The authors have no acknowledgements.

This protocol was approved by the local ethics committee, and the experiments are in accordance with the Declaration of Helsinki (1964).
1. Ethical Approval and Subject Instruction
<ol>
	<li>Before starting the measurement, instruct all participants about the potential risk factors and the purpose of the study. Do not give information about the attentional foci, as this might affect the results. Ensure that the safety guidelines for the application of TMS in research settings 30 are followed. 
	NOTE: When applying TMS, there are some medical risk factors, including implanted cranial electrodes and cochlear implants, personal history of syncope or seizure, epilepsy, cerebral lesion, drug/medication interactions, recent drug withdrawal, pregnancy, or illness. TMS should not be administered in children.</li>
	<li>In the study, include healthy participants (n = 14) between 18 and 35 years old. Exclude subjects with any orthopedic and/or neurological/mental diseases. Ensure that all participants are right-handed.</li>
</ol>
2. Experimental Design and Setup
<ol>
	<li>Divide the group in two. Instruct one half of the group on IF instructions first, followed by EF instructions in the second experimental session (see section 4.2.2 for the verbal instructions). Instruct the other half in a counterbalanced order. 
	NOTE: The experiment consists of a total of four laboratory sessions (see Figure 1) that must be separated by a minimum of 72 h. The first two sessions consist of measuring the maximal force (Fmax) and the TTF of submaximal sustained index finger abduction (see step 4). The third and fourth sessions consist of measuring the activity of inhibitory circuits within the M1 during the task by means of subTMS and ppTMS (see Figure 1).</li>
</ol>
3. Subject Preparation
<ol>
	<li>Seat the participant in an adjustable and comfortable chair throughout the whole experiment. Place a monitor 1 m in front of the participant.</li>
	<li>Place the left arm in a comfortable and relaxed position under the table, resting on the left leg. If needed, adjust the position of the arm with a pillow. Place the right arm of the subject in a custom-built splint in pronated position (see Figure 2). 
	NOTE: Here, the splint is made of thermoplastic and fit all participants (for details, see16). In addition, the splint was conceived to restrict the degrees of freedom of the wrist joint (see Figure 2B). The only movements allowed were the abduction and adduction of the metacarpophalangeal joint of the index finger of the right hand.</li>
	<li>Align the finger joint with the axis of rotation of the custom-made device. Once the optimal position is found, record manually and take a picture of the antero-posterior and medio-lateral positions of the splint to use comparable positions in sessions 2, 3, and 4.</li>
</ol>
4. Sessions 1 and 2: Behavioral Tests
<ol>
	<li>Maximal isometric contractions (see Figure 1A).
	<ol>
		<li>Align the axes of rotation of the goniometer and the metacarpophalangeal joint and fix the goniometer properly using screws (see Figure 2). Place the force transducer in a way that allows for maximum voluntary contractions (see Figure 2B).</li>
		<li>Connect the EMG cable (FDI muscle), the force transducer, and the goniometer cables to the appropriate amplifier and/or analog to digital (A-D) converter.</li>
		<li>Have the participant perform 3 maximal isometric abductions of the index finger, with a 30-s break between each contraction, and determine the Fmax. 
		NOTE: The Fmax is determined as the highest peak in the force signal obtained from the force transducer. Explain to the participant that maximal contractions consist of a gradual increase in force from 0 N to the individual maximum. Importantly, instruct participants to perform an isometric contraction against the stationary force transducer. Participants should abduct the index finger at the metacarpophalangeal joint and push as hard as possible against the force transducer. A 3-s time span should be given per contraction, and participants should be instructed to sustain the maximal force for 2 s16,25,26. Between each contraction, give the participants a 30-s break.</li>
		<li>Have the subject push the lever against the force transducer, without giving any instruction about the focus of attention. 
		NOTE: The same task will be done at the beginning of session 2 to ensure that the Fmax and the position in the splint have not changed between sessions.</li>
		<li>After maximal contractions, remove the force transducer, allowing the index finger to move freely in the transverse plane (abduction/adduction).</li>
		<li>Calculate the Fmax from the maximal isometric abductions (step 4.1.3) using the raw data on the computer. Determine 30% (Fmax * 0.3; sessions 1 and 2) and 10% (Fmax * 0.1; sessions 3 and 4) of Fmax. 
		NOTE: Consider the Fmax as the highest peak found in the force signal obtained from the force transducer. In the following sessions, the different contraction intensities (30% and 10%) will be calculated from the Fmax obtained at this stage of the experiment.</li>
		<li>Fill a bottle of water to the amount representing the 30% of Fmax obtained from step 4.1.6. Attach the weight of Fmax to the rope of the device (see Figure 2A). 
		NOTE: The volumetric mass density of water is 1 kg/L. Thus, if the 30% of Fmax of one participant represents 0.4 kg, adjust the weight of the bottle to the equivalent of 0.4 kg.</li>
	</ol>
	</li>
	<li>Sustained contractions until TTF (see Figure 1A).
	<ol>
		<li>Instruct the participants about the task. 
		NOTE: Participants must hold the finger in the target position by counteracting the weight (see Figure 2), performing an abduction of the index finger. The task must be performed until task failure. The task failure is determined as a deviation greater than 10 degrees from the target position. The deviation is measured by the goniometer and displayed on the monitor (see Figure 2B).</li>
