Priming With Intermittent Theta Burst Transcranial Magnetic Stimulation Promotes Spinal Plasticity Induced by Peripheral Patterned Electrical Stimulation

Abstract

This study explored the effect of corticospinal activity on spinal plasticity by examining the interactions between intermittent theta burst transcranial magnetic stimulation (iTBS) of the motor cortex and peripheral patterned electrical stimulation (PES) of the common peroneal nerve (CPN). Healthy volunteers (n = 10) received iTBS to the tibialis anterior (TA) muscle zone of the motor cortex and PES of the CPN in three separate sessions: (1) iTBS-before-PES, (2) iTBS-after-PES, and (3) sham iTBS-before-PES. The PES protocol used 10 100-Hz pulses every 2 s for 20 min. Reciprocal inhibition (RI) from the TA to soleus muscle and motor cortical excitability of the TA and soleus muscles were assessed at baseline, before PES, and 0, 15, 30, and 45 min after PES. When compared to the other protocols, iTBS-before-PES significantly increased changes in disynaptic RI for 15 min and altered long-loop presynaptic inhibition immediately after PES. Moreover, the iTBS-induced cortical excitability changes in the TA before PES were correlated with the enhancement of disynaptic RI immediately after PES. These results demonstrate that spinal plasticity can be modified by altering cortical excitability. This study provides insight into the interactions between modulation of corticospinal excitability and spinal RI, which may help in developing new rehabilitation strategies.

Keywords: H-reflex; disynaptic reciprocal inhibition; non-invasive brain stimulation; presynaptic inhibition; spinal plasticity.

FIGURE 1

Experimental paradigm for intermittent theta burst stimulation (iTBS) before and after patterned electrical stimulation (PES). (A) Time course of the experiment. (B) Sequence of interventions.

FIGURE 2

The effects of iTBS before and after PES on RI (A–C). The values (%) of RI_2ms (A), RI_20ms (B), and RI_100ms (C) indicate the delta amount of inhibition, which was calculated by subtracting the values obtained at each testing time point from the baseline values. The values are presented as the mean ± standard error of the measurements in the figure and as the mean (SD) in the table. In the table, A shows iTBS-before-PES, B shows iTBS-after-PES, and C shows sham iTBS-before-PES. Asterisks indicate significant differences (P < 0.05) between Pre-PES and each intervention time point, or within the interventions.

FIGURE 3

The effects of iTBS before and after PES on motor-evoked potentials (MEPs). MEP amplitudes at the tibialis anterior (TA; A) and soleus (SOL; B) muscles were normalized to the baseline amplitude (%) for each paradigm. The values (%) in the figures are presented as the mean ± standard error. The tables show the mean (±SD) for iTBS-before-PES (A), iTBS-after-PES (B), and sham iTBS-before-PES (C). Asterisks indicate significant differences (P < 0.05) among the interventions.

FIGURE 4

Correlations between change in reciprocal inhibition (RI) and MEPs. Correlation between percent changes in RI_2ms (A), RI_20ms (B), and RI_100ms (C) at Post0 time-point and the normalized MEPs in the TA muscle, for the iTBS-before-PES condition.

FIGURE 5

Hypothetical model for the modulatory effect of iTBS over the motor cortex on the subsequent induction of spinal plasticity induced by PES. White circles in the spinal cord denote spinal motor neurons. Black circles denote Ia inhibitory interneurons. Pre-conditioning by using iTBS changes cortical excitability and the state of Ia inhibitory interneurons, which receive convergent input from the motor cortex. The pre-state changes in the interneurons enhance the induction and maintenance of spinal plasticity induced by PES. TA, tibialis anterior; SOL, soleus.