves the acquisition of time series of MR images while the brain is at "resting-state" and serves as a biomarker for various neurological conditions. The acquired resting-state blood-oxygen-level-dependent (BOLD) data, however, can be corrupted with various artefacts (head movements, physiological movements like breathing etc.). Several preprocessing pipelines have been developed to counter the effect of these known artefacts. However, there might be some artefacts that could not have been attenuated from the signal and might lead to incorrect assessment. Therefore, the thesis proposes model-based filtering of the minimally preprocessed (free from known artefacts) resting-state BOLD signal. It was observed that these signals have long memory dependencies. Hence, the usage of autoregressive fractional integrative process filters is proposed for this purpose.
Furthermore, the utility of the approach is demonstrated by removing the effect of white noise from a synthetic signal with statistical properties similar to the resting-state BOLD signal. Afterwards, the proposed method is implemented on the minimally preprocessed resting-state BOLD data of 98 subjects from the Human Connectome Project. The results suggest that the proposed filter, in contrast to the low-pass filter, attenuates the higher frequencies but do not eliminate them. Additionally, four different evaluation measures (power spectrum, functional connectivity using Pearson's correlation and coherence, and eigenmode analysis) were considered. The results provide evidence that the proposed method can be used as an additional step in the already existing preprocessing pipeline to mitigate some artefacts that could not have been filtered out. Besides, the results also provide evidence that the proposed scheme is suitable to capture the dynamics of resting-state BOLD signals.

Human force proprioception has previously been shown to be important in manual control tasks. Recent experiments suggest that force proprioception is more accurate than position proprioception. Still, knowledge about proprioceptive qualities and their relevance in manual control is lacking or inconsistent. This research aims to experimentally establish the respective difference in force and position perception performance and attempts to demonstrate its influence on the neuromuscular system in manual control tasks and on which manipulator properties are optimal. The first experiment confirmed that the force sensing Golgi Tendon Organ (GTO) is more accurate than position sensing Muscle Spindles, by measuring smaller human just noticeable differences of force than of position in an experiment of discriminating side-stick manipulator stiffness at various conditions.
Offline simulations of a detailed model of the neuromuscular system in a manual control task validated higher GTO activity with non-zero stiffness manipulators than zero stiffness. The second experiment measured human control behavior in a double integrator controlled element pursuit task with varying manipulator stiffness intended to affect GTO activity. Zero stiffness manipulators showed worse tracking performance and lower degree of linearity of human control inputs which is related to less accurate control actions and higher uncertainty of quasi-linear human operator models. The two experiments combined demonstrate that humans' neuromuscular force sensors are more accurate than position sensors and that higher manipulator stiffness inducing higher force sensor activity results in more accurate control behavior.

Background: Determining how the reflex voluntarily modulates while performing activities of daily living (ADL), and understanding how this modulation might differ between healthy subjects and patients with motor disorders, can aid in developing a rehabilitative program to improve the functional performance of thewrist. The current study designs an ideal experimental protocol that would test reflex modulation as a response to perturbations during a goal-directed movement. Methods: A total of twelve participants participated in the five experiments (mean age 25.9 9 ± 3.6 years in the range 22 - 34, seven men and five women, all right-handed and with no history of neuromuscular impairment). The TU Delft Human Research Ethics Committee gave approval for the current study. The experimental protocol is separated into three pilot experiments, one main experiment and an addendum experiment after proven effectiveness of the protocol. The main experiment is conducted with ten subjects. The design process was iterative. The experiments were tested, designed and implemented on a wrist manipulator (PoPe). The transient perturbations are designed to be Ramp-and-Hold (R&H) perturbations of amplitude 0.08rad, 2rad/s with a 180ms hold, causinga stretch reflex response in the flexor carpi radialis (FCR). Results: The main experiment showed that the short-latency (M1) and long-latency (M2) areas in the FCR significantly differ with respect to the posture at which a perturbation is elicited. Upon showing the effectiveness, the experiment is further improved with the implementation of continuous pseudo-random binary signal (PRBS) perturbations to allow for continuous measuring of the stretch reflex, and thereby increasing protocol efficiency. Conclusions: The designed experimental protocol is, therefore, effective in observing reflex modulation during a goal-directed movement performed by the wrist.

