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 Effects (Supplementary File 2) forms from other researchers-they are readily shared across the TMS community. NOTE: For the purpose of this experiment, forms were obtained from Simone Rossi.</li>
	<li>Train all investigators on consenting and informing participants of all risks, side effects, and potential adverse events. If necessary, the Principal Investigator (PI) takes a TMS course if further knowledge is needed. Prior to running participants, ensure that the PI performs a pilot test of the protocol including consent and debriefing.</li>
	<li>Recruit participants through flyers around campus. Screen participants in person; initial contact need not be in person. Ensure that the flyers describe the compensation and risks in general terms only, including any special circumstances (e.g., COVID).</li>
	<li>Ensure participants read the consent form aloud including specific questions including: Are you a current student of ____PI______? Do you have a: history of epilepsy, family history of epilepsy? Do you have a history of seizures? Do you have any of the following-stroke, cranial metal implants, structural brain lesion, implanted device, pacemaker, medication pump, cochlear implant, implanted brain stimulator, metal worker? Do you have a history of head trauma with loss of consciousness? Do you have a high potential for pregnancy? Are you younger than 18? Are you older than 65?</li>
	<li>Excuse any participants affirming any questions from the study.</li>
	<li>Before being enrolled, ensure that the Screening Checklist is administered.</li>
	<li>Pay all participants $25 for their participation and treat in accordance with guidelines of the Institutional&#160;Review Board at Montclair State University and of the American Psychological Association.</li>
	<li>Deliver all TMS within the parameter appropriate for the institution (see Discussion).</li>
	<li>Participant safety and comfort is critical so at all points forward, ask and monitor the participants closely both verbally and visually. Nervousness can be the norm which in some cases leads to more difficult outcomes and this is monitored.</li>
</ol>
2. TMS equipment handling
<ol>
	<li>Use a single-pulse TMS device for all stimulation. Trigger the device by simultaneous depression of hand and foot switches manually by the PI. Use the maximum stimulation rate of the stimulator (i.e., 0.75 Hz).</li>
	<li>Use a 70 mm figure-of-eight coil throughout the experiment. Ensure that the coil never reaches dangerous/shut-off temperatures during the experiment. Backup coils are ready in case needed as replacements.</li>
	<li>Present all stimuli using a laptop computer. Open up the software (e.g., Testable) and login to the account. Click on the appropriate experiment.</li>
	<li>Scale the monitor using a credit card. Enter demographic information. Clean/sanitize the laptop before and after each participant is tested.</li>
	<li>Determine the motor threshold using visual inspection (5/10 evoked Abductor Pollicis Brevis) or via an EMG (Electromyograph).</li>
	<li>Use swim caps to preserve markings. Use a standard coil holder for training and as demonstration only, not for active stimulation.</li>
	<li>Use cloth tape measures to take coordinates for CZ and OZ from the 10/20 system and take MPFC from a previous study on overclaiming10. To determine MPFC, take 1/3 of the distance of nasion to inion, and MPFC is 1.5 cm anterior to this location. This will focus at the BA 10/9 (Medial Frontal Gyrus).</li>
	<li>Confirm measurements at the PI&#39;s discretion using the fiducial method in which a vitamin E tablet is adhered to the cap of the coil location which will contrast easily in a standard MRI. Due to the cost, this option is limited.</li>
</ol>
3. COVID - 19
<ol>
	<li>Due to COVID-19, include the following protocols14. In the Consent Form, add a disclaimer: &#34;As a participant in this study, you will spend time in an indoor space within close proximity of the researcher. This poses a significant additional risk to getting COVID-19. We are taking the following precautions to protect you such as: Only PI will be within 6 ft of participant; Only one assistant is allowed in the vicinity but they must stay socially distanced; The participant must wear two masks; PI must wear two masks, gloves and a face shield; The assistant must wear a mask and a face shield; All contact equipment is sanitized.&#34;</li>
