brain research 1557 (2014) 83–89
Available online at www.sciencedirect.com
www.elsevier.com/locate/brainres
Research Report
Influence of position and stimulation parameters on intracortical inhibition and facilitation in human tongue motor cortex Mohit Kotharia,c,n, Peter Svenssona,b, Jørgen Feldbæk Nielsenc, Lene Baad-Hansena a
Section of Clinical Oral Physiology, Department of Dentistry, Aarhus University, Aarhus C, Denmark MINDLab, Center for Functionally Integrative Neuroscience, Aarhus University Hospital, Aarhus C, Denmark c Hammel Neurorehabilitation and Research Centre, Research Unit, Hammel, Denmark b
art i cle i nfo
ab st rac t
Article history:
Paired-pulse transcranial magnetic stimulation (ppTMS) can be used to assess short-interval
Accepted 7 February 2014
intracortical inhibitory (SICI) and facilitatory (ICF) networks. Many methodological parameters
Available online 15 February 2014
may however influence the outcome. The aim of the study was to examine the influence of
Keywords:
body positions (recline and supine), inter-stimulus intervals (ISI) between the test stimulus (TS)
Paired pulse transcranial magnetic
and conditioning stimulus (CS) and intensities of the TS and CS on the degree of SICI and ICF.
stimulation (ppTMS)
In studies 1 and 2, fourteen and seventeen healthy volunteers participated respectively. ppTMS
Short-interval intra-cortical
was applied over the “hot-spot” of the tongue motor cortex and motor evoked potentials (MEPs)
inhibitory (SICI) and facilitatory (ICF)
were recorded from contralateral tongue muscles. In study 1, single pulse and three ppTMS ISIs,
Test stimulus (TS)
2, 10, and 15 ms, were applied 8 times each in three blocks (TS: 120%, 140% and 160% of resting
Conditioning stimulus (CS)
motor threshold (rMT); CS: 80% of rMT) in two different body positions (recline and supine)
Body positions
randomly. In study 2, single pulse and four ppTMS ISIs, 2, 2.5, 3, and 3.5 ms, were applied 8 times each in randomized order in two blocks (CS: 70% and 80% of rMT; TS: 120% of rMT). There was a significant effect of body position (P¼ 0.049), TS intensities (Po0.001) and ISIs (Po0.001) and interaction between intensity and ISIs (P¼0.042) in study 1. In study 2, there was a significant effect of ISI (Po0.001) but not CS intensity (P¼0.984) on MEP amplitude. These results may be applied in future studies on the mechanisms of cortical plasticity in the tongue motor pathways using ppTMS and SICI and ICF. & 2014 Elsevier B.V. All rights reserved.
1.
Introduction
Transcranial magnetic stimulation (TMS) is a widely used, non-invasive and pain free technique to assess the functional n
integrity of descending corticospinal and corticoneural pathways in the human motor cortex through the intact scalp (Abbruzzese and Trompetto, 2002; Baad-Hansen et al., 2009; Curra et al., 2002; Muellbacher et al., 2001; Rogasch and
Corresponding author. Fax: þ45 86195665. E-mail addresses: [email protected], [email protected] (M. Kothari).
http://dx.doi.org/10.1016/j.brainres.2014.02.017 0006-8993 & 2014 Elsevier B.V. All rights reserved.
84
brain research 1557 (2014) 83–89
Fitzgerald, 2012; Rothwell, 1997; Tyc and Boyadjian, 2006). Several studies on corticomotor control with TMS have demonstrated changes in motor evoked potentials (MEPs) in human limb muscles following modulation of, for example, spinally innervated muscles (Blicher and Nielsen, 2009; Lotze et al., 2003; Perez et al., 2004; Ridding et al., 1995; Rothwell, 1997; Ziemann et al., 1996) but relatively little is known about the regulation of the cranial nerve innervated human tongue muscles (Baad-Hansen et al., 2009; Halkjaer et al., 2006; Muellbacher et al., 2001; Svensson et al., 2003, 2006). A rapid and controlled coordination of sensory and motor function is essential for a number of complex orofacial behaviors involving the tongue muscles, such as swallowing, mastication, respiration, and speech (Furuya et al., 2012; Hiiemae and Palmer, 2003; Sawczuk and Mosier, 2001). Tongue muscle related TMS studies show that acquisition of new motor skills, application of experimental intra-oral pain, or sensory deprivation by a lingual nerve block lead to significant shortterm changes in corticomotor control of the tongue muscles in humans (Adachi et al., 2008; Boudreau et al., 2007, 2013; Halkjaer et al., 2006; Kothari et al., 2013; Sessle et al., 2005; Svensson et al., 2003, 2006). Intracortical circuits in the motor cortex can be activated at TMS intensity below that required to activate the descending motor pathways (Di Lazzaro et al., 1998; Kujirai et al., 1993; Ziemann et al., 1996). With a subthreshold conditioning stimulus (CS) followed by suprathreshold test stimulus (TS), short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) can be studied (Kujirai et al., 1993), with the so-called paired-pulse TMS (ppTMS) technique. The underlying neural mechanisms that accompany changes in cortical plasticity are unclear but ppTMS studies have revealed that a motor training task of the limbs causes rapid disinhibition within intra-cortical circuits (Blicher et al., 2009; Garry et al., 2004; Liepert et al., 1998). SICI and ICF related to motor function of the hands, arm, and leg have been examined (Blicher and Nielsen, 2009; Lotze et al., 2003; Perez et al., 2004) and there are very few studies describing these mechanisms in detail for cranial muscles (Baad-Hansen et al., 2009; Muellbacher et al., 2001). SICI and ICF vary with the level of pre-activation of the targeted muscle and the intensities of CS and TS (Muellbacher et al., 2001; Reis et al., 2008). Romaniello et al. (2000) suggested that the use of preactivation levels is essential to evoke masseter muscle MEPs. In contrast, pre-activation of the tongue muscles is not needed in order to evoke MEPs in the tongue motor cortex (Baad-Hansen et al., 2009; Boudreau et al., 2007; Halkjaer et al., 2006; Kothari et al., 2013; Svensson et al., 2006, 2003). This is an advantage in intervention studies, since the level of pre-activation may potentially introduce difficulties in interpretation of training effects on intra-cortical mechanism due to difficulties in matching pre-activation levels before and after training (Baad-Hansen et al., 2009; Romaniello et al., 2000). However, the body position of the participant may potentially influence the baseline level of EMG activity of the tongue muscles (Otsuka et al., 2000; Pae et al., 1994; Sauerland and Mitchell, 1975). It has been reported that tonic tongue muscle EMG activity (as well as phasic activity related to spontaneous respiration) increases significantly in the supine position with respect to the upright position, to counteract
the relapse of the tongue, thus maintaining adequate upper airway patency (Otsuka et al., 2000; Pae et al., 1994; Sauerland and Mitchell, 1975). Presently, there are no studies exploring the influence of the body positions, stimulus intensity of the conditioning and test stimulus and different interstimulus intervals (ISIs) between the CS and TS without pre-activation of the tongue muscles in the detection of possible intracortical effects in the tongue motor area. The aims of the present study were: (1) to examine the influence of body positions (recline and supine) and different ISI (2, 10 and 15 ms) between the TS (3 different intensities: 120%, 140% and 160% of resting motor threshold (rMT)) and CS (80% of rMT) on intracortical modulatory mechanisms and (2) to examine the influence of different intensities of the CS (70% and 80% of rMT) with a constant TS (120% of rMT) on the degree of SICI (2, 2.5, 3 and 3.5 ms).
2.
Results
MEPs from the tongue could be evoked in all participants. However, the waveforms of the tongue varied between participants and simple biphasic MEPs as well as more complex and polyphasic MEPs were encountered (Fig. 1). The mean rMT of the tongue motor cortex for study 1 was 52.571.9% irrespective of the body positions (recline and supine) and for study 2 it was 55.072.0% of the maximum output of the magnetic stimulator.
2.1.
Study 1
2.1.1.
Effect of body positions (recline and supine)
For tongue motor cortex stimulation there was an overall effect of body positions (P¼ 0.049) in the analysis on absolute values. Post-hoc test revealed that the recline position was significantly different from the supine position (P ¼0.050), showing higher MEP amplitude in the recline position compared to the supine position (Fig. 1). There was no effect of body positions (P¼ 0.580) in normalized (relative) analysis.
