Precise Coil Positioning in Navigated Transcranial Magnetic Stimulation (nTMS) in Medication- Resistant Major Depressive Disorder (MDD): A Feasibility Study
Phase: NA
Conditions: Depressive Disorder, Major
Sponsor: Magstim

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1) Cover Sheet: 
 
Title: Precise Coil Positioning in Navigated Transcranial Magnetic Stimulation (nTMS) Feasibility in 
Depression Patients Trial 
 
Short Title: Confident Trial 
 
Protocol Number: MGS-2018-SS 
 
Date: November26, 2018 
 
Sponsor:   Magstim, Inc. 9855 W. 78th St, Suite 12; 844-624-7846 
 
Study Principal Investigator: Lothar Krinke PhD, Magstim, Inc. 844-624-7846  
Research Site key individual: Nicole Krummel, Georgia Behavioral Health Professionals, TMS 
Operations Leader, 678-426-2930 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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2) Purpose and Background:  
Objective: The objective of this study is to evaluate the feasibility of adding a navigational system to traditional 
repetitive Transcranial Magnetic Stimulation (rTMS, referred to in this application as nTMS) as a way to 
establish and maintain precise coil positioning (contact, rotation, and tilt) and consistent brain region targeting 
throughout a nTMS treatment session and in subsequent nTMS sessions.  Success will be evaluated via data 
analysis of information captured during nTMS, which will evaluate coordinates, contact, rotation, and tilt 
parameters of the stimulation pulses delivered.  The study will be conducted with patients who have been 
selected as traditional rTMS candidates and have met the criteria for rTMS, which includes, but is not limited to 
the following:  Adults with Major Depressive Disorder (MDD) who have failed to achieve satisfactory 
improvement from prior antidepressant medication in the current episode. For the purposes of this study, nTMS 
is referring to the use of a navigation device in combination with delivery of traditional rTMS.   
 
Aim 1: Determine the percentage of successful nTMS treatment sessions.  A successful nTMS treatment session 
is defined as the following:  80% of the TMS pulse trains are delivered while the coil is within acceptance 
criteria measured by tracking the following parameters:  coil deviations from digitally saved target location, 
which includes contact (mm), rotation (°), and tilt (°) parameters.  The acceptance criteria are met with coil 
position at the time of pulse delivery as follows: coil rotation within ±15° of target; coil tilt within ±15° of 
target; in-plane deviation within ±5mm of target; contact deviation within ±2mm of target. 
Aim 2: Determine Patient Health Questionnaire (PHQ-9) change measured weekly from baseline to after 30 
sessions of nTMS, collect Patient comfort data, measure Operator confidence and collect coil position data for 
nTMS sessions to determin future product improvements and clinical studies.   
 
The goal of this proposal is to establish nTMS as a means of precise administration of transcranial magnetic 
stimulation.   Ultimately, data from this study will be used to design larger, comparative studies to establish 
superior efficacy profiles in the treatment of MDD. 
 
Background: rTMS is an FDA-approved, non-invasive brain stimulation treatment for MDD that uses an 
electromagnet coil to deliver rapid magnetic pulses to a targeted area of the prefrontal cortex.  The magnetic 
pulses induce a weak electrical current in the brain, stimulating neuronal activity.  In the treatment of MDD, the 
electromagnetic coil is placed over the patient’s head to stimulate the DLPFC region of the brain.  While this 
stimulation location has been used for some time now, recent studies have shown that the focal magnetic fields 
produced by rTMS are affected by how the device coil is positioned during treatment3,9.  Therefore, it is 
becoming clear that positioning and maintaining the coil at the optimal rotation and angle in relation to the 
patient’s scalp, and consistently treating the exact same place within the DLPFC region may be crucial for 
optimal rTMS efficacy.   
 
 
 
Existing Literature: rTMS is used to successfully treat individuals with MDD.  However, discrepancies exist in 
the effect sizes and variable outcomes between subjects.   
 
Coil Location: Individual anatomical variability and inter-expert variability have been argued to be the two 
main sources of error during rTMS therapy6. Both of these hurdles can be overcome with the addition of a 
neuronavigation system to rTMS. In fact, the use of neuronavigation has been reported to decrease the 
variability of the results reported from rTMS therapy on depressed patients5.  Further, variability in localizing 

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the DLPFC is significantly lower when the rTMS is conducted with a neuronavigational method11,9.  A direct 
comparison study of MRI-guided and fMRI-guided navigated rTMS compared to traditional rTMS revealed a 
significantly larger effect size in the population who went through neuronavigation 12.  These data support the 
addition of neuronaviagation to the standard rTMS treatment regimen.  
 
Coil Orientation: Coil orientation is an important factor to take into account in order to increase the response 
rate to rTMS treatment8. Both brain gyrification15 conductivity anisotropy (which leads to certain current flow 
directions) (Opitz et al., 2011) play a role in the electrical field’s dependence on coil orientation8. Therefore, 
even when the coil is precisely located on the defined treatment location, the optimum coil orientation to elicit a 
motor-evoked potential (MEP) can be different; this was exquisitely described by the work of Balslev and 
colleagues (2007) who assessed the effect of eight different coil orientations on MEPs1. Even minor changes in 
coil placement can affect the motor-evoked potentials13; therefore, the coil positioning needs to be continuously 
checked for high accuracy by adjusting the coil position or orientation during the rTMS session as needed14.  
 
Of particular relevance is the perpendicularity of the e-field to the cortex is essential for the effectiveness of the 
rTMS treatment10.  There is an extensive body of research on how to optimize the effect of rTMS by 
maximizing the strength of the e-field as the coil is applied perpendicular to the treatment target and how 
accurate coil orientation can improve the treatment results3,9. For example, targeting the DLPFC for MDD 
treatment has often shown optimal results with 45 degrees coil orientation relative to parasagittal plane 2. On a 
similar note, Opitz and colleagues emphasize the need for individualized target definition for rTMS, and argue 
that the sensitivity of coil orientation is dependent on the TMS site, that is, the more posterior the target, the 
more susceptive it will be to the changes in coil orientation.  
 
Significance:  Taken together, these data validate that different variables such as location and orientation of the 
coil need to be carefully considered to optimize the treatment for each individual patient. We argue that this 
level of mm accuracy and reproducibility can hardly be achieved without neuronavigation.  The proposed work 
will confirm feasibility of use of nTMS to achieve precise and targeted stimulation outcomes. Such precise 
neuronavigation holds the future potential to optimize treatment outcomes for patients, resulting in improved 
effect-sizes, reproducibility, and consistency within and between patients.  Such opportunity to improve 
consistency advances the field of rTMS by defining stimulation parameters and ensuring those parameters are 
met on a patient-by-patient basis, optimizing individualized treatment.  
 
