Name: assessing corticospinal excitability during goal-directed reaching behavior
Uploaded: 2022-12-02T12:40:00.000+00:00
Duration: 5 min 5 s
Description: Watch this Scientific Journal Video about Assessing Corticospinal Excitability During Goal-Directed Reaching Behavior at JoVE.com

This research was made possible in part by the generous funding of the Knight Campus Undergraduate Scholars program and the Phil and Penny Knight Foundation

All methods detailed here were performed in compliance with IRB protocol and approval (University of Oregon IRB protocol number 10182017.017). Informed consent was obtained from all subjects.
1. Reaching apparatus
<ol>
	<li>Place a large graphics tablet flat on a desktop.</li>
	<li>Use an adjustable 80-20 aluminum frame to position the task monitor 6-8 in above the tablet in parallel, with the screen facing upward (for a blueprint, check here: https://github.com/greenhouselab/Reach_TMS and&#160;Supplementary Figure 1). 
	NOTE: This setup allows for participants to reach across the tablet and acquire targets presented on the task monitor while occluding vision of their reaching arm.</li>
	<li>Use the setup described in Kim et al.3 as a reference.</li>
</ol>
2. Machine interfaces
<ol>
	<li>Connect the tablet to the computer via a USB port. Connect the task monitor to the computer via the HDMI port. Connect the rear TMS port to the computer via a DB-9 cable.</li>
	<li>Connect the EMG system to the computer via a PCI-6220 card DAQ. Connect the photodiode to the EMG system via a BNC cable.</li>
</ol>
3. Photodiode sensor
<ol>
	<li>Attach a photodiode sensor to the BNC cable. Secure the photodiode sensor with tape to the top-right corner of the task monitor, with the sensor facing the screen, &#8804; 1 cm away. 
	NOTE: This will record the timing of stimuli presented on the task monitor as analog data in an independent input channel.</li>
</ol>
4. Software
<ol>
	<li>Download VETA Toolbox26 (https://github.com/greenhouselab/Veta) for MATLAB 2018 to interface with the hardware for data collection.</li>
	<li>Download the reaching task code (https://github.com/greenhouselab/Reach_TMS) developed for the control of experimental parameters and interfacing with the tablet.</li>
</ol>
5. Participant screening and informed consent
<ol>
	<li>Screen the subject for contraindications to TMS. Exclusion criteria include a personal or family history of seizure, headache, brain trauma, fainting, chronic stress or anxiety, problems with sleep, and any neuroactive medication. Additional exclusion criteria include any metal implants in the brain or skull and any recreational drug or alcohol use in the 24 h prior to testing. Inclusion criteria included right-handedness and age between 18 and 35 years.</li>
	<li>Provide a written explanation of the procedure and associated risks, clarifying any further questions the participant may have.</li>
	<li>Obtain informed consent from participants.</li>
</ol>
6. Subject setup
<ol>
	<li>Position the subject in a comfortable chair facing the tablet. Ensure that the knees are flexed to 90&#176; with the legs under the desk.</li>
	<li>Prepare the skin and place EMG electrodes.
	<ol>
		<li>Use fine-grain sandpaper to gently abrade the skin at the site of the right first dorsal interossei (FDI), extensor carpi radialis, and anterior deltoid muscles, as well as the C4 prominence at the base of the neck, to detect electrical artifacts produced by the TMS pulse. 
		NOTE: Muscle recording sites can be adapted based on user needs.</li>
		<li>Swab each abraded area with an alcohol prep pad once per electrode site to clean.</li>
		<li>Place one EMG electrode on each site. Ensure that the electrodes run perpendicular to the muscle fibers. Place the ground electrode on the bony prominence of the right elbow.</li>
		<li>Secure each electrode with medical tape.</li>
	</ol>
	</li>
	<li>Check the quality of the EMG recording. Use the VETA toolbox to visualize all EMG traces and ensure they are free of artifacts. If EMG traces are noisy, ensure the ground is properly placed and that all electrodes make proper contact with the skin.</li>
