Structural neuroimaging correlates of resilience and susceptibility to maternal immune activation

Infectious or non-infectious maternal immune activation (MIA) is an environmental risk factor for mental disorders with neurodevelopmental origins. Whilst there is increasing evidence for significant health consequences, the effects of MIA on the offspring are variable and we indeed demonstrated that mouse offspring exposed to MIA could be stratified into susceptible or resilient for multiple behavioural dysfunctions. Here, we aim to identify the neuroanatomical correlates of this resilience and susceptibility using structural MRI. MIA was induced in C57BL6/N mice and offspring were clustered into resilient or susceptible groups using 2-step-recursive clustering (Mueller et al. 2021). A subset of resilient, susceptible and control offspring were sacrificed for ex vivo structural MRI. Group differences in neuroanatomy were analysed voxel-wise using tensor- based morphometry with FDR correction. To map brain and behaviour data into single multivariate model, we applied sparse partial least squares analysis (sPLS). There were no statistically significant group-wise differences in either regional brain volumes or diffusion imaging parameters after FDR correction. Multivariate sPLS identified a single statistically significant latent variable (p=0.017). Multivariate maps associated anxiety-like, social, cognitive and sensorimotor gating deficits with volumes of multiple prefrontal and limbic grey matter regions and volumes of major white matter tracts. We showed that the neural correlates of susceptibility and resilience to MIA are best-described using multivariate analysis of both neuroanatomical and behavioural data. These data have relevance for advancing our understanding of the variable neurodevelopmental effects induced by MIA and for biomarker-guided approaches in preclinical psychiatric research.