Name: measuring and manipulating functionally specific neural pathways in the human motor system with transcranial magnetic stimulation
Uploaded: 2020-02-23T15:00:00
Description: Watch this Scientific Journal Video about Measuring and Manipulating Functionally Specific Neural Pathways in the Human Motor System with Transcranial Magnetic Stimulation at JoVE.com

This work was supported by the University of Michigan: MCubed Scholars Program and School of Kinesiology.

The following three TMS methods are described below. First, two methods are described to measure cortico-cortical connectivity using dual-site transcranial magnetic stimulation (dsTMS) while participants are either 1) at rest (resting state) or 2) performing an object-directed reach-to-grasp movement (task-dependent). Second, a cortical paired associative stimulation (cPAS) method is described to modulate the interplay between two brain areas in a controlled manner by pairing cortical stimuli (e.g., posterior parietal an...

The dual-site TMS method described here can be employed to investigate functional interactions between different cortical areas interconnected with the primary motor cortex while a participant is at rest or planning a goal-directed action. While brain imaging is correlative, basic knowledge from dual-site TMS methods can reveal causal brain-behavior relations associated with changes in cortico-cortical circuits. In addition, cortical paired associative stimulation with two TMS coils applied in areas interconnected with M...

Noninvasive brain stimulation is a promising assessment tool and treatment for many neurological disorders, such as Parkinson&#39;s disease, Alzheimer&#39;s disease, and stroke1,2,3,4. There is accumulating evidence establishing the relationship between the behavioral manifestations of neurological diseases and abnormalities of cortical excitability, neuroplasticity, cortico-cortical and cortico-subcortical connectivity5,6. Therefore, basic knowledge about brain network dynamics and plasticity in neurological conditions can provide invaluable insight into disease diagnosis, progression, and response to therapy. Functional magnetic resonance imaging (fMRI) is a useful tool to understand the complex relations between brain and behavior in both healthy and diseased brain networks and has the potential to improve treatment based on a network perspective7,8,9. However, fMRI is correlational in nature and cannot provide a causal link between brain function and behavior, nor manipulate functional connectivity to restore abnormal neural circuits associated with behavioral impairments in patients10,11,12. Transcranial magnetic stimulation (TMS) can both causally measure and modulate human brain function and behavior in health and disease3,13,14,15.
TMS is a safe, noninvasive method to stimulate the human brain16,17 and can be used to induce and measure plasticity18. This method can advance our understanding of causal relationships between individual brain areas and behavior10,11,12,19 and their specific functional interactions with other nodes of a brain network20,21,22,23. To date, most studies have focused on the human motor system, given that TMS to the hand area of the motor cortex (M1) can produce motor evoked potentials (MEPs) as physiological readouts for changes associated with motor behavior24, allowing examination of different inhibitory and excitatory circuits at the system level in the human brain25. Recent advances using a conditioning test TMS approach with two coils show that it is possible to measure functional interactions between different cortical areas. In the motor system, dual-site TMS experiments show that inputs from cortical areas interconnected with M1 can change with task demands, age, or disease14,26. Seminal work by Ferbert and colleagues has found that applying a conditioning stimulus to M1 prior to a test stimulus of the other M1 can result in inhibition of the MEP amplitude, a phenomenon known as short interval interhemispheric inhibition (SIHI)28. A number of TMS studies using this approach have also shown that M1 is strongly interconnected with the contralateral M1, ventral premotor cortex (PMv), dorsal premotor cortex (PMd), supplementary motor area (SMA), pre-SMA, primary sensory cortex (S1), dorsolateral prefrontal cortex (DLPFC), and posterior parietal cortex (PPC) at rest27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42. Interestingly, the effect of stimulation from these cortical areas on motor cortical excitability are anatomically, temporally, and functionally specific to the ongoing brain activity during the preparation of a movement (state- and context-dependent43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,69). However, very few studies using dual-site TMS have characterized patterns of functional cortico-cortical connectivity with motor and cognitive impairments in patients with brain disorders70,71,72. This affords opportunities to develop new methods for assessing and treating motor and cognitive disorders.
