Associations between white matter microstructure and infants' working memory

Abstract

Working memory emerges in infancy and plays a privileged role in subsequent adaptive cognitive development. The neural networks important for the development of working memory during infancy remain unknown. We used diffusion tensor imaging (DTI) and deterministic fiber tracking to characterize the microstructure of white matter fiber bundles hypothesized to support working memory in 12-month-old infants (n=73). Here we show robust associations between infants' visuospatial working memory performance and microstructural characteristics of widespread white matter. Significant associations were found for white matter tracts that connect brain regions known to support working memory in older children and adults (genu, anterior and superior thalamic radiations, anterior cingulum, arcuate fasciculus, and the temporal-parietal segment). Better working memory scores were associated with higher FA and lower RD values in these selected white matter tracts. These tract-specific brain-behavior relationships accounted for a significant amount of individual variation above and beyond infants' gestational age and developmental level, as measured with the Mullen Scales of Early Learning. Working memory was not associated with global measures of brain volume, as expected, and few associations were found between working memory and control white matter tracts. To our knowledge, this study is among the first demonstrations of brain-behavior associations in infants using quantitative tractography. The ability to characterize subtle individual differences in infant brain development associated with complex cognitive functions holds promise for improving our understanding of normative development, biomarkers of risk, experience-dependent learning and neuro-cognitive periods of developmental plasticity.

Figure 1

Flow Chart of the DTI Fiber Tract-based Analysis. The first step, DTI preprocessing includes quality control of the tensor estimation and computation of DTI indices: FA, RD and AD. The second step, atlas construction, includes image registration and mapping DTIs to common space: a) construction of an unbiased pediatric FA atlas using group-wise diffeomorphic registration, b) mapping all datasets into the pediatric FA atlas with Demons registration, and c) mapping DTIs to common space and averaging the transformed DTIs to get the final pediatric DTI atlas. The third and final step, fiber tract profile calculation, includes standard fiber tractography in atlas space, followed by DTI indices profile extraction along the fiber tracts using the atlas transformation computed in step two.

Figure 2

DTI Fractional Anisotropy (FA) Maps of White Matter Tracts. FA maps are color-coded by local fiber direction. The colors, red, green, and blue represent white matter fibers running along the right-left, anterior-posterior, and superior-inferior axes, respectively. Locations of white matter tracts are assigned on the color maps. Reference lines in sagittal images indicate respective locations of axial and coronal images. Temporal-parietal segment (TPS), inferior longitudinal fasiculus (ILF), body of the corpus callosum (CC Body), anterior cingulum (Ant. Cing), anterior thalamic radiations (ATR) part of the anterior limb of the internal capsule, superior thalamic radiations (STR) part of the posterior limb of the internal capsule.

Figure 3

White Matter Fiber Bundles from Tractography of DTI Data. This figure contains two glass brain images showing the reconstructed fibers included in this study-- a. Working Memory Tracts: anterior cingulum (dark blue), superior thalamic radiations (bright green), genu (dark green), temporal-parietal segment (orange), anterior thalamic radiations (purple), arcuate fasciculus (light blue). b. Control Tracts: optic nerves (bright green), corpus callosum body (orange), splenium (dark green), inferior longitudinal fasciculi (blue), spinothalamic radiations (purple). Standard streamline DTI tractography was performed on a pediatric atlas built from all 1-year old study subjects.

Figure 3

White Matter Fiber Bundles from Tractography of DTI Data. This figure contains two glass brain images showing the reconstructed fibers included in this study-- a. Working Memory Tracts: anterior cingulum (dark blue), superior thalamic radiations (bright green), genu (dark green), temporal-parietal segment (orange), anterior thalamic radiations (purple), arcuate fasciculus (light blue). b. Control Tracts: optic nerves (bright green), corpus callosum body (orange), splenium (dark green), inferior longitudinal fasciculi (blue), spinothalamic radiations (purple). Standard streamline DTI tractography was performed on a pediatric atlas built from all 1-year old study subjects.

Figure 4

Association Between Working Memory and White Matter Tracts. Scatter plots highlight examples of significant associations between infants’ working memory and key white matter tracts: Genu, Arcuate, Anterior Cingulum. Plots show the positive association of working memory with FA and the negative association with RD. Only the Left (L) Arcuate and L Ant. Cingulum are shown above, however scatter plots for these tracts in the right hemisphere are very similar. Partial correlations and uncorrected p-values highlight the magnitude of these associations.