Justification for study involving humans: Humans are the best model for this investigation as rTMS is already 
used in patient populations and the addition of navigational ability to this treatment would represent a 
refinement to the treatment.  Therefore, it is optimal to test the navigational device within the context of its 
therapeutic setting; this requires use of human subjects. 
 
Magstim Transcranial Magnetic Stimulators were first approved for clinical use in 2008. The current Magstim 
device was FDA cleared in August 2018. 
 
 
3) Subjects:  
Number of subjects: 50 subjects are expected to be recruited to achieve successful completion of a total of 25 
subjects.  

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Gender of Subjects: Men and women will be recruited in accordance with their demographic representation 
within Georgia for the treatment of MDD.  No one will be excluded based on gender.  Pregnant women will be 
excluded due to the lack of knowledge about the potential effects of the treatment on a fetus. 
Age of Subjects: All subjects will be between 18-80 years of age.  Minors are excluded from this study as 
minors have unique brain development patterns and activity and as such, a separate, minor-specific study would 
be conducted to evaluate this population. 
Racial and Ethnic Origin: Recruitment is expected to be in alignment with the demographic distributions of 
race and ethnic origin in Georgia (the clinic sites).  No one will be excluded from the study based on race or 
ethnic origin.   
Inclusion Criteria:  Diagnosis of medication-resistant MDD; Age 18 years or older; Normal findings in the 
medical history, physical, and neurological examination 
Exclusion Criteria:   History of seizure disorder; History of neuroleptic medications/prior use of neuroleptics;, 
Presence of implanted medical pump, metal plate, or metal object in skull or eye; Pregnant women 
Vulnerable Subjects: Vulnerable subjects are not included in this study. 
Contraception: As the study is only over the course of five treatment sessions, it is unlikely that an individual 
will become pregnant and have knowledge that they have become pregnant.  If an individual becomes pregnant 
and notifies study staff, they will be removed from the study.   
 
4) Methods and Procedures: 
Design: This study is a feasibility trial. Each participant will receive 30 sessions of 10Hz (4 seconds per cycle) 
rTMS over the left DLPFC. At the prescribing psychiatrist’s discretion, patients may receive 20Hz (2 seconds 
per cycle).  Both treatment protocols have the same number of pulses delivered per session. The rTMS 
interventions will be guided by a neuronavigation system (StimGuide TMS Navigation System, Magstim, Ltd. 
Carmarthenshire, UK) for navigation to the treatment location and to ensure consistent placement and 
orientation of the coil during and between each session.  For the purpose of this protocol, these sessions are 
referred to as nTMS.  Coil position data will be captured for sessions 6 through 30 to determine the primary 
outcome, which is Percentage of successful treatment sessions.  
 
The primary outcome measure will be the percentage of successful nTMS treatment sessions pooled from 
sessions 6 through 30 for each study subject.  A successful nTMS treatment session is defined as:  80% of the 
TMS pulse trains are delivered while the coil is within acceptance criteria measured by tracking the following 
parameters:  coil deviations from digitally saved target location, which includes contact (mm), rotation (°), and 
tilt (°) parameters.  The acceptance criteria are met with coil position at the time of pulse delivery as follows: 
coil rotation within ±15° of target; coil tilt within ±15° of target; in-plane deviation within ±5mm of target; 
contact deviation within ±2mm of target. 
 
 
The secondary outcome measures are: 
• Patient Health Questionnaire (PHQ-9) change from baseline (prior to the first day of treatment but not 
on the first day of treatment) to after 30 sessions of nTMS. 
• Patient comfort measured on a scale from 1 to 5; with 1 being uncomfortable and 5 being extremely 
comfortable at the completion of the last nTMS session. 
• Operator confidence on a scale of 1 to 5; 1 being not confident at all in using StimGuide to consistently 
find the treatment site and deliver therapy to 5 being very confident in using StimGuide to consistently 
find the treatment site and deliver therapy at the end of the study. 

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• Coil position for every pulse train for each patient’s nTMS session 6 through 30. 
 
Procedure: The participant will be placed comfortably in the treatment chair in the field of view of technology 
for optical tracking, which tracks items with reflective spheres. A head reference, which is a lightweight 3-inch 
plastic piece with 4 reflective spheres, will be placed on the right side of the participant’s forehead via either a 
headband or adhesive electrodes. Anatomical registration of the participant’s scalp landmarks will be conducted 
by gently placing the tip of a pointer tool, which is a lightweight plastic piece with 4 reflective spheres, onto the 
participant’s nasion, left ear, and right ear.  
 
Motor threshold (MT), the lowest stimulation intensity to elicit a muscular response, will be determined using a 
light hand-held MT coil.  The position of the coil will be adjusted to find the motor hotspot.  EMG electrodes 
will be placed on the right APB (AbductorPollicis Brevis).  The MT coil will be moved in a 1 cm grid-like 
fashion while delivering pulses.  A TMS-induced motor evoked potential (MEP) will have an amplitude greater 
than 50 uV.  The largest recorded amplitude pulse > 50 uV will be selected as the MT, and registered as a target 
in StimGuide.  The power intensity will be lowered until the lowest intensity elicits 5 out of 10 consecutive 
pulses that elicit a MEP of at least 50 uV.  
  
The MT and location of the motor hotspot will be saved in the StimGuide TMS navigation system with the 
corresponding power intensity.  If using the Beam F3 method, a mark will be placed at the F3 location, and the 
coil will be placed at 45 degrees tangential to the head.  The treatment site will be registered in StimGuide.  If 
using the 5.5 cm (anterior to MT hotspot) method, StimGuide will guide the operator to the location, and the 
coil will be placed at 45 degrees tangential to the head.  The treatment site will be registered in StimGuide  
 
For the subsequent sessions, nTMS treatment will be delivered using the saved information. The StimGuide 
TMS navigation system will inform the operator of any deviation in rotation and angle of the treatment coil, or 
displacement of the treatment coil while it is being placed onto the treatment site and during the entire session.  
Such real-time feedback will ensure accurate placement of the coil from session to session while simultaneously 
ensuring optimized coil angling within treatment sessions; together, such dynamic navigation will enable 
nimble, individualized treatment that increases the likelihood of success for nTMS.  
 
