Development and early life stress sensitivity of the rat cortical microstructural similarity network.

The rat offers a uniquely valuable animal model in neuroscience, but we currently lack an individual-level understanding of the in vivo rat brain network. Here, leveraging longitudinal measures of cortical magnetization transfer ratio (MTR) from in vivo neuroimaging between postnatal days 20 (weanling) and 290 (mid-adulthood), we design and implement a computational pipeline that captures the network of structural similarity (MIND, morphometric inverse divergence) between each of 53 distinct cortical areas. We first characterized the normative development of the network in a cohort of rats undergoing typical development (N=47), and then contrasted these findings with a cohort exposed to early life stress (ELS, N=40). MIND as a metric of cortical similarity and connectivity was validated by cortical cytoarchitectonics and axonal tract-tracing data. The normative rat MIND network had high between-study reliability and complex topological properties including a rich club. Similarity changed during post-natal and adolescent development, including a phase of fronto-hippocampal convergence, or increasing inter-areal similarity. An inverse process of increasing fronto-hippocampal dissimilarity was seen with post-adult aging. Exposure to ELS in the form of maternal separation appeared to accelerate the normative trajectory of brain development - highlighting embedding of stress in the dynamic rat brain network. Our work provides novel tools for systems-level study of the rat brain that can now be used to understand network-based underpinnings of complex lifespan behaviors and experimental manipulations that this model organism allows.