The Fronto-Temporal Cortex Has Increased Subcortical Connectivity In Utero and Plasticity in Adulthood.

The adult cerebral cortex is a heterogeneous structure with prominent functional differences between regions. However, less is known about how different regions acquire and maintain their functionality. Here, we leveraged connectomes and brain transcriptomes from human fetal and adult brains of both sexes to investigate early and late differences between cortical regions. We show that at 24 postgestational weeks fronto-temporal regions are disproportionally connected to subcortical regions, highlighting their role in early integrative cortical-subcortical communication. In adulthood, fronto-temporal cortex has lower myelin content and exhibits lower expression of marker genes of perineuronal nets, while showing higher expression of undifferentiated progenitor cells markers. These results suggest that in the adult brain the function of fronto-temporal regions reflects a heightened state of plasticity, possibly to maximize flexible neural responses. In contrast, the function of parietal and occipital regions aligns with decreased plasticity needed to support stable neural dynamics. Linking physiology to pathology, we show that the greater plasticity of the fronto-temporal cortex is coupled to higher oncogenic vulnerability-frontal and temporal regions have greater incidence of gliomas and express higher levels of genes upregulated in glioma even in the absence of malignancy, suggesting a greater glioma-like normative expression state. Together, these findings highlight the divergent patterns of connectivity in utero and plasticity in adulthood between cortical regions and provide a framework in which functional differences across cortical regions reflect differences in connectivity and plasticity.