Elsevier

Neuroscience

Volume 365, 4 December 2017, Pages 48-56
Neuroscience

Alterations of the amplitude of low-frequency fluctuation in healthy subjects with theta-burst stimulation of the cortex of the suprahyoid muscles

https://doi.org/10.1016/j.neuroscience.2017.09.027Get rights and content

Highlights

  • Low-frequency fluctuations (ALFF) can be used to detect the after-effect of TBS stimulation over swallowing motor cortex.

  • cTBS induces decreased after-effects while iTBS results in increased after-effects on spontaneous brain activation.

  • iTBS can alter the after-effects of cTBS applied on the contralateral swallowing cortex.

Abstract

Theta burst stimulation (TBS) has emerged as a promising tool for the treatment of swallowing disorders; however, the short-term after-effects of brain activation induced by TBS remain unknown. Here, we measured the changes in spontaneous brain activation using the amplitude of low-frequency fluctuation (ALFF) approach in subjects who underwent different TBS protocols. Sixty right-handed healthy participants (male, n = 30; female, n = 30; mean age = 23.5 y) were recruited in this study and randomly assigned to three groups that underwent three different TBS protocols. In group 1, continuous TBS (cTBS) was positioned on the left hemisphere of the suprahyoid muscle cortex. For group 2, intermittent TBS (iTBS) was placed on the left hemisphere of the suprahyoid muscle cortex. Group 3 underwent combined cTBS/iTBS protocols in which iTBS on the right hemisphere was performed immediately after completing cTBS on the left suprahyoid muscle cortex. Compared to pre-TBS, post-cTBS showed decreased ALFF in the anterior cingulate gyrus (BA 32); post-iTBS induced an increase in ALFF in the bilateral precuneus (BA 7); and post-cTBS/iTBS induced a decrease in ALFF in the brainstem, and resulted in increased ALFF in the middle cingulate gyrus (BA 24) as well as the left precentral gyrus (BA 6). Compared the effect of post-TBS protocols, increased ALFF was found in left posterior cerebellum lobe and left inferior parietal lobule (BA 40) (post-cTBS vs post-iTBS), and decreased ALFF exhibited in paracentral lobule (BA 4) (post-iTBS vs post-cTBS/iTBS). These findings indicate that multiple brain areas involved in swallowing regulation after stimulation of TBS over the suprahyoid muscles. cTBS induces decreased after-effects while iTBS results in increased after-effects on spontaneous brain activation. Moreover, iTBS can eliminate the after-effects of cTBS applied on the contralateral swallowing cortex and alter the activity of contralateral motor cortex and brainstem. Our findings provide a novel evidence for the short-term effect of TBS on spontaneous brain activation.

Introduction

Swallowing is an essential life-sustaining function. Historically, the central neural control of swallowing was believed to be almost entirely dependent on brainstem reflexive mechanisms, which are thought to play a crucial role in the planning and execution of safe swallowing (Torii et al., 2012); however, in recent years, with the development of brain imaging and noninvasive brain stimulation techniques, the notion that the bilateral cerebral system is involved in human swallowing is increasingly accepted (Kern et al., 2001, Martin et al., 2001, Doeltgen et al., 2015). Dysphagia has a huge impact on quality of life and is associated with malnutrition and aspiration pneumonia and results in high mortality (Doeltgen et al., 2015); however, efficient treatment options for dysphagia recovery are still limited. Recently, rehabilitation-based interventions have been proposed for the treatment of dysphagia (Cabib et al., 2016). A large number of studies have reported that repetitive transcranial magnetic stimulation (rTMS) could change the excitability of the swallowing-associated motor cortex and result in an improvement of swallowing function in unilateral post-stroke dysphagic patients (Khedr et al., 2009, Yang et al., 2012). These findings indicated that rTMS is an effective treatment to induce cortical plasticity after stroke (Khedr et al., 2009, Verin and Leroi, 2009). rTMS was believed to induce a lasting effect on cortical excitability at the site of stimulation and on remote sites that are functionally connected with the target region (Suppa et al., 2008). Furthermore, the newly proposed theta burst stimulation (TBS), a novel form of rTMS employing a lower intensity relative to conventional rTMS protocols, to increase or reduce cortical excitability in subjects for up to 60 min after the end of stimulation, became a promising tool for cortical reorganization after stroke (Huang et al., 2005). Interestingly, different patterns of TBS delivery have opposite effects on the synaptic efficiency of the stimulated cortex. Increased cortical excitability is primarily found with intermittent stimulation, e.g., intermittent theta-burst stimulation (iTBS), while a single uninterrupted stimulation such as continuous TBS (cTBS) tends to suppress cortical excitability (Gamboa et al., 2010, Rahnev et al., 2013). Recent studies detected alterations of the motor-evoked potential (MEP) on the pharyngeal muscles induced by TBS (Huang and Mouraux, 2015, Suppa et al., 2016); however, few studies have ever explored the effect of TBS on the motor cortex excitability of swallowing muscles (Gow et al., 2004). Moreover, little is known about the alteration of spontaneous neuronal activity following the application of different patterns of TBS on the swallowing cortex.

