1. Preparation
<ol class="lalpha">
<li>To begin, obtain a baseline anatomical scan of your subject. This should be done several days before the actual experiment.</li>
<li>Next, load the scan into your frameless stereotactic software package.</li>
<li>Finally, locate and target your stimulation coordinates. In this case, we will be targeting the left inferior parietal lobule.</li>
</ol>
2. The Initial Scan
<ol class="lalpha">
<li>On the day of the experiment, your subject will, once again, start in the MRI machine.</li>
<li>Begin with an anatomical scan.</li>
<li>Next, conduct three functional experimentation runs. For this experiment, the task is quite simple: A fixation point is presented in the subject's central field of vision, and he/she is to simply stare at it passively.</li>
</ol>
3. TMS Preparation
<ol class="lalpha">
<li>Because the effects of rTMS are transitory, time is of the essence when combining TMS and fMRI. It is imperative you get the subject back into the scanner as soon as possible after stimulation cessation. Because of this, you'll want to use a portable TMS device stationed in a room adjacent to or as close as possible to the scanning-bay as possible. In this case, we're using a portable set-up in an observation suite next door to the scanner.</li>
<li>Load your subject's pre-targeted baseline MRI into the stereotactic software package.</li>
<li>Finally, link and calibrate your stimulating coil with the stereotaxy equipment - in this case, we'll align a set of infrared sensors to register coil centrality.</li>
</ol>
4. Determining TMS Parameters
<ol class="lalpha">
<li>When the subject arrives, sit him/her comfortably in a chair.</li>
<li>Next, calibrate your subject's head with the sterotaxy equipment. In this case, we'll use infrared sensors to register several positioning anchors: both ears, the nose, and the nasion.</li>
<li>Determine your subject's resting motor threshold.</li>
<li>If we want to excite the subject's cortex, we will set the TMS machine to 20 Hz with a stimulation power of 110% motor threshold. If we want to inhibit the subject's cortex, we will set the TMS machine to 1 Hz at 110% motor threshold. Although you'll want to explore both parameters throughout the course of a full study, we will only look at a 20 Hz excitatory rTMS chain in this article.</li>
<li>Finally, set up a stimulation pattern of 2 second trains with 28 second rest periods.</li>
</ol>
5. TMS Stimulation
<ol class="lalpha">
<li>Prior to stimulation, prepare the subject to go directly in the scanner following TMS. This includes removal of metal and ensuring the subject has used the restroom.</li>
<li>Holding the coil tangential to the scalp, use your stereotaxy equipment to locate and target the subject's stimulation site.</li>
<li>Turn on the machine's coil cooling system.</li>
<li>Begin stimulation! For this protocol, we will conduct 45 total stimulation trains. At 2 seconds a train with 28 second breaks, we will have a total stim time of 23 minutes.</li>
</ol>
6. Back to the Scanner
<ol class="lalpha">
<li>Once stimulation is complete, it is important to get the subject back into the scanner as soon as possible. To make this transition as seamless as possible, ensure your scanner is prepared and ready to go. Our advice is to raise the body platform, and reduce the number and duration of localizer scans to a bare minimum.</li>
</ol>
7. Final Scan
<ol class="lalpha">
<li>Because the effects of rTMS are transitory, the final scanning session should begin with the functional runs. Again, we'll conduct three, 6-minute runs of passive fixation.</li>
<li>After the experimental runs are complete, finish with an anatomical scan.</li>
</ol>
8. Representative Results
<img src="/files/ftp_upload/2271/2271fig1.jpg" alt="Figure 1" /> Figure 1.The data suggests that 20 Hz rTMS stimulation to the left inferior parietal lobule, although facilitating local excitability, acts to decrease functional connectivity within the default network.

