Beyond the Low Frequency Fluctuations: Morning and Evening Differences in Human Brain.

Human performance, alertness, and most biological functions express rhythmic fluctuations across a 24-h-period. This phenomenon is believed to originate from differences in both circadian and homeostatic sleep-wake regulatory processes. Interactions between these processes result in time-of-day modulations of behavioral performance as well as brain activity patterns. Although the basic mechanism of the 24-h clock is conserved across evolution, there are interindividual differences in the timing of sleep-wake cycles, subjective alertness and functioning throughout the day. The study of circadian typology differences has increased during the last few years, especially research on extreme chronotypes, which provide a unique way to investigate the effects of sleep-wake regulation on cerebral mechanisms. Using functional magnetic resonance imaging (fMRI), we assessed the influence of chronotype and time-of-day on resting-state functional connectivity. Twenty-nine extreme morning- and 34 evening-type participants underwent two fMRI sessions: about 1 h after wake-up time (morning) and about 10 h after wake-up time (evening), scheduled according to their declared habitual sleep-wake pattern on a regular working day. Analysis of obtained neuroimaging data disclosed only an effect of time of day on resting-state functional connectivity; there were different patterns of functional connectivity between morning (MS) and evening (ES) sessions. The results of our study showed no differences between extreme morning-type and evening-type individuals. We demonstrate that circadian and homeostatic influences on the resting-state functional connectivity have a universal character, unaffected by circadian typology.

Evaluation of changes in biochemical composition of fetal brain between 18th and 40th gestational week in proton magnetic resonance spectroscopy.

INTRODUCTION: The aim of this study is to determine the right 1H MRS spectra of the brain in fetuses of different age, and then to define what metabolic changes occur between 18th and 40th weeks of pregnancy. METHODS: 1H MRS studies of 32 fetuses aged 18-40 gestational weeks were performed, in which the MRI excluded central nervous system malformations. The studied group included 11 fetuses aged 18-25 weeks (the second half of the second trimester), 14 fetuses aged 26-33 weeks (the first half of the third trimester), and seven fetuses aged 34-40 weeks (the second half of the third trimester). The relative ratios of metabolites concentrations to the sum of all metabolites were calculated. RESULTS: Increase in the concentrations of N-acetylaspartate (NAA), Cr, Cho, and myo-inositol (mI) with gestational age is statistically significant. Only increase in Glx is statistically insignificant. In the analyzed period of pregnancy also, an insignificant increase of NAA/Σ and Cr/Σ ratios and a decrease of mI/Σ, Cho/Σ and Glx/Σ ratios were noticed. CONCLUSIONS: Changes in the 1H MRS spectrum are visible with increasing age of the fetus. All studied substances in fetal brain change their concentrations during pregnancy, which may be associated with the synaptic and dendritic development as well as myelination. Knowledge about the chemical changes in the fetal brain can provide valuable information in studies of the mechanisms of pregnancy and fetal development, define steps of brain metabolic development and explain reasons of pathologies.

Sex differences in brain metabolite concentrations in healthy children - proton magnetic resonance spectroscopy study (1HMRS).

PURPOSE: The aim of this 1HMRS study was to define sex-related differences in metabolic spectrum between healthy children. Forty-nine girls and boys aged 6-15 years were examined. MATERIAL AND METHODS: Volume of interest was located in seven brain regions: frontal lobes, basal ganglia, hippocampi, and cerebellum. RESULTS: Statistical analysis of the results showed significantly higher (p < 0.05) myo-inositol concentrations relative to the total concentrations in the boys than the girls, as well as higher absolute N-acetyl aspartate concentrations in the left frontal lobes in girls. No other significant differences were shown, except for trends in differences. CONCLUSIONS: In clinical practice the diagnostic process first of all focuses on assessing concentrations of metabolites to relative cerebellum concentration. Thus, the findings of the present study allow the conclusion that when analysing the results of 1HMRS studies in children it is not necessary to take into account the child's gender.

From fetus to older age: A review of brain metabolic changes across the lifespan.

