CIBC fellowship (JA) and NSERC grant (RZ). We are grateful to Roch M. Comeau (Brainsight) for his help regarding the infrared camera, the MR compatible trackers and other hardware support. We are also grateful to Brian Hynes (Hybex Innovations Inc.) who designed the multi-jointed arm for coil holder and provided some of the figures displayed in the video. And a special thanks to all the MR technicians and M. Ferreira from the McConnell Brain Imaging Centre of the Montreal Neurological Institute who helped us optimizing the design of the experiment.

The protocol is divided in a two-day session (not necessarily consecutive). The first day consists of an fMRI localizer composed with an anatomical and a functional MR scans to define for each participant the areas to be targeted with TMS. The second day consists in the fMRI sessions pre- and post-TMS where TMS is applied inside the scanner using a special MR compatible TMS coil (Magstim Ltd., Wales, UK) and a frameless stereotactic system (Brainsight). The latter is used to position in real-time the TMS coil on cortical areas relative to each participant's anatomical and functional data.
1. Localizer Session
<ul>
 <li>Start with acquiring a high-resolution anatomical image of your participant.</li>
 <li>Then, acquire functional images using a gradient echo EPI pulse and a sparse sampling paradigm in order to minimize any BOLD effect or auditory masking due to MRI scanning noise 14,15. In our case, fMRI is carried out during a melody task in which participants have to determine if two consecutive 5-note melodies are the same or different 2,16. A nondiscrimination auditory control task is also included, in which subjects hear two equal-length patterns of five notes, all at the same pitch of C5 and are instructed to click the left button following the second stimulus. Periods of silence are also inserted randomly among the task trials in each run. In total, 72 trials are presented in a randomized order: 24 trials of melody discrimination, 24 auditory control trials and 24 periods of silence, for a total duration of 12 min 16 sec. </li>
 <li>Define the stimulation site using anatomical and/or functional landmarks. One has to be aware that TMS is limited regarding the depth of the stimulation site because of the attenuation of the electric field strength in depth, and cannot expect to reach areas deeper than 3 cm6,17 . A crucial step is to use similar landmarks for each participant, which could be difficult because of the differences in anatomy and function between participants. Here, we target Heschl's gyrus in each participant, located using both anatomical and functional landmarks. We use masks of Heschl's gyrus provided by the Harvard-Oxford structural atlases (<a href="http://www.fmrib.ox.ac.uk/fsl/data/atlas-descriptions.html" target="_blank">http://www.fmrib.ox.ac.uk/fsl/data/atlas-descriptions.html</a>) and the TMS target is defined individually by the peak of activation within the Heschl's gyrus 2. In addition, we also define the vertex position, which will be used as a control site to control for non-specific effects of TMS such as acoustic and somatosensory artifacts. The vertex is defined anatomically as a point midway between the inion and the bridge of the nose, and equidistant from the right and left intertragal notches. The order of site of stimulation (i.e. Heschl's gyrus or vertex) is counterbalanced across individuals.</li>
</ul>
2. Pre- and Post-TMS fMRI Experiment
Pre-TMS fMRI session
<ul>
 <li> Prepare the participant to go directly in the scanner. This includes removal of metal and filling the TMS and MR screening form.</li>
 <li>Start the MR acquisition with an anatomical and a functional scans (identical to the one carried out in the localizer session, see section 1).</li>
</ul>
Frameless stereotaxy and TMS in the MRI environment
The frameless stereotaxy system is composed of an infrared camera (Polaris Spectra), some tools and trackers (Brainsight) used for the registration procedure and a computer. The computer is located outside of the scanner room, but positioned at the entrance of the scanner room and the scanner door is kept opened during the TMS application. The tools and trackers are MR compatible, as well as the tripod (home-made) supporting the infrared camera and are therefore used inside the scanner room. The infrared camera is not MR-compatible, and therefore is positioned inside the scanner room, near the scanner door at approximately two meters from the scanner bed (see discussion for safety procedure). The TMS stimulator system is located in a room adjacent to the MRI scanner room. We use an MRI compatible TMS coil located inside the scanner room and connected to the TMS system via a 7-m cable through an RF filter tube.
<ul>
 <li> Load your participant's anatomical and functional images and the stimulation targets into the stereotactic software package (e.g. Brainsight). Here, we will be targeting the right Heschl's gyrus.</li>
