ReviewEfficacy and Time Course of Theta Burst Stimulation in Healthy Humans
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.
Section snippets
Material and methods
Articles for the present analyses were retrieved from the scientific search engine PubMed in a period between January 2005 and October 2014. Theta burst stimulation in title or abstract was used as search criterion, which yielded 327 initial publications. From these studies a selection of 64 articles was made based upon the following criteria: (1) Experiments with awake healthy adult participants as either main target population or control group in a clinically-oriented study were included; (2)
Results
The mixed model regression for the time course of iTBS600 yielded a significant main effect of MEP amplitude (F = 9.115, P < 0.001, Ω2 = 0.37). Individual parameter estimates revealed significant elevated MEP sizes compared to baseline up to 60 min (Table 2, Fig. 1A). The time course of iTBS600 was best explained by a linear function (y = −0.290x + 33.370, r2 = 0.093; Fig. 1B). CTBS300 was significantly decreased (F = 9.115, P < 0.001, Ω2 = 0.37) and parameter estimates revealed that this
Discussion
The aim of the present study was to quantify the magnitude and time course of the three most commonly used TBS paradigms for modulating motor cortical excitability levels. Results for iTBS600 show an increase in cortical excitability for at least 60 min with a maximum of 35.54 ± 3.32% post intervention and a decline over time in a linear fashion (Fig. 1B). CTBS600 causes inhibition of −22.87 ± 2.75% at its peak and returns back to baseline in a linear fashion after 50 min (Fig. 1C). These
Conclusions
The present study quantified the magnitude and time course of TBS-induced effects on motor cortical excitability by systematically reviewing the available literature involving 102 experiments performed in 64 studies. ITBS600 has been shown to increase cortical excitability up to 60 min, whereas cTBS600 decreases cortical excitability up to 50 min. CTBS300 induces similar effects to cTBS600, but lasts only for approximately 20 min. Our results offer normative data of TBS-induced effects and
References (129)
- et al.
Use and safety of a new repetitive transcranial magnetic stimulator
Electroencephalogr Clin Neurophysiol
(1996) - et al.
Theta burst stimulation of the human motor cortex
Neuron
(2005) - et al.
A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition
Clin Neurophysiol
(2006) - et al.
Consensus: motor cortex plasticity protocols
Brain Stimul
(2008) - et al.
Inter-individual variability in response to non-invasive brain stimulation paradigms
Brain Stimul
(2014) - et al.
The after-effect of human theta burst stimulation is NMDA receptor dependent
Clin Neurophysiol
(2007) - et al.
Further evidence for NMDA dependence of the after-effects of human theta burst stimulation
Clin Neurophysiol
(2007) - et al.
Theta-burst stimulation: remote physiological and local behavioral after-effects
Neuroimage
(2008) - et al.
Repetitive TMS over the human oculomotor cortex: comparison of 1-Hz and theta burst stimulation
Neurosci Lett
(2006) - et al.
