Elsevier

Clinical Neurophysiology

Volume 121, Issue 12, December 2010, Pages 2097-2103
Clinical Neurophysiology

Somatosensory evoked potentials and high frequency oscillations are differently modulated by theta burst stimulation over primary somatosensory cortex in humans

https://doi.org/10.1016/j.clinph.2010.05.014Get rights and content

Abstract

Objective

The effects of theta burst stimulation (TBS) have been extensively investigated in primary motor cortex, where it leads to long-lasting LTP/LTD-like effects on synaptic plasticity. This study aimed to extend these observations to sensory cortex.

Methods

Fourteen healthy subjects participated in the study. Conditioning 600-pulse intermittent TBS (iTBS) and continuous TBS (cTBS) were delivered to left somatosensory cortex (S1) with an intensity of 80% active motor threshold. Somatosensory evoked potentials (SEPs) were evoked by median nerve electrical stimulation at right wrist. High frequency oscillations (HFOs) were obtained by digital filtering of original SEPs and divided into early and late subcomponents, relative to N20peak latency.

Results

Repeated-measures ANOVA showed that iTBS facilitated N20onset–N20peak at 15 min and N20peak–P25 at 15 and 30 min after conditioning, whereas cTBS did not. iTBS left the early and late HFOs unchanged. Conversely, cTBS facilitated the early HFOs, whereas it inhibited the late HFOs at 15 min after conditioning.

Conclusions

S1-iTBS facilitated SEPs without changes in HFOs whereas cTBS modulated early and late HFOs without changes in SEPs.

Significance

S1-TBS produces lasting changes in the excitability of intracortical circuits generating SEPs and HFOs differentially through mechanisms of LTP/LTD-like synaptic plasticity.

Introduction

Plastic changes in the cortical maps of primary somatosensory area (S1) occur in response to several experimental interventions such as manipulation of peripheral sensory inputs (Pons et al., 1991, Buonomano and Merzenich, 1998), repetitive intracortical microstimulation (ICMS) (Recanzone et al., 1992, Dinse et al., 1997, Heusler et al., 2000) and behavioural training protocols (Cheetham et al., 2007). The effects are thought to be relevant for behavioural performance and perceptual learning (Buonomano and Merzenich, 1998, Heusler et al., 2000, Tsodyks and Gilbert, 2004, Cheetham et al., 2007, Feldman, 2009) and probably involve synaptic mechanisms of N-methyl-d-aspartate (NMDA)-dependent long term potentiation (LTP) and long term depression (LTD).

In human studies, recent work has suggested that forms of repetitive transcranial magnetic stimulation (rTMS) can be used as possible probes of synaptic plasticity (Hallett, 2007, Ridding and Rothwell, 2007, Siebner et al., 2009). When applied over the primary motor cortex (M1) a short period of rTMS can lead to after-effects on M1 excitability tested by motor evoked potentials (MEPs) that can last from minutes to hours. The direction (i.e. facilitation or inhibition) and neural populations affected are determined by the train duration, frequency, pattern and intensity of the TMS pulses (Fitzgerald et al., 2006, Hallett, 2007, Ridding and Rothwell, 2007, Siebner et al., 2009).

rTMS also produces after-effects on the human central sensory system. Regular rate rTMS over S1 has not been found to have any effect on SEPs (Enomoto et al., 2001, Ogawa et al., 2004, Restuccia et al., 2007). However, the more recently introduced paradigm of theta burst stimulation (TBS) (Huang et al., 2005) has been more successful: intermittent theta burst stimulation (iTBS) enhances SEPs N20onset–N20peak (Katayama and Rothwell, 2007) whereas continuous theta burst stimulation (cTBS) transiently reduces later SEPs components (P25–N33) (Ishikawa et al., 2007).

Conventional SEPs are also accompanied by high frequency oscillations (HFOs) which consist of oscillatory bursts in the range of 500–1000 Hz superimposed on the early activity of SEPs. HFOs are commonly separated in two subcomponents (early and late) in reference to the N20peak latency. The early subcomponent is thought to be generated by activity of thalamo-cortical and pyramidal neurons whereas the late subcomponent is thought to be related to S1 inhibitory interneuronal activity. Two studies investigating the effect of low frequency S1-rTMS (0.5 Hz and 1 Hz rTMS, respectively) have shown that although it has no effect on conventional SEPs, it does enhance the early component of the HFO while depressing the late component (Ogawa et al., 2004, Restuccia et al., 2007). It has been also shown that 10 Hz rTMS over S1 significantly increases the late subcomponent of HFOs (Restuccia et al., 2007).

