Content 18.doc

The responsible conduct of research. The normative frameworks Chapter 18. Emerging responsibilities in neuroscience1
Éric Racine2,3
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Summary
Introduction: Neuroethics
First scenario: Incidental finding of abnormalities in neuroimaging research
Second scenario: Improving human capabilities using neurotechnology
Third scenario: Communicating and interpreting research results

Discussion: A multidimensional framework for responsibility in neuroscience


Conclusion: A call to the disquieted moral conscience
References
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Summary
Neuroscience represents a dynamic and competitive area of biomedical research where
responsibilities for researchers and society are emerging. This chapter introduces the context in
which certain ethical issues emerge in neuroscience as well as the ensuing challenges for
researcher responsibility. Three scenarios from different fields of neuroscience illustrate some of
these challenges: (1) the incidental finding of abnormalities in neuroimaging research; (2) the
1 August, 2005 2 Eric Racine, PhD Director Neuroethics Research Unit Institut de recherches cliniques de Montréal (IRCM) Office 1535 110, Pine Avenue West Montreal (Quebec) H2W 1R7 Email: eric.racine@ircm.qc.ca 3 Writing of this chapter was made possible by a postdoctoral fellowship from the Social Sciences and Humanities Research Council of Canada. creation of neurotechnologies that can lead to cognitive enhancement and (3) the responsible
communication of research results. Within the context of an analysis of the emerging issues, we
propose a multidimensional vision of responsibility that includes integrity and the obligation to
produce accurate scientific knowledge, the social responsibilities pertaining to the eventual use of
this knowledge as well as the obligation for self-reflection in research and in the training of
researchers.
Introduction: Neuroethics
Like genetic research, neuroscience represents a dynamic and competitive area of biomedical
research. Unlike genetics, the brain sciences have not been until recently the object of a
systematic and interdisciplinary ethical reflection (Illes et al, 2005). However, neuroscience is
increasingly moving to medical applications such as neurostimulation, with problematic ethical
issues arising such as consent from vulnerable patients (Abbott, 2005) and the allocation of
resources (Ausman, 2004). Non-medical applications of neuroimaging in the judicial field
(Garland, 2004) and in the field of education (Gura, 2005) hold the attention of the public and
spark debates in the neuroscience and bioethics communities. Taking into account recent
advances, neuroscience represents a field of research where responsibilities for researchers and of
society are appearing, and though there has not been much thought given to the anticipation of
the changes to come, that is beginning to change with the emergence of the field of neuroethics
(Wolpe, 2004b).
This chapter introduces the context in which ethical issues emerge in neuroscience and the
ensuing challenges for researcher responsibility. Three scenarios from different areas of
neuroscience illustrate some of these challenges: (1) the incidental finding of abnormalities in
neuroimaging; (2) the creation of neurotechnologies which can lead to human performance
enhancement and (3) the responsible communication of research results. Within an analysis of the
emerging issues, we propose a multidimensional vision of responsibility that includes integrity
and the obligation to produce accurate scientific knowledge, the social responsibilities pertaining
to the eventual use of this knowledge as well as the obligation of self-reflection in research and in
the training of researchers. We thus hope to provoke a debate on the ethical issues of
neuroscience without conveying the impression that our analysis is exhaustive or proposes final
solutions. In addition, the emphasis on emerging issues should neither overshadow the tradition
of ethical thought in neurology and psychiatry nor the importance of formal research ethics
guidelines.

First scenario: Incidental finding of abnormalities in neuroimaging research
It must first be mentioned that research in neuroimaging raises a number of ethical issues (Table
I). Among those are the standardization of research practices, the use of neuroimaging for
predictive purposes, the growing commercialization of imaging and related conflicts of interest,
the balanced presentation of research results to prevent their hasty use, justice and access to
diagnostic services as well as respect for privacy and confidentiality. Currently, there are growing
concerns about the ethics of neuroimaging among the general public (Editorial, 2002; Jaffe,
2004) and scientists (Editorial, 2001; Editorial, 2003; Editorial, 2004; Utall, 2001). The
responsibilities of researchers are directly summoned.
