R.M. was supported by Medical Research Council (career development fellowship). J.R. was supported by the Wellcome Trust (project grant awarded to K.E.W and R.M.).&#160;We wish to thank Jennifer Chesters for her help in making the video.&#160;

1. Preparation
<ol>
	<li>Ask the participant to fill out a safety screening form (see e.g. 21). Note: Participants who have contraindications for TMS should not be stimulated; the most common contraindications are: lack of sleep, medication (e.g.&#160;antidepressants), and a family history of epilepsy.</li>
	<li>Explain the TMS procedure and the experimental details to the participant and obtain informed consent.</li>
	<li>Using alcohol, clean the skin&#160;above the belly of the FDI muscle in the right hand and in the reference site (e.g.&#160;tendon of the FDI muscle) and attach electrodes on these sites.</li>
	<li>Clean the skin on the right side of the OO muscle with alcohol and&#160;attach one electrode to the right corner of the upper lip and one electrode to the right corner of the lower lip.</li>
	<li>Clean the skin around the site for the ground electrode (e.g.&#160;on the forehead) and attach the electrode.</li>
	<li>Connect the wires of electrodes into an electrode box attached to an EMG recording system.</li>
	<li>Check the EMG signals recorded from the hand and lip muscles when the participant is contracting and relaxing these muscles (by visually inspecting them using e.g. Spike2 software). If the signals look noisy when the participant relaxes the lip and hand muscles, twist the electrode cables, re-clean the skin at the electrode site and/or ask the participant to uncross their legs, remove their shoes and have their feet on the floor (better grounding).</li>
	<li>Protect the participant&#39;s hearing by using earplugs.</li>
	<li>Put the cap on the participant&#39;s head in order to be able to mark the position of the TMS coil.</li>
</ol>
2. Localization of Motor Hand Representation
<ol>
	<li>Mark the vertex on the cap (by attaching a little sticker or by using a pen) and measure the distance from the vertex to the left preauricular point. Move 33% of this distance from the vertex towards the left preauricular point and mark this spot.</li>
	<li>Place the center&#160;of the figure-of-eight TMS coil on this spot. Orient the handle of the coil 45 degrees from the midline.</li>
	<li>Deliver the first TMS pulse e.g. by pressing a foot pedal. Choose a low intensity (e.g. 40% of the max stimulator intensity) if the participant&#39;s motor threshold is not known. Move the coil slightly and/or increase the intensity, if no MEP or muscle twitch is visible in the hand.</li>
	<li>When an MEP is elicited, keep moving the coil in 5-mm steps around this area in order to find an appropriate &#34;hot spot&#34;, i.e. the site and coil orientation that elicits the maximal MEPs at a certain intensity. Keep at least a 5-sec break between the pulses. Observe the participants hand to check which muscles twitch. When the spot in which the MEPs are the largest is found, mark this &#34;hot spot&#34; and the orientation of the coil on the cap.</li>
</ol>
3. Localization of Motor Lip Representation
<ol>
	<li>Mark a spot 2-3 cm from the FDI spot along a straight line towards the corner of the left eye (the location of the motor representation is more anterior and inferior than that of the hand representation).</li>
	<li>Place the coil on this spot. Ask the participant to purse the lip muscles; this lowers the motor threshold and, therefore, makes it easier to find the motor lip representation.</li>
	<li>Tell the participant that the TMS pulses may feel more intense in this location than in the previous location and that s/he may feel twitches in his/her face (due to peripheral stimulation) and involuntary eye-blinks. Ask the participant to inform the experimenter at any point if the stimulation becomes unpleasant or painful or if they wish to stop the stimulation.</li>
	<li>Deliver the first pulses. If no MEPs are elicited, move the coil slightly and/or increase the intensity. Keep at least a 5-sec break between the pulses. When an MEP is elicited, keep moving the&#160;coil around this area in 5-mm steps in order to find a &#34;hot spot&#34; for the OO muscle. Note: The shape of the lip MEPs is often multiphasic and their shape can vary from participant to participant. Also, the motor threshold is often higher for the lip muscle than for the hand muscles.</li>
</ol>
4. Defining Intensity for Single Pulse Experiments
<ol>
	<li>Train the participant to maintain a constant level of contraction, if MEPs will be recorded from contracted lip muscles. Note: Providing visual feedback about the power of the EMG signal (e.g.&#160;by using Spike2 software) helps during the training; training can be stopped when the participant is able keep the level of contraction stable for at least 1 min.</li>
	<li>Place the coil on the hot spot for the OO muscle. Deliver 10 pulses with fixed intensity. Keep at least a 5-sec break between the pulses. Estimate the sizes of MEPs by visually inspecting them. Increase the intensity, if MEPs are very small or there was no MEP on every trial. Deliver 10 pulses again. Keep increasing the intensity until a robust MEP is elicited on every trial (e.g.&#160;with amplitude of approximately 0.3 mV when the lip muscle is relaxed or with amplitude of approximately 1 mV when the lip muscle is contracted). Use this intensity during the single-pulse experiment. Note: It is a good practice to report stimulator intensities in publications.</li>
</ol>
5. Defining Active Motor Threshold for rTMS Experiments
<ol>
	<li>Ask the participant to contract the lip muscles as hard as they can. Determine the amplitude of this maximal contraction (by visually inspecting the EMG signal).</li>
	<li>Ask the participant to reduce the contraction of the lips. Guide him/her to reach the contraction level that is roughly 20% of the maximum. Ask the participant to keep this level for 1 min. Give him/her a short break and repeat the practice as many times as needed. Note: Providing visual feedback about the power of the EMG signal (e.g.&#160;by using Spike2 software) helps during the training; training can be stopped when the participant is able keep the level of contraction stable for at least 1 min.</li>
	<li>Deliver 10 pulses over the hotspot for OO while the participant is contracting the lip at 20% of the maximum. Count how many MEPs were elicited. If there was an MEP (with peak-to-peak amplitude of at least 0.2 mV) in fewer than 5 out of 10 trials, increase the intensity. If there was an MEP on more than 5 out of 10 trials, lower the intensity. Repeat until a minimum intensity level that elicits MEPs on at least 50% of the trials (active motor threshold) has been found.</li>
	<li>Ask the participant to relax the lip muscles and deliver 10 pulses at the intensity of active motor threshold. Check that no MEPs were elicited (i.e.&#160;stimulation intensity is sub-threshold). If no MEPs were elicited, use this intensity (i.e.&#160;100% of active motor threshold) during the rTMS train (while the lip muscle is relaxed). If MEPs were elicited, go back to 5.3.</li>
</ol>
6. Low-frequency rTMS
<ol>
	<li>Deliver TMS pulses at a frequency of up to 1 Hz for 15-min during the rTMS train. When using the MagStim BiStim system that consists of two stimulators, trigger these stimulators alternatingly (i.e.&#160;each stimulator delivers a pulse every 3 sec.) in order to create a monophasic pulse sequence of 0.66 Hz. Note: Spike2 software together with the EMG acquisition system (by Cambridge Electronics) can be used to create a sequence of trigger pulses. Note: In practice, the maximum intensity for 0.66 Hz pulse train using the MagStim BiStim system and standard coils is 65% of the maximum stimulator output. This limit relates to the maximum pulse frequency of each stimulator (0.33 Hz), over-heating of the coils and participant comfort.</li>
	<li>Monitor recordings from the lip and the hand muscles during the rTMS train to ensure no MEPs are elicited that would indicate an increase in excitability or spreading effects to the neighboring representation. Also monitor the participant for signs of discomfort or changes in the level of alertness.</li>
	<li>Change the coil after 7.5 min in order to avoid overheating. Note: This step can be omitted when using special coils that are cooled during the stimulation; heating of the coils can affect the strength of the magnetic field.</li>
</ol>

