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. Author manuscript; available in PMC: 2023 Aug 26.
Published in final edited form as: Handb Clin Neurol. 2013;118:335–343. doi: 10.1016/B978-0-444-53501-6.00028-7

Neuroethical issues in clinical neuroscience research

JAMES A ANDERSON 1, MARLEEN EIJKHOLT 2, JUDY ILLES 2,*
PMCID: PMC10460147  NIHMSID: NIHMS1924320  PMID: 24182390

Abstract

In this chapter, we use the special features of neuroimaging to illustrate research ethics issues for the clinical neurologic sciences, and focus on one particularly compelling case: studies involving first-episode schizophrenic treatment-naïve individuals (FESTNIs) (Eijkholt et al., 2012). FESTNIs are scanned prior to the administration of medication in order to control for the confounding effects of treatment. By concentrating on this program of research, we capture the distinctive ethical challenges associated with neuroimaging research overall, and foreground the issues particular to neuroimaging research involving FESTNIs that have yet to receive sufficient attention in the literature. We highlight assessment of risks and burdens, including risks associated with treatment delays and incidental findings; assessment of benefit, including direct benefit, social value, and scientific quality; subject selection; justice questions related to responsiveness and poststudy access; and, finally, issues related to consent and capacity.

Keywords: clinical neuroscience, ethics, neuroethics, neuroimaging, neurology, research ethics

INTRODUCTION

Challenges common to research ethics in the global arena are addressed by guidance offered by the Federal Policy for the Protection of Human Subjects (Common Rule) (45 CFR 46) in the United States, by the Tri-council Policy (2) in Canada, by the Helsinki Agreement in Europe, and others. They are designed to protect participants in research studies by raising questions, such as: Does study participation represent a favorable balance of risks and benefits? Will the selection of subjects be fair? Will the consent of participants be informed and voluntary?

These familiar challenges often manifest in unexpected ways in complex paradigms such as neuroimaging studies, due to the multidimensionality of the subject matter and the relative novelty of the technologies involved. Neuroimaging research also raises a number of ethical issues that are, if not unique to neuroimaging, especially prominent in this context. For example, challenges related to incidental findings are clearly of this kind. Issues related to hype are another, due to the unbridled enthusiasm with which neuroimaging technologies have been embraced by both the scientific community and the public. In this chapter, we use the special features of neuroimaging to illustrate research ethics issues for the neurologic sciences, and focus on one particularly compelling case: studies involving first-episode schizophrenic treatment-naïve individuals (FESTNIs) (Eijkholt et al., 2012). FESTNIs are scanned prior to the administration of medication in order to control for the confounding effects of treatment. By concentrating on this program of research, we capture the distinctive ethical challenges associated with neuroimaging research overall, and foreground the issues particular to neuroimaging research involving FESTNIs that have yet to receive sufficient attention in the literature. We highlight assessment of risks and burdens, including risks associated with treatment delays and incidental findings; assessment of benefit, including direct benefit, social value, and scientific quality; subject selection; justice questions related to responsiveness and poststudy access; and, finally, issues related to consent and capacity. These issues are common to, and exemplify, a wide range of challenges for neurology and clinical neuroscience overall. We use FESTNI as one example from this domain, recognizing nonetheless important distinctions between neurology and psychiatry, while anticipating their continuing rapprochement.

ETHICAL CHALLENGES IN NEUROIMAGING RESEARCH: AN OVERVIEW

Neuroimaging research raises a host of ethical challenges that can be roughly grouped into two sometimes overlapping categories: downstream ethical challenges pertaining to the social and medical implications of neuroimaging research, and more proximate ethical challenges relating to human participation in neuroimaging studies in the here and now.

A central downstream challenge turns on the implications of neuroimaging research for concepts of human agency, free will, and responsibility ( Libet et al., 1983; Soon et al., 2008). The concern here is that improved understanding of the mechanisms by which the brain causes behavior will undermine traditional concepts related to these phenomena (Roskies, 2006). These issues, in turn, raise serious challenges to legal systems, as legal responsibility is typically linked to agency or control. If neuroscientists were to demonstrate conclusively that some persons – or even all persons – are not in control of their actions, how would such results shape legal practice or change the criminal justice system?

