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Transcranial magnetic stimulation: A historical evaluation and future
prognosis of therapeutically relevant ethical concerns
Article  in  Journal of medical ethics · March 2011
DOI: 10.1136/jme.2010.039966 · Source: PubMed

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 Clinical ethics

Transcranial magnetic stimulation: a historical
evaluation and future prognosis of therapeutically
relevant ethical concerns
Jared C Horvath,1 Jennifer M Perez,1 Lachlan Forrow,2 Felipe Fregni,3
Alvaro Pascual-Leone1
1

Correspondence to
Mr J C Horvath, Berenson-Allen
Center for Noninvasive Brain
Stimulation, Beth Israel
Deaconess Medical Center and
Harvard Medical School, 330
Brookline Ave KS-158, Boston,
MA 02215, USA;
jhorvat2@bidmc.harvard.edu

ABSTRACT
Transcranial Magnetic Stimulation (TMS) is
a non-invasive neurostimulatory and neuromodulatory
technique increasingly used in clinical and research
practices around the world. Historically, the ethical
considerations guiding the therapeutic practice of TMS
were largely concerned with aspects of subject safety in
clinical trials. While safety remains of paramount
importance, the recent US Food and Drug Administration
approval of the Neuronetics NeuroStar TMS device for
the treatment of specific medication-resistant depression
has raised a number of additional ethical concerns,
including marketing, off-label use and technician
certification. This article provides an overview of the
history of TMS and highlights the ethical questions that
are likely arise as the therapeutic use of TMS continues
to expand.

Received 1 September 2010
Revised 14 October 2010
Accepted 31 October 2010

INTRODUCTION

Berenson-Allen Center for
Noninvasive Brain Stimulation,
Beth Israel Deaconess Medical
Center and Harvard Medical
School, Boston, USA
2
Beth Israel Deaconess Medical
Center and Harvard Medical
School, Boston, USA
3
Laboratory of Neuromodulation,
Spaulding Rehabilitation
Hospital, Boston, USA

Transcranial Magnetic Stimulation (TMS) is a noninvasive neurostimulatory and neuromodulatory
technique increasingly used in clinical and research
practices around the world. Although originally
developed as a diagnostic tool, TMS can transiently
or lastingly modulate cortical excitability (either
increasing or decreasing it) via the application of
localised magnetic field pulses. This and other
neurobiological effects can be leveraged for therapeutic applications in neurology, psychiatry and
rehabilitation. Historically, the ethical considerations guiding the therapeutic practice of TMS
were largely concerned with aspects of subject
safety in clinical trials. While safety remains of
paramount importance, the recent US Food and
Drug Administration (FDA) approval of the
Neuronetics Inc. (Malvern, PA, USA) NeuroStar
TMS device for the treatment of specific medication-resistant depression has raised a number of
additional ethical concerns. Some of these are
derivatives of previously identified issues, but
others, such as marketing, off-label use and technician certification, have not been well explored. As
the therapeutic potential for TMS expands to
include a wide range of neuropsychiatric conditions, including those where patients have few
alternative treatment options, ethical issues are
likely to continue to grow rapidly. This article
provides an overview of the historical, present and
future ethical issues associated with the therapeutic
use of TMS and discusses ways in which these
issues might be addressed.
Horvath JC, Perez JM, Forrow L, et al. J Med Ethics (2010). doi:10.1136/jme.2010.039966