</ol>
7. Transcranial magnetic stimulation
<ol>
	<li>Turn on the TMS machine.</li>
	<li>Find the TMS hot spot of the right FDI muscle via stimulation of the left M1.
	<ol>
		<li>Place the coil ~5 cm lateral and 2 cm anterior to the vertex of the head, oriented ~45&#176; off the midline.</li>
		<li>Administer TMS pulses once every 4 s while repositioning the coil in increments of approximately 5 mm in the anterior-posterior and medial-lateral plane.</li>
		<li>Beginning at 30% maximum stimulator output, gradually increase the TMS intensity by 2% increments until MEPs are observed.</li>
		<li>Once the optimum location is identified, at which MEPs can be reliably elicited on the majority (~75%) of pulses at the lowest possible stimulator intensity, determine the resting motor threshold (RMT) by finding the intensity level that produces MEPs with a peak-to-peak amplitude of &#62;50 &#181;V on five out of 10 pulses.</li>
		<li>Mark the position by gently placing thin strips of reflective tape on the participant&#39;s head along the perimeter of the coil. Maintain coil positioning either by manually holding the coil or using a stand to support it.</li>
	</ol>
	</li>
</ol>
8. Reaching task setup
<ol>
	<li>Put a Velcro glove on the right hand of the participant to facilitate a relaxed power grip posture.</li>
	<li>Attach the stylus to the glove and advise the subject to keep the hand relaxed between reaching movements.</li>
	<li>Communicate the task instructions, which are as follows: Guide the cursor to the home position on the bottom of the screen. You will see a cue at one of two target locations. When the target fills in with color, reach through the target as fast and as accurately as possible. Then return to the home position. Indicate locations of home positions, cues, and targets (Figure 1A).</li>
	<li>Coach the participant to slice through targets with the stylus as quickly and as accurately as possible. Turn off the lights in the task room to obscure the participant&#39;s vision of arm movements and improve the visibility of the task monitor.</li>
</ol>
9. Task design
<ol>
	<li>Control visual stimulus presentation with Psychtoolbox 3.0 in Matlab 2018 (Supplementary Coding File 1).</li>
	<li>Use the following parameters to match the current data: 20 practice trials; 270 test trials; TMS on 4/5 of test trials; TMS either coincides with the preparatory cue onset (baseline TMS) or 100 ms before the imperative cue (delay TMS) with equal frequency; 1/10 of total trials are catch trials, in which the imperative cue does not appear; the home position is a circle with a 2 cm radius positioned in the bottom center of the workspace; two circular targets with 1 cm radius are positioned 15 cm from the home position at +45&#176; and -45&#176; away from the midline.</li>
	<li>Set the event order and durations as follows: preparatory cue at 900 ms and imperative cue at 900 ms.</li>
</ol>
10. TMS administration
<ol>
	<li>The VETA toolbox concurrently administers TMS and records EMG&#160;https://github.com/greenhouselab/Veta.</li>
	<li>Control the timing of the TMS pulses with the VETA toolbox to coincide with the chosen behavioral events (i.e., the onset of the preparatory cue or 100 ms preceding target onset).</li>
	<li>Deliver TMS with sufficient frequency to ensure a sufficient number of MEPs for analysis. 
	NOTE: As written, the task code will deliver a TMS pulse on 4/5 of total trials either at the onset of the preparatory cue-to elicit baseline MEPs-or 100 ms before the imperative cue-to elicit delayed MEPs. Parameters can be adjusted in the code according to user needs. Trials without TMS can be used to evaluate behavioral performance in the absence of TMS. This is useful for determining any possible influence of TMS on performance.</li>
</ol>

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All authors declare that there are no conflicts of interest

