The facilitatory effects of intermittent theta burst stimulation on corticospinal excitability are enhanced by nicotine

AbstractTheta-burst stimulation (TBS) is a patterned form of repetitive transcranial magnetic stimulation (rTMS) that has been used to induce long-term modulation (plasticity) of corticospinal excitability in a drastically shorter duration protocol than conventional rTMS protocols. In this study we tested the reliability of the effects of two well defined TBS protocols, continuous TBS (cTBS) and intermittent TBS (iTBS), especially in relation to sham TBS, within and across the same 24 participants. All TBS protocols were repeated after approximately 1 month to assess the magnitude and reliability of the modulatory effects of each TBS protocol. Baseline and post-TBS changes in motor evoked potentials (MEP—measure of corticospinal excitability) amplitudes were compared across the cTBS, iTBS and sham TBS protocols and between the initial and retest visits. Overall, across participants, at the initial visit, iTBS facilitated MEPs as compared to baseline excitability, with sham eliciting the same effect. cTBS did not show a significant suppression of excitability compared to baseline MEPs at either visit, and even facilitated MEPs above baseline excitability at a single time point during the repeat visit. Otherwise, effects of TBS were generally diminished in the repeat visit, with iTBS and sham TBS replicating facilitation of MEPs above baseline excitability at similar time points. However, no protocol demonstrated consistent intra-individual modulation of corticospinal excitability upon retest. As the first study to test both iTBS and cTBS against sham TBS across repeat visits, our findings challenge the efficacy and reliability of TBS protocols and emphasize the importance of accounting for sham effects of TBS. Furthermore, given that therapeutic effects of TBS are hypothetically derived from consistent and repeated modulation of brain activity, the non-replicability of plasticity and sham effects call into question these basic mechanisms.

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Double-Sine-Wave Quadri-Pulse Theta Burst Stimulation of Precentral Motor Hand Representation Induces Bidirectional Changes in Corticomotor Excitability

Frontiers in Neurology ◽

10.3389/fneur.2021.673560 ◽

2021 ◽

Vol 12 ◽

Author(s):

Nikolai H. Jung ◽

Bernhard Gleich ◽

Norbert Gattinger ◽

Anke Kalb ◽

Julia Fritsch ◽

...

Keyword(s):

Developmental Disorders ◽

Single Pulse ◽

Sine Wave ◽

Corticospinal Excitability ◽

Precentral Gyrus ◽

Current Direction ◽

Induced Current ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Theta Burst

Neuronal plasticity is considered to be the neurophysiological correlate of learning and memory and changes in corticospinal excitability play a key role in the normal development of the central nervous system as well as in developmental disorders. In a previous study, it was shown that quadri-pulse theta burst stimulation (qTBS) can induce bidirectional changes in corticospinal excitability (1). There, a quadruple burst consisted of four single-sine-wave (SSW) pulses with a duration of 160 μs and inter-pulse intervals of 1.5 ms to match I-wave periodicity (666 Hz). In the present study, the pulse shape was modified applying double-sine-waves (DSW) rather than SSW pulses, while keeping the pulse duration at 160 μs. In two separate sessions, we reversed the current direction of the DSW pulse, so that its second component elicited either a mainly posterior-to-anterior (DSW PA-qTBS) or anterior-to-posterior (DSW AP-qTBS) directed current in the precentral gyrus. The after-effects of DSW qTBS on corticospinal excitability were examined in healthy individuals (n = 10) with single SSW TMS pulses. For single-pulse SSW TMS, the second component produced the same preferential current direction as DSW qTBS but had a suprathreshold intensity, thus eliciting motor evoked potentials (PA-MEP or AP-MEP). Single-pulse SSW TMS revealed bidirectional changes in corticospinal excitability after DSW qTBS, which depended on the preferentially induced current direction. DSW PA-qTBS at 666 Hz caused a stable increase in PA-MEP, whereas AP-qTBS at 666 Hz induced a transient decrease in AP-MEP. The sign of excitability following DSW qTBS at I-wave periodicity was opposite to the bidirectional changes after SSW qTBS. The results show that the pulse configuration and induced current direction determine the plasticity-effects of ultra-high frequency SSW and DSW qTBS at I-wave periodicity. These findings may offer new opportunities for short non-invasive brain stimulation protocols that are especially suited for stimulation in children and patients with neurological or neurodevelopmental disorders.

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Reversed Effects of Intermittent Theta Burst Stimulation following Motor Training That Vary as a Function of Training-Induced Changes in Corticospinal Excitability

Neural Plasticity ◽

10.1155/2015/578620 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

Tino Stöckel ◽

Jeffery J. Summers ◽

Mark R. Hinder

Keyword(s):

Motor Learning ◽

Sham Group ◽

Group Performance ◽

Motor Task ◽

Corticospinal Excitability ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Before And After ◽

And Performance ◽

Theta Burst

Intermittent theta burst stimulation (iTBS) has the potential to enhance corticospinal excitability (CSE) and subsequent motor learning. However, the effects of iTBS following motor learning are unknown. The purpose of the present study was to explore the effect of iTBS on CSE and performance following motor learning. Therefore twenty-four healthy participants practiced a ballistic motor task for a total of 150 movements. iTBS was subsequently applied to the trained motor cortex (STIM group) or the vertex (SHAM group). Performance and CSE were assessed before motor learning and before and after iTBS. Training significantly increased performance and CSE in both groups. In STIM group participants, subsequent iTBS significantly reduced motor performance with smaller reductions in CSE. CSE changes as a result of motor learning were negatively correlated with both the CSE changes and performance changes as a result of iTBS. No significant effects of iTBS were found for SHAM group participants. We conclude that iTBS has the potential to degrade prior motor learning as a function of training-induced CSE changes. That means the expected LTP-like effects of iTBS are reversed following motor learning.