Neuroimaging - as with all medical imaging techniques - is useful insofar as clinical information is obtained which would otherwise be inaccessible. It is for this reason that computerized tomography is used to detect cerebral haemorrhages and magnetic resonance imaging (MRI) to identify cerebral tumours (Gilman, 1998). However, the powerful properties of neuroimaging techniques create challenges for researchers regarding the responsible conduct of research. In fact, even in the context of research, neuroimaging can expose abnormalities in healthy subjects. These discoveries are called "incidental findings" (or IF). They can be defined as abnormalities having a potential clinical significance even though these abnormalities are not recognized prior to the brain scan (Illes, 2003). We will now consider two true cases of IFs in neuroimaging in order to illustrate some of the ethical challenges. The following illustration is inspired by the testimony of Sarah Hilgenberg, a medical student at Stanford University (Hilgenberg, 2005). Luckily, this story ended happily, as the surgeries were successful and without complication. Sarah continues her studies in medicine, transformed by this experience as a patient and a student. Sarah's real-life experience depicted in the vignette below does not seem to be isolated. An anonymous correspondent recently described in Nature how an incidental finding of a cerebral tumour completely modified his life trajectory (Anonymous, 2005). This university researcher, who describes himself as "fascinated by the brain", volunteered for a study of one of his colleagues. He had always wanted to see his brain through magnetic resonance imaging (MRI). However, once the scan was completed, the person in charge of the centre informed him that an abnormality was discovered. As the subject had previously taught neuroanatomy, he recognized a tumour the size of a golf ball located close to the carotid artery, in the region of the brain stem. The person in charge of the centre suggested that he consult a neurosurgeon, which he decided to do. The neurosurgeon informed the subject, who had now become a patient, that 5% of these operations lead to complications in which case a stroke must be induced in the entire left hemisphere of the brain, in order to prevent death. However, at the time that this incident was unfolding, this man and his wife were expecting the birth of their first child. They decided to review their insurance policy in case that one of the two future parents lost their university job. Considering that this surgery could cause him to lose his job, he wondered if it was necessary to disclose to his insurance company the information contained in this non-clinical scan. He opted for honesty. Consequence: coverage was refused. At the time of writing to Nature, this university researcher was facing a surgical intervention that could cost him his job and have serious consequences for him and his family. The management of incidental findings raises important questions regarding the responsibility of researchers, and the responsibility of the institutions where structural and functional neuroimaging studies are undertaken. In fact, preliminary studies suggest that such incidental findings, while rare, occur on a regular basis. A study conducted on the scans of 1000 asymptomatic volunteers recruited as controls for various studies of the National Institutes of Health shows the presence of an abnormality in 18% of these controls. According to the classification used by the authors, 1.8% required a routine consultation while 1.1% required emergency consultation (Katzman et al, 1999). Subsequent studies confirmed the presence of abnormalities in "healthy" subjects. A study by Illes and collaborators, aiming at re-examining scans obtained for research using MRI and Functional Magnetic Resonance Imaging (fMRI) shows that 47% (71/151) of adult subjects had abnormalities. Of these 71 cases, 10 (6,6%) needed a clinical follow-up: seven a routine exam and three an emergency exam (Illes et al, 2004b). Using the same methodology, this same team studied scans acquired from the paediatric population (N=225), and 21% of the scans were found to contain abnormalities. Eight per cent: (17/225) needed a routine exam and one case required an emergency consultation (Kim et al, 2002). In August 2002, Sarah Hilgenberg, a young student, leaves Boston to undertake medical studies at Stanford University in California. She makes this long trip by car with all her personal belongings. Once at Stanford, she receives, as do some other students, an invitation from two senior students to go camping and hiking in the Sierra Nevadas the following weekend. Sarah starts her session and doesn't hear from her camping group. A little while later, she receives the following invitation addressed to all the members of her camping group by Matt, one of the senior students: "I hope that your first week of anatomy wasn't too painful. Two research subjects cancelled their appointment for their brain scan tomorrow. Would some of you be interested in having your brain scanned during a memory test? It will only last an hour and a half and you will be paid 40 dollars. I have openings at nine o'clock and noon tomorrow. Your roommates and partners are also welcome." Sarah accepts this invitation without hesitation, but she did not at all suspect what awaited. She arrives at the imaging centre, meets Matt and signs a brief questionnaire. Everything proceeds normally and after