Exploring and optimizing neuroplasticity by non-invasive brain stimulation in the elderly: Effects, and Mechanisms

Abstract

Background: The cornerstone of learning and memory is neuroplasticity, which faces a decline in the elderly. A diminution of long-term potentiation, but not long-term depression takes place in aged animal models, results in humans are however more diverse. Recently, the use of interventions that counteract age-related cognitive and motor decline in the elderly population has gained more attention. The non-invasive brain stimulation technique transcranial direct current stimulation (tDCS) affects neuroplasticity and cognitive performance. Since information about optimal tDCS protocols in old humans is scarce, respective studies are needed. Objective: We conducted three studies to examine age-dependent plasticity differences between healthy younger and older adult humans, and to evaluate the dose-dependency of tDCS-induced motor cortex plasticity and motor sequence learning. In experiment 1, age-related differences in motor cortex plasticity induced by standard tDCS protocols were examined in different age groups. In experiment 2, we titrated the impact of stimulation duration and intensity of cathodal tDCS in elderly participants. Lastly, the effect of different intensities of anodal tDCS on motor sequence learning in elderly individuals was investigated in experiment 3. Method: For experiment 1, 60 participants in three age groups (Young: 18-30, Pre-Elderly: 50-65, and Elderly: 66-80 years) were recruited. For neuroplasticity induction, anodal and cathodal tDCS with 1mA for 15 minutes, and sham stimulation were applied over the primary motor cortex. In experiment 2, 39 volunteers of two age groups (Pre-Elderly: 50-65, and Elderly: 66-80 years) were recruited. Participants received cathodal stimulation over the primary motor cortex with different intensities (1, 2, and 3 mA), and durations (15, 20, and 30 minutes), and a sham intervention. In experiments one and two, TMS-induced motor evoked potentials (MEPs) were used to track motor cortical excitability before and for up to 120 minutes after intervention. In experiment 3, 25 Elderly participants (above 65 years old) were tested with 1, 2, and 3 mA of anodal or sham stimulation over the primary motor cortex while they were performing the Serial Reaction Time task (SRTT). In addition, motor memory consolidation was measured 24 hours after the stimulation. Results: In experiment 1, in comparison to sham, anodal tDCS increased excitability in the Young and Pre-Elderly groups, but failed to produce MEP alterations in the Elderly group. However, cathodal tDCS diminished excitability independent of age. In experiment two, motor cortical excitability was decreased by 1 and 3 mA of cathodal stimulation in both groups, but it was increased by 2 mA only in the Pre-Elderly group. In experiment 3, motor sequence learning was successful, and was maintained up to the next day, regardless of the stimulation protocol. Conclusion: These outcomes contribute to our understanding of plasticity dynamics in humans at higher ages, and determine tDCS protocols for these groups. However, they also show that a respective plasticity enhancement is not necessarily associated with improved motor learning in the elderly– at least with the protocols performed in the present study. Therefore, while the obtained results shed further light on age-related plasticity differences, applying stimulation effects to improve performance requires further research.