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The histaminergic involvement in selective processes underlying its role in human sensori-motor performance is largely unknown. Recently, selective effects of central H1 -inverse agonism on sensory visual processes were observed in electrophysiological-but not behavioral data; a discrepancy suggested to result from speeded response-choice related processes. This study attempts to establish the effects on visual processes and identify putative compensatory mechanisms related to increased visual and response-choice task demands by assessing H1 -inverse agonism induced changes in blood oxygenation level dependent (BOLD) response. Twelve participants received oral doses of dexchlorpheniramine 4 mg, lorazepam 1 mg, and placebo in a three-way crossover designed study. Brain activity was assessed for choice reaction time task performance in a 3 T magnetic resonance scanner 2 h after drug administration. Participants responded with their left or right hand and index or middle finger as indicated by the laterality of stimulus presentation and identity of the stimulus, respectively. Stimuli were intact or visually degraded and responses were compatible or incompatible with the laterality of stimulus presentation. Both dexchlorpheniramine and lorazepam affected the BOLD response in the occipital cortex indicating affected visual information processing. Dexchlorpheniramine decreased BOLD response in the dorsal precuneus and left precentral gyrus as part of a motor network, which however might not be interpreted as a compensatory mechanism, but may be the upstream consequence of impaired visual processing. Hum Brain Mapp, 2013. (c) 2013 Wiley Periodicals, Inc.