A TMS PRIMER
TMS is a neurophysiologic technique that allows
for non-invasive stimulation of the human brain.1 2
Introduced approximately 25 years ago, TMS can
be combined with various brain mapping methodologies (eg, electroencephalography, positron emission tomography or functional MRI), to study
intra-cortical excitation and inhibition balance,
cortico-cortical and cortico-subcortical connectivity
and interactions, and brain plasticity. Repetitive
transcranial magnetic stimulation (rTMS) has been
shown to transiently disrupt neuronal activity for
periods exceeding stimulation duration. This
modulated brain activity may prove useful in both
the determination of causal relationships between
focal brain activity and emergent behaviour as well
as in the treatment of numerous neurological and
psychiatric illnesses.
The physical principles of TMS were discovered
in 1881 by English physicist Michael Faraday, who
observed that a pulse of electric current passing
through a wire coil generates a magnetic field. The
rate of change of this magnetic field determines the
induction of a secondary current in a nearby
conductor. During TMS, the stimulating coil is held
over a subject’s head and produces an electric
current in the subject’s brain via electro-magnetic
induction. This current in turn depolarises neurons
and can generate various physiological and behavioural effects depending on the targeted brain area.
Because magnetic fields can pass the skull with
almost no resistance, TMS can induce relatively
large currents in targeted cortical areas.
The design of magnetic stimulators is relatively
straightforward, consisting of a main unit and
a stimulating coil. The main unit is composed of
a charging system, one or more energy storage
capacitors, a discharge switch and circuitry used to
control pulse-shape, energy recovery and other
variable functions. The factors essential to the
effectiveness of a magnetic stimulator are the speed
of magnetic field rise time and the maximisation of
the peak coil energy. Therefore, large energy storage
capacitors and efficient energy transfer from the
capacitor to the coil are important (typically energy
storage capacity is around 2000J with a 500J
transfer from the capacitor to the stimulating coil
in less than 100 microseconds via a thyristor, an
electrical device capable of switching large currents
in a short time). The peak discharge current needs
to be several thousand amperes in order to induce
currents in the brain of sufficient magnitude to
depolarise neural elements (about 10 mA/cm2).
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 Clinical ethics
Figure 1 A timeline of notable uses
and discoveries in electrical and
magnetic stimulation leading up to the
development of the first reliable
magnetic brain stimulator in
1984e1985.

The precise mechanisms underlying the neural effects of TMS
are largely unknown.1 Currents induced by TMS typically flow
parallel to the plane of the stimulation coil. Therefore, in
contrast with electrical cortical stimulation, TMS preferentially
activates neural elements oriented horizontally to the brain
surface. However, exactly which neural elements are activated
remains unclear and, in fact, might vary across different brain
regions and different subjects. Recent animal studies have begun
probing these important mechanistic questions.3e5

PRE-HISTORY OF TMS: AN ETHICAL PERSPECTIVE
The field of electrophysiology was born in 1771 with the
discovery of bioelectricity by the Italian physician Luigi Galvani.
Soon thereafter, Galvani’s nephew, Giovanni Aldini, began
touring the European countryside promoting his belief that
bioelectricity could unlock the secrets to dead tissue reanimation. To prove his theory, Aldini staged macabre public
demonstrations during which, via the application of direct
electric current, he induced muscular contractions in dead
animals, and, in 1803, the lifeless body of executed convict

Figure 2 A timeline of the ethical
progression of TMS, highlighting some
of the important diagnostic, research,
and therapeutic developments in the
field.

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Horvath JC, Perez JM, Forrow L, et al. J Med Ethics (2010). doi:10.1136/jme.2010.039966

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Figure 3

The compiling nature of ethical considerations.

George Forster.6 Through this incident, several important ethical
considerations began to emerge. Scientific advancements may
harness great potential, but this does not exempt scientists from
asking whether such potentialities should be explored. How
might a system of ethics be maintained that serves to protect
research subjects and to protect the integrity of and respect for
both science and mankind?
In 1874, scientific exploration of bioelectricity within muscles
and nerve fibres reached an apex when American physician
Robert Bartholow applied electrical current to the exposed dura
of Cincinnati housewife Mary Rafferty. After successful induction of slight muscular twitches, Bartholow increased the
applied current until distress, convulsion and eventually, coma
were reported.7 8 Rafferty died 72 h later. This incident highlights a dilemma pervasive throughout medical science: in the
quest for knowledge, too often experimenters can become blind
to the potentially deleterious effects of their actions. Overzealousness often clouds typically sound judgement, illustrating
the importance of and need for outside, independent risk-tobenefit assessment. Today such assessment is provided by the
Institutional Review Boards. However, the responsibility for the
proper conduct and sound ethical grounding of a given experiment ultimately remains in the hands of the investigators.
The development of electroconvulsive therapy (ECT) in 1937
ushered the field of brain stimulation into the modern ‘medical
device’ age. Developed by Italian physicians Cerletti and Bini,
ECT was intended to treat the manic symptoms of schizophrenic inpatients. However, as the popularity of the device
grew, practitioners quickly elevated ECT to the status of
psychiatric panacea. This gross overuse led to a plethora of
serious adverse psychological and physical side effects, thereby
creating a strong negative public attitude towards the therapy.
In 1976, in reaction to public backlash against ECT and similar
treatments, the FDA assumed regulatory control over all
emerging medical devices. Interestingly, ECT (along with several
other brain stimulation devices on the market prior to governmental intercession) today remains out of the purview of FDA
regulation. Although ECT is considered by many to be a highly
effective treatment for depression,9 its use remains impacted by
unfavourable public opinion. An important charge for the FDA
is to oversee the cautious development and implementation of
novel therapies so as to assure efficacy and preclude preventable
complications due to practitioner misuse that may substantiate
a stigmatisation that can limit their acceptance by patients who
could potentially benefit from their use (as exampled by ECT
misuse in the 40s and 50s).
In 1972, another incident in the annals of brain-stimulation
raised relevant therapeutic ethical concerns. Building upon Jose
Delgado’s work with behaviour modification in animals via
deep-brain electrical stimulation, two doctors from Tulane

