The New Ethics of Neuromodulation with Transcranial Magnetic Stimulation: A Critical Appraisal.

With over 16 years of experience in clinical, research, and educational activities related to transcranial magnetic stimulation (TMS), I have written this article exploring the ethical dimensions of TMS. This article aims to provide valuable and informative content for those unfamiliar with TMS as well as those just starting in the field. Specifically, this article elaborates on four principles of medical ethics, including those applicable to TMS therapy, the disparity between public medical insurance coverage and medical indications in private practice for TMS therapy, and issues concerning research ethics in practice. I also provide recommendations regarding roles and strategies for adoption by academia and those in this field dedicated to making TMS therapy accessible to a larger patient population in a suitable manner. Lastly, it is my hope that this article will serve as a contemporary "Ethics of TMS Neuromodulation", resonating with the inherent human pursuit of "truth, goodness, and beauty" for a sound mind and spirit.

The challenge of crafting policy for do-it-yourself brain stimulation.

Transcranial direct current stimulation (tDCS), a simple means of brain stimulation, possesses a trifecta of appealing features: it is relatively safe, relatively inexpensive and relatively effective. It is also relatively easy to obtain a device and the do-it-yourself (DIY) community has become galvanised by reports that tDCS can be used as an all-purpose cognitive enhancer. We provide practical recommendations designed to guide balanced discourse, propagate norms of safe use and stimulate dialogue between the DIY community and regulatory authorities. We call on all stakeholders-regulators, scientists and the DIY community-to share in crafting policy proposals that ensure public safety while supporting DIY innovation.

[Ethical considerations regarding the use of transcranial magnetic stimulation in the treatment of depression]. / Ethische overwegingen bij transcraniële magnetische stimulatie in de behandeling van depressie.

BACKGROUND: Transcranial magnetic stimulation (TMS) has proved effective in the treatment of depression. However, the step that was needed to progress from positive research results to the actual use of TMS to treat patients has raised a number of ethical concerns. The concerns extend beyond matters such as the safety of the technique, the patient's right of access to therapy and the patient's informed consent; ethics are involved because the new treatment can be mind-bending and can interfere with the patient's autonomy and decision-making capacity. AIM: To discuss ethical issues raised by the use of TMS in the treatment of depression. METHOD: We reviewed the relevant scientific literature. RESULTS: The effects of the treatment on the patient's genuine wishes and on his or her views on the efficacy of the treatment are technique-related ethical issues that have not yet been adequately addressed. Furthermore, the effects of TMS on the patient's autonomy and mental capacity and the 'last resort' argument in relation to the effectiveness of the therapy are context-related considerations that warrant further discussion. CONCLUSION: There will have to be more research and discussion among researchers and clinicians about specific ethical questions before TMS can take its rightful place in clinical practice.

Ethics of the electrified mind: defining issues and perspectives on the principled use of brain stimulation in medical research and clinical care.

In recent years, non-pharmacologic approaches to modifying human neural activity have gained increasing attention. One of these approaches is brain stimulation, which involves either the direct application of electrical current to structures in the nervous system or the indirect application of current by means of electromagnetic induction. Interventions that manipulate the brain have generally been regarded as having both the potential to alleviate devastating brain-related conditions and the capacity to create unforeseen and unwanted consequences. Hence, although brain stimulation techniques offer considerable benefits to society, they also raise a number of ethical concerns. In this paper we will address various dilemmas related to brain stimulation in the context of clinical practice and biomedical research. We will survey current work involving deep brain stimulation, transcranial magnetic stimulation and transcranial direct current stimulation. We will reflect upon relevant similarities and differences between them, and consider some potentially problematic issues that may arise within the framework of established principles of medical ethics: nonmaleficence and beneficence, autonomy, and justice.

Challenges of proper placebo control for non-invasive brain stimulation in clinical and experimental applications.