	<li>Perform all experiments in the lobby/hall outside of the normal lab as ventilation is significantly increased. All equipment is sanitizable and portable.</li>
	<li>Once COVID-19 protocols are relaxed, use normal procedures.</li>
</ol>
4. Motor threshold
<ol>
	<li>Mark swim caps along the nasion/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 (see 2.6).</li>
	<li>Using the right hemisphere pre-auricular line, then go 33% down (in the ventral direction) and begin the search for the optimal location for the Abductor Pollicis Brevis (APB) using the TMS coil. Discharge the TMS machine using the coil trigger, the footswitch, and disengaging the safety.</li>
	<li>Orient the TMS coil at 45&#176; for all searches and TMS deliveries.</li>
	<li>Start the stimulation output at 30% total machine output by using the dial on the front of the machine and 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.</li>
	<li>Once the optimal location is found (i.e., the site that provided the maximum APB response), determine the MT.</li>
	<li>Prior to starting MT determination, mark the coil tip site on the cap to allow accurate placement. Trace the entire anterior portion of the coil on to the swim cap using a magic marker.</li>
	<li>For the visual inspection method, use approximately 20 pulses (varying machine intensity) to find what stimulation level results in 5/10 (50%) APB responses. The dial should be raised and lowered in response to increased or decreased finger movements. Start at 20% of machine intensity and work up. Once 5/10 responses have been obtained, record the individual&#39;s MT by noting what the machine is displaying as the intensity.</li>
	<li>For the (preferred) MEP method, place disposable electrodes on the APB and the tendon of the thumb and a ground (usually around the back of the wrist), and instead of using visual inspection, a positive MEP must be observed on the recording unit.</li>
	<li>Define a positive MEP response as an MEP with &#8805;50 &#181;V peak-to-peak amplitude.</li>
	<li>Similar to visual inspection, stimulate until 5/10 positive MEPs are observed. The MEPs should be greater than 50 &#181;V. If 50% of the MEPs are above (and 50% below), MT has been identified.</li>
	<li>Once established, set the TMS machine to the appropriate stimulation level. 90% of the motor threshold is an ideal balance between effective active TMS and safety. Do not exceed 45% of the machine&#39;s total output. There are occasions that a person&#39;s MT is 60% of the machine&#39;s total output, but this is rare.</li>
</ol>
5. Active single-pulse TMS
<ol>
	<li>Randomly select the order of all sites (e.g., SMA, PZ, MPFC, or Sham over CZ; Figure 5).</li>
	<li>Place the coil over the active site and start a presentation software, (e.g., Testable (see below)). Stimulation should proceed automatically and in sync with stimuli.</li>
	<li>Always have a spare coil in case of overheating.</li>
</ol>
6. Presentation
<ol>
	<li>Collect all behavioral data using a presentation software (e.g., Testable) This software is easily configured, and scripts are simple. 
	NOTE: Three separate blocks are created-one for each of the brain conditions. Demographics to be collected are first chosen using Testable&#39;s automatic selection routine. Then real words and fake words are placed into the scripting software. The size and duration of the words are chosen, as is the location on the screen of the stimulus words.</li>
	<li>Once the script is made, collect demographics first and perform screen calibration. This is done matching the slider to a credit card. Perform all experiments on a computer. All responses are made on the built-in keyboard and sensor pad.</li>
	<li>Give two practice trials and introduce the analog scale. 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.
	<ol>
		<li>If the word is familiar to them (such as &#39;desk&#39;) it should be given a high rating.</li>
		<li>If they &#39;sort of&#39; know the word, they are to give a medium rating (such as &#39;chlorophyll&#39;).</li>
		<li>If it is not that familiar to them, they will assign a low rating (such as &#39;5HTTlpr&#39;). A total of 144 words should be used (36 per brain site).</li>
	</ol>
	</li>
	<li>Participants have unlimited time to respond. Following the response on the analog scale, the next word is presented.</li>
</ol>

