Williams, David; (2004) The functional significance of oscillatory local field potential activity in the Parkinsonian subthalamic nucleus. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

It has long been evident that oscillations are manifest in the local field potential (LFP) activity recorded in regions of the brain as diverse as olfactory, somatomotor, parietal and occipital cortex within primates. Further investigations have demonstrated similar oscillatory activity within cerebellum and thalamus in primates and sub-primates and in recent years within the LFP activity of the human basal ganglia. However, the capricious nature of much of the frequency content particularly in the beta band, in many of these areas, has resulted in speculation concerning the functional significance of this activity. The current thesis sought to test the hypothesis that oscillatory activity, particularly in the beta band (ca. 13-30 Hz), evident in the LFP activity of the parkinsonian subthalamic nucleus (STN) has significance in the motor related function of the nucleus. In order to examine this fundamental proposition a series of predictions derived from this hypothesis have been tested. Firstly, that given the known anatomical connectivity of the STN, receiving prominent projections from cortex and in turn sending projections to globus pallidus interna (GPi) and substantia nigra pars reticulata (SNr), activity of functional relevance should display similar patterns of connectivity. Secondly, that suppression of average power in the beta band of LFP activity associated with the presentation of movement-related cues should display response bias for functionally relevant stimuli. Thirdly, that these modulations of power observed in human subjects in response to behaviourally relevant stimuli should correlate not merely in gross terms with behaviour, but in a consistent discernable manner with aspects of behavioural performance. The present work shows in simultaneous recordings of the electroencephalogram (EEG) and STN LFP that significant coherence exists between regions exhibiting both beta band oscillatory activity and anatomical cortico-striatal connectivity in cortex, and the parkinsonian STN; phase analysis further suggesting a cortical drive. This connectivity appears dopamine dependent with coherent activity in the beta band most evident on withdrawal of l-dopa medication, while coherence in the gamma band (ca. 60-80 Hz) is pronounced with l-dopa. Furthermore, beta band activity, previously shown to display suppression with movement is not only shown to exhibit similar modulation after cues allowing movement preparation, but to a greater extent with more informative cues than less informative. Finally, in contrast to prior efforts to display a relationship between beta oscillations and behaviour in the motor system, it is shown that there exists a consistent relationship between beta oscillation suppression and motor performance apparent across single trial data. These observations in the context of other work in both cortex and sub-cortex appear consistent with the functional significance of oscillatory activity in the parkinsonian STN and allow the formation of a further hypothesis as to its function and mechanism.

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