		<li>Randomize the order of session (see step 2.1; EF or IF condition). Verbally instruct the participants on the adequate condition (IF or EF).
		<ol>
			<li>For the EF condition, instruct as follows: &#34;Concentrate on the position of the goniometer. Hold this position as long as possible. When the position of the goniometer changes, the thickness of the red line on the screen changes. Correct the position of the goniometer until the red line is thin again.&#34; Instruct the participant to &#34;control and concentrate on the position of the goniometer&#34; every 30 s.</li>
			<li>For the IF condition, instruct as follows: &#34;Concentrate on the position of your finger. Hold this position as long as possible. When the position of your finger changes, the thickness of the red line on the screen changes. Correct the position of your finger until the red line is thin again.&#34; Instruct the participant to &#34;contract and concentrate on his finger muscles&#34; every 30 s.</li>
		</ol>
		</li>
		<li>Have the participants hold the finger in the target position by counteracting the weight (see Figure 2), performing an abduction of the index finger. Have them perform the task until task failure.</li>
		<li>Press the &#34;record&#34; button on the recording software to start recording the goniometer signal and wait until task failure. Once task failure is reached, press the &#34;stop recording&#34; button on the recording software to stop the recording and save the goniometer signal on the computer. Remove the participant&#39;s hand from the orthopedic splint; the first session is now over.</li>
		<li>Respecting the minimum inter-session period (72 h), repeat steps 4.2.1-4.2.4. In addition, allow a minimum of a 72-h break between sessions 2 and 3 and sessions 3 and 4.</li>
	</ol>
	</li>
</ol>
5. Sessions 3 and 4: Brain Stimulation
<ol>
	<li>Surface electromyography (sEMG) recordings.
	<ol>
		<li>Shave the hair on the skin over the right FDI muscle, if needed, and then slightly abrade the skin using abrading gel. Disinfect the abraded area with a solution containing 80% ethanol and 1% glycerin. Allow the ethanol to evaporate.</li>
		<li>Place the Ag/AgCl bipolar surface electrodes in a belly-tendon montage on the FDI, with 1-cm interelectrode distance. Place the reference electrode on the phalanx of the digitus medius.</li>
		<li>Connect the EMG cable (FDI muscle) and the goniometer cable to an EMG amplifier and to an A-D converter.</li>
		<li>Use Ag/AgCl bipolar surface electrodes to record and measure muscular activity and electrophysiological responses elicited by brain stimulation from the FDI muscle. 
		NOTE: For the final analysis (subTMS-induced EMG suppression and peak-to-peak MEP amplitude), the EMG signal (from the FDI) must be adjusted as follows: amplification of x1000, Butterworth band-pass filtering of 10-1000 Hz, and sampling of 4 kHz. Store all EMG data on a computer for offline analysis.</li>
	</ol>
	</li>
	<li>Repeat steps 3.1 and 3.2.</li>
	<li>Transcranial magnetic stimulation
	<ol>
		<li>Fix the reflective markers on the participant&#39;s forehead with double-sided adhesive tape. 
		NOTE: Reflective markers allow for the constantly delivery of TMS to the target area over M1 by using a neuronavigation system (see Figure 2). The advantage of the neuronavigation system is that the coil position can be recorded relative to the skull position in space and be checked at any time throughout the entire experiment.</li>
		<li>Use a 95-mm focal figure of eight coils attached to a TMS stimulator to deliver stimuli to the contralateral motor cortical hand area. 
		NOTE: Check that the stimulator allows for paired-pulse stimulation paradigms (session 4). In addition, the induced current must be directed posterior to anterior and must be delivered in reverse mode. The wave form should be monophasic.</li>
		<li>Find the optimal position (hot spot) of the coil relative to the skull for eliciting motor evoked potentials (MEPs) in the FDI muscle by performing a classical mapping procedure.
		<ol>
			<li>Start by placing the coil approximately 0.5 cm anterior to the vertex and over the midline, with the coil handle pointing at 45&#176; towards the contralateral forehead. 
			NOTE: This will ensure that the induced current flow is approximately perpendicular to the central sulcus31.</li>
			<li>To get the participants used to the TMS stimuli, start at intensities below 25% of maximum stimulator output (MSO). Then, start to increase the stimulation intensity and move the coil in the medio-lateral and rostro-frontal direction to discover the hot spot.</li>
		</ol>
		</li>
		<li>Once the hot spot is found, record the optimal position with the neuronavigation system.Determine the active motor threshold (aMT) by adjusting the intensity of the stimulator output. Define the aMT as the minimum intensity required to evoke MEP peak-to-peak amplitudes in the EMG of the FDI larger than 0.1 mV in three out of five consecutive trials21.</li>
	</ol>
	</li>
	<li>Session 3: SubTMS-induced EMG suppression (see Figure 1B).
	<ol>
		<li>Prepare the weight representing the 10% of Fmax by filling the bottle of water (see step 4.1.7). 
		NOTE: The 10% of Fmax are selected based on the Fmax (the best of 3 trials) performed in step 4.1.3. In the subthreshold TMS protocol, only 10% of the Fmax has to be selected, as it has previously been shown that fatigue has an influence on subTMS-induced EMG suppression32,33. For the same reason, the subTMS session must be carried out on a separate session. The volume of water used here is between 0.3 L (smallest 30% of Fmax) and 1.2 L (biggest 30% of Fmax).</li>
		<li>Instruct participants about the task; the motor task consists of holding the index finger in the target position by counteracting the light weight of 10% (abduction of the index finger; the same task as in sessions 1 and 2, but with less weight).</li>
		<li>As the participants remain relaxed in a comfortable position, find the optimal intensity for eliciting subTMS-EMG suppression, without giving any instruction about the focus of attention. To do this, successively diminish in steps of 2% MSO from the aMT determined previously.</li>
		<li>While they are still seated in the relaxed and comfortable position, have the participants perform two separate isometric index finger abductions at 10% of Fmax and record the EMG signal of the FDI. During this isometric index finger abduction, record (by pressing the &#34;record&#34; button on the recording software) 20 trials with and 20 trials without TMS, with a randomized interstimulus interval (ISIs) ranging from 0.8 to 1.1 s16,25,26,33,34 in a 100-ms time window. 
		NOTE: This interval ensures that participants do not have to perform the motor task for too long and therefore minimizes fatiguing effects. After each series, check the subTMS-induced EMG suppression.
		<ol>
			<li>Apply a full-wave rectification by converting all negative amplitudes to positive amplitudes in the EMG signals. Average the EMG signals using time-normalized averaging35. 
			NOTE: The onset of subTMS-EMG suppression is defined as the moment when the difference between the trials with and those without TMS is negative for at least 4 ms in a time window from 20 to 50 ms after the TMS: EMGDiff = EMGWithout- EMGWith.</li>
		</ol>
		</li>
		<li>Repeat step 5.4.3 until the optimal stimulation intensity is found, indicated by the largest EMG suppression. 
		NOTE: The optimal intensity is found at around 80% of aMT16.</li>
		<li>Give the participant the adequate instructions (see step 4.2.2) regarding the condition (IF or EF). Repeat the instructions before each series (step 4.2.2).</li>
		<li>While they remain seated in the relaxed and comfortable position, have the participants perform four separate isometric index finger abductions (2 times with each focus: EF and IF) at 10% of Fmax and record the EMG signal of the FDI.
		<ol>
			<li>During this isometric index finger abduction, record (by pressing the &#34;record&#34; button on the recording software) 40 trials with and 40 trials without TMS, with randomized ISIs for each condition (i.e., IF and EF) in a counterbalanced order. Use the same intensity for each condition (determined in point 5.4.5).</li>
		</ol>
		</li>
		<li>Between each series, allow a break of a minimum of 5 min to minimize any bias that may be induced by fatigue.</li>
	</ol>
	</li>
	<li>Session 4: ppTMS (see Figure 1B). 
	NOTE: The paired-pulse paradigm is composed of a conditioning stimulus at 0.8 aMT, followed by a suprathreshold control stimulus at 1.2 aMT.
	<ol>
		<li>Repeat steps 5.1-5.4. In brief, place EMG electrodes over the FDI muscle, seat the participant in an adjustable and comfortable chair, and place the left arm in a comfortable and relaxed position under the table (i.e., on the left leg). Find the hotspot for TMS over the M1.</li>
		<li>Set the intensity on the stimulator, the ISI at 2.5 ms36, and the interval between paired and single-pulse TMS at 0.25 Hz.</li>
		<li>Give the participant adequate instructions (see step 4.2.2) regarding the condition (i.e. IF or EF). Repeat the instructions before each series.</li>
		<li>Have the participants perform four separate isometric index finger abductions (2 times with each focus: EF and IF) at 10% of Fmax and record the EMG signal of the FDI. During the isometric contraction, record 20 TMS stimuli for each condition (i.e., IF and EF) in a counterbalanced order. 
		NOTE: One set of 20 stimuli must be composed of 10 conditioned MEPs (paired-pulse at 0.8-1.2 aMT) and 10 control MEPs (single-pulse at 1.2 aMT). Use the same intensity for each condition (determined in step 5.5.2).</li>
		<li>Between each series, allow a break of a minimum of 5 min to minimize any bias that may be induced by fatigue.</li>
	</ol>
	</li>
</ol>
6. Data Processing and Analysis
<ol>
	<li>SubTMS.
	<ol>
		<li>As explained above (step 5.1.1.3), rectify and average the EMG for analysis.</li>
		<li>Detect the onset of subTMS-EMG suppression (see Figure 4). 
		NOTE: It is defined as the moment when the difference between the average of all trials with and those without TMS is negative for at least 4 ms in a time window from 20-50 ms after the TMS.</li>
		<li>To detect the end of subTMS-EMG suppression, define the moment after the onset of suppression (step 6.1.2) when the difference between the average of all trials with and those without TMS is positive again for at least 4 ms (see Figure 4a).</li>
		<li>Calculate the subTMS-induced EMG as follows: 
		EMGDiff = EMGWithout &#8211; EMGWith.
		<ol>
			<li>Compute the cumulative trapezoidal numerical integration from the onset to the end of the suppression to quantify the amount of subTMS-induced EMG suppression.</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>ppTMS.
	<ol>
		<li>Use the following formula to express the magnitude of SICI as a percentage relating to the control MEP: 
		100 &#8211; (conditioned MEP/control MEP &#215; 100).
		<ol>
			<li>Use the results as percentage values for the final analysis.</li>
		</ol>
		</li>
		<li>Calculate peak-to-peak MEP amplitudes (in mV; in the EF and IF conditions) and compare the two conditions in the final analysis.</li>
	</ol>
	</li>
	<li>EMG.
	<ol>
		<li>As background EMG has an influence on the magnitude of MEPs37, determine the EMG activity by computing the root-mean-square value in a 100-ms window before the TMS.</li>
	</ol>
	</li>
</ol>

The authors have nothing to disclose.

This protocol shows two possible methods to investigate the activity of inhibitory circuits within the M1 using TMS. More precisely, these two protocols have been used in this study to investigate the impact of attentional foci on the activity of inhibitory circuits within the M1.
One limitation of the presented method is that it is not always possible to cause a subTMS-induced EMG suppression without a facilitation preceding it. In this study, for example, four subjects had to be removed from...

It is now generally accepted that adopting an EF compared to an IF or neutral focus of attention promotes motor performance and learning in numerous settings1. It has been shown, for example, that adopting an EF leads to benefits in accuracy2,3, balance4,5,6, force production7,8, jumping performance7,9,10,11, movement speed12, oxygen consumption13,14, and fatiguing tasks15,16.
On the other side, since brain activation is the basis of all movements, several aspects of the neural control of movement have been investigated. For example, the level and the ability to modulate intracortical inhibition within the M1 has been shown to have a strong influence on motor function, such as interlimb coordination17, postural control18, and dexterity19. Furthermore, populations with poorer motor control abilities than young adults, such as elderly subjects or children (born preterm20), usually show less pronounced inhibitory control. Thus, although the role of inhibitory processes is not yet well understood, inhibitory processes nevertheless seem to be important to the quality of motor execution in general.
A possibility to investigate intracortical inhibitory circuitries is to use non-invasive transcranial magnetic stimulation (TMS). The most commonly used stimulation protocol applies paired-pulse TMS (ppTMS) to induce SICI. This protocol uses a conditioning stimulus below the motor threshold to reduce the amplitude of the suprathreshold control stimulus response elicited at an interstimulus interval of 1-5 ms21,22,23,24. Then, reported as the percentage of the control stimulus, the amplitudes of the motor-evoked potentials (MEPs) can be compared across conditions, giving information about cortical inhibitory activity and modulation within the M1.
Another stimulation protocol to assess the activity of intractortical inhibitory circuits applies single pulses, where all stimuli are delivered at intensities below the motor threshold (i.e., subTMS). This protocol induces suppression in the ongoing EMG activity18,25,26. This so-called subTMS-induced EMG suppression can be compared in terms of amount and duration. Although this protocol is not so commonly used, it has certain advantages compared to the standard SICI protocol. This protocol does not disturb motor execution, as it does not induce suprathreshold stimuli. Both methods test the responsiveness of intracortical gamma-aminobutyric acid (GABA) inhibitory interneurons23,27.
Despite the well-known benefits of using an EF compared to an IF on motor performance1, the underlying neural processes remain largely unknown. In a former fMRI study28, it was shown that blood-oxygen level-dependent (BOLD) activation was enhanced in the M1, primary somatosensory, and insular cortices when subjects executed a finger sequence and adopted an EF compared to an IF. As excitatory and inhibitory activity cannot be differentiated by fMRI29, another recent study16 stipulated that the enhanced activity in the M1 associated with an EF could, in fact, be due to the enhanced activity of intracortical inhibitory circuits. More precisely, this study showed that the excitability of inhibitory GABAergic neurons can be modulated instantly by the type of attentional focus adopted in one and the same person.
The main aim of the present protocol is to show two possible ways to compare the immediate effects of cognitive manipulation (i.e., focus of attention instructions) on the activity of intracortical inhibitory circuits within the M1. SubTMS and ppTMS are both used. In addition, this protocol shows one possible way to explore the influence of attentional foci on motor behavior in a very controlled way by investigating the TTF of submaximal isometric sustained contraction of the FDI.