The methods outlined above offer a novel approach to studying motor preparation in the context of reaching behaviors. Although reaching represents a popular model task in the study of motor control and learning, there is a need for precisely evaluating the CS dynamics associated with reaching behavior. TMS offers a noninvasive, temporally precise method of capturing CS activity at discrete time points during reaching. The approach described here combines two independent subfields-TMS and reaching-into a single paradigm that involves the simultaneous recording of kinematic and electrophysiological metrics. 
While the methods described have the potential to reveal important insights into action control in the context of reaching, there are certain limitations and considerations. Most importantly, the reliability of MEP measurements depends on the stability of the EMG activity prior to TMS administration, as well as the number of MEPs captured27. It is critical that EMG data quality be assessed prior to data collection. For sufficient statistical power, a minimum of 20 MEP measurements per task condition are recommended. Additionally, while changes in the MEP represent a quantitative change in CS excitability, the nature of TMS and the resultant MEP produce a rather crude, summary metric of CS activity, and their causal relationship to behavior should be interpreted with caution15. Furthermore, the graphics tablet requires that the stylus maintain contact with the tablet surface, which limits the range of reaching tasks and grip apertures that can be employed. 
Despite the limitations of this specific protocol, the combination of TMS and EMG for indexing motor system excitability during behavioral tasks other than reaching is well established15. Advantages of this combined approach include the ability to measure CS excitability dynamics even in the absence of overt movement, as well as in task-irrelevant muscles. This approach also offers high temporal precision, on the order of milliseconds. Additionally, the protocol described here can be adapted to work with any number of EMG devices that interface directly with a stimulus presentation computer via the listed input/output devices. 
Given these advantages, the protocol can help bridge the gap between human and animal studies. A large body of research in non-human primates has examined the electrophysiological mechanisms associated with reaching and motor learning in the context of reaching. Further investigations in humans using the combined TMS and EMG approach can help to bridge non-human electrophysiology and human behavioral findings. Previous studies of MEPs in the context of reaching have shown a facilitatory effect of TMS during reach and grasp preparation when the parietal cortex, premotor cortex, and parietal-M1 circuits were stimulated prior to movement8,14. However, the amplitudes of resting evoked potentials measured with electroencephalography 75 to 150 ms after TMS over the M1 were reduced following force field adapatation13. The nuanced relationship between reaching preparation, adaptation, and changes in CS warrants further investigation. Moreover, by using the same set of tools and methods across laboratories, replication will be more achievable, and this will aid the interpretability of study results.
While the focus here is on TMS of the M1, several studies have utilized dual-site TMS to investigate interactions between cortical areas (e.g., parietal cortex and M1). While many of these studies were conducted during rest, a handful of studies examined cortico-cortical interactions in the context of reach planning and execution. Dual-site TMS showed stimulation of the posterior parietal cortex facilitated M1 excitability at 50 ms and ~100 ms following an auditory "go" cue to initiate a prepared contralateral reach28. Additional methods have been established for dual coil TMS approaches that include applications during goal-directed reach-to-grasp behaviors29. The protocol described here complements these previous studies and methods and can be readily adapted for dual-site TMS studies as well.
The example task code consists of a delayed response task with two potential targets. Parameters such as trial numbers, target and cursor characteristics, visual feedback, and TMS delivery can be adjusted to address a variety of research questions. Data recorded with this approach include behavioral kinematics from the tablet and electrophysiological measurements from the EMG. Preliminary results revealed that TMS and behavioral measurements exhibit reliable timing and sufficient sensitivity to variability in reach directions across trials. These methods and results stand as proof of concept for future investigations into the neural mechanisms of reaching via TMS using this approach.

Goal-directed reaching is a fundamental motor behavior that allows humans to interact with and manipulate the external environment. The study of reaching in the fields of motor physiology, psychology, and neuroscience has produced rich and extensive literature that includes a variety of methodologies. Early studies of reaching used direct neural recordings in non-human primates to investigate neural activity at the level of single neurons1,2. More recent studies have investigated reaching using behavioral paradigms that employ sensorimotor adaptation to explore the nature of motor learning and control3,4,5. Such behavioral tasks combined with functional magnetic resonance imaging and electroencephalography can measure whole brain activity during reaching in humans6,7. Other studies have applied online TMS to investigate various features of reach preparation and execution8,9,10,11,12,13,14. However, there remains a need for an open-source and flexible approach that combines the behavioral assessment of reaching with TMS. While the utility of combining TMS with behavioral protocols is very well established15, here, we specifically examine the application of TMS within the context of reaching using an open-source approach. This is novel in that other groups who have published using this combination of methods have not made their tools readily available, prohibiting direct replication. This open-source approach facilitates replication, data sharing, and the possibility of multi-site studies. Additionally, should others wish to pursue novel research questions with similar tools, the open-source code can act as a launch pad for innovation, as it is readily adaptable.
TMS offers a noninvasive means of probing the motor system at precisely controlled time points16. When applied over the primary motor cortex (M1), TMS can elicit a measurable deflection in the electromyogram of a targeted muscle. The amplitude of this voltage wave, known as the motor evoked potential (MEP), provides an index of the momentary excitability state of the corticospinal (CS) pathway-a resultant analog of all excitatory and inhibitory influences on the CS pathway17. In addition to providing a reliable within-subject measurement of intrinsic CS excitability, TMS can be combined with other behavioral or kinematic metrics to investigate the relationships between CS activity and behavior in a temporally precise manner. Many studies have utilized a combination of TMS and electromyography (EMG) to address a variety of questions about the motor system, particularly since this combination of methods makes it possible to investigate MEPs under a vast array of behavioral conditions15. One area where this has proven particularly useful is in the study of action preparation, most often through the study of single-joint movements18. However, there are comparatively fewer TMS studies of naturalistic multi-joint movements such as reaching.
The current goal was to design a delayed-response reaching task that includes behavioral kinematics, online single-pulse TMS administration, and simultaneous EMG recording from multiple muscles. The task includes a two-dimensional point-to-point reaching paradigm with online visual feedback using a horizontally oriented monitor such that visual feedback matches reach trajectories (i.e., a 1:1 relationship during veridical feedback and no transformation between visual feedback and motion). The current design also includes a set of trials with a visuomotor perturbation. In the provided example, this is a 20&#176; rotational shift in the cursor feedback. Previous studies have used a similar reaching paradigm to address questions about the mechanisms and computations associated with sensorimotor adaptation19,20,21,22,23,24,25. Furthermore, this approach makes it possible to assess motor system excitability dynamics at precise time points during online motor learning.
Because reaching has proven to be a fruitful behavior for investigating learning/adaptation, assessing CS excitability in the context of this behavior has enormous potential to shed light on the neural substrates involved in these behaviors. These may include local inhibitory influences, changes in tuning properties, the timing of neural events, etc., as have been established in non-human primate research. However, these features have been more difficult to quantify in humans and clinical populations. Neural dynamics can also be investigated in the absence of overt movement in humans using the combined TMS and EMG approach (i.e., during the preparation of movement or at rest).
The tools presented are open-source, and the code is easily adaptable. This novel paradigm will produce important insights into the mechanisms involved in the preparation, execution, termination, and adaptation of reaching movements. Moreover, this combination of methods has the potential to uncover relationships between electrophysiology and reaching behavior in humans.

