Associations between dopamine D2-receptor binding and cognitive performance indicate functional compartmentalization of the human striatum

Abstract

Based on pharmacological, neuroanatomical, and lesion studies in animals, a functional compartmentalization of the striatal complex has been proposed. However, this has not been convincingly demonstrated in human subjects. Most functions ascribed to the striatum have been linked to its dense dopaminergic innervation, from motor control to higher-order brain functions (e.g., cognition), making the dopamine system a suitable probe for striatal function. Limbic striatum, a region involved in reward processing, has recently been implicated also in episodic memory function. Here we examined striatal dopamine D2-receptor binding in 16 healthy subjects using PET and the radioligand [(11)C]raclopride, in relation to cognitive performance. Receptor availability in limbic striatum was related to performance in tests of episodic memory, but not to tests of verbal fluency and general knowledge. By contrast, D2 binding in associative and sensorimotor striatum was less strongly related to episodic memory, but showed associations to the non-episodic tasks. These findings provide biochemical evidence for a functional compartmentalization of human striatum, and serve as a starting point for a more detailed investigation of striatal biomarkers in the normal brain as well as in neurodegenerative disorders.