Using this technique, it also has been found that repeated pairs of cortical TMS applied to cortical areas interconnected with M1 such as contralateral M168,69,70, PMv76,77,78, SMA71, and PPC80,81,82 can induce changes in synaptic efficiency in specific neural pathways based on the Hebbian principle of associative plasticity83,84,85,86 and enhance behavioral performance72,73,74. Still, few studies have used this approach to study circuit and plasticity dysfunction in neurological disorders2,75,76,77,78,79,80,81,82,83,84,90,91,92,93,94,95,96. It remains to be shown whether strengthening functionally specific neural pathways with TMS can restore activity in dysfunctional circuits, or whether the prospective strengthening of intact circuity can augment resilience97 in brain networks supporting motor and cognitive function across the lifespan and in disease. The lack of fundamental understanding of the neural mechanisms underlying neurological disorders and effects of stimulation on interconnected dysfunctional brain networks limits current treatment.
Despite its capability, TMS has yet to become a standard part of the armamentarium of neuroscience and clinical tools for understanding brain-behavior relations, pathophysiology of brain disorders, and the effectiveness of treatment. Therefore, to realize its potential and support its large-scale application, standardizing TMS methods is important because it is more likely to increase the rigor of future TMS experiments and reproducibility across independent laboratories. This article outlines how TMS can be used to both measure and manipulate functional interactions. Here, we describe this technique in the motor system (e.g., parieto-motor pathway44) by measuring TMS-based output measures (e.g., MEPs), where the method is best understood. However, it is important to note that this protocol also can be adapted to target functional coupling of other subcortical85, cerebellar86,87, and cortical areas.73,74,88 In addition, neuroimaging techniques such as EEG89,90,91 and fMRI92,93 can be used to assess the TMS-induced changes in activity and connectivity26,94. We conclude by proposing that the study of the functional involvement of circuit-level cortical connectivity with these TMS methods in both health and disease makes it possible to develop targeted diagnoses and innovative therapies based on more sophisticated network models of brain-behavior relations.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Alpha B.I. D50 coil (coated)</td>
			<td>Magstim</td>
			<td></td>
			<td>50mm coil</td>
		</tr>
		<tr>
			<td>BrainSight 2.0 Software</td>
			<td>Rogue Research</td>
			<td></td>
			<td>Neuronavigation software</td>
		</tr>
		<tr>
			<td>BrainSight frameless Stereotactic System</td>
			<td>Rogue Research</td>
			<td></td>
			<td>Neuronavigation equiptment</td>
		</tr>
		<tr>
			<td>D702 Coil</td>
			<td>Magstim</td>
			<td></td>
			<td>70mm coil</td>
		</tr>
		<tr>
			<td>Discovery MR750</td>
			<td>General Electric</td>
			<td></td>
			<td>3.0T MRI machine</td>
		</tr>
		<tr>
			<td>Disposable Earplugs</td>
			<td>3M</td>
			<td></td>
			<td>Foam earplugs</td>
		</tr>
		<tr>
			<td>ECG Electrodes 30mm x 24mm</td>
			<td>Coviden-Kendall</td>
			<td>H124SG</td>
			<td>Disposable electrodes</td>
		</tr>
		<tr>
			<td>Four Channel Isolated Amplifier</td>
			<td>Intronix Technologies Corporation</td>
			<td>2024F</td>
			<td>EMG amplifier</td>
		</tr>
		<tr>
			<td>gGAMMAcap</td>
			<td>g.tec Medical Engineering</td>
			<td></td>
			<td>EEG head cap</td>
		</tr>
		<tr>
			<td>Micro1401-3</td>
			<td>Cambridge Electronic Design</td>
			<td></td>
			<td>Scientific data recorder and processing machine</td>
		</tr>
		<tr>
			<td>Nuprep Skin Prep Gel</td>
			<td>Weaver and Company</td>
			<td></td>
			<td>Skin prep abrasive gel</td>
		</tr>
		<tr>
			<td>Signal v.7</td>
			<td>Cambridge Electronic Design</td>
			<td></td>
			<td>Data acquisition and analysis software</td>
		</tr>
		<tr>
			<td>The Magstim BiStim2</td>
			<td>Magstim</td>
			<td></td>
			<td>Transcranial magnetic stimulator (two 2002 units)</td>
		</tr>
	</tbody>
</table>

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.

Figure 5 shows the size of an exemplar MEP response elicited in the FDI muscle by TMS for an unconditioned test stimuli (TS alone to M1, blue trace) or conditioned stimuli from PPC (CS-TS, red trace) while the participant was at rest (top panel) or planning a goal-directed grasping action to an object (bottom panel). At rest, the PPC exerts an inhibitory influence on ipsilateral M1, as shown by the decrease in MEP amplitudes potentiated by a subthreshold CS delivered over PPC 5 ms before a s...