The flash visual evoked potential (FVEP) is an electrical potential recorded with electroencephalogram (EEG) at the occipital cortex. Current FVEP assessment may be elaborated with the acquisition of stimulus response (SR) relation of the visual system. A drawback of this adjustment is the time required for data acquisition. This study aimed to develop an optimal (rapid) stimulus paradigm for assessing the SR relationship using FVEP.SR relationships were obtained using two different protocols in eight healthy participants; one considered 100 stimuli for 10 different intensity levels (standard technique), the other considered 1000 stimuli of varying intensity levels within a fixed intensity range (novel technique). Hypothetically the novel technique produces a similar SR relationship but requiring reduced number of stimuli. However, the present study did not find a significant intensity dependency on the FVEP. Consequently, no mathematical model for the SR relation was fit to the data, and exploration of the novel technique was excluded. Instead, the present study investigated the minimal number of stimuli required to acquire a representative FVEP component. Secondly, the potential change of FVEP components during the experiment was investigated. This study demonstrates that it is possible to acquire a reliable FVEP component with on average 54 stimuli (gross mean (39) + 1 SD (14)), independent of stimulus intensity. Additionally, this study demonstrated that the FVEP components change significantly (p<0.05) for most stimulus intensities when 1000 or more flashes are used; amplitudes increased with time for low intensity stimulation, while amplitudes reduced with time for high intensity stimulation. Although the present study did not find an intensity dependency of the FVEP component, it demonstrated that stimulation time is an important parameter when acquiring SR relationships using FVEP. The stimulation time certainly influenced the SR relationship calculated in the present study. Further studies can and should reduce the number of stimuli to produce a representative SR relationship using FVEP.

This thesis describes the process of selecting different greenhouse gas emission reduction technologies for the application on a redesign of a multi-purpose heavy-lift vessel. Only technologies were considered which did not negatively influence the operability or arrangement of the redesign. The best performing combination of technologies was identified using performance indicators which measured the economic and GHG emission reduction performance. The best performing combination of GHG emission reduction technologies results in an emission reduction potential of 20.6% compared to the currently operated vessel. It is concluded from this study that when only considering technologies on a redesign of a multi-purpose heavy-lift vessel which do not negatively influence the operability or arrangement, the IMO GHG emission reduction goals cannot be met.

Biologically inspired neural networks are a promising approach to understand the causes and improve the treatments of brain damage. Parkinson's disease is a progressive nervous system disorder that affects mainly movements, speech and cognitive problems. It symptoms cannot be cured, though medications can significantly improve the condition. Among the symptoms, tremor is the only one which remains unaffected by medications and is only responsive to deep-brain stimulation. A simplified, cortico-thalamo-cerebellar model will be simulated with spiking neural networks to evaluate the disease effects under dopamine depletion and connectivity weight changes. Confirming previous findings, striatal dopamine depletion was not found to cause tremor, nor its injection to affect tremor severity. The model showed evidence that parkinsonian weight changes in the pallidal inner feedback loop (GPi-GPe) are responsible of creating a suitable environment for the PD tremor oscillations to rise in the thalamus. Furthermore, both the GPi and the GPe present enhanced maximal activity coherent with muscular co-contraction onsets showing evidence of abnormal basal ganglia firing during re-emergent tremor. These findings may connect abnormal basal ganglia activity to the main parkinsonian motor impairments and may help explaining the beneficial effects of deep-brain stimulation on tremor severity.

Freezing of Gait (FoG) is a debilitating walking problem affecting over 50\% of Parkinson's Disease (PD) patients. Rhythmic cues during FoG can help patients to resume walking. FoG can be detected from lower limb acceleration data, but current detection algorithms lack context, resulting in false positive detection and initiation of cues when these are not required. Cues are only required during ambulatory motion. Adding a task classification model to an FoG detection device can help to increase specificity. Furthermore, using this model, an activity log of PD patients can be kept in the home environment, thereby facilitating disease evaluation. A decision tree model using Bayesian classifiers was developed for task classification. Predictors were extracted from raw data of an ankle-worn tri-axial accelerometer and the best predictors were determined at each decision node using feature selection methods. The proposed decision tree model (trained using healthy subject data) was tested on PD patient data to evaluate transferability. Furthermore, to compare performance and computational speed, our Bayesian decision node classifiers were compared to Naive Bayes classifiers. The proposed model was over 30 times faster, compared to the computational speed of using Naive Bayes classifiers at the decision nodes. Ambulatory windows were identified with a sensitivity over 91% for both healthy subjects and PD patients, showing that the Bayesian decision tree model developed in this study can provide context for an FoG detection wearable, to enable effective cueing. This will help patients to walk more confidently and to keep active.

The ability to control and adapt joint stiffness is essential in human motor control. Both control loops on the spinal as well as cortical level are likely to play a role in this regulation. However, the cortical mechanisms involved with the online adaptive control of joint stiffness remain largely unresolved. This study aimed at identifying cortical areas associated with the process of joint stiffness modulation using electroencephalography (EEG). EEG was recorded in twelve healthy right-handed individuals performing an active posture control task while receiving continuous random force perturbations applied using a robotic manipulator. To provoke a change in the neuromuscular control strategy, i.e. adaptation of joint stiffness, external viscous loads were applied or removed between tasks or instantaneously within tasks. Linear time-invariant system identification techniques were used to estimate joint stiffness between tasks. Cortical oscillatory dynamics were analysed for eight clusters of independent components, which were found using independent component analysis (ICA) and a subsequent dipole source localization method. Power spectral analysis of the time-invariant trials revealed significant enhancement of theta and beta oscillations in the left sensorimotor cortex (S1/M1) and suppression of delta rhythms in the supplementary motor area (SMA) when external damping was present. Analysis of event-related spectral perturbations (ERSPs) in the time-variant trials revealed delta and theta band enhancement in the SMA and sensorimotor cortex following immediately after external damping removal, as well as broadband enhancement in the prefrontal cortex (anterior cingulate cortex (ACC)). Moreover, we found more pronounced modulations in cortical activity with an unexpected decrease in external damping as compared to an increase in viscous loads. These results suggest that multiple cortical areas are likely to be involved in modulating joint stiffness when stability is at risk being the sensorimotor cortex, SMA and prefrontal cortex, whereas adaptive processes in response to increased stability margins might be regulated on a subcortical level.

