The Study Of Mechanism Of Action Of Deep Brain Stimulation And Development Of Deep Brain Stimulator

Parkinson's disease (PD) which is characterized by a clinical triad of akinesia, rigidity and tremor marked by degeneration of dopaminergic neurons in the substantia nigra pars compacta. Compared to conventional medicine and surgical treatment, deep brain stimulation (DBS) with minor tissue damage and marked clinical effect and controlled side-effects has become the best surgical intervention to date for PD. However, in despite of well known clinical effect, the mechanism under action of DBS is still under investigation. Since this technique is monopolized by international company, the expense is keeping the price high and is beyond the affordability of common patients. Thus, the development of DBS with independent intellectual property is looming ahead.Design solution of low-power DBS, and the effect of DBS on neural activity were studied by simulataneous recording. Based on the results from experiment results, a novel inhibiton-driving hypothesis of action of DBS was proposed. Besides, selectivity of complex stimulus waveform was addressed by computational simulation. There are five main parts of current work, as following:1) The technical details of DBS design were presented. And the protype of DBS which meet the clinical parameters requirement was developed. Meanwhile, for the demand of low-power, compact size by DBS, a novel dynamic mix-mode buck-boost topology was developed.2) The changes of neural activity of subthalamic nucleus and substantia nigral recticular pars were addressed using simulatenous recording technique, and hypothesis of mechanism of action of deep brain stimulation was proposed. Aimed at neural recording severely corrupted by stimulation artifact which would effect subsequently analysis, a coherent adaptive model algorithm was studied and applied to remove stimulus artifact and experiment results showed this algorithm can achieve good performances of stimulus artifact removal and meanwhile well recover the neural response even completely submerged by noise. Based this algorithm and DBS protype developed by our lab, the neural activities of suthalamic nucleus and sustantia nigra reticular pars were recorded during ongoing deep brain stimulation of subthalamic nucleus of the rats. These changes of neural activity mode and mean discharge rate of normal rats and animal model were determined and analyzed. And these effect of amplitude and frequency of stimulation waveform on neural respond were studied and analyzed, and the effect of sitmulation on mean discharge rate also was addressed. Finally, comparing and analyzing these results and based current international results, the mechanism of action of deep brain stimulation was discussed and a novel hypothesis, "Inhibition"-"driving", was proposed.3) Based on a model of subthalamic neurons, the effects of parameters of stimulus on excitability of neural cells were determined and a novel complex stimulus waveorm with stimulation selectivity was developed and studied.