Experiment versus Standard of Care: All of the stimulation treatment received as part of this protocol is part of 
the standard of care recommended for these participants.  Only patients whose physicians have referred them to 
have rTMS will participate.  Therefore, all study visits related to this project are also part of the standard care 
the patient would normally receive.  The only portion of the care the participant will receive that is unique to the 
experimental portion of this protocol is combining the navigational component/device with the standard rTMS 
component for five of their rTMS treatment sessions.  If a patient does not wish to participate in this study, they 
still will receive rTMS as recommended by their physician.   
 
Frequency and Duration of Procedure: The initial appointment will last approximately 60 minutes; each 
subsequent appointment will last approximately 45 minutes.   The initial appointment will take longer due to the 
additional effort to establish and save the navigational target to be used in subsequent appointments All 
experimental procedures are conducted at the same clinic at which patients would receive their standard rTMS 
treatment; therefore, there is no change in location for participants whether they participate in the study or 
simply receive their standard care.  The patients will complete a PHQ-9 prior to receiving the first nTMS 

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session as baseline (prior to the first day of treatment but not on the first day of treatment) and weekly until after 
the last nTMS session has been completed.  
 
Timeline: Patients will be recruited to participate in the study for 30 treatment sessions.   It is anticipated that all 
enrollment activities will be concluded by May 15, 2019 with the analysis completion anticipated by the end of 
June 2019. 
 
End of the study: After 30 nTMS treatments, the patient will have completed the study.  The primary and 
secondary outcome measures will be analyzed after the last patient has competed 30 sessions, every patient 
competed the patient comfort survey and PHQ-9 assessment and every operator has completed the operator 
confidence survey Patients may receive additional treatments in a continued access phase of the study. No 
additional study data will be collected during this phase. 
 
 
Hazards: No procedures or situations related to this work are expected to be hazardous. 
 
Sample Collection: There is no sample collection associated with this protocol. 
 
Data: Information and clinical data collected as part of the study will be labeled with the subject’s initials and a 
study number, which will be in a locked file cabinet in the locked in the study coordinator’s office.  The record 
linking the patient name to the study ID number will be kept indefinitely in a confidential manner.  Only study 
staff will have access to the study information. All other data will be stored for six years and then be destroyed. 
Information related to neuronavigation and tms treatment will also be entered into a secure web-based computer 
database (Magstim Insight).  Coil positional data is stored within Magstim StimGuide.   
Data Storage and Confidentiality: 
 
Patient identifiable information and clinical data collected as part of the study will be kept in the Magstim 
Insight (“Insight”) platform. Insight is a secure, cloud based, patient data management system developed by The 
Magstim Company Ltd. Access to the Insight system is controlled using user credentials (username and 
password), while communication to the Insight system is encrypted using SSL. Access to the Insight platform 
will be controlled by the PI, or an authorized study coordinator granted access by the PI. 
 
Each participant in the study will be assigned unique coded (non-patient identifiable) identifier which is stored 
as part of the patient record within the Insight platform. These unique identifiers will be used when registering 
the patients within the Magstim StimGuide (“StimGuide”) system. 
 
StimGuide will be used to store data relevant to the coils position during a treatment session, along with the co-
ordinates of the participants motor threshold and treatment locations. StimGuide employs Microsoft Bitlocker 
technology to encrypt all data stored on its internal hard drive. Access to StimGuide also requires the use of 
standard user credentials (username, password). 
 
Positional data shall be exported from StimGuide for analysis by Magstim, Inc. in order the determine the 
positional accuracy of the TMS coil for each treatment session.  The exported data shall not contain any patient 
identifiable information as all data is associated with the unique coded identifiers as described previously. 
 

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Once the study is completed all access to the data stored within Insight shall be disabled. The data will be kept 
for a period of 6 years at which time is shall be securely deleted. 
 
Participation in this study is completely voluntary. Each participant has the right to choose not to participate or 
to withdraw participation at any point in this study without affecting his/her health care or other services to 
which they are entitled. 
 
 Confidentiality: 
 
The screening for ineligible candidates will be destroyed after the project's completion (12 months). The 
information relating to an enrolled subjects contact/personal details will be kept within the Insight platform. 
 
Direct identifiers such as name, address, and telephone number will be maintained within the Insight platform 
and shall be kept for six years in accordance with HIPAA.  If new information is obtained about safety during 
the course of this study, participants will be contacted for re-consent.   
 
Data stored within StimGuide is anonymized by the use of code identifiers. 
 
The clinical data will be stripped of all identifying information. This detail will be thoroughly covered during 
the consent process. Additional details on confidentiality have been covered in Sections 13 
 
 
5) Potential Risks 
Risk Category: Minimal Risk.  The probability and magnitude of harm or discomfort anticipated in the research 
are not greater than those ordinarily encountered in daily life or during the performance of routine physical or 
psychological examinations or tests. 
 
Potential Risks: The stimulation parameters for nTMS (traditional rTMS) are safe and have been used on many 
people to study the brain over recent decades.  Most people do not find the stimulation painful, but occasionally 
strong contractions of scalp muscles can cause some discomfort and headache.  If the patient finds the 
procedure too uncomfortable, they may discontinue at any time.  Headaches usually go away promptly with 
nonprescription medication.  The noise of the magnet may affect hearing, so earplugs are worn during nTMS.  
Magnetic stimulation will not be performed in people who have pacemakers, implanted pumps or stimulators, 
metal objects inside the eye or skull, or who have a history or risk of seizure.  This study uses a stimulation 
protocol that has medical (FDA) clearance for the treatment of MDD and has been used for many research 
studies of various other conditions. The risk of inducing a seizure with nTMS is considered very low (less than 
1%) and similar to the incidence of seizures associated with antidepressant medications.  Safety studies using 
TMS in patients with neurological disorders have demonstrated no permanence.  Risks to a fetus are not known 
and that information is made clear in the Patient Consent Form.  It is expected that nTMS (the addition of a 
navigational system to rTMS) offers no additional risks to patients. 
  
There are risks of stress, emotional distress, inconvenience, and possible loss of privacy and confidentiality 
associated with participating in a research study.  There may be other risks that are currently unknown.   
 

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Protection Against Risks: These risks are expected to be reversible for the most part, with the exception of 
hearing damage (mitigated by the ear plugs), loss of confidentiality (mitigated with data management 
safeguards), and seizure (mitigated by exclusion criteria).  Discomfort and headache can be treated with OTC 
medication.   Personnel will be trained to monitor for risks and to remove individuals from the study for whom 
participation appears to be producing unexpected negative reactions. 
 
