A Guide to the Metabolic Pathways and Function of Metabolites Observed in Human Brain 1H Magnetic Resonance Spectra

Abstract

The current knowledge of the normal biochemistry of compounds that give rise to resonances in human brain proton magnetic resonance spectra measureable at readily available field strengths (i.e. ≤3 T) is reviewed. Molecules covered include myo- and scyllo-inositol, glycerophospho- and phospho-choline and choline, creatine and phosphocreatine, N-acetylaspartate, N-acetylaspartylglutamate, glutamate, glutamine, γ-aminobutyrate, glucose, glutathione and lactate. The factors which influence changes in the levels of these compounds are discussed. As most proton resonances in the brain at low field are derived from a combination of moieties whose biochemistry is complex and interrelated, an understanding of the mechanisms underlying why these species change is crucial to meaningful interpretation of human brain spectra.

Glutamatergic and Neuronal Dysfunction in Gray and White Matter: A Spectroscopic Imaging Study in a Large Schizophrenia Sample

“…However, increased Glx in right frontal WM early in the illness could directly affect axons and result in NAAc reductions. 47 Overall, our findings are consistent with an NMDAR hypofunction process of glutamatergic sub-lethal excitotoxicity in GM and WM, which progresses but without neuronal loss. Effective antipsychotic treatment probably reduces glutamatergic turnover but not enough to completely arrest the underlying process.…”

“…Early in the illness we find an increase in Glx in GM and WM, consistent with greater glutamatergic turnover. 47 Later in the illness this process remains, but additional differential tissue-specific changes occur: in GM, higher NAAc suggestive of neuronal compaction 47 ; in WM, reduced NAAc and total-creatine, suggestive of axonal dysfunction and altered energy metabolism, respectively. Longitudinal GM (0.6%/y) and WM (0.3%/y) volume reductions (which decrease with age) have been documented in schizophrenia 8 as well as in un-affected twins, 48 suggestive of disease progression.…”

Human Auditory Cortex Neurochemistry Reflects the Presence and Severity of Tinnitus

“…These correlations are illustrated in Figure 4. Because choline is present in higher concentrations in WM than GM (Rae, 2014) and tissue composition correlated with age and hearing loss, we repeated significant correlation analyses after partialing out age, hearing loss, and all tissue fractions from both RAC choline concentration and the subject variable of interest. It should be kept in mind that such extensive partialization removes a lot of variance from the data, so the same strength of correlation Table 1.…”

“…Therefore, GABA deficiency may underlie excessive sound-evoked (Gu et al, 2010) and spontaneous (Adjamian et al, 2012) activity that has been observed previously in tinnitus in humans, even after matching for hearing loss and hyperacusis. However, GABA systems may have a more complex role in tinnitus; a recent study found evidence of increased GABAmediated tonic inhibition in the auditory thalami of rats with noise-induced tinnitus (Sametsky et al, 2015). This excess inhibition was in turn linked to abnormal burst firing of thalamic neurons, which has been argued to trigger abnormal cortical activity linked to tinnitus (Llinás et al, 1999).…”

The effect of striatal dopamine depletion on striatal and cortical glutamate: A mini-review

“…For example, the accumulation of 18 F-labeled 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine ([ 18 F]F-DOPA) in the brain measured with PET can be used as a quantitative index of dopamine synthesis capacity (Nanni et al, 2007;Pretze et al, 2014 (Rae, 2014). These include glutamate, glutamine, glutamate + glutamine (Glx), creatine (Cr), myo-inositol (Myo), and N-acetyl-aspartate (NAA), among several others (Rae, 2014).…”