This works was supported by grants from the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. ST was supported by a Vanier Canada Graduate scholarship from the Canadian Institutes of Health Research. MM acknowledges the support from Biotechnology Research Center (BTRC) grant P41 RR008079 and P41 EB015894 (NIBIB), and NCC P30 NS076408.
We would like to acknowledge Romain Valabr&#232;gue (Centre de NeuroImagerie de Recherche &#8211; CENIR, Paris, France) and Brice Tiret (Centre Recherche de l&#8217;Institut Universiatire de G&#233;riatrie (CRIUGM), Montr&#233;al, Canada; Commissariat &#224; l&#39;&#233;nergie atomique et aux &#233;nergies alternatives (CEA), Paris, France) for developing processing tools, and Edward J. Auerbach (Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, USA). The MEGA-PRESS and FASTESTMAP sequences were developed by Edward J. Auerbach and Ma&#322;gorzata Marja&#324;ska and were provided by the University of Minnesota under a C2P agreement.

The study was approved by the Research and Community Ethics Boards of Unit&#233; de Neuroimagerie Fonctionnelle and University of Montr&#233;al and was done in compliance with the code of ethics as stated in the Declaration of Helsinki. All subjects gave written informed consent following careful screening for MRI compatibility and were financially compensated for their participation.
1. tDCS Material
<ol>
	<li>Make sure all necessary materials are available before starting the experiment (s...

The present paper aimed to describe a standard protocol for combining tDCS and 1H-MRS using a 3 T scanner. In the next section, methodological factors will be discussed.
Critical Steps 
Contraindications Screening 
Previous to the experiment, it is crucial to screen participants for any contraindication regarding the use of tDCS and 1H-MRS. The use of the following exclusion criteria is recommended for tDCS: a psychiatric or neurologic...