having briefly answered some other questions, she arrives at home. Suddenly, she receives a call from Matt in the With a quavering voice he tells her: "We found something abnormal on your scan". Matt reveals that he made her quickly leave the imaging centre in order to consult a neurologist. Disbelieving and in tears, Sarah arrives at the imaging centre. In order to accelerate her admission to the hospital, she and Matt arrive by foot at the emergency room of the medical centre, which is a stone's throw from the imaging centre and the Faculty of Medicine. Sarah slips on a hospital gown and meets a neurologist. She is now not only a medical student, but a patient. The neurologist makes an emergency call to a technician in order to prevent delaying the diagnostic exam until Monday morning. Sarah waits for one hour accompanied by an associate dean of medical education. She meets the neurologist after the exam. "Sarah, you have an AVM", he tells her. "Do you know what that is?" She makes a sign that she doesn't know. That means "Arteriovenous malformation". Sarah's parents then arrive at Stanford. Together they meet an AVM expert and decide together that two embolizations and a resection are necessary. Sarah is anxious and distressed while awaiting surgery. Vignette (extracted from Hilgenberg, 2005) The majority of incidental findings prove to be benign incidents after closer examination. However, their presence in a research environment raises important questions for the responsibility of researchers and they represent a source of medical and ethical concern (Illes et al, 2002). Many questions emerge, and answers depend on diverging ethical principles as well as the various views on researcher responsibility. Respect for the autonomy of subjects and patients as well as a concern for transparency leads to an obligation to convey information to research subjects (Philips, 2005). Certain precedents regarding research ethics particularly in the United States following the case of Grimes vs Kennedy Krieger Institute which was taken to the appeals court of Maryland (Mastroianni and Kahn, 2002; Wendler, 2004), support the responsibility to reveal information having an impact on the health of participants, even in the context on non-clinical research. The question then remains as to how this should be done. Should we anticipate a consultation with a neuroradiologist (Illes et al, 2002; Kim et al, 2002)? Who should pay for such services? Should the risk of detecting abnormalities be mentioned in the research consent form? Table I:
Emerging ethical challenges in neuroimaging

Explanation
Challenges
The creation of standards permitting the introduction of functional neuroimaging into medical practice and facilitating the reproduction of experiments between laboratories faces numerous obstacles (Desmond et al, 2002; Ford et Kubu, 2005; Rosen and Gur, 2002a; Rosen et al, 2002b). methods and replicating studies. The increased diagnostic and predictive use of neuroimaging, similarly to genetic testing in the To improve the lot of the patients and to absence of symptoms, most notably in cases of Alzheimer's disease, schizophrenia and prevent discrimination and stigmatization depression may one day be a reality (Andreassen, 1997; Hyman, 2003; Pezawas et al, 2005; Rosen and Gur, 2002a ). Some fear that this could lead to the prediction of behaviours such as sexual orientation or racial prejudices (Wolpe, 2002). Neuroimaging services are sometimes sold directly to consumers, without medical consultation. To prevent conflicts of interest in the offer This practice occurs most often in the United States (Illes et al, 2003; Illes et al, 2004a) but is developing in Canada. Certain practices are considered quackery (Health Canada, 2005). At the obligations towards consumers and patients. same time we are witnessing conflicts of interest in the medical community (Cho, 2002). The public over-invests the power of neuroimages, which leads to an increased risk of hasty interpretation and application (Bruer, 1998; Check, 2005; Racine et al, 2005a; Racine et al, To identify the precautions to take in the generalization of results. The shortcomings in the availability of imaging services has lead to the flourishing of diagnostic To reflect on the role of neuroscientists in services offered by the private sector in Canada (Canadian Institute for Health Information, social justice and in the debate on the future 2004; Bernstein and Mikulis, 2004). Those who can pay for this service can avoid waiting in line of our health system and the role the private by passing ahead of other patients waiting for a diagnostic service, and thus access more rapidly Numerous recent articles have revealed the fears of the public regarding the protection of privacy, not only to protect access to databanks containing a large number of scans (Mazziotta, applications of the social neurosciences. 2000; Toga, 2002), but also access to personal thoughts with neuroimaging tools (Editorial, To identify the appropriate safety measures necessary to protect privacy and confidentiality. A right to information would possibly be accepted by clinicians, but what about the researchers
who do not have clinical training, and who are not regulated by a code of professional ethics that
includes a prima facie duty to patients? Should these researchers be held to the same type and
level of responsibility? Do all researchers have the necessary training to be held responsible for
the detection and disclosure of abnormalities?