Watch this Scientific Journal Video about Measuring and Manipulating Functionally Specific Neural Pathways in the Human Motor System with Transcranial Magnetic Stimulation at JoVE.com

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

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 ...

This technique provides insight into how brain circuits go awry, in psychiatric and neurological disorders. And how we can manipulate brain activity to repair these dysfunctional circuits to enhance behavior. By directly activating and inhibiting brain excitability and circuitry, this technique enables shifting of neuro-scientific focus from observation to causation, and provides a deeper understanding of the brain and behavior.Non-invasive brain stimulation can be used to both assess and treat many neurological disorders and can help improve diagnoses and therapies, based on more sophisticated models of brain behavior connections. This method can not only counteract altered connectivity patterns in the motor system, but also in cognitive networks associated with physiological aging, psychiatric and neurological disorders. After screening participants for right handedness and any contraindications to TMS and MRI, inform each participant about the study objectives, procedures, and risks approved by the local institutional review board and obtain written consent.For placement of the EMG electrodes, have the participant sit comfortably in the experimental chair, with both arms supported in a relaxed position and provide a chin rest to keep the head movement to a minimum during the stimulation. Use a mild abrasive to clean the skin over the muscle of interest. Using a belly tendon electrode arrangement, place one disposable silver silver chloride electrode on the belly muscle, and another on a nearby bony landmark as a reference site on both hands of the participant.Then connect a ground electrode to the owners styloid process, then check between each electrode in the skin to confirm a complete contact. Placing tape over the surface of the electrode to improve the skin surface contact as necessary. Before the TMS session, upload the participants structural MRI scan to a neuro-navigation system.Within the scan, place a trajectory marker at the hand knob the anatomical landmark that corresponds to M-one. In the left precentral gyrus 45 degrees from the mid sagittal line, and approximately perpendicular to the central sulcus. Record and name the anatomical landmark, with the neuro-navigation system, and place a second trajectory marker over the non-motor area of interest.Then record and name the second location with the neuro-navigation system. First, calibrate each TMS coil with the calibration block, and place the head tracker securely on the head of the participant so that the tracker is in view throughout the duration of the experiment. Co-register the anatomical landmarks on the participants head, to the neuro-navigation system.To localize and threshold with coil two, first position the center of the coil over the target M-one location, to induce a posterior-anterior current direction in the brain. To find the optimal location for activation of the target muscle, deliver pulses to M-one at 30%of the machines maximum stimulator output, and observe whether the delivered stimulation produces a muscle twitch. Determine the amplitude of the motor-evoked potential recorded with the EMG electrodes from the muscle activity displayed by the data acquisition system.If a motor-evoked potential or a visible muscle twitch is not observed, continue to increase the stimulator output by 5%increments. When a response is observed, lower the intensity in a stepwise manner to the lowest intensity, that produces at least five out of 10 motor-evoked potential responses with an amplitude of at least 50 micro volts, while the participant is abreast to determine the resting motor threshold. To localize and threshold with coil M-one, use the M-one coil to determine the optimal stimulation location.Determine the lowest stimulator intensity needed to generate motor-evoked potentials of at least one millivolt, in five out of 10 trials in the target hand muscle, when the muscle is completely relaxed. Then mark and record the position of the M-one coil, within the neuro-navigation system. For dual-site TMS when the participant is in the resting state, connect the figure eight-shaped coils to two individual TMS stimulators.Deliver the test stimuli over M-one with the M-one coil, and deliver the conditioning stimuli to the other area of interest with coil two. Determine the percentage of the maximum stimulator output intensity for the conditioning stimulus for coil two as demonstrated. For the test stimulus, use the previously determined intensity that elicits motor-evoked potential amplitudes of approximately one millivolt in the targeted quiescent hand muscle, and set the precise interstimulus interval between the conditioning and test stimuli.Position the M-one coil over the left M-one and position coil two over the other area of interest. Deliver the test stimuli alone trials with the M-one coil. For the paired pulse trials, deliver the conditioning stimuli with coil two followed by the testing stimuli to the M-one coil at the predetermined interstimulus interval, using a four second data acquisition sweep for each trial, followed by one second inter-trial interval.To deliver the program to TMS pulses, use the trigger button on the TMS machine for the supplied control software, or use the custom-made coding script from the external controller. Using the previously described method, examine the functional interactions between different cortical areas interconnected to M-one, but during the preparatory phase of a task that engages the network. To deliver repeated pairs of monophasic pulses to two different cortical areas over short periods using a custom-made coding script, generate 100 pairs of stimuli at 0.2 hertz for 8.3 minutes per stimulus.For the experimental cPAS to M-one condition, deliver the first pulse of each stimuli pair over the non-motor area with coil two, before delivering the second pulse over M-one with the M-one coil, with an interstimulus interval of five milliseconds. Pulse intensity for both coils, should be previously determined during thresholding and localization. After obtaining baseline corticospinal measurements with the M-one coil, obtain corticospinal measurements with the M-one coil at different times after cPAS, to examine the time course of the TMS induced effect on brain excitability.Here the size of a representative motor-evoked potential response elicited in the first dorsal interosseous muscle by TMS for an unconditioned test, or conditioned stimulus from the posterior parietal cortex, while the participant was at rest, or planning a goal directed grasping action to an object as shown. At rest, the posterior parietal cortex exerts an inhibitory influence on ipsilateral M-one, as shown by the decrease in MEP amplitudes, potentiated by a sub-threshold conditioning stimulus delivered over PPC, five milliseconds prior to a super threshold testing stimulus over M-one. During the preparation of a grasp action, this net inhibitory drive at rest from the posterior parietal cortex, switch to facilitation.Normalization of the motor-evoked potential amplitudes to testing stimuli alone trials for each condition, and plotting as a ratio for motor-evoked potential amplitude reveal that the posterior parietal cortex M-one interaction was facilitated from rest, when planning an object directed grasp. In these analysis, the changes in motor-evoked potential amplitudes during the administration of the cPAS protocol, can be observed. Motor-evoked potential amplitudes induced by paired stimulation of the posterior parietal cortex and M-one, gradually increased over time during the stimulation protocol, suggesting plastic effects at the level of the parietal-motor connection, M-one corticospinal neurons or both.The size of the motor-evoked potential amplitudes increased 10 minutes after the cPAS protocol, suggesting that motor excitability after effects were induced after administration of the repeated pairs of cortical stimuli over the posterior parietal cortex and the M-one. This protocol can be applied to other brain regions or used in conjunction with brain imaging to study cortical connectivity and its effect on cognition, sensory perception and mood. Standardizing these dual sight protocols, will enable improvements in experimental design and the optimization of targeted therapies.Reducing morbidity and impairments in neurological and psychiatric disorders.

measuring-manipulating-functionally-specific-neural-pathways-human

Research

JoVE Journal

Neuroscience

Combining Transcranial Magnetic Stimulation and fMRI to Examine the Default Mode Network

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful rest."1,2,3 It is thought the default mode network corresponds to self-referential or "internal mentation".2,3
It has been hypothesized that, in humans, activity within the default mode network is correlated with certain pathologies (for instance, hyper-activation has been linked to schizophrenia 4,5,6 and autism spectrum disorders 7 whilst hypo-activation of the network has been linked to Alzheimer's and other neurodegenerative diseases 8). As such, noninvasive modulation of this network may represent a potential therapeutic intervention for a number of neurological and psychiatric pathologies linked to abnormal network activation. One possible tool to effect this modulation is Transcranial Magnetic Stimulation: a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized magnetic field pulses.9
In order to explore the default mode network's propensity towards and tolerance of modulation, we will be combining TMS (to the left inferior parietal lobe) with functional magnetic resonance imaging (fMRI). Through this article, we will examine the protocol and considerations necessary to successfully combine these two neuroscientific tools.

In this article, we examine the methodology and considerations relevant to the combination of TMS and fMRI to examine the effects of brain stimulation on the default network.

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful ...

Electrode Positioning and Montage in Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a technique that has been intensively investigated in the past decade as this method offers a non-invasive and safe alternative to change cortical excitability2. The effects of one session of tDCS can last for several minutes, and its effects depend on polarity of stimulation, such as that cathodal stimulation induces a decrease in cortical excitability, and anodal stimulation induces an increase in cortical excitability that may last beyond the duration of stimulation6. These effects have been explored in cognitive neuroscience and also clinically in a variety of neuropsychiatric disorders &#x2013; especially when applied over several consecutive sessions4. One area that has been attracting attention of neuroscientists and clinicians is the use of tDCS for modulation of pain-related neural networks3,5. Modulation of two main cortical areas in pain research has been explored: primary motor cortex and dorsolateral prefrontal cortex7. Due to the critical role of electrode montage, in this article, we show different alternatives for electrode placement for tDCS clinical trials on pain; discussing advantages and disadvantages of each method of stimulation.

Transcranial direct current stimulation (tDCS) is an established technique to modulate cortical excitability1,2. It has been used as an investigative tool in neuroscience due to its effects on cortical plasticity, easy operation, and safe profile. One area that tDCS has been showing encouraging results is pain alleviation 3-5.

Transcranial direct current stimulation (tDCS) is a technique that has been intensively investigated in the past decade as this method offers a ...

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

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has been increasingly used over the past decade in the treatment of neurological and psychiatric disorders such as stroke and depression. Yet, the mechanisms underlying its ability to modulate brain excitability to improve clinical symptoms remains poorly understood 33. To help improve this understanding, proton magnetic resonance spectroscopy (1H-MRS) can be used as it allows the in vivo quantification of brain metabolites such as &#947;-aminobutyric acid (GABA) and glutamate in a region-specific manner 41. In fact, a recent study demonstrated that 1H-MRS is indeed a powerful means to better understand the effects of tDCS on neurotransmitter concentration 34. This article aims to describe the complete protocol for combining tDCS (NeuroConn MR compatible stimulator) with 1H-MRS at 3 T using a MEGA-PRESS sequence. We will describe the impact of a protocol that has shown great promise for the treatment of motor dysfunctions after stroke, which consists of bilateral stimulation of primary motor cortices 27,30,31. Methodological factors to consider and possible modifications to the protocol are also discussed.

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

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has been increasingly used over the past decade in the treatment of ...

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) ...

Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex

Transcranial magnetic stimulation (TMS) is a non-invasive method that produces neural excitation in the cortex by means of brief, time-varying magnetic field pulses. The initiation of cortical activation or its modulation depends on the background activation of the neurons of the cortical region activated, the characteristics of the coil, its position and its orientation with respect to the head. TMS combined with simultaneous electrocephalography (EEG) and neuronavigation (nTMS-EEG) allows for the assessment of cortico-cortical excitability and connectivity in almost all cortical areas in a reproducible manner. This advance makes nTMS-EEG a powerful tool that can accurately assess brain dynamics and neurophysiology in test-retest paradigms that are required for clinical trials. Limitations of this method include artifacts that cover the initial brain reactivity to stimulation. Thus, the process of removing artifacts may also extract valuable information. Moreover, the optimal parameters for dorsolateral prefrontal (DLPFC) stimulation are not fully known and current protocols utilize variations from the motor cortex (M1) stimulation paradigms. However, evolving nTMS-EEG designs hope to address these issues. The protocol presented here introduces some standard practices for assessing neurophysiological functioning from stimulation to the DLPFC that can be applied in patients with treatment resistant psychiatric disorders that receive treatment such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy (MST) or electroconvulsive therapy (ECT).

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

Transcranial magnetic stimulation (TMS) is a non-invasive method that produces neural excitation in the cortex by means of brief, time-varying magnetic ...

Bilateral Assessment of the Corticospinal Pathways of the Ankle Muscles Using Navigated Transcranial Magnetic Stimulation

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans and can be assessed using transcranial magnetic stimulation (TMS). Given the role of distal leg muscles in upright postural and dynamic tasks, such as walking, a growing research interest in the assessment and modulation of the corticospinal tracts relative to the function of these muscles has emerged in the last decade. However, methodological parameters used in previous work have varied across studies making the interpretation of results from cross-sectional and longitudinal studies less robust. Therefore, use of a standardized TMS protocol specific to the assessment of leg muscles&#39; corticomotor response (CMR) will allow for direct comparison of results across studies and cohorts. The objective of this paper is to present a protocol that provides the flexibility to simultaneously assess the bilateral CMR of two main ankle antagonistic muscles, the tibialis anterior and soleus, using single pulse TMS with a neuronavigation system. The present protocol is applicable while the examined muscle is either fully relaxed or isometrically contracted at a defined percentage of maximum isometric voluntary contraction. Using each subject&#39;s structural MRI with the neuronavigation system ensures accurate and precise positioning of the coil over the leg cortical representations during assessment. Given the inconsistency in CMR derived measures, this protocol also describes a standardized calculation of these measures using automated algorithms. Though this protocol is not conducted during upright postural or dynamic tasks, it&#160;can be used to assess bilaterally any pair of leg muscles, either antagonistic or synergistic, in both neurologically intact and impaired subjects.

The present protocol describes the simultaneous, bilateral assessment of the corticomotor response of the tibialis anterior and soleus during rest and tonic voluntary activation using a single pulse transcranial magnetic stimulation and neuronavigation system.

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans ...