<table><tbody><tr><td>MC3A-100</td><td>Advanced Mechanical Technologies Inc., Watertown, MA, USA</td><td>-</td><td>Force transducer</td></tr><tr><td>BlueSensor P</td><td>Ambu A/S, Bellerup, Denmark</td><td>-</td><td>Ag/AgCl surface electrodes for EMG</td></tr><tr><td>Polaris Spectra</td><td>Northern Digital, Waterloo, ON, Canada</td><td>-</td><td>neuronavigation system, active or passive markers tracker</td></tr><tr><td>Localite TMS Navigator Version 2.0.5</td><td>LOCALITE GmbH, Sankt Augustin, Germany</td><td>-</td><td>navigation system for transcranial magnetic stimulation (TMS)</td></tr><tr><td>MagVenture MagPro X100</td><td>MagVenture A/S, Farum, Denmark</td><td>9016E0711</td><td>Transcranial magnetic stimulator</td></tr><tr><td>MagVenture D-B80</td><td>MagVenture A/S, Farum, Denmark</td><td>9016E0431</td><td>TMS coil (figure of eight)</td></tr><tr><td>Goniometer</td><td>N/A</td><td>-</td><td>Custom-made goniometer</td></tr><tr><td>Othopedic splint</td><td>N/A</td><td>-</td><td>Custom-made splint</td></tr><tr><td>Recording software</td><td>LabView based</td><td>-</td><td>Custom-made script</td></tr></tbody></table>

intracortical inhibition within the primary motor cortex can be modulated by changing the focus of attention

It is well recognized that an external focus (EF) compared with an internal focus (IF) of attention improves motor learning and performance. Studies have indicated benefits in accuracy, balance, force production, jumping performance, movement speed, oxygen consumption, and fatiguing task. Although behavioral outcomes of using an EF strategy are well explored, the underlying neural mechanisms remain unknown. A recent TMS study compared the activity of the primary motor cortex (M1) between an EF and an IF. More precisely, this study showed that, when adopting an EF, the activity of intracortical inhibitory circuits is enhanced.
On the behavioral level, the present protocol tests the influence of attentional foci on the time to task failure (TTF) when performing submaximal contractions of the first dorsal interosseous (FDI). Additionally, the current paper describes two TMS protocols to assess the influence of attentional conditions on the activity of cortical inhibitory circuits within the M1. Thus, the present article describes how to use single-pulse TMS at intensities below the motor threshold (subTMS) and paired-pulse TMS, inducing short-interval intracortical inhibition (SICI) when applied to the M1. As these methods are assumed to reflect the responsiveness of GABAergic inhibitory neurons, without being affected by spinal reflex circuitries, they are well suited to measuring the activity of intracortical inhibitory circuits within the M1.
The results show that directing attention externally improves motor performance, as participants were able to prolong the time to task failure. Moreover, the results were accompanied by a larger subTMS-induced electromyography suppression and SICI when adopting an EF compared to an IF. As the level of cortical inhibition within the M1 was previously demonstrated to influence motor performance, the enhanced inhibition with an EF might contribute to the better movement efficiency observed in the behavioral task, indicated by a prolonged TTF with an EF.

The Influence of Attentional Foci on Motor Performance:
The behavioral tests in the current study were used to prove the feasibility of the motor task and to identify the subjects who reacted positively when applying an EF. In line with previous studies (see1 for a review), our results show a prolonged TTF when the participants adopted an EF compared to an IF (see Figure 3). Thu...

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Intracortical Inhibition Within the Primary Motor Cortex Can Be Modulated by Changing the Focus of Attention

Using two different transcranial magnetic stimulation (TMS) protocols, this manuscript describes how to measure and compare cortical inhibition within the primary motor cortex when adopting different attentional foci.

It is well recognized that an external focus (EF) compared with an internal focus (IF) of attention improves motor learning and performance. Studies have ...

intracortical-inhibition-within-primary-motor-cortex-can-be-modulated

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9.9K Views.  University of Fribourg. Dit manuscript wordt met behulp van twee verschillende Transcraniële magnetische stimulatie (TMS) protocollen, beschreven hoe om te meten en vergelijken van corticale remming binnen de primaire motorische cortex, bij de vaststelling van verschillende attentional foci.

Video: Intracortical Inhibition Within the Primary Motor Cortex Can Be Modulated by Changing the Focus of Attention

Corticospinal Excitability Modulation During Action Observation

This study used the transcranial magnetic stimulation/motor evoked potential (TMS/MEP) technique to pinpoint when the automatic tendency to mirror someone else's action becomes anticipatory simulation of a complementary act. TMS was delivered to the left primary motor cortex corresponding to the hand to induce the highest level of MEP activity from the abductor digiti minimi (ADM; the muscle serving little finger abduction) as well as the first dorsal interosseus (FDI; the muscle serving index finger flexion/extension) muscles. A neuronavigation system was used to maintain the position of the TMS coil, and electromyographic (EMG) activity was recorded from the right ADM and FDI muscles. Producing original data with regard to motor resonance, the combined TMS/MEP technique has taken research on the perception-action coupling mechanism a step further. Specifically, it has answered the questions of how and when observing another person's actions produces motor facilitation in an onlooker's corresponding muscles and in what way corticospinal excitability is modulated in social contexts.

Single-pulse transcranial magnetic stimulation over the primary motor cortex, neuronavigation, and registration of electromyographic activity of hand muscles were used in this study to explore corticospinal excitability while participants were observing action sequences.

This study used the transcranial magnetic stimulation/motor evoked potential (TMS/MEP) technique to pinpoint when the automatic tendency to mirror someone ...

