Lobule-specific dosage considerations for cerebellar transcranial direct current stimulation during healthy aging – a computational modeling study using age-specific MRI templates

Abstract

The world population aged 60 years and older is expected to double between 2015 and 2050. Aging is associated with a decline in cognitive and motor performances which are a part of geriatric syndromes. Aging is also associated with the loss of cerebellar volume where the cerebellum has a considerable contribution in cognitive and motor functions. Therefore, cerebellar transcranial direct current stimulation (ctDCS) has been proposed to study and facilitate cerebellar function during aging. However, the one-size-fits-all approach used for ctDCS can lead to variability in the cerebellar lobule-specific dosing due to age-related changes in the cerebellar structure. Therefore, we investigated lobular electric field (EF) distribution during healthy aging for age groups of 18 to 89 years where computational modeling was based on age-appropriate human brain magnetic resonance imaging (MRI) templates (http://jerlab.psych.sc.edu/NeurodevelopmentalMRIDatabase/). A fully automated open-source pipeline (Realistic vOlumetric-Approach to Simulate Transcranial Electric Stimulation – ROAST) was used for the age-group specific EF modeling. Then, we extracted the EF distribution at the 28 cerebellar lobules based on a spatially unbiased atlas (SUIT) for the cerebellum. Our computational results showed that the EF strength increased significantly at certain important cerebellar lobules (e.g., Crus I and Crus II relevant for cognitive function) contralateral (contra) to the targeted (ipsi) cerebellar hemisphere at an older age that reduced the ctDCS specificity. Specifically, two-way ANOVA showed that the lobules as well as the age-group (and their interaction term) had a significant effect (p<0.01). Post-hoc multiple comparison tests at Alpha=0.01 using Bonferroni critical values showed that Right (Ipsi) Crus I, Right (Ipsi) Crus II, Right (Ipsi) VI, Vermis VIIb, Vermis VIIIa, Right (Ipsi) VIIb, Left (Contra) VIIIb, Left (Contra) IX, Right (Ipsi) VIIIa, Right (Ipsi) VIIIb, Vermis VIIIb, Right (Ipsi) IX, and Vermis IX, and the age-group 18, 18.5, 19, 20-24, 45-49, 50-54, 70-74, 75-79, 85-89 years experienced higher electric field strength (>0.11V/m). Since there is a dichotomy between the sensorimotor cerebellum and the cognitive cerebellum, therefore, subject-specific MRI based head modeling for lobule-specific dosage considerations will be necessary for clinical translation of ctDCS to address geriatric cerebellar syndromes.