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To measure N-acetyl aspartyl glutamate (NAAG) and N-acetyl aspartate (NAA) concentrations in visual cortex activated by a continuous stimulation in a 3 T field. NAAG and NAA spectra were obtained with MEGA-PRESS pulse sequence (TE/TR = 140/2000 ms; δONNAAG/δOFFNAAG = 4.61/4.15 ppm; δONNAA/δOFFNAA = 4.84/4.38 ppm) in 14 healthy volunteers at rest and upon stimulation by a radial checkerboard flickering at a frequency of 8 Hz. Spectra of all subjects were frequency and phase aligned and then averaged. Additionally, to obtain the time-dependency data, spectra were divided into time sections of 64 s each. The intensities of NAA, NAAG and lactate + macromolecular (Lac + MM) signals were defined by integration of the real part of spectra. The heights of the central resonance of NAAG and NAA signals were measured. The NAAG and NAA concentrations, measured with 2.5% and 0.5% error, respectively, were unaffected by visual activation. A significant increase in the Lac + MM signal by ~ 12% is clearly observed. No stimulation-induced time dependency was found for NAAG or NAA, while the increase in Lac + MM was gradual. The concentration values in visual cortex are in good agreement with the 7 T MRS measurements: [NAAG] = 1.55 mM, [NAA] = 11.95 mM. The MEGA-PRESS pulse sequence together with the spectral preprocessing techniques allowed to demonstrate that the concentrations of NAAG and NAA in the visual cortex remain constant during continuous visual stimulation within the margin of error. An increase in the lactate signal intensity signifies the activation of the anaerobic glycolysis in activated visual cortex.

Purpose To separately measure N-acetyl aspartul glutamate (NAAG), N-acetyl aspartate (NAA), aspartate (Asp), and glutamate (Glu) concentrations in white matter (WM) using J-editing techniques in patients with mild traumatic brain injury (mTBI) in the acute phase. Methods Twenty-four patients with closed concussive head injury and 29 healthy volunteers were enrolled in the current study. For extended 1 H MRS examination, patients and controls were equally divided into two subgroups. In subgroup 1 (12 patients/15 controls), NAAG and NAA concentrations were measured in WM separately with MEGA-PRESS (echo time/repetition time [TE/TR] = 140/2000 ms; δ ON NAA / δ OFF NAA = 4.84/4.38 ppm, δ ON NAAG / δ OFF NAAG = 4.61/4.15 ppm). In subgroup 2 (12 patients/14 controls), Asp and Glu concentrations were acquired with MEGA-PRESS (TE/TR = 90/2000 ms; δ ON Asp / δ OFF Asp = 3.89/5.21 ppm) and TE-averaged PRESS (TE from 35 ms to 185 ms with 2.5-ms increments; TR = 2000 ms) pulse sequences, respectively. Results tNAA and NAAG concentrations were found to be reduced, while NAA concentrations were unchanged, after mild mTBI. Reduced Asp and elevated myo-inositol (mI) concentrations were also found. Conclusion The main finding of the study is that the tNAA signal reduction in WM after mTBI is associated with a decrease in the NAAG concentration rather than a decrease in the NAA concentration, as was thought previously. This finding highlights the importance of separating these signals, at least for WM studies, to avoid misinterpretation of the results. NAAG plays an important role in selectively activating mGluR3 receptors, thus providing neuroprotective and neuroreparative functions immediately after mTBI. NAAG shows potential for the development of new therapeutic strategies for patients with injuries of varying severity.

—Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain; it plays an important role in various types of synaptic plasticity and pathology. In the present work, proton magnetic resonance spectroscopy (1H-MRS) and two modified MEGA-PRESS pulse sequences, that is, –GABAMEGA-PRESS and +GABAMEGA-PRESS, were used to investigate the effect of visual stimulation on the GABA level in the human visual cortex in vivo. With –GABAMEGA-PRESS, it was possible to acquire the 1H-NMR signal of methylated protons of GABA with the chemical shift δ = 3.01 ppm without the signals from macromolecules. When +GABAMEGA-PRESS was used, the GABA signal was a superposition of resonances of methylene protons of GABA and macromolecules. The effect of constant visual stimulation on the level of N-acetylaspartate and total level of glutamate and glutamine was also estimated. Constant visual stimulation had no effect on the levels of N-acetylaspartate and glutamine in the visual cortex. The –GABA signal intensity decreased with a statistically significant decrease in the level of GABA signal intensity leading to inactivation of GABA synthesis. No statistically significant changes in the intensity of the +GABA resonance were found, probably due to the effect of visual stimulation on macromolecules. In order to test this hypothesis, a signal from macromolecules was acquired using a specifically designed inversion-recovery pulse sequence. It was shown that the intensity of this signal is unaffected by visual stimulation and the absence of changes in the intensity of the +GABA signal during the stimulation has to be considered as the masking effect of macromolecular signal.