<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. 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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><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 ...

employing-transcranial-magnetic-stimulation-resource-limited

Research

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Neuroscience

1.8K Views.  Montclair State University. Vitale ontdekkingen in de neurowetenschappen kunnen worden gedaan in omgevingen met beperkte middelen. Hier beschrijven we hoe u transcraniële magnetische stimulatie kunt gebruiken met behulp van geldige en betrouwbare methoden. Single pulse en laagfrequent TMS biedt causale, niet correlationele hersengedragsrelaties.Hierdoor kan men veel sterkere conclusies trekken over relaties tussen hersengedrag. TMS wordt routinematig gebruikt om depressie te behandelen. Door minderheden en ander...

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

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

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

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

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

Behavior

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

The effect of a stimulus to the brain depends not only on the parameters of the stimulus but also on the dynamics of brain activity at the time of the stimulation. The combination of electroencephalography (EEG) and transcranial magnetic stimulation (TMS) in a real-time brain state-dependent stimulation system allows the study of relations of dynamics of brain activity, cortical excitability, and plasticity induction. Here, we demonstrate a newly developed method to synchronize the timing of brain stimulation with the phase of ongoing EEG oscillations using a real-time data analysis system. This real-time EEG-triggered TMS of the human motor cortex, when TMS is synchronized with the surface EEG negative peak of the sensorimotor &#181;-alpha (8-14 Hz) rhythm, has shown differential corticospinal excitability and plasticity effects. The utilization of this method suggests that real-time information about the instantaneous brain state can be used for efficacious plasticity induction. Additionally, this approach enables personalized EEG-synchronized brain stimulation which may lead to the development of more effective therapeutic brain stimulation protocols.

This paper describes real-time electroencephalography-triggered transcranial magnetic stimulation to study and modulate human brain networks.

The effect of a stimulus to the brain depends not only on the parameters of the stimulus but also on the dynamics of brain activity at the time of the ...

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 ...

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 ...

Non-Invasive Modulation and Robotic Mapping of Motor Cortex in the Developing Brain

Mapping the motor cortex with transcranial magnetic stimulation (TMS) has potential to interrogate motor cortex physiology and plasticity but carries unique challenges in children. Similarly, transcranial direct current stimulation (tDCS) can improve motor learning in adults but has only recently been applied to children. The use of tDCS and emerging techniques like high&#8211;definition tDCS (HD-tDCS) require special methodological considerations in the developing brain. Robotic TMS motor mapping may confer unique advantages for mapping, particularly in the developing brain. Here, we aim to provide a practical, standardized approach for two integrated methods capable of simultaneously exploring motor cortex modulation and motor maps in children. First, we describe a protocol for robotic TMS motor mapping. Individualized, MRI-navigated 12x12 grids centered on the motor cortex guide a robot to administer single-pulse TMS. Mean motor evoked potential (MEP) amplitudes per grid point are used to generate 3D motor maps of individual hand muscles with outcomes including map area, volume, and center of gravity. Tools to measure safety and tolerability of both methods are also included. Second, we describe the application of both tDCS and HD-tDCS to modulate the motor cortex and motor learning. An experimental training paradigm and sample results are described. These methods will advance the application of non-invasive brain stimulation in children.

We demonstrate protocols for the modulation (tDCS, HD-tDCS) and mapping (robotic TMS) of the motor cortex in children.

Mapping the motor cortex with transcranial magnetic stimulation (TMS) has potential to interrogate motor cortex physiology and plasticity but carries ...

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 ...

Stimulating Mouse Brain with a Low-Cost EEG and Millimeter-Sized Coil

Low-Cost Electroencephalographic Recording System Combined with a Millimeter-Sized Coil to Transcranially Stimulate the Mouse Brain In Vivo

A low-cost electroencephalographic (EEG) recording system is proposed here to drive transcranial magnetic stimulation (TMS) of the mouse brain in vivo, utilizing a millimeter-sized coil. Using conventional screw electrodes combined with a custom-made, flexible, multielectrode array substrate, multi-site recording can be carried out from the mouse brain. In addition, we explain how a millimeter-sized coil is produced using low-cost equipment usually found in laboratories. Practical procedures for fabricating the flexible multielectrode array substrate and the surgical implantation technique for screw electrodes are also presented, which are necessary to produce low-noise EEG signals. Although the methodology is useful for recording from the brain of any small animal, the present report focuses on electrode implementation in an anesthetized mouse skull. Furthermore, this method can be easily extended to an awake small animal that is connected with tethered cables via a common adapter and fixed with a TMS device to the head during recording.The present version of the EEG-TMS system, which can include a maximum of 32 EEG channels (a device with 16 channels is presented as an example with fewer channels) and one TMS channel device, is described. Additionally, typical results obtained by the application of the EEG-TMS system to anesthetized mice are briefly reported.

Author Spotlight: Low-Cost Electroencephalographic Recording System Combined with a Millimeter-Sized Coil to Transcranially Stimulate the Mouse Brain In Vivo  

A low-cost electroencephalographic recording system combined with a millimeter-sized coil is proposed to drive transcranial magnetic stimulation of the mouse brain in vivo. Using conventional screw electrodes with a custom-made, flexible, multielectrode array substrate, multi-site recording can be carried out from the mouse brain in response to transcranial magnetic stimulation.

A low-cost electroencephalographic (EEG) recording system is proposed here to drive transcranial magnetic stimulation (TMS) of the mouse brain in vivo, ...

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

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