Introduction: Parkinson’s disease (PD) is characterized by a loss of dopamine producing cells in a brainstem nucleus called the substantia nigra pars compacta. The loss of these cells impacts the function of several brain regions, especially the basal ganglia structures, which are intimately involved in voluntary movement control as well as cognition and other functions. Tremor in the extremities, stiffness of joints, gait and balance problems are some of the cardinal motor symptoms of PD.
However, the exact combination of symptoms (both motor and non-motor) expressed in a patient and its severity varies from person to person. Imaging studies have shown differences in the dopamine uptake patterns in the basal ganglia nuclei between the various parkinsonian phenotypes.
Objective: This study aims to quantify the physiological changes in the activity patterns of neurons in the globus pallidus and subthalamic nucleus and to contrast the changes between various PD phenotypes. The STN and pallidum are of specific interest because deep brain stimulation (DBS) therapy or lesioning in these structures has shown to be effective in minimizing many of the motor symptoms of PD.
Methods: Patient’s enrolled for DBS or lesion surgery to alleviate parkinsonian symptoms were identified from a movement disorders database. Patients for whom both the complete OFF medication unified Parkinson's disease rating score (UPDRS) and electrophysiology data from the globus pallidus or STN were available where included in this study. Patients were sorted into the tremor dominant or akinetic rigid group based on their UPDR score. The average scores relating to tremor symptoms were divided by the average rigidity and posture scores to create a ratio. Patients were then put into groups according to their ratio score. The times of occurrence of action potentials from single neurons were identified from the electrophysiology records. These timestamps were used to calculate the average discharge rate of the cell and to identify and quantify the presence of bursting and oscillatory activity.
Results: A total of 61 patients have been identified from the database. 23% (n=14) patients were characterized as tremor-dominant and 77% (n=47) as akinetic-rigid. A total of 40 electrophysiology recordings from the pallidum and 27 from the subthalamic nucleus (STN) are available for the tremor- dominant group. For the akinetic-rigid group 305 and 145 cells are available from the pallidum and STN respectively. We are currently in the process of quantifying and comparing the neuronal activity patterns.
Discussion: The Underlying mechanisms that result in PD are still unclear. It is also unknown why deep brain stimulation has the therapeutic effect that it does. An understanding of the changes in basal ganglia structures during PD and specifically the differences between the different subsets of PD will enable us to further our understanding of how PD develops. Measuring the different firing patterns may also help us understand the physiological mechanism behind DBS benefits and help physicians target the best structures to maximize the therapeutic effects of DBS.
This research was supported by the Undergraduate Research Opportunities Program (UROP).
Activity patterns in the Globus Pallidus, Thalamus and Sub-thalamic Nucleus in Akinetic-Rigid and Tremor Predominant Parkinsonian Patients.
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