A kinetic model of the process response of nervous tissue to an external signal stimulus is proposed. The model is based on the multistage and non-linear nature of the dynamic process of changes of N-acetylaspartate concentration. The existence of multiple steady states explains the trigger effect of the system. The effect of substrate inhibition for this system was studied as a necessary factor of N-acetylaspartate’s autostabilization as a key metabolite in the brain. The appearance of N-acetylaspartate’s “anti-peak” causes a wave of its hydrolysis products, such as aspartic acid and acetic acid.

Previously using 31P magnetic resonance spectroscopy (MRS) we have demonstrated that one hyperbaric oxygenation (HBO) session (with O2 pressure 1.2 atm) directly activates cerebral energetics: the decrease in creatine phosphate (PCr) and, possibly, the increase in nicotinamide adenine dinucleotide. The aim of this study is to elucidate the effect of one HBO session on the concentrations of metabolites detectible by 1H MRS, and on the connectivity in Default Mode Network. Absolute concentrations of the metabolites were calculated. The reduction of N-acetyl aspartate by 3% was found in mediolateral prefrontal cortex (MPFC) with p

Intracellular concentrations of N acetyaspartate (NAA), aspartate (Asp) and glutamate (Glu) were determined for the first time in human brain in vivo, and the effect of severe traumatic brain injury on NAA synthesis in acute and late post-traumatic period was investigated. In MRI‑negative frontal lobes one day after injury Asp and Glu levels were found to decrease by 45 and 35%, respectively, while NAA level decreased by only 16%. A negative correlation between NAA concentration and the ratio of Asp/Glu concentrations was found. In the long-term period, Glu level returned to normal, Asp level remained below normal by 60%, NAA level was reduced by 65% relative to normal, and Asp/Glu ratio significantly decreased. The obtained results revealed leading role of the neuronal aspartate-malate shuttle in violation of NAA synthesis.

For the first time the intracellular concentrations of N-acetylaspartate (NAA), aspartate (Asp), and glutamate (Glu) were measured in human brain in vivo, and the effect of severe traumatic brain injury on NAA synthesis in acute and remote posttraumatic phases was revealed. In non-damaged (MRI-negative) lobes the next day after injury, Asp and Glu decreased by 45% and 35%, respectively, while NAA decreased only by 16%. A negative correlation between NAA and Asp/Glu ratio was found. The Glu level returned to the norm long after injury, Asp remained below the norm by 60%, NAA decreased by 65% relative to the norm, and Asp/Glu decreased significantly. The results obtained educe the leading role of neuronal aspartate-malate shuttle in NAA synthesis alterations.

The MEGA-PRESS pulse sequence was used for determination of overlapping signals in the (1)H-MRS spectra of the human brain. For the first time, the balance of GABA glutamate/glutamine concentrations was estimated quantitatively in the human brain of patients with ultra-high risk of schizophrenia. It was found that GABA concentration and GABA/GLX ratios were significantly reduced in the left frontal lobe of UHR subjects.

Introduction31P MRS is a unique way of in vivo energy metabolism research. This method allowed revealing schizophrenia-induced disturbances of energy exchange in resting state [1]. We use 31P MRS in presence of visual stimulation that allows neuronal energy-consuming processes studying.ObjectiveRevealing of stimulation effects on high-energy phosphates (PCr, ATP) in early-stage schizophrenia.AimDiscovery of energy processes contribution in schizophrenia pathogenesis.MethodsTwelve right-handed 18–26 years old male patients with early-staged schizophrenia (F20, ICD-10) and 20 age-matched healthy right-handed controls. Spectra were acquired on Philips Achieva 3.0 T using Rapid Biomed 31P/1H birdcage coil and 2D ISIS pulse sequence. fMRI was used for accurate 2D slice positioning, spectroscopy voxels containing primary visual cortex (V1) were averaged (see Fig. 1). Two 31P spectra of V1 were obtained: firstly in resting state and then during 6 minutes of continuous stimulation by 6 Hz flashing checkerboard. Spectra were processed in jMRUI.ResultsExcitation reduced PCr in the norm and had no effect on schizophrenia (see Fig. 2). No excitation-induced ATP changes in both groups were revealed.ConclusionAlteration in PCr behavior in this study witnesses for deviations in energy-consuming processes in schizophrenia. A new scheme of neuronal response to stimulation in schizophrenia is offered.Disclosure of interestThe authors have not supplied their declaration of competing interest.