Neglect is a complex human neuropsychological disorder characterized by a failure to attend to novel or meaningful stimuli presented to the side contra-lateral to a brain lesion, in the absence of a primary sensory or motor dysfunction. Some manifestation of neglect is found in nearly half of all cases of cortical brain damage, and the presence of neglect is the single best predictor of a poor prognosis for recovery. Neglect can be devastating to patients and their families and is extremely difficult to treat. Currently, there are no effective therapies for neglect. Recovery, when it occurs, is spontaneous but often is incomplete. A rodent model has been developed to examine the neural basis of neglect and recovery from neglect, following unilateral lesion of cortical area AGm. As in humans with neglect, spontaneous recovery does not occur in rats following complete AGm lesions that result in the full spectrum of neglect deficits, including contra-lateral inattention, extinction, and allesthesia. Therefore recovery must be induced. Behavioral and pharmacological manipulations have been found that will induce recovery in rats, and anatomical and behavioral studies have shown that the dorsocentral striatum (DCS) appears to be the site of action for the mechanisms of the induced behavioral recovery. Neuroplasticity and recovery in spinal cord and motor cortex can be induced by the use of anti-Nogo-A antibodies. However, the efficacy of these compounds has never been examined with cognitive-spatial disorders like neglect. The proposed studies will test the hypothesis that when neglect is produced by a unilateral lesion of cortical area AGm, induced sprouting in DCS by axons from the contralesional AGm promotes behavioral recovery. We will utilize three anti-Nogo-A antibodies to investigate the causal relationship between induced plasticity and recovery, and to define the critical window of time during which these agents must be delivered in order to promote recovery The proposed experiments have significant clinical implications. Neglect is a severe and prevalent clinical disorder, and at present there are no generally accepted treatments. The rodent model exhibits many of the same deficits found in human neglect patients. If plasticity and recovery can be induced in the rat model, and are shown to be causally related, this may lead to a significant lasting treatment or a cure for this cognitive disorder in humans.
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