Reproducibility of Single-Pulse, Paired-Pulse, and Intermittent Theta-Burst TMS Measures in Healthy Aging, Type-2 Diabetes, and Alzheimer’s Disease

Abstract

Background: Transcranial magnetic stimulation (TMS) can be used to assess neurophysiology and the mechanisms of cortical brain plasticity in humans in vivo. As the use of these measures in specific populations (e.g., Alzheimer’s disease; AD) increases, it is critical to understand their reproducibility (i.e., test–retest reliability) in the populations of interest.Objective: Reproducibility of TMS measures was evaluated in older adults, including healthy, AD, and Type-2 diabetes mellitus (T2DM) groups.Methods: Participants received two identical neurophysiological assessments within a year including motor thresholds, baseline motor evoked potentials (MEPs), short- and long-interval intracortical inhibition (SICI, LICI) and intracortical facilitation (ICF), and MEP changes following intermittent theta-burst stimulation (iTBS). Cronbach’s α coefficients were calculated to assess reproducibility. Multiple linear regression analyses were used to investigate factors related to intraindividual variability.Results: Reproducibility was highest for motor thresholds, followed by baseline MEPs, SICI and LICI, and was lowest for ICF and iTBS aftereffects. The AD group tended to show higher reproducibility than T2DM or controls. Intraindividual variability of baseline MEPs was related to age and variability of RMT, while the intraindividual variability in post-iTBS measures was related to baseline MEP variability, intervisit duration, and Brain-derived neurotrophic factor (BDNF) polymorphism.Conclusion: Increased reproducibility in AD may reflect pathophysiological declines in the efficacy of neuroplastic mechanisms. Reproducibility of iTBS aftereffects can be improved by keeping baseline MEPs consistent, controlling for BDNF genotype, and waiting at least a week between visits.Significance: These findings provide the first direct assessment of reproducibility of TMS measures in older clinical populations. Reproducibility coefficients may be used to adjust effect- and sample size calculations for future studies.

Reliability of single and paired pulse transcranial magnetic stimulation parameters across eight testing sessions

“…10ms ICF was found to have poor-fair reliability which was influenced by the choice of averaging (mean/median). Consistent with previous reports, it was the least reliable of the measures we assessed [2][3][4].…”

“…It is therefore important that the reliability of these measures is extensively examined and demonstrated. Several studies have sought to explore this [1][2][3][4][5], and have typically included assessment of reliability across 2-3 sessions for the following measures: motor threshold (MT); TMS recruitment/input output (IO) curves; short interval intracortical inhibition (SICI); and intracortical facilitation (ICF). These have revealed varying degrees of reliability across the different parameters [6].…”

Transcranial magnetic stimulation predicts cognitive decline in patients with Alzheimer’s disease

“…However, several works of recent literature demonstrated that interindividual variability in patients with AD is very low respect to healthy individuals 16 17 40. In particular, Fried and colleagues40 investigated the reproducibility of single, paired-pulse TMS and patterned repetitive TMS, finding that measures of iTBS-induced LTP-like plasticity were the more reproducible among patients with AD, suggesting that the same pathological processes that cause certain measures to be abnormal in AD also exert a stabilising effect on TMS measures 40. The relatively high reproducibility of LTP in AD would suggest validating its use as surrogate biomarker of AD cortical pathology.…”

Similar effect of intermittent theta burst and sham stimulation on corticospinal excitability: A 5‐day repeated sessions study

“…For the purposes of the present experiment, the most important measure is the day‐to‐day intraindividual variation in response to iTBS. Few previous studies have examined whether the effect of TBS on the motor cortex is repeatable in the same subjects on different occasions (Fried, Jannati, Davila‐Perez, & Pascual‐Leone, ; Hinder et al., ; Vallence et al., ). Even though these studies found that the effect of TBS may be similar on different days at a group level, within individual repeatability was low in the latest studies (Fried et al., ; Vallence et al., ), as estimated by low ICC value.…”

“…Few previous studies have examined whether the effect of TBS on the motor cortex is repeatable in the same subjects on different occasions (Fried, Jannati, Davila‐Perez, & Pascual‐Leone, ; Hinder et al., ; Vallence et al., ). Even though these studies found that the effect of TBS may be similar on different days at a group level, within individual repeatability was low in the latest studies (Fried et al., ; Vallence et al., ), as estimated by low ICC value. However, ICC can underestimate the repeatability of data which is expressed as a ratio, that is, normalization of the data reduces the total variance of the data, which in turn, reduces the ICC estimates of variability (Koo & Li, ).…”