A new study linking the brain’s glutamatergic signaling system, specifically NMDA receptors, with the structural brain patterns that underpin children’s mathematics and reading abilities has been published in Nature Communications. Led by Yuan Zhang of Stanford University, the research analysed data from 991 typically developing children aged 7 to 14 across two groups, one drawn from the Healthy Brain Network and the other from Stanford-led studies. The initial sample included 760 children with an average age of 9.7 years, 275 of whom were girls; the replication sample comprised 231 children, average age 9.2, with 98 girls.
The researchers argued that mathematics and reading rely on networks of brain regions rather than a single dedicated area. They sought to understand how the brain’s chemical signaling systems relate to the development of these networks, focusing on glutamate and GABA, with NMDA receptors on brain cells playing a key role in plasticity—the ability of connections between neurons to change with experience.
Unlike prior work that examined neurotransmitter levels in isolated brain regions, this study looked at the brain-wide distribution of 19 different receptor systems by comparing gray matter patterns with an existing atlas of receptor distribution. NMDA receptors produced the most consistent findings across both groups; the regions where gray matter volume was more strongly linked to math and reading performance tended to have higher densities of NMDA receptors. The associations accounted for between 8% and 20% of the regional variation observed.
Other chemical systems, including those involving dopamine, acetylcholine, serotonin and GABA, yielded weaker or inconsistent results. In particular, acetylcholine and histamine showed associations for mathematics in one sample but not the other, making NMDA receptors the only system to replicate across both cohorts for both academic skills.
There were distinct differences between mathematics and reading. For mathematics, the NMDA receptor distribution aligned with structural patterns across several networks, including the default mode network, the salience network and higher-order visual networks. For reading, the robust association was concentrated within a network involved in higher-level visual processing that supports recognising written words.
Scores in mathematics and reading were strongly correlated, and further analyses suggested that the NMDA associations largely reflect brain structure shared by both skills. The researchers proposed that glutamate-related signaling may be a common biological feature of academic learning expressed through somewhat different brain systems depending on the task.
“NMDA receptor distribution showed robust and spatially selective associations with brain structural organization for both mathematical and reading abilities across two independent cohorts,” Zhang and colleagues stated.
Limitations should be noted. The researchers did not measure NMDA receptors or glutamate levels in the children themselves. Instead, receptor maps came from imaging of more than 1,200 healthy adults, used as a reference against which the children’s brain structures were compared, and since neurotransmitter systems evolve during development, adult maps may not perfectly reflect children’s brains.
Because the analysis compared patterns across brain regions rather than measuring receptors in individual children, the study does not prove that higher NMDA receptor density makes a child better at math or reading. It was cross-sectional and included only typically developing children aged 7 to 14, so it cannot establish how glutamate signaling shapes the development of these skills.
The study, “Glutamatergic signaling underlies brain structural organization for mathematical and reading abilities in children,” was authored by Yuan Zhang, Hyesang Chang, Dawlat El-Said and Vinod Menon.
