title: The effects of the glutamate antagonist memantine on brain activation to an auditory perception task.
abstract: Glutamate is critically involved in the regulation of cognitive functions in humans. There is, however, sparse evidence regarding how blocking glutamate action at the receptor site during a cognitive task affects brain activation. In the current study, the effects of the glutamate antagonist memantine were examined with functional magnetic resonance imaging (fMRI). Thirty-one healthy adults were scanned twice in a counter-balanced design, either in a no-drug session or after administration of memantine for 21 days. The subjects performed a simple auditory perception task with consonant-vowel stimuli. Group-level spatial independent component analysis (ICA) was used to decompose the data and to extract task-related activations. The focus was on four task-related ICA components with frontotemporal localization. The results showed that glutamate-blockage resulted in a significant enhancement in one component, with no significant effect in the other three components. The enhanced effect of memantine was in the middle temporal gyrus, superior frontal gyrus, and middle frontal gyrus. It is suggested that the results reflect effects of glutamatergic processes primarily through non-N-methyl-D-aspartate (NMDA) receptor pathways. Moreover, the results demonstrate that memantine can be used as a probe which allows for studying the effect of excitatory neurotransmission on neuronal activation.
authors.affiliation: Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway. heidi.wageningen@psybp.uib.no
authors.forename: Heidi
authors.initials: H
authors.lastname: van Wageningen
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Jørgensen
authors.forename: Karsten
authors.initials: K
authors.lastname: Specht
authors.forename: Tom
authors.initials: T
authors.lastname: Eichele
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hugdahl
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000328:Adult; D001307:Auditory Perception / Q000187:drug effects*; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D025341:Principal Component Analysis; D055815:Young Adult
chemical_list: D018691:Excitatory Amino Acid Antagonists; D010100:Oxygen; D008559:Memantine