Additional downstream challenges emerge from basic research conducted over the last decade developing neuroimaging-based techniques for mind reading through neural signatures of intention, anticipation, or deception. Images purporting to demonstrate deception have already been submitted to courts in the United States (Moriarty, 2008). Commercial firms like NoLieMRI and Cephos Corporation are aggressively marketing functional magnetic resonance imaging (fMRI)-based lie detection services for just this purpose, despite near universal calls for caution by the scientific community (Greely and Illes, 2007). Concerns for the practical protection of civil liberties and the vast potential for misuse fuel already difficult questions about the protection of privacy, benefit over risk, and expenditures of resources inherent to such research. Are neuroscientists responsible for managing the social uptake of their research? If so, how does this responsibility play out in practice? What responsibility does the media have in advancing public trust in science and in mitigating fear?

Downstream questions also arise in the medical arena. In recent decades, neuroimaging has yielded revolutionary new understandings of mental health disorders (Linden, 2012), but its practical application to improved approaches to and management of mental illness has been considerably less linear. How do images of the brain affect the self-understanding of persons living with mental illness? Do they ameliorate or exacerbate the perceptions of others toward them (Borgelt et al., 2011)? How can neuroimages be translated clinically to promote good lifestyles, prevent the onset of symptoms for those at risk, tailor therapy for those affected, and provide follow-up information that helps patients to maintain gains? The urgency of these questions is increased by tensions between a hopeful but cautious academic community on the one hand, and a fast-paced commercial sector that is moving full steam ahead on the other.

Another equally charged set of questions related to the medical application of neuroimaging arises from studies conducted over the past decade with patients in disordered states of consciousness. These studies hold promise for better diagnosis and prognosis of patients after brain injury, and may even offer those with residual cognitive function the means to communicate with the world outside them (Owen et al., 2006; Coleman et al., 2009; Monti et al., 2010). While the scientific community remains divided on the real potential of the technology in this context, and urges a continued focus on research (Winslade, 2007), families of patients, professional organizations such as the American Academy of Neurology, and the press are keen to discuss actionability. The ethical issues surrounding moving forward are deep and far-reaching, and concern issues ranging from decision-making about end-of-life care to healthcare policy and regulation.

These and other issues associated with neuroimaging have received extensive scrutiny in the neuroethics literature, as well as elsewhere in this handbook. Challenges of this type will not be the focus of this chapter, though we touch on some of these broader issues in the course of our discussion. Instead we focus our attention on more proximate challenges related to the actual conduct of neuroimaging studies and the human participants involved as a compelling case for examining research ethics issues. These more immediate ethical challenges have received comparatively less attention in the neuroethics literature. There are probably a number of reasons for this state of affairs, but familiarity is no doubt one of them. Informed consent and risk–benefit analysis, for example, are crucial but well-characterized concerns in research ethics. The downstream issues discussed above, by comparison, are relatively novel, underanalyzed, and utterly compelling – explaining in part the attention they have been given. It is likely, however, that the main reason the proximate challenges associated with neuroimaging research have remained largely beneath the neuroethical radar is the widespread perception that neuroimaging is minimally risky (Pinxten, 2009; Racine et al., 2011) and, therefore, ethically unproblematic.

In many instances this perception is accurate: noninvasive imaging techniques such as MRI are relatively benign. That said, there are known risks associated with MRI. These include the risks associated with metal projectiles and the dislodgment of medical implants; the risks associated with the injection of contrast agents, the use of sedatives, the noise produced by the imager, and the effects of magnetic radiation; and finally, psychologic risks such as anxiety and claustrophobia (Marshall et al., 2007; Marshall and Hadskis, 2009). Additional ethical challenges emerge from the goals and design of the study, as well as the proposed study population. When neuroimaging research involves vulnerable participants, for example, additional scrutiny is warranted.

In the rest of this chapter we will focus for the most part on the proximate challenges associated with the particular subset of neuroimaging studies involving FESTNIs. We first wrote about this topic in International Journal of Law and Psychiatry (Eijkholt et al., 2012). We return to the topic here because doing so allows us both to highlight the ethical challenges associated with neuroimaging research overall, and to foreground issues particular to neuroimaging research involving FESTNIs that have yet to receive sufficient attention in the literature.

NEUROIMAGING RESEARCH INVOLVING FESTNIS

To date, neuroimaging techniques provide the only means of direct access to the living brain. For this reason, since their earliest inception, these techniques have been used to study mental illness (Linden, 2012). The hope is that neuroimaging will play a central role in building a biologic foundation for the understanding of mental illness.

Schizophrenia was one of the first psychiatric disorders targeted by imagers. Early work aimed to identify structural and functional abnormalities in cross-sectional studies of populations with chronic schizophrenia (Shapiro, 1993). One of the first consistent discoveries was enlargement of the lateral and third ventricles in affected people (Linden and Fallgatter, 2009), and many hailed this discovery as proof that schizophrenia was a brain-based disease.

