Substrates of metacognition on perception and metacognition on higher-order cognition relate to different subsystems of the mentalizing network.

Humans have the ability to reflect upon their perception, thoughts, and actions, known as metacognition (MC). The brain basis of MC is incompletely understood, and it is debated whether MC on different processes is subserved by common or divergent networks. We combined behavioral phenotyping with multi-modal neuroimaging to investigate whether structural substrates of individual differences in MC on higher-order cognition (MC-C) are dissociable from those underlying MC on perceptual accuracy (MC-P). Motivated by conceptual work suggesting a link between MC and cognitive perspective taking, we furthermore tested for overlaps between MC substrates and mentalizing networks. In a large sample of healthy adults, individual differences in MC-C and MC-P did not correlate. MRI-based cortical thickness mapping revealed a structural basis of this independence, by showing that individual differences in MC-P related to right prefrontal cortical thickness, while MC-C scores correlated with measures in lateral prefrontal, temporo-parietal, and posterior midline regions. Surface-based superficial white matter diffusivity analysis revealed substrates resembling those seen for cortical thickness, confirming the divergence of both MC faculties using an independent imaging marker. Despite their specificity, substrates of MC-C and MC-P fell clearly within networks known to participate in mentalizing, confirmed by task-based fMRI in the same subjects, previous meta-analytical findings, and ad-hoc Neurosynth-based meta-analyses. Our integrative multi-method approach indicates domain-specific substrates of MC; despite their divergence, these nevertheless likely rely on component processes mediated by circuits also involved in mentalizing. Hum Brain Mapp 37:3388-3399, 2016.