The idea of applying electricity to the human brain to modulate its activity has been studied since ancient times. In fact, writings from as early as the 11th century have been found that describe the use of the torpedo electric fish in the treatment of epileptic seizures1. Yet, it is not until recently that non-invasive brain stimulation has received widespread interest in the scientific community as it was shown to produce modulatory effects on cognitive function and motor response2. While transcranial magnetic stimulation (TMS) has been extensively studied since the early 1980&#39;s3, recent interest in transcranial direct current stimulation (tDCS) has increased as it is now considered a viable treatment option for a wide range of neuropathologies, such as stroke4, alcohol addiction5, and chronic pain6. tDCS has many advantages over neurostimulation techniques like TMS, for example, since it is relatively inexpensive, painless, well tolerated by patients, and portable, thus making it possible to administer at bedside7. In fact, only a small percentage of patients experience a mild tingling sensation during stimulation8. However, this sensation usually disappears after a few seconds9. Consequently, tDCS allows robust double-blind, sham-controlled studies since a majority of participants cannot differentiate sham stimulation from real stimulation9,10.
tDCS involves the induction of a constant low-amperage electric current (1-2 mA) applied to the cortex via surface electrodes positioned on the scalp of the subject. The electrodes are usually placed into saline-soaked sponges or directly on the scalp with an EEG-type paste. To conduct a tDCS study, four main parameters need to be controlled by the experimenter: 1) the duration of stimulation; 2) the intensity of stimulation; 3) the electrode size; and 4) the electrode montage. In standard protocols, the &#8220;active&#8221; electrode is positioned over the region of interest while the reference electrode is usually placed over the supraorbital region. The current flows from the positively charged anode towards the negatively charged cathode. The effect of tDCS on primary motor cortex (M1) is determined by the polarity of the stimulation where anodal stimulation enhances the excitability of a population of neurons and cathodal stimulation reduces it 11. Unlike TMS, the induced current is insufficient to produce action potentials in cortical neurons. The changes in cortical excitability are believed to be due to the modulation of the membrane neuronal threshold leading to either the hyperpolarization of membrane potentials or a facilitation of depolarization of neurons depending on the direction of the current flow 8,11. The duration of the excitability changes can persist for up to 90 min after the offset of stimulation, depending on stimulation duration 11,12.
tDCS and Motor Rehabilitation
The M1 has been extensively used as a target of stimulation since excitability changes elicited by tDCS can be quantified through motor evoked potentials (MEPs) induced by single pulse TMS 3. Early studies showing the possibility of measuring polarity-specific excitability changes induced by tDCS have used M1 as a target of stimulation 11,12. Since then, M1 has remained one of the primary targets of tDCS in studies involving both clinical populations and healthy subjects because of its importance in motor function, memory formation, and consolidation of motor skills 12.
The brain relies on a complex interaction between motor regions of both hemispheres to perform a movement 14. When one area is damaged, after suffering a stroke for example, inter-hemispheric interactions are altered. Studies on brain plasticity have shown that the motor areas of the brain adapt to this modification in different ways 15. First, the intact, surrounding regions of the damaged area can become overactived, leading to inhibition of the damaged area - a process called intra-hemispheric inhibition. Second, the homologous region of the damaged area can become overactivated and exert inhibition on the injured hemisphere - a process called inter-hemispheric inhibition. The affected M1 can therefore be twice penalized: first by the lesion and second by the inhibition coming from both the unaffected M1 and the surrounding region of the affected M1 16. A recent study has shown that increased excitability in the unaffected hemisphere is linked to slower rehabilitation 17, which has been described as maladaptive inter-hemispheric competition 18.
Understanding the plasticity occurring after a stroke may lead to the development of neuromodulation protocols that can restore interhemispheric interactions 19. Three main tDCS treatments have been proposed in patients with motor deficits following stroke 20,21. The first treatment aims to reactivate the injured motor cortex by unilateral anodal stimulation (a-tDCS). In this case, stimulation aims at directly increasing activity in perilesional areas, which are believed to be essential for recovery. In fact, studies have shown improvement of the paretic upper or lower limb following this treatment 22-26. The second treatment was developed with the aim of reducing the over-activation of the contralesional hemisphere by applying unilateral cathodal tDCS (c-tDCS) over the intact M1. Here, stimulation aims at indirectly increasing activity in perilesional areas through interhemispehric interactions. Results from these studies have shown improvement of motor function after c-tDCS 4,27-29. Finally, the third treatment aims at combining the excitatory effects of a-tDCS over the injured M1 with the inhibitory effects of c-tDCS over the unaffected M1 using bilateral tDCS. Results have shown improvements in motor function after bilateral tDCS 27,30,31. Moreover, one study demonstrated greater improvements following bilateral tDCS compared to both unilateral methods 32.
Physiological Mechanisms of tDCS
Despite the increasing use of tDCS in the treatment of stroke, the physiological mechanism underlying its effects remains unknown 33. A better understanding of the physiological effects could help develop better treatment options and could lead to standardized protocols. As mentioned earlier, the effects of tDCS can last for up to 90 min after the offset of stimulation 11,12. Therefore, hyperpolarization/depolarization processes cannot completely explain long lasting effects 33,34. Different hypotheses have been suggested regarding the physiological mechanism underlying tDCS after-effects on M1 including changes in neurotransmitter release, protein synthesis, ion channel function, or receptor activity 34,35. Insights into this matter were first acquired through pharmacological studies showing a suppression of the after effects of anodal and cathodal stimulation on M1 excitability by the glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonist dextromethorphan36,37 whereas the opposite effect was shown using a NMDA receptor agonist38. NMDA receptors are thought to be involved in learning and memory function through long term potentiation (LTP) and long term depression (LTD), both mediated by glutamatergic and GABAergic neurons39,40. Animal studies are in line with this hypothesis as they have shown that a-tDCS induces LTP13.
Despite the important progress made in our understanding of the mechanisms of action underlying tDCS effects, pharmacological protocols present important limitations. Indeed, drug action cannot be as spatially specific as tDCS, especially in the context of human experimentation, and the mechanism of action of their effects is mostly due to post-synaptic receptors 34. Therefore, there is a need to investigate more directly the effects of tDCS on the human brain. Proton magnetic resonance spectroscopy (1H-MRS) is a good candidate as it allows non-invasive in vivo detection of neurotransmitter concentrations in a specific region of interest. This method is based on the principle that every proton-containing neurochemical in the brain has a specific molecular structure and consequently, produces chemically specific resonances that can be detected by 1H-MRS 41. The acquired signal from the brain&#8217;s volume of interest is generated from all protons that resonate between 1 and 5 ppm. The acquired neurochemicals are represented on a spectrum and plotted as a function of their chemical shift with some clearly distinguishable peaks, but where many resonances from the different neurochemicals overlap. The signal intensity of each peak is proportional to the concentration of the neurometabolite 41. The amount of neurochemicals that can be quantified depends on the strength of the magnetic field 42,43. However, low-concentration metabolites, which are obscured by very strong resonances, are hard to quantify at lower field strength such as 3 T. One way to obtain information about such overlapping signals is to remove the strong resonances via spectral editing. One of such techniques is a MEGA-PRESS sequence, which allows detection of &#947;-aminobutyric acid (GABA) signals 44,45.
Only a few studies have investigated the effect of tDCS on the brain metabolism using 1H-MRS in motor 34,46 and non-motor regions47. Stagg and collaborators 34 assessed the effects of a-tDCS, c-tDCS, and sham stimulation on M1 metabolism. They found a significant reduction in GABA concentration following a-tDCS, and a significant reduction of glutamate+glutamine (Glx) and GABA following c-tDCS. In another study, it was reported that the amount of changes in GABA concentration induced by a-tDCS over M1 was related to motor learning 46.
These studies highlight the potential of combining 1H-MRS with tDCS to increase our understanding of the physiological mechanism underlying the effect of tDCS on motor function. In addition, the use of clinical protocols such as a-tDCS and c-tDCS over M1 is useful because their behavioral effects are well studied and can be directly related to physiological results. Therefore, a standard protocol for combining bilateral tDCS and 1H-MRS is demonstrated in healthy participants using a 3 T MRI system. Bihemispheric tDCS is presented to contrast data with a previous MRS study where unilateral cathodal or unilateral anodal tDCS were applied over motor cortex 34. The protocol is described specifically for stimulation with a NeuroConn stimulator in a Siemens 3 T scanner performing MEGA-PRESS 1H-MRS.

