Frontal GABA levels change during working memory.

Lars Michels,Fernando Zelaya,Richard Edden,Ruth L O'Gorman,Ernst Martin,Rafael Lüchinger,Peter Klaver,Daniel Brandeis,David J Lythgoe,Thomas Koenig

doi:10.1371/journal.pone.0031933

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.

Highlights

The average adult brain utilises approximately 20% of the total energy consumption of the body
Both GABA and Glx (a combined measure of glutamate (Glu) and glutamine (Gln)) can be reliably detected in the human brain with magnetic resonance spectroscopy (MRS) [9,10], and recent studies have uncovered a link between resting GABA levels and the blood oxygen level dependent (BOLD) functional magnetic resonance imaging signal [11,12,13], the resting perfusion, and changes in cerebral blood volume during visual stimulation [13]
There was no significant difference in reaction time (RT) between WM1 and WM4 (p = 0.06, paired t-test), but subjects responded faster across working memory (WM) runs as shown by a main effect of time (F1,15 = 4.84, p = 0.05, one-way rm-ANOVA)

Summary

Introduction

The average adult brain utilises approximately 20% of the total energy consumption of the body. Neurotransmitter activity is thought to be related to the hemodynamic changes associated with brain activation, but the precise relationship between neurotransmitter levels and cerebral blood flow (CBF) has not yet been established Both GABA and Glx (a combined measure of glutamate (Glu) and glutamine (Gln)) can be reliably detected in the human brain with magnetic resonance spectroscopy (MRS) [9,10], and recent studies have uncovered a link between resting GABA levels and the blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal [11,12,13], the resting perfusion, and changes in cerebral blood volume during visual stimulation [13]. Changes in GABA have been observed with motor learning [14] and during transcranial magnetic stimulation [15,16], and changes in glutamate have been detected following acute pain stimulation [17,18] and during visual stimulation [19], suggesting that MRS measures of GABA and glutamate are sensitive to baseline neurotransmitter levels and to regional modulations of task-related neurotransmitter activity

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