6) Potential Benefits: 
There is the possibility of nTMS directly improving symptoms related to medication-resistant MDD.   
 
Improved consistency and optimization of treatment delivery is expected to provide reproducible outcomes with 
little variability, thus improving predictability of patient outcomes. 
 
The knowledge gained in this proposed research could lead to an optimization of nTMS delivery and improved 
care of patients with medication-resistant MDD.  In this case, improved quality of life could be expected with 
the successful and effective development of nTMS therapies. 
 
7) Subject Identification, Recruitment, and Consent/Assent 
Method of Subject Identification and Recruitment:  
Patients already referred for routine rTMS treatment for MDD will be recruited (via referrals from physician) to 
instead receive nTMS for the first five treatment sessions, followed by standard rTMS for the remainder of their 
treatment period.  Since the physician will speak to the potential subjects about the possibility of participating in 
the study during an appointment time that was already scheduled and in a room that is used for patient visits, 
this will be a private conversation.  Since the physician is the person referring the patient to receive rTMS 
treatment, the physician is the best person to describe the option for inclusion of the navigational system as part 
of a research study.   Following a description of the options, the study coordinator will have no further 
interaction with the patient about the study.  Instead, to minimize undue influence, the study coordinator will 
meet with interested patients to review the details and obtain consent. 
 
HIPAA: Since identifiable information will be gathered, HIPAA Authorization forms will be signed by each 
participant as part of their recruitment. 
 
Process of Consent: The process of consent will take place at the clinic, following a standard appointment with 
the patient’s physician. This process will occur in the clinic and no more 10 days prior to the first nTMS 
treatment.  Subjects may take as much time as needed to consider participation in the study.  The study staff will 
make every effort to meet with the potential subjects as many times as needed to clarify any portions of the 
consent form.  The potential subject may take the consent form home with them and they will have a number 
provided to them to call the study staff if they are interested in participating or have follow-up questions.   Any 
oral or written information will be provided to participants in their own language.  Nicole Krummel is the 
authorized individual authorized to provide consent.  
 
Subject Comprehension: Subjects will be encouraged to ask questions during the consenting process.  
Additionally, the study coordinator will ask the potential subjects if they have any questions and will attempt to 
assess their comprehension of the study by asking them to state their understanding of the research portion of 
the study prior to signing the consent form. The recruiting clinician will ensure that the subject themselves or 

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representatives of the subjects have sufficient knowledge and comprehension of all elements of the informed 
consent and are able to make an informed decision about participation 
 
Documentation of Consent: Consent will be documented via signed informed consent forms.  These forms will 
be maintained in a secure way that is accessible only to the study staff. The study PI, Lothar Krinke, is 
responsible for ensuring that valid consent is obtained and documented for all subjects.  
 
Costs to Subject: All participants are receiving rTMS treatment as part of their standard of care.  Therefore, 
there is no additional cost to them in terms of their time, transportation, or the addition of neuronavigation to the 
protocol.   
 
Contact Information for Concerns:  
This research is being overseen by Aspire Independent Review Board (“IRB”). An IRB is a group of people 
who perform independent review of research studies. You may talk to them at 1-877-366-5414 (toll free) if: 
      You have questions, concerns, or complaints that are not being answered by the research team. 
      You are not getting answers from the research team. 
      You cannot reach the research team. 
      You want to talk to someone else about the research. 
      You have questions about your rights as a research subject. 
- 
Withdrawal of Subjects: Any subject is free to withdraw from the study at any time. 
Additionally, the investigator can remove a participant from the study at any time if she believes that continuing 
is not in his/her best medical interest, or if he/she is unable to comply with the requirements of the study. 
Any subjects withdrawn or removed from the study will not be considered to have completed the study and 
therefore, no data from these individuals will be utilized in the evaluation of the results (except for the purposes 
of reporting an adverse event). 
 
Sharing of Results with Subjects/Incidental Findings: Results will not be disseminated to participants.  
However, all participants are receiving navigation as part of this study and therefore no “unblinding” would be 
needed/useful. 
 
8) Consent Form 
A consent form is attached for review. 
 
9) Compensation of Subjects/Payment or Participation 
Subjects are not compensated for their participation. In the event that this research activity results in an injury, 
treatment will be available, including first aid emergency treatment, and follow-up care as needed.  Care for 
such injuries will be billed in the ordinary manner, to the subject or their insurance company.  Any participant 
who thinks they have suffered a research related injury should notify the study coordinator right away.  No 
commitment is made by the study site to provide free medical care or money for injuries to participants in this 
study.  
 
10) Data and Confidentiality 
 

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Coil position data for every treatment session will be captured and stored in the study database.  Only data from 
session 6 through 30 will be used to for the primary endpoint determination to allow for operators and patients 
to get used to the procedure during the first 10 sessions.  PHQ-9 will be obtained from every patient prior to the 
first nTMS session and weekly until after the last session has been completed.  The patient comfort survey will 
be administered after the last session has been completed.  The operator survey will be administered after the 
last study patients has exited the study. 
 
Statistical Plan: This is a pilot study and therefore, the data will be used to assess feasibility, adverse events, 
time, cost, etc. in an attempt to predict an appropriate sample size and optimize design prior to a larger-scale 
study. 
Data Monitoring to Ensure Safety: This study is not considered greater than minimal risk.  
Since the rTMS system is a 510(k)-cleared HORIZON system, any adverse event will be reported to MAUDE.  
When informed of an adverse event involving a cleared device in the US, Magstim will investigate and if , 
report the event in accordance with QP027 – Incident Reporting Procedure and the Medical Device Reporting 
(MDR) regulation (21 CFR 803). Furthermore, Magstim also has in place a Quality Procedure to initiate field 
corrections should this be required QP059 Field (Safety) Corrective Action Procedure. If an adverse event 
occurs related to the navigation system, a non-510(k)-cleared StimGuide, that adverse event will be reported via 
the IDE program.  
Additionally, any serious adverse event, this will be reported to the IRB immediately (within 24 hours).  Any 
recommendations will be implemented. 
Data Storage and Confidentiality:  Information and clinical data collected as part of the study will be labeled 
with participant initials and a study number; information (without the name) will be entered into a computer 
database and locked file cabinet in the study site coordinator, Nicole Krummel’s office.  The record linking the 
name to the MRN study ID number will be kept indefinitely at the MRN in a confidential manner in case the 
participant needs future access to their data.  Only study staff will have access to the study information. All 
other data will be stored for six years and then be destroyed. Access to the data will be limited to the PIXXXX 
 
Identification information and data collected from each participant will be entered into the Magstim Insight 
online data warehouse. 
 
