While the vestibular system is widely known for helping to maintain balance, posture, and stable vision, mounting research has also demonstrated its importance in cognition and aging. Recent studies have found that peripheral vestibular loss is significantly associated with deficits in spatial cognitive function in older adults. However, the exact neural pathways through which vestibular loss affects spatial cognitive ability in older adults are unknown. Clinical and subclinical studies have shown that vestibular loss is associated with structural and functional alterations in the spatial cognitive network. Yet, studies on the entorhinal cortex (ERC) and trans–entorhinal cortex (TEC)—two key cortical regions in the vestibular spatial cognitive network are scarce. This cross–sectional study examines the relationship between vestibular end–organ function and morphometric changes in the ERC and TEC. We used a subset of 103 patients from the Baltimore Longitudinal Study for Aging who had T1–weighted MRI and vestibular physiological data during the same visit to investigate the relationship between age–related vestibular function and the shape of the ERC and TEC. The vestibular end–organ function was evaluated through the cervical vestibular–evoked myogenic potential (cVEMP) test to assess saccular function, the ocular VEMP (oVEMP) test to evaluate the utricular function, and the video head–impulse test (vHIT) to assess semicircular canal function based on vestibular ocular reflex (VOR). Shape alterations were evaluated in terms of surface expansion/contraction relative to the average ERC or TEC shape. Reduced saccular function was associated with surface expansion in the pro–rhinal region of the left ERC, which is hypothesized to be involved in spatial cognitive function, in the intermediate caudal and intermediate superior regions of the right ERC, and the sulcal region of the right TEC. Reduced utricular function was associated with surface contraction in the left lateral TEC and the anterior sulcal and transentorhinal regions of the left ERC, and surface expansion in the lateral region of the left ERC. Reduced canal function is predominantly associated with surface contraction in the pro–rhinal and lateral regions of the right ERC and with posterior sulcal and transentorhinal regions of the right TEC. These end-organ–specific and differential findings highlight the complex relationship between vestibular function and the shapes of the ERC and TEC, key regions that subserve spatial cognitive ability and other crucial cognitive abilities. Future work will determine whether these structural alterations related to vestibular loss may underlie the observed deficits in spatial cognitive ability in older adults and Alzheimer′s disease.

The authors have declared no competing interest.

This work was supported in part by the National Institute on Aging [grant number R01 AG057667], National Institute on Deafness and Other Communication Disorders [grant number R03 DC015583], and National Institute of Biomedical Imaging and Bioengineering [grant number P41-EB031771] and by the Intramural Research Program, National Institute on Aging, National Institutes of Health.

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All participants provided written informed consent. The BLSA study protocol (03-AG-0325) was approved by the National Institute of Environmental Health Sciences Institutional Review Board.

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