2.1.2. Effect of test stimulus intensity and interstimulus interval In the analysis on absolute values, there was an overall effect of TS intensities (120%, 140% and 160% of rMT; P ¼0.004) and ISI (single pulse, 2, 10 and 15 ms; Po0.001) (Fig. 2). Post-hoc test showed that 160% TS was significantly different from 120% TS (P ¼0.003) showing higher MEP amplitudes. There was no significant difference between 120% TS and 140% TS (P ¼0.190) or between 140% TS and 160% TS (P¼ 0.150). Another post-hoc test revealed that statistically significant SICI was present during ppTMS with ISI of 2.0 ms (P¼ 0.021) and significant ICF was present during ppTMS stimulation with ISI of 10 ms (P ¼0.050) and 15 ms (P¼ 0.010) compared with single pulse stimulation (Fig. 2). There was a significant interaction between TS intensities and ISIs (P ¼0.002). The post-hoc test showed that TS intensities of 140% and 160% of rMT induced significantly higher MEPs compared with 120% of rMT for single pulse (Po0.001), 10 ms (Po0.001) and 15 ms (Po0.001). Even 160% of rMT induced significantly higher
brain research 1557 (2014) 83–89
85
Fig. 2 – Mean7SEM absolute motor evoked potentials (MEPs) from paired-pulse transcranial magnetic stimulation (ppTMS) and single pulse TMS. Three different stimulus intensities of the test stimulus (TS) were applied with different interstimulus intervals (single pulse, ppTMS with ISIs: 2.0, 10, and 10.5 ms) between the TS and conditioning stimulus (80% of resting motor threshold (rMT)). MEPs were recorded from the contralateral side of the tongue dorsum. n indicates overall significant difference from single pulse, i.e. significant intracortical facilitation (ICF) and short-interval intracortical inhibition (SICI) (Po0.001). Fig. 1 – Example of single (last) sweep tongue motor evoked potentials from the contralateral side of the tongue dorsum of one healthy volunteer at two different body positions (recline and supine) evoked by paired-pulse transcranial magnetic stimulation (ppTMS) with test stimulus of 160% of resting motor threshold combined with a conditioning stimulus of 80% of rMT. Different interstimulus intervals of 2, 10, and 15 ms and single stimulation were applied.
MEPs compared with 140% of rMT for single pulse stimulation (P¼ 0.030), 10 ms (Po0.001) and 15 ms (Po0.001). Finally, 160% of rMT TS intensity showed higher MEPs compared with 120% of rMT for 2 ms (Po0.001). In the analysis on normalized data, which was performed to evaluate the effect of TS intensities and ISIs on the degree of SICI and ICF, there was no significant main effect of TS intensities (P¼ 0.063) but there was an overall significant effect of ISI (Po0.001). A post-hoc test revealed that based on the normalized data no statistically significant SICI was present during ppTMS with ISI of 2.0 ms (P¼0.800) but significant ICF was present during ppTMS stimulation with ISI of 10 ms (Po0.001) and 15 ms (Po0.001) compared with single pulse stimulation. There was a statistically significant interaction between TS intensities and ISIs (P¼ 0.042). The post-hoc test showed that for TS intensity of 120% of rMT, there was no significant SICI (P¼ 0.999) but there was significant ICF at ISIs of 10 and 15 ms compared with single pulse (Po0.001). At 140% and 160% of rMT, no significant SICI or ICF was detected
compared with single pulse (P40.225). Between the TS intensities, 120% of rMT induced higher degrees of ICF compared with 140 and 160% of rMT (Po 0.028). There was no significant difference in the degree of SICI (P¼ 1.00) or ICF (P¼1.00) between 160% and 140% of rMT.
2.2.
Study 2
2.2.1. Effect of conditioning stimulus intensity and interstimulus interval For tongue motor cortex stimulation, there was no significant difference in MEPs between the two CS intensities (70% and 80% of rMT; P¼ 0.984) but there was an overall effect of ISI on MEP amplitudes (Po0.001). Post-hoc tests revealed that statistically significant SICI was present during ppTMS stimulation with 2.0 ms (P¼ 0.003), 2.5 ms (P ¼0.002), 3.0 ms (Po0.001), and 3.5 ms (Po0.001) compared with single pulse stimulation (Fig. 3). However, there was no significant difference in the degree of SICI induced by ISIs of 2.0, 2.5, 3.0, or 3.5 ms (P40.982). There was no significant interaction between different intensities of CS and ISIs (P ¼0.790).
3.
Discussion
In this study, tongue MEPs could be evoked by TMS in accordance with earlier studies with similar amplitudes and activation thresholds (Baad-Hansen et al., 2009; Kothari et al., 2013;
86
brain research 1557 (2014) 83–89
Fig. 3 – Mean7SEM motor evoked potentials (MEPs) from paired-pulse transcranial magnetic stimulation (ppTMS) normalized to single pulse TMS. Two different stimulus intensities of the conditioning stimulus (CS) were applied with different interstimulus intervals (single pulse, ppTMS with ISIs: 2.0, 2.5, 3.0, and 3.5 ms) between the CS and test stimulus. MEPs were recorded from the contralateral side of the tongue dorsum. n indicates significant difference from single pulse, i.e. significant short-interval intracortical inhibition (SICI) (Po0.003).
Svensson et al., 2003, 2006; Taylor and Gandevia, 2001). The main finding of the study 1 was that reclined body position produced significantly higher tongue MEPs compared to when participants were in supine position. Some studies on healthy participants have shown that changes in static position of the shoulder influences the corticospinal excitability of an intrinsic hand muscle, as tested by TMS at rest (Ginanneschi et al., 2005; Mazzocchio et al., 2008). However, to our knowledge there has been no study performed to find the effect of body positions (recline and supine) on tongue MEPs but there are various studies performed to find the effect of tongue position and body positions on swallowing or speech (Buchaillard et al., 2009; Inagaki et al., 2009a, 2009b; Stone et al., 2007). The present finding may be an important addition to the knowledge about the neurophysiology of the tongue motor cortex and the tongue muscles in different body positions. The difference in MEP size between body positions may be due to different tongue positions and thereby possibly different levels of muscle activity. However, drowsiness while being in supine position may also have played a role as a number of physiological changes occur during bedrest (supine position), such as changes in baroreflex function, a decrease in vagal tone and a loss of circulatory blood volume (Kamiya et al., 1998).
The second main finding of the study 1 was that the three different TS intensities and 4 different ISIs (single pulse stimulation, 2, 10 and 15 ms) evoked different degrees of SICI and ICF of the MEP responses. It has been shown that ICF tends to be weaker with increasing TS intensity in the FDI (Daskalakis et al., 2004) muscle and this was also the case in our present study. It is still a point of research to find whether ICF may be merely a ‘rebound’ phenomenon from the robust inhibition at shorter interstimulus interval or whether it represents a different phenomenon (Daskalakis et al., 2004). Ziemann et al. (1996) concluded that separate neuronal populations were likely to mediate intracortical inhibition and facilitation. When comparing the present study data with the Muellbacher et al. study, it is important to notice that the present study data was carried out using stimulus intensities of the test and conditioning stimulus relative to the rMT and not to the active MT (Muellbacher et al., 2001). The main finding of the study 2 was that the two stimulus intensities of the CS and 4 different short ISIs evoked similar degrees of SICI of the MEP responses. In the present study, statistically significant SICI in the contralateral tongue motor cortex was demonstrated with 4 different ISIs (2, 2.5, 3, and 3.5 ms) compared to single pulse stimulation. Ziemann et al. (1996) demonstrated that in the abductor digiti minimi (ADM) muscle, SICI occurs at lower CS intensities than ICF, becoming stronger with increasing intensities. In comparison with our earlier study where only 2.0 and 3.0 ms ISI between the CS and the TS were applied (Baad-Hansen et al., 2009), we also applied 2.5 and 3.5 ms ISIs, since it has been shown for spinally innervated muscles that short-interval intracortical facilitation (SICF) occurs within this time interval (Peurala et al., 2008). In summary, none of the two stimulus intensities of the CS and the short ISIs were superior to the others in inducing intracortical modulatory effects. As in our earlier study, the wave-forms in the present study varied between participants and simple biphasic MEPs as well as more complex and polyphasic MEPs were encountered (Baad-Hansen et al., 2009). We have previously analyzed the correlation between peak-to-peak amplitudes and area under the curve (AUC) of tongue MEPs and since it was shown that there was a highly significant correlation between these two methods of quantification, we decided to use the peakto-peak amplitude in this study (Baad-Hansen et al., 2009). The knowledge about control of spinally innervated muscles may not apply in the same way to the cranial muscles, since the organization of the cranial and spinal sensorimotor systems differs in many ways (Cohen et al., 1993; Ridding et al., 2000). This demands to perform studies in both systems. In our previous study on the effect of simple tongue protrusion training on SICI and ICF in the tongue motor cortex, no training-induced changes were observed using TS intensity of 120% and CS intensity of 80% of rMT (Baad-Hansen et al., 2009) in contrast to limb studies (Blicher and Nielsen, 2009; Garry et al., 2004; Liepert et al., 1998). In addition, training-induced cortical plasticity was observed in different tongue training paradigms and further documented that plasticity was evident within 30 min post-training and may last up to at least 7 days (Kothari et al., 2013; Svensson et al., 2003, 2006). In conclusion, recline body position evoked larger MEPs than in supine position. Significantly greater ICF was evoked
brain research 1557 (2014) 83–89
with 120% TS compared with 140 and 160% TS intensities. None of the two CS stimulus intensities in study 2 were superior to the others in inducing intracortical modulatory effects. These methodological results indicate that future studies on cortical plasticity and the effect of tongue training on intracortical modulatory mechanisms in the tongue motor cortex should of course carefully standardize stimulus parameters but also body position during TMS measurements.
