Efficacy and Time Course of Theta Burst Stimulation in Healthy Humans

Highlights

• Magnitude and time course of sixty-four theta burst stimulation studies were reviewed.

• Intermittent theta burst stimulation potentiates the cortex up to 60 min.

• If applied for 40 s continuous theta burst stimulation depresses the cortex up to 50 min.

• If applied for 20 s continuous theta burst stimulation depresses the cortex up to 20 min.

• Results offer normative data for future theta burst stimulation studies on normal and abnormal cortical plasticity.

Abstract

Background

In the past decade research has shown that continuous (cTBS) and intermittent theta burst stimulation (iTBS) alter neuronal excitability levels in the primary motor cortex.

Objective

Quantitatively review the magnitude and time course on cortical excitability of cTBS and iTBS.

Methods

Sixty-four TBS studies published between January 2005 and October 2014 were retrieved from the scientific search engine PubMED and included for analyses. The main inclusion criteria involved stimulation of the primary motor cortex in healthy volunteers with no motor practice prior to intervention and motor evoked potentials as primary outcome measure.

Results

ITBS applied for 190 s significantly increases cortical excitability up to 60 min with a mean maximum potentiation of 35.54 ± 3.32%. CTBS applied for 40 s decreases cortical excitability up to 50 min with a mean maximum depression of −22.81 ± 2.86%, while cTBS applied for 20 s decreases cortical excitability (mean maximum −27.84 ± 4.15%) for 20 min.

Conclusion

The present findings offer normative insights into the magnitude and time course of TBS-induced changes in cortical excitability levels.

Introduction

Over the past two decades researcher have developed numerous transcranial magnetic stimulation (TMS) paradigms to modulate cortical excitability levels. These paradigms include low (1 Hz) and high frequency (≥5 Hz) repetitive TMS (rTMS), paired associative stimulation (PAS) and theta burst stimulation (TBS) [1], [2], [3], [4], [5], [6], [7]. In particular, TBS has gained much interest, which is arguably due to its efficacy and the short stimulation period [4]. Rooted in basic research for the induction of long-term potentiation (LTP) and long-term depression (LTD) in animal brains, TBS applied to the primary motor cortex (M1) has shown to induce frequency-dependent potentiation and depression of cortical excitability [4], [8], [9]. The continuous TBS (cTBS) protocol involves triplets of pulses with a frequency of 50 Hz delivered every 0.2 s (5 Hz), which depresses cortical excitability levels [4], [10]. Even though some studies show successful depression of cortical excitability levels after 300 pulses (cTBS₃₀₀) for 20 s [4], [11], [12], the majority of studies uses 600 pulses during 40 s of stimulation (cTBS₆₀₀) [4], [10]. Intermittent TBS (iTBS) involves series of 10 bursts of 50 Hz triplets delivered every 0.2 s (5 Hz) separated by 8 s non-stimulation intervals. Commonly, iTBS consists of 600 pulses delivered over a 190 s period and is able to increase cortical excitability levels in the M1 (iTBS₆₀₀) [4], [13]. Whereas initial studies examined effects of TBS applied to the M1, TBS is nowadays also applied over non-motor cortical regions [14], [15], [16], [17], [18], [19], [20], [21].

Although the existing literature suggests that TBS applied to the motor cortex is effective, there is to our knowledge no systematic study that has quantified its magnitude and time course of TBS-related effects on cortical excitability. To this end, the present quantitative review aimed to give a normative overview of TBS administered in healthy volunteers to provide a normative estimate of motor cortical plasticity of the human cerebrum.