Functional circuitry underlying visual neglect

Abstract

Visuospatial neglect is a common neurological syndrome caused by unilateral brain damage to the posterior and inferior parietal cerebral cortex, and is characterized by an inability to respond or orient to stimuli presented in the contralesional hemifield. Neglect has been elicited in experimental models of the rat, cat and monkey, and is thought to result in part from a pathological state of inhibition exerted on the damaged hemisphere by the hyperexcited intact hemisphere. We sought to test this theory by assessing neural activity levels in multiple brain structures during neglect using 2-deoxyglucose (2DG) as a metabolic marker of neural activity. Neglect was induced in two ways: (i) by cooling deactivation of posterior parietal cortex or (ii) in conjunction with broader cortical blindness produced by unilateral lesion of all contiguous visual cortical areas spanning occipital, parietal and temporal regions. The direction and magnitude of changes in 2DG uptake were measured in cerebral cortex and midbrain structures. Finally, the 2DG uptake was assessed in a group of cats in which the lesion-induced neglect component of blindness was cancelled by cooling of either the contralateral posterior parietal cortex or the contralateral superior colliculus (SC). Overall, we found that (i) both lesion- and cooling-induced neglect are associated with decreases in 2DG uptake in specific ipsilateral cortical and midbrain regions; (ii) levels of 2DG uptake in the intermediate and deep layers of the SC contralateral to both cooling and lesion deactivations are increased; (iii) changes in 2DG uptake were not identified in the contralateral cortex; and (iv) reversal of the lesion-induced neglect component of blindness is associated with a reduction of contralesional 2DG uptake to normal or subnormal levels. These data are in accord with theories of neglect that include mutually suppressive mechanisms between the two hemispheres, and we show that these mechanisms operate at the level of the SC, but are not apparent at the level of cortex. These results suggest that the most effective therapies for visual neglect will be those that act to decrease neural activity in the intermediate layers of the SC contralateral to the brain damage.

Abnormalities in skilled reaching movements are improved by peripheral anesthetization of the less-affected forelimb after sensorimotor cortical infarcts in rats

“…The finding that skilled reaching movements were, instead, partially normalized by anesthetization of the other forelimb indicates that the interhemispheric and bimanual effects of peripheral anesthetization reported in humans most likely extend to rat reaching function. This seems important in light of recent findings indicating competitive interactions between the hemispheres that become unbalanced by unilateral brain damage and which might be targeted for therapeutic interventions [43,47,48,49]. The present results suggest that rat models of skilled reaching may be useful for studying the role of interhemispheric interactions in recovery of somatomotor function after unilateral brain damage.…”

Functional imaging reveals rapid reorganization of cortical activity after parietal inactivation in monkeys

“…Evidence for this proposal is derived from TMS studies in neglect patients showing that spatial extinction can be transiently alleviated by deactivating the hemisphere opposite to the lesion (19,61,62) and by demonstrating hyperexcitability of parietal-motor pathways in the intact hemisphere (18). Similarly, studies in cats have shown a restoration of spatial functions as a consequence of deactivation of homolog areas in the hemisphere opposite to the lesion (14,29,63).…”

A non-spatial bias favouring fixated stimuli revealed in patients with spatial neglect

“…This finding suggests that parieto-occipital cortex normally exerts a facilitatory influence on the ipsilateral and an inhibitory influence on the contralateral colliculus. In spatial neglect following a cortical lesion, the ipsilesional colliculus has a lower (inhibition) and the contralesional colliculus a higher glucose metabolism (disinhibition, Rushmore et al, 2006), which could contribute to the directional bias favouring ipsilesional items. An important feature of the superior colliculus is its subdivision in two functionally distinct regions.…”