In the present study, we have tested whether TBS can also affect HFOs, and whether, as with rTMS, these effects are different to those on conventional SEPs. Finally, given the strong anatomical and functional connections between S1 and M1 (Buonomano and Merzenich, 1998, Heusler et al., 2000, Tsodyks and Gilbert, 2004, Cheetham et al., 2007, Feldman, 2009), we also asked whether S1-TBS had any influence on excitability of M1. Ishikawa et al. (2007) had found that S1-cTBS had no effect on MEP evoked by single pulse TMS of M1: the present work extends this to S1-iTBS.

Section snippets

Subjects

A total of 14 right-handed healthy subjects (11 men and 3 women, aged 24–38 [mean ± SD; 30.2 ± 4.4 years]) participated in the study. Nine of the subjects completed all conditions in a counterbalanced manner; a further five completed only the iTBS paradigm. At least 1 week separated each experimental session (effect of iTBS or cTBS). None of the subjects were taking drugs acting on the central nervous system during any of the experimental sessions. Informed consent was obtained from each subject.

Results

No subjects experienced any unexpected side effects during the experimental sessions.

In summary, iTBS over S1 significantly enhanced N20onset–N20peak at 15 min and N20peak–P25 at 15 and 30 min after conditioning whereas it did not modify HFOs. Conversely, cTBS significantly enhanced early HFOs and inhibited late HFOs at 15 min after conditioning without significant changes in N20onset–N20peak and N20peak–P25. Both iTBS and cTBS left MEPs unchanged. SEPs and HFOs responses recorded in two

Discussion

In the present study, we found that somatosensory evoked potentials and high frequency oscillations are differentially modulated by theta burst stimulation over primary somatosensory cortex in humans. S1-iTBS facilitated N20onset–N20peak at 15 min and N20peak–P25 at 15 and 30 min after conditioning but had no effect on HFOs. In contrast, S1-cTBS facilitated early HFOs and inhibited late HFOs at 15 min but had no effect on the SEP. Finally, we also found that S1-TBS left the excitability of

Acknowledgements

We thank all participants of this study, and Mr. Richard Symonds and Mr. Peter Owbridge for their special technical support.

The author (T.K.) has been funded by The Ito Foundation for the Promotion of Medical Science (Sapporo, Japan).

References (43)

  • S. Ishikawa et al.

    Effect of theta burst stimulation over the human sensorimotor cortex on motor and somatosensory evoked potentials

    Clin Neurophysiol

    (2007)
  • T. Katayama et al.

    Modulation of somatosensory evoked potentials using transcranial magnetic intermittent theta burst stimulation

    Clin Neurophysiol

    (2007)
  • F. Klostermann et al.

    Intrathalamic nonpropagating generators of high-frequency (1000 Hz) somatosensory evoked potential (SEP) bursts recorded subcortically in man

    Clin Neurophysiol

    (2002)
  • R.J. Leo et al.

    Repetitive transcranial magnetic stimulation (rTMS) in experimentally induced and chronic neuropathic pain: a review

    J Pain

    (2007)
  • H. Mochizuki et al.

    Recovery function of and effects of hyperventilation on somatosensory evoked high-frequency oscillation in Parkinson’s disease and myoclonus epilepsy

    Neurosci Res

    (2003)
  • T. Murakami et al.

    High-frequency oscillations change in parallel with short-interval intracortical inhibition after theta burst magnetic stimulation

    Clin Neurophysiol

    (2008)
  • S. Nakano et al.

    The later part of high-frequency oscillations in human somatosensory evoked potentials is enhanced in aged subjects

    Neurosci Lett

    (1999)
  • A. Ogawa et al.

    Slow repetitive transcranial magnetic stimulation increases somatosensory high-frequency oscillations in humans

    Neurosci Lett

    (2004)
  • I. Ozaki et al.

    High frequency oscillations in early cortical somatosensory evoked potentials

    Electroencephalogr Clin Neurophysiol

    (1998)
  • I. Ozaki et al.

    Dipole orientation differs between high frequency oscillations and N20m current sources in human somatosensory evoked magnetic fields to median nerve stimulation

    Neurosci Lett

    (2001)
  • H.R. Siebner et al.

    How does transcranial magnetic stimulation modify neuronal activity in the brain? Implications for studies of cognition

    Cortex

    (2009)
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    These authors contributed equally to this work.

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