Motor Adaptation and Automaticity in People with Parkinson’s Disease and Freezing of Gait

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by cell death in the substantia nigra pars compacta, resulting in motor symptoms of tremor, rigidity, bradykinesia and gait impairment. Freezing of gait (FOG) is one serious gait disturbance, characterized by a transient inability produce effective stepping during walking and turning, and affects roughly half of people with PD at some point during their disease. Despite the ongoing research on the behavioral, neurological, and cognitive characteristics of people with FOG (PD+FOG), the mechanisms underlying freezing are still poorly understood. The overall aim of this work was to further investigate motor behavior in PD+FOG to provide insight into its potential mechanisms. The first experiment investigated possible cerebellar dysfunction in PD+FOG by examining visuomotor adaptation, a well-known cerebellar-dependent process. We found that there were no differences in reaching or walking adaptation between freezers and non-freezers, however non-freezers exhibited smaller after-effects compared to freezers and healthy older adults. Furthermore, adults with PD, as well as older and younger adults adapt walking patterns slower than reaching patterns, indicating walking is a more complex task requiring greater sensorimotor processing to modify. Overall, this study showed that cerebellar function, in terms of its role in sensorimotor adaptation, is relatively preserved in PD and FOG. In the second experiment, we examined motor automaticity of saccadic eye movements and reaching. Reduced automaticity is a likely motor-cognitive mechanism that contributes to freezing behavior, however automaticity in other motor systems has yet to fully described. Using an anti-saccade task, we found that PD+FOG participants were slower to respond to both automatic and non-automatic eye movements, and had increased saccade velocity variability compared to PD-FOG and controls. These changes were not related to disease severity or general cognition. In contrast, both PD groups were slower to execute (greater latency) reaching movements during both pro- and anti-reaching, but no freezer non-freezer differences were noted. PD+FOG reached with lower peak velocity compared to older adults but were similar to PD-FOG during both automatic and non-automatic conditions. These data show that changes in automaticity and control exist outside locomotor centers, indicating freezing may be a global motor disturbance. Altogether, the work in this dissertation furthers our knowledge on motor control in PD+FOG and provides additional evidence that freezing affects non-gait motor function

Motor patterns evaluation of people with neuromuscular disorders for biomechanical risk management and job integration/reintegration

Neurological diseases are now the most common pathological condition and the leading cause of disability, progressively worsening the quality of life of those affected. Because of their high prevalence, they are also a social issue, burdening both the national health service and the working environment. It is therefore crucial to be able to characterize altered motor patterns in order to develop appropriate rehabilitation treatments with the primary goal of restoring patients' daily lives and optimizing their working abilities. In this thesis, I present a collection of published scientific articles I co-authored as well as two in progress in which we looked for appropriate indices for characterizing motor patterns of people with neuromuscular disorders that could be used to plan rehabilitation and job accommodation programs. We used instrumentation for motion analysis and wearable inertial sensors to compute kinematic, kinetic and electromyographic indices. These indices proved to be a useful tool for not only developing and validating a clinical and ergonomic rehabilitation pathway, but also for designing more ergonomic prosthetic and orthotic devices and controlling collaborative robots

Fear of falling, falls and near falls in Parkinson’s disease

ABSTRACTAIM: The overall aim of this longitudinal PhD project was to gain increased knowledge about factors associated with fear of falling (FOF) falls and near falls, as well as to contribute to improved clinical fall prediction for peoplewith mild Parkinson’s disease (PD).METHODS: People diagnosed with PD and receiving care at the university hospital outpatient neurology clinic were assessed during the “on” phase using a broad range of rating scales and clinical tests targeting balance and gait problems as well as motor and non-motor symptoms. The participants then registered all prospective falls and near falls for six months by using a diary.RESULTS: Paper I identified everyday walking difficulties as the strongest factor independently associated with FOF, followed by independence in daily activities, functional balance, and fatigue. Paper II identified FOF to be the strongest factor independently associated with prospective falls and/or near falls, followed by history of near falls, and retropulsion during an unexpected shoulder pull. Paper III showed that the discriminate ability of a recently suggested clinical 3-Step Falls Prediction Model (3-step model) is acceptable and better than that of single predictors. Extended analyses showed that a new model for prediction of falls and/or near falls (including history of near falls, tandem gait and retropulsion) had better discriminant ability than the 3-step model. Paper IV found that different standardizations of the 10-Meter Walk Test (10MWT) for measuring gait speed yielded very similar results, including cut-off scores for future falls, suggesting that the clinical conduct of 10MWT can be simplified.CONCLUSIONS: Everyday walking difficulties should be a primary target when attempting to reduce FOF in mild PD, and balance training should focus on self-generated perturbations caused by everyday activities ratherthan external perturbations. Moreover, FOF and asking about prior near falls seem to be important issues for prediction of falls and near falls early in the disease course. The 3-step model can be recommended as a clinicalprediction tool but a new model may be considered a promising alternative. Clinical gait speed measurement by the 10MWT can be simplified by not using acceleration distance or repeated trials in mild PD

Oscillation-specific nodal alterations in early to middle stages Parkinsons disease.

