Fetal temporal sulcus depth asymmetry has prognostic value for language development

Brain asymmetry is a common feature across various species, with functional laterality observed in behaviors such as escape responses and eye use. In mammals, cortical thickness asymmetries exist, and primates display structural asymmetries in regions like the planum temporale and Sylvian fissure. Humans uniquely exhibit a longer left and deeper right superior temporal sulcus (STS), with substantial cytoarchitectonic differences. This STS asymmetry, with a rightward depth asymmetry in most individuals, is already apparent in fetal brains and is thought to be an anatomical marker for language abilities. The STS is crucial in language processing, with the left STS involved in speech perception and semantic processing, and the right STS contributing to social cognition. Identifying neural features predicting language development is scientifically important and clinically relevant for fetal counseling. While prior studies linked structural temporal lobe asymmetry and language in children and patients with language deficits, a longitudinal study tracing this relationship from fetal development to childhood was lacking. This study addresses this gap by evaluating the impact of prenatal STS depth asymmetries on childhood language function, localization, and white matter tract organization.

Previous research has established the presence of brain asymmetries across various species, with functional laterality influencing behaviors. Studies on mammals and primates revealed cortical thickness and structural asymmetries in specific brain regions. Humans demonstrate unique left-right asymmetries in the superior temporal sulcus (STS), considered a marker for language abilities. The left STS is primarily associated with speech perception and semantic processing, while the right STS plays a role in social cognition. Cross-sectional studies have linked structural temporal lobe asymmetry with language function in healthy children and those with language deficits. However, a longitudinal study tracking this relationship from fetal development to childhood has been missing. This study bridges this gap by examining the impact of prenatal STS depth asymmetries on language development.

This longitudinal study involved 38 children (aged 6-13 years) whose mothers underwent fetal MRI scans for various clinical reasons; all fetal MRIs were ultimately diagnosed as normal. Fetal MRI scans allowed for the measurement of STS depth asymmetry from 25 weeks gestational age onward (resulting in 29 participants in the quantitative analysis). Neuropsychological examinations assessed various language functions (expressive vocabulary, language comprehension, verbal fluency, verbal memory) using standardized tests. fMRI measured language localization, and DTI analyzed language-related white matter tracts. The laterality index (LI) of STS depth was calculated for each fetus. Statistical analyses, including multiple linear regressions (adjusted for nonverbal perceptual reasoning and other factors), correlated fetal STS asymmetry with later language abilities, localization, and white matter tract organization. Data met assumptions of normality and independence of errors. Corrections for multiple comparisons were performed using Bonferroni correction and Family-Wise Error (FWE) correction.

The study found that most fetuses exhibited a deeper right STS compared to the left. However, less right lateralization of fetal STS depth was significantly associated with better verbal abilities (expressive vocabulary, verbal fluency, verbal memory) in childhood (6–13 years later). Fetal STS depth asymmetry accounted for over 40% of the variance in these verbal skills. Children with less rightward fetal STS depth asymmetry showed more left temporal language localization in childhood. While fractional anisotropy measures of white matter tracts showed little hemispheric difference, analysis of tract volumes revealed a correlation between more left lateralization of fetal STS depth and a greater volume of the left superior longitudinal fasciculus III. No significant association was found between fetal STS asymmetry and language comprehension or other white matter tract laterality indices.

This study's findings demonstrate a significant association between fetal STS depth asymmetry and later language abilities, specifically verbal skills. The considerable variance in verbal skills explained by fetal STS asymmetry highlights the importance of this early anatomical marker. The correlation with left temporal language localization supports the hypothesis that earlier left-sided development favors language learning. The lack of association with language comprehension may relate to the distributed neural networks involved in this process. The limited findings concerning white matter tracts could be due to the insensitivity of laterality indices in this context. The study’s language-specific findings underscore the critical role of the temporal region in early language development.

This pilot study provides evidence that fetal STS depth asymmetry is a significant predictor of later language development, particularly verbal skills. Less pronounced rightward asymmetry is associated with better verbal abilities and increased left temporal language localization. While larger studies are needed to confirm these findings and investigate potential sex differences, this research suggests the potential for fetal STS asymmetry to serve as a diagnostic biomarker for language development.

The relatively small sample size (29 participants in the main analyses), variability in gestational age at fetal MRI, and the use of two different MRI devices are limitations. The exclusion of fetuses with non-visible STS and the age range at testing (6-13 years) also affect the generalizability of the findings. The sex imbalance in the sample, reflecting clinical referral patterns, may affect the interpretation of findings. Further, the potential influence of nonlinear growth effects and increases in normal variance with gestational age, which might not have been fully accounted for due to the small sample, warrants consideration.