<table><tbody><tr><td>2-Port Native PCI Express&amp;nbsp;</td><td>StarTech.com</td><td>RS232 Card with 16950 UART&amp;nbsp;</td><td>Must be compatible with desktop computer</td></tr><tr><td>Adjustable 80-20 aluminum frame</td><td>any</td><td></td><td></td></tr><tr><td>Alcohol prep pads</td><td>any</td><td></td><td>EMG preparation</td></tr><tr><td>Bagnoli Bipolar Electrodes</td><td>Delsys</td><td>DE 2.1</td><td></td></tr><tr><td>Bagnoli Reference Electrode</td><td>Delsys</td><td>USX2000</td><td>2&amp;rdquo; (5cm) Round</td></tr><tr><td>Bagnoli-8 EMG System</td><td>Delsys</td><td></td><td></td></tr><tr><td>Chair</td><td>any</td><td></td><td></td></tr><tr><td>Computer monitor for EMG/TMS</td><td>n/a</td><td></td><td></td></tr><tr><td>Desk</td><td>any</td><td></td><td></td></tr><tr><td>Desktop Computer</td><td>Dell</td><td>xps 8930</td><td>RAM: 16 GB, Storage: 1TB, Graphics: 1060 6GB&amp;nbsp;</td></tr><tr><td>EMG electrodes</td><td>Delsys</td><td>Sensor Adhesive Interface</td><td></td></tr><tr><td>Fine grain sandpaper</td><td>any</td><td></td><td>EMG preparation</td></tr><tr><td>Graphics tablet</td><td>Wacom</td><td>Intuos-4 XL</td><td></td></tr><tr><td>Handle of paint roller</td><td>any</td><td></td><td>to be used as stylus handle, hollowed out center must be large enough for stylus to sit securely inside&amp;nbsp;</td></tr><tr><td>Medical tape</td><td>any</td><td></td><td>To secure EMG electrodes</td></tr><tr><td>PCI-6220 card DAQ</td><td>National Instruments</td><td></td><td>To interface EMG system</td></tr><tr><td>Photodiode Sensor</td><td>Vishay</td><td>BPW21R</td><td>To record timing of task events into EMG trace.</td></tr><tr><td>Rear TMS port</td><td>Magstim</td><td></td><td>Included with TMS machine</td></tr><tr><td>Right-handed polyethylene glove</td><td>any</td><td></td><td>Cut out thumb and index finger of glove to expose FDI muscle</td></tr><tr><td>Sensory Adhesive Interface, 2-slot</td><td>Delsys</td><td>SC-F01</td><td></td></tr><tr><td>Stylus</td><td>Wacom</td><td>Intuos-4 grip pen</td><td></td></tr><tr><td>Tablet-to-Computer USB cable&amp;nbsp;</td><td>any</td><td></td><td>Included in Tablet purchase</td></tr><tr><td>Task Monitor</td><td>Asus</td><td>VG248</td><td></td></tr><tr><td>TMS coil</td><td>Magstim</td><td>D70 Remote Coil</td><td>7cm diameter, figure-of-eight coil</td></tr><tr><td>TMS machine</td><td>Magstim</td><td>200-2</td><td></td></tr><tr><td>TMS-to-Computer DB9 cable</td><td>any</td><td></td><td>Connects to PCIe Serial Card</td></tr><tr><td>Velcro</td><td>any</td><td></td><td>To be placed on glove and stylus handle</td></tr></tbody></table>

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.