A range of techniques are now available for modulating the activity of the brain in healthy people and people with neurological conditions. These techniques, including transcranial magnetic stimulation (TMS) and transcranial current stimulation (tCS, which includes direct and alternating current), create magnetic or electrical fields that cross the intact skull and affect neural processing in brain areas near to the scalp location where the stimulation is delivered. TMS and tCS have proved to be valuable tools in behavioural neuroscience laboratories, where causal involvement of specific brain areas in specific tasks can be shown. In clinical neuroscience, the techniques offer the promise of correcting abnormal activity, such as when a stroke leaves a brain area underactive. As the use of brain stimulation becomes more commonplace in laboratories and clinics, we discuss the safety and ethical issues inherent in using the techniques with human participants, and we suggest how to balance scientific integrity with the safety of the participant.

Transcranial direct current stimulation and aphasia: the case of mr. C.

PURPOSE: To illustrate the ethical challenges that arose from investigating a novel treatment procedure, transcranial direct current stimulation (tDCS), in a research participant with aphasia. METHOD: We review the current evidence supporting the use of tDCS in aphasia research, highlighting methodological gaps in our knowledge of tDCS. Then, we examine the case of Mr. C, a person with chronic aphasia who participated in a research protocol investigating the impact of tDCS on aphasia treatment. We describe the procedures that he underwent and the resulting behavioral and neurophysiological outcomes. Finally, we share the steps that were taken to balance beneficence and nonmaleficence and to ensure Mr. C's autonomy. RESULTS: The objective data show that while Mr. C may not have benefitted from participating in the research, neither did he experience any harm. CONCLUSION: Researchers must consider not only the scientific integrity of their studies, but also potential ethical issues and consequences to the research participants.

Transcranial magnetic stimulation: a historical evaluation and future prognosis of therapeutically relevant ethical concerns.

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.

Transcranial magnetic stimulation, deep brain stimulation and personal identity: ethical questions, and neuroethical approaches for medical practice.

Neurotechnology provides means to engage micro- and macrostructural networks of the brain to both mitigate the manifestations of several neurological and psychiatric disorders, and alter cognition and motoric activity. Such capacity also generates questions of how these interventions may affect personal identity. This paper discusses the ethical implications regarding changes to personal identity that arise from the therapeutic use of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS) technologies. In addition, we raise the question of whether changes in personal identity, as a side effect of these interventions, are ethically acceptable and whether such alterations of personality foster patients' sense of well-being and autonomy. First, we provide a series of case vignettes that afford an overview of the ways that various neurological interventions can affect personal identity. Second, we offer a brief working definition of personal identity in order to delineate an ethical framework that we deem necessary for the responsible use of neurostimulation technologies. In so doing, we argue that neurostimulation therapy, as a doctoring act, should be directed, and adherent to goals of restoring and/or preserving patients' personal identity. To this end, we offer an ethical framework that we believe enables sound decisions about the right and good use of TMS and DBS.

The emerging role for repetitive transcranial magnetic stimulation in optimizing the treatment of adolescent depression.

Major depressive disorder (MDD) in adolescents is a common illness and significant public health problem. Treatment is challenging because of recurrences and limited modalities. Selective serotonin reuptake inhibitors and cognitive behavioral therapy are considered the standard of care in severe or treatment-resistant MDD in this age group. However, responses to these interventions are often suboptimal. A growing body of research supports the efficacy of repetitive transcranial magnetic stimulation (rTMS) for the treatment of MDD in adults. Induced seizures are a primary safety concern, although this is rare with appropriate precautions. There is, however, limited experience with rTMS as a therapeutic intervention for adolescent psychiatric disturbances. This review will summarize the rTMS efficacy and safety data in adults and describe all published experience with adolescent MDD. Applications in other adolescent psychiatric illnesses such as schizophrenia and attention-deficit/hyperactivity disorder are reviewed. Safety and ethical issues are paramount with investigational treatments in adolescent psychiatric illnesses. However, further research with rTMS in adolescent MDD is imperative to establish standards for optimal stimulation site, treatment parameters, and its role in treatment algorithms. These may diverge from adult data. Early intervention with neuromodulation could also hold the promise of addressing the developmental course of dysfunctional neurocircuitry.

An ethics perspective on transcranial magnetic stimulation (TMS) and human neuromodulation.