Introduction: Pes equinus with increased ankle joint stiffness is a common impairment in stroke and Cerebral Palsy (CP) patients with structural and/or neural deficits of the ankle muscles. Equinus gait is characterized by toe-strike, abnormal ankle plantarflexion and decreased ankle range of motion (ROM). A new ankle-foot orthosis (AFO) with negative stiffness was previously developed to compensate for the increased ankle joint stiffness and improve equinus gait, reducing plantarflexion and increasing ankle ROM. The goal of this project was to predict the effects of ankle stiffness compensation on equinus gait simulations.

Methods: Forward simulations of unimpaired and equinus gait were generated in
the sagittal plane with a musculoskeletal model implemented in OpenSim and a
neural controller implemented in SCONE. After validation of the unimpaired gait
simulation, a sensitivity analysis on ankle kinematics was performed, introducing
structural and/or neural alterations of the ankle muscles to achieve an equinus gait. Consecutively, equinus gait simulations were validated with previously collected data of CP patients. Finally, an AFO model was developed in OpenSim to simulate AFO-assisted gait.

Results: The unimpaired gait simulation yielded realistic results, and was robust to all alterations, generating stable gaits. Shorter Gastrocnemius fiber length and/or increased plantarflexor muscles activations, with Tibialis Anterior weakness, had the largest effect on the ankle joint kinematics and resulted in realistic CP equinus gaits. Simulations of AFO-assisted gait resulted in reduced abnormal plantarflexion, and increased ankle ROM in the condition with shorter Gastrocnemius.

Discussion and Conclusion: This study presented realistic simulations of equinus
gait, by modelling structural and/or neural alterations of the ankle muscles and
predicted improved ankle function when compensating ankle stiffness with an external force. Although higher stiffness compensation and more simulations should be obtained, this study provides a solid ground for further investigation of the AFO effects. These results can ultimately assist in the prescription and tuning of the new AFO for patients with equinus.

The human sensorimotor system can be seen as a complex network in which the brain plays an important role, resulting in a difficult-to-understand relation between proprioceptive stimuli and cortical responses. However, understanding this relationship is of added value for understanding various diseases which cause dysfunctionality. In recent years, a variety of studies have been conducted towards finding the non-linear relationship between the cortical responses and wrist joint manipulation. This research is dedicated to providing an initial set-up to create models that are able to provide accurate predictions despite noisy data. The relationship between wrist joint manipulation and the cortical response is assumed to be non-linear and the corresponding identification method is categorized in a two-step process, namely the model structure, i.e. Volterra series, and stochastic identification method, i.e. Bayesian Inference. To understand the working principle of the proposed algorithm, the method is first applied to a set of computer models. Finally, an attempt is made to model the cortical responses evoked by wrist joint manipulations

Reflexes and co-contraction are the two mechanisms used for effective limb control when humans face unexpected perturbations in their daily activities. When the environment has reduced stability margins, reflexes are tempered due to the oscillations caused by the neural time delay of the reflexive pathways. An explanation is that reflexes adapt to the dynamics of the environment and stability margins are the constraint. This view requires that humans assess stability margins, which could happen by detecting changes (i.e. oscillations) in the perturbation eliciting the reflexes. The perturbation perceived by the human is the actual perturbation filtered by the dynamics of the environment. Therefore, changes in the stability of the environment influence the perceived perturbation. The goal of this study is to determine whether reflex modulation is triggered by the environmental dynamics (i.e. damping and stability margins) or by the properties of the perturbation eliciting a reflexive response. An experiment was designed where participants were asked to minimize the displacements caused by continuous force perturbations applied to the hand while interacting with different environmental dynamics. Some of the perturbations were prefiltered to mimic the filtering effect of the environmental dynamics. Variations in the dynamics of the shoulder joint were quantified through the estimated arm admittance (i.e. displacements in response to force perturbations). The results show variations in the admittance between the perturbations mimicking the environment and the true environment at low frequencies (below 5Hz); and for different prior knowledge about the environmental dynamics (below 2Hz). These variations indicate that perturbations can be designed to mimic the environmental dynamics, and that perturbation properties and stability constraints cause changes in the motor behaviour.