4.
Experimental procedures
4.1.
Participants
Two different studies were performed and for both studies, inclusion criteria were as follows: ability to read and understand the project information. Exclusion criteria were as follows: subjects with medical, physical or psychological disorders, metal implants in head, history of epilepsy, pacemaker/medicinal pumps and pregnant woman (Wassermann, 1998). All participants gave informed consent and received financial compensation for their participation. The study was approved by the local ethics committee and performed in accordance with the Helsinki Declaration II. The session lasted approximately 1 h. In study 1, sixteen healthy participants (8 men and 8 women, aged 20–35 years, mean (7SEM) age of 27.471.9 years) were recruited at Department of Dentistry, Aarhus University where the study was performed. Two participants did not complete the study due to difficulties to locate the tongue hot-spot in the motor cortex. Thus, fourteen healthy participants completed the study (8 men and 6 women, aged 20–32 years, mean (7SEM) age of 26.871.8 years). In study 2, twenty healthy participants (9 men and 11 women, aged 19–67 years, mean (7SEM) age of 24.972.3 years) were recruited. Three subjects did not complete the study: one due to discomfort and two due to difficulties to locate the tongue hot-spot in the motor cortex. Thus, seventeen healthy participants completed the study (8 men and 9 women, aged 19–31 years, mean (7SEM) age of 22.670.8 years).
4.2.
Recording of motor evoked potentials
For both studies 1 and 2, the participants were placed on a patient examination table in supine position with the head tilted towards the right side and supported by a headrest (Kothari et al., 2013). In addition to supine position, participants in study 1 were also instructed to sit in a dental chair in a recline position to examine the influence of body positions. A swimming cap was placed over the head and anatomical features were marked with a pen to secure a stable position of the cap (Baad-Hansen et al., 2009; Halkjaer et al., 2006; Kothari et al., 2013; Svensson et al., 2003, 2006). Electromyographic (EMG) activity was recorded from the right side of the tongue dorsum (Baad-Hansen et al., 2009; Halkjaer et al., 2006; Kothari et al., 2013). Disposable self-adhesive silver chloride electrodes (Alpine Biomed, Denmark, Type 9013S0225) were placed on the right dorsal surface of the tongue (2–3 mm from midline, 10 mm from tongue tip) with an inter-electrode distance of 20 mm (Baad-Hansen et al., 2009; Halkjaer et al., 2006;
87
Svensson et al., 2003, 2006). The electrodes were connected to the amplifier to allow bipolar registration of contralateral MEPs. The EMG signals were amplified, filtered (20 Hz–1 kHz), and stored on Viking Select (Nicolet, California, USA) (Baad-Hansen et al., 2009; Halkjaer et al., 2006; Svensson et al., 2006, 2003). Transcranial magnetic stimuli (Magstim 200, The Magstim Co. Ltd., Whitland, UK, peak magnetic field¼ 2 T) were delivered with a 5-cm diameter figure-of-eight coil to the left side of the scalp (Baad-Hansen et al., 2009; Halkjaer et al., 2006; Kothari et al., 2013; Svensson et al., 2003, 2006). The coil of the stimulator was oriented 451 obliquely to the sagittal midline so that the induced current flowed in a plane perpendicular to the estimated alignment of the central sulcus (BaadHansen et al., 2009; Halkjaer et al., 2006; Svensson et al., 2006). With constant stimulus intensity, the stimulator coil was moved over the left hemisphere to determine the optimal position to elicit maximal MEP amplitudes in the tongue muscle. Three markings on the coil helped to identify the position in relation to the scalp sites. The scalp site at which EMG responses were evoked in the tongue at lowest stimuli strength (hot spot) was determined and marked with a pen on the cap (Baad-Hansen et al., 2009; Halkjaer et al., 2006; Kothari et al., 2013; Svensson et al., 2003, 2006). The rMT contralateral to stimulation was measured in the relaxed muscles with the use of descending and ascending method of limits and was defined as the minimum stimulus intensity that produced five out of ten discrete MEPs clearly discernible on the monitor from background EMG activity (tongue MEPZ5 mv) (Baad-Hansen et al., 2009; Halkjaer et al., 2006; Svensson et al., 2003).
4.3.
Intracortical excitability
Intracortical excitability was assessed according to a ppTMS protocol (Baad-Hansen et al., 2009; Di Lazzaro et al., 1998; Kujirai et al., 1993; Muellbacher et al., 2001; Ziemann et al., 1996). The ppTMS protocol consisted of a paired conditioning and test stimulus paradigm with a subthreshold CS and suprathreshold TS at different interstimulus intervals (ISIs) (Baad-Hansen et al., 2009; Muellbacher et al., 2001). MEP amplitudes of the averaged signals were measured peak to peak. In study 1, the four stimulus conditions (single pulse, ISIs: 2, 10, and 15 ms) were applied 8 times each in three blocks (TS: 120%, 140% and 160% of rMT) and averaged for two different body positions (recline and supine in randomized order). In one block, the intensity of TS was set at 120% of the contralateral rMT (block 1), and in the other block, it was set at 140% of the contralateral rMT (block 2) and in third block, it was set at 160% of the contralateral rMT (block 3) with constant CS (80% of rMT) irrespective of blocks. In study 2, four ISIs (2, 2.5, 3 and 3.5 ms) were tested and randomly intermixed with single stimulation with the TS. The five stimulus conditions (single pulse, ISIs: 2, 2.5, 3 and 3.5 ms) were applied 8 times each in two blocks and averaged. In one block, the intensity of CS was set at 70% of the contralateral rMT (block 1), and in the other block, it was set at 80% of the contralateral rMT (block 2) with constant TS
88
brain research 1557 (2014) 83–89
(120% of rMT) irrespective of blocks. The orders of the blocks were randomized.
4.4.
Statistics
All data were presented as means7SEM. In study 1, two different analyses were performed: (1) absolute averaged MEPs from ppTMS were analyzed using repeated measurement (RM) of analysis of variance (ANOVA) with body position, TS stimulation intensity and ISI as RM factors and (2) normalized (relative) averaged MEPs (averaged MEPs from ppTMS normalized to averaged MEPs from single pulse TMS) were analyzed using RM of ANOVA with body position, TS stimulation intensity and ISI as RM factors. In study 2, normalized averaged MEPs were analyzed using RM of ANOVA with CS stimulus intensity and ISI as RM factors. When appropriate, Tukey' honestly significant difference (HSD) tests with correction for multiple comparisons were performed as post-hoc tests. Values of P less than 0.05 were considered statistically significant.
Acknowledgments Funding: Danish Dental Association and Aarhus University Research Foundation. Ethical approval: Local Ethics committee, Central Denmark Region.