Measurement of Neurophysiological Signals of Ignoring and Attending Processes in Attention Control

Attention control is the ability to selectively attend to some sensory signals while ignoring others. This ability is thought to involve two processes: enhancement of sensory signals that are to be attended and the attenuation of sensory signals that are to be ignored. The overall strength of attentional modulation is often measured by comparing the amplitude of a sensory neural response to an external input when attended versus when ignored. This method is robust for detecting attentional modulation, but precludes the ability to assess the separate dynamics of attending and ignoring processes. Here, we describe methodology to measure independently the neurophysiological signals of attending and ignoring using the intermodal attention task (IMAT). This task, when combined with electroencephalography, isolates neurophysiological sensory responses in auditory and visual modalities, when either attending or ignoring, with respect to a passive control. As a result, independent dynamics of attending and of a ignoring can be assessed in either modality. Our results using this task indicate that the timing and cortical sources of attending and ignoring effects differ, as do their contributions to the attention modulation effect, pointing to unique neural trajectories and demonstrating sample utility of measuring them separately.

Attention control comprises enhancement of target signals and attenuation of distractor signals. We describe an approach to measure separately but concurrently, the neurophysiology of attending and ignoring in sustained intermodal attention, utilizing a passive control condition during which neither process is continuously engaged.

Attention control is the ability to selectively attend to some sensory signals while ignoring others. This ability is thought to involve two processes: ...

Force and Position Control in Humans - The Role of Augmented Feedback

During motor behaviour, humans interact with the environment by for example manipulating objects and this is only possible because sensory feedback is constantly integrated into the central nervous system and these sensory inputs need to be weighted in order meet the task specific goals. Additional feedback presented as augmented feedback was shown to have an impact on motor control and motor learning. A number of studies investigated whether force or position feedback has an influence on motor control and neural activation. However, as in the previous studies the presentation of the force and position feedback was always identical, a recent study assessed whether not only the content but also the interpretation of the feedback has an influence on the time to fatigue of a sustained submaximal contraction and the (inhibitory) activity of the primary motor cortex using subthreshold transcranial magnetic stimulation. This paper describes one possible way to investigate the influence of the interpretation of feedback on motor behaviour by investigating the time to fatigue of submaximal sustained contractions together with the neuromuscular adaptations that can be investigated using surface EMG. Furthermore, the current protocol also describes how motor cortical (inhibitory) activity can be investigated using subthreshold TMS, a method known to act solely on the cortical level. The results show that when participants interpret the feedback as position feedback, they display a significantly shorter time to fatigue of a submaximal sustained contraction. Furthermore, subjects also displayed an increased inhibitory activity of the primary cortex when they believed to receive position feedback compared when they believed to receive force feedback. Accordingly, the results show that interpretation of feedback results in differences on a behavioural level (time to fatigue) that is also reflected in interpretation-specific differences in the amount of inhibitory M1 activity.

Controlling an identical movement with position or force feedback results in different neural activation and motor behavior. This protocol describes how to investigate behavioral changes by looking at neuromuscular fatigue and how to evaluate motor cortical (inhibitory) activity using subthreshold TMS with respect to the interpretation of augmented feedback.

During motor behaviour, humans interact with the environment by for example manipulating objects and this is only possible because sensory feedback is ...

Non-invasive Assessment of Changes in Corticomotoneuronal Transmission in Humans

The corticospinal pathway is the major pathway connecting the brain with the muscles and is therefore highly relevant for movement control and motor learning. There exists a number of noninvasive electrophysiological methods investigating the excitability and plasticity of this pathway. However, most methods are based on quantification of compound potentials and neglect that the corticospinal pathway consists of many different connections that are more or less direct. Here, we present a method that allows testing excitability of different fractions of the corticospinal transmission. This so called H-reflex conditioning technique allows one to assess excitability of the fastest (monosynaptic) and also polysynaptic corticospinal pathways. Furthermore, by using two different stimulation sites, the motor cortex and the cervicomedullary junction, it allows not only differentiation between cortical and spinal effects but also assessment of transmission at the corticomotoneural synapse. In this manuscript, we describe how this method can be used to assess corticomotoneural transmission after low-frequency repetitive transcranial magnetic stimulation, a method that was previously shown to reduce excitability of cortical cells. Here we demonstrate that not only cortical cells are affected by this repetitive stimulation but also transmission at the corticomotoneuronal synapse at the spinal level. This finding is important for the understanding of basic mechanisms and sites of neuroplasticity. Besides investigation of basic mechanisms, the H-reflex conditioning technique may be applied to test changes in corticospinal transmission following behavioral (e.g., training) or therapeutic interventions, pathology or aging and therefore allows a better understanding of neural processes that underlie movement control and motor learning.

The aim of the present study was to assess changes in transmission at the corticomotoneuronal synapses in humans after repetitive transcranial magnetic stimulation. For this purpose, an electrophysiological method is introduced that allows assessment of pathway specific corticospinal transmission, i.e. differentiation of fast, direct corticospinal pathways from polysynaptic connections.

The corticospinal pathway is the major pathway connecting the brain with the muscles and is therefore highly relevant for movement control and motor ...

