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

Author:

Thomson Alice R12ORCID,Hwa Hannah1,Pasanta Duanghathai1,Hopwood Benjamin1,Powell Helen J1,Lawrence Ross3,Tabuenca Zeus G4,Arichi Tomoki25ORCID,Edden Richard A E67,Chai Xiaoqian8,Puts Nicolaas A12

Affiliation:

1. Institute of Psychiatry, Psychology & Neuroscience, King’s College London Department of Forensic and Neurodevelopmental Sciences, , 16 De Crespigny Park, London, SE5 8AF, United Kingdom

2. Department of Neuro­developmental Disorders MRC Centre for Neurodevelopmental Disorders, , New Hunt's House, Guy's Campus, King's College London, London, SE1 1UL, United Kingdom

3. Johns Hopkins University Division of Cognitive Neurology, Department of Neurology, , 1629 Thames Street Suite 350, Baltimore, MD 21231, United States

4. University of Zaragoza Department of Statistical Methods, , Pedro Cerbuna 12, Zaragoza, 50009, Spain

5. Centre for the Developing Brain , Department of Perinatal Imaging & Health, 1st Floor, South Wing, St Thomas’ Hospital, London, SE1 7EH, United Kingdom

6. Johns Hopkins University School of Medicine Russell H. Morgan Department of Radiology and Radiological Science, The , 601 North Caroline Street, Baltimore, MD 21287, United States

7. Kennedy Krieger Institute F.M. Kirby Research Centre for Functional Brain Imaging, , 707 North Broadway, Baltimore, MD 21205, United States

8. Department of Neurology and Neurosurgery , McGill University, QC H3A2B4, Canada

Abstract

Abstract Human brain development is ongoing throughout childhood, with for example, myelination of nerve fibers 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 the 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+ (GABA plus macromolecules), Glx (glutamate + glutamine), total choline (tCho) and total creatine (tCr) concentrations. Glx and GABA+ concentrations steeply decrease across childhood, with more stable trajectories across early adulthood. tCr and tCho concentrations increase from childhood to early adulthood. Total N-acetyl aspartate (tNAA) and Myo-Inositol (mI) concentrations are relatively stable across development. 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.

Funder

Canada First Research Excellence Fund

Natural Sciences and Engineering Research Council of Canada

Medical Research Council Centre for Neurodevelopmental Disorders, King’s College London

MRC Transition Support Award

Medical Research Council PhD award

Johns Hopkins Therapeutic Cognitive Neuroscience Fund

Publisher

Oxford University Press (OUP)

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