Biology subjects

Puts, N.

Publications and source records attributed to Puts, N..

5 recordsLinked to original sources

bioRxiv2025

Characterising the association between posterior parietal metabolite levels and cortical macrostructure in a cohort spanning childhood to adulthood.

Postnatal brain development is characterised by dynamic macrostructural changes, including cortical thinning and cortical flattening during childhood and adolescence. These macro-structural changes are parallel with developmental changes in brain neurochemistry, probed in the human brain using Magnetic Resonance Spectroscopy (MRS). This includes neurotransmitters such glutamate and gamma-aminobutyric acid (GABA), as well as building blocks of neuronal and associated tissue such as N-acetyl aspartate (NAA), and those involved in metabolism such as creatine (Cr). While previous research has linked MRS-measured neuro-metabolite levels to bulk tissue composition (e.g., gray matter, white matter, and cerebrospinal fluid), the relationship between neurochemistry and more granular macrostructural metrics, such as cortical thickness, area, volume, and local gyrification, remains unexplored. This study investigates the association between MRS-measured neuro-metabolite levels in the posterior parietal cortex (PPC) and PPC-voxel cortical macrostructural metrics in a developmental cohort of 86 individuals aged 5-35 years. We also examine whether PPC metabolite concentrations associate with whole-brain structural metrics to determine whether associations are region-specific or more broadly generalisable. Our findings reveal significant positive associations between PPC cortical thickness, volume, local gyrification index (LGI) and Glx (glutamate + glutamine) levels, likely because differences in cortical microstructure, including dendritic arbour complexity, contributes to variation in both cortical macrostructure and Glx activity across development. Additionally, PPC Glx:GABA+ ratio negatively associated with subcortical gray matter volume, while PPC total NAA positively associated with cerebral white matter volume, suggesting a link between regional neurochemistry and broader brain structure. These results highlight the importance of accounting for macrostructural and broader brain structural characteristics when interpreting the neuroanatomical correlates of MRS-measured metabolites, beyond controlling for bulk tissue composition. This approach is particularly crucial when comparing neuro-metabolite levels across groups with known structural differences, such as developmental cohorts or individuals with neurodevelopmental conditions. Key pointsO_LIPosterior parietal cortex (PPC) Glx levels are positively associated with PPC cortical thickness and local gyrification index, likely because differences in cortical microstructure, including dendritic arbour complexity, contributes to both cortical macrostructure and neuro-metabolic traits across development. C_LIO_LIThe PPC Glx:GABA+ ratio is negatively associated with subcortical gray matter volume, while PPC total NAA is positively associated with cerebral white matter volume, suggesting a link between regional neurochemistry and broader brain structure. C_LIO_LIThese findings emphasise the importance of considering more detailed macrostructural characteristics, as well as bulk tissue composition (white matter, gray matter, cerebral spinal fluid), when interpreting MRS-measured metabolite differences. C_LI

neuroscience↗

bioRxiv2024

Decoupling of GABA and Glutamine-Glutamate Dynamics and their role in tactile perception: An fMRS Study

Tactile processing is fundamental for our daily lives. In particular, adaptation, the mechanism by which neural (and behavioural) responses change due to repeated stimulation, is key in adjusting our responses to the environment and is often affected in neurodevelopmental conditions such as autism and ADHD. While GABA and glutamate--the main inhibitory and excitatory neurotransmitters-- are known to be fundamental for encoding sensory input, we know little regarding the dynamic responses of the GABA and glutamatergic systems during tactile processing. Here, we examine how GABA and glutamine+glutamate (Glx) in vivo dynamics change during repetitive tactile stimulation and how these changes relate to tactile perception in a healthy population, using functional magnetic resonance spectroscopy (fMRS). Our study showed that repetitive tactile stimulation induced a decoupling between GABA and Glx during the first stimulation blocks as suggested by a negative correlation between GABA and Glx, which changed from a positive correlation at baseline. Subsequently, a multivariate time series analysis showed a predictive temporal relationship between Glx and GABA, showing that changes in these metabolites are temporally linked with an estimated lag of 6 seconds informing on a complex metabolite response function. The absence of gross metabolite change suggests that Glx and GABA adjust in relation to each other in response to repeated tactile stimulation. Furthermore, individual differences in the changed GABA and Glx levels correlated with perceptual measures of touch. Together, our study highlights the complex relationship between GABA and glutamate in tactile processing and demonstrates that experience-dependence plasticity induces a decoupling between these key metabolites. Further study into their dynamic interplay may be key to understanding adaptation as meso-levels in the brain and how these mechanisms differ in neurodevelopmental and neurological conditions.

neuroscience↗

bioRxiv2023

The developmental trajectory of 1H-MRS brain metabolites from childhood to adulthood.

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 {gamma}-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 by 1H-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.

neuroscience↗

bioRxiv2023

GABA and Glutamate response to social processing; a functional MRS study

Several studies have suggested that atypical social processing in multiple psychiatric conditions (e.g., autism) is associated with differences in excitation and inhibition, through changes in the levels of glutamate and GABA levels. While associations between baseline metabolite levels and behaviours can be insightful, assessing the neurometabolic response of GABA and Glutamate during social processing may inform altered neurochemical function in more depth. Thus far, there have been no attempts to determine whether changes in metabolite levels are detectable using functional magnetic resonance spectroscopy (fMRS) during social processing in a control population. We performed MEGA-PRESS edited fMRS to measure the dynamic response of GABA and glutamate in the superior temporal sulcus (STS) and visual cortex (V1) while viewing social stimuli, using a design that allows for analysis in both block and event-related approaches. Sliding window analyses were used to investigate GABA and glutamate dynamics at higher temporal resolution. A small decrease in GABA levels was observed during social stimulus presentation in V1, but no change was observed in STS. Conversely, non-social stimulus elicited changes in both GABA and glutamate levels in both regions. We discuss the feasibility of using fMRS analysis approaches to assess changes in metabolite response during social processing.

neuroscience↗

bioRxiv2022

Variation in glutamate and GABA genes and their association with brain structure and chemistry in autism

The excitatory/inhibitory (E/I) imbalance hypothesis posits that an imbalance between glutamatergic and GABAergic neurotransmission contributes to autism symptomatology. Whether this is due to altered GABAergic or glutamatergic functioning, or both, remains largely unknown. We integrated genetic, brain structure and brain chemistry data to investigate the relationship between E/I genetic variation and expression, glutamate concentrations and cortical thickness (CT). Participants (60 autism and 104 neurotypical controls, aged 8-13 years) underwent magnetic resonance imaging and spectroscopy for glutamate quantification in the anterior cingulate cortex (ACC) and left dorsal striatum. Genetic involvement in these regional glutamate concentration levels was investigated using competitive gene-set association and polygenic scores (PGS). Further, glutamate as well as GABA gene-set expression profiles were investigated in relation to CT. Aggregated genetic variation in the glutamate gene-set was associated with ACC but not striatal glutamate concentrations. PGS analysis, however, showed a genome-wide PGS for autism to be predictive of striatal but not ACC glutamate levels. Expression profiles of GABAergic-but not glutamatergic genes were associated with differences in cortical thickness between groups. This study showed differential involvement of aggregated glutamatergic and GABAergic genetic variation in brain structure and chemistry in autism, which suggests regional variability in E/I imbalance.

neuroscience↗