Though this general conclusion remains valid, investigators have since discovered substantial variation in brain features associated with schizophrenia depending on factors such as age of onset, illness duration, and treatment history (Harrison and Roberts, 2000). These variations have made it very difficult to draw precise conclusions concerning the neurobiology of schizophrenia, stalling efforts to elucidate prognostic and diagnostic biomarkers of disease.

In an effort to overcome these difficulties, imagers have sought to control for confounding factors by focusing their efforts on FESTNIs (Szymanski et al., 1995). FESTNIs are typically in their late teens or early 20s (Frangou and Byrne, 2000) and are experiencing the symptoms of schizophrenia for the first time (Harrison, 1999; Leung et al., 2011). By definition, FESTNIs also share treatment-free histories at the time of study.

Imagers hope that studies involving FESTNIs will provide a more accurate cross-sectional understanding of the anatomic and functional anomalies characteristics of schizophrenia. Imagers also hope that studies involving FESTNIs will provide an accurate baseline for longitudinal studies designed to elucidate changes in structure and function over time (Brown and Eyler, 2006).

ETHICAL CHALLENGES IN NEUROIMAGING RESEARCH INVOLVING FESTNIS

It is important to begin by noting that schizophrenia is a major mental illness involving a range of symptoms. These symptoms include delusions, paranoia, and hallucinations, low affect, and social withdrawal (Kay et al., 1987). The prognosis for this major mental illness is often dire due to the lack of effective treatment and social support, and high levels of stigmatization (Landeen et al., 2007). Persons diagnosed with schizophrenia frequently acquire comorbid disorders such as addictions and iatrogenic disorders (Batel, 2000) and almost invariably suffer significant employment and interpersonal difficulties.

The ethical challenges associated with imaging research involving FESTNIs flow first and foremost from the vulnerability of the population targeted for study recruitment. However, ethical challenges also flow from the goals and design of these studies. It is ethically significant, for example, that FESTNIs are identified when they arrive in the emergency department or psychiatric ward where they are examined and diagnosed with schizophrenia for the first time. It is at this point that they are approached concerning participation in imaging research.

In the rest of the chapter we discuss the ethical challenges associated with this research program. Specifically, we focus on: assessment of risks and burdens, including risks associated with treatment delays and incidental findings; assessment of benefit, including direct benefit, social value, and scientific quality; subject selection; justice questions related to responsiveness and poststudy access; and, finally, issues related to consent and capacity.

Assessment of risks and burdens

Risks associated with the scan itself

Imaging research involving FESTNIs involves all or most of the predictable potential physical risks mentioned above, e.g., dislodgment of metal objects, anxiety, and claustrophobia. In neuroimaging studies with subjects presumed to be healthy, these can be managed such that they pose no more than minimal risk to participants. In the case of imaging research involving FESTNIs, however, it may be more difficult to achieve this goal.

FESTNIs are experiencing an episode of schizophrenia for the first time. Given the novelty of the experience, symptoms such as auditory hallucinations, and the circumstances of the research setting, such as immersion in an MR scanner, may be particularly troubling. FESTNIs suffering from paranoid delusions may be further prone to false beliefs concerning mind reading, or believe that researchers are technologically manipulating thoughts and behaviors. The tasks involved in many imaging studies may also pose a threat to FESTNIs. Take, for example, lip-reading tasks or tasks involving the judgment of facial expressions (Surguladze et al., 2001; Gur et al., 2002; Reske, 2009). While these tasks may not seem burdensome to healthy individuals, they may pose special risks for individuals who are hearing voices or who are experiencing paranoid delusions.

By highlighting these issues, we do not mean to marginalize persons suffering from schizophrenia by characterizing them as vulnerable, or to imply that research involving FESTNIs is necessarily unethical. Nor do we mean to suggest that FESTNIs always lack the capacity to make an informed decision to participate in research of this kind (more on this later). We do want to suggest, however, that imagers enrolling FESTNIs ought to take special care to mitigate the risks described above when they design and conduct their studies.

It is likely, of course, that researchers are already taking many such steps. Based on the published literature in this area, however, it is far from clear whether researchers have recognized these concerns and, if they have, what measures they have taken to deal with them (Garnett et al., 2011; Anderson et al., 2012b). In light of this gap, we suggest that all imaging studies involving FESTNIs be customized to ensure that the risks and burdens of participation by this population are minimized and that these steps are reported in all publications (Anderson et al., 2012a). Avoiding tasks that may exacerbate or provoke anxiety, paranoia, delusions, or hallucinations, piggy-backing research procedures on to procedures that are part of standard clinical practice, and ensuring that debriefing is a routine part of scan follow-up will be positive steps to achieve this goal.

