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.
Highlights
Non-invasive brain stimulation (NBS) techniques such as transcranial direct current stimulation and theta burst stimulation (TBS) have delivered promising results in older adults by inducing long-term potentiation (LTP) and longterm depression (LTD) like effects upon corticospinal excitability (CSE), accompanied in some instances by corresponding changes in behavior (Zimerman and Hummel, 2010). Hummel et al (2010) reported significant improvements in older adults on the Jebsen–Taylor Hand function test following the administration of 20 min of anodal tDCS, relative to sham, which outlasted the stimulation period by approximately 30 min
In regards to non-invasive brain stimulation (NBS)-induced plasticity, we recently reported that there was no significant influence of this brain derived neurotrophic factor (BDNF) polymorphism on CSE following 30 min of 1 mA anodal transcranial direct current stimulation (atDCS) in healthy older adults with a relatively small sample
The current study provides new information concerning the role of the BDNF Val66Met polymorphism in moderating atDCSinduced motor cortex plasticity in older adults
Summary
Non-invasive brain stimulation (NBS) techniques such as transcranial direct current stimulation (tDCS) and theta burst stimulation (TBS) have delivered promising results in older adults by inducing long-term potentiation (LTP) and longterm depression (LTD) like effects upon corticospinal excitability (CSE), accompanied in some instances by corresponding changes in behavior (Zimerman and Hummel, 2010). Hummel et al (2010) reported significant improvements in older adults on the Jebsen–Taylor Hand function test following the administration of 20 min of anodal tDCS (atDCS), relative to sham, which outlasted the stimulation period by approximately 30 min. A crucial issue and one that must be addressed if aspirations for clinically relevant interventions are to be realized, is the high intra- and inter-individual variability that has been reported in response to various NBS protocols (Hamada et al, 2013; Hinder et al, 2014; Wiethoff et al, 2014) In this regard, the majority of previous studies suggesting that there are behavioral benefits of atDCS (Zimerman et al, 2013) have focused primarily on the mean effects observed at the group level, with little discussion of the degree to which each individual within the cohort responds to the intervention. A greater understanding of the influence of these factors is likely to be critical in determining whether NBS has any therapeutic utility
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