title: Frontal GABA levels change during working memory.
abstract: Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but changes in neurotransmitter levels have not been demonstrated in humans during a cognitive task, and the relationship between neurotransmitter dynamics and hemodynamic activity during cognition has not yet been established. We evaluate the concentration of the major inhibitory (GABA) and excitatory (glutamate + glutamine: Glx) neurotransmitters and the cerebral perfusion at rest and during a prolonged delayed match-to-sample working memory task. Resting GABA levels in the dorsolateral prefrontal cortex correlated positively with the resting perfusion and inversely with the change in perfusion during the task. Further, only GABA increased significantly during the first working memory run and then decreased continuously across subsequent task runs. The decrease of GABA over time was paralleled by a trend towards decreased reaction times and higher task accuracy. These results demonstrate a link between neurotransmitter dynamics and hemodynamic activity during working memory, indicating that functional neuroimaging metrics depend on the balance of excitation and inhibition required for cognitive processing.
authors.affiliation: Center for MR-Research, University Children's Hospital, Zurich, Switzerland. lars.michels@kispi.uzh.ch
authors.forename: Lars
authors.initials: L
authors.lastname: Michels
authors.forename: Ernst
authors.initials: E
authors.lastname: Martin
authors.forename: Peter
authors.initials: P
authors.lastname: Klaver
authors.forename: Richard
authors.initials: R
authors.lastname: Edden
authors.forename: Fernando
authors.initials: F
authors.lastname: Zelaya
authors.forename: David J
authors.initials: DJ
authors.lastname: Lythgoe
authors.forename: Rafael
authors.initials: R
authors.lastname: Lüchinger
authors.forename: Daniel
authors.initials: D
authors.lastname: Brandeis
authors.forename: Ruth L
authors.initials: RL
authors.lastname: O'Gorman
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008570:Memory, Short-Term; D059906:Neuroimaging; D018377:Neurotransmitter Agents / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism*; D011930:Reaction Time; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents; D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid