Lobule-Specific Dosage Considerations for Cerebellar Transcranial Direct Current Stimulation During Healthy Aging: A Computational Modeling Study Using Age-Specific Magnetic Resonance Imaging Templates

Abstract

Objective: Aging is associated with a decline in cognitive and motor performances, which are a part of geriatric syndromes. Since aging is associated with morphological changes in the cerebellum and cerebellar morphology is a good predictor of cognitive and motor performances, so the study of cerebellar role in age-related decline in performance is necessary. Cerebellar transcranial direct current stimulation (ctDCS) has been proposed to study and facilitate the cerebellar function. However, lobule-specific dosing has not been investigated in healthy aging. This is important because the same electrode montage across different individuals for ctDCS (called the "one-size-fits-all" approach) can lead to inter-individual differences in the lobule-specific dosing of the electric field (EF). These differences can be due to the inter-individual variability and age-related changes in the cerebellar structure. To investigate such lobule-specific dosing differences in healthy aging, we modeled the lobular EF distribution across groups of 18 to 89 years for a commonly used "one-size-fits-all" ctDCS montage.

Materials and methods: A fully automated open-source pipeline performed age-group specific computational modeling of EF using 18 age-appropriate human brain magnetic resonance imaging (MRI) templates. The 18 age-appropriate human brain MRI templates were obtained from a database found online at https://jerlab.sc.edu/projects/neurodevelopmental-mri-database/. We extracted the EF magnitude (called EF strength) across the 28 cerebellar lobules based on a spatially unbiased cerebellar atlas. We investigated the aging effects on various measures of specificity including the ratio of the mean lobular EF at the lobules beneath the active electrode (ipsilateral [right] lobules VIIIa, VIIIb, IX) divided by the mean EF across both the targeted (ipsi) and the contralateral (contra) cerebellar hemisphere.

Results: Two-way ANOVA showed that the lobules as well as the age group (and their interaction term) had a significant effect (p < 0.01) on the EF strength. Specifically, EF strength increased significantly at the neighboring cerebellar lobules (e.g., ipsilateral [right] lobules VIIb, Crus I and Crus II) of the targeted cerebellar hemisphere at an old age (70-74, 75-79, and 85-89 years) that reduced the specificity of ctDCS at the ipsilateral (right) lobules VIIIa, VIIIb, IX beneath the active electrode. We also found that the maximum EF strength in the cerebellar hemispheres decreased with an increase in the volume of the cerebrospinal fluid (CSF) and a decrease in the cerebellar volume with aging in a linear manner.

Discussion: We found that cerebellar shrinkage and increasing thickness of the highly conductive CSF during healthy aging can lead to the dispersion of the current away from the lobules underlying the active electrode. We concluded that an individualized ctDCS approach for dosimetry is critical when ctDCS is used as an adjuvant treatment for active aging to address age-related lobule-specific cerebellar geriatric syndromes effectively. Future work is necessary to investigate age-related effects of lobule-specific ctDCS on the large-scale cognitive and motor networks using functional neuroimaging that is expected due to the cerebellum's extensive reciprocal connectivity with the cerebral cortex.

Keywords: SUIT; aging; cerebellar stimulation; cerebellar tDCS; cerebellum; cognitive performance; magnetic resonance imaging.