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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH060399-06
Application #
7035243
Study Section
Cognitive Neuroscience Study Section (COG)
Program Officer
Glanzman, Dennis L
Project Start
2000-05-01
Project End
2008-08-31
Budget Start
2006-03-01
Budget End
2008-08-31
Support Year
6
Fiscal Year
2006
Total Cost
$322,472
Indirect Cost
Name
Northern Illinois University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
001745512
City
De Kalb
State
IL
Country
United States
Zip Code
60115
Conte, William L; Kamishina, Hiroaki; Reep, Roger L (2009) Multiple neuroanatomical tract-tracing using fluorescent Alexa Fluor conjugates of cholera toxin subunit B in rats. Nat Protoc 4:1157-66
Kamishina, Hiroaki; Conte, William L; Patel, Sarika S et al. (2009) Cortical connections of the rat lateral posterior thalamic nucleus. Brain Res 1264:39-56
Wu, Jennifer H; Corwin, James V; Reep, Roger L (2009) Organization of the corticostriatal projection from rat medial agranular cortex to far dorsolateral striatum. Brain Res 1280:69-76
Conte, William L; Kamishina, Hiroaki; Reep, Roger L (2009) The efficacy of the fluorescent conjugates of cholera toxin subunit B for multiple retrograde tract tracing in the central nervous system. Brain Struct Funct 213:367-73
Conte, William L; Kamishina, Hiroaki; Corwin, James V et al. (2008) Topography in the projections of lateral posterior thalamus with cingulate and medial agranular cortex in relation to circuitry for directed attention and neglect. Brain Res 1240:87-95
Reep, Roger L; Wu, Jennifer H; Cheatwood, Joseph L et al. (2008) Quantification of synaptic density in corticostriatal projections from rat medial agranular cortex. Brain Res 1233:27-34
Kamishina, Hiroaki; Yurcisin, Geoffrey H; Corwin, James V et al. (2008) Striatal projections from the rat lateral posterior thalamic nucleus. Brain Res 1204:24-39
Brenneman, Miranda M; Wagner, Steven J; Cheatwood, Joseph L et al. (2008) Nogo-A inhibition induces recovery from neglect in rats. Behav Brain Res 187:262-72
Cheatwood, J L; Corwin, J V; Reep, R L (2005) Overlap and interdigitation of cortical and thalamic afferents to dorsocentral striatum in the rat. Brain Res 1036:90-100
Reep, R L; Corwin, J V; Cheatwood, J L et al. (2004) A rodent model for investigating the neurobiology of contralateral neglect. Cogn Behav Neurol 17:191-4

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