Interindividual Variability and Intraindividual Reliability of Intermittent Theta Burst Stimulation-induced Neuroplasticity Mechanisms in the Healthy Brain

Abstract

We combined patterned TMS with EMG in several sessions of a within-subject design to assess and characterize intraindividual reliability and interindividual variability of TMS-induced neuroplasticity mechanisms in the healthy brain. Intermittent theta burst stimulation (iTBS) was applied over M1 to induce long-term potentiation-like mechanisms as assessed by changes in corticospinal excitability. Furthermore, we investigated the association between the observed iTBS effects and individual differences in prolonged measures of corticospinal excitability. Our results show that iTBS-induced measures of neuroplasticity suffer from high variability between individuals within a single assessment visit and from low reliability within individuals across two assessment visits. This indicates that both group and individual effects of iTBS on corticospinal excitability cannot be assumed to be reliable and therefore need to be interpreted with caution, at least when measured by changes in the amplitudes of motor-evoked potentials.

A Data-Driven Approach to Responder Subgroup Identification after Paired Continuous Theta Burst Stimulation

“…Further proposals include the development of novel stimulation protocols such as quadripulse theta burst stimulation shown to effectively alter cortical excitability (Jung et al, 2016 ). If modal distribution was not analyzed, the present data would have appeared as if displaying a high variability of the responses to TMS as reported for paired cTBS AMT (Goldsworthy et al, 2012 ) and extending to intermittent TBS (iTBS; Schilberg et al, 2017 ). The high degree of variability extends to clinical settings; for example, studies in the stroke population assessing TMS as an adjunct to rehabilitation are characterized by large variability as well (Butler et al, 2005 ; Otal et al, 2015 ).…”

Concurrent human TMS-EEG-fMRI enables monitoring of oscillatory brain state-dependent gating of cortico-subcortical network activity

“…Similarly, TMS-evoked network responses differed substantially (being much more confined in low activators), echoing earlier findings on large inter-individual variability in the net effects of TMS manipulations (e.g., only 25% of participants showed all expected effects in 27 , also see refs. [28][29][30] and discussion). It should also be noted that in our sample, TMS was applied at a lower absolute intensity in the Low Activators (mean intensity 45% MSO) compared to High Activators (mean intensity 65% MSO), due to either a low resting motor threshold or participant discomfort.…”

Phase of beta-frequency tACS over primary motor cortex modulates corticospinal excitability

“…In addition, it stands to reason that local oscillation phase and frequency at the time of TMS administration may not only be crucial for the investigation of corticospinal excitability, but also for other forms of TMS application, such as motor plasticity inducing stimulation protocols or research on brain regions other than M1. Further investigations of frequency and phase-dependence of TMS efficacy could possibly help to explain recently accented high variability of TMS effects both across and within individuals (Schilberg, Schuhmann, & Sack, 2017) and lead to more robustness of TMS measures. In order to acquire meaningful and reliable results it is important to carefully investigate underlying brain mechanisms that could influence TMS effects and to improve existing or to develop new application techniques.…”