<ol>
	<li>Hickok, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+mirror+neurons+in+speech+and+language+processing.">The role of mirror neurons in speech and language processing.</a> Brain Lang. 112, 1-2 (2010).</li><li>Hickok, G., Houde, J., Rong, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sensorimotor+integration+in+speech+processing:+computational+basis+and+neural+organization.">Sensorimotor integration in speech processing: computational basis and neural organization.</a> Neuron. 69, 407-422 (2011).</li><li>Lotto, A. J., Hickok, G. S., Holt, L. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reflections+on+mirror+neurons+and+speech+perception.">Reflections on mirror neurons and speech perception.</a> Trends Cogn Sci. 13, 110-114 (2009).</li><li>Pulvermuller, F., Fadiga, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Active+perception:+sensorimotor+circuits+as+a+cortical+basis+for+language.">Active perception: sensorimotor circuits as a cortical basis for language.</a> Nat Rev Neurosci. 11, 351-360 (2010).</li><li>Scott, S. K., McGettigan, C., Eisner, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+little+more+conversation,+a+little+less+action--candidate+roles+for+the+motor+cortex+in+speech+perception.">A little more conversation, a little less action--candidate roles for the motor cortex in speech perception.</a> Nat Rev Neurosci. 10, 295-302 (2009).</li><li>Liberman, A., Mattingly, I. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+motor+theory+of+speech+perception+revised.">The motor theory of speech perception revised.</a> Cognition. 21, 1-36 (1985).</li><li>Liberman, A. M., Cooper, F. S., Shankweiler, D. P., Studdert-Kennedy, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Perception+of+the+speech+code.">Perception of the speech code.</a> Psychological Review. 74, 431-461 (1967).</li><li>Mottonen, R., Watkins, K. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Using+TMS+to+study+the+role+of+the+articulatory+motor+system+in+speech+perception.">Using TMS to study the role of the articulatory motor system in speech perception.</a> Aphasiology. 26, 1103-1118 (2012).</li><li>Fadiga, L., Craighero, L., Buccino, G., Rizzolatti, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Speech+listening+specifically+modulates+the+excitability+of+tongue+muscles:+a+TMS+study.">Speech listening specifically modulates the excitability of tongue muscles: a TMS study.</a> Eur J Neurosci. 15, 399-402 (2002).</li><li>Watkins, K. E., Strafella, A. P., Paus, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Seeing+and+hearing+speech+excites+the+motor+system+involved+in+speech+production.">Seeing and hearing speech excites the motor system involved in speech production.</a> Neuropsychologia. 41, 989-994 (2003).</li><li>Stokes, M. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Simple+metric+for+scaling+motor+threshold+based+on+scalp-cortex+distance:+application+to+studies+using+transcranial+magnetic+stimulation.">Simple metric for scaling motor threshold based on scalp-cortex distance: application to studies using transcranial magnetic stimulation.</a> J Neurophysiol. 94, 4520-4527 (2005).</li><li>Murakami, T., Restle, J., Ziemann, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Observation-execution+matching+and+action+inhibition+in+human+primary+motor+cortex+during+viewing+of+speech-related+lip+movements+or+listening+to+speech.">Observation-execution matching and action inhibition in human primary motor cortex during viewing of speech-related lip movements or listening to speech.</a> Neuropsychologia. , (2011).</li><li>Swaminathan, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+excitability+during+visual+perception+of+known+and+unknown+spoken+languages.">Motor excitability during visual perception of known and unknown spoken languages.</a> Brain Lang. 126, 1-7 (2013).</li><li>Watkins, K., Paus, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulation+of+motor+excitability+during+speech+perception:+the+role+of+Broca's+area.">Modulation of motor excitability during speech perception: the role of Broca's area.</a> J Cogn Neurosci. 16, 978-987 (2004).</li><li>Chen, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Depression+of+motor+cortex+excitability+by+low-frequency+transcranial+magnetic+stimulation.">Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation.</a> Neurology. 48, 1398-1403 (1997).</li><li>Mottonen, R., Dutton, R., Watkins, K. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Auditory-motor+processing+of+speech+sounds.">Auditory-motor processing of speech sounds.</a> Cereb Cortex. 23, 1190-1197 (2013).</li><li>Mottonen, R., van de Ven, G. M., Watkins, K. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Attention+fine-tunes+auditory-motor+processing+of+speech+sounds.">Attention fine-tunes auditory-motor processing of speech sounds.</a> J Neurosci. 34, 4064-4069 (2014).</li><li>Mottonen, R., Watkins, K. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+representations+of+articulators+contribute+to+categorical+perception+of+speech+sounds.">Motor representations of articulators contribute to categorical perception of speech sounds.</a> J Neurosci. 29, 9819-9825 (2009).</li><li>Sommer, M., Lang, N., Tergau, F., Paulus, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuronal+tissue+polarization+induced+by+repetitive+transcranial+magnetic+stimulation.">Neuronal tissue polarization induced by repetitive transcranial magnetic stimulation.</a> Neuroreport. 13, 809-811 (2002).</li><li>Meister, I. G., Wilson, S. M., Deblieck, C., Wu, A. D., Iacoboni, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+essential+role+of+premotor+cortex+in+speech+perception.">The essential role of premotor cortex in speech perception.</a> Curr Biol. 17, 1692-1696 (2007).</li><li>Rossi, S., Hallett, M., Rossini, P. M., Pascual-Leone, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safety,+ethical+considerations,+and+application+guidelines+for+the+use+of+transcranial+magnetic+stimulation+in+clinical+practice+and+research.">Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research.</a> Clin Neurophysiol. 120, 2008-2039 (2009).</li><li>D'Ausilio, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+motor+somatotopy+of+speech+perception.">The motor somatotopy of speech perception.</a> Curr Biol. 19, 381-385 (2009).</li><li>Murakami, T., Restle, J., Ziemann, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effective+connectivity+hierarchically+links+temporoparietal+and+frontal+areas+of+the+auditory+dorsal+stream+with+the+motor+cortex+lip+area+during+speech+perception.">Effective connectivity hierarchically links temporoparietal and frontal areas of the auditory dorsal stream with the motor cortex lip area during speech perception.</a> Brain Lang. 122, 135-141 (2012).</li><li>Huang, Y. Z., Edwards, M. J., Rounis, E., Bhatia, K. P., Rothwell, J. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Theta+burst+stimulation+of+the+human+motor+cortex.">Theta burst stimulation of the human motor cortex.</a> Neuron. 45, 201-206 (2005).</li><li>Hamada, M., Murase, N., Hasan, A., Balaratnam, M., Rothwell, J. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+interneuron+networks+in+driving+human+motor+cortical+plasticity.">The role of interneuron networks in driving human motor cortical plasticity.</a> Cereb Cortex. 23, 1593-1605 (2013).</li></ol>

The authors have nothing to disclose.

