Name: employing transcranial magnetic stimulation in a resource limited environment to establish brain-behavior relationships
Uploaded: 2022-04-20T13:00:00
Description: Watch this Scientific Journal Video about Employing Transcranial Magnetic Stimulation in a Resource Limited Environment to Establish Brain-Behavior Relationships at JoVE.com

LSAMP (Louis Stokes Alliance for Minority Participation), Wehner, and The Crawford Foundation, the Kessler Foundation are all thanked for their support.

The research presented here was approved by the Institutional Review Board (IRB) committee of Montclair State University. All participants have been treated within the ethical guidelines of the APA.
1. Participants
<ol>
	<li>First, obtain IRB Committee Review Approval for the protocol (see Discussion for non- Research 1 institutions). Consultation with experienced researchers is recommended. Obtain forms such as Screening (Supplementary File 1) and Side Effe...

<ol>
	<li>Academic Research and Development. Science and Engineering Indicators 2020. National Science Board, National Science Foundation Available from: <a target="_blank" href="https://incses.nsf.gov/pubs/nsb20202">https://incses.nsf.gov/pubs/nsb20202</a> (2020)</li><li>. Rutgers School of Graduate Education. Overview of R1 Serving Hispanic Institutions Available from: <a target="_blank" href="https://cmsi.gse.rutgers.edu/sites/default/files/HSI_Report_R2_0.pdf">https://cmsi.gse.rutgers.edu/sites/default/files/HSI_Report_R2_0.pdf</a> (2022)</li><li>Maeda, F., Keenan, J. P., Pascual-Leone, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interhemispheric+asymmetry+of+motor+cortical+excitability+in+major+depression+as+measured+by+transcranial+magnetic+stimulation.">Interhemispheric asymmetry of motor cortical excitability in major depression as measured by transcranial magnetic stimulation.</a> The British Journal of Psychiatry. 177 (2), 169-173 (2000).</li><li>Maeda, F., Keenan, J. P., Tormos, J. M., Topka, H., Pascual-Leone, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulation+of+corticospinal+excitability+by+repetitive+transcranial+magnetic+stimulation.">Modulation of corticospinal excitability by repetitive transcranial magnetic stimulation.</a> Clinical Neurophysiology. 111 (5), 800-805 (2000).</li><li>Pascual-Leone, A., Bartres-Faz, D., Keenan, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+magnetic+stimulation:+studying+the+brain-behaviour+relationship+by+induction+of+'virtual+lesions.">Transcranial magnetic stimulation: studying the brain-behaviour relationship by induction of 'virtual lesions.</a> Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences. 354 (1387), 1229-1238 (1999).</li><li>Amati, F., Oh, H., Kwan, V. S., Jordan, K., Keenan, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Overclaiming+and+the+medial+prefrontal+cortex:+A+transcranial+magnetic+stimulation+study.">Overclaiming and the medial prefrontal cortex: A transcranial magnetic stimulation study.</a> Cognitive Neuroscience. 1 (4), 268-276 (2010).</li><li>Tang, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stimulating+the+right+temporoparietal+junction+with+tDCS+decreases+deception+in+moral+hypocrisy+and+unfairness.">Stimulating the right temporoparietal junction with tDCS decreases deception in moral hypocrisy and unfairness.</a> Frontiers in Psychology. 8, 2033 (2017).</li><li>Kelly, K. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+deception+on+motor+cortex+excitability.">The effect of deception on motor cortex excitability.</a> Social Neuroscience. 4 (6), 570-574 (2009).</li><li>Farrow, T. F., Burgess, J., Wilkinson, I. D., Hunter, M. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+correlates+of+self-deception+and+impression-management.">Neural correlates of self-deception and impression-management.</a> Neuropsychologia. 67, 159-174 (2015).</li><li>Uddin, L. Q., Iacoboni, M., Lange, C., Keenan, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+self+and+social+cognition:+the+role+of+cortical+midline+structures+and+mirror+neurons.">The self and social cognition: the role of cortical midline structures and mirror neurons.</a> Trends in Cognitive Sciences. 11 (4), 153-157 (2007).</li><li>Luber, B., Lou, H. C., Keenan, J. P., Lisanby, S. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-enhancement+processing+in+the+default+network:+a+single-pulse+TMS+study.">Self-enhancement processing in the default network: a single-pulse TMS study.</a> Experimental Brain Research. 223 (2), 177-187 (2012).</li><li>Barrios, V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Elucidating+the+neural+correlates+of+egoistic+and+moralistic+self-enhancement.">Elucidating the neural correlates of egoistic and moralistic self-enhancement.</a> Consciousness and Cognition. 17 (2), 451-456 (2008).</li><li>Kwan, V. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessing+the+neural+correlates+of+self-enhancement+bias:+a+transcranial+magnetic+stimulation+study.">Assessing the neural correlates of self-enhancement bias: a transcranial magnetic stimulation study.</a> Experimental Brain Research. 182 (3), 379-385 (2007).</li><li>Taylor-Lillquist, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preliminary+evidence+of+the+role+of+medial+prefrontal+cortex+in+self-enhancement:+a+transcranial+magnetic+stimulation+study.">Preliminary evidence of the role of medial prefrontal cortex in self-enhancement: a transcranial magnetic stimulation study.</a> Brain Sciences. 10 (8), 535 (2020).</li><li>Bikson, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Guidelines+for+TMS/tES+clinical+services+and+research+through+the+COVID-19+pandemic.">Guidelines for TMS/tES clinical services and research through the COVID-19 pandemic.</a> Brain Stimulation. 13 (4), 1124-1149 (2020).</li><li>Lerner, A. J., Wassermann, E. M., Tamir, D. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Seizures+from+transcranial+magnetic+stimulation+2012-2016:+Results+of+a+survey+of+active+laboratories+and+clinics.">Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics.</a> Clinical Neurophysiology. 130 (8), 1409-1416 (2019).</li><li>Pascual-Leone, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safety+of+rapid-rate+transcranial+magnetic+stimulation+in+normal+volunteers.">Safety of rapid-rate transcranial magnetic stimulation in normal volunteers.</a> Electroencephalography and Clinical Neurophysiology. 89 (2), 120-130 (1993).</li><li>Rossi, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safety+and+recommendations+for+TMS+use+in+healthy+subjects+and+patient+populations,+with+updates+on+training,+ethical+and+regulatory+issues:+Expert+Guidelines.">Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines.</a> Clinical Neurophysiology. 132 (1), 269-306 (2021).</li><li>Wassermann, E. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Risk+and+safety+of+repetitive+transcranial+magnetic+stimulation:+report+and+suggested+guidelines+from+the+international+workshop+on+the+safety+of+repetitive+transcranial+magnetic+stimulation.">Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the international workshop on the safety of repetitive transcranial magnetic stimulation.</a> Electroencephalography and Clinical Neurophysiology. 108 (1), 1-16 (1998).</li></ol>