references
Abbruzzese, G., Trompetto, C., 2002. Clinical and research methods for evaluating cortical excitability. J. Clin. Neurophysiol. 19, 307–321. Adachi, K., Ding, M., Surrey, S., 2008. Role of the beta4Thr– beta73Asp hydrogen bond in HbS polymer and domain formation from multinucleate-containing clusters. Biochemistry 47, 5441–5449. Baad-Hansen, L., Blicher, J.U., Lapitskaya, N., Nielsen, J.F., Svensson, P., 2009. Intra-cortical excitability in healthy human subjects after tongue training. J. Oral Rehabil. 36, 427–434. Blicher, J.U., Jakobsen, J., Andersen, G., Nielsen, J.F., 2009. Cortical excitability in chronic stroke and modulation by training: a TMS study. Neurorehabil. Neural Repair 23, 486–493. Blicher, J.U., Nielsen, J.F., 2009. Cortical and spinal excitability changes after robotic gait training in healthy participants. Neurorehabil. Neural Repair 23, 143–149. Boudreau, S., Romaniello, A., Wang, K., Svensson, P., Sessle, B.J., Arendt-Nielsen, L., 2007. The effects of intra-oral pain on motor cortex neuroplasticity associated with short-term novel tongue-protrusion training in humans. Pain 132, 169–178. Boudreau, S.A., Lontis, E.R., Caltenco, H., Svensson, P., Sessle, B.J., Andreasen Struijk, L.N., Arendt-Nielsen, L., 2013. Features of cortical neuroplasticity associated with multidirectional novel motor skill training: a TMS mapping study. Exp. Brain Res. 225, 513–526. Buchaillard, S., Perrier, P., Payan, Y., 2009. A biomechanical model of cardinal vowel production: muscle activations and the impact of gravity on tongue positioning. J. Acoust. Soc. Am. 126, 2033–2051. Cohen, L.G., Brasil-Neto, J.P., Pascual-Leone, A., Hallett, M., 1993. Plasticity of cortical motor output organization following
deafferentation, cerebral lesions, and skill acquisition. Adv. Neurol. 63, 187–200. Curra, A., Modugno, N., Inghilleri, M., Manfredi, M., Hallett, M., Berardelli, A., 2002. Transcranial magnetic stimulation techniques in clinical investigation. Neurology 59, 1851–1859. Daskalakis, Z.J., Paradiso, G.O., Christensen, B.K., Fitzgerald, P.B., Gunraj, C., Chen, R., 2004. Exploring the connectivity between the cerebellum and motor cortex in humans. J. Physiol. 557, 689–700. Di Lazzaro, V., Restuccia, D., Oliviero, A., Profice, P., Ferrara, L., Insola, A., Mazzone, P., Tonali, P., Rothwell, J.C., 1998. Magnetic transcranial stimulation at intensities below active motor threshold activates intracortical inhibitory circuits. Exp. Brain Res. 119, 265–268. Furuya, J., Nakamura, S., Ono, T., Suzuki, T., 2012. Tongue pressure production while swallowing water and pudding and during dry swallow using a sensor sheet system. J. Oral Rehabil. 39, 684–691. Garry, M.I., Kamen, G., Nordstrom, M.A., 2004. Hemispheric differences in the relationship between corticomotor excitability changes following a fine-motor task and motor learning. J. Neurophysiol. 91, 1570–1578. Ginanneschi, F., Del Santo, F., Dominici, F., Gelli, F., Mazzocchio, R., Rossi, A., 2005. Changes in corticomotor excitability of hand muscles in relation to static shoulder positions. Exp. Brain Res. 161, 374–382. Halkjaer, L., Melsen, B., McMillan, A.S., Svensson, P., 2006. Influence of sensory deprivation and perturbation of trigeminal afferent fibers on corticomotor control of human tongue musculature. Exp. Brain Res. 170, 199–205. Hiiemae, K.M., Palmer, J.B., 2003. Tongue movements in feeding and speech. Crit. Rev. Oral Biol. Med. 14, 413–429. Inagaki, D., Miyaoka, Y., Ashida, I., Yamada, Y., 2009a. Activity pattern of swallowing-related muscles, food properties and body position in normal humans. J. Oral Rehabil. 36, 703–709. Inagaki, D., Miyaoka, Y., Ashida, I., Yamada, Y., 2009b. Influence of food properties and body position on swallowing-related muscle activity amplitude. J. Oral Rehabil. 36, 176–183. Kamiya, A., Sugiyama, Y., Iwase, S., Mano, T., 1998. Muscle sympathetic nerve activity and plasma norepinephrine during 6 degrees head-down bed rest. Environ. Med. 42, 159–162. Kothari, M., Svensson, P., Jensen, J., Kjaersgaard, A., Jeonghee, K., Nielsen, J.F., Ghovanloo, M., Baad-Hansen, L., 2013. Traininginduced cortical plasticity compared between three tonguetraining paradigms. Neuroscience 246C, 1–12. Kujirai, T., Caramia, M.D., Rothwell, J.C., Day, B.L., Thompson, P.D., Ferbert, A., Wroe, S., Asselman, P., Marsden, C.D., 1993. Corticocortical inhibition in human motor cortex. J. Physiol. 471, 501–519. Liepert, J., Classen, J., Cohen, L.G., Hallett, M., 1998. Taskdependent changes of intracortical inhibition. Exp. Brain Res. 118, 421–426. Lotze, M., Braun, C., Birbaumer, N., Anders, S., Cohen, L.G., 2003. Motor learning elicited by voluntary drive. Brain 126, 866–872. Mazzocchio, R., Gelli, F., Del Santo, F., Popa, T., Rossi, A., 2008. Effects of posture-related changes in motor cortical output on central oscillatory activity of pathological origin in humans. Brain Res. 1223, 65–72. Muellbacher, W., Boroojerdi, B., Ziemann, U., Hallett, M., 2001. Analogous corticocortical inhibition and facilitation in ipsilateral and contralateral human motor cortex representations of the tongue. J. Clin. Neurophysiol. 18, 550–558. Otsuka, R., Ono, T., Ishiwata, Y., Kuroda, T., 2000. Respiratory-related genioglossus electromyographic activity in response to head rotation and changes in body position. Angle Orthod. 70, 63–69. Pae, E.K., Lowe, A.A., Sasaki, K., Price, C., Tsuchiya, M., Fleetham, J.A., 1994. A cephalometric and electromyographic study of
brain research 1557 (2014) 83–89
upper airway structures in the upright and supine positions. Am. J. Orthod. Dentofac. Orthop. 106, 52–59. Perez, M.A., Lungholt, B.K., Nyborg, K., Nielsen, J.B., 2004. Motor skill training induces changes in the excitability of the leg cortical area in healthy humans. Exp. Brain Res. 159, 197–205. Peurala, S.H., Muller-Dahlhaus, J.F., Arai, N., Ziemann, U., 2008. Interference of short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF). Clin. Neurophysiol. 119, 2291–2297. Reis, J., Swayne, O.B., Vandermeeren, Y., Camus, M., Dimyan, M.A., Harris-Love, M., Perez, M.A., Ragert, P., Rothwell, J.C., Cohen, L.G., 2008. Contribution of transcranial magnetic stimulation to the understanding of cortical mechanisms involved in motor control. J. Physiol. 586, 325–351. Ridding, M.C., Brouwer, B., Miles, T.S., Pitcher, J.B., Thompson, P.D., 2000. Changes in muscle responses to stimulation of the motor cortex induced by peripheral nerve stimulation in human subjects. Exp. Brain Res. 131, 135–143. Ridding, M.C., Inzelberg, R., Rothwell, J.C., 1995. Changes in excitability of motor cortical circuitry in patients with Parkinson’s disease. Ann. Neurol. 37, 181–188. Rogasch, N.C., Fitzgerald, P.B., 2012. Assessing cortical network properties using TMS–EEG. Hum. Brain Mapp. 34, 1652–1669. Romaniello, A., Cruccu, G., McMillan, A.S., Arendt-Nielsen, L., Svensson, P., 2000. Effect of experimental pain from trigeminal muscle and skin on motor cortex excitability in humans. Brain Res. 882, 120–127. Rothwell, J.C., 1997. Techniques and mechanisms of action of transcranial stimulation of the human motor cortex. J. Neurosci. Methods 74, 113–122. Sauerland, E.K., Mitchell, S.P., 1975. Electromyographic activity of intrinsic and extrinsic muscles of the human tongue. Tex. Rep. Biol. Med. 33, 444–455. Sawczuk, A., Mosier, K.M., 2001. Neural control of tongue movement with respect to respiration and swallowing. Crit. Rev. Oral Biol. Med. 12, 18–37.
89
Sessle, B.J., Yao, D., Nishiura, H., Yoshino, K., Lee, J.C., Martin, R.E., Murray, G.M., 2005. Properties and plasticity of the primate somatosensory and motor cortex related to orofacial sensorimotor function. Clin. Exp. Pharmacol. Physiol. 32, 109–114. Stone, M., Stock, G., Bunin, K., Kumar, K., Epstein, M., Kambhamettu, C., Li, M., Parthasarathy, V., Prince, J., 2007. Comparison of speech production in upright and supine position. J. Acoust. Soc. Am. 122, 532–541. Svensson, P., Romaniello, A., Wang, K., Arendt-Nielsen, L., Sessle, B.J., 2006. One hour of tongue-task training is associated with plasticity in corticomotor control of the human tongue musculature. Exp. Brain Res. 173, 165–173. Svensson, P., Romaniello, A., Arendt-Nielsen, L., Sessle, B.J., 2003. Plasticity in corticomotor control of the human tongue musculature induced by tongue-task training. Exp. Brain Res. 152, 42–51. Taylor, J.L., Gandevia, S.C., 2001. Transcranial magnetic stimulation and human muscle fatigue. Muscle Nerve 24, 18–29. Tyc, F., Boyadjian, A., 2006. Cortical plasticity and motor activity studied with transcranial magnetic stimulation. Rev. Neurosci. 17, 469–495. Wassermann, E.M., 1998. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the international workshop on the safety of repetitive transcranial magnetic stimulation, June 5–7, 1996. Electroencephalogr. Clin. Neurophysiol. 108, 1–16. Ziemann, U., Rothwell, J.C., Ridding, M.C., 1996. Interaction between intracortical inhibition and facilitation in human motor cortex. J. Physiol. 496 (Pt 3), 873–881.
