Delineating the role of thalamocortical connectivity in large-scale functional brain organization: Implications for understanding atypical neurodevelopmental conditions

COEX 

This talk delves into the role of thalamocortical connectivity in the development of large-scale functional brain organization, with an emphasis on its implications for understanding neurodevelopmental disorders such as autism. To identify and interpret atypical developmental trajectories, an understanding of neurotypical development may be a good starting point. Therefore, we first investigated how thalamocortical connectivity, which is established early in life and undergoes protracted development, significantly influences the brain's functional architecture in neurotypical development. By characterizing functional connectivity gradients in the thalamus and their cortical projections, we found a developmental progression in thalamocortical connectivity, marked by the increasing differentiation of internally- and externally-oriented functional networks, with a pivotal role played by the thalamo-salience connectivity during the transition from childhood to young adulthood. Utilizing generative network computational models, we demonstrated the thalamus' role in simulating cortical networks that closely resemble “real” empirical cortical networks. Furthermore, we determined its influence on the differentiation of internal and external functional networks by selectively perturbing specific thalamo-cortical connections. Leveraging these findings from neurotypical populations, we were able to better understand the neurobiological basis of the autism spectrum disorder, which is related to atypicality in both internal (i.e., high-order cognitive) and external (i.e., low-level sensory) functions. Our findings underscore the dynamic role of thalamocortical connectivity in shaping large-scale functional brain organization across development and how it can be translated into a better understanding of atypical developmental trajectories of clinical conditions.