Diurnal changes in human brain glutamate + glutamine levels in the course of development and their relationship to sleep

Volk, Carina; Jaramillo, Valeria; Studler, Mirjam; Furrer, Melanie; O’Gorman, Ruth L.; Huber, Reto

doi:10.1016/j.neuroimage.2019.04.040

Cited by 16 publications

(11 citation statements)

References 42 publications

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“…Our Gln trajectories however do not support this, as we observe no significant changes in Gln concentrations (i.u or creatine ratios) across development, although this might be due to technical reasons (see below). Childhood decreases in Glu/Glx concentrations are consistent with observations in other MRS studies both within the parietal lobe (Volk et al 2019), and in in other brain regions (the basal ganglia, and occipital lobe; Ghiselli et al 2015; Shimizu et al 2017).…”

Section: Discussionsupporting

confidence: 89%

“…Previous attempts to characterise the neurodevelopmental dynamics of these key brain metabolites have considered narrow adult only (≥18) or child only (<18) cohorts (Chang et al 1996; Saunders et al 1999; Pfefferbaun et al 1999; Angelie et al 2001; Kaiser et al 2005; Sailasuta et al 2008; Reyngoudt et al 2012; Marsman et al 2013; Gao et al 2013; Blüml et al 2013; Hädel et al 2013; Silveri et al 2013; Ding et al 2016; Eylers et al 2016; Puts et al 2017; Schmitz et al 2018; Lind et al 2020; Saleh et al 2020; Hupfeld et al 2021), and/or have focused on very few metabolites (Ghisleni et al 2015; Volk et al 2019; Shimizu et al 2017). Combined with small sample sizes, variation in brain region, and 1 H-MRS quantification methods, this has led to highly conflicting results.…”

Section: Introductionmentioning

confidence: 99%

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The developmental trajectory of¹H-MRS brain metabolites from childhood to adulthood

Thomson,

Hwa,

Pasanta

et al. 2023

Preprint

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Human brain development is ongoing throughout childhood, with for example myelination of nerve fibres and refinement of synaptic connections continuing until early adulthood.1H-Magnetic Resonance Spectroscopy (1H-MRS)can be used to quantify the concentrations of endogenous metabolites (e.g., glutamate and γ-aminobutyric acid (GABA)) in the human brain in vivo and so can provide valuable, tractable insight into the biochemical processes that support postnatal neurodevelopment. This can feasibly provide new insight into and aid management of neurodevelopmental disorders by providing chemical markers of atypical development. This study aims to characterize the normative developmental trajectory of various brain metabolites, as measured by1H-MRS from a midline posterior parietal voxel. We find significant non-linear trajectories for GABA+, Glx, tNAA and tCr concentrations. Glx and GABA+ concentrations steeply decrease across childhood. tNAA concentrations are relatively stable in childhood but gradually decrease from early adulthood, while tCr concentrations increase from childhood to early adulthood. tCho was the only metabolite to have a strictly linear association with age. Trajectories likely reflect fundamental neurodevelopmental processes (including local circuit refinement) which occur from childhood to early adulthood and can be associated with cognitive development; we find GABA+ concentrations significantly positively correlate with recognition memory scores across post-natal development.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

The developmental trajectory of¹H-MRS brain metabolites from childhood to adulthood

Thomson,

Hwa,

Pasanta

et al. 2023

Preprint

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“…As representative references for each patient, we included five healthy controls with one whole-night EEG recording from studies conducted between 2008 and 2019 by the research group of Reto Huber from the University Children’s Hospital Zurich (Kurth et al, 2012; Wehrle et al, 2017; Volk et al, 2019; unpublished observations). Age-wise, these controls differed at most 1.1 years from the corresponding patient, resulting in an age distribution in controls (age 4.2 - 21.4 years, mean 12.4 years) that was comparable to that in patients.…”

Section: Methodsmentioning

confidence: 99%

“…The data were sampled at 500 Hz (analogously filtered between 0.01 and 200 Hz) and then digitally band-pass filtered (0.5 – 50 Hz). Scoring was done by investigators of the original studies (Kurth et al, 2012; Wehrle et al, 2017; Volk et al, 2019; unpublished observations) according to the guidelines from the AASM (Iber et al, 2007), applied to 20-sec epochs.…”

