Ensuring participant safety is central to all TMS research conducted at the CCBBI. The following guidelines outline the framework for assessing study risk, determining oversight requirements, responding to emergencies, and documenting TMS sessions. These protocols reflect best practices and the recommendations of international safety guidelines, including those from Rossi et al. (2009) and Rossi et al. (2021), Lerner et al. (2019), and operational practices from the Martinos Center for Biomedical Imaging.
Types of TMS Studies, Risk Classification, and MD Coverage
TMS studies vary widely in their purpose, population, and stimulation parameters. At CCBBI, each study is categorized as Class 1, 2, or 3 based on risk and expected benefit, in alignment with guidance from Rossi et al. (2009) and Rossi et al. (2021). This classification determines oversight needs, including whether physician coverage is required.
- Class 1 studies involve novel or high-risk stimulation, often in clinical populations, and require a licensed physician to be on-site during TMS sessions. The risk in these studies is considered to be HIGH. Examples include:
- rTMS outside of Safety Tables (healthy participants and patients).
- All TMS parameters (within or outside of safety tables) when TMS protocol increases risk for seizure (in healthy participants or patients).
- Class 2 studies typically include established protocols in either patient or healthy control groups but may involve MODERATE risk due to population characteristics or protocol design. Physician coverage may be required if repeated sessions are involved with a clinical population. Physician coverage may also be required in instances when parameters are within guidelines, but long-term effects are not known.
- Class 3 studies involve low-risk protocols (such as single- or paired-pulse TMS) in healthy participants. These do not require physician oversight if all parameters remain within established limits. The risk in these studies is considered to be LOW. Examples include:
- Single and dual pulse (<1 Hz) (healthy subjects)
- rTMS within Rossi et al. (2009) safety tables (healthy subjects)
Each study must include a justification for its risk level and adhere to corresponding safety protocols. The CCBBI Steering Committee reviews these classifications at the time of study approval.
Seizure Risk
Although TMS is widely regarded as safe when used within established parameters, the major potential safety concern is the risk of seizure. In practice, seizures following TMS are exceedingly rare—even in individuals with epilepsy. Most reported cases of TMS-induced seizure have occurred during high-frequency repetitive TMS (rTMS) delivered above 1 Hz, particularly when stimulation trains are long and intensity is high. A few seizures have been observed following single pulses, but these have occurred in individuals with pre-existing neurological conditions.
CCBBI minimizes these risks through rigorous screening, conservative protocol design, and well-defined staffing requirements. Each of these is described below.
Rigorous Participant Screening
Before participating in any TMS session at CCBBI, all individuals must undergo thorough screening to ensure their eligibility and safety. This process includes a standardized TMS Safety Questionnaire and a review of contraindications and risk factors by trained study personnel. No TMS session may proceed until a participant has been fully screened and cleared. Individuals with a history of epilepsy, unexplained loss of consciousness, brain lesions, or other known risk factors are excluded unless the study has been explicitly approved for their inclusion by the IRB and the CCBBI.
TMS Safety Questionnaire
All participants must complete the CCBBI TMS Safety Questionnaire prior to their first session. This questionnaire is designed to identify known medical contraindications and any condition that may place the participant at elevated risk during TMS.
Participants should complete the form via the following REDCap link: (updated link will be inserted here. Please see Appendix A for now)
A new questionnaire must be completed:
- Before the first TMS session
- Whenever a participant’s medical history changes
- Annually, for long-term or repeat participation
The completed questionnaire must be reviewed and approved by a Level 2 certified operator. A copy must be retained in the study file. CCBBI will also retain the REDCap copy for our records. A printable version is included in Appendix A for reference.
Contraindications and Risk Factors
TMS is generally safe when delivered within established guidelines, but certain conditions and implants significantly elevate risk. The following are considered contraindications, and individuals with any of these should not undergo TMS:
- Implanted electronic or ferromagnetic devices (e.g., pacemakers, cochlear implants, deep brain stimulators, medication pumps)
- Metal implants in the head (excluding dental fillings)
- Skull defect or prior neurosurgery
- History of stroke
- Prior TMS-related serious adverse event
- History of epilepsy, unexplained seizures, or first-degree family history of epilepsy
- Bullet fragments or embedded shrapnel
- Current pregnancy
- Uncontrolled psychiatric illness in the context of therapeutic studies
Relative risk factors, while not absolute contraindications, require careful consideration and possible protocol modifications. These include:
- Use of seizure-threshold-lowering medications (e.g., bupropion, lithium, clozapine)
- Significant head trauma history
- Recent use of substances or alcohol
- Sleep deprivation
- Excessive caffeine or stimulants
- Auditory sensitivity or tinnitus
For participants presenting with any of these conditions, the study PI must assess risk and determine whether to proceed. Additional safeguards, including MD coverage or modified stimulation parameters, may be required.
TMS Parameters and Stimulation Limits
TMS protocols must be carefully designed to fall within established safety parameters that minimize the risk of adverse effects. All stimulation administered at CCBBI must adhere to the guidelines set forth by the International Safety Consensus Group (Rossi et al., 2009) and Rossi et al. (2021), as well as any specific limits imposed by the IRB and CCBBI approval process.