 <li> After the pre-TMS fMRI acquisition, remove the upper MR head coil part of the 32-channel head coil (if using the Siemens 3T scanner and the 32-channel head coil configuration).</li>
 <li> Next, slide down the participant on the scanner bed.</li>
 <li> Fix the headband and tracker set on the participant's head.</li>
 <li> Mount the multi-jointed arm to the scanner bed and fix the MR compatible TMS coil onto the arm. </li>
 <li> Verify that all the trackers and the coil are in the field of view of the camera. Here, the camera is slightly moved to the right side of the participant to enable an easier tracking of the coil displacements when targeting the right hemisphere. </li>
 <li> Calibrate your subject's head with the stereotaxy tools (i.e. pointer tool). This is done by coregistering several landmarks on the participant's head (e.g. in our case the tip of the nose, the nasion and the tragus of both ears) with the same landmarks on the anatomical data. In this procedure, two experimenters are needed, one close to the participant's head to position the pointer tool on the participant's head, and the other experimenter at the entrance of the scanner room to perform the registration on the computer.</li>
 <li> Position the MR compatible TMS coil tangential to the scalp, and the coil trackers directed towards the infrared camera. The coil is oriented with the coil handle pointing backward and parallel to the midline 2. Fix the coil position using the screws on the multi-jointed arm. </li>
 <li> In the room adjacent to the MRI scanner, turn on the TMS system and begin stimulation. TMS is applied following a patterned protocol, i.e., continuous theta burst stimulation (cTBS) consisting in 3 pulses at 50Hz, repeated at 5Hz for 40s. We use a fixed stimulation intensity (41%) defined by the stimulator output 18,19. We chose this protocol as it has been shown to modulate cortical plasticity for a duration up to 30 min after stimulation cessation in healthy populations 20, (see discussion section for safety procedure). </li>
</ul>
Post-TMS fMRI session 
<ul>
 <li>Once stimulation is complete, it is important to get the subject back into the scanner as soon as possible. Remove the TMS coil from the scanner room, and remove the multi-jointed arm. Slide back the participant's head into the MR head coil. Ensure your scanner is prepared and ready to go. Our advice is to keep the body platform raised during the whole TMS session, and reduce the number and duration of localizer scans to a minimum.</li>
 <li>Because the effects of rTMS are transitory, the final scanning session should begin with the functional scan. Again, we conducted fMRI during a 12-min run of the melody task.</li>
 <li>After the final scan is complete, finish with an anatomical scan.</li>
</ul>
3. Representative Results
Analyses of fMRI data are conducted separately for both the pre- and post-TMS fMRI session. For each fMRI session (i.e., pre and post-TMS), the contrast between the melodies and the auditory control task shows task-related activity in the left and right Heschl's gyri, superior temporal gyri, inferior frontal gyri and precentral gyri (Figure 1 A, B). To evaluate differences between pre- and post-TMS fMRI sessions, we perform a random-effect analysis using Student's paired t-test. Significance is determined using clusters identified by a z &gt; 2 threshold and a corrected cluster threshold of p = 0.05. Figure 1 C represents the contrast post- minus pre-cTBS for a single participant. The data suggest that cTBS targeting the right Heschl's gyrus (black circle) induces an increase in fMRI response in the contralateral (left) auditory cortex, including the left Heschl's gyrus. Changes in fMRI response are also found in the left postcentral gyrus, left insula, and in the lateral occipital cortex bilaterally. However, no significant change in fMRI response is seen under the coil. In addition, similar combined TMS-fMRI protocol is repeated to stimulate the vertex (control site). Comparison of pre- and post-fMRI sessions with cTBS applied over the vertex did not show any significant effect (data not shown).
<img src="/files/ftp_upload/3985/3985fig1.jpg" alt="Figure 1"/> 
Figure 1. Analysis of individual pre-TMS fMRI data (A), post-TMS fMRI data (B) and post- minus pre-TMS fMRI data (C). A. Results of the contrast melody discrimination minus auditory control trials for a single participant in the pre-TMS fMRI session (A) and in the post-TMS fMRI session (B). From left to right: axial, coronal and sagittal views. In both (A) and (B), the TMS coil is targeting the right Heschl's gyrus (black circle) located at x=54, y=-13, z=1 (MNI152 standard space). For both pre- and post-TMS fMRI sessions, coordinates are displayed at x=-54, y=-13, z=1 (MNI152 standard space) to show changes in the left hemisphere at the site of stimulation (i.e. right Heschl's gyrus). C. Results of the contrast post- minus pre-TMS fMRI sessions using Student's paired t-test.

