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Transcranial brain stimulation laboratories at the CIMeC

This document contains the rules and the documentation for the use of the TBS labs in Mattarello (LNiF) and Rovereto (CeRiN).

1. Preamble.

Transcranial magnetic stimulation (TMS) is defined as the administration of one (single pulse TMS, or spTMS), two (paired pulse, or ppTMS) or a series (repetitive TMS, or rTMS) of magnetic stimuli to the brain. Repetitive TMS is further classified as patterned TMS (for example theta-burst stimulation) and conventional rTMS (single-frequency TMS).
Low intensity transcranial electric stimulation (TES) includes different modalities such as transcranial direct current (tDCS), alternating current (tACS) and random noise (tRNS) stimulation.

2. Equipment.

2 LNiF Mattarello and CeRiN Rovereto:

2.1 - Stimulation:

TMS

1 Magpro X100 stimulator
1 Magpro Compact stimulator
Related coils: 1 MB-B70 Butterfly, 1 MCF-P- B65 Butterfly, 2 MCF-B65 Butterfly cooled, 2 MC-B35 Butterfly
1 Magstim Rapid 4 boosters stimulator (CeRiN)
1 Magstim Bistim (two 200 units) stimulator
Related coils: 1 Double Cone 110mm, 2 Double 70mm (1 LNiF, 1 CeRiN), 2 Coil Alpha Branding Iron Range 50mm, 1 Alpha Branding Iron Range 30mm, and 1 adapter to old-model coils

TES

1 Eldith Plus Neuroconn for tDCS, tRNS, and tACS (fMRI compatible) (CeRiN)
2 BrainStim for tDCS, tRNS, and tACS

2.2 - Neuronavigation:

2 Softaxic Neuronavigation system (1 LNiF, 1 CeRiN)

2.3 - EEG, EMG, ECG, ERG recordings:

2 4-channel amplifiers CED
2 4-channel analog to digital converter CED
1 2-channel Signal wireless system Mobimini.

2.4 - Nerve stimulators:

2 digitimer DS7AH constant current stimulator

2.5 - TMS-fMRI TMS-EEG equipment:

Set up for fMRI compatible TMS, 1 remote control, 1 safety switch
1 EEG system with 64 Channels and EXG 8 bipolar Channels Brainamp fMRI and TMS compatible, Brainvision software

2.6 - Modelling and Stimulus presentation:

SimNIBS for transcranical brain stimulation (TMS & tDCS) modelling.
E-prime software.
ASF software.

3. Definition of study types to be done with TMS/TES.

3.1 Class 1

Direct benefit, potential high risk: Studies in patients with diagnostic or therapeutic primary objective with potential direct individual clinical benefit. Normal subjects should not ordinarily participate in such studies, and the risk level for patients can be theoretically high.

3.2 Class 2

Indirect benefit, moderate risk: Studies in patients where the potential clinical benefit is more speculative or where no clinical benefit is expected. In these studies, regimens that will place subjects at significant risk should employ only patients and not normal subjects.

3.3 Class 3

Indirect benefit, low risk: Studies in normal subjects and patients that are expected to yield important data on brain physiology or on safety, but have no immediate relevance to clinical problems. Normal volunteers should be permitted to participate in rTMS research when it is likely to produce data that are of outstanding scientific or clinical value.

4. Access to the lab.

For general access see Mandatory Requirements at LNiF general access rules
The lab is open only during office hours (9-18 in Mattarello and 9-17 in CERiN). The lab can be accessed by users holding a valid University badge with the necessary authorizations; in particular, it is mandatory for anyone accessing the lab to have successfully accomplished the "Course on Health and Safety in the workplace" of University of Trento. Users (Researchers and PhD students) are allowed to access instruments only after appropriate (mandatory) training about TMS & TES procedures and lab rules. To access, the TBS lab, without supervision it is necessary to have a basic life support (BLS) certification. Bachelor and master students are not allowed to work in the facility unattended.
For specific requirements see below 5.7 Specific access to the lab infrastructure.