Available online at www.sciencedirect.com
www.elsevier.com/locate/brainres
Research Report
Influence of position and stimulation parameters on intracortical inhibition and facilitation in human tongue motor cortex Mohit Kotharia,c,n, Peter Svenssona,b, Jørgen Feldbæk Nielsenc, Lene Baad-Hansena a
Section of Clinical Oral Physiology, Department of Dentistry, Aarhus University, Aarhus C, Denmark MINDLab, Center for Functionally Integrative Neuroscience, Aarhus University Hospital, Aarhus C, Denmark c Hammel Neurorehabilitation and Research Centre, Research Unit, Hammel, Denmark b
art i cle i nfo
ab st rac t
Article history:
Paired-pulse transcranial magnetic stimulation (ppTMS) can be used to assess short-interval
Accepted 7 February 2014
intracortical inhibitory (SICI) and facilitatory (ICF) networks. Many methodological parameters
Available online 15 February 2014
may however influence the outcome. The aim of the study was to examine the influence of
Keywords:
body positions (recline and supine), inter-stimulus intervals (ISI) between the test stimulus (TS)
Paired pulse transcranial magnetic
and conditioning stimulus (CS) and intensities of the TS and CS on the degree of SICI and ICF.
stimulation (ppTMS)
In studies 1 and 2, fourteen and seventeen healthy volunteers participated respectively. ppTMS
Short-interval intra-cortical
was applied over the “hot-spot” of the tongue motor cortex and motor evoked potentials (MEPs)
inhibitory (SICI) and facilitatory (ICF)
were recorded from contralateral tongue muscles. In study 1, single pulse and three ppTMS ISIs,
Test stimulus (TS)
2, 10, and 15 ms, were applied 8 times each in three blocks (TS: 120%, 140% and 160% of resting
Conditioning stimulus (CS)
motor threshold (rMT); CS: 80% of rMT) in two different body positions (recline and supine)
Body positions
randomly. In study 2, single pulse and four ppTMS ISIs, 2, 2.5, 3, and 3.5 ms, were applied 8 times each in randomized order in two blocks (CS: 70% and 80% of rMT; TS: 120% of rMT). There was a significant effect of body position (P¼ 0.049), TS intensities (Po0.001) and ISIs (Po0.001) and interaction between intensity and ISIs (P¼0.042) in study 1. In study 2, there was a significant effect of ISI (Po0.001) but not CS intensity (P¼0.984) on MEP amplitude. These results may be applied in future studies on the mechanisms of cortical plasticity in the tongue motor pathways using ppTMS and SICI and ICF. & 2014 Elsevier B.V. All rights reserved.
1.
Introduction
Transcranial magnetic stimulation (TMS) is a widely used, non-invasive and pain free technique to assess the functional n
integrity of descending corticospinal and corticoneural pathways in the human motor cortex through the intact scalp (Abbruzzese and Trompetto, 2002; Baad-Hansen et al., 2009; Curra et al., 2002; Muellbacher et al., 2001; Rogasch and
Corresponding author. Fax: þ45 86195665. E-mail addresses: [email protected], [email protected] (M. Kothari).
http://dx.doi.org/10.1016/j.brainres.2014.02.017 0006-8993 & 2014 Elsevier B.V. All rights reserved.
84
brain research 1557 (2014) 83–89
Fitzgerald, 2012; Rothwell, 1997; Tyc and Boyadjian, 2006). Several studies on corticomotor control with TMS have demonstrated changes in motor evoked potentials (MEPs) in human limb muscles following modulation of, for example, spinally innervated muscles (Blicher and Nielsen, 2009; Lotze et al., 2003; Perez et al., 2004; Ridding et al., 1995; Rothwell, 1997; Ziemann et al., 1996) but relatively little is known about the regulation of the cranial nerve innervated human tongue muscles (Baad-Hansen et al., 2009; Halkjaer et al., 2006; Muellbacher et al., 2001; Svensson et al., 2003, 2006). A rapid and controlled coordination of sensory and motor function is essential for a number of complex orofacial behaviors involving the tongue muscles, such as swallowing, mastication, respiration, and speech (Furuya et al., 2012; Hiiemae and Palmer, 2003; Sawczuk and Mosier, 2001). Tongue muscle related TMS studies show that acquisition of new motor skills, application of experimental intra-oral pain, or sensory deprivation by a lingual nerve block lead to significant shortterm changes in corticomotor control of the tongue muscles in humans (Adachi et al., 2008; Boudreau et al., 2007, 2013; Halkjaer et al., 2006; Kothari et al., 2013; Sessle et al., 2005; Svensson et al., 2003, 2006). Intracortical circuits in the motor cortex can be activated at TMS intensity below that required to activate the descending motor pathways (Di Lazzaro et al., 1998; Kujirai et al., 1993; Ziemann et al., 1996). With a subthreshold conditioning stimulus (CS) followed by suprathreshold test stimulus (TS), short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) can be studied (Kujirai et al., 1993), with the so-called paired-pulse TMS (ppTMS) technique. The underlying neural mechanisms that accompany changes in cortical plasticity are unclear but ppTMS studies have revealed that a motor training task of the limbs causes rapid disinhibition within intra-cortical circuits (Blicher et al., 2009; Garry et al., 2004; Liepert et al., 1998). SICI and ICF related to motor function of the hands, arm, and leg have been examined (Blicher and Nielsen, 2009; Lotze et al., 2003; Perez et al., 2004) and there are very few studies describing these mechanisms in detail for cranial muscles (Baad-Hansen et al., 2009; Muellbacher et al., 2001). SICI and ICF vary with the level of pre-activation of the targeted muscle and the intensities of CS and TS (Muellbacher et al., 2001; Reis et al., 2008). Romaniello et al. (2000) suggested that the use of preactivation levels is essential to evoke masseter muscle MEPs. In contrast, pre-activation of the tongue muscles is not needed in order to evoke MEPs in the tongue motor cortex (Baad-Hansen et al., 2009; Boudreau et al., 2007; Halkjaer et al., 2006; Kothari et al., 2013; Svensson et al., 2006, 2003). This is an advantage in intervention studies, since the level of pre-activation may potentially introduce difficulties in interpretation of training effects on intra-cortical mechanism due to difficulties in matching pre-activation levels before and after training (Baad-Hansen et al., 2009; Romaniello et al., 2000). However, the body position of the participant may potentially influence the baseline level of EMG activity of the tongue muscles (Otsuka et al., 2000; Pae et al., 1994; Sauerland and Mitchell, 1975). It has been reported that tonic tongue muscle EMG activity (as well as phasic activity related to spontaneous respiration) increases significantly in the supine position with respect to the upright position, to counteract
the relapse of the tongue, thus maintaining adequate upper airway patency (Otsuka et al., 2000; Pae et al., 1994; Sauerland and Mitchell, 1975). Presently, there are no studies exploring the influence of the body positions, stimulus intensity of the conditioning and test stimulus and different interstimulus intervals (ISIs) between the CS and TS without pre-activation of the tongue muscles in the detection of possible intracortical effects in the tongue motor area. The aims of the present study were: (1) to examine the influence of body positions (recline and supine) and different ISI (2, 10 and 15 ms) between the TS (3 different intensities: 120%, 140% and 160% of resting motor threshold (rMT)) and CS (80% of rMT) on intracortical modulatory mechanisms and (2) to examine the influence of different intensities of the CS (70% and 80% of rMT) with a constant TS (120% of rMT) on the degree of SICI (2, 2.5, 3 and 3.5 ms).
2.
Results
MEPs from the tongue could be evoked in all participants. However, the waveforms of the tongue varied between participants and simple biphasic MEPs as well as more complex and polyphasic MEPs were encountered (Fig. 1). The mean rMT of the tongue motor cortex for study 1 was 52.571.9% irrespective of the body positions (recline and supine) and for study 2 it was 55.072.0% of the maximum output of the magnetic stimulator.
2.1.
Study 1
2.1.1.
Effect of body positions (recline and supine)
For tongue motor cortex stimulation there was an overall effect of body positions (P¼ 0.049) in the analysis on absolute values. Post-hoc test revealed that the recline position was significantly different from the supine position (P ¼0.050), showing higher MEP amplitude in the recline position compared to the supine position (Fig. 1). There was no effect of body positions (P¼ 0.580) in normalized (relative) analysis.
