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

Author:

Yu Xi12,Ferradal Silvina3,Dunstan Jade4,Carruthers Clarisa4,Sanfilippo Joseph4,Zuk Jennifer5,Zöllei Lilla6,Gagoski Borjan278,Ou Yangming278,Grant P. Ellen278,Gaab Nadine489

Affiliation:

1. State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China

2. Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children’s Hospital, Boston, Massachusetts

3. Department of Intelligent Systems Engineering, Indiana University, Bloomington

4. Laboratories of Cognitive Neuroscience, Division of Developmental Medicine, Department of Medicine, Boston Children’s Hospital, Boston, Massachusetts

5. Department of Speech, Language & Hearing Sciences, Boston University, Boston, Massachusetts

6. A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston

7. Department of Radiology, Boston Children’s Hospital, Boston, Massachusetts

8. Harvard Medical School, Boston, Massachusetts

9. Harvard Graduate School of Education, Cambridge, Massachusetts

Abstract

ImportanceDevelopmental 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresFHD was defined as having at least 1 first-degree relative with a dyslexia diagnosis or documented reading difficulties.Main Outcomes and MeasuresWhole-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.ResultsA 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 RelevanceThese 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.

Publisher

American Medical Association (AMA)

Subject

General Medicine

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