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The vestibular system is emerging as a pre-eminent contributor to alterations in the structure and function of the central nervous system. Yet, whether age-related vestibular loss is related to volume loss in the cerebral cortical areas that receive vestibular input remains unknown. In this cross-sectional study of 117 healthy, older adults from the Baltimore Longitudinal Study of Aging, we examine the relationships between age-related vestibular functions and the gray matter volumes of the prefrontal cortex and its subregions and of the sensorimotor cortex—regions known to process vestibular information. To measure the functions of three vestibular organs, the saccule, utricle, and horizontal semi-circular canal vestibulo-ocular reflex (VOR), we performed cervical vestibular-evoked reflex (cVEMP), ocular VEMP (oVEMP), and video-head impulse tests, respectively. Log-linear multiple regression was used to investigate the relationships between average regional volume and vestibular function, adjusting for age, sex, and intracranial volume. We found that age-related changes in vestibular end-organ function differentially alter gray matter volumes in the prefrontal and sensorimotor cortices, with many findings persisting when considering left (or right) side only. Lower canal function had a degenerative effect on the volume of the prefrontal cortex concomitant with ongoing, age-related, global brain atrophy. Lower saccular function preserved the volume of the sensorimotor cortex against age-related, global brain atrophy and had no relationship with the prefrontal cortical volume. Whereas lower utricular function showed a degenerative effect on the volume of the middle frontal gyrus accompanying age-related, global brain atrophy, it showed a protective effect on the volume of the pole of the superior frontal gyrus and showed no relationship with sensorimotor cortical volume. Together, these findings suggest that vestibular function may play a role in the resilience to or acceleration of global age effects on regional brain atrophy. Moreover, these findings enhance the understanding of the role of age-related vestibular function in the structural alterations of the cerebral cortex.Key PointsAge-related vestibular function is significantly associated with gray matter volumes in the prefrontal and sensorimotor cortices in adults.Lower canal function showed a degenerative effect on the volume of the prefrontal cortex in addition to ongoing age-related brain atrophy. Lower saccular function had a protective effect against age-related atrophy on sensorimotor cortical volume. Lower utricular function showed a degenerative effect on the relative volume of the middle frontal gyrus and a protective effect on the relative volume of the pole of the superior frontal gyrus. Canal and utricular function were not associated with the relative volumes of the sensorimotor cortex, and saccular function was not associated with the relative volumes of the prefrontal cortex.Lower canal and utricular function may play an important role in the acceleration of age-related brain atrophy in the prefrontal cortex and in the middle frontal gyrus, respectively. Lower utricular function may play a role in the resilience to age-related atrophy in the pole of the superior frontal gyrus.

The human oral mucosa hosts a diverse microbiome and is exposed to potentially toxic biomaterials from dental restoratives. Mucosal health is partly determined by cell and tissue responses to challenges such as dental materials and pathogenic bacteria. An in vitro model to rapidly determine potential layer-specific responses would lead to a better understanding of mucosal homeostasis and pathology. Therefore, this study aimed to develop a co-cultured microfluidic mucosal model on-a-chip to rapidly assess mucosal remodeling and the responses of epithelial and subepithelial layers to challenges typically found in the oral environment. A gingival fibroblast-laden collagen hydrogel was assembled in the central channel of a three-channel microfluidic chamber with interconnecting pores, followed by a keratinocyte layer attached to the collagen exposed in the pores. This configuration produced apical and subepithelial side channels capable of sustaining flow. Keratinocyte, fibroblast, and collagen densities were optimized to create a co-culture tissue-like construct stable over one week. Cells were stained and imaged with epifluorescence microscopy to confirm layer characteristics. As proof-of-concept, the mucosal construct was exposed separately to a dental monomer, 2-hydroxylethyl methacrylate (HEMA), and the oral bacteria Streptococcus mutans. Exposure to HEMA lowered mucosal cell viability, while exposure to the bacteria lowered trans-epithelial electrical resistance. These findings suggest that the oral mucosa-on-a-chip is useful for studying oral mucosal interactions with bacteria and biomaterials with a histology-like view of the tissue layers.