University attempted to ‘cure’ a patient of his homosexuality.
Combining electrical stimulation of patient B-19’s septum with
forced heterosexual interactions (provided by a female prostitute), Drs Moan and Heath reported a 10-month eradication of
homosexual behaviour.10 Here we see what many modern
practitioners consider the darkest hour for brain stimulation.
When contemplating this event, it is important to remember
that our ethical perception is inextricably linked to the often
shifting social definitions of the core concepts of health and
disease. It is important, therefore, to remain cognisant of the
sociological factors that may colour our opinion and, whenever
possible, attempt to remain pluralistic when constructing any
ethical framework.

THE EVOLUTION OF TMS
The first reliable transcranial magnetic brain stimulator was
developed by Anthony Barker and colleagues and was introduced
to the world in 1984e1985. Since that time, TMS has gone
through several major stages of development, each defined by
unique achievements and concomitant considerations.

Establishing diagnostic utility
In the late 1970s, a handful of clinicians began using transcranial
electric stimulation to diagnostically measure motor conduction
time in patients suffering from multiple sclerosis. This technique, although efficacious, was limited by the extreme
discomfort it elicited in patients and subjects. TMS provided
a propitious solution to this problem: via single-pulse stimulation, practitioners could perform similar motor conduction time
tests in a much safer, far less-painful manner.11 Over the ensuing
years, physician interest in TMS remained largely within the
realm of diagnostics.
The major ethical considerations during this first stage of
TMS concerned overall device safety. Because TMS originated as
a diagnostic and investigational device, not many animal models
were developed to study short or long-term effects. As such,
TMS practitioners promoted the field rather cautiously (as
compared with ECT). A keen focus was maintained on patient
reported side-effects, especially those related to or resembling
seizure activity.

Exploring therapeutic possibilities
In 1991 the journal Neurology published an article by Dr Alvaro
Pascual-Leone et al, entitled Induction of speech arrest and counting
errors with rapid-rate transcranial magnetic stimulation.12 This paper
was one of the first to use an rTMS paradigm. Qualitatively
different from previous single-pulse methodologies, rTMS
allowed for a more sustained neurological intervention. This
new paradigm opened the door for researchers to conduct more
nuanced studies of cognitive function and neural interaction. In
1994, Pascual-Leone et al reported that rTMS could generate
lasting cortical effects that remained after the cessation of
stimulation (lasting between 3 and 4 min).13 This ability to
induce sustained physiological and cognitive effects made rTMS
a tool conducive to the field of therapeutic medicine.
The expansion of TMS from single-pulse indication to repetitive-pulse intervention greatly increased the number of TMS
ethical concerns. In addition to lasting matters of safety, practitioners and clinicians were suddenly confronted with innumerous clinical considerations, including which disorders might
be responsive to stimulatory treatment, issues of patient
response patterns, and potential interactions between rTMS and
medication. Even as labs elsewhere continued to generate ever
increasing numbers of active rTMS studies, practitioners

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undertook the daunting but necessary task of conducting Phase I
research.14e16

