Abstract
A large-scale computational model of the basal ganglia network and thalamus is proposed to describe movement disorders and treatment effects of deep brain stimulation (DBS). The model of this complex network considers three areas of the basal ganglia region: the subthalamic nucleus (STN) as target area of DBS, the globus pallidus, both pars externa and pars interna (GPe-GPi), and the thalamus. Parkinsonian conditions are simulated by assuming reduced dopaminergic input and corresponding pronounced inhibitory or disinhibited projections to GPe and GPi. Macroscopic quantities are derived which correlate closely to thalamic responses and hence motor programme fidelity. It can be demonstrated that depending on different levels of striatal projections to the GPe and GPi, the dynamics of these macroscopic quantities (synchronisation index, mean synaptic activity and response efficacy) switch from normal to Parkinsonian conditions. Simulating DBS of the STN affects the dynamics of the entire network, increasing the thalamic activity to levels close to normal, while differing from both normal and Parkinsonian dynamics. Using the mentioned macroscopic quantities, the model proposes optimal DBS frequency ranges above 130 Hz.
Highlights
1.1 Basal ganglia connectivityParkinson’s disease (PD) and dystonia, including different types, belong to the most common movement disorders and pose a considerable health burden (Chesselet and Delfs 1996; Defazio 2010; de Lau and Breteler 2006)
Our network model includes in addition to 3 areas of the basal ganglia: the subthalamic nucleus (STN), the globus pallidus internal (GPi) and external (GPe) a part of the thalamus (THA), see Fig. 1
For different values of parameters, the model reproduces phase transitions for normal, Parkinsonian, and deep brain stimulation (DBS), in the emergent dynamics which are captured with suitable macroscopic order parameters for example the change from oscillatory to bursting behaviour of mean synaptic activity in Fig. 12a, b
Summary
Parkinson’s disease (PD) and dystonia, including different types, belong to the most common movement disorders and pose a considerable health burden (Chesselet and Delfs 1996; Defazio 2010; de Lau and Breteler 2006). It is generally accepted that they arise from a dysfunction of the basal ganglia (BG), shown as simplified circuitry in Fig. 1 and result in hypokinetic or hyperkinetic symptoms, depending on which part of the circuitry is affected. Inhibitory neurons, the so-called direct pathway, project to globus pallidus pars interna (GPi). In the so-called indirect pathway, the activation of striatum inhibits the globus pallidus pars externa (GPe) which projects to the subthala-
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