No conflicts of interest declared.

We describe a protocol combining offline TMS and fMRI to investigate the functional organization of the auditory cortex. In the next sections, we will discuss the methodological factors to consider when conducting such approach. 
Acquisition and timing for post-TMS fMRI session
Order of scans acquisition and counterbalancing of pre- and post- TMS fMRI sessions
It is crucial to acquire an MR anatomical scan before and after TMS in o...

<table><tbody><tr><td>Transcranial magnetic stimulation</td><td>Magstim super Rapid2 stimulator, Rapid-2 Plus One Module</td><td>Magstim Ltd., Wales, UK</td><td></td></tr><tr><td>Coil for magnetic stimulation</td><td>MRI-compatible 70 mm figure-of-eight-coil</td><td>Magstim Ltd., Wales, UK</td><td></td></tr><tr><td>Magnetic resonance imaging</td><td>3-T Siemens Trio scanner, 32-channel Head Coil</td><td>Siemens, Inc., Germany</td><td></td></tr><tr><td>Frameless Stereotaxy</td><td>Brainsight</td><td>Rogue Research Inc., Montreal, Canada</td><td></td></tr><tr><td>Optical measurement system</td><td>Polaris Spectra</td><td>Northern Digital Inc, Ontario, Canada</td><td></td></tr><tr><td>Multi-jointed arm for coil holder</td><td>Standard</td><td>Hybex Innovations Inc., Anjou, Canada</td><td></td></tr><tr><td>MRI-Compatible Insert Earphones </td><td>Sensimetrics, Model S14</td><td>Sensimetrics Corporation, MA, USA</td><td></td></tr></tbody></table>

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

Auditory cortex pertains to the processing of sound, which is at the basis of speech or music-related processing1. However, despite considerable recent progress, the functional properties and lateralization of the human auditory cortex are far from being fully understood. Transcranial Magnetic Stimulation (TMS) is a non-invasive technique that can transiently or lastingly modulate cortical excitability via the application of localized magnetic field pulses, and represents a unique method of exploring plasticity and connectivity. It has only recently begun to be applied to understand auditory cortical function 2. 
An important issue in using TMS is that the physiological consequences of the stimulation are difficult to establish. Although many TMS studies make the implicit assumption that the area targeted by the coil is the area affected, this need not be the case, particularly for complex cognitive functions which depend on interactions across many brain regions 3. One solution to this problem is to combine TMS with functional Magnetic resonance imaging (fMRI). The idea here is that fMRI will provide an index of changes in brain activity associated with TMS. Thus, fMRI would give an independent means of assessing which areas are affected by TMS and how they are modulated 4. In addition, fMRI allows the assessment of functional connectivity, which represents a measure of the temporal coupling between distant regions. It can thus be useful not only to measure the net activity modulation induced by TMS in given locations, but also the degree to which the network properties are affected by TMS, via any observed changes in functional connectivity.
Different approaches exist to combine TMS and functional imaging according to the temporal order of the methods. Functional MRI can be applied before, during, after, or both before and after TMS. Recently, some studies interleaved TMS and fMRI in order to provide online mapping of the functional changes induced by TMS 5-7. However, this online combination has many technical problems, including the static artifacts resulting from the presence of the TMS coil in the scanner room, or the effects of TMS pulses on the process of MR image formation. But more importantly, the loud acoustic noise induced by TMS (increased compared with standard use because of the resonance of the scanner bore) and the increased TMS coil vibrations (caused by the strong mechanical forces due to the static magnetic field of the MR scanner) constitute a crucial problem when studying auditory processing. 
This is one reason why fMRI was carried out before and after TMS in the present study. Similar approaches have been used to target the motor cortex 8,9, premotor cortex 10, primary somatosensory cortex 11,12 and language-related areas 13, but so far no combined TMS-fMRI study has investigated the auditory cortex. The purpose of this article is to provide details concerning the protocol and considerations necessary to successfully combine these two neuroscientific tools to investigate auditory processing. 
Previously we showed that repetitive TMS (rTMS) at high and low frequencies (resp. 10 Hz and 1 Hz) applied over the auditory cortex modulated response time (RT) in a melody discrimination task 2. We also showed that RT modulation was correlated with functional connectivity in the auditory network assessed using fMRI: the higher the functional connectivity between left and right auditory cortices during task performance, the higher the facilitatory effect (i.e. decreased RT) observed with rTMS. However those findings were mainly correlational, as fMRI was performed before rTMS. Here, fMRI was carried out before and immediately after TMS to provide direct measures of the functional organization of the auditory cortex, and more specifically of the plastic reorganization of the auditory neural network occurring after the neural intervention provided by TMS. 
Combined fMRI and TMS applied over the auditory cortex should enable a better understanding of brain mechanisms of auditory processing, providing physiological information about functional effects of TMS. This knowledge could be useful for many cognitive neuroscience applications, as well as for optimizing therapeutic applications of TMS, particularly in auditory-related disorders.