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>DC-stimulator plus</td>
			<td>NeuroConn</td>
			<td>30DCS01E</td>
			<td>MR compatible device</td>
		</tr>
		<tr>
			<td>NuPrep preparation gel</td>
			<td>Weaver and Co.</td>
			<td>#10-61</td>
			<td></td>
		</tr>
		<tr>
			<td>Ten20 conductive paste</td>
			<td>Weaver and Co.</td>
			<td>#10-20-4</td>
			<td></td>
		</tr>
		<tr>
			<td>Electrode prepping pad</td>
			<td>Grass technologies</td>
			<td>MD0017</td>
			<td>70% isopropyl alcohol and pumice</td>
		</tr>
		<tr>
			<td>Saline solution</td>
			<td>Local drugstore sample</td>
			<td></td>
			<td>0.9% sodium chloride</td>
		</tr>
		<tr>
			<td>Non permanent hydro-marker</td>
			<td>Sharpie</td>
			<td>SHPE20WH</td>
			<td></td>
		</tr>
		<tr>
			<td>SYNGO MR VB17</td>
			<td>Siemens AG</td>
			<td></td>
			<td>MRI software</td>
		</tr>
		<tr>
			<td>MAGNETOM Trio A Tim System</td>
			<td>Siemens AG</td>
			<td></td>
			<td>MRI scanner version</td>
		</tr>
		<tr>
			<td>Matlab 2013a (Version 8.1)</td>
			<td>MathWorks Inc</td>
			<td></td>
			<td>processing and analysis software</td>
		</tr>
		<tr>
			<td>LCModel 6.3</td>
			<td>LC MODEL inc</td>
			<td></td>
			<td>see: s-provencher.com</td>
		</tr>
		<tr>
			<td>FASTESTMAP</td>
			<td colspan="2">Developers: Edward J. Auerbach and Ma&#322;gorzata Marja&#324;ska</td>
			<td>shimming sequence</td>
		</tr>
		<tr>
			<td>MEGA-PRESS</td>
			<td colspan="2">Developers: Edward J. Auerbach and Ma&#322;gorzata Marja&#324;ska</td>
			<td>MRS sequence</td>
		</tr>
	</tbody>
</table>