Further, it is possible that subjects expect that a health professional will review their scans
obtained for research purposes (Rosen et al, 2002b). This type of expectation of clinical
advantages in the context of research has been dubbed a "therapeutic misconception"
(Appelbaum et al, 1987), a frequent phenomenon in oncology clinical trials. Should such
expectations of benefits be approached head-on in the consent process in order to prevent
research subjects from entertaining false hopes? Should we fear that certain subjects accuse the
researchers of not having detected an obvious abnormality? These questions demonstrate the
complexity of identifying the responsibility of researchers when faced with an incidental finding
of abnormalities in the context of neuroimaging research. They also emphasize the necessity of a
responsible and proactive ethical attitude in the practice of research.
It must, however, be remembered that the scans produced in the context of research do not
necessarily correspond to the requirements of a clinical scan. The interpretation of incidental
findings sometimes proves to be very difficult, and determining its clinical significance may
prove to be a source of difficulty. In particular, incidental findings in the field of paediatrics
complicate the evaluation of the abnormality given the complexity of predicting the future
development of a child based on neuroimaging (Hinton, 2002). In such cases, how may hasty
conclusions be prevented if incidental findings are revealed to the subject? It is important to note
that the ethical principal of non-maleficence (Beauchamp and Childress, 2001) suggests that such
a revelation risks causing unnecessary distress in subjects. In the case of patients, in particular
patients suffering from serious illness, does such a revelation risk magnifying the perception of
the seriousness of the illness? In the case of individuals who believe themselves to be healthy,
will that affect their ability to obtain a life insurance policy, as was indicated in the case
published in Nature? To eliminate this risk, should the patient be confidentially informed of the
IF and then be able to seek out help if he or she so wishes (not being referred directly to a health
professional) in order to prevent the inclusion of the IF in the medical file?
Considering the tension between the principles of respect for autonomy and beneficence on the
one hand, and the principal of non-maleficence on the other hand, it can be predicted that each
individual case of IF will lead to ethical questioning before being resolved depending on the
balance of the different ethical principles as well as the condition of the patient.
Second scenario: Improving human capabilities using neurotechnology
The expected benefits of neuroscience are traditionally associated with the alleviation of
neurological and psychiatric illness. Without losing sight of the immense benefits of the
treatments and increased understanding of illness, we will consider the issues associated with the
use of neurotechnology for the purposes of enhancement. We are aware that we are approaching
a controversial subject, where science and speculation are entangled. Nevertheless, we believe it
is important to illustrate, with the help of this example, the necessity of a prospective discussion
about the broadened social responsibilities of researchers and the future consequences of such applications. In order to grasp the scope of the enhancement issue, it must first be mentioned that the use of pharmaceuticals is increasing, and represents a growing health expenditure. Among drug expenditures, neuropharmaceuticals are well represented (Canadian Institute of Health Information, 2005). In itself, this dynamic raises numerous questions concerning the habits of patients, the practices of health professionals, as well as the responsibility of industry and government. About fifteen years ago, the growing use of Prozac provoked a lively debate about the possibility of feeling "better than well" (DeGrazia, 2000; Elliott, 2000). Today, the possibilities of pharmacological enhancement and lifestyle-related use - practices relying on fundamental medical unknowns - are multiplied in conjunction with the intensification of marketing by pharmaceutical companies (Chatterjee, 2004; Dees, 2004; Farah, 2005; Farah et al, 2004). Table II presents the results of recent studies in neuroscience. Opportunities of neuropharmacological enhancement that could potentially affect concentration, memory, and sleep are featured. Also identified are the ethical issues associated with these possibilities, such as the clarification of the limits of enhancing neurotechnologies and the consequences of such uses. Source of immense hopes for treatment, these advances could also lead - according to some authors - to a cosmetic neurology (Chatterjee, 2004) associated with multiple ethical issues. The "opportunities" for enhancement could intensify the questions of distributive justice and cast doubt over the meaning of medical intervention, and of medicine in our society (Racine, 2002b). Coercion represents another considerable issue if we consider both the precedents in the use of enhancing products such as amphetamines