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系统疾病，其特征在于对脑损伤对侧空间中的物体缺乏有意识的感知、意识、注意和认知。在猫的空间忽视模型中，单侧后顶叶和下顶叶皮层的失活引起对侧半野中物体的深度忽视。奇怪的是，对侧半球的同伦区域的额外失活逆转了这种忽视。这个模型系统提供了一个机会，调查神经机制，当损坏时，产生忽视，并制定一个有效的治疗策略，以扭转忽视人类。 拟议工作的具体目的是测试三个假设：1）使用重复经颅磁刺激（rTMS）来逆转猫模型中的忽视，2）了解更多关于病变和刺激对注意力网络的主要和次要功能影响，以及3）病变和rTMS对远处结构的相互作用，因为病变的影响出现了，当它稳定时。所获得的知识将有助于开发治疗和干预策略，以应用于遭受忽视的人类患者。 动物研究提供了研究忽视综合征及其矛盾逆转的最佳可能性，以高度系统的方式和相当严格的解剖学。我们的空间忽视模型将允许系统识别和解剖受病变影响的通路，提供对忽视逆转背后的大脑机制的见解，导致治疗策略的发展，以康复并最终逆转人类患者的神经忽视。 我们的首要目标是尽量减少rTMS参数，但提供最大的治疗持续时间。这是一个现实的目标，可以实现与拟议的整个动物的行为测定，并补充了全脑网络分析顶叶病变的功能影响和相互作用，并应用TMS对神经元。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.