The clinical push
One of the first proof-of-principle TMS studies specifically
focused on a therapeutic application of repetitive TMS in
a neuropsychiatric disease was published by Kolbinger et al,
who examined the effects of rTMS on 15 patients suffering
from drug-resistant depression.17 Of the 10 patients receiving
non-sham stimulation, all showed significant improvement.
This transition to proof-of-principle studies did not eradicate
previous ethical concerns; rather, it added new considerations to
the ever relevant previous concerns. The inclusion of lengthy
and repetitive patient treatment protocols (as opposed to transitory research protocols) raised questions about the long-term
cortical effects of TMS. The apprehension felt by many clinicians and scientists was reflected in a letter entitled Shocking
Safety Concerns,18 published several months after a successful
proof-of-principle trial conducted by Pascual-Leone et al.19 In
this missive, Browne gave voice to the fear that history might
repeat itself in the later phase realisation of a treatment’s
detrimental effects (eg, prolonged use of Vioxx, a drug prescribed
for the acute treatment of pain, was found to increase the risk of
heart-disease only after the drug had been widely used).20 Due in
large part to the concerns voiced by Brown and others, TMS
practitioners largely agreed that, in order to maintain a circumspect developmental trajectory, it was imperative to outline
universal safety and procedural standards.
To this end, a group of leading TMS authorities convened in
1996 and published the first detailed safety and ethical guidelines
for TMS in both the clinical and the laboratory setting.21
Perhaps borrowing a lesson from the unchecked stimulation
methodologies of the past (eg, ECT), this assemblage set out
written standards which would serve to maintain prudence and
discretion in a field that could easily be derailed by one or two
rogue practitioners. Despite the relative nascence of the TMS
device, the International Federation of Clinical neurophysiology
demonstrated foresight by adopting and implementing these
standards worldwide (although, to be fair, these guidelines did
not cover all the aspects of TMS safety, such as long-term
effects).

Clinical expansion
With safety guidelines in place and numerous successful proofof-principle trials affirming potential benefits, TMS became
more established. Clinics offering off-label therapies for myriad
neurological and psychological pathologies began appearing
worldwide.22 23
As is common with novel treatments, initial rTMS patient
populations consisted primarily of patients who had exhausted
other, more established forms of treatment. As such, for many
patients, rTMS became a ‘last hope’ intervention, which raises
an ethical issue relevant to many young technologies: when
a treatment population consists of desperate individuals willing
to endure potentially unsafe procedures to obtain relief, an
objective focus on potential signs of diminished autonomy as
a result of neuropsychiatric illness, desperation or both, becomes
doubly important. This is especially true when obtaining
informed consent.24 25 This problem may be further aggravated
by patients seeking and receiving misleading information via
secondary sources such as the internet. Therefore, additional
safeguards may need to be instituted to avoid potential problems
or mistakes when exploring novel treatment methods within
vulnerable populations.
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As rTMS became more widespread, on-label treatment for
depression was approved by the regulatory agencies of numerous
countries, including Brazil, Israel, Australia and Canada. This
swift expansion created an explosion of ethical concerns in the
world of brain stimulation. How are practical guidelines to be
enforced with the migration of patients over borders to obtain
treatment unavailable in their home countries? How is honesty
to remain in side-effect reporting when said reports directly
affect business? These questions remain important today and
the need to revisit and continually update TMS safety guidelines
and recommendations for global clinical implementation is
imperative.
In addition to clinical expansion, practitioners developed
various new stimulation paradigms impacting the risk-to-benefit
profile of TMS. For example, theta-burst stimulation, a highfrequency stimulatory pattern, can induce rapid long-term
potentiation and long-term depression effects via the mimicry of
powerful brain oscillations. Theta-burst stimulation allows for
longer-lasting and more profound modulation of cortical excitability with shorter stimulation duration. Consider also varied
coil shapes, varied stimulation pulse characteristics, varied
stimulation sites and varied power levels, and a picture of TMS
as a broad, permutated methodology begins to emerge. With this
breadth, issues of proper technician and practitioner procedural
training and certification became important. With increasing
numbers of individuals seeking TMS therapy, ensuring patients
received the best possible treatment by a doctor well versed in
both the appropriate methodology and all relevant device
considerations became of paramount concern (and remains so
today).

2008 Consensus conference
The guidelines established in 1998 for the application of TMS in
research and clinical settings were reviewed in a consensus
conference which took place in 2008. The resulting publication
updated limits for the combination of rTMS frequencies,
intensities and train durations to reduce risk of seizure induction.26 The article provided the scientific community with an
up-to-date evaluation of the safety record of research and clinical
applications of TMS. In addition, the article introduced several
important questions, such as the use of novel parameters, while
underscoring several long-standing questions that remained
unanswered, such as the risk of TMS in patients with neuropsychiatric disorders.
In the decade spanning the conferences, the uses of TMS
expanded exponentially, growing to include new research
applications, clinical applications and cross-modality integration
(including combining TMS with electroencephalography, positron emission tomography, and functional MRI). Despite these
advancements, the initial safety guidelines developed at the 1998
conference were found to have stood the test of a decade’s worth
of work. While standards must continue to be regularly
reviewed and updated, the safety record of TMS to date
confirms that potential future ethical problems can often be
largely avoided with proper ‘preventive ethics’ foresight and
restraint in the present.27

