Rehabilitation of Neural Spatial Neglect

描述(由申请人提供)：我们的长期目标是恢复神经空间忽视。单侧忽视是由单侧脑损伤引起的一种复杂的神经功能障碍，其特征是对脑损伤对侧空间中的物体缺乏意识、意识、注意和认知。在空间忽视的CAT模型中，单侧后顶叶和下顶叶皮质的失活导致对侧半球物体的严重忽视。矛盾的是，对侧大脑半球同源区域的额外失活逆转了这种忽视。这个模型系统提供了机会来研究当受到损害时产生忽视的神经机制，并开发一种有效的治疗策略来逆转人类的忽视。 拟议工作的具体目的是检验三个假设：1)在CAT模型中使用重复经颅磁刺激(RTMS)来扭转忽视；2)更多地了解病变和刺激对注意网络的初级和次级功能影响；以及3)当病变的影响出现时-当病变稳定时，病变和rTMS对远处结构的相互作用。所获得的知识将有助于开发治疗和干预策略，应用于遭受忽视的人类患者。 动物实验为研究疏忽综合征及其矛盾的逆转提供了最好的可能性，以高度系统化的方式和相当的解剖学严谨性。我们的空间忽视模型将允许系统地识别和剖析受病变影响的通路，为逆转忽视的大脑机制提供洞察力，导致制定治疗策略以康复并最终扭转人类患者的神经忽视。 我们的首要目标是最大限度地减少rTMS参数，同时提供最长的治疗时间。这是一个现实的目标，可以通过所提出的全动物行为分析来实现，并辅之以关于顶叶病变和应用TMS对神经元的功能影响和相互作用的全脑网络分析。这些数据对忽视的神经康复具有明显的翻译重要性，并可能对其他神经学和精神疾病产生更广泛的影响。

DESCRIPTION (provided by applicant): 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.