Recently, there has been much interest in exploring the neural substrates of the human brain using resting-state fMRI (rs-fMRI). Low-frequency (0.01–0.08 Hz) fluctuations (LFF) in rs-fMRI are considered to be physiologically important and closely related to spontaneous neural activities in the brain (Biswal et al., 1995, Fox and Raichle, 2007). There are a number of strategies that can be adopted for studying rs-fMRI. Among them, a newly proposed approach, known as low-frequency fluctuations (ALFF), aims to measure the amplitude of low-frequency oscillations (LFOs) quantitatively, was introduced to detect local blood-oxygen level dependent (BOLD) signal variation due to regional spontaneous activity (Zang et al., 2007). This method tests the whole-brain BOLD activity strength on a voxel-wise basis. Studies of rs-fMRI in healthy subjects have indicated that ALFF is able to identify physiological states of the brain (Yang et al., 2007, Zou et al., 2013). Furthermore, this method has been increasingly used to investigate spontaneous brain activity in patients with neural disorders including ADHD (Zang et al., 2007, Yang et al., 2011), schizophrenia (Huang et al., 2010), Alzheimer’s disease (Wang et al., 2011), and MDD (Jiao et al., 2011, Wang et al., 2012); however, to our best knowledge, no study has used ALFF to examine the spontaneous activity alterations induced by TBS application on the swallowing cortex.

The suprahyoid muscles play an important role in the forward and upward movement of the hyoid-throat complex in the process of swallowing (Furukawa et al., 2000, Spek et al., 2008) and were frequently regarded as the target swallowing muscles for the treatment of patients with dysphagia (Hybels et al., 2001, Wichniak et al., 2011, Morgan et al., 2012). The aim of this work was to explore the spontaneous brain activity alterations induced by different TBS protocols applied on the cortex of the suprahyoid muscles. We hypothesized that cTBS and iTBS targeted to the suprahyoid muscles related brain cortex would result in opposite effects on spontaneous brain activity. Additionally, it was reported that the reduction of swallowing response time following the initial ‘virtual lesion’ induced by applying inhibitory TMS was reversed by the subsequent exciting TMS (Mistry et al., 2007). Another study found that contralesional hemispheric reorganisation was associated with spontaneous recovery of swallowing function following stroke (Hamdy et al., 1996). These results indicate the importance of interhemispheric balance for swallowing motor function. Given the cTBS placed on the left cortex of suprahyoid muscles could be used as ‘virtual lesion’ in the present study, we hypothesized that the subsequent iTBS on the contralateral motor cortex would alter the effect of cTBS. To test these hypotheses, we compared the spontaneous brain activity alterations induced by different patterns of TBS applied on the motor cortex of the suprahyoid muscles using the ALFF approach.

Section snippets

Participants

Sixty right-handed, young, healthy participants (male, n = 30; female, n = 30; mean age = 23.5 ± 4.4 years) were recruited from a local community through advertisements for this study. All of the volunteers were free of neurological and/or psychiatric disorders, any previous exposure to neuropsychiatric medications, previous swallowing disorders, or previous experience of enrollment in TMS and MRI studies. All the participants had no regular smoking or drinking tea. The subjects were randomly assigned

Statistical analysis

Demographics including age and gender were compared between the three groups. Categorical data were analyzed with the Chi-square test, and continuous variables were analyzed with one-way analysis of variance (ANOVA) using SPSS 16.0 (SPSS Inc., Chicago, IL, USA). p < 0.05 was considered statistically significant. A one-way ANOVA was used to compare the baseline ALFF in three groups using REST software. A paired t-test was performed to investigate the difference in ALFF maps between the post-TBS

Demographic comparison

The demographic data are presented in Table 1. There were no significant differences between the three groups in gender and age (p > 0.05).

ALFF comparison among three groups in pre-TBS condition

No significant difference in ALFF with pre-TBS among the three groups (p > 0.05).

