Dopaminergic Modulation of Working Memory for Spatial but Not Object Cues in Normal Humans

Abstract

It appears that functionally segregated visual pathways exist in the primate brain for the processing of visuospatial versus nonspatial information. Functional segregation has been demonstrated for the early associative processing of sensory information but may also exist at higher levels of cognitive analysis. Namely, connections between the dorsal visual system and dorsolateral prefrontal cortex (PFC) appear to mediate spatial working memory, which is modulated by dopamine receptor fields in the principal sulcal region of the PFC. It is speculated that nonspatial working memory may be modulated within connections between ventral visual processing regions and the inferior convexity of the PFC. Whether dopamine facilitates nonspatial memory through connections between the ventral visual system and ventral PFC has not been examined. In this study, normal humans completed spatial and nonspatial working memory tasks under pharmacological challenges with a dopamine receptor agonist (bromocriptine) and antagonist (haloperidol) in a double-blind placebcxontrolled repeated measures design. Findings indicated facilitation of spatial delayed working memory functions by bromocriptine and impairment of spatial working memory functions by haloperidol. Neither drug was effective in manipulating nonspatial memory performance. Control tasks were included to measure drug effects on basic sensorimotor and attentional processes. Findings suggest that separate processing mechanisms for remembering "What" versus "Where" an object is may exist at structural, but also neurochemical, levels in the human brain.