Functional-structural co-dependent brain mapping of metamemory in amnestic mild cognitive impairment

Abstract

Background: Metamemory, a measure of introspective awareness of memory performance, provides an internally-generated drive, profoundly impacting external memory activities. Given its role in regulating memory along internal-external axis, understanding metamemory and underlying neural mechanisms in amnestic mild cognitive impairment (aMCI) is crucial for memory improvement. The present study was aimed to explore metamemory alterations and structural and functional remodeling characteristics underlying metamemory, as well as key brain regions that potentially moderated its intrinsic associations with age, education, and first-order cognition in aMCI. Methods: Sixty-seven aMCI patients and fifty-two healthy controls underwent neuropsychological assessments and magnetic resonance imaging in this case-control study. Generalized linear models analyzed metamemory-related neuroimaging characteristics. Moderation analysis examined their roles in relationships with age, education, and first-order cognition. Results: Patients with aMCI exhibited lower estimation of performance in prediction (EOP-pre) (P < 0.001) and postdiction (EOP-post) (P = 0.002). Amplitude of low-frequency fluctuation (ALFF) of left parahippocampal gyrus (PHG.L) (P = 0.026) and mediodorsal medial magnocellular (ltMDm) (P = 0.001), along with group × ALFF interaction effects in right cuneus (P = 0.010) and inferior parietal gyrus (P = 0.011) affected metamemory. Functional connectivity between ltMDm and left anterior cingulate cortex-pregenual (ACCpre.L) alleviated the association between metamemory and recall (P = 0.030). PHG.L ALFF enhanced the association between education and metamemory (P = 0.043). Conclusions: Metamemory in aMCI was associated with parietotemporal and thalamic functional remodeling. Regions including ltMDm, ACCpre.L, and PHG.L influenced its intrinsic relationships with education/recall, providing new insights for aMCI interventions.