… [T]he evaluation of healthcare activities is an ethical minefield, strewn with explosive material not easily detected by the naked eye… it is our duty to rush in where others fear to tread, even if in the process we find ourselves being maligned as insensitive troublemakers…
(Williams 1992).
NEUROIMAGING has been to neuroethics what free will and determinism have been, albeit for much longer, to philosophy: pillars for scholarly inquiry and curiosity, and entries to dialogue, debate, and discovery. Early in the days of functional neuroimaging using magnetic resonance imaging (MRI) technology, Illes and colleagues (Illes et al. 2003) explored studies at the juncture of this exciting new way of interrogating signals from the brain using probes for behavioral response drawn from philosophy. With interest piqued by reproducible measures of regional blood flow in the human brain under well-defined conditions such as existential problem-solving, decision making, and trust, we meticulously documented emerging trends involving functional MRI (fMRI) studies among the several thousand papers published at the time. In this short chapter here, we build on that work and examine the hypothesis that almost 20 years after the first wave of such studies, the focus on neuroimaging and its application to complex and profoundly personal human behaviors has not abated. Infact, while many topics have captivated scholars interested in neuroethics, as the chapters in this volume show, we assert that neuroimaging studies remain an unwavering source of energy for the field. Toward this goal, we review some of the reasons that they have provoked so much attention in neuroethics and elsewhere, present a 2002–2008 update to the trends we documented for 1991–2001, compare this second generation of data to the first, and share our observations.
Consideration of the ethical, legal, and social implications of emerging technologies in science and medicine has historically lagged behind the discovery of the technological capabilities themselves. Delays in contemplating the acceptability and potential applications of biomedical advances have posed significant problems for the scientific community and the public alike. Consider for example, the impact on science when significant advances preceded thorough consideration of the potential ethical and social impact of genetic screening (Rothenberg and Terry 2002), the cloning of humans (Cho et al. 1999), and even genetically modified foods (Thompson and Hannah 2008). Advanced capabilities for understanding human thought and behavior enabled by modern neurotechnologies have brought their own substantial challenges to the forefront of scientific and public scrutiny. Unlike the past, however, scientists and scholars with interests at the intersection of neuroscience and ethics have been proactively anticipating ethical, legal and social issues in this domain of scientific pursuit, raising pointed questions about the brain and human nature, whether the information is what people in fact want or ought to know, and how best to communicate it.
The understanding of why people behave as they do is closely tied to aspects of everyday life including society’s laws and religious beliefs. Neuroimaging is producing increasingly comprehensive explanations of human behavior in biological terms. To this end, neuroethicists have been asking: How does the biological basis of phenomena directly related to human motivation, reasoning and social attitudes affect how people think of others and themselves? Shall any knowledge be forbidden or left untapped and is the lament of some concerned scholars and citizens that we ought to leave some human phenomena unexplored legitimate? Innovations in neurotechnology bring to the foreground the need for an appraisal of the place and the limits of technology in the relationship between mind and brain and, ultimately, between values, people, and society.
Underlying many of the claims concerning the power of modern neuroimaging is the belief that functional imaging offers a direct picture of the human brain at work (Illes 2007). Such belief brings both promise and apprehension, and in this regard there has been a historical interest in ethics in neuroimaging. The widespread use of accessible, noninvasive neuroimaging techniques, such as fMRI, raises social and legal issues including privacy of thought, prediction of violence or disease, truthfulness, and personal responsibility for behavior (Illes and Racine 2005; Aggarwal 2009; Fenton et al. 2009). Will advances in neuroimaging give the criminal justice system revolutionary or troubling new tools (Meegan 2008)? Will data on how people process information influence how they are treated by society (Farah 2005)? Do they raise the potential for unjustified discrimination (Glannon 2006)? The increasing attention to ethics in neuroscience is not surprising, therefore, given unique concerns surrounding apparent new capabilities to monitor and translate motivation into action.
In Illes et al. (2003), we reported on peer-reviewed journal articles of studies using fMRI, alone or in combination with other imaging techniques, published between 1991 and 2001. We analyzed and coded each article by publication type—original research or review—and into one or more classifications for study type: motor, primary sensory, integrative sensory, basic cognition, higher-order cognition, emotion, clinical, methods development, non-human primate. The journals in which all coded papers were published were also tracked.