INTRODUCTION: The knowledge of metabolic changes across the lifespan is poorly understood. Thus we systematically reviewed the available literature to determine the changes in brain biochemical composition from fetus to older age and tried to explain them in the context of neural, cognitive, and behavioural changes. METHODS: The search identified 1262 articles regarding proton magnetic resonance spectroscopy (1H MRS) examinations through December 2017. The following data was extracted: age range of the subjects, number of subjects studied, brain regions studied, MRS sequence used, echo time, MR system, method of statistical analysis, metabolites analyzed, significant differences in metabolites concentrations with age as well as the way of presentation of the results. RESULTS: 82 studies that described brain metabolite changes with age were identified. Reports on metabolic changes related to healthy aging were analyzed and discussed among six basic age groups: fetuses, infants, children, adolescents, adults, and the elderly as well as between groups and during the whole lifetime. DISCUSSION: The results presented in the reviewed papers provide evidence that normal aging is associated with a number of metabolic changes characteristic for every period of life. Therefore, it can be concluded that the age matching is essential for comparative studies of disease states using 1H MRS.

Brain aging: Evaluation of pH using phosphorus magnetic resonance spectroscopy.

AIM: Very important aspects of aging include age-related changes occurring in the brain. The aim of the present study was to identify the standard pH value in the entire brain volume using phosphorus magnetic resonance spectroscopy in healthy individuals of both sexes in different age groups, and then to determine whether there are differences in these values. METHODS: A total of 65 individuals aged 20-32 years (mean age 24.5 ± 2.1 years, 31 women and 34 men) and 31 individuals aged 60-81 years (mean age 64.9 ± 5.5 years, 17 women and 14 men) were studied. The phosphorus magnetic resonance spectroscopy examination was carried out using a 1.5-T magnetic resonance system. The signal was acquired from the volume of interest that covered the whole brain. RESULTS: A vast majority of the examined individuals had slightly alkaline brain pH regardless of age. In the ≥20 years group, pH was 7.09 ± 0.11, and in the ≥60 years group, the average pH was 7.03 ± 0.05. This comparison of the pH identified in all the tested individuals shows a negative correlation of pH with age. CONCLUSIONS: The present findings might provide a valuable basis for further research into "healthy aging" as well as pathology in older adults. Geriatr Gerontol Int 2018; 18: 881-885.

Brain Maturation-Differences in Biochemical Composition of Fetal and Child's Brain.

INTRODUCTION: The aim of this study was to evaluate differences in 1H MRS spectra of the brain of fetuses and children from 6 to 11 years of age. MATERIAL AND METHODS: 21 healthy fetuses in the third trimester and 22 children were examined using the proton nuclear magnetic resonance. The relative metabolite concentrations to the sum of all metabolites were calculated. RESULTS: In the 1H MRS spectra of the brain from fetuses and children, there are the same characteristic peaks: N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (mI). NAA/Σ, NAA/Cr, and Cr/Σ concentrations are significantly higher and Cho/Σ, Cho/Cr, mI/Σ, and mI/Cr are significantly lower in children than in the fetuses. CONCLUSIONS: It was found that the brain metabolism changes from fetal life to childhood. The results of this study may provide a valuable basis for further research on brain maturation and "healthy aging."

Regional Differences in the Concentrations of Metabolites in the Brain of Healthy Children: A Proton Magnetic Resonance Spectroscopy (1HMRS) Study.

BACKGROUND: The aim of this 1HMRS study was to identify any potential regional differences in the metabolic spectrum in the brains of healthy children. MATERIAL/METHODS: Forty-nine healthy children aged 6-15 years (mean 11.6 years) were examined, including 21 girls and 28 boys. A 1.5T MR system (xi Signa HD 1.5T General Electric) was used in patient examinations. The VOI (Volume of Interest) was defined in 7 locations: the frontal lobe in the right and left hemispheres, the basal ganglia in the right and left hemispheres, hippocampus in the right and left hemispheres and cerebellum. SAGE 7.0 software was used for the analysis of data obtained from the 1HMRS study. Differences in the concentrations of metabolites in various regions of the brain in children were verified using the t-test for independent samples. RESULTS: There were significant differences in concentration levels between various brain regions for all the examined metabolites. NAA was the metabolite characterized by the greatest regional variation with significant differences being observed between all locations. Only in the case of Lip/Cr and the ratio of the Lip concentration to the sum of the concentrations of all the metabolites no significant differences could be observed. CONCLUISONS: The results of the study show that a child's brain is inhomogeneous. The results underline the need of the regional differences in the concentrations of metabolites being taken into account when comparing the results of 1HMRS studies in children.