Neuroscience

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

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific frequency and in turn modulate ongoing cortical oscillatory activity. This neurotool allows the establishment of a causal link between endogenous oscillatory activity and behavior. Most of the tACS studies have shown online effects of tACS. However, little is known about the underlying action mechanisms of this technique because of the AC-induced artifacts on Electroencephalography (EEG) signals. Here we show a unique approach to investigate online physiological frequency-specific effects of tACS of the primary motor cortex (M1) by using single pulse Transcranial Magnetic Stimulation (TMS) to probe cortical excitability changes. In our setup, the TMS coil is placed over the tACS electrode while Motor Evoked Potentials (MEPs) are collected to test the effects of the ongoing M1-tACS. So far, this approach has mainly been used to study the visual and motor systems. However, the current tACS-TMS setup can pave the way for future investigations of cognitive functions. Therefore, we provide a step-by-step manual and video guidelines for the procedure.

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.

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific ...

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

We describe the development of a reproducible, child-friendly motor response inhibition task suitable for online Transcranial Magnetic Stimulation (TMS) characterization of primary motor cortex (M1) excitability and inhibition. Motor response inhibition prevents unwanted actions and is abnormal in several neuropsychiatric conditions. TMS is a non-invasive technology that can quantify M1 excitability and inhibition using single- and paired-pulse protocols and can be precisely timed to study cortical physiology with high temporal resolution. We modified the original Slater-Hammel (S-H) stop signal task to create a &#34;racecar&#34; version with TMS pulses time-locked to intra-trial events. This task is self-paced, with each trial initiating after a button push to move the racecar towards the 800 ms target. GO trials require a finger-lift to stop the racecar just before this target. Interspersed randomly are STOP trials (25%) during which the dynamically adjusted stop signal prompts subjects to prevent finger-lift. For GO trials, TMS pulses were delivered at 650 ms after trial onset; whereas, for STOP trials, the TMS pulses occurred 150 ms after the stop signal. The timings of the TMS pulses were decided based on electroencephalography (EEG) studies showing event-related changes in these time ranges during stop signal tasks. This task was studied in 3 blocks at two study sites (n=38) and we recorded behavioral performance and event-related motor-evoked potentials (MEP). Regression modelling was used to analyze MEP amplitudes using age as a covariate with multiple independent variables (sex, study site, block, TMS pulse condition [single- vs. paired-pulse], trial condition [GO, successful STOP, failed STOP]). The analysis showed that TMS pulse condition (p&#60;0.0001) and its interaction with trial condition (p=0.009) were significant. Future applications for this online S-H/TMS paradigm include the addition of simultaneous EEG acquisition to measure TMS-evoked EEG potentials. A potential limitation is that in children, the TMS pulse sound could&#160;affect behavioral task performance.

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 Task.

We describe the development of a reproducible, child-friendly motor response inhibition task suitable for online Transcranial Magnetic Stimulation (TMS) ...

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

Understanding interactions between brain areas is important for the study of goal-directed behavior. Functional neuroimaging of brain connectivity has provided important insights into fundamental processes of the brain like cognition, learning, and motor control. However, this approach cannot provide causal evidence for the involvement of brain areas of interest. Transcranial magnetic stimulation (TMS) is a powerful, noninvasive tool for studying the human brain that can overcome this limitation by transiently modifying brain activity. Here, we highlight recent advances using a paired-pulse, dual-site TMS method with two coils that causally probes cortico-cortical interactions in the human motor system during different task contexts. Additionally, we describe a dual-site TMS protocol based on cortical paired associative stimulation (cPAS) that transiently enhances synaptic efficiency in two interconnected brain areas by applying repeated pairs of cortical stimuli with two coils. These methods can provide a better understanding of the mechanisms underlying cognitive-motor function as well as a new perspective on manipulating specific neural pathways in a targeted fashion to modulate brain circuits and improve behavior. This approach may prove to be an effective tool to develop more sophisticated models of brain-behavior relations and improve diagnosis and treatment of many neurological and psychiatric disorders.

This article describes new approaches to measure and strengthen functionally specific neural pathways with transcranial magnetic stimulation. These advanced noninvasive brain stimulation methodologies can provide new opportunities for the understanding of brain-behavior relations and development of new therapies to treat brain disorders.

Understanding interactions between brain areas is important for the study of goal-directed behavior. Functional neuroimaging of brain connectivity has ...

Conventional and Threshold-Tracking Transcranial Magnetic Stimulation Tests for Single-handed Operation

Most single-pulse transcranial magnetic stimulation (TMS) parameters (e.g., motor threshold, stimulus-response function, cortical silent period) are used to examine corticospinal excitability. Paired-pulse TMS paradigms (e.g., short- and long-interval intracortical inhibition (SICI/LICI), short-interval intracortical facilitation (SICF), and short- and long-latency afferent inhibition (SAI/LAI)) provide information about intracortical inhibitory and facilitatory networks. This has long been done by the conventional TMS method of measuring changes in the size of the motor-evoked potentials (MEPs) in response to stimuli of constant intensity. An alternative threshold-tracking approach has recently been introduced whereby the stimulus intensity for a target amplitude is tracked. The diagnostic utility of threshold-tracking SICI in amyotrophic lateral sclerosis (ALS) has been shown in previous studies. However, threshold-tracking TMS has only been used in a few centers, in part due to the lack of readily available software but also perhaps due to uncertainty over its relationship to conventional single- and paired-pulse TMS measurements.
A menu-driven suite of semi-automatic programs has been developed to facilitate the broader use of threshold-tracking TMS techniques and to enable direct comparisons with conventional amplitude measurements. These have been designed to control three types of magnetic stimulators and allow recording by a single operator of the common single- and paired-pulse TMS protocols.
This paper shows how to record a number of single- and paired-pulse TMS protocols on healthy subjects and analyze the recordings. These TMS protocols are fast and easy to perform and can provide useful biomarkers in different neurological disorders, particularly neurodegenerative diseases such as ALS.

