Lactate Changes Quantified by fMRS: A Meta-Analysis

Over the past 15 years, the number of studies employing functional magnetic resonance spectroscopy (fMRS) has tripled, driven in part by improvements in scanner performance and a growing interest in the investigation of metabolic dynamics associated with the modulation of brain activity. Higher static magnetic fields, enhancements in gradient strength and stability, more sensitive RF coil designs, and refinements in quantification approaches have considerably increased spectral quality and temporal resolution. Together, these developments have further strengthened the unique ability of fMRS to monitor in vivo metabolic changes. Given its role in oxidative metabolism and its relevance in brain energetics, lactate (Lac) is one of the most studied metabolites, following the most important excitatory (glutamate [Glu]) and inhibitory (GABA) neurotransmitters. This meta-analysis aims to obtain an estimate of mean Lac changes in the healthy human brain during a task, by grouping together the papers published to date according to magnetic field strength, spectroscopic sequence echo time, and task design. Across all included studies, an increase in Lac concentration during stimulation is reported by all the papers included in this meta-analysis, with a statistically significant increase between the stimulation and rest periods of 22%. Studies using visual stimuli reported a significantly higher increase of Lac compared to studies employing motor or cognitive tasks. No significant differences emerged between studies at different magnetic field strengths or echo times. This meta-analysis, however, revealed a substantial methodological heterogeneity, highlighting the need for greater standardization in fMRS methodologies.