Section: Methodsmentioning

confidence: 99%

“…perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted September 30, 2020. ; https://doi.org/10.1101/2020.09.28.20203265 doi: medRxiv preprint Reto Huber from the University Children's Hospital Zurich (Kurth et al, 2012;Wehrle et al, 2017;Volk et al, 2019;unpublished observations). Age-wise, these controls differed at most 1.1 years from the corresponding patient, resulting in an age distribution in controls (age 4.2 -21.4 years, mean 12.4 years) that was comparable to that in patients.…”

Section: Participantsmentioning

confidence: 99%

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Altered EEG markers of synaptic plasticity in a human model of NMDA receptor deficiency: anti-NMDA receptor encephalitis

Gefferie

Maric

Critelli

et al. 2020

Preprint

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Plasticity of synaptic strength and density is a vital mechanism enabling memory consolidation, learning, and neurodevelopment. It is strongly dependent on the intact function of N-methyl-D-aspartate receptors (NMDAR). The importance of NMDAR is further evident as their dysfunction is involved in many diseases such as schizophrenia, Alzheimer's disease, neurodevelopmental disorders, and epilepsies. Synaptic plasticity is thought to be reflected by changes of sleep slow wave slopes across the night, namely higher slopes after wakefulness at the beginning of sleep than after a night of sleep. Hence, a functional NMDAR deficiency should theoretically lead to altered overnight changes of slow wave slopes. Here we investigated whether pediatric patients with anti-NMDAR encephalitis, being a very rare but unique human model of NMDAR deficiency due to autoantibodies against receptor subunits, indeed show alterations in this sleep EEG marker for synaptic plasticity. We retrospectively analyzed 12 whole-night EEGs of 9 patients (age 4.3-20.8 years, 7 females) and compared them to a control group of 45 healthy individuals with the same age distribution. Slow wave slopes were calculated for the first and last hour of non-rapid eye movement (NREM) sleep (factor 'hour') for patients and controls (factor 'group'). There was a significant interaction between 'hour' and 'group' (p = 0.013), with patients showing a smaller overnight decrease of slow wave slopes than controls. Moreover, we found smaller slopes during the first hour in patients (p = 0.022), whereas there was no group difference during the last hour of NREM sleep (p = 0.980). Importantly, the distribution of sleep stages was not different between the groups, and in our main analyses of patients without severe disturbance of sleep architecture, neither was the incidence of slow waves. These possible confounders could therefore not account for the differences in the slow wave slope values, which we also saw in the analysis of the whole sample of EEGs. These results suggest that quantitative EEG analysis of slow wave characteristics may reveal impaired synaptic plasticity in patients with anti-NMDAR encephalitis, a human model of functional NMDAR deficiency. Thus, in the future, the changes of sleep slow wave slopes may contribute to the development of electrophysiological biomarkers of functional NMDAR deficiency and synaptic plasticity in general.

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Altered EEG markers of synaptic plasticity in a human model of NMDA receptor deficiency: Anti-NMDA receptor encephalitis

et al. 2021

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Diurnal changes in human brain glutamate + glutamine levels in the course of development and their relationship to sleep

Cited by 16 publications

References 42 publications

The developmental trajectory of¹H-MRS brain metabolites from childhood to adulthood

The developmental trajectory of¹H-MRS brain metabolites from childhood to adulthood

Altered EEG markers of synaptic plasticity in a human model of NMDA receptor deficiency: anti-NMDA receptor encephalitis

Altered EEG markers of synaptic plasticity in a human model of NMDA receptor deficiency: Anti-NMDA receptor encephalitis

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Diurnal changes in human brain glutamate + glutamine levels in the course of development and their relationship to sleep

Cited by 16 publications

References 42 publications

The developmental trajectory of1H-MRS brain metabolites from childhood to adulthood

The developmental trajectory of1H-MRS brain metabolites from childhood to adulthood

Altered EEG markers of synaptic plasticity in a human model of NMDA receptor deficiency: anti-NMDA receptor encephalitis

Altered EEG markers of synaptic plasticity in a human model of NMDA receptor deficiency: Anti-NMDA receptor encephalitis

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The developmental trajectory of¹H-MRS brain metabolites from childhood to adulthood

The developmental trajectory of¹H-MRS brain metabolites from childhood to adulthood