Esmaeili, M. | bioRxiv Science

bioRxiv2024

Brain-Cognitive Gaps in relation to Dopamine and Health-related Factors: Insights from AI-Driven Functional Connectome Predictions

A key question in human neuroscience is to understand how individual differences in brain function relate to cognitive differences. However, the optimal condition of brain function to study between-person differences in cognition remains unclear. While many studies have developed objective biomarkers to accurately predict intelligence and general cognition, consensus on domain-specific markers has not yet emerged. Brain age has been proposed as a potential candidate, but recent research suggests that brain age offers minimal additional information on cognitive decline beyond what chronological age provides, prompting a shift toward approaches focused directly on cognitive prediction. Using a deep learning approach, we evaluated the predictive power of the functional connectome during various states (resting state, movie-watching, and n-back) on episodic memory and working memory performance. Our findings show that while connectomes during task, especially during movie watching, better predict both episodic and working memory, resting state connectomes are equally effective in predicting episodic memory. Furthermore, individuals with a negative brain-cognition gap (where brain predictions underestimate actual performance) exhibited lower physical activity and higher cardiovascular risk compared to those with a positive gap. This shows that knowledge of the brain-cognition gap provides insights into factors contributing to cognitive resilience. Further lower PET-derived measures of dopamine binding were linked to a greater brain-cognition gap, mediated by regional functional variability. Together, our findings highlight the importance of brain state in connectome-based cognitive prediction and introduce the brain cognitive gap as a potentially informative, dopamine-modulated marker of vulnerability to compromise brain function.

neuroscience↗

bioRxiv2019

Loss of Competence in early development is mediated by loss of chromatin accessibility

As development proceeds, inductive cues are interpreted by competent tissues in a spatially and temporally restricted manner. While key inductive signaling pathways within competent cells are well-described at a molecular level, the mechanisms by which tissues lose responsiveness to inductive signals are not well understood. Localized activation of Wnt signaling before zygotic gene activation in Xenopus laevis leads to dorsal development, but competence to induce dorsal genes in response to Wnts is lost by the late blastula stage. We hypothesize that loss of competence is mediated by changes in histone modifications leading to a loss of chromatin accessibility at the promoters of Wnt target genes. We use ATAC-seq to evaluate genome-wide changes in chromatin accessibility across several developmental stages. Based on overlap with p300 binding, we identify thousands of putative cis-regulatory elements at the gastrula stage, including sites that lose accessibility by the end of gastrulation and are enriched for pluripotency factor binding motifs. Dorsal Wnt target gene promoters are not accessible after the loss of competence in the early gastrula while genes involved in mesoderm and neural crest development maintain accessibility at their promoters. Inhibition of histone deacetylases increases acetylation at the promoters of dorsal Wnt target genes and extends competence for dorsal gene induction by Wnt signaling. Histone deacetylase inhibition, however, is not sufficient to extend competence for mesoderm or neural crest induction. These data suggest that chromatin state regulates the loss of competence to inductive signals in a context-dependent manner.

developmental biology↗