Watch this Scientific Journal Video about Mapping the After-effects of Theta Burst Stimulation on the Human Auditory Cortex with Functional Imaging at JoVE.com

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 cortex.

Auditory cortex pertains to the processing of sound, which is at the basis of speech or music-related processing1. However, despite considerable recent ...

mapping-after-effects-theta-burst-stimulation-on-human-auditory

Universidad de Cartagena UDEC

Research

JoVE Journal

Biology

13.8K Views.  McGill University. 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 cortex.

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

Functional Magnetic Resonance Imaging (fMRI) with Auditory Stimulation in Songbirds

The neurobiology of birdsong, as a model for human speech, is a pronounced area of research in behavioral neuroscience. Whereas electrophysiology and molecular approaches allow the investigation of either different stimuli on few neurons, or one stimulus in large parts of the brain, blood oxygenation level dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) allows combining both advantages, i.e. compare the neural activation induced by different stimuli in the entire brain at once. fMRI in songbirds is challenging because of the small size of their brains and because their bones and especially their skull comprise numerous air cavities, inducing important susceptibility artifacts. Gradient-echo (GE) BOLD fMRI has been successfully applied to songbirds 1-5 (for a review, see 6). These studies focused on the primary and secondary auditory brain areas, which are regions free of susceptibility artifacts. However, because processes of interest may occur beyond these regions, whole brain BOLD fMRI is required using an MRI sequence less susceptible to these artifacts. This can be achieved by using spin-echo (SE) BOLD fMRI 7,8 . In this article, we describe how to use this technique in zebra finches (Taeniopygia guttata), which are small songbirds with a bodyweight of 15-25 g extensively studied in behavioral neurosciences of birdsong. The main topic of fMRI studies on songbirds is song perception and song learning. The auditory nature of the stimuli combined with the weak BOLD sensitivity of SE (compared to GE) based fMRI sequences makes the implementation of this technique very challenging.

Functional Magnetic Resonance Imaging fMRI with Auditory Stimulation in Songbirds

This article shows an optimized procedure for imaging of the neural substrates of auditory stimulation in the songbird brain using functional Magnetic Resonance Imaging (fMRI). It describes the preparation of the sound stimuli, the positioning of the subject and the acquisition and subsequent analysis of the fMRI data.

The neurobiology of birdsong, as a model for human speech, is a pronounced area of research in behavioral neuroscience. Whereas electrophysiology and ...