During the past two decades, TMS has become a widely used method in cognitive neuroscience, because it can provide information that is complementary to neuroimaging. It has also provided speech scientists with new tools to investigate whether the motor speech production system could be involved in speech perception. Specifically, TMS provides an important means of testing experimentally whether the neural circuits that control speech articulation are facilitated whilst listening to speech and, whether these circuits contribute to speech perception.
This article described how the motor lip representation can be stimulated using TMS, and how both single-pulse and repetitive TMS techniques have been used to examine the role of the motor cortex in speech perception. The studies reported here provide evidence that the motor cortex contributes to speech processing in the human brain. Other TMS paradigms have also been used to investigate speech processing in the motor system. Dual TMS pulses delivered over the motor lip and tongue representations before auditory syllables have been shown to facilitate recognition of lip- and tongue-articulated syllables, respectively22. A paired-coil paradigm can be used to investigate effective connectivity between the lip representation and other cortical regions during speech perception23. It was shown that the effective connectivity between the motor lip representation and temporo-parietal junction and the inferior frontal cortex is enhanced during listening to speech, but not during listening to white noise. Continuous theta-burst stimulation (cTBS) over the temporo-parietal junction abolished its effective connectivity with the motor lip representation, providing further evidence that these cortical regions are functionally coupled during listening to speech23. The advantage of cTBS over low-frequency rTMS is that a relatively short train of cTBS (e.g.&#160;40 sec) can produce a long-lasting disruption in the motor cortex (up to 60 min)24. However, the effects of cTBS on motor excitability are highly variable across participants25.
Combining TMS with other neuroimaging techniques that measure whole brain activity can provide insight into how TMS affects neural processes in both neighboring and more distal cortical regions. Brain regions undoubtedly interact with one another during perceptual and cognitive processes, and so it is unsurprising that an induced &#34;virtual lesion&#34; in one brain area would modulate functioning of other brain areas engaged in the same process. In order to advance understanding of the neural basis of speech perception, it is essential to investigate how the articulatory motor cortex interacts with the auditory regions in the superior temporal cortex during listening to speech and how these interactions contribute to speech perception. The combination of TMS with brain imaging techniques provides a means to address these questions. For example, it is possible to examine influences of TMS-induced disruptions in the articulatory system on processing of speech signals in the superior temporal cortex using electroencephalography (EEG), magnetoencephalography (MEG), functional MRI and positron emission tomography (PET). Experiments combining low-frequency rTMS and EEG demonstrate that TMS-induced disruption in the articulatory motor cortex modulates automatic discrimination of speech, but not non-speech, sounds in the auditory system, showing that these systems interact during speech processing16. Combination of rTMS with MEG is also a powerful method to investigate the timing of auditory-motor interactions17.
Nevertheless, the link between speech production and perception is still poorly understood. TMS combined with speech tasks and additional neuroimaging techniques can help scientists to improve understanding of the neural bases of speech perception and production and whether they overlap.

Speech perception is a demanding skill that requires encoding of complex and highly variable incoming auditory signals. Whilst it is uncontroversial that the auditory cortex plays a critical role in speech processing, whether the motor regions that control the movements of the articulators (e.g.&#160;lips) during speech production also contribute to speech perception remains a topic of active investigation and scientific debate1-5. The idea that motor representations are involved in speech perception is not novel. According to Liberman&#39;s motor theory of speech perception6,7 the listener perceives speech by simulating the &#34;intended articulatory gestures&#34; of the speaker. TMS has proven to be a powerful tool in investigating the putative role of the articulatory motor cortex during speech perception (for a review, see 8). This article focuses on stimulation of the lip motor representation using single-pulse and repetitive TMS techniques.
Single-pulse TMS has provided a highly effective means of investigating the link between the motor cortex and speech processing8-10. Single TMS pulses applied to the primary motor cortex (M1) elicit motor evoked potentials (i.e.&#160;MEPs) in the contralateral target muscle that can be recorded using electromyography (EMG). MEPs recorded from the hand muscles (first dorsal interosseus; FDI) peak approximately 24 msec after the pulse, whereas MEPs recorded from the lip muscles (orbicularis oris; OO) peak approximately 15 msec&#160;after the pulse (see Figure 1). This reflects differences in the distance from the motor cortex to the lips and hand muscles; the cortico-bulbar pathway to the lips is shorter than the cortico-spinal pathway to the hands. The intensity of the pulse required to elicit an MEP differs greatly across participants, most likely reflecting neuroanatomical differences and differences in the skull thickness11. The amplitude of the MEP is dependent on the functional state of the motor system, with pulses of a constant intensity inducing larger MEPs when the target muscle is contracted compared to when the muscle is relaxed. MEP measurements provide an accurate means of localizing the cortical representations of different muscles in each participant as well as normalizing the TMS intensity between subjects. This method also provides a direct measure (i.e. MEP amplitude) of motor excitability relative to an independent variable of interest. For instance, single-pulse TMS studies have shown that stimulation of the lip-representation induces larger MEPs (i.e. increased excitability) when listening to speech and viewing speech-related lip movements10,12,13. A combined PET and single-pulse TMS study showed that the excitability of the speech motor system during auditory speech perception is modulated in part by activity in the posterior left inferior frontal gyrus14.
Whilst single-pulse TMS can demonstrate changes in the excitability of the motor system during speech perception it does not indicate whether the motor cortex contributes to speech processing. Repetitive TMS (rTMS) can be used to induce a temporary disruption (i.e. &#34;a virtual lesion&#34;) in the motor cortex15. This &#34;virtual lesion&#34; approach enables investigation of speech perception during controlled, short-term disruption to a focal area of the motor system. The &#34;virtual lesions&#34; caused by TMS differ from real lesions in patients which often cover widespread cortical regions leading to functional reorganization of the brain over time. Patient studies typically compare behavior of the patients to a control group and rarely provide knowledge of performance prior to the stroke/lesion. By using rTMS it is possible to investigate a participant&#39;s ability to perform speech perception tasks with and without motor disruptions and, therefore, examine whether these disruptions contribute to performance.
Sub-threshold low-frequency rTMS can be used to disrupt the motor lip representation temporarily and it has been used to investigate the role of the articulatory motor cortex in speech perception16-18. In these experiments, monophasic pulse sequences were used because monophasic low-frequency rTMS has been shown to be more effective in decreasing cortical excitability compared to&#160;biphasic rTMS19. The size of MEPs recorded from the lips decreases after a 15-min train of sub-threshold monophasic TMS pulses applied at rates below 1 Hz i.e.&#160;motor excitability is suppressed18. This rTMS-induced disruption also impairs listeners&#39; ability to categorically perceive acoustic continua ranging between two speech sounds that differed in place of articulation (e.g. &#39;ba&#39; vs. &#39;da&#39; and &#39;pa&#39; vs. &#39;ta&#39;). The impaired performance after disruption to the lip motor cortex suggests that the motor system contributes to speech perception. Disruption of the hand motor representation has no effect on categorical perception of speech sounds. These findings are consistent with earlier findings showing that low-frequency rTMS applied to premotor cortex impairs performance in a phonetic discrimination task when using syllables presented in noise compared to a color discrimination control task matched on difficulty, task structure and response type20. These studies demonstrate that rTMS is an extremely effective means of exploring the auditory-motor circuits that may support both speech production and perception. Low-frequency rTMS can also be used in conjunction with neuroimaging techniques to further investigate this issue (see Discussion).

