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The neuronal tricarboxylic acid and glutamate/glutamine (Glu/Gln) cycles play important roles in brain function. These processes can be measured in vivo using dynamic 1H–[13C] MRS during administration of 13C‐labeled glucose. Proton‐observed carbon‐edited (POCE) MRS enhances the signal‐to‐noise ratio (SNR) compared with direct 13C‐MRS. Ultra‐high field further boosts the SNR and increases spectral dispersion; however, even at 7 T, Glu and Gln 1H‐resonances may overlap. Further gain can be obtained with selective POCE (selPOCE). Our aim was to create a setup for indirect dynamic 1H–[13C] MRS in the human brain at 7 T. A home‐built non‐shielded transmit–receive 13C‐birdcage head coil with eight transmit–receive 1H‐dipole antennas was used together with a 32‐channel 1H‐receive array. Electromagnetic simulations were carried out to ensure that acquisitions remained within local and global head SAR limits. POCE‐MRS was performed using slice‐selective excitation with semi‐localization by adiabatic selective refocusing (sLASER) and stimulated echo acquisition mode (STEAM) localization, and selPOCE‐MRS using STEAM. Sequences were tested in a phantom containing non‐enriched Glu and Gln, and in three healthy volunteers during uniformly labeled 13C‐glucose infusions. In one subject the voxel position was alternated between bi‐frontal and bi‐occipital placement within one session. [4‐13C]Glu‐H4 and [4‐13C]Gln‐H4 signals could be separately detected using both STEAM‐POCE and STEAM‐selPOCE in the phantom. In vivo, [4,5‐13C]Glx could be detected using both sLASER‐POCE and STEAM‐POCE, with similar sensitivities, but [4,5‐13C]Glu and [4,5‐13C]Gln signals could not be completely resolved. STEAM‐POCE was alternately performed bi‐frontal and bi‐occipital within a single session without repositioning of the subject, yielding similar results. With STEAM‐selPOCE, [4,5‐13C]Glu and [4,5‐13C]Gln could be clearly separated. We have shown that with our setup indirect dynamic 1H–[13C] MRS at 7 T is feasible in different locations in the brain within one session, and by using STEAM‐selPOCE it is possible to separate Glu from Gln in vivo while obtaining high quality spectra. [ABSTRACT FROM AUTHOR]

Objective: Obesity is associated with alterations in eating behavior and neurocognitive function. In this study, we investigate the effect of obesity on brain energy utilization, including brain glucose transport and metabolism. Methods: A total of 11 lean participants and 7 young healthy participants with obesity (mean age, 27 years) underwent magnetic resonance spectroscopy scanning coupled with a hyperglycemic clamp (target, ~180 mg/dL) using [1‐13C] glucose to measure brain glucose uptake and metabolism, as well as peripheral markers of insulin resistance. Results: Individuals with obesity demonstrated an ~20% lower ratio of brain glucose uptake to cerebral glucose metabolic rate (Tmax/CMRglucose) than lean participants (2.12 ± 0.51 vs. 2.67 ± 0.51; p = 0.04). The cerebral tricarboxylic acid cycle flux (VTCA) was similar between the two groups (p = 0.64). There was a negative correlation between total nonesterified fatty acids and Tmax/CMRglucose (r = −0.477; p = 0.045). Conclusions: We conclude that CMRglucose is unlikely to differ between groups due to similar VTCA, and, therefore, the glucose transport Tmax is lower in individuals with obesity. These human findings suggest that obesity is associated with reduced cerebral glucose transport capacity even at a young age and in the absence of other cardiometabolic comorbidities, which may have implications for long‐term brain function and health. [ABSTRACT FROM AUTHOR]

The olfactory bulb (OB) plays a fundamental role in the sense of smell and has been implicated in several pathologies, including Alzheimer's disease. Despite its importance, high metabolic activity and unique laminar architecture, the OB is not frequently studied using MRS methods, likely due to the small size and challenging location. Here we present a detailed metabolic characterization of OB metabolism, in terms of both static metabolite concentrations using 1H MRS and metabolic fluxes associated with neuro‐energetics and neurotransmission by tracing the dynamic 13C flow from intravenously administered [1,6‐13C2]‐glucose, [2‐13C]‐glucose and [2‐13C]‐acetate to downstream metabolites, including [4‐13C]‐glutamate, [4‐13C]‐glutamine and [2‐13C]‐GABA. The unique laminar architecture and associated metabolism of the OB, distinctly different from that of the cerebral cortex, is characterized by elevated GABA and glutamine levels, as well as increased GABAergic and astroglial energy metabolism and neurotransmission. The results show that, despite the technical challenges, high‐quality 1H and 1H–[13C] MR spectra can be obtained from the rat OB in vivo. The derived metabolite concentrations and metabolic rates demonstrate a unique metabolic profile for the OB. The metabolic model provides a solid basis for future OB studies on functional activation or pathological conditions. [ABSTRACT FROM AUTHOR]