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P138 Influence of the difference of induced current direction on measurement of corticospinal excitability changes after continuous and intermittent theta burst stimulation

Clinical Neurophysiology ◽

10.1016/j.clinph.2016.10.260 ◽

2017 ◽

Vol 128 (3) ◽

pp. e83

Author(s):

T. Sasaki ◽

S. Tokushige ◽

S. Terada ◽

A. Yugeta ◽

Y. Terao ◽

...

Keyword(s):

Corticospinal Excitability ◽

Current Direction ◽

Induced Current ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

The Difference ◽

Theta Burst

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Probing changes in corticospinal excitability following theta burst stimulation of the human primary motor cortex

Clinical Neurophysiology ◽

10.1016/j.clinph.2015.06.014 ◽

2016 ◽

Vol 127 (1) ◽

pp. 740-747 ◽

Cited By ~ 16

Author(s):

Mitchell R. Goldsworthy ◽

Ann-Maree Vallence ◽

Nicolette A. Hodyl ◽

John G. Semmler ◽

Julia B. Pitcher ◽

...

Keyword(s):

Motor Cortex ◽

Primary Motor Cortex ◽

Corticospinal Excitability ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Theta Burst ◽

Stimulation Of

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Human Theta Burst Stimulation Combined with Subsequent Electroacupuncture Increases Corticospinal Excitability

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/8824530 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Jiali Li ◽

Meng Ren ◽

Wenjing Wang ◽

Shutian Xu ◽

Sicong Zhang ◽

...

Keyword(s):

Motor Evoked Potentials ◽

Short Interval ◽

Silent Period ◽

Intracortical Inhibition ◽

Corticospinal Excitability ◽

Conduction Time ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Clinical Trial Registry ◽

Theta Burst

Objective. Intermittent theta burst stimulation (iTBS) is a widely used noninvasive brain stimulation for the facilitation of corticospinal excitability (CSE). Previous studies have shown that acupuncture applied to acupoints associated with motor function in healthy people can reduce the amplitude of the motor-evoked potentials (MEPs), which reflects the inhibition of CSE. In our work, we wanted to test whether the combination of iTBS and electroacupuncture (EA) would have different effects on CSE in humans. Methods. A single-blind sham-controlled crossover design study was conducted on 20 healthy subjects. Subjects received 20 minutes’ sham or real EA stimulation immediately after sham or real iTBS. MEPs, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), cortical silent period (CSP), and central motor conduction time (CMCT) were recorded before each trial, and immediately, 20 minutes, and 40 minutes after the end of stimulation. Results. In the sham iTBS group, EA produced a reduction in MEPs amplitude, lasting approximately 40 minutes, while in the real iTBS group, EA significantly increased MEPs amplitude beyond 40 minutes after the end of stimulation. In sham EA group, the recorded MEPs amplitude showed no significant trend over time compared to baseline. Among all experiments, there were no significant changes in SICI, ICF, CSP, CMCT, etc. Conclusion. These data indicate that immediate application of EA after iTBS significantly increased corticospinal excitability. This trial was registered in the Chinese Clinical Trial Registry (registration no. ChiCTR1900025348).

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Intermittent theta burst stimulation facilitates functional connectivity from the dorsal premotor cortex to primary motor cortex

PeerJ ◽

10.7717/peerj.9253 ◽

2020 ◽

Vol 8 ◽

pp. e9253

Author(s):

Hai-Jiang Meng ◽

Na Cao ◽

Jian Zhang ◽

Yan-Ling Pi

Keyword(s):

Motor Cortex ◽

Primary Motor Cortex ◽

Premotor Cortex ◽

Intracortical Inhibition ◽

Corticospinal Excitability ◽

Dorsal Premotor Cortex ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Intracortical Facilitation ◽

Theta Burst

Background Motor information in the brain is transmitted from the dorsal premotor cortex (PMd) to the primary motor cortex (M1), where it is further processed and relayed to the spinal cord to eventually generate muscle movement. However, how information from the PMd affects M1 processing and the final output is unclear. Here, we applied intermittent theta burst stimulation (iTBS) to the PMd to alter cortical excitability not only at the application site but also at the PMd projection site of M1. We aimed to determine how PMd iTBS–altered information changed M1 processing and the corticospinal output. Methods In total, 16 young, healthy participants underwent PMd iTBS with 600 pulses (iTBS600) or sham-iTBS600. Corticospinal excitability, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were measured using transcranial magnetic stimulation before and up to 60 min after stimulation. Results Corticospinal excitability in M1 was significantly greater 15 min after PMd iTBS600 than that after sham-iTBS600 (p = 0.012). Compared with that after sham-iTBS600, at 0 (p = 0.014) and 15 (p = 0.037) min after iTBS600, SICI in M1 was significantly decreased, whereas 15 min after iTBS600, ICF in M1 was significantly increased (p = 0.033). Conclusion Our results suggested that projections from the PMd to M1 facilitated M1 corticospinal output and that this facilitation may be attributable in part to decreased intracortical inhibition and increased intracortical facilitation in M1. Such a facilitatory network may inform future understanding of the allocation of resources to achieve optimal motion output.

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