Stimulation Frequency and Intensity
TMS protocols are typically categorized by frequency and pattern:
- Single-pulse TMS: One pulse at a time, used for motor mapping or evoked potentials.
- Paired-pulse TMS: Two pulses at specific intervals, often used to assess intracortical inhibition or facilitation.
- Low-frequency rTMS: ≤ 1 Hz, generally associated with inhibitory effects.
- High-frequency rTMS: > 1 Hz, associated with excitatory effects, often delivered in short trains.
- Theta Burst Stimulation (TBS): Bursts of 3 pulses at 50 Hz, repeated every 200 ms (5 Hz). Includes intermittent (iTBS) and continuous (cTBS) variants.
The maximum stimulation intensity used in TMS research is typically expressed as a percentage of maximum stimulator output (MSO), calibrated individually based on each participant’s resting motor threshold (RMT). Most protocols use an intensity between 100% and 120% of RMT, which generally corresponds to 50–80% of MSO in healthy adults. Research protocols can utilize a maximum stimulation intensity based on either MSO or based on RMT. However, an MSO of 80% is the upper limit for all studies at CCBBI unless the study protocol has been explicitly approved for this purpose.
For any protocol involving high-frequency rTMS or TBS, investigators must clearly document the following in the CCBBI TMS Application:
- Frequency of stimulation
- Train duration
- Inter-train interval
- Total number of pulses per session
These values must fall within safety limits established in consensus publications (See Appendix B), and any protocol outside of these limits must receive additional CCBBI review and justification.
Conducting Safe TMS Sessions
Every TMS session must be conducted with at least two trained staff members present. One of these must hold Level 2 certification and is responsible for administering stimulation, monitoring the participant, and responding to any adverse events. Participants should be in clear view of the operator at all times and verbal communication must be maintained throughout the session.
Sessions must be conducted strictly within the parameters approved by the IRB and CCBBI. This includes intensity, frequency, train duration, and total stimulation time. Emergency procedures and contact information is posted visibly in the testing room and must be reviewed by staff prior to each session.
Individuals with implanted electronic devices (e.g., pacemakers, cochlear implants), a history of epilepsy or unexplained seizures, skull defects, or pregnancy must not undergo TMS unless the study protocol has been explicitly approved for these conditions. All participants must complete the CCBBI TMS Safety Questionnaire and meet all eligibility requirements before being cleared for stimulation.
Emergency Response Procedures
In the event of a seizure, loss of consciousness, or other acute adverse event, stimulation must be stopped immediately using the system’s Enable/Disable button. This is also true when a participant begins to exhibit early signs of a potential seizure—such as facial twitching, sudden confusion, or abnormal hand movement.
After stimulation has been stopped and head coil removed, the participant should be gently supported and guided to a safe position, ideally lying on their side to prevent aspiration. No effort should be made to restrain the participant’s movements during a seizure. Instead, staff should focus on preventing injury by clearing the area and supporting the head. TMS should not resume under any circumstances during a seizure. If the participant becomes unconscious or begins to convulse:
- Immediately stop stimulation and remove the coil.
- If needed, gently guide the participant to the floor; do not restrain their movements. If you are unable to guide the participant to the floor, the chair can be reclined so that the participant can recover in a vertical position.
- Protect the head and clear nearby equipment to prevent injury.
- Time the seizure—most last less than two minutes.
- Once the convulsions stop, place the participant on their side (recovery position).
- Monitor breathing, color, and responsiveness.
Call 911 as soon as convulsions begin. Do not attempt to move the participant or give water, food, or medication. One staff member should remain with the participant while the other calls 911. The participant should not be restrained but should be protected from injury during the episode. If a physician is assigned to the study, they should be contacted immediately. For less severe symptoms—such as dizziness or discomfort—stimulation should be stopped, and the participant monitored closely. Emergency services should be contacted if symptoms persist or escalate.
These procedures are summarized in a wall poster (Appendix C) located in the TMS testing room. All TMS personnel are expected to be familiar with this response plan and capable of executing it calmly and efficiently.
Reporting Adverse Events
Serious adverse events must be reported to the CCBBI Director, Dr. Ruchika Prakash, the study PI, and the IRB immediately. All events, regardless of severity, should be documented in the CCBBI internal log. The PI is responsible for ensuring that adverse events are also reported according to the terms of the study’s IRB approval.
Documentation and Record-Keeping
Every use of the TMS room—whether for training, teaching, data collection, or any other purpose—must be recorded in the physical logbook located in the TMS suite.
In addition, each data collection session must be documented using the electronic TMS Session Log Sheet, which is stored on the Stimulus Computer and should be uploaded to the designated OneDrive folder located on the Desktop. Logs must be completed immediately following each session and will be reviewed by CCBBI staff.
The TMS Session Log Sheet should include the session date and time, names of attending personnel, stimulation parameters, confirmation of safety screening, and a brief summary of the session outcome, including any technical issues or protocol deviations. A sample log sheet is provided in Appendix D.