Patterns of Neural Functional Connectivity in Infants at Familial Risk of Developmental Dyslexia.

Importance: Developmental dyslexia is a heritable learning disability affecting 7% to 10% of the general population and can have detrimental impacts on mental health and vocational potential. Individuals with dyslexia show altered functional organization of the language and reading neural networks; however, it remains unknown how early in life these neural network alterations might emerge. Objective: To determine whether the early emergence of large-scale neural functional connectivity (FC) underlying long-term language and reading development is altered in infants with a familial history of dyslexia (FHD). Design, Setting, and Participants: This cohort study included infants recruited at Boston Children's Hospital between May 2011 and February 2019. Participants underwent structural and resting-state functional magnetic resonance imaging in the Department of Radiology at Boston Children's Hospital. Infants with FHD were matched with infants without FHD based on age and sex. Data were analyzed from April 2019 to June 2021. Exposures: FHD was defined as having at least 1 first-degree relative with a dyslexia diagnosis or documented reading difficulties. Main Outcomes and Measures: Whole-brain FC patterns associated with 20 predefined cerebral regions important for long-term language and reading development were computed for each infant. Multivariate pattern analyses were applied to identify specific FC patterns that differentiated between infants with vs without FHD. For classification performance estimates, 99% CIs were calculated as the classification accuracy minus chance level. Results: A total of 98 infants (mean [SD] age, 8.5 [2.3] months; 51 [52.0%] girls) were analyzed, including 35 infants with FHD and 63 infants without FHD. Multivariate pattern analyses identified distinct FC patterns between infants with vs without FHD in the left fusiform gyrus (classification accuracy, 0.55 [99% CI, 0.046-0.062]; corrected P < .001; Cohen d = 0.76). Connections linking left fusiform gyrus to regions in the frontal and parietal language and attention networks were among the paths with the highest contributions to the classification performance. Conclusions and Relevance: These findings suggest that on the group level, FHD was associated with an early onset of atypical FC of regions important for subsequent word form recognition during reading acquisition. Longitudinal studies linking the atypical functional network and school-age reading abilities will be essential to further elucidate the ontogenetic mechanisms underlying the development of dyslexia.

Home language and literacy environment and its relationship to socioeconomic status and white matter structure in infancy.

The home language and literacy environment (HLLE) in infancy has been associated with subsequent pre-literacy skill development and HLLE at preschool-age has been shown to correlate with white matter organization in tracts that subserve pre-reading and reading skills. Furthermore, childhood socioeconomic status (SES) has been linked with both HLLE and white matter organization. It is important to understand whether the relationships between environmental factors such as HLLE and SES and white matter organization can be detected as early as infancy, as this period is characterized by rapid brain development that may make white matter pathways particularly susceptible to these early experiences. Here, we hypothesized that HLLE (1) relates to white matter organization in pre-reading and reading-related tracts in infants, and (2) mediates a link between SES and white matter organization. To test these hypotheses, infants (mean age: 8.6 ± 2.3 months, N = 38) underwent diffusion-weighted imaging MRI during natural sleep. Image processing was performed with an infant-specific pipeline and fractional anisotropy (FA) was estimated from the arcuate fasciculus (AF) and superior longitudinal fasciculus (SLF) bilaterally using the baby automated fiber quantification method. HLLE was measured with the Reading subscale of the StimQ (StimQ-Reading) and SES was measured with years of maternal education. Self-reported maternal reading ability was also quantified and applied to our statistical models as a proxy for confounding genetic effects. StimQ-Reading positively correlated with FA in left AF and to maternal education, but did not mediate the relationship between them. Taken together, these findings underscore the importance of considering HLLE from the start of life and may inform novel prevention and intervention strategies to support developing infants during a period of heightened brain plasticity.

Functional Connectivity in Infancy and Toddlerhood Predicts Long-Term Language and Preliteracy Outcomes.

Functional connectivity (FC) techniques can delineate brain organization as early as infancy, enabling the characterization of early brain characteristics associated with subsequent behavioral outcomes. Previous studies have identified specific functional networks in infant brains that underlie cognitive abilities and pathophysiology subsequently observed in toddlers and preschoolers. However, it is unknown whether and how functional networks emerging within the first 18 months of life contribute to the development of higher order, complex functions of language/literacy at school-age. This 5-year longitudinal imaging project starting in infancy, utilized resting-state functional magnetic resonance imaging and demonstrated prospective associations between FC in infants/toddlers and subsequent language and foundational literacy skills at 6.5 years old. These longitudinal associations were shown independently of key environmental influences and further present in a subsample of infant imaging data (≤12 months), suggesting early emerged functional networks specifically linked to high-order language and preliteracy skills. Moreover, emergent language skills in infancy and toddlerhood contributed to the prospective associations, implicating a role of early linguistic experiences in shaping the FC correlates of long-term oral language skills. The current results highlight the importance of functional organization established in infancy and toddlerhood as a neural scaffold underlying the learning process of complex cognitive functions.

White matter in infancy is prospectively associated with language outcomes in kindergarten.

Language acquisition is of central importance to child development. Although this developmental trajectory is shaped by experience postnatally, the neural basis for language emerges prenatally. Thus, a fundamental question remains: do structural foundations for language in infancy predict long-term language abilities? Longitudinal investigation of 40 children from infancy to kindergarten reveals that white matter in infancy is prospectively associated with subsequent language abilities, specifically between: (i) left arcuate fasciculus and phonological awareness and vocabulary knowledge, (ii) left corticospinal tract and phonological awareness, and bilateral corticospinal tract with phonological memory; controlling for age, cognitive, and environmental factors. Findings link white matter in infancy with school-age language abilities, suggesting that white matter organization in infancy sets a foundation for long-term language development.

System-Specific Patterns of Thalamocortical Connectivity in Early Brain Development as Revealed by Structural and Functional MRI.

The normal development of thalamocortical connections plays a critical role in shaping brain connectivity in the prenatal and postnatal periods. Recent studies using advanced magnetic resonance imaging (MRI) techniques in neonates and infants have shown that abnormal thalamocortical connectivity is associated with adverse neurodevelopmental outcomes. However, all these studies have focused on a single neuroimaging modality, overlooking the dynamic relationship between structure and function at this early stage. Here, we study the relationship between structural and functional thalamocortical connectivity patterns derived from healthy full-term infants scanned with diffusion-weighted MRI and resting-state functional MRI within the first weeks of life (mean gestational age = 39.3 ± 1.2 weeks; age at scan = 24.2 ± 7.9 days). Our results show that while there is, in general, good spatial agreement between both MRI modalities, there are regional variations that are system-specific: regions involving primary-sensory cortices exhibit greater structural/functional overlap, whereas higher-order association areas such as temporal and posterior parietal cortices show divergence in spatial patterns of each modality. This variability illustrates the complementarity of both modalities and highlights the importance of multimodal approaches.