Behavior

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. Researchers have used single-pulse and repetitive TMS to stimulate the lip representation in the motor cortex. The excitability of the lip motor representation can be investigated by applying single TMS pulses over this cortical area and recording TMS-induced motor evoked potentials (MEPs) via electrodes attached to the lip muscles (electromyography; EMG). Larger MEPs reflect increased cortical excitability. Studies have shown that excitability increases during listening to speech as well as during&#160;viewing speech-related movements. TMS can be used also to disrupt the lip motor representation. A 15-min train of low-frequency sub-threshold repetitive stimulation has been shown to suppress motor excitability for a further 15-20 min. This TMS-induced disruption of the motor lip representation impairs subsequent performance in demanding speech perception tasks and modulates auditory-cortex responses to speech sounds. These findings are consistent with the suggestion that the motor cortex contributes to speech perception. This article describes how to localize the lip representation in the motor cortex and how to define the appropriate stimulation intensity for carrying out both single-pulse and repetitive TMS experiments.

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 TMS.

Transcranial magnetic stimulation (TMS) has proven to be a useful tool in investigating the role of the articulatory motor cortex in speech perception. ...

Transcranial Direct Current Stimulation and Simultaneous  Functional Magnetic Resonance Imaging

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses weak electrical currents administered to the scalp to manipulate cortical excitability and, consequently, behavior and brain function. In the last decade, numerous studies have addressed short-term and long-term effects of tDCS on different measures of behavioral performance during motor and cognitive tasks, both in healthy individuals and in a number of different patient populations. So far, however, little is known about the neural underpinnings of tDCS-action in humans with regard to large-scale brain networks. This issue can be addressed by combining tDCS with functional brain imaging techniques like functional magnetic resonance imaging (fMRI) or electroencephalography (EEG).
In particular, fMRI is the most widely used brain imaging technique to investigate the neural mechanisms underlying cognition and motor functions. Application of tDCS during fMRI allows analysis of the neural mechanisms underlying behavioral tDCS effects with high spatial resolution across the entire brain. Recent studies using this technique identified stimulation induced changes in task-related functional brain activity at the stimulation site&#160;and also in more distant brain regions, which were associated with behavioral improvement. In addition, tDCS administered during resting-state fMRI allowed identification of widespread changes in whole brain functional connectivity.
Future studies using this combined protocol should yield new insights into the mechanisms of tDCS action in health and disease and new options for more targeted application of tDCS in research and clinical settings. The present manuscript describes this novel technique in a step-by-step fashion, with a focus on technical aspects of tDCS administered during fMRI.

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 effects.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses weak electrical currents administered to the scalp ...

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 ...

Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species.
Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning).

Shuttle-box avoidance learning is well-established in behavioral neuroscience. This protocol describes how shuttle-box learning in rodents can be combined with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical in vivo recordings as a tool to study multiple aspects of learning and perception.

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the ...

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. TACS employs frequency-specific stimulation of the human brain through current applied to the scalp with surface electrodes. Most current knowledge of the technique is based on behavioral studies; thus, combining the method with brain imaging holds potential to better understand the mechanisms of tACS. Because of electrical and susceptibility artifacts, combining tACS with brain imaging can be challenging, however, one brain imaging technique that is well suited to be applied simultaneously with tACS is functional magnetic resonance imaging (fMRI). In our lab, we have successfully combined tACS with simultaneous fMRI measurements to show that tACS effects are state, current, and frequency dependent, and that modulation of brain activity is not limited to the area directly below the electrodes. This article describes a safe and reliable setup for applying tACS simultaneously with visual task fMRI studies, which can lend to understanding oscillatory brain function as well as the effects of tACS on the brain.

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 tACS.

Transcranial alternating current stimulation (tACS) is a promising tool for noninvasive investigation of brain oscillations. TACS employs ...

Utilizing Repetitive Transcranial Magnetic Stimulation to Improve Language Function in Stroke Patients with Chronic Non-fluent Aphasia

Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia1. In this experiment, we demonstrate the administration of low-frequency repetitive TMS (rTMS) to an optimal stimulation site in the right hemisphere in patients with chronic non-fluent aphasia. A battery of standardized language measures is administered in order to assess baseline performance. Patients are subsequently randomized to either receive real rTMS or initial sham stimulation. Patients in the real stimulation undergo a site-finding phase, comprised of a series of six rTMS sessions administered over five days; stimulation is delivered to a different site in the right frontal lobe during each of these sessions. Each site-finding session consists of 600 pulses of 1 Hz rTMS, preceded and followed by a picture-naming task. By comparing the degree of transient change in naming ability elicited by stimulation of candidate sites, we are able to locate the area of optimal response for each individual patient. We then administer rTMS to this site during the treatment phase. During treatment, patients undergo a total of ten days of stimulation over the span of two weeks; each session is comprised of 20 min of 1 Hz rTMS delivered at 90% resting motor threshold. Stimulation is paired with an fMRI-naming task on the first and last days of treatment. After the treatment phase is complete, the language battery obtained at baseline is repeated two and six months following stimulation in order to identify rTMS-induced changes in performance. The fMRI-naming task is also repeated two and six months following treatment. Patients who are randomized to the sham arm of the study undergo sham site-finding, sham treatment, fMRI-naming studies, and repeat language testing two months after completing sham treatment. Sham patients then cross over into the real stimulation arm, completing real site-finding, real treatment, fMRI, and two- and six-month post-stimulation language testing.

We explore the use of repetitive transcranial magnetic stimulation (rTMS) to improve language abilities in patients with chronic stroke and non-fluent aphasia. After identifying a site in the right frontal gyrus for each patient that responds optimally to stimulation, we target this site during ten days of rTMS treatment.

Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia1. In this ...

Medicine

Continuous Theta Burst Stimulation of the Posterior Medial Frontal Cortex to Experimentally Reduce Ideological Threat Responses

Decades of behavioral science research have documented functional shifts in attitudes and ideological adherence in response to various challenges, but little work to date has illuminated the neural mechanisms underlying these dynamics. This paper describes how continuous theta burst transcranial magnetic stimulation may be employed to experimentally assess the causal contribution of cortical regions to threat-related ideological shifts. In the example protocol provided here, participants are exposed to a threat prime-an explicit reminder of their own inevitable death and bodily decomposition-following a downregulation of the posterior medial frontal cortex (pMFC) or a sham stimulation. Next, disguised within a series of distracter tasks, participants' relative degree of ideological adherence is assessed-in the present example, with regard to coalitional prejudice and religious belief. Participants for whom the pMFC has been downregulated exhibit less coalitionally biased responses to an immigrant critical of the participants' national in-group, and less conviction in positive afterlife beliefs (i.e., God, angels, and heaven), despite having recently been reminded of death. These results complement prior findings that continuous theta burst stimulation of the pMFC influences social conformity and sharing and illustrate the feasibility of investigating the neural basis of high-level social cognitive shifts using transcranial magnetic stimulation.

Threats reliably evoke shifts in high-level ideological investment, but little work to date has explored the neural mechanisms underlying these dynamics. This paper describes how continuous theta burst transcranial magnetic stimulation may be employed to test the contribution of the posterior medial frontal cortex (and/or other regions) to threat-related ideological shifts.

Decades of behavioral science research have documented functional shifts in attitudes and ideological adherence in response to various challenges, but ...

Functional Imaging of Auditory Cortex in Adult Cats using High-field fMRI

Current knowledge of sensory processing in the mammalian auditory system is mainly derived from electrophysiological studies in a variety of animal models, including monkeys, ferrets, bats, rodents, and cats. In order to draw suitable parallels between human and animal models of auditory function, it is important to establish a bridge between human functional imaging studies and animal electrophysiological studies. Functional magnetic resonance imaging (fMRI) is an established, minimally invasive method of measuring broad patterns of hemodynamic activity across different regions of the cerebral cortex. This technique is widely used to probe sensory function in the human brain, is a useful tool in linking studies of auditory processing in both humans and animals and has been successfully used to investigate auditory function in monkeys and rodents. The following protocol describes an experimental procedure for investigating auditory function in anesthetized adult cats by measuring stimulus-evoked hemodynamic changes in auditory cortex using fMRI. This method facilitates comparison of the hemodynamic responses across different models of auditory function thus leading to a better understanding of species-independent features of the mammalian auditory cortex.

Functional studies of the auditory system in mammals have traditionally been conducted using spatially-focused techniques such as electrophysiological recordings. The following protocol describes a method of visualizing large-scale patterns of evoked hemodynamic activity in the cat auditory cortex using functional magnetic resonance imaging.

Current knowledge of sensory processing in the mammalian auditory system is mainly derived from electrophysiological studies in a variety of animal ...

Neuroscience

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 ...