Developmental language disorders are highly prevalent in the general population. One of the earliest warning signs of many developmental disorders is delayed language acquisition, which is also associated with higher risk for subsequent reading and language disorders. However, little is known about how neural networks underlying language learning develop in early infancy and what neural and genetic mechanisms cause certain individuals to diverge onto an atypical developmental trajectory that leads to developmental language impairments. While there is a small but growing body of research using passive fMRI to examine the neural basis of language in infants (during natural sleep), no studies to date have used a longitudinal design or related early brain-based measures to subsequent behavioral outcomes. Understanding how early brain activity and connectivity relate to later language development may ultimately inform early diagnosis and interventions that will be more effective for treating developmental disorders that affect language. It is therefore essential to characterize the development of the neural networks subserving language acquisition in typically developing infants to serve as a basis for understanding how this system may go awry in developmental disorders such as specific language impairment, dyslexia, and autism spectrum disorders. Here we propose to use a longitudinal multimodal approach integrating several neuroimaging measures with genetic data to investigate developmental changes in language-relevant networks in the infant brain. By using passive fMRI during natural sleep, we will study infants at two time points: 1.5 and 9 months of age. Prior studies have shown that newborns already demonstrate a preference for their native language and that by 6 months of age, infants can implicitly identify word boundaries in continuous speech by relying on statistical and prosodic cues in the input. Using stimuli analogous to those employed in these milestone behavioral studies, passive fMRI will be conducted to probe the neural signatures of these early linguistic achievements in the infant brain. Resting-state fMRI will also be performed to characterize developmental changes in functional connectivity within language-relevant brain networks. Using diffusion tensor imaging (DTI), deterministic and probabilistic tractography will be conducted to examine the development of specific structural (i.e., white matter) tracts that connect language areas in the developing brain. In addition, we will examine how common genetic risk variants in CNTNAP2 that have been associated with language impairments in neurodevelopmental disorders may affect both activity and connectivity within language-relevant networks. Finally, we will relate th early measures of brain activity and connectivity to behavioral indices of language development assessed longitudinally (from 6 to 24 months of age). Taken together, the studies outlined in this proposal aim to investigate the functional and structural networks underlying language acquisition in the infant brain, and to further examine how these networks are affected by CNTNAP2, a gene that plays a significant role in the development of fronto-striatal networks subserving language learning. The findings from the proposed research will provide insight into the neural mechanisms underlying language learning in typical development and ultimately inform the early detection of altered developmental trajectories, which could lead to more effective interventions due to increased neuroplasticity early in development.

Public Health Relevance

These studies aim to investigate the functional and structural networks underlying language acquisition in the infant brain, and to further examine how genetic risk may modulate activity and connectivity within language- relevant brain networks. Findings from this research will provide insight into the neural mechanisms underlying language learning in typical development and ultimately inform early detection of altered developmental trajectories which, in turn, could lead to more effective interventions for developmental disorders characterized by language impairment.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31HD088102-03
Application #
9598342
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Alvarez, Ruben P
Project Start
2016-11-16
Project End
2019-11-15
Budget Start
2018-11-16
Budget End
2019-11-15
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095