2.1.2. Effect of test stimulus intensity and interstimulus interval In the analysis on absolute values, there was an overall effect of TS intensities (120%, 140% and 160% of rMT; P ¼0.004) and ISI (single pulse, 2, 10 and 15 ms; Po0.001) (Fig. 2). Post-hoc test showed that 160% TS was significantly different from 120% TS (P ¼0.003) showing higher MEP amplitudes. There was no significant difference between 120% TS and 140% TS (P ¼0.190) or between 140% TS and 160% TS (P¼ 0.150). Another post-hoc test revealed that statistically significant SICI was present during ppTMS with ISI of 2.0 ms (P¼ 0.021) and significant ICF was present during ppTMS stimulation with ISI of 10 ms (P ¼0.050) and 15 ms (P¼ 0.010) compared with single pulse stimulation (Fig. 2). There was a significant interaction between TS intensities and ISIs (P ¼0.002). The post-hoc test showed that TS intensities of 140% and 160% of rMT induced significantly higher MEPs compared with 120% of rMT for single pulse (Po0.001), 10 ms (Po0.001) and 15 ms (Po0.001). Even 160% of rMT induced significantly higher
brain research 1557 (2014) 83–89
85
Fig. 2 – Mean7SEM absolute motor evoked potentials (MEPs) from paired-pulse transcranial magnetic stimulation (ppTMS) and single pulse TMS. Three different stimulus intensities of the test stimulus (TS) were applied with different interstimulus intervals (single pulse, ppTMS with ISIs: 2.0, 10, and 10.5 ms) between the TS and conditioning stimulus (80% of resting motor threshold (rMT)). MEPs were recorded from the contralateral side of the tongue dorsum. n indicates overall significant difference from single pulse, i.e. significant intracortical facilitation (ICF) and short-interval intracortical inhibition (SICI) (Po0.001). Fig. 1 – Example of single (last) sweep tongue motor evoked potentials from the contralateral side of the tongue dorsum of one healthy volunteer at two different body positions (recline and supine) evoked by paired-pulse transcranial magnetic stimulation (ppTMS) with test stimulus of 160% of resting motor threshold combined with a conditioning stimulus of 80% of rMT. Different interstimulus intervals of 2, 10, and 15 ms and single stimulation were applied.
MEPs compared with 140% of rMT for single pulse stimulation (P¼ 0.030), 10 ms (Po0.001) and 15 ms (Po0.001). Finally, 160% of rMT TS intensity showed higher MEPs compared with 120% of rMT for 2 ms (Po0.001). In the analysis on normalized data, which was performed to evaluate the effect of TS intensities and ISIs on the degree of SICI and ICF, there was no significant main effect of TS intensities (P¼ 0.063) but there was an overall significant effect of ISI (Po0.001). A post-hoc test revealed that based on the normalized data no statistically significant SICI was present during ppTMS with ISI of 2.0 ms (P¼0.800) but significant ICF was present during ppTMS stimulation with ISI of 10 ms (Po0.001) and 15 ms (Po0.001) compared with single pulse stimulation. There was a statistically significant interaction between TS intensities and ISIs (P¼ 0.042). The post-hoc test showed that for TS intensity of 120% of rMT, there was no significant SICI (P¼ 0.999) but there was significant ICF at ISIs of 10 and 15 ms compared with single pulse (Po0.001). At 140% and 160% of rMT, no significant SICI or ICF was detected
compared with single pulse (P40.225). Between the TS intensities, 120% of rMT induced higher degrees of ICF compared with 140 and 160% of rMT (Po 0.028). There was no significant difference in the degree of SICI (P¼ 1.00) or ICF (P¼1.00) between 160% and 140% of rMT.
2.2.
Study 2
2.2.1. Effect of conditioning stimulus intensity and interstimulus interval For tongue motor cortex stimulation, there was no significant difference in MEPs between the two CS intensities (70% and 80% of rMT; P¼ 0.984) but there was an overall effect of ISI on MEP amplitudes (Po0.001). Post-hoc tests revealed that statistically significant SICI was present during ppTMS stimulation with 2.0 ms (P¼ 0.003), 2.5 ms (P ¼0.002), 3.0 ms (Po0.001), and 3.5 ms (Po0.001) compared with single pulse stimulation (Fig. 3). However, there was no significant difference in the degree of SICI induced by ISIs of 2.0, 2.5, 3.0, or 3.5 ms (P40.982). There was no significant interaction between different intensities of CS and ISIs (P ¼0.790).
3.
Discussion
In this study, tongue MEPs could be evoked by TMS in accordance with earlier studies with similar amplitudes and activation thresholds (Baad-Hansen et al., 2009; Kothari et al., 2013;
86
brain research 1557 (2014) 83–89
Fig. 3 – Mean7SEM motor evoked potentials (MEPs) from paired-pulse transcranial magnetic stimulation (ppTMS) normalized to single pulse TMS. Two different stimulus intensities of the conditioning stimulus (CS) were applied with different interstimulus intervals (single pulse, ppTMS with ISIs: 2.0, 2.5, 3.0, and 3.5 ms) between the CS and test stimulus. MEPs were recorded from the contralateral side of the tongue dorsum. n indicates significant difference from single pulse, i.e. significant short-interval intracortical inhibition (SICI) (Po0.003).
Svensson et al., 2003, 2006; Taylor and Gandevia, 2001). The main finding of the study 1 was that reclined body position produced significantly higher tongue MEPs compared to when participants were in supine position. Some studies on healthy participants have shown that changes in static position of the shoulder influences the corticospinal excitability of an intrinsic hand muscle, as tested by TMS at rest (Ginanneschi et al., 2005; Mazzocchio et al., 2008). However, to our knowledge there has been no study performed to find the effect of body positions (recline and supine) on tongue MEPs but there are various studies performed to find the effect of tongue position and body positions on swallowing or speech (Buchaillard et al., 2009; Inagaki et al., 2009a, 2009b; Stone et al., 2007). The present finding may be an important addition to the knowledge about the neurophysiology of the tongue motor cortex and the tongue muscles in different body positions. The difference in MEP size between body positions may be due to different tongue positions and thereby possibly different levels of muscle activity. However, drowsiness while being in supine position may also have played a role as a number of physiological changes occur during bedrest (supine position), such as changes in baroreflex function, a decrease in vagal tone and a loss of circulatory blood volume (Kamiya et al., 1998).
The second main finding of the study 1 was that the three different TS intensities and 4 different ISIs (single pulse stimulation, 2, 10 and 15 ms) evoked different degrees of SICI and ICF of the MEP responses. It has been shown that ICF tends to be weaker with increasing TS intensity in the FDI (Daskalakis et al., 2004) muscle and this was also the case in our present study. It is still a point of research to find whether ICF may be merely a ‘rebound’ phenomenon from the robust inhibition at shorter interstimulus interval or whether it represents a different phenomenon (Daskalakis et al., 2004). Ziemann et al. (1996) concluded that separate neuronal populations were likely to mediate intracortical inhibition and facilitation. When comparing the present study data with the Muellbacher et al. study, it is important to notice that the present study data was carried out using stimulus intensities of the test and conditioning stimulus relative to the rMT and not to the active MT (Muellbacher et al., 2001). The main finding of the study 2 was that the two stimulus intensities of the CS and 4 different short ISIs evoked similar degrees of SICI of the MEP responses. In the present study, statistically significant SICI in the contralateral tongue motor cortex was demonstrated with 4 different ISIs (2, 2.5, 3, and 3.5 ms) compared to single pulse stimulation. Ziemann et al. (1996) demonstrated that in the abductor digiti minimi (ADM) muscle, SICI occurs at lower CS intensities than ICF, becoming stronger with increasing intensities. In comparison with our earlier study where only 2.0 and 3.0 ms ISI between the CS and the TS were applied (Baad-Hansen et al., 2009), we also applied 2.5 and 3.5 ms ISIs, since it has been shown for spinally innervated muscles that short-interval intracortical facilitation (SICF) occurs within this time interval (Peurala et al., 2008). In summary, none of the two stimulus intensities of the CS and the short ISIs were superior to the others in inducing intracortical modulatory effects. As in our earlier study, the wave-forms in the present study varied between participants and simple biphasic MEPs as well as more complex and polyphasic MEPs were encountered (Baad-Hansen et al., 2009). We have previously analyzed the correlation between peak-to-peak amplitudes and area under the curve (AUC) of tongue MEPs and since it was shown that there was a highly significant correlation between these two methods of quantification, we decided to use the peakto-peak amplitude in this study (Baad-Hansen et al., 2009). The knowledge about control of spinally innervated muscles may not apply in the same way to the cranial muscles, since the organization of the cranial and spinal sensorimotor systems differs in many ways (Cohen et al., 1993; Ridding et al., 2000). This demands to perform studies in both systems. In our previous study on the effect of simple tongue protrusion training on SICI and ICF in the tongue motor cortex, no training-induced changes were observed using TS intensity of 120% and CS intensity of 80% of rMT (Baad-Hansen et al., 2009) in contrast to limb studies (Blicher and Nielsen, 2009; Garry et al., 2004; Liepert et al., 1998). In addition, training-induced cortical plasticity was observed in different tongue training paradigms and further documented that plasticity was evident within 30 min post-training and may last up to at least 7 days (Kothari et al., 2013; Svensson et al., 2003, 2006). In conclusion, recline body position evoked larger MEPs than in supine position. Significantly greater ICF was evoked
brain research 1557 (2014) 83–89
with 120% TS compared with 140 and 160% TS intensities. None of the two CS stimulus intensities in study 2 were superior to the others in inducing intracortical modulatory effects. These methodological results indicate that future studies on cortical plasticity and the effect of tongue training on intracortical modulatory mechanisms in the tongue motor cortex should of course carefully standardize stimulus parameters but also body position during TMS measurements.
