Interindividual Variability of Lower-Limb Motor Cortical Plasticity Induced by Theta Burst Stimulation

Abstract

Theta burst stimulation (TBS) has been used as a tool to induce synaptic plasticity and improve neurological disorders. However, there is high interindividual variability in the magnitude of the plastic changes observed after TBS, which hinders its clinical applications. The electric field induced by transcranial magnetic stimulation (TMS) is strongly affected by the depth of the stimulated brain region. Therefore, it is possible that the variability in the response to TBS over the lower-limb motor cortex is different for the hand area. This study investigated the variability of TBS-induced synaptic plasticity in the lower-limb motor cortex, for intermittent TBS (iTBS), continuous TBS (cTBS), and sham iTBS, in 48 healthy young participants. The motor cortical and intracortical excitability of the tibialis anterior was tested before and after TBS using TMS. The results showed that iTBS had facilitatory effects on motor cortex excitability and intracortical inhibition, whereas cTBS exerted opposite effects. Twenty-seven percent of individuals exhibited enhanced motor cortical plasticity after iTBS, whereas 63% of participants showed enhanced plasticity after cTBS. In addition, the amount of TBS-induced plasticity was correlated with the intracortical excitability and the variability of the motor evoked potential prior to TBS. Our study demonstrated the high variability of the iTBS-induced lower-limb motor cortical plasticity, which was affected by the sensitivity of intracortical interneuronal circuits. These findings provide further insights into the variation of the response to TBS according to the anatomy of the stimulated brain region and the excitability of the intracortical circuit.

Keywords: cortical plasticity; interindividual variability; lower-limb; non-invasive brain stimulation; primary motor cortex; transcranial magnetic stimulation.

Figure 1

Experimental procedure. The participants received iTBS, cTBS, and sham iTBS randomly at intervals of over 3 days. The resting motor threshold (RMT), active motor threshold (AMT), recruitment curve, and single-pulse TMS were assessed at the baseline. Single- and paired-pulse TMS were assessed before TBS (Pre) and at 0 (Post-0), 15 (Post-15), 30 (Post-30), and 45 min (Post-45) after TBS.

Figure 2

Effects of TBS on corticospinal excitability. The amplitudes of MEP are normalized to the baseline MEP values. White box plots indicate iTBS; light gray, cTBS; dark gray, sham iTBS. Median and interquartile ranges are represented by horizontal lines within boxes and whiskers (representing minimum and maximum values), respectively. The asterisk denotes significant differences between Pre and each time point within the conditions. The dagger denotes significant differences between each condition at each time point (P < 0.05).

Figure 3

Effects of TBS on short-interval intracortical inhibition and intracortical facilitation. The values of short-interval intracortical inhibition (%) (A) and the values of intracortical facilitation (%) (B) are normalized to the amplitude of test MEP at each time point. White box plots, iTBS; light gray, cTBS; dark gray, sham iTBS. Median and interquartile ranges are represented by horizontal lines within boxes and whiskers (representing minimum and maximum values), respectively. The asterisk denotes significant differences between Pre and each time point within the conditions. The dagger denotes significant differences between each condition at each time point (P < 0.05).

Figure 4

Significant correlations between each TBS response and neurophysiological factors. Correlations between the iTBS response (% of baseline MEP at Post-0) and ICF (A) and MEP-CV (B) at Pre. The correlations between the cTBS response (% of baseline MEP at Post-0) and SICI (C) and MEP-CV (D) at Pre.