Considerations for event-related gamma-aminobutyric acid functional magnetic resonance spectroscopy

The use of sequential proton magnetic resonance spectroscopy (MRS) to follow glutamate and gamma-aminobutyric acid (GABA) changes during functional task-based paradigms, functional MRS (fMRS), has increased. This technique has been used to investigate GABA dynamics during both sensory and behavioural tasks, usually with long 'block design' paradigms. Recently, there has been an increase in interest in the use of short stimuli and 'event-related' tasks. While changes in glutamate can be readily followed by collecting multiple individual transients (or shots), measurement of GABA, especially at 3 T, is usually performed using editing techniques like Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS), which by its nature is a dual shot approach. This poses problems when considering an event-related experiment, where it is unclear when GABA may change, or how this may affect the individual subspectra of the MEGA-PRESS acquisition. To address this issue, MEGA-PRESS data were simulated to reflect the effect of a transient change in GABA concentration due to a short event-related stimulus. The change in GABA was simulated for both the ON and OFF subspectra, and the effect of three different conditions (increase only during ON acquisition, increase during OFF acquisition and increase across both) on the corresponding edited GABA spectrum was modelled. Results show that a transient increase in GABA that only occurs during the ON subspectral acquisition, while not changing the results much from when GABA is changed across both conditions, will give a much larger change in the edited GABA spectrum than a transient increase that occurs only during the OFF subspectral acquisition. These results suggest that researchers should think carefully about the design of any event-related fMRS studies using MEGA-PRESS, as well as the analysis of other functional paradigms where transient changes in GABA may be expected. Experimental design considerations are therefore discussed, and suggestions are made.