Glutamate and choline levels predict individual differences in reading ability in emergent readers

Abstract

Reading disability is a brain-based difficulty in acquiring fluent reading skills that affects significant numbers of children. Although neuroanatomical and neurofunctional networks involved in typical and atypical reading are increasingly well characterized, the underlying neurochemical bases of individual differences in reading development are virtually unknown. The current study is the first to examine neurochemistry in children during the critical period in which the neurocircuits that support skilled reading are still developing. In a longitudinal pediatric sample of emergent readers whose reading indicators range on a continuum from impaired to superior, we examined the relationship between individual differences in reading and reading-related skills and concentrations of neurometabolites measured using magnetic resonance spectroscopy. Both continuous and group analyses revealed that choline and glutamate concentrations were negatively correlated with reading and related linguistic measures in phonology and vocabulary (such that higher concentrations were associated with poorer performance). Correlations with behavioral scores obtained 24 months later reveal stability for the relationship between glutamate and reading performance. Implications for neurodevelopmental models of reading and reading disability are discussed, including possible links of choline and glutamate to white matter anomalies and hyperexcitability. These findings point to new directions for research on gene-brain-behavior pathways in human studies of reading disability.

Keywords: MRS; decoding; individual differences; phonological processing; reading; reading disability.

Figure 1.

Sagittal and axial sections depicting the 3 × 3 × 1.5 cm MRS voxel in the midline occipital cortices with MNI z-coordinate of voxel center indicated (bottom left). Metabolite spectra in a single participant: MR subspectrum at 4-telsa (top left), cortical GABA detected by J-editing (top right). Gln, Glutamine.

Figure 2.

Relationship between metabolites and reading ability. Scatterplot of correlations between (a) Glu and Reading Composite scores, and (b) Cho and Reading Composite scores. Readers meeting criteria for TD readers are shown in dark gray squares, RD readers are shown in black triangles, and readers that did not meet either group criteria are shown in light gray circles. Bar graphs present (c) Glu and (d) Cho mean levels in TD and RD readers. Error bars represent SEM. Metabolites levels are expressed as ratios to Cr.