Bradykinesia models of Parkinson’s disease

This entry describes a plethora of experimental observations from PD bradykinesia in humans and animals ranging across neuronal, electromyographic and behavioral levels and discusses related theoretical and computational models developed to reproduce and explain these findings. Some computational models of bradykinesia have focused entirely on the effects of dopamine depletion in the basal ganglio-thalamo-cortical relations, whereas others emphasize dopamine depletion in cortico-spino-muscular interactions. Future models will have to produce a more comprehensive and detailed neural model of basal ganglia-thalamo-cortico-spino-muscular interactions, in order to study more systematically the effects of dopamine depletion in these nuclei and integrate into a ‘unified theory’ all the known neurophysiological, EMG and behavioral observations associated with parkinsonism

Technological advances in deep brain stimulation:Towards an adaptive therapy

Parkinson's disease (PD) is neurodegenerative movement disorder and a treatment method called deep brain stimulation (DBS) may considerably reduce the patient’s motor symptoms. The clinical procedure involves the implantation of a DBS lead, consisting of multiple electrode contacts, through which continuous high frequency (around 130 Hz) electric pulses are delivered in the brain. In this thesis, I presented the research which had the goal to improve current DBS technology, focusing on bringing the conventional DBS system a step closer to adaptive DBS, a personalized DBS therapy. The chapters in this thesis can be seen as individual building blocks for such an adaptive DBS system. After the general introduction, the first two chapters, two novel DBS lead designs are studied in a computational model. The model showed that both studied leads were able to exploit the novel distribution of the electrode contacts to shape and steer the stimulation field to activate more neurons in the chosen target compared to the conventional lead, and to counteract lead displacement. In the fourth chapter, an inverse current source density (CSD) method is applied on local field potentials (LFP) measured in a rat model. The pattern of CSD sources can act as a landmark within the STN to locate the potential stimulation target. The fifth and final chapter described the last building block of the DBS system. We introduced an inertial sensors and force sensor based measurement system, which can record hand kinematics and joint stiffness of PD patients. A system which can act as a feedback signal in an adaptive DBS system

Evaluation of the Effects of Various Exercise Interventions on Parkinson’s Disease

The overall purpose of the current thesis was to evaluate the influence of various exercise strategies on Parkinson’s disease (PD). While countless exercise interventions have been investigated by PD, results have been weak and inconclusive at best. As such, there are currently no scientifically-validated recommendations for an optimal exercise intervention. The four studies comprising this thesis have attempted to address the shortcomings of previous literature, namely, inconsistent use of outcome measures, lack of PD symptomatic measures, varying lengths of exercise interventions, absence of a non-exercise control group, continued assessment of participants after exercise has ended, and verifying replicabilty of findings. The first study was focused on identifying objective outcome measures that are predictive or reflective of the classic symptoms associated with PD. Symptomatic assessment was conducted using the Unified Parkinson’s disease Rating Scale (UPDRS), the current gold standard for assessment of PD symptom severity. Objective outcome measures included the timed-up-and-go (TUG), grooved pegboard (GP), and spatiotemporal aspects of self-paced gait (velocity, step length). Backward elimination regression analysis demonstrated that the place phase of the GP was the most predictive of UPDRS score. Interestingly, no objective outcome measures were strongly correlated with change on the symptomatic subsets that they were believed to be theoretically evaluating. The results point to the continued need to identify objective outcome measures reflective of symptomatic assessment. Further, exercise rehabilitation trials should combine outcome measures with symptomatic assessment to ensure that improvements are reflective of symptomatic improvement. The second study compared the influence of four exercise interventions (in contrast to a non-exercising control group) on the symptoms of PD. The exercise interventions included aquatic exercise, aerobic training, strength training and sensory focused exercise (PD SAFEx). Each participant exercised three times per week for a twelve week period and the same trained evaluator (blinded to group assignment) performed symptomatic assessment of all participants before exercise began (pre-test), after exercise ended (post-test) and following a minimum six week non-exercise period (washout). Results displayed that the strength training and PD SAFEx interventions had the greatest symptomatic benefit from pre-test to post-test. The aerobic intervention had no apparent change to symptom severity across all three testing periods. Overall, the current study suggests that PD SAFEx and strength training are more beneficial for individuals with PD than aerobic or aquatic exercise. The third study attempted to determine the influence of increased focus on sensory feedback by comparing two identical exercise interventions that differed only in the presence (PD SAFEx) or absence (non-SAFE) of increased attention on sensory (specifically proprioceptive) feedback. Symptomatic assessment was combined with objective outcome measures that assessed upper limb motor control, functional gait and spatiotemporal aspects of self-paced gait. Findings suggested that both exercise interventions resulted in similar benefits on the objective outcome measures, including upper limb motor control (assessed using the grooved pegboard), functional gait (assessed using the timed-up-and-go) and velocity and step length of self-paced gait. Interestingly, only the PD SAFEx intervention resulted in improved PD symptoms assessed using the UPDRS and symptomatic improvement was maintained after a six week non-exercise period. Thus, the increased focus on sensory feedback present in the PD SAFEx intervention appears to have an important additional influence on the symptoms of PD. The final study assessed whether improved PD symptoms following a sensory attention focused exercise (PD SAFEx) intervention could be replicated across multiple administrations and secondly, whether the effect could be replicated when administered by minimally trained individuals in the community. The PD SAFEx intervention was administered to four separate groups at the Movement Disorders Research and Rehabilitation Center (MDRC) and twice at an exercise facility in the community (YMCA). Over the six administrations of the PD SAFEx intervention, similar symptomatic improvements were realized by participants. Interestingly, the community based intervention appeared to gain a greater symptomatic benefit than the PD SAFEx intervention administered by leaders knowledgeable in movement disorders and the underlying neurological deficits focused on in the PD SAFEx intervention suggests that the feasibility of global distribution of the PD SAFEx intervention would be a logical direction for future research. The methodological improvements employed in the current thesis allowed for detailed and thorough comparisons to be drawn between various exercise interventions. It has been shown that strength training and PD SAFEx interventions have the greatest symptomatic benefit for individuals with PD. Further, the beneficial effect of increased focus on sensory feedback and the simplicity of application of the PD SAFEx intervention suggest that the PD SAFEx intervention should be further explroed for its ability to be globally implemented

The use of current steering during subthalamic deep brain stimulation to alleviate upper limb symptoms of Parkinson\u27s disease

Subthalamic (STN) deep brain stimulation (DBS) is an established treatment to alleviate the appendicular motor symptoms of Parkinson\u27s Disease (PD). Current steering during DBS allows the unequal fractionation of current between two electrodes on the lead, resulting in a non-spherical electrical field. It is hypothesized that the way the electrical field is shaped will affect a patient’s upper limb symptom alleviation. Seven PD patients who underwent bilateral STN-DBS were tested over four weeks post-operation. 16 current fractionation settings were tested each week at an amplitude that increased weekly. Optimal setting was defined as the setting that provided the best symptom improvement based on kinematic data detected by a motion capture system and the Unified Parkinson\u27s Disease Rating Scale. Results assessing right and left upper limb symptoms gave 14 optimal settings in seven patients, of which eight settings employed current steering either unilaterally or bilaterally, and six settings employed bilateral monopolar stimulation. Thus, the use of current steering was patient-dependent and limb-dependent; factors contributing to this finding include differences in lead placement, symptom heterogeneity, and possible differences in STN functionality