<table border="0" cellpadding="0" cellspacing="0" style="width:1221px;" width="1220">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:273px;">Name of Material/ Equipment</td>
			<td style="width:307px;">Company</td>
			<td style="width:311px;">Catalog Number</td>
			<td style="width:331px;">Comments/Description</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:23px;">TMS stimulator</td>
			<td>Magstim Limited, Wales, U.K.</td>
			<td>Magstim BiStim (two MagStim 200s connected)</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">2 TMS coils</td>
			<td>Magstim Limited, Wales, U.K.</td>
			<td>70-mm figure-of-eight coil, D70 Alpha</td>
			<td></td>
		</tr>
		<tr height="25">
			<td height="25" style="height:25px;">Electrodes for recording EMG signal</td>
			<td>Covidien llc, MA, USA.</td>
			<td colspan="2">Kendall Neonatal ECG electrodes, 22 mm x 30 mm</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Electrode box (for EMG recording)</td>
			<td>Cambridge Electronic Design Limited, U.K.</td>
			<td>CED 1902-11/4 Electrode Adaptor</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Data acquisition unit (for EMG)</td>
			<td>Cambridge Electronic Design Limited, U.K.</td>
			<td>Micro1401-3</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Amplifier (for EMG)</td>
			<td>Cambridge Electronic Design Limited, U.K.</td>
			<td>1902</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Software for EMG recording and analyses</td>
			<td>Cambridge Electronic Design Limited, U.K.</td>
			<td>Spike2, version 7</td>
			<td></td>
		</tr>
	</tbody>
</table>

stimulating the lip motor cortex with transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) has proven to be a useful tool in investigating the role of the articulatory motor cortex in speech perception. Researchers have used single-pulse and repetitive TMS to stimulate the lip representation in the motor cortex. The excitability of the lip motor representation can be investigated by applying single TMS pulses over this cortical area and recording TMS-induced motor evoked potentials (MEPs) via electrodes attached to the lip muscles (electromyography; EMG). Larger MEPs reflect increased cortical excitability. Studies have shown that excitability increases during listening to speech as well as during&#160;viewing speech-related movements. TMS can be used also to disrupt the lip motor representation. A 15-min train of low-frequency sub-threshold repetitive stimulation has been shown to suppress motor excitability for a further 15-20 min. This TMS-induced disruption of the motor lip representation impairs subsequent performance in demanding speech perception tasks and modulates auditory-cortex responses to speech sounds. These findings are consistent with the suggestion that the motor cortex contributes to speech perception. This article describes how to localize the lip representation in the motor cortex and how to define the appropriate stimulation intensity for carrying out both single-pulse and repetitive TMS experiments.

