DRCMR, Good Laboratory practice and safety considerations for magnetic brain stimulation

Introduktion
Target, Scope and Definitions
Good Lab Practice
Responsability and Organization
References
Appendix

Introduktion
Non-invasive brain stimulation, such as Transcranial Magnetic Stimulation (TMS) and transcranial current stimulation (tCS), is a common tool for both research and therapeutic uses and is generally regarded as safe. However, rare occurrences of brain stimulation induced loss of consciousness (LoC) have been reported. The vast majority of LoCs can be attributed to a vasodepressor (neurocardiogenic) syncope - a reaction to anxiety and psycho-physical discomfort - that can often be prevented by proper monitoring of the research participant and thorough explanation of all experimental procedures. Additionally, rare cases of brain stimulation induced seizures have occurred. Good general lab practice and safety standards are important to ensure optimal participant safety.

Tatget, Scope and Definitions
Target group: All investigators actively involved in non-invasive brain stimulation research projects at the MR-research section.
Scope: Establishing good laboratory practices for non-invasive brain stimulation.
Responsible investigators in order of involvement: 
Primary Investigator (direct responsibility). The primary investigator is responsible that the course of action, described in this document, is followed.
RGL: Research Group Leader responsible to ensure that the experiment complies with the international safety guidelines (Rossi S et al. 2009) and that all investigators directly involved in TMS/tDCS are familiar with these guidelines and have acquired the internal TMS-license.
Research subjects: Any research subjects participating in research projects at the MR-section

Good Lab Practice
To ensure best possible participant safety:
- All investigators have to obtain a TMS license before independently conducting brain stimulation experiments. The license should be kept in the researchers personal dossier. The license consists of 1) two experimental sessions with Brain Stimulation Method Group leader or appointed experienced TMS researcher. 2) Self-study of the international safety-guidelines and 3) 2-3 experiments under supervision of an experienced TMS researcher.
- All investigators are aware of the emergency procedure (Appendix 1-2) and can locate the safety instructions in the laboratory.
- All investigators should make sure that a working phone is accessible in the room when doing experiments.
- All experiments are in compliance with the international safety guidelines. Since most seizures occurred in individuals with known risk factors for brain stimulation induced seizures every participant is screened for contraindications to brain stimulation at the beginning of the experiment (Appendix 3)
- Participants on medication that increases the risk of a TMS induced seizure should not be included in TMS studies unless explicitly stated so in the ethics protocol for the study. A list with medications increasing the risk of a TMS induced seizure is placed in every laboratory.
- Preferably two people should be present during each experiment. If not feasible a second person should be on-call during the experiment (e.g. reachable by phone and able to be in the lab within 5 minutes). If research participants with specific risk factors are investigated (e.g. patient populations) two people have to be present during stimulation.
- The primary investigator should attentively monitor the research subject throughout the experiment and explain each experimental procedure.

Responsibility and Organization
The leadership of the MR research section is responsible for that all relevant employees are aware, and comply to these instructions.
All relevant departments, including the MR research section and the emergency department at Hvidovre Hospital, approve the present instructions.

References
Rossi S, Hallett M, Rossini PM, Pascual-Leone A. 2009. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 120:2008-2039.
Rossi, Simone, et al. "Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: expert guidelines." Clinical Neurophysiology 132.1 (2021): 269-306.

Appendix
Appendix1 - Emergency procedure.pdf
Appendix2 - Procedure ved nedsat bevidsthed.pdf
Appendix 3 - TMS_screeningsskema_V1.pdf