Novel MRI-based Biotypes of Human Neurodevelopment associated with Impulsivity performance

Introduction Adequate neurodevelopment is critical to the proper advancement of cognitive and emotional processing; however, variation in neurodevelopment has emerged as a potential risk factor for subsequent drug use. The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing and longitudinal study to determine the developmental trajectories of the brain and how experiences impact brain development, which makes it an ideal framework study to determine proper neurodevelopmental trajectories associated with healthy executive function behavioral development and their neurobiology. Method Based on the availability of ABCD (Release 5.1) tabulated data, we selected 1368 subjects with neuroimaging records on multiple time points. To focus on the frontal cortex, we preprocess 20 ROIs (including ten regions with right and left cerebral hemispheres) cortical thickness measurements for SuStaIn. Once SuStaIn determined the potential control and phenotype (subtypes) group, we conducted t-tests between the control and phenotype groups on their delay discounting measurements. To overserve possible trajectories, we also investigated the correlation of the thickness measurements with delay discounting under the suggested phenotype by SuStaIn. Results SuStaIn identified four subtypes and one potential control group, validated by cross-validation test as the optimal solution for balancing model accuracy and complexity. Among the t-tests on delay discounting results between the control group and each subtype, subtype1 tends to show low significance on the 3-month indifference point (p=0.067), subtype 2 identifies a significant reduction in impulsivity on the 1-month indifference point (p=0.017), subtype 4 stands significant reduction at on 3-month indifference point (p=0.0092) and significance on 1-year indifference point (p=0.00418). For the correlations between each selected ROI, we identified a negative correlation (R=-0.18, p=0.0095) between the thickness of the left hemisphere caudal-anterior-cingulate and delay discounting indifference point at 3 months. Conclusion We successfully identified four subtypes of the ABCD, which may be putative abnormal trajectories of executive function accelerated development. Three of the four subtypes reflect impulsive behavioral phenotype, and one displays an association with cortical thinning. Overall, we present evidence that there are putative neurobiological signs of potential executive function disruption as early as nine years of age.