Successful execution of the described methods includes the recording of tablet data, EMG traces, and reliable elicitation of MEPs. An experiment was completed that included 270 test trials with TMS delivered on 4/5 of the trials (216 trials).
Data were collected from 16 participants (eight females; eight males) aged 25 &#177; 10 years, all of whom self-reported as right-handed. We assessed the effectiveness of the visual perturbation on behavioral performance by deriving a learning function for one representative participant. These data are presented in Figure 1B and show that the participant&#39;s hand target error adjusted to the perturbation and washout conditions as expected. We also evaluated the standard deviation of the target error during baseline reaches, which approximated 4.5&#176; (Figure 1B). This is consistent with previous studies24.
One TMS pulse was delivered on each trial. Half of the pulses were delivered at baseline, and half were delivered during a preparatory delay period (Figure 2A). An average of 91 &#177; 23 baseline and 88 &#177; 20 delay MEPs were successfully recorded per participant, corresponding to 84% and 81% success rates, respectively. MEPs were counted only when amplitudes exceeded .05 mV. Reach trajectories were successfully captured from the graphics tablet on all trials, excluding catch trials (i.e., trials in which the &#34;go&#34; cue was not presented and trials in which participants either failed to initiate a reach or initiated before the imperative cue).
The average delay period (duration between the preparatory and imperative cue) was 915 &#177; 0.5 ms (mean &#177; standard deviation). Baseline TMS was administered 26 &#177; 8 ms after preparatory cue onset, and delay TMS was 126 &#177; 3 ms prior to imperative cue onset (Figure 2B). The consistent deviation from the intended TMS administration time in each case indicates that further optimization is needed to account for undesired latencies introduced by hardware or software components. However, the relatively low proportional variance in these latencies suggests these are mostly fixed delays that can be controlled with additional pilot testing and indicate that the timing of events is generally reliable across trials.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/64238/64238fig01.jpg" /> 
Figure 1: Behavioral data collected from the tablet. (A) The workspace includes the home position (dark blue), two targets (cyan), and a representative set of reach trajectories from the pre-exposure block of a single participant. (B) Target error was calculated as the distance in degrees from the endpoint of the reach to the center of the target. Trial bins are the mean of two consecutive trials per bin, and the data are separated by experimental blocks: Pre-exposure (unshaded), exposure (red), washout in the absence of feedback (green), and washout with veridical feedback (unshaded). <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/64238/64238fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/64238/64238fig02.jpg" /> 
Figure 2: Example MEP traces. (A) Representative MEPs and corresponding photodiode trace for both experimental epochs (baseline and delay). (B) Negative baseline MEP latency (-26 &#177; 8 ms) indicates that the TMS stimulus arrived after the preparatory cue, while positive delay MEP latency (126 &#177; 3 ms) indicates that the TMS stimulus arrived before the desired time point (100 ms prior to the imperative cue). Latencies are averaged across all participants (n = 16). <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/64238/64238fig02large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
Supplementary Figure 1: Blueprint of the reaching apparatus. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/64238/TabletStand.pdf" target="_blank">Please click here to download this File.</a>
Supplementary Coding file 1: Code for visual stimulation. The delayed_reach_TMS.m file contains a task code for controlling the tablet, stimulus presentation, transcranial magnetic stimulation, and electromyography recording. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/64238/delayed_reach_TMS.m" target="_blank">Please click here to download this File.</a>

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Assessing Corticospinal Excitability During Goal-Directed Reaching Behavior

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 ...

assessing-corticospinal-excitability-during-goal-directed-reaching

Nanyang Technological University

Research

JoVE Journal

Neuroscience

1.6K Views.  University of Oregon. Bereiken is een fundamentele vaardigheid die mensen in staat stelt om met de omgeving te communiceren. Verschillende studies hebben tot doel het bereiken van gedrag te karakteriseren met behulp van een verscheidenheid aan methodologieën. Dit artikel biedt een open-source toepassing van transcraniële magnetische stimulatie om de toestand van corticospinale prikkelbaarheid bij mensen te beoordelen tijdens het bereiken van taakprestaties.

Video: Assessing Corticospinal Excitability During Goal-Directed Reaching Behavior

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 ...

Behavior

Methods to Explore the Influence of Top-down Visual Processes on Motor Behavior

Kinesthetic awareness is important to successfully navigate the environment. When we interact with our daily surroundings, some aspects of movement are deliberately planned, while others spontaneously occur below conscious awareness. The deliberate component of this dichotomy has been studied extensively in several contexts, while the spontaneous component remains largely under-explored. Moreover, how perceptual processes modulate these movement classes is still unclear. In particular, a currently debated issue is whether the visuomotor system is governed by the spatial percept produced by a visual illusion or whether it is not affected by the illusion and is governed instead by the veridical percept. Bistable percepts such as 3D depth inversion illusions (DIIs) provide an excellent context to study such interactions and balance, particularly when used in combination with reach-to-grasp movements. In this study, a methodology is developed that uses a DII to clarify the role of top-down processes on motor action, particularly exploring how reaches toward a target on a DII are affected in both deliberate and spontaneous movement domains.

It is unclear how top-down signals from the ventral visual stream affect movement. We developed a paradigm to test motor behavior towards a target on a 3D depth inversion illusion. Significant differences are reported in both deliberate, goal-directed movements and automatic actions under illusory and veridical viewing conditions.

Kinesthetic awareness is important to successfully navigate the environment. When we interact with our daily surroundings, some aspects of movement are ...