4.1 What kind of studies can be done?

4.1.1 LNiF:

Mattarello: TMS/TES will not be used as a diagnostic nor as a therapeutic devices, but rather as experimental tools in a research environment in Class 3 studies. TMS/TES will be conducted:
only on healthy volunteers, with full informed consent of the participant and within protocols:

4.1.2 CERiN:

Rovereto: TMS/TES will be used as a therapeutic devices (but not as diagnostic device) in Class 1, 2 and 3 studies. TMS/TES will be conducted on healthy volunteers and on patients, with full informed consent of the participant and within protocols:

4.2 Differences between sp/ppTMS and rTMS

4.2.1 spTMS and ppTMS

They are established as a safe and useful tools for investigating various aspects of human neurophysiology in healthy participants (Rossi et al., 2009). spTMS and ppTMS can be carried out in non-medical settings and in the absence of medical supervision.

4.2.2 rTMS

It potentially carries a significant risk and, therefore, require medical supervision and the presence of emergencies facilities.

4.3 Who can directly deliver TMS/TES?

The person who practically delivers spTMS, ppTMS, rTMS and TES does not need to be a medical professional (MD) or a specialized technician.
TMS or TES must only be performed by researchers who have trained in its delivery and who maintain an appropriate level of skill through the regular practice of TMS or tES. Morever they must have undergone recent training on the management of medical emergencies: a Basic Life Support (BLS) course.
Such courses are organized by a specialised company, in agreement with the Responsible of the lab and with Valeria Nencini valeria.nencini at unitn.it from the CIMeC administration.

4.4 How to propose a TMS/TES experiment.

At least one of the researchers involved in a TMS/TES study should be intimately familiar with the TMS/tES techniques (see 4.3). The following is a schedule for a PI who wishes to start a TMS/TES experiment:
1. (Optional but recommended) preliminary informal discussion with the Lab Responsible.
2. Choose a LNiF PI
3. Submit LNiF_Research_Proposal_Form_A (necessary for all research project applications) or submit LNIF_Research_Proposal_Form_B (necessary only if you request CIMEC funds for the project)
4. Base on your proposal you might need to submit your project to the Responsible Physician for his/her check
5. Give a Project Proposal Presentation for technical and scientific feedback
6. Obtain Ethical Committee Approval for the project
7. Communicate to Ehtical Committe and Admin the starting date of your project.
8. Send Ethical Committee and Admin updated versions in case of request for extensions or project's changes (involved people, n. of subjects). Note that if you are going to ask for an extension of the number of subjects and your project is using CIMeC's funds, you must ask in advance for the Director's authorization for the extension of your budget.
9. After the end of the project, show the scientific results of the research project, by handing in a written report and by giving a presentation Project Results Presentation
10. Please note that access to the CERiN lab must be discussed before any proposal with the Director of the CERiN.

4.5 Duties of the experimenter.

4.5.1.

Book a timeslot for the experiment through an electronic scheduling system. This can only be done if the researcher has the necessary authorizations and a project number that documents the approval of the study in question by CIMeC and the Ethical Committee.

4.5.2.

Screening on TMS/TES participants using the Italian or the English version of the approved questionnaire (see below: 7. Reference material for download).
Providing the participant with documentation for informed consent.

4.5.3.

Signing of the consent form.

4.5.4.

Signing of the privacy statement.

4.5.5.

Ensure the proper handling of stimulation devices. This includes making sure that stimulation stays within the published safety limits as in Rossi et al., 2009 for TMS, and that participants wear ear protection and Antal et al., 2017 for TES.

4.5.6.

Monitor participants for signs of distress e.g., headache, dizziness. This means that it is duty of the experimenter to make sure that there is an operator ALWAYS present in the lab while stimulating.

4.5.7.

Survey on TMS/TES using the Italian or the English version (see below: 7. Reference material for download). Document all incidents including minor discomfort of participants related to the experiment.

4.5.8.

Make sure that the operators are familiar with the emergency procedure (see point 5.6)

4.5.9.