Background: Different oscillations of brain networks could carry different dimensions of brain integration. We aimed to investigate oscillation-specific nodal alterations in patients with Parkinsons disease (PD) across early stage to middle stage by using graph theory-based analysis. Methods: Eighty-eight PD patients including 39 PD patients in the early stage (EPD) and 49 patients in the middle stage (MPD) and 36 controls were recruited in the present study. Graph theory-based network analyses from three oscillation frequencies (slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz; slow-3: 0.073-0.198 Hz) were analyzed. Nodal metrics (e.g. nodal degree centrality, betweenness centrality and nodal efficiency) were calculated. Results: Our results showed that (1) a divergent effect of oscillation frequencies on nodal metrics, especially on nodal degree centrality and nodal efficiency, that the anteroventral neocortex and subcortex had high nodal metrics within low oscillation frequencies while the posterolateral neocortex had high values within the relative high oscillation frequency was observed, which visually showed that network was perturbed in PD; (2) PD patients in early stage relatively preserved nodal properties while MPD patients showed widespread abnormalities, which was consistently detected within all three oscillation frequencies; (3) the involvement of basal ganglia could be specifically observed within slow-5 oscillation frequency in MPD patients; (4) logistic regression and receiver operating characteristic curve analyses demonstrated that some of those oscillation-specific nodal alterations had the ability to well discriminate PD patients from controls or MPD from EPD patients at the individual level; (5) occipital disruption within high frequency (slow-3) made a significant influence on motor impairment which was dominated by akinesia and rigidity. Conclusions: Coupling various oscillations could provide potentially useful information for large-scale network and progressive oscillation-specific nodal alterations were observed in PD patients across early to middle stages

Altered activation and connectivity of the supplementary motor cortex at motor initiation in Parkinson's disease patients with freezing

OBJECTIVE Motor initiation failure is a key feature of freezing of gait (FOG) due to Parkinson's disease (PD). The supplementary motor cortex (SMC) plays a central role in its pathophysiology. We aimed at investigating SMC activation, connectivity and plasticity with regard to motor initiation in FOG. METHODS Twelve patients with FOG and eleven without FOG underwent a multimodal electrophysiological evaluation of SMC functioning including the Bereitschaftspotential and movement-related desynchronisation of cortical beta oscillations. SMC plasticity was modulated by intermittent theta burst stimulation (iTBS) and its impact on gait initiation was assessed by a three-dimensional gait analysis. RESULTS Prior to volitional movements the Bereitschaftspotential was smaller and beta power was less strongly attenuated over the SMC in patients with FOG compared to those without. Pre-motor coherence between the SMC and the primary motor cortex in the beta frequency range was also stronger in patients with FOG. iTBS resulted in a relative deterioration of gait initiation. CONCLUSIONS Reduced activation of the SMC along with increased SMC connectivity in the beta frequency range hinder a flexible shift of the motor set as it is required for gait initiation. SIGNIFICANCE Altered SMC functioning plays an important role for motor initiation failure in PD-related FOG

Fall Prevention Using Linear and Nonlinear Analyses and Perturbation Training Intervention

abstract: Injuries and death associated with fall incidences pose a significant burden to society, both in terms of human suffering and economic losses. The main aim of this dissertation is to study approaches that can reduce the risk of falls. One major subset of falls is falls due to neurodegenerative disorders such as Parkinson’s disease (PD). Freezing of gait (FOG) is a major cause of falls in this population. Therefore, a new FOG detection method using wavelet transform technique employing optimal sampling window size, update time, and sensor placements for identification of FOG events is created and validated in this dissertation. Another approach to reduce the risk of falls in PD patients is to correctly diagnose PD motor subtypes. PD can be further divided into two subtypes based on clinical features: tremor dominant (TD), and postural instability and gait difficulty (PIGD). PIGD subtype can place PD patients at a higher risk for falls compared to TD patients and, they have worse postural control in comparison to TD patients. Accordingly, correctly diagnosing subtypes can help caregivers to initiate early amenable interventions to reduce the risk of falls in PIGD patients. As such, a method using the standing center-of-pressure time series data has been developed to identify PD motor subtypes in this dissertation. Finally, an intervention method to improve dynamic stability was tested and validated. Unexpected perturbation-based training (PBT) is an intervention method which has shown promising results in regard to improving balance and reducing falls. Although PBT has shown promising results, the efficacy of such interventions is not well understood and evaluated. In other words, there is paucity of data revealing the effects of PBT on improving dynamic stability of walking and flexible gait adaptability. Therefore, the effects of three types of perturbation methods on improving dynamics stability was assessed. Treadmill delivered translational perturbations training improved dynamic stability, and adaptability of locomotor system in resisting perturbations while walking.Dissertation/ThesisDoctoral Dissertation Biomedical Engineering 201