ALFF comparison between post-TBS and pre-TBS condition in the three groups

Compared with pre-cTBS, post-cTBS applied on the left motor cortex of the suprahyoid muscles showed decreased ALFF in the anterior cingulate gyrus (ACC) (BA 32) (Table 2 and Fig. 1A).

Compared to the condition of pre-iTBS, post-iTBS applied on the left motor cortex of the suprahyoid

Discussion

This study explores alterations in the spontaneous neural activity in a resting-state between different patterns of TBS stimulation applied on the motor cortex of the suprahyoid muscles. Compared to baseline, cTBS placed on the left motor cortex of the suprahyoid muscles led to decreased ALFF on the anterior cingulate gyrus and iTBS produced increased ALFF on the bilateral precuneus respectively. Furthermore, we found that iTBS can eliminate the effect induced by cTBS on the contralateral motor

Author contributions

X.H.W. contributed in the experimental design and writing of the manuscript. C.H.G., Y.L.L. and X.H.R. were involved in literature review, data collection, and writing of the manuscript. L.L.L., S.D.Y. and X.C. contributed to the analysis of MRI data. L.S.J. and Y.L.L. was involved in the data collection. G.Q.X. and Y.L. contributed in the experimental design, and in the writing process.

Acknowledgments

This research was partly supported by the the National Science Foundation of China (grant no. 81371441 and 81572230 for Yue Lan), the Guangdong Provincial Science and Technology Program (grant no. 2013B051000036 and 2014B020212001 for Yue Lan), the Guangzhou Municipal Science and Technology Program (grant no. 2016201604030036 for Yue Lan), Science and Technology Planning Project of Guangdong Province (grant no. 2013B021800063 for Xinhua Wei) and the Science and Technology Planning Project of

References (56)

  • S. Kaderali et al.

    The role of human brain area hMT+ in the perception of global motion investigated with repetitive transcranial magnetic stimulation (rTMS)

    Brain Stimulat

    (2015)
  • S.Y. Lowell et al.

    Sensory stimulation activates both motor and sensory components of the swallowing system

    NeuroImage

    (2008)
  • A.T. Sack

    Parietal cortex and spatial cognition

    Behav Brain Res

    (2009)
  • P. Talelli et al.

    Exploring Theta Burst Stimulation as an intervention to improve motor recovery in chronic stroke

    Clin Neurophysiol

    (2007)
  • A. Wichniak et al.

    Patients with insomnia and subthreshold depression show marked worsening of insomnia after discontinuation of sleep promoting medication

    Prog Neuropsychopharmacol Biol Psychiatry

    (2011)
  • H. Yang et al.

    Amplitude of low frequency fluctuation within visual areas revealed by resting-state functional MRI

    NeuroImage

    (2007)
  • H. Yang et al.

    Abnormal spontaneous brain activity in medication-naive ADHD children: a resting state fMRI study

    Neurosci Lett

    (2011)
  • M.J. Alberts et al.

    Aspiration after stroke: lesion analysis by brain MRI

    Dysphagia

    (1992)
  • A. Babaei et al.

    Intrinsic functional connectivity of the brain swallowing network during subliminal esophageal acid stimulation

    Neurogastroenterol Motil

    (2013)
  • B. Biswal et al.

    Functional connectivity in the motor cortex of resting human brain using echo-planar MRI

    Magn Reson Med

    (1995)
  • C. Cabib et al.

    Neurorehabilitation strategies for poststroke oropharyngeal dysphagia: from compensation to the recovery of swallowing function

    (2016)
  • S.B. Eickhoff et al.

    The human parietal operculum. II. Stereotaxic maps and correlation with functional imaging results

    Cereb Cortex

    (2006)
  • C. Ertekin

    Voluntary versus spontaneous swallowing in man

    Dysphagia

    (2011)
  • M.D. Fox et al.

    Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging

    Nat Rev Neurosci

    (2007)
  • O.L. Gamboa et al.

    Simply longer is not better: reversal of theta burst after-effect with prolonged stimulation

    Exp Brain Res

    (2010)
  • S. Hamdy et al.

    The cortical topography of human swallowing musculature in health and disease

    Nat Med

    (1996)
  • S. Hamdy et al.

    Identification of the cerebral loci processing human swallowing with H2(15)O PET activation

    J Neurophysiol

    (1999)
  • G. Huang et al.

    MEP latencies predict the neuromodulatory effect of cTBS delivered to the ipsilateral and contralateral sensorimotor cortex

    PLoS ONE

    (2015)
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    Xiuhang Ruan, Guangqing Xu and Cuihua Gao contributed equally to this article and should be considered co-first authors.

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