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 ...

Investigating Motor Skill Learning Processes with a Robotic Manipulandum

Skilled reaching tasks are commonly used in studies of motor skill learning and motor function under healthy and pathological conditions, but can be time-intensive and ambiguous to quantify beyond simple success rates. Here, we describe the training procedure for reach-and-pull tasks with ETH Pattus, a robotic platform for automated forelimb reaching training that records pulling and hand rotation movements in rats. Kinematic quantification of the performed pulling attempts reveals the presence of distinct temporal profiles of movement parameters such as pulling velocity, spatial variability of the pulling trajectory, deviation from midline, as well as pulling success. We show how minor adjustments in the training paradigm result in alterations in these parameters, revealing their relation to task difficulty, general motor function or skilled task execution. Combined with electrophysiological, pharmacological and optogenetic techniques, this paradigm can be used to explore the mechanisms underlying motor learning and memory formation, as well as loss and recovery of function (e.g. after stroke).

A paradigm is presented for training and analysis of an automated skilled reaching task in rats. Analysis of pulling attempts reveals distinct subprocesses of motor learning.

Skilled reaching tasks are commonly used in studies of motor skill learning and motor function under healthy and pathological conditions, but can be ...

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.

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 ...

A Modified Lean and Release Technique to Emphasize Response Inhibition and Action Selection in Reactive Balance

Assessment of reactive balance traditionally imposes some type of perturbation to upright stance or gait followed by measurement of the resultant corrective behavior. These measures include muscle responses, limb movements, ground reaction forces, and even direct neurophysiological measures such as electroencephalography. Using this approach, researchers and clinicians can infer some basic principles regarding how the nervous system controls balance to avoid a fall. One limitation with the way in which these assessments are currently used is that they heavily emphasize reflexive actions without any need to revise automatic postural reactions. Such an exclusive focus on these highly stereotypical reactions would fail to adequately address how we can modify these reactions should the need arise (e.g., avoiding an obstacle with a recovery step). This would appear to be a glaring omission when one considers the enormous complexity of the environments we face daily. Overall, the status quo when evaluating the neural control of balance fails to truly expose how higher brain resources contribute to preventing falls in complex settings. The present protocol offers a way to require suppression of automatic, but inappropriate corrective balance reactions, and force a selection among alternative action choices to successfully recover balance following postural perturbation.

Here we offer a protocol that allows the user to selectively change affordances and/or constraints on movements that are relevant for recovering balance after postural perturbation.

Assessment of reactive balance traditionally imposes some type of perturbation to upright stance or gait followed by measurement of the resultant ...

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 ...

An Emerging Target Paradigm to Evoke Fast Visuomotor Responses on Human Upper Limb Muscles

To reach towards a seen object, visual information has to be transformed into motor commands. Visual information such as the object&#8217;s color, shape, and size are processed and integrated within numerous brain areas, then ultimately relayed to the motor periphery. In some instances, a reaction is needed as fast as possible. These fast visuomotor transformations, and their underlying neurological substrates, are poorly understood in humans as they have lacked a reliable biomarker. Stimulus-locked responses (SLRs) are short latency (&#60;100 ms) bursts of electromyographic (EMG) activity representing the first wave of muscle recruitment influenced by visual stimulus presentation. SLRs provide a quantifiable output of rapid visuomotor transformations, but SLRs have not been consistently observed in all subjects in past studies. Here we describe a new, behavioral paradigm featuring the sudden emergence of a moving target below an obstacle that consistently evokes robust SLRs. Human participants generated visually guided reaches toward or away from the emerging target using a robotic manipulandum while surface electrodes recorded EMG activity from the pectoralis major muscle. In comparison to previous studies that investigated SLRs using static stimuli, the SLRs evoked with this emerging target paradigm were larger, evolved earlier, and were present in all participants. Reach reaction times (RTs) were also expedited in the emerging target paradigm. This paradigm affords numerous opportunities for modification that could permit systematic study of the impact of various sensory, cognitive, and motor manipulations on fast visuomotor responses. Overall, our results demonstrate that an emerging target paradigm is capable of consistently and robustly evoking activity within a fast visuomotor system.

