Poster #18 - Functional Connectivity Patterns Distinguish Familial Risk of Dyslexia in Infancy and Predict Subsequent Phonological Development

• In Event: 1-005 - Poster Session 01
  In Poster Session: PS 01 Section - Biological Processes: Neuroscience and Genetics

Integrative Statement

Developmental dyslexia is a heritable learning disability characterized by specific difficulties with reading, spelling, and decoding abilities. Dyslexia has a familial prevalence of 0.4-0.6, compared to a general prevalence of < 0.1 (Snowling & Melby-Lervåg, 2016). Previous research has shown that children with a familial risk of dyslexia (FHD+) exhibit reduced performance on pre-literacy and language tasks (e.g. phonological awareness) and atypical neural mechanisms before reading onset (Guttorm et al. 2001; Raschle et al., 2010). Several dyslexia-susceptibility genes have been reported. The majority of these genes seem to play an important role in early brain development in utero, including neuronal migration and axonal growth, which have been hypothesized to play a causal role in the development of an atypical reading network by disrupting the cortico-cortical circuits underlying auditory and, subsequently, phonological processing (Galaburda et al., 2006; Giraud & Ramus, 2013). Supporting this hypothesized developmental pathway, atypical auditory processing has been observed in FHD+ infants, which was further correlated with subsequent poor phonological and reading skills (e.g., Leppanen et al., 2010). Reduced connectivity strength of white matter tracts important for reading has also been observed in a small sample of FHD+ compared to FHD- infants (Langer et al., 2017). However, it is unknown whether (a) a genetic risk for dyslexia is associated with atypical early functional connectivity (FC) as measured with resting-state functional imaging and (b) whether FC in infancy is associated with subsequent development of language and pre-literacy skills in preschool.
To address this question, 73 infants (38 female, 26 FHD+ and 47 FHD-) were selected from our ongoing longitudinal project which examines neural mechanisms of developmental dyslexia from infancy to school-age. Structural and resting-state functional MRI data were collected during natural sleep in infancy (age: 272 ± 102 days). At 5 years old, 27 participants were invited back to evaluate their oral language and phonological processing abilities using the Woodcock-Johnson IV assessment (Schrank et al., 2014). Multivariate pattern analyses (MVPA) were applied to evaluate whether the FC pattern associated with each of 78 anatomical regions (derived from the Infant AAL templates, Shi et al., 2011) could differentiate between FHD+ and FHD- infants. Subsequent prediction analyses were further conducted to estimate whether the FC pattern associated with each significant region from the MVPA analyses was predictive of subsequent language and phonological abilities, using the partial least-squares regression approach.
Ten regions, seven located in the temporal lobe, showed distinctive FC patterns between FHD+ and FHD- infants (Table 1). Among these ten regions, the FC pattern associated with the left middle temporal pole in infancy could significantly predict subsequent phonological skills at age 5 (p < 0.005), while FC associated with the right Heschl gyrus was predictive of oral language skills (p < 0.05). These findings suggest that a genetic risk of dyslexia might be associated with alterations in early functional brain development which seems crucial for the development of subsequent language skills, especially phonological awareness, which is one of the strongest predictors of reading outcome in preschool/early kindergarten children.

Authors

• Xi Yu, Boston Children's Hospital
  Presenting Author

• Silvina Ferradal, Boston Children's Hospital
  Non-Presenting Author

• Danielle Sliva, Boston Children's Hospital
  Non-Presenting Author

• Jade Dunstan, Boston Children's Hospital
  Non-Presenting Author

• Clarisa Carruthers, Boston Children's Hospital
  Non-Presenting Author

• Joseph Sanfilippo, Boston Children's Hospital
  Non-Presenting Author

• Jennifer Zuk, Boston Children's Hospital/Harvard Medical School
  Non-Presenting Author

• Lilla Zöllei, Massachusetts General Hospital/Harvard Medical School
  Non-Presenting Author

• Emma Body, Massachusetts General Hospital
  Non-Presenting Author

• Borjan Gagoski, Boston Children's Hospital
  Non-Presenting Author

• P. Ellen Grant, Boston Children's Hospital/Harvard Medical School
  Non-Presenting Author

• Nadine Gaab, Boston Children's Hospital/Harvard Medical School
  Non-Presenting Author