in the context of the American military, as well as the high rate of Ritalin use among schoolchildren, and especially among boys (Farah, 2005). It remains however, to be seen if enhancement of a cognitive function is possible and what would be its consequences. In addition to neuropharmacology, other areas of research in neuroscience are resulting in neurotechnologies with the potential to enhance human performance. For example, the hope of developing a functional interface between neuronal tissue and computer components has been a driving force behind neuroengineering research for decades (Nicolelis, 2001). Recent advances suggest that the dream of a functional brain-machine interface is coming closer to reality, so to speak (Donoghue, 2002; Hetling and Baig-Silva, 2004; Nicolelis, 2001; Nicolelis, 2003; Schwartz, 2004; Wickelgren, 2003) even though many significant challenges remain. Currently, the treatment of Parkinson's disease constitutes one of the most important medical successes attributed to these interfaces (Walter and Vitek, 2004). However, the applications of cerebral implants could extend (Abbott, 2005). For example, a Torontonian group recently published results suggesting the efficacy of neurostimulators (deep-brain stimulation type) in the treatment of major depression (Mayberg et al, 2005). Some have questioned if it will one day be possible to add sensory modalities or to accelerate the processing of information and cognitive processes in healthy individuals (Maguire and McGee, 1999). Nicolelis, a prominent researcher in this field, has suggested that these technologies could provoke "a revolution in the way future generations interact with computers, virtual objects and remote environments, by allowing never-before-experienced augmentation of perceptual, motor and cognitive capabilities" (Nicolelis, 2001). Presently, the invasive character of these interfaces limits these possibilities, but what would happen if these interfaces became safer and less invasive? Table II:
Examples of potential neuropharmacological enhancers

Enhancement
Explanation
Challenges
opportunities
The public is generally worried about the use of methylphenidate (Ritalin) for the treatment of Attention Deficit/Hyperactivity Disorder (ADHD) (Diller, 1996). Research suggests that Ritalin can improve normal performance in the accomplishment of various tasks and in the functioning of short-term memory (Elliot et al, 1997; Mehta et al, 2000). One study indicates that the recreational use of methylphenidate amounts to 17% among 283 respondents in an American liberal arts college Molecules that can compensate for cognitive deficits and memory, mainly those caused by neurodegenerative illnesses such as Alzheimer's disease could possibly become enhancers of cognitive performance (Lynch, 2002; To predict the biological, Rose, 2002). One study reports that Donepezil, an acytylcholinesterase inhibitor currently used in the treatment of Alzheimer's disease, improves the performance of commercial airline pilots in the context of simulation flights (Yesavage et al, 2003). A pilot study suggests that a β-adrenergic receptor blocking agent (Propranolol), which apparently acts on the activity of the amygdala, could prevent or weaken the consolidation of undesirable memories associated with post-traumatic stress (Pitman et al, 2002). In January of 2003, the biopharmaceutical company Cephalon filed a request (subsequently rejected) to approve modafinil (marketed under the name Provigil and originally developed to relieve narcolepsy) for the treatment of minor symptoms of fatigue. By the admission of Cephalon, 90% of prescriptions for Provigil do not conform to the indications for use contained in the instructions (off-label use), and uses have been reported where the objective is performance enhancement in sports, or to remedy jet-lags (Vastag, 2004). The military interest for these devices and performance enhancement in general is undeniable (Blank, 1999; Wickelgren, 2003). Representatives from the Defence Advanced Research Projects Agency (DARPA), an agency that funds many major brain-machine interface projects in the United States, has confirmed that their intentions are to eventually enhance the performance of military personnel, for example, by allowing the surveillance of cerebral activity of personnel (Hoag, 2003). Other non-invasive neurostimulation techniques such as Transcranial Magnetic Stimulation (TMS) are used for the treatment of depression in Canada. One study suggests that TMS could possibly serve to enhance cognitive performances temporarily and reversibly (Snyder et al, 2003). Since the Food and Drug Administration standards for the approval of medical devices differ from the standards in place for the approval of drugs, some are concerned about the rapid approval of the further uses of neurostimulators and the influence of conflicting interests (Carey, 2005). The companies that develop these devices could be interested in broadening their use and sale. One of the main companies in this field, Medtronics, was accused in 2003 of paying kickbacks to neurosurgeons who carried out spinal fusion surgeries (Ausman, 2004). This example illustrates that the process of developing