Results from single pulse experiments
In single pulse experiments, the dependent measure is the MEP amplitude. The size of the MEPs is typically measured either as peak-to-peak amplitude13,18 or area under the curve10. The lip MEPs can be recorded from either the relaxed muscle or a slightly contracted muscle. In the latter case, the TMS pulses can be delivered with a lower intensity, because the contraction lowers the motor threshold. It is very important that the level of the contraction stays constant throughout the experiment, because the strength of the contraction affects the MEP amplitudes. The stronger the contraction is, the larger the MEPs are. Therefore, it is important to train the participant to maintain a constant level of contraction before defining the TMS intensity, if MEPs are recorded from the contracted muscle. Visual feedback helps during the training (see Protocol 4.1.). Sometimes the threshold is so high that the intensity of the TMS pulses is uncomfortable for the participant and the experiment cannot be carried out. Also, it is not always possible to find the lip representation or record robust MEPs, especially when the lip muscles are relaxed. It is a good practice to report the number of participants in whom the experiment could not be carried out in publications. Figure 1 shows MEPs recorded from a relaxed and contracted lip muscle for a single participant. The intensity of the TMS pulses was kept constant across three levels of contraction. The motor excitability increases when the muscle is contracted, and consequently the MEPs get larger.
<img alt="Figure 1" fo:content-width="4in" src="/files/ftp_upload/51665/51665fig1highres.jpg" width="400" /> 
Figure 1.&#160;The effect of muscle contraction on lip MEPs. The MEPs were measured from one participant while she (1) relaxed her lips, (2) contracted the lips as slightly as she could (&#60; 5% of the maximum), and (3) when she contracted the lips about 20% of the maximum. The intensity of the mono-phasic TMS pulses was the same in all three conditions (58% of the maximum intensity). 6 MEPs were recorded in each condition (overlaid in the figure). The figure illustrates that the MEPs get larger when the level of contraction increases. A cortical silent period is clearly visible in the condition with strongest contraction. <a href="https://www.jove.com/files/ftp_upload/51665/51665fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
Motor excitability of the lip representation increases during listening to speech and viewing speech-related lip movements. Figure 2 shows lip MEP recorded during listening to speech and nonverbal noise, and during watching eye movements and speech related lip movements10. In this study MEPs were recorded from slightly contracted lip muscles. The level of the contraction was added as a covariate in the MEP analysis and used to adjust the MEP size. The lip MEPs elicited by left M1 stimulation were significantly enhanced during listening to speech and watching speech-related lip movements relative to the baseline condition, whereas the lip MEPs elicited by right M1 stimulation were not modulated during any of the conditions.
<img alt="Figure 2" fo:content-width="5in" fo:src="/files/ftp_upload/51665/51665fig2highres.jpg" src="/files/ftp_upload/51665/51665fig2.jpg" /> 
Figure 2.&#160;MEPs during perception of auditory and visual speech in one participant. The MEPs were recorded from the slightly contracted lips muscle while the left motor cortex was stimulated. The MEPs were enhanced during listening to speech and viewing speech related lip movements. Figure modified from 10.
A recent study investigated the specificity of changes in excitability in the lip motor cortex during observation of visual mouth movements13. Z-scores for lip MEPs recorded during visual perception of known speech (English), unknown speech (Hebrew), non-speech mouth movements (gurning) and a still face are presented in Figure 3. These z-scores were calculated relative to the mean of all conditions. TMS pulses were delivered over the left M1 and MEPs recorded from the relaxed lip muscle. MEPs were larger during observation of known speech than unknown speech or non-speech mouth movements. The MEPs recorded during observation of a still face were as large as during observation of English speech. These findings suggest that the lip motor cortex participates in processing of visual signals during speech communication. <a href="https://www.jove.com/files/ftp_upload/51665/51665fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" fo:content-width="5in" fo:src="/files/ftp_upload/51665/51665fig3highres.jpg" src="/files/ftp_upload/51665/51665fig3.jpg" /> 
Figure 3.&#160;Motor excitability during perception of visual speech. A. Participants were presented videos of known speech (i.e.&#160;English), unknown speech (i.e.&#160;Hebrew), non-speech mouth movements (i.e.&#160;gurns) and a still mouth. One TMS pulse was delivered during each video. Inter-pulse-interval (IPI) varied between 5 and 8 seconds. B. The figure shows standardized amplitudes of MEPs (&#177; SEM) measured from the lip during observation of videos. The z-scores were calculated relative to the mean of all conditions. The MEPs were significantly larger during observation of known speech than unknown speech (p = 0.001) or gurns (p &#60; 0.05). Differences in MEP amplitudes between conditions reflect differences in the excitability of the lip representation in the motor cortex. Figure modified from13. <a href="https://www.jove.com/files/ftp_upload/51665/51665fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
Results from rTMS experiments
It had been shown that low-frequency rTMS over the hand motor representation can reduce the motor excitability and induce a temporary disruption in this area (i.e. &#34;a virtual lesion&#34;)15. rTMS over the lip motor representation also reduces excitability of this area18. Changes in MEPs amplitudes after 15-min of low-frequency stimulation over the lip representation in the left M1 cortex are shown in Figure 4. The MEPs recorded from the lips were suppressed 7 min after the end of the repetitive TMS train, but had started to recover 15 min after. This suppressed excitability shows that low-frequency rTMS disrupted functioning of the lip representation in the motor cortex for about 15 min.
The TMS-induced disruptions in the articulatory motor cortex impair participants&#39; performance in the demanding speech perception tasks. Figure 5 shows how TMS-induced disruption of the lip representation modulated performance in a same-different discrimination task18. The participants were presented with pairs of synthetic syllables both before low-frequency rTMS and after it. Their task was to indicate whether syllables were the same or different. The TMS-induced disruption impaired the participant&#39;s ability to discriminate synthetic speech sounds that are lip-articulated from speech sounds that are not articulated by the lips (&#39;ba&#39; vs. &#39;da&#39; and &#39;pa&#39; vs. &#39;ta&#39;). However, this disruption did not influence their ability to discriminate two speech sounds that are not articulated by the lips (&#39;ka&#39; vs. &#39;ga&#39; and &#39;da&#39; vs. &#39;ga&#39;). This suggests that the lip representation contributes to speech perception in an articulator specific manner.
<img alt="Figure 4" fo:content-width="5in" fo:src="/files/ftp_upload/51665/51665fig4highres.jpg" src="/files/ftp_upload/51665/51665fig4.jpg" /> 
Figure 4.&#160;Effects of rTMS on motor excitability and speech discrimination. A. The graph presents mean changes (&#177; SEM) in peak-to-peak amplitudes of post-rTMS MEPs in relation to pre-rTMS MEPs. The MEPs were recorded from the lip muscles and the rTMS was applied over lip motor cortex in left hemisphere in both experiments 1 and 2. The post-rTMS MEPs were recorded ~7 min (post1) and ~15 min (post2) after the end of the 15-min low-frequency rTMS train. MEPs were significantly suppressed after rTMS in both experiments 1 and 2. B. Participants were presented with synthetic speech sounds from eight-step acoustic continua between two speech sounds. The &#34;across-category&#34; pairs were selected based on the place of category boundaries that were determined for each participant individually. The participants performed same-different discrimination task pre and post low-frequency rTMS over the lip motor representation. Changes in proportions of &#34;different&#34; responses (&#177; SEM) are plotted. After TMS, participants were poorer in discriminating across-category pairs that included lip-articulated speech sounds (&#39;ba&#39; vs. &#39;da&#39; and &#39;pa&#39; vs. &#39;ta&#39;) than before rTMS. Discriminability of other pairs stayed stable. Figures are modified from18. **p &#60; .01, ***p &#60; .001. <a href="https://www.jove.com/files/ftp_upload/51665/51665fig4large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Watch this Scientific Journal Video about Stimulating the Lip Motor Cortex with Transcranial Magnetic Stimulation at JoVE.com

Stimulating the Lip Motor Cortex with Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) has proven to be a useful tool in investigating the role of the articulatory motor cortex in speech perception.&#160; This article describes how to record motor evoked potentials (MEPs) from the lip muscles and how to disrupt the motor lip representation using repetitive TMS.

Transcranial magnetic stimulation (TMS) has proven to be a useful tool in investigating the role of the articulatory motor cortex in speech perception. ...

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18.8K ビュー.  University of Oxford. 経頭蓋磁気刺激（TMS）は音声知覚における調音運動皮質の役割を調査する際に有用なツールであることが証明された。この記事では、モータが唇の筋肉から電位（MEPを）誘発し、どのように反復的なTMSを用いてモータリップ表現を破壊するために録音する方法を説明します。 

ビデオ: Stimulating the Lip Motor Cortex with Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) has proven to be a useful tool in investigating the role of the articulatory motor cortex in speech perception.&#160; This article describes how to record motor evoked potentials (MEPs) from the lip muscles and how to disrupt the motor lip representation using repetitive...

multifunctional setup for studying human motor control using transcranial magnetic stimulation, electromyography, motion capture, and virtual reality

Multifunctional Setup for Studying Human Motor Control Using Transcranial Magnetic Stimulation, Electromyography, Motion Capture, and Virtual Reality

Transcranial magnetic stimulation, electromyography, and 3D motion capture are commonly used non-invasive techniques for investigating neuromuscular function in humans. In this paper, we describe a protocol that synchronously samples data generated by all three of these tools along with the unique addition of virtual reality stimulus presentation and...

effects of transcranial alternating current stimulation on the primary motor cortex by online combined approach with transcranial magnetic stimulation

Effects of Transcranial Alternating Current Stimulation on the Primary Motor Cortex by Online Combined Approach with Transcranial Magnetic Stimulation

Transcranial Alternating Current Stimulation (tACS) allows the modulation of cortical excitability in a frequency-specific fashion. Here we show a unique approach which combines online tACS with single pulse Transcranial Magnetic Stimulation (TMS) in order to "probe" cortical excitability by means of Motor Evoked Potentials.

combined transcranial magnetic stimulation and electroencephalography of the dorsolateral prefrontal cortex

Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex

The protocol presented here is for TMS-EEG studies utilizing intracortical excitability test-retest design paradigms. The intent of the protocol is to produce reliable and reproducible cortical excitability measures for assessing neurophysiological functioning related to therapeutic interventions in the treatment of neuropsychiatric diseases such as major...

measuring and manipulating functionally specific neural pathways in the human motor system with transcranial magnetic stimulation

Measuring and Manipulating Functionally Specific Neural Pathways in the Human Motor System with Transcranial Magnetic Stimulation

