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Title: Insights into the neural basis of paradoxical kinesia in Parkinson's disease
Author: Anzak, A.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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Enhancements in peak motor performance have been demonstrated in response to intense stimuli both in healthy subjects and in the form of ‘paradoxical kinesis’ in patients with Parkinson’s disease. Might the latter phenomenon thus reflect a physiological process? The first study outlined in this thesis suggests this may be the case, as maximal effort grips in healthy subjects undergo dramatic enhancements when the imperative visual cue is accompanied by an intense auditory tone. Analogous enhancements in motor performance are demonstrated in a second study of patients with Parkinson’s disease and age-matched healthy controls. Remarkably, the facilitating effect of loud auditory tones is similar whether patients are off or on dopaminergic medication, suggesting a potentially non-dopaminergic basis for the phenomenon. A role of sub-cortical systems in the performance enhancements engendered by intense stimuli is next considered. Local field potentials recorded from the subthalamic nuclei of patients with Parkinson’s disease, whilst they undertake the above established paradigm, identify both theta/alpha (5-12 Hz) and high gamma/high frequency (55-375 Hz) activity as exhibiting remarkable scaling with maximal motor responses to the visual cue alone, but having little explanatory influence on performance enhancements beyond this. In the final study, a short-latency evoked potential in subthalamic nucleus local field potential recordings, which scales in amplitude with both stimulus intensity and corresponding enhancements in biomechanical measures of maximal handgrips, is identified. Interference with this potential through high frequency deep brain stimulation of the same nucleus, leads to a diminished behavioural effect of stimulus intensity. Recordings of a similar evoked potential in the related pedunculopontine nucleus – a key component of the reticular activating system – provide support for this neural signature as a physiological correlate of ascending arousal, propagated from the reticular activating system to exert an ‘energizing’ influence on motor circuitry through the subthalamic nucleus.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available