Large-scale meta-analysis of human medial frontal cortex reveals tripartite functional organization

The functional organization of human medial frontal cortex (MFC) is a subject of intense study. Using functional magnetic resonance imaging (fMRI), the MFC has been associated with diverse psychological processes including motor function, cognitive control, affect, and social cognition. However, there have been few large-scale efforts to comprehensively map specific psychological functions to sub-regions of medial frontal anatomy. Here we applied a meta-analytic data-driven approach to nearly 10,000 fMRI studies to identify putatively separable regions of MFC and determine which psychological states preferentially recruit their activation. We identified regions at several spatial scales on the basis of meta-analytic co-activation, revealing three broad functional zones along a rostro-caudal axis composed of 2-4 smaller sub-regions each. Multivariate classification analyses aimed at identifying the psychological functions most strongly predictive of activity in each region revealed a tripartite division within MFC, with each zone displaying a relatively distinct functional signature. The posterior zone was associated preferentially with motor function, the middle zone with cognitive control, pain, and affect, and the anterior with reward, social processing and episodic memory. Within each zone, the more fine-grained sub-regions showed distinct, but subtler, variations in psychological function.  These results provide hypotheses about the functional organization of medial prefrontal cortex that can be tested explicitly in future studies.