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The Use of Magnetic Resonance Spectroscopy as a Tool for the Measurement of Bi-hemispheric Transcranial Electric Stimulation Effects on Primary Motor Cortex Metabolism

This article aims to describe a basic protocol for combining transcranial direct current stimulation (tDCS) with proton magnetic resonance spectroscopy (1H-MRS) measurements to investigate the effects of bilateral stimulation on primary motor cortex...

determining the motor threshold on non-braided hair during transcranial magnetic stimulation (tms)

Determining the Motor Threshold on Non-Braided Hair During Transcranial Magnetic Stimulation (TMS)

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Brain State-dependent Brain Stimulation with Real-time Electroencephalography-Triggered Transcranial Magnetic Stimulation

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repetitive transcranial magnetic stimulation to the unilateral hemisphere of rat brain

Repetitive Transcranial Magnetic Stimulation to the Unilateral Hemisphere of Rat Brain

We applied repetitive transcranial magnetic stimulation (rTMS) to the unilateral hemisphere of rat brain, by placing a 25-mm figure-8 coil 1 cm lateral to the vertex on the biauricular line and angulating the coil by 45&#176;. An in-house water cooling system was used for rTMS for more than 20 min.

repeated transcranial magnetic stimulation combined with action observation training in children with spastic cerebral palsy

Author Spotlight: Repetitive Transcranial Magnetic Stimulation Combined with Movement Observation in Cerebral Palsy

Children with spastic cerebral palsy (SCP) have limb spasticity, movement disorders, and abnormal posture due to injury to the cerebral cortex motor area, resulting in inability to stand and walk normally. Therefore, alleviating limb spasticity and enhancing gross motor function in children with SCP have become important therapeutic goals.

Combined Intervention Training for Children with Spastic Cerebral Palsy 

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treating clinical depression with repetitive deep transcranial magnetic stimulation using the brainsway h1-coil

Treating Clinical Depression with Repetitive Deep Transcranial Magnetic Stimulation Using the Brainsway H1-coil

Here we present a protocol outlining the methodology for treatment of Major Depressive Disorder using the deep Transcranial Magnetic Stimulation (dTMS)...

utilizing transcranial magnetic stimulation to study the human neuromuscular system

Utilizing Transcranial Magnetic Stimulation to Study the Human Neuromuscular System

Transcranial magnetic stimulation (TMS) is a non-invasive tool to gain insight on the physiology and function of the human nervous system.  Here, we present our TMS techniques to study cortical excitability of the upper limb and lumbar...

neuronavigation-guided repetitive transcranial magnetic stimulation for aphasia

Neuronavigation-guided Repetitive Transcranial Magnetic Stimulation for Aphasia

This study is designed to test the hypothesis that neuronavigational system-guided transcranial magnetic stimulation has higher accuracy for targeting the intended target as demonstrated by eliciting a greater degree of virtual aphasia in healthy subjects, measured by delay in reaction time to picture...

measuring the contralateral silent period induced by transcranial magnetic stimulation

This video demonstrates a technique for measuring the contralateral silent period (cSP) using transcranial magnetic stimulation. Position the patient&#39;s hand prone and place an electrode on the first dorsal interosseous (FDI) muscle. Then, place a force-measuring device between the thumb and index finger. Identify the primary motor cortex (M1) region of the brain. Maintain a standardized pressure on the force-measuring device and stimulate the M1 region to record the muscle activity, termed...

Measuring the Contralateral Silent Period Induced by Transcranial Magnetic Stimulation

﻿participant screening for transcranial magnetic stimulation

Participant Screening for Transcranial Magnetic Stimulation  

﻿Participant Screening for Transcranial Magnetic Stimulation

the sol braiding method for handling thick hair during transcranial magnetic stimulation: an address for potential bias in brain stimulation

Author Spotlight: Increasing TMS Accessibility Through Braiding Techniques for Diverse Hair Types

Hair type commonly seen in historically underrepresented minorities appears to interfere with transcranial magnetic stimulation (TMS). Here we describe a hair braiding method (The Sol Braiding Technique) that improves...

Enhancing TMS Efficacy with Sol Braiding Technique in Diverse Populations

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Repeated Transcranial Magnetic Stimulation Combined with Action Observation Training in Children with Spastic Cerebral Palsy

simultaneous transcranial alternating current stimulation and functional magnetic resonance imaging

Simultaneous Transcranial Alternating Current Stimulation and Functional Magnetic Resonance Imaging

Transcranial alternating current stimulation (tACS) is a promising tool for noninvasive investigation of brain oscillations, though its effects are not completely understood. This article describes a safe and reliable setup for applying tACS simultaneously with functional magnetic resonance imaging, which can increase understanding oscillatory brain function and effects of...

online transcranial magnetic stimulation protocol for measuring cortical physiology associated with response inhibition

Online Transcranial Magnetic Stimulation Protocol for Measuring Cortical Physiology Associated with Response Inhibition

We describe an experimental procedure to quantify excitability and inhibition of primary motor cortex during a motor response inhibition task by using Transcranial Magnetic Stimulation throughout the course of a Stop Signal...

functional magnetic resonance imaging (fmri) of the visual cortex with wide-view retinotopic stimulation

Author Spotlight: Insights into Visual Cortex Research Through Wide-View fMRI Mapping 

We have developed techniques for mapping the visual cortex function utilizing more of the visual field than is commonly used. This approach has the potential to enhance the evaluation of vision disorders and eye...

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Functional Magnetic Resonance Imaging (fMRI) with Auditory Stimulation in Songbirds

The neurobiology of birdsong, as a model for human speech, is a pronounced area of research in behavioral neuroscience. Whereas electrophysiology and molecular approaches allow the investigation of either different stimuli on few neurons, or one stimulus in large parts of the brain, blood oxygenation level dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) allows combining both advantages, i.e. compare the neural activation induced by different stimuli in the entire brain at once. fMRI in songbirds is challenging because of the small size of their brains and because their bones and especially their skull comprise numerous air cavities, inducing important susceptibility artifacts. Gradient-echo (GE) BOLD fMRI has been successfully applied to songbirds 1-5 (for a review, see 6). These studies focused on the primary and secondary auditory brain areas, which are regions free of susceptibility artifacts. However, because processes of interest may occur beyond these regions, whole brain BOLD fMRI is required using an MRI sequence less susceptible to these artifacts. This can be achieved by using spin-echo (SE) BOLD fMRI 7,8 . In this article, we describe how to use this technique in zebra finches (Taeniopygia guttata), which are small songbirds with a bodyweight of 15-25 g extensively studied in behavioral neurosciences of birdsong. The main topic of fMRI studies on songbirds is song perception and song learning. The auditory nature of the stimuli combined with the weak BOLD sensitivity of SE (compared to GE) based fMRI sequences makes the implementation of this technique very challenging.

Functional Magnetic Resonance Imaging fMRI with Auditory Stimulation in Songbirds

This article shows an optimized procedure for imaging of the neural substrates of auditory stimulation in the songbird brain using functional Magnetic Resonance Imaging (fMRI). It describes the preparation of the sound stimuli, the positioning of the subject and the acquisition and subsequent analysis of the fMRI data.

