Conductance-based model of the basal ganglia in Parkinson's Disease

Abstract

Parkinson's Disease (PD) is associated with a reduced level of dopamine in the substantia nigra pars compacta (SNc) which is one of five nuclei in the basal ganglia, a part of the brain that plays a key role in voluntary movement. There are three pathways for information transmission through the basal ganglia: the 'Direct' pathway, going straight to the Globus Pallidus internal (GPi) from the Striatum, the 'Indirect' pathway through the Globus Pallidus external (GPe) and the Subthalamic Nucleus (STN) to the GPi and the 'Hyperdirect' pathway through the STN from the cortex to the GPi. Due to loss of dopamine and its different effects on these pathways, there is an excessive inhibition of the thalamus and disruption of movement in PD. Increased synchrony and oscillations in the tremor and beta frequency bands in the STN, GPe and GPi nuclei are observed in PD. Deep Brain Stimulation (DBS), used to treat the main motor symptoms of PD in medically refractory patients has been shown to reduce pathological tremor and beta band activity in the basal ganglia. However, it is unclear how the different pathways are affected by reduced dopamine levels, what the origins of these oscillations are or what the mechanisms by which DBS quenches them are. In this study, a conductance-based model of basal ganglia, including two major pathways, indirect and hyperdirect is proposed to investigate pathological oscillations in PD and explore possible origins for tremor and beta band synchronization. The model is also used to illustrate the effect of DBS on pathological tremor and beta band oscillations when applied to the STN.