Data relating to the coils position during treatment is recorded by the Magstim StimGuide system. 
 
Participation in this study is completely voluntary. Each participant has the right to choose not to participate or 
to withdraw participation at any point in this study without affecting his/her health care or other services to 
which they are entitled.  
 
Confidentiality: The screening for ineligible candidates will be destroyed after the project's completion (12 
months). The document containing contact/personal information for enrolled participants will be kept on a 
password-protected computer. 
 

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Direct identifiers such as name, address, and telephone number will be maintained in a password-protected 
computer in the locked office of the principal investigator and kept for six years in accordance with HIPAA.  If 
new information is obtained about safety during the course of this study, participants will be contacted for re-
consent.   
 
The clinical data will be stripped of all identifying information. This detail will be thoroughly covered during 
the consent process.  
 
Privacy of Subject: Potential subjects will be approached by research personnel in a private room in the clinic.  
They will be assured that only research personnel will have access to the information provided.  All information 
provided will be maintained in a secured research area for which only study staff have access.   
 
All nTMS appointments are conducted within the clinic.  The door is kept closed during experiment 
appointments.  Because normal rTMS treatments are also conducted at this clinic and the participants are 
already receiving those treatments as part of their standard of care, there would be no obvious indication that the 
individual is a part of the research study.  All other standard privacy measures (associated with standard of care 
in the clinic) will be maintained.   
 
 
11) Background and Experience of Investigators 
 
PI CV/resume and Human Subjects Protection training certificate is attached 
Research Staff: most current human subjects protection training certificate is attached. 
 
The Principal Investigator: As PI in this project, Dr. Lothar Krinke PhD will be responsible for supervising and 
coordinating all aspects of the research. Dr. Krinke has the expertise and experience to perform this role well in 
the proposed research. 
Research Coordinator:  Nicole Krummel will serve as the research coordinator and will be responsible for the 
day-to-day coordination of the trial.  Nicole will ensure compliance with regulatory and training requirements 
for any other research staff.  She is experienced at recruiting research subjects and ensuring their confidential 
participation.  The PI will directly oversee the research coordinator. 
Study Staff: 
Study Site:  2 Clinics:  This facility contains all the TMS, rTMS and Neuronavigation devices necessary for 
successful completion of the study.  It is also a private location ensuring subject privacy. 
 
 
12) Instruments 
Device data collection will be managed electronically as noted. Consent data and simple survey tools will be 
managed in accordance with confidentiality standards noted earlier in the document.  
 
 
13) APPROVAL FORM FROM PARTICIPATING ORIGINATING INSTITUTIONS (where applicable) 
 
Not applicable 
 
14) Devices 

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Medical Devices:  Please respond to all questions in this section.  
A Horizon Performance System device and StimGuide TMS Neuronavigation System are used in the study 
(The Magstim Company Limited, Spring Gardens, Whitland, Carmarthenshire, SA34 0HR, UK).   
 
Has an Investigational Device Exemption (IDE) application been submitted to the FDA?  
No an IDE has not been submitted to the FDA 
 
The device meets the requirements for an abbreviated IDE if all of the following are TRUE. Please articulate 
responses to all of the following:  
The device is not banned. TRUE.  The Horizon Performance System is FDA-approved for the treatment of 
medication-resistant depression under K180907.   
The device is not a significant risk device.  TRUE.   Evidence-based guidelines have been published on the safe 
use of rTMS as a therapeutic device (Lefaucheur, et al., 2014) 
 
The sponsor or investigator will label the device in accordance with 21CFR812.5.  TRUE.  The devices are 
labeled accordingly. 
 
The sponsor or investigator will comply with the requirements of 21CFR812.46 with respect to monitoring 
investigations.  TRUE.  The investigator will comply with the requirements regarding monitoring of 
investigations. 
 
The sponsor or investigator will maintain research records required under 21CFR812.140 (b) and (5) and 
make the reports required under 21CFR812.150 (b) (1) through (3) and (5) through (10).  TRUE.  The 
investigator will maintain research records as described. 
 
The sponsor or investigator will ensure that participating investigators maintain the records required by 
21CFR812.140 (a)(3)(i) and make the reports required under 21CFR812.150(a) (1) (2) (5) and (7).  TRUE.   
The investigator will ensure that all study staff and investigators maintain records as described above. 
 
The sponsor or investigator will comply with the prohibitions in 21CFR812.7 against promotion and other 
practices.  TRUE.  The investigator will comply with all prohibitions against promotion and other practices. 
 
Please complete the section below to determine if an IDE is required:  
Is the device FDA-approved for marketing and is it being used or investigated in accordance with its labeling.- 
-The Horizon Performance System has been cleared by the FDA for the treatment of Major Depressive Disorder 
in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication in 
the current episode. 
-The StimGuide TMS Neuronavigation System is not cleared by the FDA. 
 
Is the device a diagnostic device?  
No. 
Is the device undergoing consumer preference testing, testing of a modification, or testing of a combination of 
two or more devices in commercial distribution?  
No. 

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Is the device testing for the purpose of determining safety and effectiveness? 
No.  This is a feasibility study. 
 
Is the device a custom device as defined in 21CFR812.3(b)? 
No. 
 
Provide a detailed description of device storage and accountability procedures:  
Devices for the study will be sent from Magstim headquarters in Whitland, Wales to US Headquarters in White 
Bear Lake, MN only upon approval from the IRB.  
 
Who will have access to the device?   
The access to the device will be limited to the study staff who are trained in the safe operation of these devices.  
 
What security safeguards are in place to ensure proper accountability, access, and storage of the device?   
The devices are stored with the locked at the Georgia Behavioral Health office at Sandy Springs, 5775 
Peachtree Dunwoody Road in Sandy Springs, Georgia, Suite 200, Atlanta, GA 30432.  In addition to the 
security at the clinic, the specific room in which the devices are maintained is also locked when not in use.  
Only the study staff have access to the room.  The PI assumes accountability for the devices and their proper 
use. 
 
If the device is experimental, will it be labeled “Investigational Use Only”?   
Yes. 
 