The neurobiology of birdsong, as a model for human speech, is a pronounced area of research in behavioral neuroscience. Whereas electrophysiology and ...

Simultaneous EEG Monitoring During Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a technique that delivers weak electric currents through the scalp. This constant electric current induces shifts in neuronal membrane excitability, resulting in secondary changes in cortical activity. Although tDCS has most of its neuromodulatory effects on the underlying cortex, tDCS effects can also be observed in distant neural networks. Therefore, concomitant EEG monitoring of the effects of tDCS can provide valuable information on the mechanisms of tDCS. In addition, EEG findings can be an important surrogate marker for the effects of tDCS and thus can be used to optimize its parameters. This combined EEG-tDCS system can also be used for preventive treatment of neurological conditions characterized by abnormal peaks of cortical excitability, such as seizures. Such a system would be the basis of a non-invasive closed-loop device. In this article, we present a novel device that is capable of utilizing tDCS and EEG simultaneously. For that, we describe in a step-by-step fashion the main procedures of the application of this device using schematic figures, tables and video demonstrations. Additionally, we provide a literature review on clinical uses of tDCS and its cortical effects measured by EEG techniques.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has shown initial therapeutic effects in several neurological conditions. The main mechanism underlying these therapeutic effects is the modulation of cortical excitability. Therefore, online monitoring of cortical excitability would help guide stimulation parameters and optimize its therapeutic effects. In the present article we review the use of a novel device that combines simultaneous tDCS and EEG monitoring in real time.

Transcranial  direct current stimulation (tDCS) is a technique that delivers weak electric  currents through the scalp. This constant electric current ...

Transcranial Direct Current Stimulation and Simultaneous  Functional Magnetic Resonance Imaging

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses weak electrical currents administered to the scalp to manipulate cortical excitability and, consequently, behavior and brain function. In the last decade, numerous studies have addressed short-term and long-term effects of tDCS on different measures of behavioral performance during motor and cognitive tasks, both in healthy individuals and in a number of different patient populations. So far, however, little is known about the neural underpinnings of tDCS-action in humans with regard to large-scale brain networks. This issue can be addressed by combining tDCS with functional brain imaging techniques like functional magnetic resonance imaging (fMRI) or electroencephalography (EEG).
In particular, fMRI is the most widely used brain imaging technique to investigate the neural mechanisms underlying cognition and motor functions. Application of tDCS during fMRI allows analysis of the neural mechanisms underlying behavioral tDCS effects with high spatial resolution across the entire brain. Recent studies using this technique identified stimulation induced changes in task-related functional brain activity at the stimulation site&#160;and also in more distant brain regions, which were associated with behavioral improvement. In addition, tDCS administered during resting-state fMRI allowed identification of widespread changes in whole brain functional connectivity.
Future studies using this combined protocol should yield new insights into the mechanisms of tDCS action in health and disease and new options for more targeted application of tDCS in research and clinical settings. The present manuscript describes this novel technique in a step-by-step fashion, with a focus on technical aspects of tDCS administered during fMRI.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique. It has successfully been used in basic research and clinical settings to modulate brain function in humans. This article describes the implementation of tDCS and simultaneous functional magnetic resonance imaging (fMRI), to investigate the neural basis of tDCS effects.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses weak electrical currents administered to the scalp ...

Transcranial Magnetic Stimulation for Investigating Causal Brain-behavioral Relationships and their Time Course

Transcranial magnetic stimulation (TMS) is a safe, non-invasive brain stimulation technique that uses a strong electromagnet in order to temporarily disrupt information processing in a brain region, generating a short-lived &#8220;virtual lesion.&#8221; Stimulation that interferes with task performance indicates that the affected brain region is necessary to perform the task normally. In other words, unlike neuroimaging methods such as functional magnetic resonance imaging (fMRI) that indicate correlations between brain and behavior, TMS can be used to demonstrate causal brain-behavior relations. Furthermore, by varying the duration and onset of the virtual lesion, TMS can also reveal the time course of normal processing. As a result, TMS has become an important tool in cognitive neuroscience. Advantages of the technique over lesion-deficit studies include better spatial-temporal precision of the disruption effect, the ability to use participants as their own control subjects, and the accessibility of participants. Limitations include concurrent auditory and somatosensory stimulation that may influence task performance, limited access to structures more than a few centimeters from the surface of the scalp, and the relatively large space of free parameters that need to be optimized in order for the experiment to work. Experimental designs that give careful consideration to appropriate control conditions help to address these concerns. This article illustrates these issues with TMS results that investigate the spatial and temporal contributions of the left supramarginal gyrus (SMG) to reading.

Transcranial magnetic stimulation (TMS) is a technique for non-invasively disrupting neural information processing and measuring its effect on behavior. When TMS interferes with a task, it indicates that the stimulated brain region is necessary for normal task performance, allowing one to systematically relate brain regions to cognitive functions.

Transcranial magnetic stimulation (TMS) is a safe, non-invasive brain stimulation technique that uses a strong electromagnet in order to temporarily ...

Modulating Cognition Using Transcranial Direct Current Stimulation of the Cerebellum

Numerous studies have emerged recently that demonstrate the possibility of modulating, and in some cases enhancing, cognitive processes by exciting brain regions involved in working memory and attention using transcranial electrical brain stimulation. Some researchers now believe the cerebellum supports cognition, possibly via a remote neuromodulatory effect on the prefrontal cortex. This paper describes a procedure for investigating a role for the cerebellum in cognition using transcranial direct current stimulation (tDCS), and a selection of information-processing tasks of varying task difficulty, which have previously been shown to involve working memory, attention and cerebellar functioning. One task is called the Paced Auditory Serial Addition Task (PASAT) and the other a novel variant of this task called the Paced Auditory Serial Subtraction Task (PASST). A verb generation task and its two controls (noun and verb reading) were also investigated. All five tasks were performed by three separate groups of participants, before and after the modulation of cortico-cerebellar connectivity using anodal, cathodal or sham tDCS over the right cerebellar cortex. The procedure demonstrates how performance (accuracy, verbal response latency and variability) could be selectively improved after cathodal stimulation, but only during tasks that the participants rated as difficult, and not easy. Performance was unchanged by anodal or sham stimulation. These findings demonstrate a role for the cerebellum in cognition, whereby activity in the left prefrontal cortex is likely dis-inhibited by cathodal tDCS over the right cerebellar cortex. Transcranial brain stimulation is growing in popularity in various labs and clinics. However, the after-effects of tDCS are inconsistent between individuals and not always polarity-specific, and may even be task- or load-specific, all of which requires further study. Future efforts might also be guided towards neuro-enhancement in cerebellar patients presenting with cognitive impairment once a better understanding of brain stimulation mechanisms has emerged.

Transcranial direct current stimulation (tDCS) over the cerebellum exerts a remote effect on the prefrontal cortex, which can modulate cognition and performance. This was demonstrated using two information-processing tasks of varying complexity, whereby only cathodal tDCS improved performance when the task was difficult, but not easy.

Numerous studies have emerged recently that demonstrate the possibility of modulating, and in some cases enhancing, cognitive processes by exciting brain ...