The protocol (and variations of) outlined here has been used in over 50 studies at Montclair State University. The entire set-up can be created for under $15,000 (US). Further, we have found our coordinates match well with underlying brain structures using fiducial procedures.
Variations of&#160;this method are often used. For example, control conditions can include stimulating different brain areas, applying TMS different timings (i.e, apply TMS at a timing that should have no effect), using ...

There are a number of challenges to investigating brain-behavior correlates at research institutions with limited resources (often referred to as &#39;teaching universities&#39;). According to data provided by the National Science Foundation (NSF), almost all academic research is completed by a small percentage of higher education institutions in the United States. When examining over 4,400 post-secondary degree-granting institutions, the top 115 universities/institutes perform and publish 75% of all research1. In the United States, there are 131 research 1 (R1: The highest status level a university can achieve in terms of research ranking) universities which receive the bulk of federal funding.
This top-heavy funding disparity limits research options for many principal investigators as well as students; for example, only 1.9% of R1 universities are Hispanic-Serving institutes. Further, non-R1 institutes are limited in terms of research space, grants awarded, and time made available for research, and these schools often do not have medical school affiliations2. Given these obstacles, we provide the methods that have successfully allowed for the investigation of brain-behavior relationships in deception in a resource limited environment. While these methods are suitable for any institute, we believe that those at smaller/teaching intensive universities will receive the maximum benefit from these methods.
Our laboratory has focused primarily on the brain regions responsible for producing self-deception and self-enhancement. Establishing causation in terms of the underlying cortical regions is achievable by a number of techniques, and these data help confirm correlative neuroimaging methods and experimental patient trials3,4,5.
To investigate self-deception with causal neuroimaging techniques, a number of innovative methods have been employed, mainly with single pulse Transcranial Magnetic Stimulation (TMS) and repetitive TMS (rTMS6;&#160;Figure 1). While tDCS (transcranial Direct Cortical Stimulation) has been employed successfully7 and can be modified to replicate the methods, procedures, and results presented here, the flexibility of TMS still makes it the optimal choice for the neuromodulation of self-deception. At its most common implementation, researchers inhibit, excite, disrupt, or measure cortical excitability (not covered here, but see reference8).
The Medial Prefrontal Cortex (MPFC) appears to be involved in self-deceptive responding9. Given the role of the Cortical Midline Structures (CMS) in terms of self-awareness in general10, it is not surprising that self-deception is correlated with MPFC activity. To determine causation in terms of frontal regions, TMS was relied on to create &#39;virtual lesions&#39; while measuring bouts of self-deception11. Measuring self-deception has been achieved via two main methods: Self-enhancement and overclaiming6.
We have found that disruption of the MPFC leads to the reduction of self-deception6,8,11,12,13. Furthermore, we have discovered that such a reduction (i.e., the lowering of self-deception) is related to a decrease in a person&#39;s affect (i.e., negative mood increases and positive mood decreases).
Because neuro-navigation/individual MRI&#39;s are not employed (due to expense, most laboratories do not have these resources), concern may be raised over positioning and accuracy in TMS targeting. We have compensated for this by occasionally doing fiducial procedures in which a contrast target (e.g., a vitamin E tablet) is placed on the cap and the participant(s) is/are subsequently scanned in a structural MRI11,12. These methods have confirmed the accuracy of the methods outlined here, and we are targeting the medial aspect of the MPFC at the border of BA 10/9 which lies above the Medial Frontal Gyrus (0, ~40, ~30).
Clearly, higher spatial resolution can be obtained using other methods such as neuro-navigation, however, these methods are not employed without drawbacks which include participant drop-out, participant exclusion, increased length of experimental duration, additional training and screening, added expense and often multiple site visits for participants. Therefore, the methods presented here offer an excellent alternative to neuro-navigation in many circumstances.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Android Samsung Tablet (for MEPs)</td>
			<td>Samsung</td>
			<td>SM-T500NZSAXAR</td>
			<td></td>
		</tr>
		<tr>
			<td>Cloth Measuring Tape</td>
			<td>GDMINLO</td>
			<td>B08TWNCDNS(AMZ)</td>
			<td></td>
		</tr>
		<tr>
			<td>Figure of 8 Copper TMS Coil</td>
			<td>Magstim</td>
			<td>4150-00</td>
			<td>This is the current model</td>
		</tr>
		<tr>
			<td>Lenovo T490 Laptop</td>
			<td>Lenovo</td>
			<td>20RY0002US</td>
			<td></td>
		</tr>
		<tr>
			<td>Magstim 200 Single Pulse</td>
			<td>MagStim</td>
			<td>Magstim200/2</td>
			<td>This is the current model</td>
		</tr>
		<tr>
			<td>Magstim Standard Coil Holder</td>
			<td>MagStim</td>
			<td>AFC/SS</td>
			<td>This is the current model</td>
		</tr>
		<tr>
			<td>Speedo Swim Caps</td>
			<td>Speedo</td>
			<td>751104-100</td>
			<td></td>
		</tr>
		<tr>
			<td>Testable.Org Account and Software</td>
			<td>Testable</td>
			<td>NA</td>
			<td></td>
		</tr>
		<tr>
			<td>Trigno 2 Lead Sensor (for MEPs)</td>
			<td>DelSys</td>
			<td>SP-W06-018B</td>
			<td></td>
		</tr>
		<tr>
			<td>Trigno Base and Plot Software (for MEPs)</td>
			<td>DelSys</td>
			<td>DS-203-D00</td>
			<td></td>
		</tr>
	</tbody>
</table>

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.

