title: Electrode Position and Current Amplitude Modulate Impulsivity after Subthalamic Stimulation in Parkinsons Disease-A Computational Study.
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 andde novoimpulse 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.
authors.affiliation: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras Chennai, India.
authors.forename: Alekhya
authors.initials: A
authors.lastname: Mandali
authors.affiliation: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras Chennai, India.
authors.forename: V Srinivasa
authors.initials: VS
authors.lastname: Chakravarthy
authors.affiliation: Department of Neurology, Comprehensive Care Centre for Movement Disorders Trivandrum, India.
authors.forename: Roopa
authors.initials: R
authors.lastname: Rajan
authors.affiliation: Achutha Menon Centre for Health Science Studies, Sree Chitra Tirunal Institute for Medical Sciences and Technology Trivandrum, India.
authors.forename: Sankara
authors.initials: S
authors.lastname: Sarma
authors.affiliation: Department of Neurology, Comprehensive Care Centre for Movement Disorders Trivandrum, India.
authors.forename: Asha
authors.initials: A
authors.lastname: Kishore
keywords: Iowa gambling task; Parkinson's disease; impulsivity; reinforcement learning; sub thalamic stimulation