The study of neuromuscular control of movement in humans is accomplished with numerous technologies. Non-invasive methods for investigating neuromuscular function include transcranial magnetic stimulation, electromyography, and three-dimensional motion capture. The advent of readily available and cost-effective virtual reality solutions has expanded the capabilities of researchers in recreating &#8220;real-world&#8221; environments and movements in a laboratory setting. Naturalistic movement analysis will not only garner a greater understanding of motor control in healthy individuals, but also permit the design of experiments and rehabilitation strategies that target specific motor impairments (e.g. stroke). The combined use of these tools will lead to increasingly deeper understanding of neural mechanisms of motor control. A key requirement when combining these data acquisition systems is fine temporal correspondence between the various data streams. This protocol describes a multifunctional system&#8217;s overall connectivity, intersystem signaling, and the temporal synchronization of recorded data. Synchronization of the component systems is primarily accomplished through the use of a customizable circuit, readily made with off the shelf components and minimal electronics assembly skills.

Transcranial magnetic stimulation, electromyography, and 3D motion capture are commonly used non-invasive techniques for investigating neuromuscular function in humans. In this paper, we describe a protocol that synchronously samples data generated by all three of these tools along with the unique addition of virtual reality stimulus presentation and feedback.

The study of neuromuscular control of movement in humans is accomplished with numerous technologies. Non-invasive methods for investigating neuromuscular ...

Repetitive transcranial magnetic stimulation (rTMS) is widely used for several neurological conditions, as it has gained acknowledgement for its potential therapeutic effects. Brain excitability is non-invasively modulated by rTMS, and rTMS to the language areas has proved its potential effects on treatment of aphasia. In our protocol, we aim to artificially induce virtual aphasia in healthy subjects by inhibiting Brodmann area 44 and 45 using neuronavigational TMS (nTMS), and F3 of the International 10-20 EEG system for conventional TMS (cTMS). To measure the degree of aphasia, changes in reaction time to a picture naming task pre- and post-stimulation are measured and compare the delay in reaction time between nTMS and cTMS. Accuracy of the two TMS stimulation methods is compared by averaging the Talairach coordinates of the target and the actual stimulation. Consistency of stimulation is demonstrated by the error range from the target. The purpose of this study is to demonstrate use of nTMS and to describe the benefits and limitations of the nTMS compared to those of cTMS.

This study is designed to test the hypothesis that neuronavigational system-guided transcranial magnetic stimulation has higher accuracy for targeting the intended target as demonstrated by eliciting a greater degree of virtual aphasia in healthy subjects, measured by delay in reaction time to picture naming.

Repetitive transcranial magnetic stimulation (rTMS) is widely used for several neurological conditions, as it has gained acknowledgement for its potential ...

Concurrent Electroencephalography Recording During Transcranial Alternating Current Stimulation (tACS)

Oscillatory brain activities are considered to reflect the basis of rhythmic changes in transmission efficacy across brain networks and are assumed to integrate cognitive neural processes. Transcranial alternating current stimulation (tACS) holds the promise to elucidate the causal link between specific frequencies of oscillatory brain activity and cognitive processes. Simultaneous electroencephalography (EEG) recording during tACS would offer an opportunity to directly explore immediate neurophysiological effects of tACS. However, it is not trivial to measure EEG signals during tACS, as tACS creates a huge artifact in EEG data. Here we explain how to set up concurrent tACS-EEG experiments. Two necessary considerations for successful EEG recording while applying tACS are highlighted. First, bridging of the tACS and EEG electrodes via leaking EEG gel immediately saturates the EEG amplifier. To avoid bridging via gel, the viscosity of the EEG gel is the most important parameter. The EEG gel must be viscous to avoid bridging, but at the same time sufficiently fluid to create contact between the tACS electrode and the scalp. Second, due to the large amplitude of the tACS artifact, it is important to consider using an EEG system with a high resolution analog-to-digital (A/D) converter. In particular, the magnitude of the tACS artifact can exceed 100 mV at the vicinity of a stimulation electrode when 1 mA tACS is applied. The resolution of the A/D converter is of importance to measure good quality EEG data from the vicinity of the stimulation site. By following these guidelines for the procedures and technical considerations, successful concurrent EEG recording during tACS will be realized.

Concurrent Electroencephalography Recording During Transcranial Alternating Current Stimulation tACS

In this article we explain how to set up a concurrent transcranial alternating current stimulation and EEG experiment.

Oscillatory brain activities are considered to reflect the basis of rhythmic changes in transmission efficacy across brain networks and are assumed to ...

Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses electromagnetic coils to stimulate areas of the brain non-invasively. Deep transcranial magnetic stimulation (dTMS) with the Brainsway H1-coil system specifically is a type of rTMS indicated for treating patients with major depressive disorder (MDD) who are resistant to medication. The unique H1-coil design of this device is able to stimulate neuronal pathways that lie deeper in the targeted brain areas than those reached by conventional rTMS coils. dTMS is considered to be low-risk and well tolerated, making it a viable treatment option for people who have not responded to medication or psychotherapy trials for their depression.
Randomized, sham-control studies have demonstrated that dTMS produces significantly greater improvement in depressive symptoms than sham dTMS treatment in patients with major depression that has not responded to antidepressant medication. In this paper, we will review the methodology for treating major depression with dTMS using an H1-coil.

Here we present a protocol outlining the methodology for treatment of Major Depressive Disorder using the deep Transcranial Magnetic Stimulation (dTMS) system.

Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses ...

Previous rodent models of repetitive transcranial magnetic stimulation (rTMS) adopted whole-brain stimulation instead of unilateral hemispheric rTMS, which is unlike the protocols used for human subjects. We report a successful application of rTMS to the unilateral hemisphere of rat brain. The rTMS was delivered with a low-frequency (1 Hz), high-frequency (20 Hz), or sham stimulation protocol to one side of the brain by using a small 25-mm figure-8 coil. We placed the center of the coil 1 cm lateral to the vertex on the biauricular line and angulated the coil 45&#176; to the ground to minimize a potential direct effect of rTMS on the contralateral cortex. We also used an in-house water cooling system to enable repetitive magnetic stimulation for more than 20 min, even at a 20-Hz stimulation frequency. Increases in the transcriptions of immediate early genes (Arc, Junb, and Egr2) were greater after rTMS than after sham stimulation. After 5 consecutive days of 20-min 1-Hz rTMS, bdnf mRNA expression was significantly higher in stimulated cortex than in contralateral side. The model presented herein will elucidate the molecular mechanisms of rTMS by allowing analysis of the inter-hemispheric difference in its effect.

We applied repetitive transcranial magnetic stimulation (rTMS) to the unilateral hemisphere of rat brain, by placing a 25-mm figure-8 coil 1 cm lateral to the vertex on the biauricular line and angulating the coil by 45&#176;. An in-house water cooling system was used for rTMS for more than 20 min.

Previous rodent models of repetitive transcranial magnetic stimulation (rTMS) adopted whole-brain stimulation instead of unilateral hemispheric rTMS, ...