A Computational Model of Deep Brain Stimulation for Parkinson’s Disease Tremor

ABSTRACT Parkinson’s Disease (PD) is a progressive neurological disorder that is typically characterized by a range of motor dysfunctions and its impact extends beyond physical abnormalities into emotional well-being and cognitive symptoms. The loss of dopaminergic neurons in the Substantia nigra pars compacta (SNc) leads to an array of dysfunctions in the functioning of Basal Ganglia (BG) circuitry that manifests into PD. While active research is being carried out in finding the root cause of SNc cell deaths, various therapeutic techniques are prevalent to manage the symptoms of PD. The most common approach in managing the symptoms is replenishing the lost dopamine in the form of taking dopaminergic medications such as Levodopa amidst its long-term complications. Another commonly used intervention for PD is deep brain stimulation (DBS), which is a invasive technique where an electrode is surgically inserted into the skull and a high frequency current of appropriate characteristics is delivered to the brain region. DBS is most commonly used when levodopa medication efficacy reduces and also in combination with levodopa medication that will help reducing the required dosage of medication prolonging the therapeutic effect. DBS is also a go to option when motor complications such as dyskinesias emerge as a side effect of medication. Several studies have also reported that though DBS is found to be effective in suppressing severe motor symptoms such as tremor and rigidity, it has adverse effect on cognitive capabilities. Henceforth it is important to understand the exact mechanism of DBS in alleviating the motor symptoms. A computational model of DBS stimulation for motor symptoms will offer great insights in understanding the mechanisms underlying the DBS and in this line in our current study we model a cortico-basal ganglia circuitry of arm reaching where we simulate healthy controls (HC) and PD symptoms as well as the DBS effect on the PD tremor. With DBS current characteristics of 220 pA, 130 Hz and 100 microseconds pulse-width we were able to see maximum therapeutic effect using our model. This model can be extended to accommodate cognitive dynamics in future so as to study the impact of DBS on cognitive symptoms and optimizing the parameters to get optimal performance effect across modalities.