Effects of theta burst stimulation protocols on phosphene threshold
Clin Neurophysiol
(2006)
Effect of theta burst stimulation over the human sensorimotor cortex on motor and somatosensory evoked potentials
Clin Neurophysiol
Functional MRI-navigated repetitive transcranial magnetic stimulation over supplementary motor area in chronic tic disorders
Brain Stimul
Theta burst stimulation does not reliably depress all regions of the human motor cortex
Clin Neurophysiol
Pattern-specific role of current orientation used to deliver theta burst stimulation
Clin Neurophysiol
High-frequency oscillations change in parallel with short-interval intracortical inhibition after theta burst magnetic stimulation
Clin Neurophysiol
Comparative assessment of best conventional with best theta burst repetitive transcranial magnetic stimulation protocols on human motor cortex excitability
Clin Neurophysiol
The effect of continuous theta burst stimulation over premotor cortex on circuits in primary motor cortex and spinal cord
Clin Neurophysiol
Theta burst stimulation over the human primary motor cortex modulates neural processes involved in movement preparation
Clin Neurophysiol
Low-intensity, short-interval theta burst stimulation modulates excitatory but not inhibitory motor networks
Clin Neurophysiol
Impact of repetitive theta burst stimulation on motor cortex excitability
Brain Stimul
Lack of LTP-like plasticity in primary motor cortex in Parkinson's disease
Exp Neurol
A comparison of two different continuous theta burst stimulation paradigms applied to the human primary motor cortex
Clin Neurophysiol
Early, severe and bilateral loss of LTP and LTD-like plasticity in motor cortex (M1) in de novo Parkinson's disease
Clin Neurophysiol
Paired associative stimulation increases motor cortex excitability more effectively than theta-burst stimulation
Clin Neurophysiol
Primary motor cortex involvement in initial learning during visuomotor adaptation
Neuropsychologia
Altered neurophysiologic response to intermittent theta burst stimulation in Tourette syndrome
Brain Stimul
Effects of theta burst stimulation on motor cortex excitability in Parkinson's disease
Clin Neurophysiol
Abnormal experimentally- and behaviorally-induced LTP-like plasticity in focal hand dystonia
Exp Neurol
A comparison of neuroplastic responses to non-invasive brain stimulation protocols and motor learning in healthy adults
Neurosci Lett
The effects of individualized theta burst stimulation on the excitability of the human motor system
Brain Stimul
Inter-subject variability of LTD-like plasticity in human motor cortex: a matter of preceding motor activation
Brain Stimul
Inter- and intra-individual variability following intermittent theta burst stimulation: implication for rehabilitation and recovery
Brain Stimul
Reproducibility of the effects of theta burst stimulation on motor cortical plasticity in healthy participants
Clin Neurophysiol
Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis
J Clin Epidemiol
Interhemispheric effects of high and low frequency rTMS in healthy humans
Clin Neurophysiol
Exploring the effect of inducing long-term potentiation in the human motor cortex on motor learning
Brain Stimul
Plasticity of motor threshold and motor-evoked potential amplitude – a model of intrinsic and synaptic plasticity in human motor cortex?
Brain Stimul
Patterned stimulation at the theta frequency is optimal for the induction of hippocampal long-term potentiation
Brain Res
Theta oscillations in the hippocampus
Neuron
LTP and LTD: an embarrassment of riches
Neuron
The electrophysiology of adenosine in the mammalian central nervous system
Prog Neurobiol
Corticothalamic resonance, states of vigilance and mentation
Neuroscience
Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex
Brain
Induction of plasticity in the human motor cortex by paired associative stimulation
Brain
Theta-burst repetitive transcranial magnetic stimulation suppresses specific excitatory circuits in the human motor cortex
J Physiol
Effect of physiological activity on an NMDA-dependent form of cortical plasticity in human
Cereb Cortex
Theta burst stimulation induces after-effects on contralateral primary motor cortex excitability in humans
J Physiol
The role of dorsal premotor area in reaction task: comparing the “virtual lesion” effect of paired pulse or theta burst transcranial magnetic stimulation
Exp Brain Res
The role of the cerebellum in sub- and supraliminal error correction during sensorimotor synchronization: evidence from fMRI and TMS
J Cogn Neurosci
Theta-burst stimulation over human frontal cortex distorts perceptual stability across eye movements
Cereb Cortex
Cited by (188)
Lateral Prefrontal Stimulation of Active Cortex With Theta Burst Transcranial Magnetic Stimulation Affects Subsequent Engagement of the Frontoparietal Network
2024, Biological Psychiatry: Cognitive Neuroscience and NeuroimagingNon-invasive brain stimulation for patients and healthy subjects: Current challenges and future perspectives
2024, Journal of the Neurological Sciences
Financial disclosures: The authors report no biomedical financial interests or potential conflicts of interest.