High temporal resolution functional magnetic resonance spectroscopy in the mouse upon visual stimulation.

Functional magnetic resonance spectroscopy (fMRS) quantifies metabolic variations upon presentation of a stimulus and can therefore provide complementary information compared to activity inferred from functional magnetic resonance imaging (fMRI). Improving the temporal resolution of fMRS can be beneficial to clinical applications where detailed information on metabolism can assist the characterization of brain function in healthy and sick populations as well as for neuroscience applications where information on the nature of the underlying activity could be potentially gained. Furthermore, fMRS with higher temporal resolution could benefit basic studies on animal models of disease and for investigating brain function in general. However, to date, fMRS has been limited to sustained periods of activation which risk adaptation and other undesirable effects. Here, we performed fMRS experiments in the mouse with high temporal resolution (12 s), and show the feasibility of such an approach for reliably quantifying metabolic variations upon activation. We detected metabolic variations in the superior colliculus of mice subjected to visual stimulation delivered in a block paradigm at 9.4 T. A robust modulation of glutamate is observed on the average time course, on the difference spectra and on the concentration distributions during active and recovery periods. A general linear model is used for the statistical analysis, and for exploring the nature of the modulation. Changes in NAAG, PCr and Cr levels were also detected. A control experiment with no stimulation reveals potential metabolic signal "drifts" that are not correlated with the functional activity, which should be taken into account when analyzing fMRS data in general. Our findings are promising for future applications of fMRS.