In case of emergency provide first assistance, apply the procedure detailed in point 5.6.

4.6 Duties of the supervising physician

For some protocols (i.e., rTMS) a supervising physician is needed.

4.6.2

The supervising physician is required to perform the medical screening on TMS participants using the Italian or the English version of the approved questionnaire (see reference material on the wiki page). By signing the screening form the supervising physician will assume liability for the experiment. Therefore it is required to have insurance for professional damage to a third party.

4.6.3

Supervising physicians will have to get personally in touch with participants only in case of emergencies during rTMS and TMS on the premises of the LNiF and in circumstances that are immediately related to the specific experiment.

4.6.4

Provide first aid in case of an incident during the experiment and after the experiment as long as the participant is on CiMeC premises

4.6.5

Be available for providing additional information on the circumstances of any occurring incident. The availability of a supervising physician for any rTMS study at LNiF is ensured by the following procedure:

  • A physician authorized for supervising rTMS studies will mark her or his availability in an electronic scheduling system.
  • The researcher responsible for the rTMS study in question will book time slots in which a physician is available.
  • The researcher contacts the authorized supervising physician before the start of the experiment in order to perform screening and to ensure the physicians presence on CIMeC premises.
  • In that contact the physician commits his full availability to consultation and emergency services described in point 3 above.

4.6.6.

Document all incidents including minor discomfort of participants related to the experiment on the related part of the screening questionnaire.

5. Rules of conduct regarding safety issues

5.1 Allowed protocols

All protocols must be within the standard ones defined in Rossi et al., 2009 for TMS and Antal et al., 2015 for TES. In particular for rTMS it is mandatory to comply with the safety limits in the dimensions of 1) frequency; 2) intensity and 3) duration of the train. These limits can be found in Rossi et al., 2009. In particular, in rTMS experiment all intensity stimulations must be defined as a function of individual motor threshold, that must be calculated with EMG measurement of MEPs in the case of frequencies above 1 Hz.

5.2 Monitoring of subjects during and after rTMS and TMS.

Subjects need to be visually monitored constantly during the experiment. As soon as the participant shows any signs of distress, experimenters will stop the experiment. Participants undergoing TMS for their very first time should be observed for 10 minutes before leaving the premises. This means that the participant should NEVER be left alone in the lab during stimulation under any circumstances. If for some reason the experimenter needs to leave the room, then stimulation should be interrupted.
A stated in Rossi et al., 2009 neurophysiological monitoring is NOT required with standard protocols within safety limits.
The responsible researcher's contact should be given to participants, printed on the consent information sheet, in case of need of any clarifications.

5.3 Time of the day.

TMS/TES can be performed ONLY during office hours (9-18 in Mattarello and 9-17 in the CERiN).

5.4 Participant protection.

The only required equipment is earplugs that should be positioned prior to any stimulation.

5.5 Session duration and frequency.

A single participant should not undergo single sessions longer than 90 minutes of stimulation (excluding the subject preparation time). Single subjects should not undergo more than 12 TMS/TES sessions in one year.

5.6 Emergency management procedure.

The only two conditions that require emergency interventions are syncope and seizure. In both cases the experimenter will have to deal with an unconscious patient.

  • The participant is laid on the floor. Blankets and pillows are available in the TBS lab in order to minimize mechanical injury during a seizure and these should be used promptly.
  • - Experimenters have received training on how to deal with medical emergencies and therefore be able to provide basic first aid. This means to follow all the steps described in the BLS procedure (Check for safety of the operator, check for airways, breathing, circulation, etc.). In the case of rTMS-related medical emergencies, even before starting the first aid procedures, experimenters will immediately alert the supervising physician.
  • - spTMS and ppTMS are considered safe procedures, therefore any unlikely emergency occurring during those protocols should be treated as an any other emergency happening on the premises (presence of medical personnel not required).
  • - Soon after the event, once emergency has receded, the supervising person will write an accident/incident report, providing the details of the person involved, location, nature of reported problems and witnesses.

