Facilitatory non-invasive brain stimulation in older adults: the effect of stimulation type and duration on the induction of motor cortex plasticity.

Despite holding significant promise for counteracting the deleterious effects of ageing on cognitive and motor function, little is known of the effects of facilitatory non-invasive brain stimulation (NBS) techniques on corticospinal excitability (CSE) in older adults. Thirty-three older adults (≥60 years) participated in four NBS sessions on separate days, receiving 10- and 20-min anodal transcranial direct current stimulation (atDCS), and 300 and 600 pulses of intermittent theta burst stimulation (iTBS) over the left M1. Motor-evoked potentials measured in the contralateral hand served as a measure of CSE before and for 30 min following each NBS intervention. At the group level, generalized post-stimulation CSE increases were observed (p < 0.001) with no significant differences between the two durations of each stimulation type (atDCS: p = 0.5; iTBS: p = 0.9). For individuals exhibiting overall facilitatory change to atDCS ('responders', n = 10), 20-min atDCS resulted in longer lasting CSE facilitation than 10 min. No such difference was observed between the two iTBS protocols. Considerable variability was observed inter-individually, where 52-58 % of the cohort exhibited the expected facilitation after each of the NBS protocols-as well as intra-individually, where 45-48 % of the cohort maintained consistent post-stimulation responses across the varying durations and types of stimulation. In conclusion, as shown previously in young adults, older adults demonstrate substantial variability in response to different facilitatory NBS protocols. Studies to assess the intra-individual reliability of these protocols are critical to progress towards translation of appropriate protocols (i.e. those that elicit the greatest response for each individual) into clinical practice

A systems biology approach to defining regulatory mechanisms for cartilage and tendon cell phenotypes

Phenotypic plasticity of adult somatic cells has provided emerging avenues for the development of regenerative therapeutics. In musculoskeletal biology the mechanistic regulatory networks of genes governing the phenotypic plasticity of cartilage and tendon cells has not been considered systematically. Additionally, a lack of strategies to effectively reproduce in vitro functional models of cartilage and tendon is retarding progress in this field. De- and redifferentiation represent phenotypic transitions that may contribute to loss of function in ageing musculoskeletal tissues. Applying a systems biology network analysis approach to global gene expression profiles derived from common in vitro culture systems (monolayer and three-dimensional cultures) this study demonstrates common regulatory mechanisms governing de- and redifferentiation transitions in cartilage and tendon cells. Furthermore, evidence of convergence of gene expression profiles during monolayer expansion of cartilage and tendon cells, and the expression of key developmental markers, challenges the physiological relevance of this culture system. The study also suggests that oxidative stress and PI3K signalling pathways are key modulators of in vitro phenotypes for cells of musculoskeletal origin