Modeling Epilepsy and Parkinson’s Disease and the Impact of Electrical Brain Stimulation

Parkinson's disease (PD) is neurological disorder characterized by degeneration of dopaminergic neurons in motor circuits of the brain. Pathologically synchronous activity within the corticothalamic-basal ganglia (CTBG) network has been identified to play an important role in the motor symptoms of the disease; however, the mechanisms underpinning this aberrant activity remain an open matter of debate. While the efficacy of deep brain stimulation (DBS) treatments is apparent in their clinical outcomes, it is not clear what impact stimulation has on large scale brain activity and how this leads to an effective therapy in PD. Additionally, it remains to be shown what DBS parameters are most therapeutically effective as these have traditionally been estimated via trial and error. Chapter 1 presents an overview of the relevant background material, including the pathophysiology of PD, DBS treatments, and large scale brain modeling, with a particular focus on the neural field theory used in this thesis. Chapter 2 unifies existing neural field models of generalized epilepsy in the corticothalamic (CT) system, and PD in the CTBG system, and explores parallels between the two disorders. Chapter 3 further develops the neural field model of the CTBG system and introduces a novel theory of DBS of the subthalamic nucleus (STN). The results show how pathologically synchronous CTBG activity in the beta frequency band (13-30 Hz) are produced via weakly damped resonances in key loops formed between the basal ganglia and cortex. Furthermore, it is demonstrated how DBS suppresses this enhanced beta activity by reducing aberrant gains in a frequency dependent manner. Chapter 4 expands upon the work in Ch. 3 using the DBS model to compare the suppressive effects of several stimulation protocols, including target nuclei, on pathological levels of beta activity within the basal ganglia, and coherence between the basal ganglia and cortical populations