Risks associated with treatment delays

Prima facie, imaging research involving FESTNIs necessitates the postponement of medically necessary therapeutic procedures. This follows from the goals and design of the research. Participants are recruited after they are diagnosed with schizophrenia for the first time but before they receive treatment. Though a standard scan only takes 45 minutes, additional delays can occur because scanners are a relatively scarce commodity and access is difficult, particularly for research purposes. Even when studies are piggy-backed on imaging protocols undertaken for clinical reasons, delays are minimized but may not be eliminated.

To our knowledge the risks associated with treatment delays in this context have not been discussed in either the imaging or ethics literature before our own work in this area (Eijkholt et al., 2012). We recommend that all imaging protocols involving FESTNIs detail the steps taken to minimize the delay of treatment required by participation, specify maximum tolerable delays of treatment, and explicitly delineate methods for monitoring the participant during the period of treatment delay.

Risks associated with incidental findings

Incidental findings are “observations of potential clinical significance unexpectedly discovered in healthy subjects or in patients recruited to brain imaging research studies and unrelated to the purpose or variables of the study” (Illes et al., 2006). Incidental findings are ethically challenging for a number of reasons. First and foremost, they raise difficult questions concerning the duty of care and the duty to warn owed research participants by researchers. From the perspective of the researcher, these questions are both practical and philosophic. How should a finding of potential clinical significance be handled in the research setting? How should participant welfare be protected and privacy be safeguarded? What duties belong to basic research scientists who do not have medical training? Whose responsibility is it to communicate the finding to a subject or surrogate, to follow up, and to treat if needed (Illes and Chin, 2008)?

From the participant’s perspective, consenting to a research study in which incidental findings are a possibility means taking on a number of potentially serious risks, ranging from the shock and anxiety triggered by coming face to face with unwelcome and potentially bad news, through to the costs associated with follow-up (Illes et al., 2004; Wolf et al., 2008) and potential implications related to insurance (Apold and Downie, 2011). Complicating this situation is the fact that, depending on the research protocol, information with uncertain medical significance could be delivered by a nonphysician researcher who may or may not have appropriate skills to do so (Illes et al., 2006). The probability and magnitude of these risks may be significantly increased when participants are vulnerable.

During the last decade, much clarity has been achieved through empiric research (Kim et al., 2002; Illes et al., 2004; Kirschen et al., 2006; Morris et al., 2009; Booth et al., 2010; Jordan et al., 2010; Lumbreras et al., 2010; Palmour et al., 2011) and consensus discussions (Illes et al., 2002, 2004, 2006, 2008; Illes, 2006; Kirschen et al., 2006; Brown and Hasso, 2008; Illes and Chin, 2008; Parker, 2008; Wolf et al., 2008; Morris et al., 2009) concerning the ethics of incidental findings in neuroimaging research with healthy adult human subjects, and to a lesser extent in children (Kim et al., 2002; Kumra et al., 2006; Wilfond and Carpenter, 2008). Only recently have efforts explicitly tackled the difficult problem of incidental findings in research involving persons who suffer from mood and anxiety disorders (Borgelt et al., in preparation). Findings from this work are highlighting how important it is for investigators who conduct neuroimaging studies involving FESTNIs to follow extant guidelines concerning the inclusion of plans for the management of incidental findings in their protocols, and the provision of this information in the consent forms given to participants.

Assessment of benefit

Direct benefit

All influential codes of human research ethics demand that the risks posed by medical research be proportionate to the foreseeable benefits. In the research ethics literature a distinction is drawn between two kinds of benefit: benefits to participants and benefits to society. To date, imaging studies involving FESTNIs have not been designed to offer participants the prospect of direct preventive, diagnostic, or therapeutic benefits. Of course, a participant may benefit directly from the discovery and subsequent management of a clinically significant finding arising incidentally during participation in research, but these benefits cannot be weighed in the risk/direct benefit calculus justifying trial conduct precisely because they are unrelated (or incidental) to the goals of study (Parker, 2008). Thus, the risks to participants associated with neuroimaging research involving FES-TNIs must be weighed against the downstream social benefits of the knowledge produced. This raises two specific challenges: therapeutic misconception and scientific quality.

