Human brain functional MRS reveals interplay of metabolites implicated in neurotransmission and neuroenergetics

While functional MRI (fMRI) localizes brain activation and deactivation, functional MRS (fMRS) provides insights into the underlying metabolic conditions. There is much interest in measuring task-induced and resting levels of metabolites implicated in neuroenergetics (e.g., lactate, glucose, or β-hydroxybutyrate (BHB)) and neurotransmission (e.g., γ-aminobutyric acid (GABA) or pooled glutamate and glutamine (Glx)). Ultra-high magnetic field (e.g., 7T) has boosted the fMRS quantification precision, reliability, and stability of spectroscopic observations using short echo-time (TE) ¹H-MRS techniques. While short TE ¹H-MRS lacks sensitivity and specificity for fMRS at lower magnetic fields (e.g., 3T or 4T), most of these metabolites can also be detected by J-difference editing (JDE) ¹H-MRS with longer TE to filter overlapping resonances. The ¹H-MRS studies show that JDE can detect GABA, Glx, lactate, and BHB at 3T, 4T and 7T. Most recently, it has also been demonstrated that JDE ¹H-MRS is capable of reliable detection of metabolic changes in different brain areas at various magnetic fields. Combining fMRS measurements with fMRI is important for understanding normal brain function, but also clinically relevant for mechanisms and/or biomarkers of neurological and neuropsychiatric disorders. We provide an up-to-date overview of fMRS research in the last three decades, both in terms of applications and technological advances. Overall the emerging fMRS techniques can be expected to contribute substantially to our understanding of metabolism for brain function and dysfunction.