FDA APPROVAL
In 2007, O’Reardon et al published the results of an industrysponsored, multisite, randomised clinical trial in which 301
patients with major depression, who had previously failed to
respond to at least one adequate antidepressant treatment trial,
underwent either active or sham TMS over the left dorsolateral
prefrontal cortex.28 The patients, who were medication-free at

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the time of the study, received TMS five times per week over
4e6 weeks. The data demonstrated that a sub-population of
patients, those who were relatively less resistant to medication
(having failed not more than two good pharmacological trials),
showed a statistically significant improvement on several
secondary outcome measures. Supported by these results,
Neuronetics Inc, the study-sponsoring company, obtained
approval from the FDA for the clinical treatment of specific
forms of medication-refractory depression (FDA approval
K061053).
FDA approval (granted in October 2008) was limited to the
NeuroStar TMS device (manufactured by Neuronetics Inc) for
the protocol of stimulation employed in the study (highfrequency, 10 HzdrTMS applied daily for 4e6 weeks at suprathreshold intensity) within a highly specific subpopulation of
patients (adults who have failed to achieve satisfactory
improvement from one, but no more than one, adequate
antidepressant medication trial).
When research studies are sponsored by industries, one must
consider scientific rigour and issues of conflicting interest.
Ensuring research remains free of undue influence is critical, but
there are certain circumstances in which industry sponsorship
may not be a detrimental occurrence. For example, with FDA
approval granted to Neuronetics, the door has opened for additional companies, devices and treatments to receive serious FDA
consideration. More importantly, patients who once lacked an
efficacious, safe treatment option now have an alternative with
proper risk-to-benefit balance assurances.
Recently, a National Institutes of Health-sponsored, multi-site
TMS depression trial was undertaken.29 The researchers were
able to successfully reproduce the results from the earlier
Neuronetics study. In addition to strengthening the therapeutic
profile of TMS, this outcome proved important for three additional reasons: first, with a National Institutes of Health sponsored trial, much of the potential for researcher and patient bias
was eliminated. Second, with successful replication, many
questions and/or concerns engendered from the earlier industrysponsored trial were assuaged. Finally, the risk of false positive
findings from the initial trial was greatly decreased.
The narrow FDA-approved on-label indication poses ethical
questions. The patient criteria leave many potential patients to
consider off-label options. Also, studies have revealed that the
benefits of rTMS treatment may lapse after 4e6 months.30
Unfortunately, the FDA has not approved long-term TMS
maintenance and care. This leaves the issues of prolonged
symptom alleviation and continued treatment up for ethical
debate. As TMS continues to advance as a therapeutic option,
such questions will undoubtedly become increasingly common.
As such, we must ensure that naturalistic studies are officially
reported so as to increase the pool of analysable safety data.31
The existing safety guidelines for TMS differentiate between
relative and absolute contraindications, thus providing important guidance in selection of suitable TMS candidates. Patients
exhibiting relative contraindications may have, for example,
a history of epilepsy or lesions of the brain; they may also be
taking medication that lowers the seizure threshold. Patients
with an absolute contraindication to TMS are those patients
who have implanted metallic hardware in close contact to the
discharging coil (eg, cochlear implants). Performing TMS on
patients demonstrating an absolute contraindication carries
the risk of inducing malfunctioning of such implanted
devices.26 Therefore, when it comes to deciding whether
a patient is eligible for TMS, the risk-to-benefit ratio is crucial,
and the clinician or investigator should carefully weigh the

presence of both types of contraindications while assessing
whether TMS is appropriate. However, because TMS data is
still limited, more concrete recommendations are not possible
at this time.
In the USA, FDA approval does not ensure coverage by health
insurance companies. Thus, not all patients who meet the FDA
guidelines and may benefit from TMS can afford to be treated.
Likewise, many patients seeking off-label therapy cannot afford
treatment, as neither on or off-label TMS is covered by health
insurance in the USA. This leaves payment options to the
individual clinics. Is there a way for clinics to set pricing so all
patients in need, regardless of socioeconomic status, can access
treatment? Although this concern may only be pertinent under
the present US healthcare system, as TMS continues to advance
as a treatment option, economic questions unique to each
country’s individual medical structure will undoubtedly become
increasingly common and must be addressed.
Another subject worth exploring pertains to TMS advertisements. FDA approval comes with the privilege of therapeutic
advertising for on-label application of rTMS for depression.
However, advertisement can also attract patients who may
want off-label rTMS use. Who should the advertisements
target? How should the disclosure of side-effects be dealt with?
Surely TMS treatment for depression can be made appealing
based on what it does not do (eg, it does not cause some of the
side-effects associated with other common antidepressant
medications), but perhaps it would be more prudent to market
TMS for what the literature indicates it can do. Even though
they would almost certainly be non-binding, consensus standards regarding the content of promotional advertising for TMS
would be beneficial before practitioners or companies move
forward.

