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...

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 border="1">
 <tbody>
 <tr>
 <td>Material Name</td>
 <td>Type</td>
 <td>Company</td>
 </tr>
 <tr>
 <td>Transcranial magnetic stimulation</td>
 <td>Magstim super Rapid2 stimulator, Rapid-2 Plus One Module </td>
 <td>Magstim Ltd., Wales, UK </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>
 </tr>
 <tr>
 <td>Magnetic resonance imaging</td>
 <td>3-T Siemens Trio scanner, 32-channel Head Coil </td>
 <td>Siemens, Inc., Germany</td>
 </tr>
 <tr>
 <td>Frameless Stereotaxy</td>
 <td>Brainsight </td>
 <td>Rogue Research Inc., Montreal, Canada </td>
 </tr>
 <tr>
 <td>Optical measurement system</td>
 <td>Polaris Spectra </td>
 <td>Northern Digital Inc, Ontario, Canada </td>
 </tr>
 <tr>
 <td>Multi-jointed arm for coil holder</td>
 <td>Standard</td>
 <td>Hybex Innovations Inc., Anjou, Canada</td>
 </tr>
 <tr>
 <td>MRI-Compatible Insert Earphones </td>
 <td>Sensimetrics, Model S14 </td>
 <td>Sensimetrics Corporation, MA, USA </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 ...

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13.7K 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.