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.

Figure 6 shows the position of the VOI located on the representation of hand in M1 where all MRS measures were taken. In figure 6D, a 3D visualization shows a clear representation of the tDCS electrodes positioned on the scalp over the putative primary motor cortex. Figure 7 shows representative &#8220;EDIT OFF&#8221; and difference (&#8220;DIFF&#8221;) spectra acquired in M1. Peaks corresponding to Glx, GABA+MM as well as NAA can be clearly seen.
<p class="jove_cont...

Watch this Scientific Journal Video about The Use of Magnetic Resonance Spectroscopy as a Tool for the Measurement of Bi-hemispheric Transcranial Electric Stimulation Effects on Primary Motor Cortex M

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

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 ...

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20.0K 次观看.  University of Montréal. 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.

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

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...

effects of transcranial alternating current stimulation on the primary motor cortex by online combined approach with transcranial magnetic stimulation

Effects of Transcranial Alternating Current Stimulation on the Primary Motor Cortex by Online Combined Approach with Transcranial Magnetic Stimulation

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.

stimulating the lip motor cortex with transcranial magnetic stimulation

Stimulating the Lip Motor Cortex with Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) has proven to be a useful tool in investigating the role of the articulatory motor cortex in speech perception.&#160; This article describes how to record motor evoked potentials (MEPs) from the lip muscles and how to disrupt the motor lip representation using repetitive...

combined transcranial magnetic stimulation and electroencephalography of the dorsolateral prefrontal cortex

Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex

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...

repetitive transcranial magnetic stimulation to the unilateral hemisphere of rat brain

Repetitive Transcranial Magnetic Stimulation to the Unilateral Hemisphere of Rat Brain

We applied repetitive transcranial magnetic stimulation (rTMS) to the unilateral hemisphere of rat brain, by placing a 25-mm figure-8 coil 1 cm lateral to the vertex on the biauricular line and angulating the coil by 45&#176;. An in-house water cooling system was used for rTMS for more than 20 min.

simultaneous transcranial alternating current stimulation and functional magnetic resonance imaging

Simultaneous Transcranial Alternating Current Stimulation and Functional Magnetic Resonance Imaging

Transcranial alternating current stimulation (tACS) is a promising tool for noninvasive investigation of brain oscillations, though its effects are not completely understood. This article describes a safe and reliable setup for applying tACS simultaneously with functional magnetic resonance imaging, which can increase understanding oscillatory brain function and effects of...

mapping the after-effects of theta burst stimulation on the human auditory cortex with functional imaging

Mapping the After-effects of Theta Burst Stimulation on the Human Auditory Cortex with Functional Imaging

Auditory processing is the basis of speech and music-related processing. Transcranial Magnetic Stimulation (TMS) has been used successfully to study cognitive, sensory and motor systems but has rarely been applied to audition. Here we investigated TMS combined with functional Magnetic Resonance Imaging to understand the functional organization of auditory...

determining the motor threshold on non-braided hair during transcranial magnetic stimulation (tms)

