Authors: Xi Yu, Silvina Ferradal, Jade Dunstan, Clarisa Carruthers, Joseph Sanfilippo, Jennifer Zuk, Lilla Zöllei, Borjan Gagoski, Yangming Ou, P. Ellen Grant, Nadine Gaab.

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

Publication: JAMA Network Open (American Medical Association). 5(10):e2236102 2022 | DOI: 10.1001/jamanetworkopen.2022.36102

[Full Text]


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.

Tagged as: altbrain, default network, family history, fMRI, infants, neural connectivity, and resting state connectivity


Yu X, Ferradal S, Dunstan J, et al. Patterns of Neural Functional Connectivity in Infants at Familial Risk of Developmental Dyslexia. JAMA Netw Open. 2022;5(10):e2236102. doi:10.1001/jamanetworkopen.2022.36102

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