Present and future ethical considerations for the scientific
use of TMS
As the clinical and research utility of TMS grows, questions
concerning treatment guidelines must be considered. What
criteria should we adopt before recommending TMS as
a possible treatment for depression or other neuropsychological
diseases? Of course, all pertinent informationdsmall effect sizes
in TMS trials, safety data, alternative treatments, even potential
future effectsdmust be fully disclosed to the patient. The truth
about what TMS can and cannot offer must be explicitly stated,
and every effort to balance a patient’s hopes and expectations
with the unpredictable reality of science must be made. Perhaps
it would be useful to create an easily-accessible website
providing the public with up-to-date TMS information from
objective and authoritative sources.
Similarly, as the risk-to-benefit ratio depends on inter-individual differences, practitioners are needed with experience with
TMS and with the relevant patient population. Ultimately this
requires the development of universal training guidelines and
accreditation requirements for TMS clinicians. Who should
deliver TMS? How should we ensure practitioners are using
TMS correctly and safely? Currently, there are no TMS training
requirements, although it is advised that practitioners be well
versed in the basics of brain physiology and TMS mechanisms,
protocols and safety issues.26 It is apparent, though, that
stronger regulations, or at least guidelines, are needed.
In neuroscientific research settings, TMS can occasionally
produce seemingly detrimental effects, most typically mild and
transient memory deficits. In studies designed to explore these
effects on performance tasks, the effects are brief and do not raise
particular safety issues.26 Still, these studies challenge the risk-to-

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benefit ratio. To what extent is it ethical to induce changes in
a subjects’ brain if the benefit is strictly increased scientific
knowledge? Taken one step further, if a therapeutic paradigm is
developed that largely mimics one of these research protocols,
there is a possibility transient deficits may be produced in the
clinic. Although it is not always possible to translate effects
generated in healthy populations to clinical patients, the inclusion of cognitive interference on the list of possible treatment side
effects is worthy of consideration and discussion.
Finally, recent research combining TMS with genetic testing
has revealed that the therapeutic utility of rTMS, particularly in
the treatment of drug resistant patients, might be increased by
identifying genetic predictors of certain rTMS effects.
Combining TMS with genetic testing, though, presents
compound ethical challenges: one must keep in mind the ethical
considerations applicable to TMS research while evaluating the
complex host of issues pertaining to genetic testing. Current
research suggests that genetic factors may influence the response
to TMS, but is the current evidence strong enough to merit
genetic testing on all TMS subjects? The broad range of genetic
factors, epigenetic effects and TMS parameters leaves scientists
with an intricate array of testing possibilities. Given the
postulated role of synaptic plasticity in brain injury and disease,
and the epidemiologic evidence concerning the role of BDNF in
the synaptic plasticity of the adult brain,32 there does seem to be
a potential therapeutic potential for future interventions.
However, that potential comes at a cost. Genetic material must
first be obtained (and drawing blood certainly poses a discomfort
for research participants) and then stored. To address some of
these issues, Knoppers and Chadwick highlight the notion of
honest and reciprocal exchange between researcher and participant.33 The autonomy and the contribution of the research
participant must be recognised and respected to the fullest in
protocols calling for genetic testing. Informed consent and
communication with potential participants must be clear, and
the objectives transparent. Moreover, participants should fully
understand that they have the option to take part in a protocol,
and that they can decide whether to have their DNA banked,
coded, analysed, even replicated and potentially commercialised.

Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.

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CONCLUSION
As TMS continues to gain momentum in the field of therapeutic
medicine, it is likely to pave the way to additional future noninvasive brain stimulation and neuromodulation techniques. For
example, transcranial direct current stimulation is a rapidly
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safety and ethics of non-invasive brain stimulation. Our ethical
perspective will inevitably evolve with changes in cultural and
societal values, but hopefully the issues we have outlined here
will provide a strong foundation for approaching the future. As
in any discussion, the most essential questions are not those we
have the answers to, but rather those which remain uncertain.
Should we fail to ask and carefully consider these questions
proactively, we risk effecting serious adverse consequences
within one or more patients due to future TMS mal-use. If this
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