Metacognitive ability predicts hippocampal and prefrontal microstructure

Micah Allen1,2, James C. Glen1, Daniel Müllensiefen3, Dietrich Samuel Schwarzkopf1,4, 2 Martina F. Callaghan2, Geraint Rees1,2 3 4 1Institute of Cognitive Neuroscience, UCL 5 2Wellcome Trust Center for Neuroimaging at UCL 6 3Department of Psychology, Goldsmiths, University of London 7 4Experimental Psychology, 26 Bedford Way, WC1H 0AP 8 9 Abstract: 10 The ability to introspectively evaluate our experiences to form accurate metacognitive beliefs, 11 or insight, is an essential component of decision-making. Previous research suggests 12 individuals vary substantially in their level of insight, and that this variation predicts brain 13 volume and function, particularly in the anterior prefrontal cortex (aPFC). However, the 14 neurobiological mechanisms underlying these effects are unclear, as qualitative, macroscopic 15 measures such as brain volume can be related to a variety of microstructural features. Here we 16 used a newly developed, high-resolution (800μm isotropic) multi-parameter mapping 17 technique in 48 healthy individuals to delineate quantitative markers of in vivo histological 18 features underlying metacognitive ability. Specifically, we examined how neuroimaging 19 markers of local grey matter myelination, macromolecular and iron content relate to insight. 20 Extending previous volumetric findings, we found that metacognitive ability, as determined by 21 a signal-detection theoretic model, was positively related to the myelo-architectural integrity 22 of aPFC grey matter. Interestingly, perceptual metacognition predicted decreased 23 macromolecule content coupled with increased iron in the hippocampus and precuneus, areas 24 previously implicated in meta-memory rather than meta-perception. Further, the relationship 25 of hippocampal-precuneus and prefrontal microstructure to an auditory memory measure was 26 respectively mediated or suppressed by metacognitive ability, suggesting a dynamic trade-off 27 between participant’s memory and metacognition. These results point towards a novel 28 understanding of the relationship between memory, brain microstructure, and metacognition. 29 30 Significance Statement: 31 By combining a signal-theoretic model of individual metacognitive ability with state of the art 32 quantitative neuroimaging, our results shed new light on the neurobiological mechanisms 33 underlying introspective insight. Myelination and iron are core determinants of both healthy 34 brain maturation and neurodegeneration; particularly in the hippocampus where iron 35 accumulation is linked to oxidative stress and inflammation. Our results may thus indicate that 36 metacognition depends upon the development and integrity of a memory-related brain network, 37 potentially revealing novel biomarkers of neurodegeneration. These results highlight the power 38 of quantitative mapping to reveal neurobiological correlates of behaviour. 39 40 SUBMITTED TO JOURNAL OF NEUROSCIENCE 41