3D Kinematic Analysis for the Functional Evaluation in the Rat Model of Sciatic Nerve Crush Injury

Compared to the Sciatic Functional Index (SFI), kinematic analysis is a more reliable and sensitive method for performing functional evaluations of sciatic nerve injury rodent models. In this protocol, we describe a novel kinematic analysis method that uses a three-dimensional (3D) motion capture apparatus for functional evaluations using a rat sciatic nerve crush injury model. First, the rat is familiarized with treadmill walking. Markers are then attached to the designated bone landmarks and the rat is made to walk on the treadmill at the desired speed. Meanwhile, the posterior limb movements of the rat are recorded using four cameras. Depending on the software used, marker tracings are created using both automatic and manual modes and the desired data are produced after subtle adjustments. This method of kinematic analysis, which uses a 3D motion capture apparatus, offers numerous advantages, including superior precision and accuracy. Many more parameters can be investigated during the comprehensive functional evaluations. This method has several shortcomings that require consideration: The system is expensive, can be complicated to operate, and may produce data deviations due to skin shifting. Nevertheless, kinematic analysis using a 3D motion capture apparatus is useful for performing functional anterior and posterior limb evaluations. In the future, this method may become increasingly useful for generating accurate assessments of various traumas and diseases.

We introduce a kinematic analysis method that uses a three-dimensional motion capture apparatus containing four cameras and data processing software for performing functional evaluations during fundamental research involving rodent models.

Compared to the Sciatic Functional Index (SFI), kinematic analysis is a more reliable and sensitive method for performing functional evaluations of ...

Simultaneous Application of Transcranial Direct Current Stimulation during Virtual Reality Exposure

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that changes the likelihood of neuronal firing through modulation of neural resting membranes. Compared to other techniques, tDCS is relatively safe, cost-effective, and can be administered while individuals are engaged in controlled, specific cognitive processes. This latter point is important as tDCS may predominantly affect intrinsically active neural regions. In an effort to test tDCS as a potential treatment for psychiatric illness, the protocol described here outlines a novel procedure that allows the simultaneous application of tDCS during exposure to trauma-related cues using virtual reality (tDCS+VR) for veterans with posttraumatic stress disorder (NCT03372460). In this double-blind protocol, participants are assigned to either receive 2 mA tDCS, or sham stimulation, for 25 minutes while passively watching three 8-minute standardized virtual reality drives through Iraq or Afghanistan, with virtual reality events increasing in intensity during each drive. Participants undergo six sessions of tDCS+VR over the course of 2-3 weeks, and psychophysiology (skin conductance reactivity) is measured throughout each session. This allows testing for within and between session changes in hyperarousal to virtual reality events and adjunctive effects of tDCS. Stimulation is delivered through a built-in rechargeable battery-driven tDCS device using a 1 (anode) x 1 (cathode) unilateral electrode set-up. Each electrode is placed in a 3 x 3 cm (current density 2.22 A/m2) reusable sponge pocket saturated with 0.9% normal saline. Sponges with electrodes are attached to the participant&#8217;s skull using a rubber headband with the electrodes placed such that they target regions within the ventromedial prefrontal cortex. The virtual reality headset is placed over the tDCS montage in such a way as to avoid electrode interference.

This manuscript outlines a novel protocol to allow the simultaneous application of transcranial direct current stimulation during exposure to warzone trauma-related cues using virtual reality for veterans with posttraumatic stress disorder.

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that changes the likelihood of neuronal firing through ...

Employing Transcranial Magnetic Stimulation in a Resource Limited Environment to Establish Brain-Behavior Relationships

Neuroimaging is typically perceived as a resource demanding discipline. While this is the case in certain circumstances, institutions with limited resources have historically contributed significantly to the field of neuroscience, including neuroimaging. In the study of self-deception, we have successfully employed single-pulse TMS to determine the brain correlates of abilities including overclaiming and self-enhancement. Even without the use of neuro-navigation, methods provided here lead to successful outcomes. For example, it was discovered that decreases in self-deceptive responding lead to a decrease in affect. These methods provide data that are reliable and valid, and such methods provide research opportunities otherwise unavailable.&#160;Through the use of these methods, the overall knowledge base in the field of neuroscience is expanded, providing research opportunities to students such as those at our institution&#160;(Montclair State University is a Hispanic-Serving Institute) who are often denied such research experiences.

Transcranial Magnetic Stimulation (TMS) and low-frequency TMS (lfTMS) have&#160;been demonstrated to be major contributors to brain literature. Here we highlight the methods for investigating the cortical correlates of self-deception using TMS.