Determining the Motor Threshold on Non-Braided Hair During Transcranial Magnetic Stimulation (TMS)

how to use the h1 deep transcranial magnetic stimulation coil for conditions other than depression

How to Use the H1 Deep Transcranial Magnetic Stimulation Coil for Conditions Other than Depression

The H1 deep transcranial magnetic stimulation coil is FDA-cleared for the treatment of depression. We demonstrate how to utilize the H1 for other conditions, such as auditory hallucinations and PTSD, by moving the helmet to different locations over the subject's...

measuring and manipulating functionally specific neural pathways in the human motor system with transcranial magnetic stimulation

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

This article describes new approaches to measure and strengthen functionally specific neural pathways with transcranial magnetic stimulation. These advanced noninvasive brain stimulation methodologies can provide new opportunities for the understanding of brain-behavior relations and development of new therapies to treat brain...

functional magnetic resonance imaging (fmri) of the visual cortex with wide-view retinotopic stimulation

Author Spotlight: Insights into Visual Cortex Research Through Wide-View fMRI Mapping 

We have developed techniques for mapping the visual cortex function utilizing more of the visual field than is commonly used. This approach has the potential to enhance the evaluation of vision disorders and eye...

Functional Magnetic Resonance Imaging (fMRI) of the Visual Cortex with Wide-View Retinotopic Stimulation

functional magnetic resonance spectroscopy at 7 t in the rat barrel cortex during whisker activation

Functional Magnetic Resonance Spectroscopy at 7 T in the Rat Barrel Cortex During Whisker Activation

After checking by blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI) that the corresponding somatosensory barrel field cortex area (called S1BF) is correctly activated, the main goal of this study is to quantify lactate content fluctuations in the activated rat brains by localized proton magnetic resonance spectroscopy (1H-MRS) at 7...

transcranial direct current stimulation and simultaneous  functional magnetic resonance imaging

Transcranial Direct Current Stimulation and Simultaneous  Functional Magnetic Resonance Imaging

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique. It has successfully been used in basic research and clinical settings to modulate brain function in humans. This article describes the implementation of tDCS and simultaneous functional magnetic resonance imaging (fMRI), to investigate the neural basis of tDCS...

the combined use of transcranial direct current stimulation and robotic therapy for the upper limb

The Combined Use of Transcranial Direct Current Stimulation and Robotic Therapy for the Upper Limb

The combined use of transcranial direct current stimulation and robotic therapy as an add-on for conventional rehabilitation therapy may result in improved therapeutic outcomes due to modulation of brain plasticity. In this article, we describe the combined methods used in our institute for improving motor performance after...

the sol braiding method for handling thick hair during transcranial magnetic stimulation: an address for potential bias in brain stimulation

Author Spotlight: Increasing TMS Accessibility Through Braiding Techniques for Diverse Hair Types

Hair type commonly seen in historically underrepresented minorities appears to interfere with transcranial magnetic stimulation (TMS). Here we describe a hair braiding method (The Sol Braiding Technique) that improves...

Enhancing TMS Efficacy with Sol Braiding Technique in Diverse Populations

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neuronavigated focalized transcranial direct current stimulation administered during functional magnetic resonance imaging

Author Spotlight: Optimizing tDCS Electrode Placement via Neuronavigation for Improved Brain Targeting

This protocol describes the method of neuronavigated electrode placement for focal, transcranial direct current stimulation (tDCS) administered during functional magnetic resonance imaging (fMRI).