4.
Experimental procedures
4.1.
Participants
Two different studies were performed and for both studies, inclusion criteria were as follows: ability to read and understand the project information. Exclusion criteria were as follows: subjects with medical, physical or psychological disorders, metal implants in head, history of epilepsy, pacemaker/medicinal pumps and pregnant woman (Wassermann, 1998). All participants gave informed consent and received financial compensation for their participation. The study was approved by the local ethics committee and performed in accordance with the Helsinki Declaration II. The session lasted approximately 1 h. In study 1, sixteen healthy participants (8 men and 8 women, aged 20–35 years, mean (7SEM) age of 27.471.9 years) were recruited at Department of Dentistry, Aarhus University where the study was performed. Two participants did not complete the study due to difficulties to locate the tongue hot-spot in the motor cortex. Thus, fourteen healthy participants completed the study (8 men and 6 women, aged 20–32 years, mean (7SEM) age of 26.871.8 years). In study 2, twenty healthy participants (9 men and 11 women, aged 19–67 years, mean (7SEM) age of 24.972.3 years) were recruited. Three subjects did not complete the study: one due to discomfort and two due to difficulties to locate the tongue hot-spot in the motor cortex. Thus, seventeen healthy participants completed the study (8 men and 9 women, aged 19–31 years, mean (7SEM) age of 22.670.8 years).
4.2.
Recording of motor evoked potentials
For both studies 1 and 2, the participants were placed on a patient examination table in supine position with the head tilted towards the right side and supported by a headrest (Kothari et al., 2013). In addition to supine position, participants in study 1 were also instructed to sit in a dental chair in a recline position to examine the influence of body positions. A swimming cap was placed over the head and anatomical features were marked with a pen to secure a stable position of the cap (Baad-Hansen et al., 2009; Halkjaer et al., 2006; Kothari et al., 2013; Svensson et al., 2003, 2006). Electromyographic (EMG) activity was recorded from the right side of the tongue dorsum (Baad-Hansen et al., 2009; Halkjaer et al., 2006; Kothari et al., 2013). Disposable self-adhesive silver chloride electrodes (Alpine Biomed, Denmark, Type 9013S0225) were placed on the right dorsal surface of the tongue (2–3 mm from midline, 10 mm from tongue tip) with an inter-electrode distance of 20 mm (Baad-Hansen et al., 2009; Halkjaer et al., 2006;
87
Svensson et al., 2003, 2006). The electrodes were connected to the amplifier to allow bipolar registration of contralateral MEPs. The EMG signals were amplified, filtered (20 Hz–1 kHz), and stored on Viking Select (Nicolet, California, USA) (Baad-Hansen et al., 2009; Halkjaer et al., 2006; Svensson et al., 2006, 2003). Transcranial magnetic stimuli (Magstim 200, The Magstim Co. Ltd., Whitland, UK, peak magnetic field¼ 2 T) were delivered with a 5-cm diameter figure-of-eight coil to the left side of the scalp (Baad-Hansen et al., 2009; Halkjaer et al., 2006; Kothari et al., 2013; Svensson et al., 2003, 2006). The coil of the stimulator was oriented 451 obliquely to the sagittal midline so that the induced current flowed in a plane perpendicular to the estimated alignment of the central sulcus (BaadHansen et al., 2009; Halkjaer et al., 2006; Svensson et al., 2006). With constant stimulus intensity, the stimulator coil was moved over the left hemisphere to determine the optimal position to elicit maximal MEP amplitudes in the tongue muscle. Three markings on the coil helped to identify the position in relation to the scalp sites. The scalp site at which EMG responses were evoked in the tongue at lowest stimuli strength (hot spot) was determined and marked with a pen on the cap (Baad-Hansen et al., 2009; Halkjaer et al., 2006; Kothari et al., 2013; Svensson et al., 2003, 2006). The rMT contralateral to stimulation was measured in the relaxed muscles with the use of descending and ascending method of limits and was defined as the minimum stimulus intensity that produced five out of ten discrete MEPs clearly discernible on the monitor from background EMG activity (tongue MEPZ5 mv) (Baad-Hansen et al., 2009; Halkjaer et al., 2006; Svensson et al., 2003).
4.3.
Intracortical excitability
Intracortical excitability was assessed according to a ppTMS protocol (Baad-Hansen et al., 2009; Di Lazzaro et al., 1998; Kujirai et al., 1993; Muellbacher et al., 2001; Ziemann et al., 1996). The ppTMS protocol consisted of a paired conditioning and test stimulus paradigm with a subthreshold CS and suprathreshold TS at different interstimulus intervals (ISIs) (Baad-Hansen et al., 2009; Muellbacher et al., 2001). MEP amplitudes of the averaged signals were measured peak to peak. In study 1, the four stimulus conditions (single pulse, ISIs: 2, 10, and 15 ms) were applied 8 times each in three blocks (TS: 120%, 140% and 160% of rMT) and averaged for two different body positions (recline and supine in randomized order). In one block, the intensity of TS was set at 120% of the contralateral rMT (block 1), and in the other block, it was set at 140% of the contralateral rMT (block 2) and in third block, it was set at 160% of the contralateral rMT (block 3) with constant CS (80% of rMT) irrespective of blocks. In study 2, four ISIs (2, 2.5, 3 and 3.5 ms) were tested and randomly intermixed with single stimulation with the TS. The five stimulus conditions (single pulse, ISIs: 2, 2.5, 3 and 3.5 ms) were applied 8 times each in two blocks and averaged. In one block, the intensity of CS was set at 70% of the contralateral rMT (block 1), and in the other block, it was set at 80% of the contralateral rMT (block 2) with constant TS
88
brain research 1557 (2014) 83–89
(120% of rMT) irrespective of blocks. The orders of the blocks were randomized.
4.4.
Statistics
All data were presented as means7SEM. In study 1, two different analyses were performed: (1) absolute averaged MEPs from ppTMS were analyzed using repeated measurement (RM) of analysis of variance (ANOVA) with body position, TS stimulation intensity and ISI as RM factors and (2) normalized (relative) averaged MEPs (averaged MEPs from ppTMS normalized to averaged MEPs from single pulse TMS) were analyzed using RM of ANOVA with body position, TS stimulation intensity and ISI as RM factors. In study 2, normalized averaged MEPs were analyzed using RM of ANOVA with CS stimulus intensity and ISI as RM factors. When appropriate, Tukey' honestly significant difference (HSD) tests with correction for multiple comparisons were performed as post-hoc tests. Values of P less than 0.05 were considered statistically significant.
Acknowledgments Funding: Danish Dental Association and Aarhus University Research Foundation. Ethical approval: Local Ethics committee, Central Denmark Region.