The initial search for relevant articles yielded 3426 unique returns published across 498 different journals. Regression analyses showed a significant increase for the original research and review papers, numbers of journals, and studies reporting clinical results and methods development. More importantly for our purposes, studies classified as higher-order cognition and emotion—i.e. non-clinical studies considered to have direct translation for everyday behaviors such as human motivation, reasoning and social attitudes—also increased significantly, at a rate of 0.8% per year. Given those results, Illes et al. called for more ethics input than before to the increasing application of neuroscience research to complex human phenomena. In addition, we appealed for a wider perspective on the construction of scientific knowledge in general in the context of such studies, and its meaning in the context of brain and mind, identity and personhood (Illes and Racine 2005).
Has the landscape changed over the past 10 years of fMRI research? Here we sought to understand whether the increasing application of fMRI technology to non-clinical studies considered to have direct meaning for everyday behavior was a transient phenomenon due, for example, to the new opportunity for noninvasive, repeatable imaging with high spatial resolution, or a continuing one with enduring characteristics. To this end, we updated the taxonomy developed by Illes et al. (2003) for application to studies over the next decade (Table 22.1).
Our search for new studies began in 2002, the endpoint for the original study, and the year coincident with the Dana Foundation meeting that “[brought] together scientists, ethicists, humanists, and those concerned with social policy to reflect on the broad implications of current and ongoing research on the human brain” (Marcus 2002). The formal search for the updated database closed at the end of 2008. For consistency and comparability to the previous study, the comprehensive database of all articles using functional neuroimaging techniques was compiled using PubMed and OVID search engines. As before, the search included all permutations and acronyms of the term “functional magnetic resonance imaging,” although we only considered original research studies this time. The database was manually cleaned for duplications, as well as for irrelevant returns such as fMRI investigations of non-cerebral activity (e.g. renal or cardiac function).
Table 22.1 Examples of major categories with “real-world implications”: higher order cognition; self and mental states
After establishing intercoder reliability (Cohen’s Kappa = 0.95), two of us (C.F. and S.L.) blind to journal, year, and author each coded half of the articles based on paper titles and, as necessary, abstracts, as having ‘implications for real-world contexts’ (Table 22.1) or not. Review articles and investigations using non-human animals were excluded from further categorization.
Table 22.2 Examples of article codes
After a first round of independent review, we further categorized all relevant articles having “real-world implications” into one of the two categories as primary, and added a code for the secondary category if appropriate (Table 22.2). For example, a study such as “fMRI evidence for a three-stage model of deductive reasoning” (Knauff et al. 2006) was coded as higher order cognition, and the study, “The self as a moral agent: linking the neural bases of social agency and moral sensitivity” (Moll et al. 2007) was coded as both (Table 22.2). In all cases, discrepancies between reviewers’ codes were decided by consensus upon joint review or in consultation with the third author.
The searches returned a total of 12, 967 articles across 1378 unique journals. Of these, 1198 (9%) met the criterion for real-world implications as we defined it. The number of journal articles and journals publishing these articles increased steadily from 2002–2008 at an average rate of 186 new articles (t7 = 4.745, p <0.01) and 38 journals (t7 = 2.739, p <0.05), annually (Figure 22.1, primary axis).
In 2007 and 2008, reports of such studies exceeded 10% of the total number of functional neuroimaging articles per year. There were more than twice as many articles pertaining to self and mental states (67%, n = 797) than those of higher order cognition (27%, n = 326), and tenfold more than pertaining to both (6%, n = 75). This pattern did not change significantly over time (p >0.7; Figure 22.2).
FIG. 22.1 Solid lines: number of journal articles, journals (primary y-axis) and articles with implications for real-world contexts (secondary y-axis) from 1991–2008. Data from Illes et al., 2003 are shown in the shaded area. Dashed line: results of an automated query for fMRI studies with real-world implications (Garnett et al. 2010), also yielding up to date data. The automatic returns are predictably more conservative than the manual coding from which they are derived. 2009 data are likely low yields given still incomplete PubMed indexing for that year at the time of this writing (February 2010).
FIG. 22.2 Relative percentages of articles related to self and mental states, higher order cognition, both self and mental states and higher-order cognition from papers coded as having real-world validity between 2002–2008.
