Investigating the Metabolic Changes due to Visual Stimulation using Functional Proton Magnetic Resonance Spectroscopy at 7 T

Abstract

Proton magnetic resonance spectroscopy ( 1 H-MRS) has been used to demonstrate metabolic changes in the visual cortex on visual stimulation. Small (2% to 11%) but significant stimulation induced increases in lactate, glutamate, and glutathione were observed along with decreases in aspartate, glutamine, and glycine, using 1 H-MRS at 7 T during single and repeated visual stimulation. In addition, decreases in glucose and increases in c-aminobutyric acid (GABA) were seen but did not reach significance. Changes in glutamate and aspartate are indicative of increased activity of the malate-aspartate shuttle, which taken together with the opposite changes in glucose and lactate, reflect the expected increase in brain energy metabolism. These results are in agreement with those of Mangia et al. In addition, increases in glutamate and GABA coupled with the decrease in glutamine can be interpreted in terms of increased activity of the neurotransmitter cycles. An entirely new observation is the increase of glutathione during prolonged visual stimuli. The similarity of its time course to that of glutamate suggests that it may be a response to the increased release of glutamate or to the increased production of reactive oxygen species. Together, these observations constitute the most detailed analysis to date of functional changes in human brain metabolites.

Are glutamate and lactate increases ubiquitous to physiological activation? A 1H functional MR spectroscopy study during motor activation in human brain at 7Tesla

“…The plots of the metabolite changes of the group analysis clearly illustrated a new steady state reached by the metabolites. These observations and the magnitude of the changes were comparable to those reported by previous studies during visual stimulation at 7 T (Lin et al, 2012;Mangia et al, 2007b;Schaller et al, 2013). LCModel quantification of the difference spectrum (Fig.…”

“…A lactate increase of 17 ± 5% (p b 0.001) and a glutamate increase of 2 ± 1% (p b 0.005) were observed during the activation periods (Table 1). The magnitude of the observed metabolite changes is comparable to previous reports performed in the visual cortex (Lin et al, 2012;Mangia et al, 2007a;Schaller et al, 2013).…”

“…Several factors have been suggested to explain the Glu changes during activation (reviewed in Mangia et al (2012)) such as an increased flux through the malate-aspartate shuttle (Mangia et al, 2007a;McKenna et al, 2006), increased Glu/Gln cycling, or GSH synthesis (Lin et al, 2012). In addition to the Asp decrease already reported by Mangia et al, and Lin et al reported a significant change for GSH, which may support these hypotheses.…”

“…In addition to an optimized methodology, increases of chemical shift dispersion, spatial and temporal resolutions at high field are crucial for an accurate and reliable quantification of the metabolite changes. Recent studies, performed at 7 T (Lin et al, 2012;Mangia et al, 2007a;Schaller et al, 2013), reported consistent increases of lactate during visual stimulation (10-20%). However, in contrast to Lin et al, which showed a transient increase of Lac during activation, both Mangia et al (2007a) and Schaller et al (2013) observed an increase of Lac to a new steady state within the first 1-2 min of visual activation similar to that observed in this study during motor activation.…”

“…In addition to the increased chemical shift dispersion, a high time resolution is of advantage for the characterization of the small transient changes observed. Recent fMRS studies (Lin et al, 2012;Mangia et al, 2007b;Schaller et al, 2013) at high field (7 Tesla) reported small metabolite concentration changes during visual stimulation (around 0.2 μmol/g). In particular, a very small lactate concentration increase between 10 and 23% has been observed.…”