Neuronavigated Focalized Transcranial Direct Current Stimulation Administered During Functional Magnetic Resonance Imaging

utilizing transcranial magnetic stimulation to study the human neuromuscular system

Utilizing Transcranial Magnetic Stimulation to Study the Human Neuromuscular System

Transcranial magnetic stimulation (TMS) is a non-invasive tool to gain insight on the physiology and function of the human nervous system.  Here, we present our TMS techniques to study cortical excitability of the upper limb and lumbar...

neuronavigation-guided repetitive transcranial magnetic stimulation for aphasia

Neuronavigation-guided Repetitive Transcranial Magnetic Stimulation for Aphasia

This study is designed to test the hypothesis that neuronavigational system-guided transcranial magnetic stimulation has higher accuracy for targeting the intended target as demonstrated by eliciting a greater degree of virtual aphasia in healthy subjects, measured by delay in reaction time to picture...

bilateral assessment of the corticospinal pathways of the ankle muscles using navigated transcranial magnetic stimulation

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

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...

electric and magnetic field devices for stimulation of biological tissues

Electric and Magnetic Field Devices for Stimulation of Biological Tissues

This protocol describes the step-by-step process to build both electrical and magnetic stimulators used to stimulate biological tissues. The protocol includes a guideline to simulate computationally electric and magnetic fields and manufacture of stimulator devices.

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 ...

State-Dependency Effects on TMS:  A Look at Motive Phosphene Behavior

Transcranial magnetic stimulation (TMS) is 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.1,2 Within the field of TMS, the term state dependency refers to the initial, baseline condition of the particular neural region targeted for stimulation. As can be inferred, the effects of TMS can (and do) vary according to this primary susceptibility and responsiveness of the targeted cortical area.3,4,5

In this experiment, we will examine this concept of state dependency through the elicitation and subjective experience of motive phosphenes. Phosphenes are visually perceived flashes of small lights triggered by electromagnetic pulses to the visual cortex. These small lights can assume varied characteristics depending upon which type of visual cortex is being stimulated. In this particular study, we will be targeting motive phosphenes as elicited through the stimulation of V1/V2 and the V5/MT+ complex visual regions.6

In this article, we examine the effects of visually relevant state dependency on TMS induced motive phosphenic presentations.

Transcranial magnetic stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate ...

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 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 ...

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of daily activities due to lower and upper limb impairments. Intensive physical and occupational therapy are still considered main treatments, but new adjunct therapies to standard rehabilitation that may optimize functional outcomes are being studied.
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that polarizes underlying brain regions through the application of weak direct currents through electrodes on the scalp, modulating cortical excitability. Increased interest in this technique can be attributed to its low cost, ease of use, and effects on human neural plasticity. Recent research has been performed to determine the clinical potential of tDCS in diverse conditions such as depression, Parkinson&#39;s disease, and motor rehabilitation after stroke. tDCS helps enhance brain plasticity and seems to be a promising technique in rehabilitation programs.
A number of robotic devices have been developed to assist in the rehabilitation of upper limb function after stroke. The rehabilitation of motor deficits is often a long process requiring multidisciplinary approaches for a patient to achieve maximum independence. These devices do not intend to replace manual rehabilitation therapy; instead, they were designed as an additional tool to rehabilitation programs, allowing immediate perception of results and tracking of improvements, thus helping patients to stay motivated.
Both tDSC and robot-assisted therapy are promising add-ons to stroke rehabilitation and target the modulation of brain plasticity, with several reports describing their use to be associated with conventional therapy and the improvement of therapeutic outcomes. However, more recently, some small clinical trials have been developed that describe the associated use of tDCS and robot-assisted therapy in stroke rehabilitation. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

The combined use of transcranial direct current stimulation and robotic therapy as an add-on for conventional rehabilitation therapy may result in improved therapeutic outcomes due to modulation of brain plasticity. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of ...

Nuclear magnetic resonance (NMR) spectroscopy offers the opportunity to measure cerebral metabolite contents in vivo and noninvasively. Thanks to technological developments over the last decade and the increase in magnetic field strength, it is now possible to obtain good resolution spectra in vivo in the rat brain. Neuroenergetics (i.e., the study of brain metabolism) and, especially, metabolic interactions between the different cell types have attracted more and more interest in recent years. Among these metabolic interactions, the existence of a lactate shuttle between neurons and astrocytes is still debated. It is, thus, of great interest to perform functional proton magnetic resonance spectroscopy (1H-MRS) in a rat model of brain activation and monitor lactate. However, the methyl lactate peak overlaps lipid resonance peaks and is difficult to quantify. The protocol described below allows metabolic and lactate fluctuations to be monitored in an activated brain area. Cerebral activation is obtained by whisker stimulation and 1H-MRS is performed in the corresponding activated barrel cortex, whose area is detected using blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI). All steps are fully described: the choice of anesthetics, coils, and sequences, achieving efficient whisker stimulation directly in the magnet, and data processing.