We present a suite of standardized single- and paired-pulse transcranial magnetic stimulation (TMS) recording protocols, with options for conventional amplitude measurements and threshold-tracking. This program can control three different types of magnetic stimulators and is designed to enable all tests to be performed conveniently by a single operator.

Most single-pulse transcranial magnetic stimulation (TMS) parameters (e.g., motor threshold, stimulus-response function, cortical silent period) are used ...

Assessing Corticospinal Excitability During Goal-Directed Reaching Behavior

Reaching is a widely studied behavior in motor physiology and neuroscience research. While reaching has been examined using a variety of behavioral manipulations, there remain significant gaps in the understanding of the neural processes involved in reach planning, execution, and control. The novel approach described here combines a two-dimensional reaching task with transcranial magnetic stimulation (TMS) and concurrent electromyography (EMG) recording from multiple muscles. This method allows for the noninvasive detection of corticospinal activity at precise time points during the unfolding of reaching movements. The example task code includes a delayed response reaching task with two possible targets displayed &#177; 45&#176; off the midline. Single pulse TMS is delivered on the majority of task trials, either at the onset of the preparatory cue (baseline) or 100 ms prior to the imperative cue (delay). This sample design is suitable for investigating changes in corticospinal excitability during reach preparation. The sample code also includes a visuomotor perturbation (i.e., cursor rotation of &#177; 20&#176;) to investigate the effects of adaptation on corticospinal excitability during reach preparation. The task parameters and TMS delivery can be adjusted to address specific hypotheses about the state of the motor system during reaching behavior. In the initial implementation, motor evoked potentials (MEPs) were successfully elicited on 83% of TMS trials, and reach trajectories were recorded on all trials.

Reaching is a fundamental skill that allows humans to interact with the environment. Several studies have aimed to characterize reaching behavior using a variety of methodologies. This paper offers an open-source application of transcranial magnetic stimulation to assess the state of corticospinal excitability in humans during reaching task performance.

Reaching is a widely studied behavior in motor physiology and neuroscience research. While reaching has been examined using a variety of behavioral ...

Combined Peripheral Nerve Stimulation and Controllable Pulse Parameter TMS

Combined Peripheral Nerve Stimulation and Controllable Pulse Parameter Transcranial Magnetic Stimulation to Probe Sensorimotor Control and Learning

Skilled motor ability depends on efficiently integrating sensory afference into the appropriate motor commands. Afferent inhibition provides a valuable tool to probe the procedural and declarative influence over sensorimotor integration during skilled motor actions. This manuscript describes the methodology and contributions of short-latency afferent inhibition (SAI) for understanding sensorimotor integration. SAI quantifies the effect of a convergent afferent volley on the corticospinal motor output evoked by transcranial magnetic stimulation (TMS). The afferent volley is triggered by the electrical stimulation of a peripheral nerve. The TMS stimulus is delivered to a location over the primary motor cortex that elicits a reliable motor-evoked response in a muscle served by that afferent nerve. The extent of inhibition in the motor-evoked response reflects the magnitude of the afferent volley converging on the motor cortex and involves central GABAergic and cholinergic contributions. The cholinergic involvement in SAI makes SAI a possible marker of declarative-procedural interactions in sensorimotor performance and learning. More recently, studies have begun manipulating the TMS current direction in SAI to tease apart the functional significance of distinct sensorimotor circuits in the primary motor cortex for skilled motor actions. The ability to control additional pulse parameters (e.g., the pulse width) with state-of-the-art controllable pulse parameter TMS (cTMS) has enhanced the selectivity of the sensorimotor circuits probed by the TMS stimulus and provided an opportunity to create more refined models of sensorimotor control and learning. Therefore, the current manuscript focuses on SAI assessment using cTMS. However, the principles outlined here also apply to SAI assessed using conventional fixed pulse width TMS stimulators and other forms of afferent inhibition, such as long-latency afferent inhibition (LAI).

Author Spotlight: Combined Peripheral Nerve Stimulation and Controllable Pulse Parameter Transcranial Magnetic Stimulation to Probe Sensorimotor Control and Learning  

Short-latency afferent inhibition (SAI) is a transcranial magnetic stimulation protocol to probe sensorimotor integration. This article describes how SAI can be used to study the convergent sensorimotor loops in the motor cortex during sensorimotor behavior.

Skilled motor ability depends on efficiently integrating sensory afference into the appropriate motor commands. Afferent inhibition provides a valuable ...

Intracortical Inhibition Within the Primary Motor Cortex Can Be Modulated by Changing the Focus of Attention

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