Who will be responsible for: 
Device accountability.  The PI. 
Labeling/ dispensing. The PI. 
State the qualifications of this person.CV Attached 
 
Describe how the investigational device is controlled, and how accidental use outside of approved research will 
be avoided. 
The equipment is locked in the clinic.  Only the study staff have access to the locked rooms.  The software 
program used to run the equipment is password protected. 
Non-Significant Risk Determination Section 
Is the device intended as an implant (≥30 days)? 
No. 
Is the device for use supporting or sustaining human life? 
No. 
Is the device for a use of substantial importance in diagnosing, curing, mitigating or treating disease or 
preventing impairment of human health? 
No. This protocol is an exploratory study to determine whether coil positioning via nTMS can be achieved 
during and throughout treatment sessions. 
Does the use of the device present a potential for serious risk to health, safety or welfare of the subjects? 
The use of the device does not pose the potential for serious risk to health, safety or welfare of subjects.  The 
protocol parameters are well within the bounds determined by the FDA for approval for the treatment of 

Precise Coil  Positioning in nTMS in MDD 
 
 
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14 
 
depression and migraine.  The only difference is the addition of a navigation system to optimize target 
localization and adherence. 
 
Explain why the use of the device in this study poses non-significant risk, and attach any other supporting 
information. In addition, explain whether the sponsor, the FDA or any other oversight organization has already 
made a risk determination for the device. 
The device poses a non-significant risk to participants given that the parameters used are well within the FDA-
approved rTMS therapy for the treatment of depression.  The exclusion and inclusion criteria also ensure an 
added level of safety in using this device. 
 
 
15) References 
 
1.Balslev, D., Braet, W., McAllister, C., & Miall, R. C. (2007). Inter-individual variability in optimal current 
direction for transcranial magnetic stimulation of the motor cortex. Journal of neuroscience methods, 162(1-2), 
309-313. 
 
2.Brasil-Neto, J. P., Cohen, L. G., Panizza, M., Nilsson, J., Roth, B. J., & Hallett, M. (1992). Optimal focal 
transcranial magnetic activation of the human motor cortex: effects of coil orientation, shape of the induced 
current pulse, and stimulus intensity. Journal of clinical neurophysiology: official publication of the American 
Electroencephalographic Society, 9(1), 132-136. 
 
3. Janssen, A. M., Oostendorp, T. F., & Stegeman, D. F. (2015). The coil orientation dependency of the electric 
field induced by TMS for M1 and other brain areas. Journal of neuroengineering and rehabilitation, 12(1), 47. 
 
4.Lefaucheur, J.P., Andre-Obadia, N., Antal, A., Ayache, S., Baeken, C., Benninger, D.H., Cantello R.M., 
Cincotta, M., deCarvalho, M., Ridder, D.D., Devanne, H., DiLazzaro, V., Filipovic, S.R., Hummel, F.C., 
Jaaskelainen, S.K., Kimiskidis, V.K., Kock, G., Langguth, B., Nyffeler, T., Oliviero, A., Padberg, F., Poulet, E., 
Rossi, S., Rossini, P.M. Rothwell, J.C., Schonfeldt-Lecuona, C., Siebner, H.R., Slotema, C.W., Stagg, C.J., 
Valls-Sole, J., Ziemann, U., Paulus, W., Garcia-Larrea, L. (2014). Evidence-based guidelines on the therapeutic 
use of repetitive transcranial magnetic stimulation (rTMS).  Clinical Neurophysiology, 125(11), 2150-2206. 
5.Lefaucheur, J. P., Brugieres, P., Ménard-Lefaucheur, 
 
 
 
 

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 INFORMED CONSENT TO PARTICIPATE IN CLINICAL RESEARCH STUDY 
 
Title: Precise Coil Positioning in Navigated Transcranial Magnetic Stimulation (nTMS) in Medication- 
Resistant Major Depressive Disorder (MDD): A Feasibility Study 
 
Sponsor: 
 
 
 
Magstim, Inc. 
  
 
 
 
 
Protocol Number: 
  
 
MGS-2018-SS 
 
Principal Investigator:  
 
Dr. Lothar Krinke, PhD, Magstim, Inc. 
 
 
 
 
 
 
Georgia Behavioral Health Professionals 
 
 
 
 
 
5775 Peachtree Dunwoody Rd. 
 
 
 
 
 
Atlanta, GA 30342  
 
 
 
 
 
 
Georgia Behavioral Health Professionals 
 
 
 
 
 
2150 Peachford Road, Suite H  
 
 
 
 
 
Dunwoody, GA 30338 
 
 
 
  
24-Hour Telephone Number:   
(404) 256-2795 
 
 
This is a research study.  You are being asked to take part in this study because your physician has referred you 
for repetitive Transcranial Magnetic Stimulation (rTMS) as a treatment for Major Depressive Disorder (MDD).  
This study includes only individuals who voluntarily choose to participate.  Please take your time to make your 
decision.  Discuss it in confidence with your regular doctor, friends and family if you want.  Be sure to ask 
questions about anything you do not understand in this document. 
 
WHAT IS THIS STUDY ABOUT? 

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The purpose of this study is to evaluate the feasibility of adding a navigational system to traditional 
rTMS (referred to in the study as nTMS) to establish and maintain precise coil positioning (contact, 
rotation, and tilt) and consistent brain region targeting throughout a nTMS treatment session and in 
subsequent nTMS sessions.  The study device is investigational, which means that it is not approved 
by the Food and Drug Administration (FDA). 
 
This research is being done because there is evidence that variability in patient response to rTMS is due to 
inconsistent placement and positioning of the coil during treatment.  Therefore, the goal of this research is to 
confirm that the addition of navigation to rTMS is feasible; this would aid in consistent application of the 
treatment.  
 
If you participate in this study, you will receive navigation as part of your rTMS treatment (for 30 of your total 
treatments). Your rTMS treatment is standard of care. The navigation (nTMS) is the investigational procedure. 
Please ask the study staff if you have any questions about the difference.  
 
 
FINANCIAL DISCLOSRE: 
Dr. Krinke, the investigator, owns shares in the company and is the CEO. Please ask if you have any 
questions about this conflict of interest. 
 
HOW LONG IS THIS STUDY? HOW MANY OTHER PEOPLE WILL BE IN THIS STUDY?  
About 25 people will take part in this study.  You will be in the study for about one week, which involves 
attendance at only your normal appointments. You will not need any additional appointments as a result of 
taking part in this research. The first appointment will take about an hour and the follow up sessions will take 
approximately 45 minutes.  
 