neurotechnologies and the requirements associated with their marketing are sometimes in conflict with the objectives of medicine, particularly where a public health system pays a portion of the costs of medication. It is not surprising then that the medical profession is discussed more and more as being susceptible to conflicts of interest which represent a significant threat to the integrity of the medical profession and further contribute to the uncertainty on the ethical guidance for the use of neurotechnologies (Hauser, 2004). The current debate on enhancement surfaces in the scientific community and among bioethicists. It remains to be seen if such possibilities will remain science fiction or if they legitimately fuel fears and debates. The current situation suggests, nevertheless, a tendency towards the use of medication for lifestyle-related purposes (Flower, 2004), such as with Viagra (Farah, 2005). Furthermore, other medications approved for medical purposes are used for surprising uses such as for the re-growth of hair (Minoxidil, originally used for hypertension) or to accelerate weight loss (Orlistat, originally used for obesity and Subropion, originally for anorexia) (Flower, 2004). These enhancements could at first seem morally dubious. However, a more detailed examination leads to the awareness that there are always cases where being bald, or of small stature, as is indicated for the use of growth hormones, becomes a source of much difficulty and psychological distress (Allen and Frost, 2004). The interaction of enhancement practices with lifestyle uses greatly complicates the ethical
analysis of enhancement. However, the participation of researchers in current and future
discussions seems essential to an enlightened debate. In addition, the claims of enhancement may
prove to be a utopia with unsuspected harmful consequences for its proponents. Indeed, if such
illusions are not dispelled, we risk facing ill-informed abuses (Rose, 2002). Thus, in a context
where the use of certain neurotechnologies with an explicit goal of enhancement is gaining
ground, it is of utmost importance for the neuroscience community to participate in proactive
discussions regarding the uses of neurotechnologies.
Third scenario: Communicating and interpreting research results
If researchers do not share information, the public cannot be informed of the research occurring
in neuroscience, or make use of the resulting products. When the funding of research comes
partially from public sources, an obligation to share results of research ensues, if only to ensure
the free development of knowledge. This obligation can spread to other actors (e.g., industrial or
community) wishing to use the knowledge for the benefit of others. In the application of the
responsibility to communicate the fruits of one's work, the researcher risks, however, that the
information may be misunderstood or that interpretation may lead to unwise uses.
Ancient and recent history in neuroscience reveals situations where certain troubling
interpretations have been conveyed. For example, the popularization of psychosurgery (Gostin,
1980) originates partially from optimistic reports found in the media (Diefenbach et al., 1999).
Even if they have always been contested by cautious scientists, phrenologic theories and their applications in the fields of education, religion, law and health have captivated some scientists as well as the public (Hagner and Borck, 2001). It must be recalled that Gall, the father of phrenology, wanted to introduce the analysis of cranial lumps to evaluate the risk of committing subsequent offences in accused criminals (Lanteri-Laura, 1996). At the beginning of the last century in Germany, pseudo-scientific techniques for the detection of electrical activity in the brain such as diagnoscopy fascinated the public. In addition, the theories of cerebral harmony and cerebral characterology disseminated by neuroscientists as influential as Cecile and Karl Vogt, promised to transform these types of techniques into tools of social management. It appeared necessary to find means of stimulating the job sector and improving the lot of an economy, which was in a dramatic state of collapse following the First World War (Hagner 2001). Thus, certain hopes that today seem to be simplistic were founded on dubious interpretations of neuroscience. The beliefs of the public and the interpretations of neuroscience by researchers are not always well grounded, as history has shown. Today, the drive to find cures for human diseases persists. This impetus reinforces the expectations facing medical technologies and supports beliefs in alternative medicine. Consequently, certain situations still lead to attempts to hastily apply neuroscientific knowledge. For example, in the nineties, the media popularized the results from a study suggesting that the intellectual capabilities of very young children could be improved by simply listening to recordings of classical music (Rauscher, 1995). This study, conducted in fact on adults, and having been reproduced with difficulty nevertheless lead to the free distribution of recordings to all new-borns in certain American states. These public health programs are based