Our long-term aim is to rehabilitate neural spatial neglect. Unilateral neglect is a complex neurological disorder induced by unilateral brain damage that is characterized by lack of conscious perception, awareness, attention, and cognition of objects in the space contralateral to the brain damage. In a cat model of spatial neglect, unilateral deactivation of posterior and inferior parietal cortex induces a profound neglect of objects in the contralateral hemifield. Paradoxically, the neglect is reversed by additional deactivation of the homotopic region in the contralateral hemisphere. This model system offers the opportunity to investigate the neural mechanisms which, when damaged, produce neglect, and to develop an effective therapeutic strategy to reverse neglect in humans.
The Specific Aims of the proposed work are to test three hypotheses on: 1) the use of repetitive transcranial magnetic stimulation (rTMS) to reverse neglect in a cat model, 2) to learn more about the primary & secondary functional impacts of lesions and stimulations on the attention network, & 3) interactions of lesions & rTMS on distant structures as the impact of the lesion emerges & when it is stable. The knowledge gained will aid the development of therapeutic and interventional strategies for application to human patients suffering from neglect. Animal studies provide the best possibility of studying the neglect syndrome, and its paradoxical reversal, in a highly systematic way and with considerable anatomical rigor. Our model of spatial neglect will allow systematic identification and dissection of pathways affected by the lesion, provide insights into the brain mechanisms underlying the reversal of neglect, lead to the development of therapeutic strategies to rehabilitate and ultimately reverse neurological neglect in human patients. Our over riding goal is to minimize rTMS parameters yet provide maximum therapeutic duration. It is a realistic goal that can be achieved with the proposed whole-animal behavioral assays and supplemented by the brain-wide network analyses on the functional impacts and interactions of parietal lesions and applied TMS on neurons. The data are of obvious translational importance for neurorehabilitation of neglect and may have wider-ranging impact on other neurologic and psychiatric diseases.
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