Task-related modulation of cerebellar brain inhibition is maintained in older adults

Abstract

Rationale: Life expectancy has been increasing worldwide, with an increase of 6.6 years over the past 20 years. Likewise, the number of years lived without disease and/or injury, i.e., ‘healthy life expectancy’ increased as well. Yet, it increased at a slower rate as compared to the life expectancy (World health statistics; World Health Organization). Because of this discrepancy, there has been increased interest in understanding age-related neural processes associated with changes in motor function. While age-related impairments in motor functioning and learning are characterized by changes in the structural, functional and biochemical integrity of different brain areas, cerebellar integrity is a clear predictor of motor function in older adults. In keeping with this line of reasoning, investigating cerebellar neural interactions provides a unique window of opportunity to understand underlying

processes accompanied by age-related deficits in motor control. Therefore, we investigated age- related changes in cerebellar-cortical network connectivity, measuring cerebellar brain inhibition

(CBI), during bimanual coordination using a dual-site transcranial magnetic stimulation (ds-TMS) paradigm. The aim of this study was to elucidate age-related alterations in cerebellar–M1 interactions, both at rest and during the preparation of a bimanual motor task.

Methods: 20 younger (12 female; mean age 24+/- SD: 4) and 20 older (13 female; mean age 69 +/- SD:

6) right-handed adults aged between 20-40 (younger adults) or 60-80 (older adults) underwent a ds- TMS protocol. CBI was measured at rest and during the preparatory period of a bimanual tracking

task. To do so, the conditioning stimulus (CS) was applied over the right cerebellar hemisphere using a double-cone coil at an intensity of 65% maximal stimulator output (MSO) and 5ms prior to the test stimulus (TS) over left M1. Each participant underwent one experimental block of 40 trials (20 TS and 20 CS+TS) with an inter-trial interval of 10s to measure CBI at rest. Subsequently, they performed 6 task blocks in a pseudo-randomized order, measuring each task condition twice. Finally, after

participants completed all experimental blocks, tolerability was assessed using a visual analog scale (VAS).

Results: Our findings revealed that both groups demonstrated a reduction in the amount of CBI during the preparatory period of the task as compared to rest (i.e., from significant inhibition at rest towards a [partial] release of inhibition during the preparatory period of a motor task) (p<0.001). However, there was no significant difference in the amount of CBI at rest and during the preparation period of a bimanual motor task between the older and the younger adults (p=0.5897).

Conclusion: We demonstrated a task-related release of inhibition in the context of a bimanual motor task and this effect was similar for both age groups. This preservation of CBI modulation in the context of a motor task in older adults might suggest the existence of neural mechanisms that counteract the effects of aging on the cerebellum to maintain dexterous movement control, i.e., cerebellar reserve. Hence, these findings may provide insights into potential interventions for preserving motor performance in older adults.