Causal effects of cingulate morphology on executive functions in healthy young adults

Abstract

In this study, we want to explore evidence for the causal relationship between the anatomical descriptors of the cingulate cortex (surface area, mean curvature-corrected thickness, and volume) and the performance of cognitive tasks such as Card Sort, Flanker, List Sort used as instruments to measure the executive functions of flexibility, inhibitory control, and working memory. We have performed this analysis in a cross-sectional sample of 899 healthy young subjects of the Human Connectome Project. To the best of our knowledge, this is the first study using causal inference to explain the relationship between cingulate morphology and the performance of executive tasks in healthy subjects. We have tested the causal model under a counterfactual framework using stabilized inverse probability of treatment weighting and marginal structural models. The results showed that the posterior cingulate surface area has a positive causal effect on inhibition (Flanker task) and cognitive flexibility (Card Sort). A unit increase (+1 mm² ) in the posterior cingulate surface area will cause a 0.008% and 0.009% increase from the National Institute of Health (NIH) normative mean in Flankers (p-value <0.001), and Card Sort (p-value 0.005), respectively. Furthermore, a unit increase (+1 mm² ) in the anterior cingulate surface area will cause a 0.004% (p-value <0.001) and 0.005% (p-value 0.001) increase from the NIH normative mean in Flankers and Card Sort. In contrast, the curvature-corrected-mean thickness only showed an association for anterior cingulate with List Sort (p = 0.034) but no causal effect.

Keywords: brain executive functions; causal inference; cingulate cortex; counterfactual framework; inverse probability of treatment weighting; marginal structural models.