Presented here is a behavioral paradigm that elicits robust fast visuomotor responses on human upper limb muscles during visually guided reaches.

To reach towards a seen object, visual information has to be transformed into motor commands. Visual information such as the object&#8217;s color, shape, ...

In Vivo Wireless Optogenetic Control of Skilled Motor Behavior

Fine motor skills are essential in everyday life and can be compromised in several nervous system disorders. The acquisition and performance of these tasks require sensory-motor integration and involve precise control of bilateral brain circuits. Implementing unimanual behavioral paradigms in animal models will improve the understanding of the contribution of brain structures, like the striatum, to complex motor behavior as it allows manipulation and recording of neural activity of specific nuclei in control conditions and disease during the performance of the task. 
Since its creation, optogenetics has been a dominant tool for interrogating the brain by enabling selective and targeted activation or inhibition of neuronal populations. The combination of optogenetics with behavioral assays sheds light on the underlying mechanisms of specific brain functions. Wireless head-mounted systems with miniaturized light-emitting diodes (LEDs) allow remote optogenetic control in an entirely free-moving animal. This avoids the limitations of a wired system being less restrictive for animals' behavior without compromising light emission efficiency. The current protocol combines a wireless optogenetics approach with high-speed videography in a unimanual dexterity task to dissect the contribution of specific neuronal populations to fine motor behavior.

In Vivo Wireless Optogenetic Control of Skilled Motor Behavior

The present protocol describes how to use wireless optogenetics combined with high-speed videography in a single pellet reach-to-grasp task to characterize the neural circuits involved in the performance of skilled motor behavior in freely moving mice.

Fine motor skills are essential in everyday life and can be compromised in several nervous system disorders. The acquisition and performance of these ...

Quantitative Assessment of Hand Use in Unilateral Nerve Injury

Block Building Task Identifies Distinct Groups of Left/Right-hand Choice Patterns After Unilateral Peripheral Nerve Injury

Numerous methods exist to assess hand and arm function after upper extremity peripheral nerve injury, but peripheral injuries are often unilateral, and few existing methods are designed to capture the unique consequences of unilateral injury. Unilateral impairment of an upper extremity can lead to increased or decreased use of the dominant hand, and either change may be adaptive or maladaptive depending on the individual patient&#8217;s needs. To identify atypical hand usage (left/right choices), researchers and clinicians need to measure it. However, hand usage is traditionally assessed with self-report surveys, which do not necessarily reflect actual left/right-hand choices. Here, this gap in knowledge is addressed with the Block Building Task (BBT), which provides a rapid, quantitative, inexpensive assessment of left/right-hand choices in an unconstrained environment. In the BBT, participants build abstract shapes with interlocking plastic bricks, with no instructions about hand usage. The primary outcome is the fraction of reaches (i.e., for the initial pickup of each brick) made with each hand. After unilateral peripheral nerve injury, patients fell into three clusters: approximately typical hand use (44%), always use the dominant hand (44%), or never use the dominant hand (13%). Even among patients with an injured dominant hand, atypically elevated use of the dominant hand occurred regularly (36%). Notably, hand usage was not predicted by clinical characteristics, so the BBT provides an objective measurement of left/right-hand choices that are not otherwise predictable from the clinical characteristics of patients with peripheral nerve injury. The BBT protocol will be of interest to researchers or clinicians interested in the assessment of conditions with asymmetric effects on the upper limb.

The block-building task provides a rapid, objective, quantitative measurement of how often individuals choose to use their left versus right hand for reach-to-grasp action. After unilateral peripheral nerve injury, patients often shift to near-total usage of one hand, the direction of which is not predictable from other clinical factors.

Numerous methods exist to assess hand and arm function after upper extremity peripheral nerve injury, but peripheral injuries are often unilateral, and ...

Assessing Corticospinal Excitability During Goal-Directed Reaching Behavior

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