Therapeutic misconception occurs when “a research subject fails to appreciate the distinction between the imperatives of clinical research and of ordinary treatment, and therefore inaccurately attributes therapeutic intent to research procedures” (Lidz and Appelbaum, 2002). Given that FESTNIs are suffering from the symptoms of schizophrenia, have sought medical treatment for these symptoms, and are approached for research participation immediately after they are diagnosed for the first time, the risk of therapeutic misconception looms large.

Therapeutic misconception is an ethical problem because it vitiates informed consent. When a potential research participant suffers from a therapeutic misconception, the individual has misconstrued the goals of the study. The consequence is that the risk/benefit ratio associated with participation may be poorly understood. Again, the absence of discussion of this issue in the published scientific literature makes it impossible to know whether investigators conducting research in this population appreciate these risks and, if they do, the steps they are taking to mitigate them.

Social value and scientific quality

Since imaging studies involving FESTNIs do not offer the prospect of direct, risk/benefit proportionality turns entirely on the value of the knowledge the work produces. There is substantial concern in the review literature, however, about the scientific quality of imaging studies of schizophrenia (Kindermann et al., 1997; Davis et al., 2005; Nakamura et al., 2005; Brown and Eyler, 2006; Fusar-Poli et al., 2008; Agarwal et al., 2010). A major locus of criticism relates to the uncontroll led nature of many studies in this area. Of course, as we noted above, imagers began studying FESTNIs in order to control for the confounding effects of age of onset, illness duration, and treatment history. But there are many other threats to internal validity. One is the degree to which studies are designed to control for confounds such as the type and level of symptoms that vary enormously across participants (Buchsbaum, 1990; Franck et al., 2002; Davis et al., 2005; Nakamura et al., 2005; Brown and Eyler, 2006; Fusar-Poli et al., 2008; Agarwal et al., 2010). Another threat to internal validity relates to the tasks designed to target functional deficits particular to schizophrenia (Brown and Eyler, 2006) and confounds related to the emotional disposition of participants (Brown and Eyler, 2006).

Scientific quality is ethically relevant because quality is tightly related to the potential knowledge value of research and to the evaluation of risk–benefit proportionality. An invalid study is necessarily ethically problematic because it puts research subjects at risk and squanders resources. If the risks of neuroimaging research involving FESTNIS must be justified by appeal to the social value of the knowledge produced, and these studies are of questionable knowledge value, the ethical justification for these studies is thrown into doubt.

Opinion leaders in the imaging community have long called for tighter inclusion/exclusion criteria with respect to symptoms and the standardization of tasks. We reiterate this call here and take it to one further level: we recommend the creation of a consortium for neuroimaging in mental health, analogous to the Alzheimer’s Disease Neuroimaging Initiative funded by the National Institutes of Health and partners. Members of the consortium would follow standardized protocols for data acquisition and analysis, and make available repositories for data mining and sharing (Anderson et al., under review).

Subject selection

Neuroimaging trials involving FESTNIs raise questions related to subject selection. On the one hand, studies enrolling FESTNIs promise to provide ever-increasing knowledge about the neurobiology of schizophrenia. On the other hand, FESTNIs are not optimally positioned to offer voluntary informed consent. Indeed, it is likely that FESTNIs are in a worse position vis-à-vis consent than individuals with chronic schizophrenia who have more experience coping with their disease.

So, we are faced with a dilemma characteristic of all research involving human subjects: scientific progress must be balanced against the risks of research participation. In response, we suggest the following steps. First, we recommend that all imaging studies involving FES-TNIs be designed to ensure that the risks and burdens presented by participation are minimal. If this is impossible, consideration should be given to the prospective exclusion of FESTNIs who score above a chosen threshold on a validated severity scale (such as the Brief Psychiatric Rating Scale of the Positive and Negative Syndrome Scale) (Kay et al., 1987), and those who are particularly prone to psychologic risks.

Justice

Responsiveness and poststudy access

FESTNI research also raises justice questions related to responsiveness. Are the benefits and burdens of research distributed equitably? This question is particularly pressing when members of disadvantaged populations are recruited into studies. The ethical concern is that the unfair disadvantages of vulnerable populations will be used to advance the health interests of others.

Most influential codes of human research ethics (Nuffield Council on Bioethics, 1999; National Bioethics Advisory Commission, 2001; Council for International Organizations of Medical Sciences, 2002) now include policies designed to promote justice in research involving human participants. The first of these is responsiveness: “[m]edical research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the results of the research” (WMA, 2000). The second is poststudy access: “[a]t the conclusion of the study, every patient entered into the study should be assured of access to the best proven prophylactic, diagnostic and therapeutic methods identified by the study” (WMA, 2000).

