Disturbances in the function of neuronal circuitry contribute to many neurological disorders. As knowledge of the brain's connectome continues to improve, a more refined understanding of the role of specific circuits in pathological states will also evolve. Tools capable of intervening in a targeted and restricted manner will be essential not only to expand our understanding of the functional roles of such circuits, but also to therapeutically disconnect critical pathways contributing to neurological disease. This project will test a novel strategy for producing focal, non-ablative, neuronal lesions in the central nervous system. This strategy is termed Precise Intracerebral Non-invasive Guided-surgery (PING). This proposal will test the therapeutic ability of PING to attenuate seizure activity in a model of temporal lobe epilepsy.
Guiding hypothesis: Targeted disconnection of dysfunctional brain circuitry can be achieved in a precise, conformal, and non-invasive manner, and that this strategy can be implemented to control seizures in Drug Resistant Epilepsy.
The project will take advantage of the ability of low-intensity, Magnetic Resonance- guided Focused Ultrasound (MRgFUS) to transiently disrupt the blood brain barrier (BBB) in order to deliver to the brain parenchyma a neurotoxin with poor BBB permeability. This represents a targeted, non-invasive, non-ablative strategy for precise destruction of neurons. Our preliminary findings provide the first evidence of non-invasive, focal destruction of neurons in a targeted brain area that spares non- targeted structures. Our proposed study will provide the first test-of-concept of the therapeutic efficacy of PING for treating a biomedical disorder
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