Phase-Amplitude Coupling of Local Field Potentials in Subthalamic Nucleus in Parkinson’s disease
University Health Network
Parkinson’s disease (PD) is one of the commonest neurodegenerative disorders and the prevalence of which is expected to increase with an aging population in Canada and worldwide. In PD, there is degeneration of dopaminergic neurons in the basal ganglia (BG), leading to disruption of the circuits and clinical features of the disease such as rest tremor, rigidity, bradykinesia and postural instability. Deep brain stimulation (DBS) of the subthalamic nucleus (STN), one of the components of the BG, is now an established treatment for moderate to advanced PD. Although the exact mechanism of action of DBS in PD is still uncertain, research studies using DBS electrodes can help to understand the circuits of the BG and the pathophysiology of PD. Further, benefits of STN-DBS in PD patients are variable and factors affecting the efficacy of DBS are not clearly known. Although research studies have reported increased EEG-PAC in the OFF medication state in PD which gets normalized by ON medication and DBS, utility of EEG-PAC in predicting the efficacy of DBS has not been examined. Thus, we will investigate pre-operative EEG-PAC as a non-invasive predictor of STN-DBS effectiveness to help select PD patients for DBS.
Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging
Local field potential (LFP) recordings directly from DBS electrodes during the immediate postoperative period before internalization of electrode leads provide unique insights into local deep brain activities. DBS for PD is currently based on an open-loop model with fixed parameters established by labor-intensive programming that involves many clinical visits to adjust the stimulation settings to optimize benefits. Hence, there is considerable interest to identify optimal stimulation parameters and improve DBS through closed-loop or adaptive DBS using neuronal oscillations to provide the feedback signals. However, the optimal feedback signal that should reflect clinical state of the patient has not been established.
Phase-amplitude coupling (PAC) refers to the correlation of the phases of low frequency oscillations to the amplitudes of high frequency rhythms. Since the amplitude of the high frequency signal reflects neuronal spikes and phase of low frequency reflects the synaptic activities, PAC can show interactions between neuronal networks. We propose to record STN PAC from DBS electrodes and correlate the findings with clinical improvement to evaluate this measure as a potential feedback signal for closed-loop DBS and to make clinical programming easier by identifying the optimal clinical contacts for DBS.