The primary objectives of the proposed work are to determine what neural elements are activated by DBS, to develop methods to activate selectively local neurons and axons of passage, and to determine the motor effects) of stimulation of different neuronal groups. We will use computer-based modeling of thalamic neurons and the fields generated by DBS electrodes to determine the effects of stimulus parameters and electrode geometry variations on neuronal excitation and block. Hypotheses formulated from computer modeling will be tested. First, using paresthesias evoked by thalamic stimulation in awake human as a unique assay allowing Discrimination of activation of local or remote neural elements, and secondly by quantifying the motor effects:)f selective stimulation of local neurons and axons of passage. The outcomes of this research will be a thorough understanding of what neuronal elements (both type and spatial extent) are affected by DBS and methods to activate selectively targeted populations. We expect to design new stimulus waveforms and electrode geometries that will allow element- and location-specific; st1mulation of the human thalamus. These new techniques will enable us to define the populations of neurons that produce desired and undesired motor effects during DBS, and to specify the next generation of implantable electrodes and stimulators. Collectively, these results will improve the efficacy and expand the range of applications for DBS. Chronic high frequency electrical stimulation of the brain, also called deep brain stimulation,(CBD) is effective in treating a number of neurological disorders, but the mechanisms of action of unclear. A number of plausible hypotheses have been proposed, however, these hypotheses are difficult to support or refute because it is not known what neural elements (local cells, axons of passage) respond at similar stimulation thresholds. This lack of selectivity of the neural response complicates our understanding of the mechanisms of action of DBS, and limits our ability to maximally exploit DBS for therapy. However, if the responsive elements could be controlled selectively, then their differential effects may be used to expand the applications of DBS and minimize undesirable side effects.
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