This paper concerns the ethics of human neuromodulation using transcranial magnetic stimulation (TMS). We examine the challenges of modulating the brain with TMS through the research ethics lens and in clinical medicine for treating frank pathology, primarily in psychiatric diseases. We also consider contemporary issues raised in the neuroethics literature about managing unexpected findings, and relate these to TMS and to other frontier neurotechnology that is becoming openly available in the public domain. We argue that safety and informed consent are of paramount importance for TMS, but that personal values and sociocultural factors must also be considered when examining the promise of this technology and applications that ought to be highlighted for extra precautions.

Memory Interventions in the Criminal Justice System: Some Practical Ethical Considerations.

In recent years, discussion around memory modification interventions has gained attention. However, discussion around the use of memory interventions in the criminal justice system has been mostly absent. In this paper we start by highlighting the importance memory has for human well-being and personal identity, as well as its role within the criminal forensic setting; in particular, for claiming and accepting legal responsibility, for moral learning, and for retribution. We provide examples of memory interventions that are currently available for medical purposes, but that in the future could be used in the forensic setting to modify criminal offenders' memories. In this section we contrast the cases of (1) dampening and (2) enhancing memories of criminal offenders. We then present from a pragmatic approach some pressing ethical issues associated with these types of memory interventions. The paper ends up highlighting how these pragmatic considerations can help establish ethically justified criteria regarding the possibility of interventions aimed at modifying criminal offenders' memories.

The rising tide of tDCS in the media and academic literature.

Academic and public interest in tDCS has been fueled by strong claims of therapeutic and enhancement effects. We report a rising tide of tDCS coverage in the media, while regulatory action is lacking and ethical issues need to be addressed.

The promises and perils of non-invasive brain stimulation.

Non-invasive brain stimulation promises innovative experimental possibilities for psychology and neuroscience as well as new therapeutic and palliative measures in medicine. Because of its good risk-benefit ratio, non-invasiveness and reversibility as well as its low effort and cost it has good chances of becoming a widespread tool in science, medicine and even in lay use. While most issues in medical and research ethics such as informed consent, safety, and potential for misuse can be handled with manageable effort, the real promise of brain stimulation does raise one prominent moral worry: it may lay the foundation of reliable, precise and stable manipulations of the mind. This article addresses this worry and concludes that it is not the possibility of manipulation, but the shift in our understanding of our mind which stands in need of careful consideration.

Rethinking the thinking cap: ethics of neural enhancement using noninvasive brain stimulation.

Although a growing body of evidence suggests that noninvasive brain stimulation techniques such as transcranial magnetic stimulation and transcranial direct current stimulation have the capacity to enhance neural function in both brain-injured and neurally intact individuals, the implications of their potential use for cosmetic self-enhancement have not been fully explored. We review 3 areas in which noninvasive brain stimulation has the potential to enhance neurologic function: cognitive skills, mood, and social cognition. We then characterize the ethical problems that affect the practice of cosmetic neurology, including safety, character, justice, and autonomy, and discuss how these problems may apply to the use of noninvasive brain stimulation for self-enhancement.

Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research.

This article is based on a consensus conference, which took place in Certosa di Pontignano, Siena (Italy) on March 7-9, 2008, intended to update the previous safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings. Over the past decade the scientific and medical community has had the opportunity to evaluate the safety record of research studies and clinical applications of TMS and repetitive TMS (rTMS). In these years the number of applications of conventional TMS has grown impressively, new paradigms of stimulation have been developed (e.g., patterned repetitive TMS) and technical advances have led to new device designs and to the real-time integration of TMS with electroencephalography (EEG), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Thousands of healthy subjects and patients with various neurological and psychiatric diseases have undergone TMS allowing a better assessment of relative risks. The occurrence of seizures (i.e., the most serious TMS-related acute adverse effect) has been extremely rare, with most of the few new cases receiving rTMS exceeding previous guidelines, often in patients under treatment with drugs which potentially lower the seizure threshold. The present updated guidelines review issues of risk and safety of conventional TMS protocols, address the undesired effects and risks of emerging TMS interventions, the applications of TMS in patients with implanted electrodes in the central nervous system, and safety aspects of TMS in neuroimaging environments. We cover recommended limits of stimulation parameters and other important precautions, monitoring of subjects, expertise of the rTMS team, and ethical issues. While all the recommendations here are expert based, they utilize published data to the extent possible.