After checking by blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI) that the corresponding somatosensory barrel field cortex area (called S1BF) is correctly activated, the main goal of this study is to quantify lactate content fluctuations in the activated rat brains by localized proton magnetic resonance spectroscopy (1H-MRS) at 7 T.

Nuclear magnetic resonance (NMR) spectroscopy offers the opportunity to measure cerebral metabolite contents in vivo and noninvasively. Thanks to ...

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 ...

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 ...

A Pilot Study on the Repetitive Transcranial Magnetic Stimulation of A&#946; and Tau Levels in Rhesus Monkey Cerebrospinal Fluid

Previous studies have demonstrated that a non-invasive light-flickering regime and auditory tone stimulation could affect A&#946; and tau metabolism in the brain. As a non-invasive technique, repetitive transcranial magnetic stimulation (rTMS) has been applied for the treatment of neurodegenerative disorders. This study explored the effects of rTMS on A&#946; and tau levels in rhesus monkey cerebrospinal fluid (CSF). This is a single-blind, self-controlled study. Three different frequencies (low frequency, 1 Hz; high frequencies, 20 Hz and 40 Hz) of rTMS were used to stimulate the bilateral-dorsolateral prefrontal cortex (DLPFC) of the rhesus monkey. A catheterization method was used to collect CSF. All samples were subjected to liquid chip detection to analyze CSF biomarkers (A&#946;42, A&#946;42/A&#946;40, tTau, pTau). CSF biomarker levels changed with time after stimulation by rTMS. After stimulation, the A&#946;42 level in CSF showed an upward trend at all frequencies (1 Hz, 20 Hz, and 40 Hz), with more significant differences for the high-frequencies (p &lt; 0.05) than for the low frequency. 
After high-frequency rTMS, the total Tau (tTau) level of CSF immediately increased at the post-rTMS timepoint (p &lt; 0.05) and gradually decreased by 24 h. Moreover, the results showed that the level of phosphorylated Tau (pTau) increased immediately after 40 Hz rTMS (p &lt; 0.05). The ratio of A&#946;42/A&#946;40 showed an upward trend at 1 Hz and 20 Hz (p &lt; 0.05). There was no significant difference in the tau levels with low-frequency (1 Hz) stimulation. Thus, high-frequencies (20 Hz and 40 Hz) of rTMS may have positive effects on A&#946; and tau levels in rhesus monkey CSF, while low-frequency (1 Hz) rTMS can only affect A&#946; levels.

A Pilot Study on the Repetitive Transcranial Magnetic Stimulation of A&amp;#946; and Tau Levels in Rhesus Monkey Cerebrospinal Fluid

Here, we describe the procedure for a pilot study to explore the effect of repetitive transcranial magnetic stimulation with different frequencies (1 Hz/20 Hz/40 Hz) on A&#946; and tau metabolism in rhesus monkey cerebrospinal fluid.

Previous studies have demonstrated that a non-invasive light-flickering regime and auditory tone stimulation could affect A&#946; and tau metabolism in ...

﻿Participant Screening for Transcranial Magnetic Stimulation

Participant Screening for Transcranial Magnetic Stimulation  

To begin, screen the participant for any contraindications to transcranial magnetic stimulation, or TMS. Inform the participant about the study objectives and procedures. Review the risks outlined in the institution's ethics review board-approved consent document.Answer any questions about the potential risks and obtain written, informed consent before beginning any study procedures.