These standards were developed in response to controversy surrounding a series of placebo-controlled trials of short-course AZT for the prevention of vertical transmission of human immunodeficiency virus (HIV). They are typically associated with late-phase clinical trials conducted in low- or middle-income countries (LMICs). Justice concerns related to responsiveness and poststudy access, however, are not restricted to late-phase clinical trials or LMICs. Though persons from all socioeconomic classes suffer from major mental illness, including schizophrenia, persons with major mental illness are overrepresented at the lower end of the socioeconomic scale (Aldworth et al., 2010). Consequently, in jurisdictions such as the United States and other countries where many people lack adequate health coverage, justice issues may arise if the underinsured are targeted for recruitment in research.

Since most imaging technologies are cost-intensive, access to these technologies when they become part of standard clinical practice may well be a problem for persons living with schizophrenia. In order to ensure that neuroimaging studies involving FESTNIs satisfy the requirements of justice, it is essential that investigators take steps to mitigate these concerns by working toward responsiveness and poststudy access as current research moves into clinical application.

Consent and capacity

It would be a mistake to assume that persons with schizophrenia necessarily lack capacity. However, given that most imaging studies involving FESTNIs enroll participants who are actively experiencing the symptoms of schizophrenia, there are prima facie grounds for questioning whether participants are in a position to consent to research participation. Concerns about capacity are increased, furthermore, by the fact that participants are experiencing schizophrenia for the first time and are pretreatment (Pantelis et al., 2005). It is striking, therefore, that concerns related to consent and capacity are almost never mentioned in the relevant published scientific literature. At best, published papers simply state that “informed consent was obtained” (Garnett et al., 2011), as required by the International Committee of Medical Journal Editors guidelines.

In order to mitigate these concerns, we offer three recommendations. First, as noted above, we recommend the prospective exclusion of FESTNIs who score above a predetermined threshold on a reliable severity scale. Second, we recommend that, given the often acute nature of potential participants’ symptoms, all imaging studies involving FESTNIs be designed so to assess the capacity of potential participants on an individual and task-specific basis. Third, we recommend that imaging researchers conducting research in this population take special care to ensure that potential participants are not suffering from therapeutic misconception when they consent to enrollment. Fourth, and finally, we recommend that investigators include some detail concerning how informed consent was managed in their published reports (Anderson et al., 2012a; Eijkholt et al., 2012).

SUMMARY OF RECOMMENDATIONS

  1. Imaging studies involving FESTNIs should be designed to ensure that the special risks and burdens of participation by this population are minimized.

  2. Tasks that might provoke anxiety, paranoia, delusions, or hallucinations should be avoided.

  3. Whenever possible, research procedures should be piggy-backed on procedures undertaken as part of standard clinical practice in order to reduce the risks, burdens, and potential treatment delays.

  4. Debriefing and follow-up should be a routine feature of the study design.

  5. Steps taken to minimize the delay of treatment required by participation – including a maximum tolerable delay – should be specified in the protocol, and the informed consent document.

  6. Participants should be closely monitored during any period of treatment delay.

  7. Extant guidelines for the management of incidental findings should be followed.

  8. Measures should be taken to guard against therapeutic misconception when participants are consented to enrollment.

  9. Coordinated steps should be taken to improve the scientific quality of research through tighter inclusion and exclusion criteria, and standardized tasks.

  10. A consortium for neuroimaging in mental health should be created to facilitate these improvements and enable robust capabilities for data sharing and data mining.

  11. Potential participants’ capacity to consent should be evaluated on an individual and task-specific basis using a validated test for capacity.

  12. FESTNIs with severe symptoms should be excluded.

  13. Investigators should take steps to improve responsiveness and poststudy access as current research moves into clinical application.

  14. The methods undertaken to protect FESTNIs participating in neuroimaging research should be described in detail in published research reports.

CONCLUSION

In this chapter we discussed many ethical challenges associated with neuroimaging research by focusing on a particular case: studies involving FESTNIs. The case illustrated a broad range of research ethics issues arising during the design and conduct of research, including the assessment of risks and burdens, challenges of treatment delays and incidental findings, assessment of benefits, social value, and scientific quality, subject selection, justice questions, and consent and capacity. We concluded by offering pragmatic responses to these challenges, including a call for transparent reporting of the steps to take to protect the participation of human subjects in research.

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