Development of Tract-Specific White Matter Pathways During Early Reading Development in At-Risk Children and Typical Controls

Developmental dyslexia is a neurodevelopmental disorder with a strong genetic basis. Previous studies observed white matter alterations in the left posterior brain regions in adults and school-age children with dyslexia. However, no study yet has examined the development of tract-specific white matter pathways from the pre-reading to the fluent reading stage in children at familial risk for dyslexia (FHD+) versus controls (FHD−). This study examined whitematter integrity at pre-reading, beginning, and fluent reading stages cross-sectionally (n = 78) and longitudinally (n = 45) using an automated fiber-tract quantification method. Our findings depict white matter alterations and atypical lateralization of the arcuate fasciculus at the pre-reading stage in FHD+ versus FHD− children. Moreover, we demonstrate faster white matter development in subsequent good versus poor readers and a positive association between white matter maturation and reading development using a longitudinal design. Additionally, the combination of white matter maturation, familial risk, and psychometric measures best predicted later reading abilities. Furthermore, within FHD+ children, subsequent good readers exhibited faster white matter development in the right superior longitudinal fasciculus compared with subsequent poor readers, suggesting a compensatory mechanism. Overall, our findings highlight the importance of white matter pathway maturation in the development of typical and atypical reading skills

Cortical and Subcortical Contributions to Visual Category Decisions

Categorization is a fundamental cognitive process by which the brain assigns stimuli to behaviorally meaningful groups. Previous studies on visual categorization in primates have identified a hierarchy of cortical areas that are involved in the transformation of veridical sensory information into abstract category representations. However, categorization behaviors are ubiquitous across diverse animal species, even those without a neocortex, motivating the possibility that subcortical regions may contribute to abstract cognition in primates. One candidate structure is the superior colliculus (SC), a midbrain region that is evolutionarily conserved across vertebrates. Although traditionally thought to mediate only reflexive spatial orienting behaviors, especially saccades in primates, the SC is also involved in cognitive tasks that require spatial orienting. In the first part of this thesis, we investigated the involvement of the primate SC in abstract categorization, and show that the SC plays an unexpected key role in higher-order, non-spatial cognition. We trained monkeys to group motion stimuli into categories based on an arbitrary rule, and compared neural activity in the SC and the lateral intraparietal area (LIP), a cortical region previously shown to causally contribute to category decisions, while monkeys performed this task. We observed unexpectedly strong and short-latency category encoding in the SC that was more reliable and arose even earlier than in the LIP. Moreover, monkeys' performance on the categorization task was markedly impaired during reversible inactivation of the SC, indicating that the observed category signals in the SC may causally contribute to category processing. In addition, we show that category and eye movement-related signals are encoded in near-orthogonal subspaces in population activity in the SC, providing an explanation for how a motor structure like the SC can be recruited to participate in more flexible cognitive behaviors. These results extend the well-established role of the SC in spatial orienting to non-spatial, higher-order cognition. In the second part of this thesis, we investigated how behavioral task demands affect category and sensory encoding in the SC, LIP, and the middle temporal area, (MT), an early visual cortical area that is involved in motion processing. We trained monkeys to alternate between blocks of the motion categorization task and blocks in which they passively viewed the same stimuli and received a reward for maintaining fixation. The physical stimulus and stimulus location was identical in the two blocks, but only the categorization task required the monkeys to use the stimulus information to obtain a reward; therefore, we could compare, in the same neurons, how behavioral context affects stimulus encoding. We observed significantly weaker stimulus direction encoding during passive viewing than during the categorization task in all three brain areas. Moreover, although both LIP and SC encoded stimulus category during the categorization task, category encoding was largely absent during passive viewing in both areas. These results indicate that neural populations in LIP and SC can flexibly route sensory input based on current behavioral demands

Development of Tract-Specific White Matter Pathways During Early Reading Development in At-Risk Children and Typical Controls

Developmental dyslexia is a neurodevelopmental disorder with a strong genetic basis. Previous studies observed white matter alterations in the left posterior brain regions in adults and school-age children with dyslexia. However, no study yet has examined the development of tract-specific white matter pathways from the pre-reading to the fluent reading stage in children at familial risk for dyslexia (FHD+) versus controls (FHD−). This study examined whitematter integrity at pre-reading, beginning, and fluent reading stages cross-sectionally (n = 78) and longitudinally (n = 45) using an automated fiber-tract quantification method. Our findings depict white matter alterations and atypical lateralization of the arcuate fasciculus at the pre-reading stage in FHD+ versus FHD− children. Moreover, we demonstrate faster white matter development in subsequent good versus poor readers and a positive association between white matter maturation and reading development using a longitudinal design. Additionally, the combination of white matter maturation, familial risk, and psychometric measures best predicted later reading abilities. Furthermore, within FHD+ children, subsequent good readers exhibited faster white matter development in the right superior longitudinal fasciculus compared with subsequent poor readers, suggesting a compensatory mechanism. Overall, our findings highlight the importance of white matter pathway maturation in the development of typical and atypical reading skills

White Matter Alterations in Infants at Risk for Developmental Dyslexia

Developmental dyslexia (DD) is a heritable condition characterized by persistent difficulties in learning to read. White matter alterations in left-lateralized language areas, particularly in the arcuate fasciculus (AF), have been observed in DD, and diffusion properties within the AF correlate with (pre-)reading skills as early as kindergarten. However, it is unclear how early these alterations can be observed. We investigated white matter structure in 14 infants with (FHD+; ages 6.6-17.6 months) and 18 without (FHD-; ages 5.1-17.6 months) familial risk for DD. Diffusion scans were acquired during natural sleep, and early language skills were assessed. Tractography for bilateral AF was reconstructed using manual and automated methods, allowing for independent validation of results. Fractional anisotropy (FA) was calculated at multiple nodes along the tracts for more precise localization of group differences. The analyses revealed significantly lower FA in the left AF for FHD+ compared with FHD- infants, particularly in the central portion of the tract. Moreover, expressive language positively correlated with FA across groups. Our results demonstrate that atypical brain development associated with DD is already present within the first 18 months of life, suggesting that the deficits associated with DD may result from altered structural connectivity in left-hemispheric regions