A rodent model for investigating the neurobiology of contralateral neglect.

BACKGROUND: Contralateral neglect is a common and disabling sequela of right hemisphere strokes. Neglect involves attentional and cognitive deficits, including distortions of contralateral spatial and personal awareness. There are no established successful therapies for neglect, and treatment is often complicated by anosognosia. The disturbances associated with neglect are debilitating to patients and their families, and presence of neglect is a strong predictor of poor prognosis for recovery. OBJECTIVE: The present report reviews findings from 20 years of research using a rat model of neglect. In the rat, 2 cortical areas that are linked by corticocortical connections have been identified as having a major role in neglect, and these correspond to frontal and parietal fields in primates. These 2 cortical areas also have convergent projections to the dorsocentral striatum, which has been implicated as a crucial subcortical component of the cortical-striatal-thalamic circuitry involved in directed attention and neglect. We discuss the role of the dorsocentral striatum in neglect and recovery and present evidence that induced axonal sprouting may promote functional recovery following cortical lesions that produce neglect. CONCLUSIONS: The rodent model of neglect captures some of the essential behavioral and anatomic features of neglect in humans. This model has helped reveal the pathophysiology of neglect, has suggested a crucial role of the striatum in recovery from neglect, and is being used to investigate potential therapeutic approaches.

Infusion of apomorphine into the dorsocentral striatum produces acute drug-induced recovery from neglect produced by unilateral medial agranular cortex lesions in rats.

Previous studies have shown that systemic administration of apomorphine is effective in producing acute drug-induced recovery from neglect induced by unilateral medial agranular cortex (AGm) lesions. More recent studies have demonstrated that recovery from neglect may be due to plastic changes occurring in the dorsal central striatum (DCS). Further, lesions of the DCS produce neglect that does not respond to systemic administration of apomorphine, suggesting that this area may be crucial for the therapeutic effects of apomorphine. In the present study, the behavioral effects of apomorphine infused into the DCS of animals with AGm lesion-induced neglect were examined to determine whether the DCS is a site of drug action. An infusion of 0.375 micro g of apomorphine into the DCS, but not a lateral striatal control area, was effective in producing acute recovery from neglect. The results of this study support the crucial role of the DCS in recovery from neglect induced by unilateral AGm lesions and suggest that the DCS may be an important site of action for the therapeutic effects of apomorphine. Because dopamine agonist therapy has been shown to be effective in humans with neglect, the results of the current study may represent an important step in the development of future pharmacotherapies.

Effects of light deprivation on recovery from neglect and extinction induced by unilateral lesions of the medial agranular cortex and dorsocentral striatum.

A number of previous studies have indicated that an environmental manipulation, 48 h of light deprivation (LD), produces virtually complete and permanent behavioral recovery of function from neglect induced by medial agranular cortex (AGm) lesions. LD-induced behavioral recovery from neglect is correlated with physiological changes in the dorsolateral striatum, an area that contains the projection zone of AGm efferents in the dorsocentral striatum (DCS). In this study, the behavioral effects of 48 h of LD on subjects with either unilateral DCS, AGm, or combined AGm/DCS lesions were investigated to examine whether the integrity of the DCS is crucial for behavioral recovery from neglect and whether LD will have a therapeutic effect on extinction deficits. Subjects were tested for extinction to bilateral simultaneous stimulation of the forepaws, and visual, auditory and tactile neglect. Forty-eight hours of LD failed to produce behavioral recovery from neglect in rats with DCS lesions, or a therapeutic affect on extinction deficits in any of the groups. The results of this study further support the crucial role of the DCS in recovery from neglect induced by AGm lesions and suggests that the DCS may be the crucial site for the mechanisms leading to LD-induced recovery. Further, the ineffectiveness of LD on extinction suggests that components of the neglect syndrome are dissociable and may require different therapeutic interventions.

Light deprivation produces a therapeutic effect on neglect induced by unilateral destruction of the posterior parietal cortex in rats.

Light deprivation has been found to produce accelerated recovery from severe multimodal neglect induced by unilateral destruction of medial agranular cortex, the rat analog of area 8 in humans. However, neglect in humans is most often produced by destruction of the parietal association cortex. Therefore, the present study examined whether light deprivation would produce accelerated recovery from severe multimodal neglect induced by unilateral destruction of the rodent analog of the parietal association cortex. Subjects received unilateral parietal association cortex lesions, and 4 h after surgery were tested for neglect of visual, tactile, and auditory stimuli. If severe neglect was obtained, subjects experienced either light deprivation, constant light, or a 12:12 light/dark cycle for 48 h. The results indicated that, relative to the other groups, the light deprivation group demonstrated significant accelerated recovery from neglect. Recovery was evident on the first post-light deprivation behavioral test, and was maintained for the 3 weeks of behavioral testing. The results provide further support for the therapeutic effects of light deprivation on neglect induced by cortical lesions when light deprivation is administered in the immediate postoperative period.