Abstract
Background: Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) is highly effective in alleviating motor symptoms of Parkinson's disease (PD) which are not optimally controlled by dopamine replacement therapy. Clinical studies and reports suggest that STN-DBS may result in increased impulsivity and de novo impulse control disorders (ICD).Objective/Hypothesis: We aimed to compare performance on a decision making task, the Iowa Gambling Task (IGT), in healthy conditions (HC), untreated and medically-treated PD conditions with and without STN stimulation. We hypothesized that the position of electrode and stimulation current modulate impulsivity after STN-DBS.Methods: We built a computational spiking network model of basal ganglia (BG) and compared the model's STN output with STN activity in PD. Reinforcement learning methodology was applied to simulate IGT performance under various conditions of dopaminergic and STN stimulation where IGT total and bin scores were compared among various conditions.Results: The computational model reproduced neural activity observed in normal and PD conditions. Untreated and medically-treated PD conditions had lower total IGT scores (higher impulsivity) compared to HC (P < 0.0001). The electrode position that happens to selectively stimulate the part of the STN corresponding to an advantageous panel on IGT resulted in de-selection of that panel and worsening of performance (P < 0.0001). Supratherapeutic stimulation amplitudes also worsened IGT performance (P < 0.001).Conclusion(s): In our computational model, STN stimulation led to impulsive decision making in IGT in PD condition. Electrode position and stimulation current influenced impulsivity which may explain the variable effects of STN-DBS reported in patients.
Highlights
Deep brain stimulation (DBS) of the subthalamic nucleus (STN), is a surgical technique widely applied for the treatment of Parkinson’s disease (PD) when dopamine replacement therapy fails to provide sustained relief of motor symptoms or induces drug-induced dyskinesias (Benabid, 2003)
Using the spiking network model of BG, we studied the performance of the model in Iowa Gambling Task (IGT) in normal, PD with and without medication [L-DOPA and Dopamine Agonists (DAA)] and Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) conditions
We built a computational spiking basal ganglia network model to understand the effects of STN stimulation on impulsivity
Summary
Deep brain stimulation (DBS) of the subthalamic nucleus (STN), is a surgical technique widely applied for the treatment of Parkinson’s disease (PD) when dopamine replacement therapy fails to provide sustained relief of motor symptoms or induces drug-induced dyskinesias (Benabid, 2003). Several reports have highlighted the development of new onset, often transient, impulse control disorders (ICDs) following STN stimulation (Hershey et al, 2004; Smeding et al, 2007; Combs et al, 2015). This was thought to be, due to stimulation of the cognitive sub territory of STN or the spread of stimulation to adjacent parts of the cortico-limbic circuits. Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) is highly effective in alleviating motor symptoms of Parkinson’s disease (PD) which are not optimally controlled by dopamine replacement therapy. Clinical studies and reports suggest that STN-DBS may result in increased impulsivity and de novo impulse control disorders (ICD)
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