Differences in Metabolite Concentrations Between the Hemispheres of the Brain in Healthy Children: A Proton Magnetic Resonance Spectroscopy Study (1HMRS).

The aim of this (1)HMRS study was to identify hemispheric asymmetries in metabolismus in healthy children. The study group consisted of children of both sexes aged 6 to 15. Concentrations of 6 metabolites occurring in the brain were determined for 6 locations: hippocampus, frontal lobe, and basal ganglia in the left and right hemispheres. There were no hemispheric differences in the metabolites' concentrations in the brain in children when the variable of sex was disregarded. Only in the group of boys and in the group of girls did the findings show few discrepancies. In none of these groups, relative concentrations to creatine concentration were found to be significantly different between hemispheres. In clinical practice, concentrations of specific metabolites are most frequently determined relative to the concentration of creatine. Consequently, the analysis of standard (1)HMRS examinations in children does not need to take into account interhemispheric differences.

PH Measurements of the Brain Using Phosphorus Magnetic Resonance Spectroscopy ((31)PMRS) in Healthy Men - Comparison of Two Analysis Methods.

BACKGROUND: Intracellular pH provides information on homeostatic mechanisms in neurons and glial cells. The aim of this study was to define pH of the brain of male volunteers using phosphorus magnetic resonance spectroscopy ((31)PMRS) and to compare two methods of calculating this value. MATERIAL/METHODS: In this study, 35 healthy, young, male volunteers (mean age: 25 years) were examined by (31)PMRS in 1.5 T MR system (Signa Excite, GE). The FID CSI (Free Induction Decay Chemical Shift Imaging) sequence was used with the following parameters: TR=4000 ms, FA=90°, NEX=2. Volume of interest (VOI) was selected depending on the size of the volunteers' brain (11-14 cm(3), mean 11.53 cm(3)). Raw data were analyzed using SAGE (GE) software. RESULTS: Based on the chemical shift of peaks in the (31)PMRS spectrum, intracellular pH was calculated using two equations. In both methods the mean pH was slightly alkaline (7.07 and 7.08). Results were compared with a t-test. Significant difference (p<0.05) was found between these two methods. CONCLUSIONS: The (31)PMRS method enables non-invasive in vivo measurements of pH. The choice of the calculation method is crucial for computing this value. Comparing the results obtained by different teams can be done in a fully credible way only if the calculations were performed using the same formula.

Phosphorus Spectroscopy of Calf Muscles before and after Exercise.

BACKGROUND: The aim of this study was to determine (31)PMRS reference spectrum and intracellular pH of calf muscles in the dominant limb of healthy, young, male volunteers before and after intense physical effort. MATERIAL/METHODS: Examinations were performed with a 1.5 T MR system. FID CSI (Free Induction Decay Chemical Shift Imaging) sequence was used with the following parameters: TR=4000 ms, FA=90°, NEX=2 and VOI (Volume Of Interest)=8×8×8 cm(3) (512 cm(3)) involving in calf muscles. Raw data was preprocessed using SAGE (GE) software. Authors analyzed relative concentrations ratios of selected metabolites: PCr/ATP and PCr/Pi. Intracellular pH and relative concentrations ratios of each metabolite (Pi, PCr, α-ATP, ß-ATP, γ-ATP, ATP) were also calculated relative to the sum of concentrations of all metabolites. Results were compared with a t-test. RESULTS: Based on statistical analysis of results significant differences (p<0.05) were demonstrated for some of the studied metabolites and for intracellular pH. Increase in PCr concentration in relation to the sum of concentrations of all metabolites and to ATP concentration was noted. However, ß-ATP, α-ATP and ATP concentrations relative to the sum of concentrations of all metabolites become reduced. Decrease in pH after physical effort was demonstrated. There were no significant differences (p<0.05) in concentrations of remaining metabolites before and after exercise. Increase in PCr concentration relative to Pi concentration and decrease of Pi and γ-ATP concentration relative to the sum of concentrations of all metabolites were demonstrated. CONCLUSIONS: The (31)PMRS method enables assessment of concentrations of phosphorus-containing metabolites as well as intercellular pH before and after exercise. This method is still under examination, but it has already shown promise as a diagnostic tool for the future.