Creative thinking plays a vital role in almost all aspects of human life. However, little is known about the neural and genetic mechanisms underlying creative thinking. Based on a cross-validation based predictive framework, we searched from the whole-brain connectome (34,716 functional connectivities) and whole genome data (309,996 SNPs) in two datasets (all collected by Southwest University, Chongqing) consisting of altogether 236 subjects, for a better understanding of the brain and genetic underpinning of creativity. Using the Torrance Tests of Creative Thinking score, we found that high figural creativity is mainly related to high functional connectivity between the executive control, attention, and memory retrieval networks (strong top-down effects); and to low functional connectivity between the default mode network, the ventral attention network, and the subcortical and primary sensory networks (weak bottom-up processing) in the first dataset (consisting of 138 subjects). High creativity also correlates significantly with mutations of genes coding for both excitatory and inhibitory neurotransmitters. Combining the brain connectome and the genomic data we can predict individuals' creativity scores with an accuracy of 78.4%, which is significantly better than prediction using single modality data (gene or functional connectivity), indicating the importance of combining multi-modality data. Our neuroimaging prediction model built upon the first dataset was cross-validated by a completely new dataset of 98 subjects (r = 0.267, p = 0.0078) with an accuracy of 64.6%. In addition, the creativity-related functional connectivity network we identified in the first dataset was still significantly correlated with the creativity score in the new dataset (p<10). In summary, our research demonstrates that strong top-down control versus weak bottom-up processes underlie creativity, which is modulated by competition between the glutamate and GABA neurotransmitter systems. Our work provides the first insights into both the neural and the genetic bases of creativity.

It is unclear how different diets may affect human brain development and if genetic and environmental factors play a part. We investigated diet effects in the UK Biobank data from 18,879 healthy adults and discovered anticorrelated brain-wide gray matter volume (GMV)-association patterns between coffee and cereal intake, coincidence with their anticorrelated genetic constructs. The Mendelian randomization approach further indicated a causal effect of higher coffee intake on reduced total GMV, which is likely through regulating the expression of genes responsible for synaptic development in the brain. The identified genetic factors may further affect people’s lifestyle habits and body/blood fat levels through the mediation of cereal/coffee intake, and the brain-wide expression pattern of gene CPLX3, a dedicated marker of subplate neurons that regulate cortical development and plasticity, may underlie the shared GMV-association patterns among the coffee/cereal intake and cognitive functions. All the main findings were successfully replicated. Our findings thus revealed that high-cereal and low-coffee diets shared similar brain and genetic constructs, leading to long-term beneficial associations regarding cognitive, body mass index (BMI), and other metabolic measures. This study has important implications for public health, especially during the pandemic, given the poorer outcomes of COVID-19 patients with greater BMIs.