Altered spatiotemporal consistency and their genetic mechanisms in mild cognitive impairment: a combined neuroimaging and transcriptome study

The Four-dimensional (spatiotemporal) Consistency of local Neural Activities (FOCA) metric was utilized to assess spontaneous whole-brain activity. Despite its application, the genetic underpinnings of FOCA alterations in Alzheimer's Disease (AD)-related Mild Cognitive Impairment (MCI) remain largely unexplored. To elucidate these changes, we analyzed group FOCA differences in 41 MCI patients and 46 controls from the Alzheimer's Disease Neuroimaging Initiative database. Integrating the Allen Human Brain Atlas, we performed transcriptome-neuroimaging spatial association analyses to pinpoint genes correlating with MCI-related FOCA changes. We observed heightened FOCA in the frontal-parietal system and diminished FOCA in the temporal lobe and medium cingulate gyrus among MCI patients. These FOCA alterations were spatially linked to the expression of 384 genes, which were enriched in crucial molecular functions, biological processes, and cellular components of the cerebral cortex, as well as related pathways. These genes were specifically expressed in brain tissue and corticothalamic neurons, particularly during late cortical development. They also connected to various behavioral domains. Furthermore, these genes could form a protein-protein interaction network, supported by 34 hub genes. Our results suggest that local spatiotemporal consistency of spontaneous brain activity in MCI may stem from the complex interplay of a broad spectrum of genes with diverse functional features.