WHAT IF NEW INFORMATION BECOMES AVAILABLE? 
If new information in relation to the study device becomes available, that may be relevant to the purpose and 
safety of the study and your willingness to continue participation in this study, you will be informed by the 
study staff.   
 
WHAT WILL HAPPEN DURING THE STUDY? 
If you agree to take part in this research study, you will be required to sign this informed consent form 
before any procedures take place.   
 
STUDY PROCEDURES:  
During the screening and if you qualify and continue, during the study the following procedures will 
occur:   
• Questions asked about how you are feeling and current medications and medical conditions 
• Questions about your past health, possibly including requests for your medical records 
 

Precise Coil  Positioning in nTMS in MDD 
 
 
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17 
 
The study doctor will talk to you and give you a list of the things you must do to participate, such as: 
• Use of contraception by female participants during the five-treatment study period. 
• Questions asked about how you are feeling and current medications and medical conditions 
 
At your first appointment, the device will deliver pulses of stimulating energy on the left side of your 
head in order to stimulate a muscle twitch in your right hand. This will be repeated 10 times in order to 
accurately locate the best position for the treatment application on your scalp. The actual treatment 
position is forward of the motor stimulation location (in an area called the pre-frontal cortex which is 
altered in major depression). So, the coil will be moved forward to a position based on the motor spot 
for actual treatment once the optimal strength of impulse from the coil and precise location of the 
motor spot is determined and the treatment position is determined 
 
This treatment position will then be saved in the navigation system and used for the this initial and the 
subsequent 29 appointments (a total of 30 of your treatments).  
 
Please tell your regular health care providers and any emergency care providers that you are 
participating in this research study. 
 
WHAT ARE THE RISKS AND DISCOMFORTS OF PARTICIPATING IN THIS STUDY? 
The study device has been associated with the following side effects:  
 
The stimulation parameters for nTMS (traditional rTMS) are safe and have been used on many 
people to study the brain over recent decades.  Most people do not find the stimulation painful, but 
occasionally occasional side effects include:  
• strong contractions of scalp muscles can cause some discomfort and headache.   
 
Some patients have experienced dizziness and a tingling sensation. If you find the procedure too 
uncomfortable, you may discontinue at any time.  Headaches usually go away promptly with 
nonprescription medication. 
   
The noise of the magnet may affect hearing, so earplugs are worn during nTMS.   
 
Magnetic stimulation will not be performed in people who have pacemakers, implanted pumps or 
stimulators, metal objects inside the eye or skull, or who have a history or risk of seizure.  This study 
uses a stimulation protocol that has been previously used on patients.  The risk of inducing a seizure 
with nTMS is considered very low (less than 1%) and similar to the incidence of seizures associated 
with antidepressant medications.   
 
Safety studies using TMS in patients with neurological disorders have demonstrated no permanence.   
 
Risks to a fetus are not known.   
 
It is expected that nTMS (the addition of a navigational system to rTMS) offers no additional risks to 
patients. 
 

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18 
 
There may be risks to being in this study that we cannot predict.   
 
You should discuss these risks with the doctor. Many side effects go away shortly after the treatment 
stops the study drug is stopped. These risks are expected to be reversible for the most part, with the 
exception of hearing damage (prevented by the ear plugs), loss of confidentiality (safeguards are in 
place to protect your data), and seizure (you must inform the study doctor if you have any previous 
history of seizures).   
 
Discomfort and headache can be treated with over-the-counter medication.   Personnel will be trained 
to monitor for risks and to remove individuals from the study for whom participation appears to be 
producing unexpected negative reactions. 
  
Side effects occurring during the trial can be treated by the study doctor, if this is deemed necessary. 
It is important that you inform the study doctor any unusual or unpleasant effects which you should 
feel.   
 
Are there pregnancy risks? 
If you are a woman who can get pregnant, you will be required to use adequate methods of birth 
control.  If you are unsure of these methods, please discuss them with your study doctor. You cannot 
participate in this study if you are pregnant.  Since no adequate and well-controlled studies of the 
study device in pregnant women have been performed you should not become pregnant while 
participating in this study. If you think you are pregnant during the study, you must tell the study 
coordinator immediately. Risks to a fetus from TMS are not known. It is suggested that female 
participants of child bearing age take contraception for the duration they are involved in the study, but 
such use will not be confirmed. If you become pregnant, you will have to leave the study.  
 
For more information about risks and side effects, ask the study doctor.  
 
ARE THERE BENEFITS TO TAKING PART IN THE STUDY? 
If you agree to take part in this study, there may or may not be direct medical benefit to you. 
Information learned from this study may benefit others in the future. 
 
There is the possibility of nTMS directly improving symptoms related to medication-resistant MDD.   
 
Improved consistency and optimization of treatment delivery is expected to provide reproducible 
outcomes with little variability, thus improving predictability of patient outcomes. 
 
The knowledge gained in this proposed research could lead to an optimization of nTMS delivery and 
improved care of patients with medication-resistant MDD.  In this case, improved quality of life could 
be expected with the successful and effective development of nTMS therapies. 
 
WHAT, IF ANY, ARE THE ALTERNATIVES TO PARTICIPATING IN THIS STUDY? 
This study is not designed to diagnose, treat or prevent any disease.  Your alternative is to not 
participate.  If you choose not to participate in the study, you will still receive rTMS therapy (as 

Precise Coil  Positioning in nTMS in MDD 
 
 
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19 
 
recommended by your physician); you simply will not receive the use of the navigational system 
during rTMS. 
 
CONFIDENTIALITY 
Your personal information will be kept confidential to the extent permitted by law. We cannot guarantee 
absolute confidentiality.  By signing this document, you give permission to access your medical records, 
including after withdrawal, for data verification purposes.   
 
Organizations that may inspect and/or copy your research records for quality assurance and data analysis 
include groups such as: 
• The study staff and other researchers involved in the study 
• Magstim or those who work for or represent Magstim 
• The U.S. Food and Drug Administration (FDA)  
• Aspire Independent Review Board (IRB) 
 
The results from the study may be published for scientific purposes, but your identity will be kept confidential. 
 
In the rare event that your information is required to be disclosed by law to another entity, privacy 
laws may not apply, and neither the Sponsor nor Aspire IRB can protect your information. 
 
WHAT ARE THE COSTS? 
There are no additional costs associated with being in this study.  You are responsible for your regular health 
care while in this study.  You will not have to pay for the use of the navigation device during your study visits.   
 