<ol>
	<li>Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., Shulman, G. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+default+mode+of+brain+function.">A default mode of brain function.</a> Proc. Nat. Acad. Sciences. 98 (2), 676-682 (2001).</li><li>Buckner, R. L., Andrews-Hanna, J. R., Schacter, D. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+brain's+default+network:+anatomy,+function+and+relevance+to+disease.">The brain's default network: anatomy, function and relevance to disease.</a> Ann. N.Y. Acad. Sci. 1124, 1-38 (2008).</li><li>Raichle, M. E., Snyder, A. Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+default+mode+of+brain+function:+a+brief+history+of+an+evolving+idea.">A default mode of brain function: a brief history of an evolving idea.</a> Neuroimage. 37 (4), 1083-1090 (2007).</li><li>Whitfield-Gabrieli, S., Thermenos, H. W., Milanovic, S., Tsuang, M. T., Faraone, S. V., McCarley, R. W., Shenton, M. E., Green, A. I., Nieto-Castanon, A., LaViolette, P., Wojcik, J., Gabrieli, J. D., Sidman, L. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperactivity+and+hyperconnectivity+of+the+default+network+in+schizophrenia+and+in+first-degreerelatives+of+persons+with+schizophrenia.">Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degreerelatives of persons with schizophrenia.</a> Proc. Nat. Acad. Sciences. 106 (4), 1279-1284 (2009).</li><li>Pomarol-Clotet, E., Salvardor, R., Sarro, S., Gomar, J., Vila, F., Martinez, A., Guerrrero, A., Ortiz-Gil, J., Sans-Sansa, B., Capdevila, A., Cebamanos, J. M., McKenna, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Failure+to+deactivate+the+prefrontal+cortex+in+schizophrenia:+dysfunction+of+the+default+mode+network?.">Failure to deactivate the prefrontal cortex in schizophrenia: dysfunction of the default mode network?.</a> Psychol Med. 38 (8), 1185-1193 (2008).</li><li>Garrity, A. G., Pearlson, G. D., McKiernan, K., Lloyd, D., Kiehl, K. A., Calhoun, V. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Aberrant+"default+mode"+functional+connectivity+in+schizophrenia.">Aberrant "default mode" functional connectivity in schizophrenia.</a> American Journal of Psychiatry. 164, 450-457 (2007).</li><li>Kennedy, D. P., Redcay, E., Courchesne, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Failing+to+deactivate:+Resting+functional+abnormalities+in+autism.">Failing to deactivate: Resting functional abnormalities in autism.</a> Proc. Nat. Acad. Sciences. 103 (21), 8275-8280 (2007).</li><li>c Buckner, R. L., Snyder, A. Z., Shannon, B. J., LaRossa, G., Sachs, R., Fotenos, A. F., Sheline, Y. I., Klunk, W. E., Mathis, C. A., Morris, J. C., Mintun, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular,+structural,+and+functional+characterizations+of+Alzheimer's+disease:+evidence+for+a+relationship+between+default+activity,+amyloid,+and+memory.">Molecular, structural, and functional characterizations of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory.</a> Journal of Neuroscience. 34, 7709-7717 (2005).</li><li>Pascual-Leone, A., Davey, M., Wassermann, E. M., Rothwell, J., Puri, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Handbook of Transcranial Magnetic Stimulation. , (2002).</li></ol>

No conflicts of interest declared.

When conducting an offline TMS/MRI experiment, arguably the most important consideration involves the swift and effortless transition from the site of stimulation to the MRI bay. As such, it would be worth revisiting several of the aforementioned ideas suggested to aid in this transition. First: use a portable TMS machine set up in a location as close to the MRI bay as possible. Two: circumvent any automatic stand-by or equivalent mechanism programmed into the MRI equipment. Three: ensure the platform is raised an...

<ul>
	<li>MRI Equipped for fMRI (pictured in video is a Philips)</li>
	<li>TMS Device Capable of Repetitive Stimulation (pictured in video is a Magstim)</li>
	<li>Frameless Stereotaxy Equipment (pictured in video is Brainsight)</li>
	<li>Ear Plugs</li>
	<li>Chair for Subject during Stimulation</li>
	<li>Back Projection Screen or MRI Compatible Goggles</li>
	<li>Blank Stimuli Screen</li>
</ul>

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.

Watch this Scientific Journal Video about Combining Transcranial Magnetic Stimulation and fMRI to Examine the Default Mode Network at JoVE.com

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

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 ...

combining-transcranial-magnetic-stimulation-fmri-to-examine-default

Research

JoVE Journal

Neuroscience

12.8K ビュー.  Beth Israel Deaconess Medical Center. この記事では、デフォルトのネットワーク上の脳刺激の効果を調べるためにTMSとfMRIの組み合わせに関連する方法論と考慮事項を検討する。

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

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 ...

Extracting Visual Evoked Potentials from EEG Data Recorded During fMRI-guided Transcranial Magnetic Stimulation

Transcranial Magnetic Stimulation (TMS) is an effective method for establishing a causal link between a cortical area and cognitive/neurophysiological effects. Specifically, by creating a transient interference with the normal activity of a target region and measuring changes in an electrophysiological signal, we can establish a causal link between the stimulated brain area or network and the electrophysiological signal that we record. If target brain areas are functionally defined with prior fMRI scan, TMS could be used to link the fMRI activations with evoked potentials recorded. However, conducting such experiments presents significant technical challenges given the high amplitude artifacts introduced into the EEG signal by the magnetic pulse, and the difficulty to successfully target areas that were functionally defined by fMRI. Here we describe a methodology for combining these three common tools: TMS, EEG, and fMRI. We explain how to guide the stimulator&#39;s coil to the desired target area using anatomical or functional MRI data, how to record EEG during concurrent TMS, how to design an ERP study suitable for EEG-TMS combination and how to extract reliable ERP from the recorded data. We will provide representative results from a previously published study, in which fMRI-guided TMS was used concurrently with EEG to show that the face-selective N1 and the body-selective N1 component of the ERP are associated with distinct neural networks in extrastriate cortex. This method allows us to combine the high spatial resolution of fMRI with the high temporal resolution of TMS and EEG and therefore obtain a comprehensive understanding of the neural basis of various cognitive processes.

This paper describes a method for collecting and analyzing electroencephalography (EEG) data during concurrent transcranial magnetic stimulation (TMS) guided by activations revealed with functional magnetic resonance imaging (fMRI). A method for TMS artifact removal and extraction of event related potentials is described as well as considerations in paradigm design and experimental setup.

Transcranial Magnetic Stimulation (TMS) is an effective method for establishing a causal link between a cortical area and cognitive/neurophysiological ...

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 ...

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 ...

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.

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

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 ...

Combined Peripheral Nerve Stimulation and Controllable Pulse Parameter TMS

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

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

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

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

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