Brain white matter organisation in adolescence is related to childhood cerebral responses to facial expressions and harm avoidance.

While white matter structural integrity is likely to influence the responses to social-emotional stimuli and emotional regulation during development, no longitudinal data are available on such relationships. We investigated the relationships between white matter Fractional Anisotropy (FA) derived by DTI voxelwise Tract Based Spatial Statistics (TBSS) and tractography measured at ages 14-15, and cerebral event-related N400 amplitudes in response to happy, neutral and angry facial expressions and Cloninger's Harm Avoidance (HA) measured at ages 7-9. Whole-skeleton TBSS analyses revealed reduced FA associated to smaller N400 amplitudes in response to anger, and to higher HA. Region-of-Interest TBSS analyses showed high correlations (ranging -0.69-0.82, p<0.01-0.001) between FA and N400 amplitudes across the Inferior Longitudinal, the Inferior Frontoccipital, and the left Uncinate Fasciculus, and between FA and Harm Avoidance in right Uncinate Fasciculus (-0.71, p<0.01). Tractography showed that these relationships were mainly present in the left Inferior Longitudinal and the right Inferior Fronto-Occipital Fasciculus for N400 amplitudes, and in the right Uncinate Fasciculus for HA. Ventral limbic pathways' white matter organisation affects the neural responses to expressions - such as anger - that are perceptually more challenging and/or communicate social rejection, and compounds the neural pathways that predispose to avoidant behaviour and shyness with strangers.