Atypical functional connectivity of the left fusiform gyrus in infants at familial risk for developmental dyslexia

ImportanceDevelopmental dyslexia (dyslexia) is a genetic-based learning disorder affecting 7-10% of the general population and has 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 these neural network alterations emerge in association with familial(genetic) vulnerability to dyslexia. ObjectiveTo determine whether the early development of large-scale neural functional connectivity is altered as a function of familial risk for dyslexia. DesignThis cohort study included 98 infants with (FHD+) and without (FHD-) a familial history of dyslexia recruited at Boston Childrens Hospital (BCH) between May 2011 and February 2019. SettingParticipants underwent structural and resting-state functional magnetic resonance imaging in the Department of Pediatric Radiology at BCH. ParticipantsFHD+ infants were defined as having at least one first-degree relative with dyslexia or reading difficulties and infants without familial risk for dyslexia (i.e., FHD-) were controls. Main outcomes and measuresWhole-brain functional connectivity patterns associated with 20 pre-defined cerebral regions important for long-term language and reading development were computed for each infant. Multivariate pattern analyses were applied to identify specific functional connectivity patterns that differentiated between FHD+ and FHD-infants. ResultsThe final sample consisted of 35 FHD+ (8.9 {+/-} 2.4 months, 15 females) and 63 FHD- (8.3 {+/-} 2.3 months, 36 females) infants. Multivariate pattern analyses identified distinctive functional connectivity patterns between the FHD+ and FHD-infants in the left fusiform gyrus (LFFG: accuracy = 0.55, pcorrected < 0.001, effect size: Cohens d = 0.76, 99% CI of the classification performance (classification accuracy-chance level) = [0.046, 0.062]). Moreover, the top five connections with greatest contribution to the classification performance connected LFFG with the frontal and temporoparietal regions of the language network. Conclusion and relevanceThe current study demonstrates that familial vulnerability to dyslexia is associated with an early onset of atypical functional connectivity of regions important for subsequent word form recognition during reading acquisition. Longitudinal studies linking the atypical functional network and school-age reading x(dis)abilities will be essential for further elucidating the ontogenetic mechanisms underlying the development of dyslexia. Key PointsO_ST_ABSQuestionC_ST_ABSAre functional topologies of language and reading-related regions in infancy associated with familial vulnerability to developmental dyslexia? FindingsIn a cohort study examining the resting-state functional connectivity of 98 infants during natural sleep, distinctive functional connectivity patterns of the left fusiform gyrus were observed between infants with and without a familial risk for dyslexia. These differences were evident despite comparable behavioral and socio-economic/environmental characteristics between the two groups. MeaningFamilial vulnerability of dyslexia is associated with early alterations in the infant functional connectivity of key regions important for subsequent word recognition, suggesting an atypical neural scaffold for reading acquisition.