A computer simulation study on the effects of brain nuclei stimulation on the activity of a neuronal circuit involved in Parkinson's disease

Author(s)

Marcelo Ramos Romano

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Engenharia Elétrica e de Computação
• Defense date: 2020-11-16

Examining board members

Leonardo Abdala Elias; Carina Marconi Germer; Antonio Augusto Fasolo Quevedo

• Advisor: Renan Cipriano Moioli; Leonardo Abdala Elias

Abstract

Parkinson's disease (PD) has been postulated to result from the degeneration of dopaminergic neurons in the substantia nigra. Parkinsonian tremor is thought to emerge from increased cortical oscillations, especially in alpha (8-15Hz) and beta (15- 35Hz) bands. The electrical stimulation of deep brain nuclei (DBS) is a kind of therapy for PD treatment, so that periodic signals (electrical pulses with a fixed frequency) are typically applied to the subthalamic nucleus (STN). A hypothesis that can be raised is that random signals can also be used in therapies to reduce cortical oscillations and, consequently, reduce parkinsonian tremor. In addition, another form of stimulation still poorly studied is the spinal cord stimulation, which has been proven beneficial in recent experimental studies. In the present study, a computational model of the motor circuit encompassing the cortex, the basal ganglia, and thalamus, that represents a rodent model of PD, was used with the purpose of studying different types of stimulation in this brain neuronal circuit. From the computational model, after an initial phase of model validation, simulations were performed with stochastic inputs of different intensities applied to the STN in order to analyze the effects of stochastic stimulation on the activity of the neurons that form this motor circuit. In addition, both deterministic and stochastic inputs were also applied to the thalamus (TH), which was assumed, for the sake of simplicity, to mimic the spinal cord stimulation, because the ascending pathways converge to the thalamus. Time-domain, frequency-domain, and information theory metrics were used in order to evaluate the response of the neurons encompassing the nuclei of this model. Finally, the model was validated for data from a primate model, which is phylogenetically closer to humans. Stochastic stimulation of the STN was successful in reducing the oscillations and the exaggerated coupling in the beta band between the nuclei, and the observed benefit was strongly linked to a high-frequency firing of STN neurons. As some studies already pointed for deterministic stimulation, stimulations with a stochastic signal with the spectrum limited to low frequencies were also ineffective in reducing the parkinsonian oscillations of the model. Stochastic stimulation has some interesting properties such as: signal amplitude compatible with deterministic stimulations (< 10?Arms/cm²), simplicity (only one parameter to be controlled as compared to the three for deterministic stimulations), and the possibility of including both intermediate- and high-frequency contents to the stimuli, which seems to be beneficial for axial symptoms (for instance, gait freezing and postural instabilities (AU)

• FAPESP's process: 18/11075-5 - A computer simulation study on the effects of stochastic stimulation on the activity of a brain circuit involved in Parkinson's disease
• Grantee: Marcelo Ramos Romano
• Support Opportunities: Scholarships in Brazil - Master