Figure 2, from Taylor-Lilquist et al.14, involved four brain sites: MPFC, SMA, PZ, and a Sham site. These sites were utilized to determine the correlates of overclaiming. Overclaiming is a participant indicating that they know a word when it is actually not a word. 12 participants were tested in both social and non-social settings. The social settings represented pressure to either know a word (high-social pressure; n=6) or not know a word (low-social pressure; n=6). ...

Watch this Scientific Journal Video about Employing Transcranial Magnetic Stimulation in a Resource Limited Environment to Establish Brain-Behavior Relationships at JoVE.com

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

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.

Neuroimaging is typically perceived as a resource demanding discipline. While this is the case in certain circumstances, institutions with limited ...

Vital discoveries in neuroscience can be made in resource limited environments. Here, we detail how to employ transcranial magnetic stimulation using valid and reliable methods. Single pulse and low frequency TMS provides causal, not correlational brain behavior relationships.This allows one to make much stronger conclusions about brain behavior relationships. TMS is used routinely to treat depression. By training minorities and other resource limited students in TMS, we are expanding the pool of trained professionals.TMS is used in almost every clinical and scientific application. However, it has been able to answer questions on consciousness and self-awareness that have baffled great thinkers for centuries. Anyone starting out with TMS should work on motor systems because you can actually see the effects of TMS immediately with a hand or leg movement.The other possibility is working on the visual system and asking participants to report the phosphenes that they see. Both systems give feedback immediately to the learning student. Begin by marking swim caps along the nasion or inion line and the midpoint taken using a magic marker.Measure pre-auricular points and take those midpoints, as well. From here, plot 10/20 coordinates. Using the right hemisphere pre-auricular line, go 33%down in the ventral direction and begin searching for the optimal location for the Abductor Pollicis Brevis or APB using the TMS coil.Discharge the TMS machine using the coil trigger, the foot switch, and disengaging the safety. Orient the TMS coil at 45 degrees for all searches in TMS deliveries, then start the stimulation output at 20%total machine output by using the dial on the front of the machine. Raise in 2%increments using the dial until a movement is noted.Here, as the stimulation is increased in terms of intensity, move the location also. There is a careful interplay between coil movement and stimulation intensity. Mark the coil tip site on the cap to allow an accurate placement and trace the entire anterior portion of the coil onto the swim cap using a magic marker.Once the optimal location is found, that is the site that provided the maximum APB response, determined the MT.For the visual inspection method, start at 20%of machine intensity and workup. The dial should be raised and lowered in response to increased or decreased finger movements. Use approximately 20 pulses to find what stimulation level results in 5 out of 10 APB responses.Once 5 out of 10 responses have been obtained, record the individual's MT by noting what the machine is displaying as the intensity. For the MEP method, place disposable electrodes on the APB and the tendon of the thumb and a ground. Define a positive MEP response as an MEP with greater than or equal to 50 microvolts peak-to-peak amplitude.Similar to visual inspection, stimulate until 5 out of 10 positive MEPs are observed. The MEPs should be greater than 50 microvolts. If 50%of the MEPs are above, it can be said that MT has been identified.Set the TMS machine to the appropriate stimulation level. 90%of the motor threshold is an ideal balance between effective, active TMS and safety. Randomly select the order of all sites.Place the coil over the active site and start a presentation software. Stimulation should proceed automatically and in sync with stimuli. Collect all behavioral data using the presentation software.Give two practice trials and introduce the analog scale to the participants. All participants easily adjust to the equipment. The instructions are given orally and the participants are told to rate how well they know the word.If the word is familiar to them, it should be given a high rating. If they sort of know the word, they are to give a medium rating. If the word is not that familiar to them, they will assign a low rating.A total of 144 words should be used. Participants have unlimited time to respond. Following the response on the analog scale, the next word is presented.Self-deception can be modulated using TMS. Participants were given social pressure to know words in one condition and no social pressure in another condition. The social pressure was a series of verbal prompts that indicated that every person knew these words and they were easy or that the words were difficult and most people did not know them.Means and the standard errors are presented here. Because social cognition is a medial prefrontal cortex, or MPFC function, it was assumed that TMS delivered in an inhibitory manner would decrease overclaiming. This was found to be the case.Measuring out the 10/20 system and correctly gauging motor threshold is important for safety and reliable results. Instead of the 10/20 system, narrow navigation can be used. TMS was a first major technique that determined causal relationships between brain and behavior.Additionally, it is now a major therapeutic technique using the treatment of depression.