on debatable interpretations of cerebral development and synaptogenesis (Bruer, 1998). Another example: today we can read in the media that the results of neuroimaging studies provide new bases for social practices as diverse as marketing, education, and ethics. Often conducted on a small number of subjects and according to idiosyncratic experimental designs, these studies have a number of limits. In fact, the results of neuroimaging studies are generally based on a method where the baseline state of the resting brain (a debated concept) is subtracted from the activity associated with the accomplishment of a specific task (e.g., a memorization assignment, a reading exercise). Typical conclusions are that the activity specific to the experimental condition is associated with the task, which raises numerous epistemological questions (Desmond et al, 2002; Illes and Racine, 2005b; Rosen et al, 2002b). In addition, fMRI, for example, is sensitive to the proportion of oxygenated and deoxygenated haemoglobin: it does not directly measure neuronal activity, but one of its probable consequences, the recruitment of oxygenated blood to sustain the increased metabolic activity in the active neurons (Logothetis et al, 2001). These important nuances are rarely reported in detail in newspapers and magazines (Racine et al., 2005a). Thus, it becomes apparent that the responsible interpretation of scientific knowledge is a challenge that also arises in the contemporary context. What does the public understand of all the scientific complexity inherent in contemporary neurotechnology? Examination of the press, one of the sources of public information, shows that dubious interpretations and certain exaggerations are conveyed (Racine, 2005a). A survey on neuroscience literacy suggests that neuroimaging modalities are poorly understood by the public (Herculano-Houzel, 2002). Thus, we are far from an understanding of the limits of neurotechnology and a fair appreciation of its scientific contribution. Should we be concerned about the observed trends? The risks associated with the communication
and the sharing of results should be weighed against the actual and expected benefits. A more
enlightened approach must be construed regarding the responsibility of researchers when they
share their results. For example, among the precautions, the methodological limits could be
emphasized. There remains much to be accomplished to better define the level of neuroscientific
literacy of the public. Likewise, little is known concerning the sources of information available to
the public and to patients, due to the new communication media such as the Internet. However,
the use of new neurotechnologies must be based on responsible interpretations that facilitate the
transfer of knowledge and an improvement in quality of life for patients.
Discussion: A multidimensional framework for responsibility in neuroscience
Our analysis of three examples from contemporary neuroscience suggests that challenges for the
responsibility of researchers and clinicians are emerging. We will now outline a framework to
approach responsibility of researchers in neuroscience (Table III, inspired by Racine, 2002a).
Essentially, it consists of guideposts that may stimulate ethical reflection on the practice of
research.
Scientific responsibility and integrity
Do I respect and honour scientific rigor in all aspects of my work?
Current pressures push researchers to heights of scientific productivity, but this dynamic also
raises question pertaining to the integrity of researchers (Tyers et al, 2005) and to their
fundamental commitment towards scientific knowledge and its governing principles (Young,
2005). A study published recently in Science suggests that serious professional misconduct
happens in an appreciable proportion (and probably underestimated) of both junior and senior
scientists (Marinson et al, 2005). The causes of this phenomenon are probably profound, but they
concern all researchers. To emphasize the responsibility of researchers in neuroscience and their
commitment to integrity, we can recall the phrase of the former president of the Comité
Consultatif National d'Éthique (CCNE) in France, Jean Bernard: "that which is not scientific, is
not ethical", a requirement which is inscribed in the guidelines of the Council for the
International Organization of Medical Sciences.
In addition, scientific integrity also implies a growing collaboration between researchers to
promote the development of valid and sound knowledge. We have given as an example the
collaboration between researchers in neuroimaging to ensure the reproducibility of experiments
and the sharing of research methodologies (Table I). In such a case, we can hope that the
expected benefits will be realized more rapidly than if the efforts were only weakly concerted.
Numerous obstacles may slow down this process: the low availability of funding for the formal
replication of studies or for the preservation of large databanks allowing the consolidation of
knowledge (Merali and Giles, 2005), to the sharing of analytical software used to process the data
(Desmond et al, 2002).
Responsibility-responsiveness
Are the interests of others part of my research practices?