INVESTIGATOR PAYMENT                                        
 
The Prinicipal Investigator is the CEO of Magstim, Inc. As CEO, he receives salary from Magstim. 
The study site will be receiving no payment for participation in the study. The study site coordinator 
will receive regular compensation from Georgia Behavioral Health professionals as due course for her 
role in the delivery of patient care during the study.  
 
WILL YOU BE COMPENSATED DURING THE STUDY? 
You will not be compensated for participating in and completing this research study. 
 
WHAT HAPPENS IF YOU HAVE COMPLICATIONS OR ARE INJURED? 
If you have serious side effects, complications or are injured because of participating in this study, 
please contact the study doctor promptly.  If this research activity results in an injury, treatment will be 
available, including first aid emergency treatment, and follow-up care as needed.  Care for such 
injuries will be billed in the ordinary manner, to you or your insurance company. No commitment is 
made by the study site to provide free medical care or money for injuries to participants in this study.  
 

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YOUR RIGHTS AS A RESEARCH SUBJECT 
Taking part in this study is voluntary.  You may choose not to take part or may leave the study at any time.  
Leaving the study will not result in any penalty or loss of benefits to which you are entitled.  However, if you 
decide to stop participating in the study, we encourage you to talk to the study doctor and your regular doctor 
first.   
 
YOUR RESPONSIBILITIES AS A RESEARCH SUBJECT 
You will be asked to adhere to all instructions issued by the study doctor and other study staff. 
Furthermore, you should answer all asked questions truthfully.  
 
Should you not comply with instructions, the study doctor may stop your study participation. Your 
study doctor may also exclude you from this trial if he/she deems it beneficial for your health, or if you 
do not meet the study requirements.   Your participation in this study may be ended if the Sponsor 
stops the study for any reason.    
 
WHOM TO CALL IF YOU HAVE QUESTIONS 
For questions, concerns or complaints or information about the study or a research-related injury, 
contact the study doctor at the number on page 1. 
 
This research is being overseen by Aspire Independent Review Board (“IRB”). An IRB is a group of 
people who perform independent review of research studies. You may talk to them at 1-877-366-5414 
(toll free) if: 
• You have questions, concerns, or complaints that are not being answered by the research 
team. 
• You are not getting answers from the research team. 
• You cannot reach the research team. 
• You want to talk to someone else about the research. 
• You have questions about your rights as a research subject. 
 
Although Aspire IRB has approved the information provided in this informed consent form and has 
granted approval for the investigator to conduct the study this does not mean Aspire has approved 
your being part of the study.  You need to read the information in this informed consent form for 
yourself and decide whether or not you want to be in this study. 
 
 

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21 
 
SIGNATURE AND CONSENT TO BE IN THE STUDY 
Your signature below means that you have read the above information about this study and have had 
a chance to ask questions to help you understand what you will be expected to do and that you agree 
to participate in this study.  Your signature also means that you have had all your questions answered 
to your satisfaction and that you have been told that you can change your mind later if you want to.  
You will be given a signed and dated copy of this agreement.  By signing this consent form, you are 
not giving up any of your legal rights. 
 
 
_______________________________________________ __________/________ 
SIGNATURE OF SUBJECT 
 
 
 
 
 
DATE  
 
 
 
________________________________________________ 
PRINTED NAME OF SUBJECT 
 
 
I confirm that a copy of this consent form has been given to this person to read and that this person 
has been told about the study.  The contents of the consent form describing the study has been 
discussed with this person and I have made every effort to answer all questions to his or her 
satisfaction.  I have watched this person sign the consent form. 
 
 
_______________________________________________ __________/________ 
SIGNATURE OF PERSON OBTAINING CONSENT  
 
DATE  
 
 
 
_______________________________________________ 
PRINTED NAME OF PERSON OBTAINING CONSENT 
 
 
 I., Wendling, S., Pommier, M., & Bellivier, F. (2007). The value of navigation-guided rTMS for the treatment 
of depression: an illustrative case. Neurophysiologie Clinique/Clinical Neurophysiology, 37(4), 265-271. 
 
6.Nauczyciel, C., Hellier, P., Morandi, X., Blestel, S., Drapier, D., Ferre, J. C., ... & Millet, B. (2011). 
Assessment of standard coil positioning in transcranial magnetic stimulation in depression. Psychiatry 
research, 186(2-3), 232-238. 
 
7.Opitz, A., Fox, M. D., Craddock, R. C., Colcombe, S., & Milham, M. P. (2016). An integrated framework for 
targeting functional networks via transcranial magnetic stimulation. Neuroimage, 127, 86-96. 
 
8.Opitz, A., Windhoff, M., Heidemann, R. M., Turner, R., & Thielscher, A. (2011). How the brain tissue shapes 
the electric field induced by transcranial magnetic stimulation. Neuroimage, 58(3), 849-859. 
 
9.Richter, L., Neumann, G., Oung, S., Schweikard, A., & Trillenberg, P. (2013). Optimal coil orientation for 
transcranial magnetic stimulation. PLoS One, 8(4), e60358. 

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10.Ruohonen, J., & Karhu, J. (2010). Navigated transcranial magnetic stimulation. Neurophysiologie 
clinique/Clinical neurophysiology, 40(1), 7-17. 
 
11.Rusjan, P. M., Barr, M. S., Farzan, F., Arenovich, T., Maller, J. J., Fitzgerald, P. B., & Daskalakis, Z. J. 
(2010). Optimal transcranial magnetic stimulation coil placement for targeting the dorsolateral prefrontal cortex 
using novel magnetic resonance image‐guided neuronavigation. Human brain mapping, 31(11), 1643-1652. 
 
12.Sack, A. T., Cohen Kadosh, R., Schuhmann, T., Moerel, M., Walsh, V., & Goebel, R. (2009). Optimizing 
functional accuracy of TMS in cognitive studies: a comparison of methods. Journal of cognitive 
neuroscience, 21(2), 207-221. 
 
13.Schmidt, S., Cichy, R. M., Kraft, A., Brocke, J., Irlbacher, K., & Brandt, S. A. (2009). An initial transient-
state and reliable measures of corticospinal excitability in TMS studies. Clinical Neurophysiology, 120(5), 987-
993. 
 
14.Sparing, R., Hesse, M. D., & Fink, G. R. (2010). Neuronavigation for transcranial magnetic stimulation 
(TMS): where we are and where we are going. Cortex, 46(1), 118-120. 
 
15.Thielscher, A., Opitz, A., & Windhoff, M. (2011). Impact of the gyral geometry on the electric field induced 
by transcranial magnetic stimulation. Neuroimage, 54(1), 234-243.