Abstract
Objective: To evaluate whether a common polymorphism (Val66Met) in the gene for brain-derived neurotrophic factor (BDNF)—a gene thought to influence plasticity—contributes to inter-individual variability in responses to continuous theta-burst stimulation (cTBS), and explore whether variability in stimulation-induced plasticity among Val66Met carriers relates to differences in stimulation intensity (SI) used to probe plasticity.Methods: Motor evoked potentials (MEPs) were collected from 33 healthy individuals (11 Val66Met) prior to cTBS (baseline) and in 10 min intervals immediately following cTBS for a total of 30 min post-cTBS (0 min post-cTBS, 10 min post-cTBS, 20 min post cTBS, and 30 min post-cTBS) of the left primary motor cortex. Analyses assessed changes in cortical excitability as a function of BDNF (Val66Val vs. Val66Met) and SI.Results: For both BDNF groups, MEP-suppression from baseline to post-cTBS time points decreased as a function of increasing SI. However, the effect of SI on MEPs was more pronounced for Val66Met vs. Val66Val carriers, whereby individuals probed with higher vs. lower SIs resulted in paradoxical cTBS aftereffects (MEP-facilitation), which persisted at least 30 min post-cTBS administration.Conclusions: cTBS aftereffects among BDNF Met allele carriers are more variable depending on the SI used to probe cortical excitability when compared to homozygous Val allele carriers, which could, to some extent, account for the inconsistency of previously reported cTBS effects.Significance: These data provide insight into the sources of cTBS response variability, which can inform how best to stratify and optimize its use in investigational and clinical contexts.
Highlights
Transcranial magnetic stimulation (TMS) has received considerable attention in both research and clinical settings due to its ability to probe and transiently modulate cortical activity
Comparisons between the two groups revealed that there were no significant differences in age [Val66Val mean (M) ± standard deviation (SD) = 23.5 ± 5.7 vs. Val66Met M = 25.5 ± 7.0] or mean motor evoked potentials (MEPs) amplitudes at baseline (Val66Val M = 1.03 ± 0.2 mV vs. Val66Met M = 0.86 ± 0.4 mV; p’s > 0.10)
RMT significantly differed for Val66Val (M = 48.7 ± 8.3) vs. Val66Met carriers (M = 41.6 ± 8.1; p = 0.03), there were no significant differences in SI—whether defined relative to the individual (% resting motor threshold (rMT); Val66Val M = 116.3 ± 7.4 vs. Val66Met M = 120.2 ± 14.2) or the stimulator (MSO; Val66Val M = 56.5 ± 9.8 vs. Val66Met M = 49.7 ± 9.4; p’s > 0.07)
Summary
Transcranial magnetic stimulation (TMS) has received considerable attention in both research and clinical settings due to its ability to probe and transiently modulate cortical activity. It has proven to be a powerful tool for interrogating brain structure-function relationships, pertaining to a wide range of motor and cognitive abilities (Devlin and Watkins, 2006; Lowe et al, 2018; Medaglia et al, 2018) as well as social (Ferrari et al, 2016; Era et al, 2018, 2020) and emotional processes (Moors et al, 2019; Fini et al, 2020), and to characterize and index fundamental neurophysiologic properties, including but not limited to cortical excitability (Pascual-Leone et al, 1998), interhemispheric interactions (Mochizuki et al, 2004), and activity-induced neuroplasticity (Bolognini et al, 2009). While the short implementation time has made TBS a very attractive tool for research and clinical investigations, it is not immune to the observed response variability
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