Jha, A; (2013) Functional Networks in Parkinson’s Disease. Doctoral thesis (PhD), UCL (University College London).

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Abstract

Parkinson’s Disease (PD) is a common neurodegenerative condition characterised pathologically by progressive dopaminergic cell loss in the substantia nigra pars compacta, dopamine depletion and resulting cortico- basal ganglia circuit dysfunction. There is a considerable variation in symptoms and treatment response between patients and therefore a need to individualise treatments, such as dopamine replacement therapy, and deep brain stimulation (DBS). We therefore require a better understanding of how different motor and non-motor symptoms emerge from the cortico-basal ganglia dysfunction characteristic of PD. In this thesis, I investigated the hypothesis that distinct symptoms in PD may be due to the dysfunction of distinct cortico-basal ganglia circuits. I characterised cortico-basal ganglia coupling by simultaneously recording cortical activity with magnetoencephalography (MEG) and basal ganglia activity from intracranial electrodes placed during DBS surgery for PD. Coupling was measured in terms of coherence – a frequency specific measure of coupling. I found that resting cortico-basal ganglia networks had distinct cortical topographies at different frequencies. Frontal regions coupled to both the subthalamic nucleus (STN) and the pedunculopontine nucleus region (PPNR) in the beta frequency band whilst temporal, parietal and cerebellar areas coupled in the alpha range. I hypothesised that activity in the frontal beta network may relate to executive function, and found that local synchronisation in two frontal cortical hubs was related to stopping an on-going movement – a crucial executive function. In a related experiment in PD patients, transient frontal – basal ganglia coupling was again apparent during motor inhibition, but how this is related to behavioural performance needs further investigation. These results are useful in highlighting how cortico-basal ganglia networks can be separated both spatially and spectrally and how the function and dysfunction of these networks can be interrogated in PD patients. Future work should determine how different stimulation parameters differentially affect these distinct circuits.

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