@article {Allen046359, author = {Micah Allen and James C. Glen and Daniel M{\"u}llensiefen and Dietrich Samuel Schwarzkopf and Martina F. Callaghan and Geraint Rees}, title = {Metacognitive ability predicts hippocampal and prefrontal microstructure}, elocation-id = {046359}, year = {2016}, doi = {10.1101/046359}, publisher = {Cold Spring Harbor Laboratory}, abstract = {The ability to introspectively evaluate our experiences to form accurate metacognitive beliefs, or insight, is an essential component of decision-making. Previous research suggests individuals vary substantially in their level of insight, and that this variation predicts brain volume and function, particularly in the anterior prefrontal cortex (aPFC). However, the neurobiological mechanisms underlying these effects are unclear, as qualitative, macroscopic measures such as brain volume can be related to a variety of microstructural features. Here we used a newly developed, high-resolution (800{\textmu}m isotropic) multi-parameter mapping technique in 48 healthy individuals to delineate quantitative markers of in vivo histological features underlying metacognitive ability. Specifically, we examined how neuroimaging markers of local grey matter myelination, macromolecular and iron content relate to insight. Extending previous volumetric findings, we found that metacognitive ability, as determined by a signal-detection theoretic model, was positively related to the myelo-architectural integrity of aPFC grey matter. Interestingly, perceptual metacognition predicted decreased macromolecule content coupled with increased iron in the hippocampus and precuneus, areas previously implicated in meta-memory rather than meta-perception. Further, the relationship of hippocampal-precuneus and prefrontal microstructure to an auditory memory measure was respectively mediated or suppressed by metacognitive ability, suggesting a dynamic trade-off between participant{\textquoteright}s memory and metacognition. These results point towards a novel understanding of the relationship between memory, brain microstructure, and metacognition.Significance Statement By combining a signal-theoretic model of individual metacognitive ability with state of the art quantitative neuroimaging, our results shed new light on the neurobiological mechanisms underlying introspective insight. Myelination and iron are core determinants of both healthy brain maturation and neurodegeneration; particularly in the hippocampus where iron accumulation is linked to oxidative stress and inflammation. Our results may thus indicate that metacognition depends upon the development and integrity of a memory-related brain network, potentially revealing novel biomarkers of neurodegeneration. These results highlight the power of quantitative mapping to reveal neurobiological correlates of behaviour.}, URL = {https://www.biorxiv.org/content/early/2016/03/30/046359}, eprint = {https://www.biorxiv.org/content/early/2016/03/30/046359.full.pdf}, journal = {bioRxiv} }