Duration-dependent effects of the BDNF Val66Met polymorphism on anodal tDCS induced motor cortex plasticity in older adults: a group and individual perspective

Abstract

The brain derived neurotrophic factor (BDNF) Val66Met polymorphism and stimulation duration are thought to play an important role in modulating motor cortex plasticity induced by non-invasive brain stimulation (NBS). In the present study we sought to determine whether these factors interact or exert independent effects in older adults. Fifty-four healthy older adults (mean age = 66.85 years) underwent two counterbalanced sessions of 1.5 mA anodal transcranial direct current stimulation (atDCS), applied over left M1 for either 10 or 20 min. Single pulse transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability (CSE) before and every 5 min for 30 min following atDCS. On a group level, there was an interaction between stimulation duration and BDNF genotype, with Met carriers (n = 13) showing greater post-intervention potentiation of CSE compared to Val66Val homozygotes homozygotes (n = 37) following 20 min (p = 0.002) but not 10 min (p = 0.219) of stimulation. Moreover, Met carriers, but not Val/Val homozygotes, exhibited larger responses to TMS (p = 0.046) after 20 min atDCS, than following 10 min atDCS. On an individual level, two-step cluster analysis revealed a considerable degree of inter-individual variability, with under half of the total sample (42%) showing the expected potentiation of CSE in response to atDCS across both sessions. Intra-individual variability in response to different durations of atDCS was also apparent, with one-third of the total sample (34%) exhibiting LTP-like effects in one session but LTD-like effects in the other session. Both the inter-individual (p = 0.027) and intra-individual (p = 0.04) variability was associated with BDNF genotype. In older adults, the BDNF Val66Met polymorphism along with stimulation duration appears to play a role in modulating tDCS-induced motor cortex plasticity. The results may have implications for the design of NBS protocols for healthy and diseased aged populations.

Preconditioning tDCS facilitates subsequent tDCS effect on skill acquisition in older adults

“…At neurophysiological level, tDCS placing anode electrode placed over M1 with the current intensity of 1.5 mA increases MEP amplitude in young (Karok and Witney 2013, Tremblay et al 2013a, Williams et al 2013) and older adults (Puri et al 2016, Puri et al 2015.…”

“…Despite the abundance of research reporting tDCS effects on plasticity, in recent years large inter-individual variability in response to tDCS has been recognized (Datta et al 2012, Puri et al 2015, Wiethoff et al 2014. For example, Fujiyama et al observed that approximately 20% of participants (8 out of 39) did not show the expected corticospinal excitability increase following tDCS with anode placed over M1.…”

“…For example, Fujiyama et al observed that approximately 20% of participants (8 out of 39) did not show the expected corticospinal excitability increase following tDCS with anode placed over M1. Of particular relevance is a recent paper that considered responses to tDCS in 54 healthy older (mean age = 66.9 years) (Puri et al 2015), in which participants underwent two sessions receiving tDCS with the anode placed over M1 with different stimulation durations (i.e., 10 min and 20 min). Less than half (46%) of older adults exhibited the expected potentiation in corticospinal excitability in both sessions.…”

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

“…Despite the aforementioned seminal studies that reported robust group level effects of 'hotspot' and marked using a felt-tip pen (Puri et al 2015).…”

Does transcranial direct current stimulation enhance cognitive and motor functions in the ageing brain? A systematic review and meta- analysis

“…The role of genetic variation in the after-effects of various NIBS protocols, including the BDNF Val66Met polymorphism, has been the subject of a number of recent studies. Met carriers exhibit reduced BDNF secretion and impaired performance on learning and memory (Cheeran et al, 2008;Di Lazzaro et al, 2012) or greater post-intervention increases in cortical excitability in Met carriers (Antal et al, 2010;Teo et al, 2014) including a study of older adults (Puri et al, 2015).…”