employing-transcranial-magnetic-stimulation-resource-limited

Research

JoVE Journal

Neuroscience

A Novel Approach for Documenting Phosphenes Induced by Transcranial Magnetic Stimulation

Stimulation of the human visual cortex produces a transient perception of light, known as a phosphene. Phosphenes are induced by invasive electrical stimulation of the occipital cortex, but also by non-invasive Transcranial Magnetic Stimulation (TMS)1 of the same cortical regions. The intensity at which a phosphene is induced (phosphene threshold) is a well established measure of visual cortical excitability and is used to study cortico-cortical interactions, functional organization 2, susceptibility to pathology 3,4 and visual processing 5-7. Phosphenes are typically defined by three characteristics: they are observed in the visual hemifield contralateral to stimulation; they are induced when the subject s eyes are open or closed, and their spatial location changes with the direction of gaze 2. Various methods have been used to document phosphenes, but a standardized methodology is lacking. We demonstrate a reliable procedure to obtain phosphene threshold values and introduce a novel system for the documentation and analysis of phosphenes. We developed the Laser Tracking and Painting system (LTaP), a low cost, easily built and operated system that records the location and size of perceived phosphenes in real-time. The LTaP system provides a stable and customizable environment for quantification and analysis of phosphenes.

Phosphenes are transient percepts of light that can be induced by applying Transcranial Magnetic Stimulation (TMS) to visually sensitive regions of cortex. We demonstrate a standard protocol for determining the phosphene threshold value and introduce a novel method for quantifying and analyzing perceived phosphenes.

Stimulation of the human visual cortex produces a transient perception of light, known as a phosphene. Phosphenes are induced by invasive electrical ...

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 ...

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 ...

Transcranial Electrical Brain Stimulation in Alert Rodents

Transcranial electrical brain stimulation can modulate cortical excitability and plasticity in humans and rodents. The most common form of stimulation in humans is transcranial direct current stimulation (tDCS). Less frequently, transcranial alternating current stimulation (tACS) or transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range, is used. The increase of noninvasive electrical brain stimulation research in humans, both for experimental and clinical purposes, has yielded an increased need for basic, mechanistic, safety studies in animals. This article describes a model for transcranial electrical brain stimulation (tES) through the intact skull targeting the motor system in alert rodents. The protocol provides step-by-step instructions for the surgical set-up of a permanent epicranial electrode socket combined with an implanted counter electrode on the chest. By placing a stimulation electrode into the epicranial socket, different electrical stimulation types, comparable to tDCS, tACS, and tRNS in humans, can be delivered. Moreover, the practical steps for tES in alert rodents are introduced. The applied current density, stimulation duration, and stimulation type may be chosen depending on the experimental needs. The caveats, advantages, and disadvantages of this set-up are discussed, as well as safety and tolerability aspects.

This protocol describes a surgical set-up for a permanent epicranial electrode socket and an implanted chest electrode in rodents. By placing a second electrode into the socket, different types of transcranial electrical brain stimulation can be delivered to the motor system in alert animals through the intact skull.

Transcranial electrical brain stimulation can modulate cortical excitability and plasticity in humans and rodents. The most common form of stimulation in ...

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 ...

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 ...