Reading disability is a brain-based difficulty in acquiring fluent reading skills that affects significant numbers of children. Although neuroanatomical and neurofunctional networks involved in typical and atypical reading are increasingly well characterized, the underlying neurochemical bases of individual differences in reading development are virtually unknown. The current study is the first to examine neurochemistry in children during the critical period in which the neurocircuits that support skilled reading are still developing. In a longitudinal pediatric sample of emergent readers whose reading indicators range on a continuum from impaired to superior, we examined the relationship between individual differences in reading and reading-related skills and concentrations of neurometabolites measured using magnetic resonance spectroscopy. Both continuous and group analyses revealed that choline and glutamate concentrations were negatively correlated with reading and related linguistic measures in phonology and vocabulary (such that higher concentrations were associated with poorer performance). Correlations with behavioral scores obtained 24 months later reveal stability for the relationship between glutamate and reading performance. Implications for neurodevelopmental models of reading and reading disability are discussed, including possible links of choline and glutamate to white matter anomalies and hyperexcitability. These findings point to new directions for research on gene-brain-behavior pathways in human studies of reading disability.

After recovering from the acute COVID-19 illness, a substantial proportion of people continue experiencing post-acute sequelae of COVID-19 (PASC), also termed "long COVID". Their quality of life is adversely impacted by persistent cognitive dysfunction and affective distress, but the underlying neural mechanisms are poorly understood. The present study recruited a group of mostly young, previously healthy adults (24.4 ± 5.2 years of age) who experienced PASC for almost 6 months following a mild acute COVID-19 illness. Confirming prior evidence, they reported noticeable memory and attention deficits, brain fog, depression/anxiety, fatigue, and other symptoms potentially suggestive of excitation/inhibition imbalance. Proton magnetic resonance spectroscopy (1H-MRS) was used to examine the neurochemical aspects of cell signaling with an emphasis on GABA levels in the occipital cortex. The PASC participants were compared to a control (CNT) group matched in demographics, intelligence, and an array of other variables. Controlling for tissue composition, biological sex, and alcohol intake, the PASC group had lower GABA+/water than CNT, which correlated with depression and poor sleep quality. The mediation analysis revealed that the impact of PASC on depression was partly mediated by lower GABA+/water, indicative of cortical hyperexcitability as an underlying mechanism. In addition, N-acetylaspartate (NAA) tended to be lower in the PASC group, possibly suggesting compromised neuronal integrity. Persistent neuroinflammation may contribute to the pathogenesis of PASC-related neurocognitive dysfunction. [ABSTRACT FROM AUTHOR]

Several coronavirus disease 2019 (COVID-19) studies have focused on neuropathology. In this issue of the JCI, Qin, Wu, and Chen et al. focused specifically on people whose acute infection lacked obvious neurological involvement. Severely infected patients showed abnormal gray matter volumes, white matter diffusion, and cerebral blood flow compared with healthy controls and those with mild infection. The data remain associative rather than mechanistic, but correlations with systemic immune markers suggest effects of inflammation, hypercoagulation, or other aspects of disease severity. Mechanistic research is warranted. Given the lack of obvious neurological symptoms, neurocognitive assessments were not performed, but the findings suggest that such assessments may be warranted in severely affected patients, even without obvious symptoms. Further, studying CNS involvement of other disorders with overlapping pathophysiologies such as inflammation, coagulation, hypoxia, or direct viral infection may reveal the causes for COVID-19-related neuropathology., The absence of obvious neurological symptoms We read with interest the article in this issue of the JCI by Qin, Wu, and Chen et al. (1). Patients with severe coronavirus [...]

Hypoglycemia occurs frequently during intensive insulin therapy in patients with both type 1 and type 2 diabetes and remains the single most important obstacle in achieving tight glycemic control. Using [...]

When a person consumes ethanol, the body quickly begins to convert it to acetic acid, which circulates in the blood and can serve as a source of energy for the [...]