The brain cortical similarity network: Development and sensitivity to early life stress in a rat model

Understanding how early life experiences shape brain network development is a key challenge in the neuroscience of mental health disorders. To address this, we used magnetic resonance imaging (MRI) similarity network analysis to study the effects of stress in the rat, an important animal model in neuropsychiatry. We measured magnetization transfer ratio (MTR) at each of 53 distinct cortical areas and estimated a cortical similarity network for each individual scan, in two independent experimental datasets. We first characterized normative network development in rats scanned repeatedly between postnatal days 20 (weanling) and 290 (mid-adulthood) (N=47), and then contrasted these findings with a cohort exposed to early life stress in the form of repeated maternal separation (RMS, N=40). The normative rat cortical similarity network exhibited biologically meaningful organization, aligning with prior cytoarchitectonic and tract-tracing data, and displayed complex topological features, including rich club organization. During postnatal and adolescent development, brain regions became more similar, including an early phase of fronto-hippocampal convergence. Early increases in inter-areal similarity were reversed in a later phase of fronto-hippocampal divergence in mid-adulthood. RMS exposure altered inter-areal similarity, especially between frontal and parahippocampal regions, that were also most active developmentally and in aging. Our results reveal how normative cortical network changes in the developing brain are influenced by early life stress. These findings suggest a new translational framework for elucidating how environmental risk factors lead to atypical development of cortical networks.