references
Abbruzzese, G., Trompetto, C., 2002. Clinical and research methods for evaluating cortical excitability. J. Clin. Neurophysiol. 19, 307–321. Adachi, K., Ding, M., Surrey, S., 2008. Role of the beta4Thr– beta73Asp hydrogen bond in HbS polymer and domain formation from multinucleate-containing clusters. Biochemistry 47, 5441–5449. Baad-Hansen, L., Blicher, J.U., Lapitskaya, N., Nielsen, J.F., Svensson, P., 2009. Intra-cortical excitability in healthy human subjects after tongue training. J. Oral Rehabil. 36, 427–434. Blicher, J.U., Jakobsen, J., Andersen, G., Nielsen, J.F., 2009. Cortical excitability in chronic stroke and modulation by training: a TMS study. Neurorehabil. Neural Repair 23, 486–493. Blicher, J.U., Nielsen, J.F., 2009. Cortical and spinal excitability changes after robotic gait training in healthy participants. Neurorehabil. Neural Repair 23, 143–149. Boudreau, S., Romaniello, A., Wang, K., Svensson, P., Sessle, B.J., Arendt-Nielsen, L., 2007. The effects of intra-oral pain on motor cortex neuroplasticity associated with short-term novel tongue-protrusion training in humans. Pain 132, 169–178. Boudreau, S.A., Lontis, E.R., Caltenco, H., Svensson, P., Sessle, B.J., Andreasen Struijk, L.N., Arendt-Nielsen, L., 2013. Features of cortical neuroplasticity associated with multidirectional novel motor skill training: a TMS mapping study. Exp. Brain Res. 225, 513–526. Buchaillard, S., Perrier, P., Payan, Y., 2009. A biomechanical model of cardinal vowel production: muscle activations and the impact of gravity on tongue positioning. J. Acoust. Soc. Am. 126, 2033–2051. Cohen, L.G., Brasil-Neto, J.P., Pascual-Leone, A., Hallett, M., 1993. Plasticity of cortical motor output organization following
deafferentation, cerebral lesions, and skill acquisition. Adv. Neurol. 63, 187–200. Curra, A., Modugno, N., Inghilleri, M., Manfredi, M., Hallett, M., Berardelli, A., 2002. Transcranial magnetic stimulation techniques in clinical investigation. Neurology 59, 1851–1859. Daskalakis, Z.J., Paradiso, G.O., Christensen, B.K., Fitzgerald, P.B., Gunraj, C., Chen, R., 2004. Exploring the connectivity between the cerebellum and motor cortex in humans. J. Physiol. 557, 689–700. Di Lazzaro, V., Restuccia, D., Oliviero, A., Profice, P., Ferrara, L., Insola, A., Mazzone, P., Tonali, P., Rothwell, J.C., 1998. Magnetic transcranial stimulation at intensities below active motor threshold activates intracortical inhibitory circuits. Exp. Brain Res. 119, 265–268. Furuya, J., Nakamura, S., Ono, T., Suzuki, T., 2012. Tongue pressure production while swallowing water and pudding and during dry swallow using a sensor sheet system. J. Oral Rehabil. 39, 684–691. Garry, M.I., Kamen, G., Nordstrom, M.A., 2004. Hemispheric differences in the relationship between corticomotor excitability changes following a fine-motor task and motor learning. J. Neurophysiol. 91, 1570–1578. Ginanneschi, F., Del Santo, F., Dominici, F., Gelli, F., Mazzocchio, R., Rossi, A., 2005. Changes in corticomotor excitability of hand muscles in relation to static shoulder positions. Exp. Brain Res. 161, 374–382. Halkjaer, L., Melsen, B., McMillan, A.S., Svensson, P., 2006. Influence of sensory deprivation and perturbation of trigeminal afferent fibers on corticomotor control of human tongue musculature. Exp. Brain Res. 170, 199–205. Hiiemae, K.M., Palmer, J.B., 2003. Tongue movements in feeding and speech. Crit. Rev. Oral Biol. Med. 14, 413–429. Inagaki, D., Miyaoka, Y., Ashida, I., Yamada, Y., 2009a. Activity pattern of swallowing-related muscles, food properties and body position in normal humans. J. Oral Rehabil. 36, 703–709. Inagaki, D., Miyaoka, Y., Ashida, I., Yamada, Y., 2009b. Influence of food properties and body position on swallowing-related muscle activity amplitude. J. Oral Rehabil. 36, 176–183. Kamiya, A., Sugiyama, Y., Iwase, S., Mano, T., 1998. Muscle sympathetic nerve activity and plasma norepinephrine during 6 degrees head-down bed rest. Environ. Med. 42, 159–162. Kothari, M., Svensson, P., Jensen, J., Kjaersgaard, A., Jeonghee, K., Nielsen, J.F., Ghovanloo, M., Baad-Hansen, L., 2013. Traininginduced cortical plasticity compared between three tonguetraining paradigms. Neuroscience 246C, 1–12. Kujirai, T., Caramia, M.D., Rothwell, J.C., Day, B.L., Thompson, P.D., Ferbert, A., Wroe, S., Asselman, P., Marsden, C.D., 1993. Corticocortical inhibition in human motor cortex. J. Physiol. 471, 501–519. Liepert, J., Classen, J., Cohen, L.G., Hallett, M., 1998. Taskdependent changes of intracortical inhibition. Exp. Brain Res. 118, 421–426. Lotze, M., Braun, C., Birbaumer, N., Anders, S., Cohen, L.G., 2003. Motor learning elicited by voluntary drive. Brain 126, 866–872. Mazzocchio, R., Gelli, F., Del Santo, F., Popa, T., Rossi, A., 2008. Effects of posture-related changes in motor cortical output on central oscillatory activity of pathological origin in humans. Brain Res. 1223, 65–72. Muellbacher, W., Boroojerdi, B., Ziemann, U., Hallett, M., 2001. Analogous corticocortical inhibition and facilitation in ipsilateral and contralateral human motor cortex representations of the tongue. J. Clin. Neurophysiol. 18, 550–558. Otsuka, R., Ono, T., Ishiwata, Y., Kuroda, T., 2000. Respiratory-related genioglossus electromyographic activity in response to head rotation and changes in body position. Angle Orthod. 70, 63–69. Pae, E.K., Lowe, A.A., Sasaki, K., Price, C., Tsuchiya, M., Fleetham, J.A., 1994. A cephalometric and electromyographic study of
brain research 1557 (2014) 83–89
upper airway structures in the upright and supine positions. Am. J. Orthod. Dentofac. Orthop. 106, 52–59. Perez, M.A., Lungholt, B.K., Nyborg, K., Nielsen, J.B., 2004. Motor skill training induces changes in the excitability of the leg cortical area in healthy humans. Exp. Brain Res. 159, 197–205. Peurala, S.H., Muller-Dahlhaus, J.F., Arai, N., Ziemann, U., 2008. Interference of short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF). Clin. Neurophysiol. 119, 2291–2297. Reis, J., Swayne, O.B., Vandermeeren, Y., Camus, M., Dimyan, M.A., Harris-Love, M., Perez, M.A., Ragert, P., Rothwell, J.C., Cohen, L.G., 2008. Contribution of transcranial magnetic stimulation to the understanding of cortical mechanisms involved in motor control. J. Physiol. 586, 325–351. Ridding, M.C., Brouwer, B., Miles, T.S., Pitcher, J.B., Thompson, P.D., 2000. Changes in muscle responses to stimulation of the motor cortex induced by peripheral nerve stimulation in human subjects. Exp. Brain Res. 131, 135–143. Ridding, M.C., Inzelberg, R., Rothwell, J.C., 1995. Changes in excitability of motor cortical circuitry in patients with Parkinson’s disease. Ann. Neurol. 37, 181–188. Rogasch, N.C., Fitzgerald, P.B., 2012. Assessing cortical network properties using TMS–EEG. Hum. Brain Mapp. 34, 1652–1669. Romaniello, A., Cruccu, G., McMillan, A.S., Arendt-Nielsen, L., Svensson, P., 2000. Effect of experimental pain from trigeminal muscle and skin on motor cortex excitability in humans. Brain Res. 882, 120–127. Rothwell, J.C., 1997. Techniques and mechanisms of action of transcranial stimulation of the human motor cortex. J. Neurosci. Methods 74, 113–122. Sauerland, E.K., Mitchell, S.P., 1975. Electromyographic activity of intrinsic and extrinsic muscles of the human tongue. Tex. Rep. Biol. Med. 33, 444–455. Sawczuk, A., Mosier, K.M., 2001. Neural control of tongue movement with respect to respiration and swallowing. Crit. Rev. Oral Biol. Med. 12, 18–37.
89
Sessle, B.J., Yao, D., Nishiura, H., Yoshino, K., Lee, J.C., Martin, R.E., Murray, G.M., 2005. Properties and plasticity of the primate somatosensory and motor cortex related to orofacial sensorimotor function. Clin. Exp. Pharmacol. Physiol. 32, 109–114. Stone, M., Stock, G., Bunin, K., Kumar, K., Epstein, M., Kambhamettu, C., Li, M., Parthasarathy, V., Prince, J., 2007. Comparison of speech production in upright and supine position. J. Acoust. Soc. Am. 122, 532–541. Svensson, P., Romaniello, A., Wang, K., Arendt-Nielsen, L., Sessle, B.J., 2006. One hour of tongue-task training is associated with plasticity in corticomotor control of the human tongue musculature. Exp. Brain Res. 173, 165–173. Svensson, P., Romaniello, A., Arendt-Nielsen, L., Sessle, B.J., 2003. Plasticity in corticomotor control of the human tongue musculature induced by tongue-task training. Exp. Brain Res. 152, 42–51. Taylor, J.L., Gandevia, S.C., 2001. Transcranial magnetic stimulation and human muscle fatigue. Muscle Nerve 24, 18–29. Tyc, F., Boyadjian, A., 2006. Cortical plasticity and motor activity studied with transcranial magnetic stimulation. Rev. Neurosci. 17, 469–495. Wassermann, E.M., 1998. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the international workshop on the safety of repetitive transcranial magnetic stimulation, June 5–7, 1996. Electroencephalogr. Clin. Neurophysiol. 108, 1–16. Ziemann, U., Rothwell, J.C., Ridding, M.C., 1996. Interaction between intracortical inhibition and facilitation in human motor cortex. J. Physiol. 496 (Pt 3), 873–881.