5.7 Training procedures for researchers and specific access to the TBS lab infrastructure.

The TBS lab can be accessed by users holding a valid University badge with the necessary authorizations.
TMS/TES must only be performed by researchers trained in its delivery and who maintain an appropriate level of skill through the regular practice of TMS/TES and continuing professional development. In order to use the TBS laboratory, a researcher has to go through these mandatory stages:

  • you must have taken and passed the course on Health and Safety in the workplace see LNiF general access rules
  • you must have a take a first-level TMS/TES course and passed the following exam and get a qualified training by one of the instructors while assisting the ongoing projects.
  • you must have undergone recent training on the management of medical emergencies: a Basic Life Support (BLS) course.
  • you must have an "active" project.
  • by applying certain established criteria, instructors will then judge their trainee's ability to carry out a study autonomously; if the judgment is positive, the trainee will be allowed to access the lab without supervisor.

6. Multimodal studies

At the present stage Multimodal Studies that can be implemented at the LNiF include offline rTMS-fMRI and online / offline TMS-EEG. Due to their non-conventional nature, projects using either methodology need to be discussed with the relative LNiF PIs.

7. Reference material for download:

 

References:

Transcranial Magnetic Stimulation (TMS)
  • Rossi S, Hallett M, Rossini PM, Pascual Leone A and Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009;120(12):2008-39. doi: 10.1016/j.clinph.2009.08.016. Link
  • Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, Di Lazzaro V, Ferreri F, Fitzgerald PB, George MS, Hallett M, Lefaucheur JP, Langguth B, Matsumoto H, Miniussi C, Nitsche MA, Pascual Leone A, Paulus W, Rossi S, Rothwell JC, Siebner HR, Ugawa Y, Walsh V, Ziemann U. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol. 2015;126(6):1071-107. doi: 10.1016/j.clinph.2015.02.001. Link

 

Low Intensity Transcranial Electric Stimulation (TES)
  • A. Antal, I. Alekseichuk, M. Bikson, J. Brockmöller, A.R. Brunoni, R. Chen, L.G. Cohen, G. Dowthwaite, J. Ellrich, A. Flöel, F. Fregni, M.S. George, R. Hamilton, J. Haueisen, C.S. Herrmann, F.C. Hummel, J.P. Lefaucheur, D. Liebetanz, C.K. Loo, C.D. McCaig, C. Miniussi, PC Miranda, V Moliadze, MA Nitsche, R Nowak, F Padberg, A Pascual-Leone, W Poppendieck, A Priori, S Rossi, PM Rossini, J Rothwell, MA Rueger, G Ruffini, K Schellhorn, HR Siebner, Y Ugawa, V Walsh, A Wexler, U Ziemann, M Hallett, W Paulus Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines Clin Neurophysiol. 2017 http://dx.doi.org/10.1016/j.clinph.2017.06.001
  • Woods AJ, Antal A, Bikson M, Boggio PS, Brunoni AR, Celnik P, Cohen LG, Fregni F, Herrmann CS, Kappenman ES, Knotkova H, Liebetanz D, Miniussi C, Miranda PC, Paulus W, Priori A, Reato D, Stagg C, Wenderoth N, Nitsche MA. A technical guide to tDCS, and related non-invasive brain stimulation tools. Clin Neurophysiol. 2016 ;127(2):1031-48. doi: 10.1016/j.clinph.2015.11.012. Link
  • Fregni F, Nitsche MA, Loo CK, Brunoni AR, Marangolo P, Leite J, Carvalho S, Bolognini N, Caumo W, Paik NJ, Simis M, Ueda K, Ekhitari H, Luu P, Tucker DM, Tyler WJ, Brunelin J, Datta A, Juan CH, Venkatasubramanian G, Boggio PS, Bikson M. Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel. Clin Res Regul Aff. 2015 Mar 1;32(1):22-35 Link
Created by davide.tabarelli. Last Modification: Tuesday 24 of October, 2017 15:19:36 CEST by elena.tonolli.1.