Research that is conducted on human subjects entails that people are volunteering to science. This
balance between the subject as an instrument of research, and the subject as a human being may
lead to his or her exploitation and reduction to a simple means in the service of research. The case
of IFs in the context of neuroimaging sparks difficult ethical problems in this respect. An altruistic management of these findings appears desirable: the subject is not just a tool of research. The dignity of his or her person must be recognized. In the management of IFs, the competence and the resources of the research teams must be considered. However, an empathetic and concerned attitude giving way to the interests of others is necessary in the practice of research. Civic and democratic responsibility Do I adopt a broad outlook on the consequences and social implications of neuroscience? Knowledge transfer to the public is necessary. We will recall that many researchers receive part of their research funds from the public, and that the public has the right in return to expect recognition for this participation (Leshner, 2005). Positive experiences of multidirectional communication enabling researchers to exchange with the public have occurred in Canada and elsewhere (Abelson et al, 2003). However, transfer of knowledge does not always go without saying, and numerous difficulties can arise for researchers wanting to share their results and the exercise of a civic and democratic responsibility. As has already been discussed, the public does not always have a thorough understanding of the information presented. Controversial studies on social behaviours give rise to premature uses such as using neuroimaging as a lie detector in the form of "brain fingerprinting" (Wolpe, 2005). The use of neuroimaging as proof in criminal law to obtain clemency from the jury (People vs. Weinstein; Presidents Council on Bioethics, 2004) as well as the use of neuroimaging to survey the preferences of consumers (Editorial, 2002; Editorial, 2004), are two other examples. We have emphasized the pitfalls that occur when premature applications and interpretations become widespread. Researchers must individually ask themselves if they are directly or indirectly contributing to the clarification of the limits of knowledge in order to present a fair insight into the expected benefits of neuroscience. Prospective responsibility Do I participate in discussions on the future of neuroscience and its applications? There are situations where science and science fiction intermingle. The example of performance enhancement with the help of neurotechnology is an example of such a scientific and ethical controversy. Researchers may sometimes have doubts about certain potential applications, but they must at least remain open to more distant scenarios and exercise proactive responsibility to consider the remote consequences of their actions. The debate about enhancement is currently taking place, and scientists must intervene to clarify if such possibilities are real or not, and what would be their impact. Prospective responsibility must be promoted. Responsibility of self-reflection Do I inquire about and reflect on the precedents of my discipline, its ethical successes and errors? In conclusion we will emphasize a dimension of scientific responsibility that is a backbone for the others: the necessity of self-reflection on one's own research. Historical precedents illustrate how researchers in neuroscience have supported the most infamous acts such as those leading to the extermination of the most vulnerable, in the sad case of the German Third Reich (Shevell, 1999). Contrary to this dismal cruelness and inhumanity, we must also keep it mind the illustrious history of neuroscience. Some great neuroscientists have marked history and humanity, their work positively changing lives by promoting a deepened understanding of the nervous system, the development of therapies and the humanization of neurological and
psychiatric illness. Certain figures, or at least certain of their attitudes (as no one is without fault)
stand out as models of caution and self-reflection. For example, while many neuroscientists of the
era criticized dualism and supported monism, the great British neurophysiologist Charles
Sherrington refused to promote this attitude. A cautious and reflective man, he believed that
considering the knowledge of his era, such attitudes would threaten culture and human values
(Smith, 2001). We must acknowledge that there are challenges in personal reflection in all fields
of research activity. However, certain movements such as the introduction of the humanities into
the medical curriculum (medical humanities) may prove to be the paths that broaden the
education of researchers and physicians to help them develop skills in critical and constructive
self-reflection.
Table III:
Some dimensions of responsibility in neuroscience (from Illes et al 2005; Racine, 2002a)

Responsibility
Description
Examples of daily acts
• An effort to validate methods and multi- site dialogue for the use of new technologies. • Balanced presentation of the merits and • Participation in ethical reflection on the • Analysis of the history of neuroscience and its applications to better understand the challenges that currently emerge and to identify possible solutions to these challenges.

Conclusion: A call to the disquieted moral conscience
In exploring the diverse facets of normal and pathological functioning of the nervous system,
researchers in neuroscience participate in the development of interventions in neurology and
psychiatry. They thus contribute to the improvement in the quality of life of patients suffering
from illness for which there is often still too few treatment options. In addition, a better medico-
scientific explanation may serve to dispel prejudices and to deepen our understanding of illness
and those who suffer from it.
However, responsible conduct in research yields multiple issues that challenge researchers and
clinicians. The examples of incidental findings in neuroimaging, the enhancement use of
neurotechnology as well as public communication of results demonstrate that it is necessary to
consider responsibility according to a multidimensional framework that reiterates the
fundamental character of scientific integrity and also incorporates dimensions such as self-
reflection that are less obvious in the formal research ethics guidelines. Hopefully, the proposed
framework will nourish personal reflection concerning the ethical issues and applications of
neuroscience, and a discussion on the responsible attitudes of researchers will follow. In fact, if
formal guidelines assist researchers in ethically conducting their research, researchers remain
accountable for their actions. As the bioethicist Hubert Doucet has stated regarding ethical
reflection in genetics, beyond codes and guidelines, a disquieted moral conscience is an asset
possibly as valuable as the rules that can suppress self-reflection and awareness of individual
responsibility (Doucet, 1994).
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