Controlling pathological activity of Parkinson basal ganglia based on excitation and inhibition optogenetic models and monophasic and biphasic electrical stimulations.

We examined electrical and optogenetic stimulations to explore their benefits and the effective range of their network effects. The error index () and beta-activity of a network were considered by us as appropriate phenomena to compare stimulations. The basal ganglia (BG) network model considers areas of the brain affected by Parkinson's disease (PD). It consists of the thalamus (TH), subthalamic nucleus (STN), globus pallidus interna (GPi,), and globus pallidus externa (GPe). To control the BG in PD, we stimulated the STN, GPe, and GPi with deep brain stimulation (DBS) and optogenetic stimulation, and to examine TH performance, we used the sensorimotor cortex (SMC). BG network performance was evaluated by measuring how TH responded to SMC input, and how STN, GPe, and Gpi were affected by DBS and optogenetic stimulation as evaluated using and beta-activity. By comparing the firing rates obtained from four applied stimulations at optimal conditions of the model, the effect of each stimulation was studied. The results indicated that applying monophasic DBS causes STN, GPi, and GPe cells to fire regularly, and biphasic DBS leads to increased oscillations between firings of STN cells; three-state optogenetic inhibition using halorhodopsin (NpHR) synchronizes the firing of GPe and GPi, and suppresses the neural activity of STN; and four-state optogenetic excitation using channelrhodopsin-2 (ChR2) incites the STN to excite and depolarize neural activity. All these events avoided pathological activation of PD and returned the performance to that of the healthy state. Finally, to evaluate our suggested method, we measured the beta-activity of monophasic and biphasic DBS and optogenetic inhibition and excitation by varying the electrical stimulation intensity (A) and optical stimulation intensity (A) and obtained optimal values for each state. According to our results, increasing A does not cause immediate decrease of beta-activity in monophasic and biphasic DBS. Increasing A causes immediate decrease of beta-activity in NpHR, which then remains constant. In ChR2 there is no significant relation between beta-activity and A.