HEMISPATIAL NEGLECT TARGETING AROUSAL AND SPATIAL DEFICITS: TREATMENT RESPONSE

Moss Rehabilitation Hospital, Philadelphia PA

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Linked publications & trials

Abstract

Impairment and functional limitation from Hemispatial neglect may be a function in general non-lateralized arousal and/or lateralized deficits in spatial processing in the contralesional (left) hemispace. Both general arousal and lateralized spatial processing may depend pre-dominantly upon a right-lateralized network of neural structures. The proposed studies will examine the relationships between 1) behavioral experimental measures of general arousal and lateralized spatial processing, 2) clinical measures of neglect commonly used in the rehabilitation setting, 3) treatments specifically targeted at arousal and lateralized spatial processing deficits and 4) resting and activation functional magnetic resonance imaging (fMRI) measures in specific neural regions of interest. Among the major aims of the project are to elucidate the physiologic correlates of behaviorally-defined neglect and the mechanisms of action of pharmacologic and behavioral treatments of the arousal and spatial deficits characteristic of the disorder. We aim to assess the following specific hypotheses: 1. Patients with neglect (RCVA-neg) will exhibit abnormalities in resting perfusion in the right posterior inferior parietal lobe and right dorsolateral frontal and prefrontal cortices, and abnormal asymmetries in functional activation of right versus left hemisphere homologues of these structures. These abnormalities will be greater in a RCVA-neg than in a RCVA (no neglect) group. 2. Neglect severity, as defined by magnitude of impairment on a battery of behavioral tests, will be positively correlated with degree of abnormality in resting perfusion in right posterior inferior parietal and right dorsolateral frontal cortices and in left-right activation asymmetries in the same structure. 3.a) Deficits in arousal will be associated with deficits in lateralized spatial processing in neglect, b) Treatments targeted at arousal will ameliorate lateralized spatial deficits, and will alter physiology in numerous right hemisphere cortical regions, including those dedicated to lateralized spatio-motor processing. Specifically, i) behavioral measures of arousal will be correlated with severity of behavioral neglect and slope of a right-left gradient on a target detection tasks, ii) for patients treatment with arousal therapy, pre to post-treatment changes in arousal measures will be correlated with changes in left-right activation asymmetries in right posterior parietal and right dorsolateral frontal and pro-frontal cortices. 4. a) Clinical behavioral neglect severity is in part a function of the "steepness" of left-right spatial processing gradient, b) Treatment of the spatial-processing asymmetry ("spatial re-mapping therapy") will ameliorate clinical neglect and will alter physiology in right hemisphere cortical regions dedicated to lateralized spatio-clinical neglect and will alter physiology in right hemisphere cortical regions dedicated to lateralized spatio- motor processing. Specifically, i) behavioral measures of neglect severity will be correlated with the slope of a left-right gradient on a target detection task, ii) for patients treated with spatial re-mapping therapy, pre to post-treatment changes in behavioral measures of neglect will be correlated with changes in the slope of a left-right gradient on a target detection task, iii) pre- to post-treatment changes in the slope of a left-right gradient on a target detection task will be correlated with changes in left-right activation asymmetries in right posterior parietal and right dorsolateral frontal and pre-frontal cortices. 5. Severity of physiologic abnormality in cortical structures dedicated to lateralized spatial processing will be predictive of response to both arousal and spatial-remapping treatments. Specifically, off-treatment resting perfusion in right posterior parietal, dorsolateral frontal, and dorsolateral prefrontal cortices will be positively correlated, and off- treatment left-right activation asymmetries in right posterior parietal dorsolateral frontal, and dorsolateral prefrontal cortices will be negatively correlated with performance improvement seen with effective treatment of neglect.