title: Neurovascular coupling in the human visual cortex is modulated by cyclooxygenase-1 (COX-1) gene variant.
abstract: Functional hyperemia, the brain's capability to alter microvascular blood flow in response to the metabolic demands of active neurons, is essential for sustained mammalian brain function. Pharmacological studies in mice suggest neurovascular coupling to centrally involve cyclooxygenase-1 (COX-1) metabolites such as prostaglandins. In humans, however, genetic variation of the COX-1 gene impacting the coupling of neural activity to hemodynamic responses (HRs) has not been investigated yet. In this study, we determined whether COX-1 genotype-dependent enzymatic function impacts HRs in humans. Specifically, using a double-blind Imaging Genetics approach utilizing functional near-infrared spectroscopy, we measured HRs following visual checkerboard stimulation. COX-1 genotype (L237M, rs5789)-dependent decrease in enzymatic function in heterozygous L/M carriers is associated with a 42% reduction of the HR amplitude. This finding is discussed in the context of potentially imbalanced neurovascular mechanisms involving arachidonic acid, which underlie vasodilatory and vasoconstrictive forces of functional hemodynamics. Generally, these findings might help to improve our understanding of pathologies such as stroke and Alzheimer's disease in which neurovascular coupling is altered. Additionally, our results may have important implications for functional brain imaging in which HRs are commonly used as a surrogate for neural activation.
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Fuechsleinstrasse 15, 97080 Wuerzburg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Hahn
authors.forename: Sebastian
authors.initials: S
authors.lastname: Heinzel
authors.forename: Michael M
authors.initials: MM
authors.lastname: Plichta
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Fallgatter
mesh_terms: D000293:Adolescent; D000328:Adult; D002560:Cerebrovascular Circulation / Q000235:genetics*; D051545:Cyclooxygenase 1 / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D006580:Genetic Carrier Screening; D014644:Genetic Variation / Q000235:genetics*; D006439:Hemodynamics / Q000235:genetics; D006801:Humans; D008297:Male; D010775:Photic Stimulation / Q000379:methods*; D014793:Visual Cortex / Q000201:enzymology*; D055815:Young Adult
chemical_list: D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human