The data suggest that the power of fMRI, alone and combined with other imaging technologies such as EEG and PET, continues to be harnessed to pursue the neurobiology of complex, human phenomena. There was early momentum in the 1990s in this direction, and it was far from fleeting. Besides a sheer increase in numbers of studies, post-2002 fMRI research has revealed neural correlates and ever more intriguing results, for example, about the pain of losing a loved one and romantic love. For the former, Eisenberger et al. (2003) demonstrated that signals of social exclusion are similar to those of physical pain, and that related activity in the anterior cingulate cortex (ACC) acts as a neural alarm system during social exclusion. For the latter, Fisher et al. (2005) used stimuli invoking romantic love to produce activation in the right ventral tegmental area and right caudate nucleus, dopaminerich areas associated with mammalian reward and motivation. Yet other studies have delved into biases and belief systems, suggesting that psychological dimensions of religion are mediated by brain networks that process intention and emotion and that engage abstract semantic processing (Harris et al. 2009; Kapogiannis et al. 2009).
In 2002, Adina Roskies provided thinkers in neuroethics with a clever way to conceptualize fMRI studies embodying a real-world component: she called them studies of the neuroscience of ethics. Besides heavily quoted definitions of neuroethics from the late William Safire and from Michael Gazzaniga, probably the next most cited is the two-part taxonomy of neuroethics provided by Roskies distinguishing these types of studies from those that focus on the conduct of research, the ethics of neuroscience. While the taxonomy appropriately characterizes the former classification of studies that we consider to have real-world relevance, and there are plenty of them as our data suggest, like all other fMRI research involving human subjects, these studies also contain fundamental research ethics issues captured by the “ethics of..” side of the taxonomy. Like studies of addiction (e.g. Volkow et al. 2004; Hall et al. 2008), minimally conscious states (e.g. Fins et al. 2008; Laureys et al. 2009), and aging (Greicius et al. 2004), fMRI of mental states has all the human subjects challenges of informed consent, capacity to consent, privacy, and confidentiality. Therefore, the simple dualism of the taxonomy inadvertently affords a special status to the studies having realworld implications where it does not necessarily belong.
While we are as guilty as others in perpetuating this oversimplification in now two studies (Illes et al. 2003; and by virtue of the data we have presented here), we wish to encourage a departure from it. We propose that ethics of neuroscience becomes the superordinate category for thinking about neuroimaging and ethics, and that new categories such as addiction neuroethics, and neuroethics of enhancement, of deep brain stimulation and of vegetative states, perhaps mirroring the formation of new interest groups within the professional Neuroethics Society (http://www.neuroethicssociety.org) be explicated as subcategories. This more fine-grain definition will unpackage the “other” studies according to the unique characteristics and scholarly focus they rightly possess and the new ethics challenges in neuroscience they bring forward. In parallel with this proposal, the chapter by Fishbach and Mindes (Chapter 21) and Fins (Epilogue) in this volume provide other illuminating strategies for meeting similar goals.
Early studies falling into the (old) category of the neuroscience of ethics were quickly criticized as intruding on the very nature of humanness and, with the potential to biologize beliefs, spirituality, and human dignity, placing them at risk (Farah and Wolpe 2004). Some commentators expressed a keen need to preserve and keep them out of the hands of scientists (President’s Council on Bioethics 2004). Yet others worried that such studies would lead neuroscience out of the science fiction of mind reading and into a reality that would give new meaning to what might be considered to be truth unto its innermost parts (the motto of the Massachusetts-based university named after Louis Dembitz Brandeis (1856–1941), Justice of the United States Supreme Court).
We reflect on these early writings and observe, first, that little has really changed about how people view themselves as moral beings, individuals and social actors as a result of relevant neuroimaging studies. In fact, after more than 15 years, there have been no shifts in religious or legal practice as a direct result of what has been learned from fMRI research, to our knowledge. Neuroscience is clearly informing policy (e.g. Greely and Illes 2007) and legal proceedings, and fMRI has now been admitted as evidence in the sentencing phase of a murder trial (Miller 2009), but to date have fundamentally changed neither policy nor the law.
Second, we observe that the publication of even some of the most remarkable studies of predictive phenomena, such as those of Haynes (Chapter 1, this volume) and Soon et al. (2008), or retrospective imaging evaluations of the truthfulness of past behaviors, have yet to find their place in the routine or daily life of the average person. There are anecdotes for attempts at the latter (Murphy and Greely, Chapter 38, this volume; McCormick and Brown, Chapter 40, this volume), and commercial endeavors around these applications, for lie detection in particular. They are enjoying considerable visibility but their readiness for prime time is dubious at best. Nevertheless, such studies are context-dependent, value-laden, and can be culturally sensitive. They create, therefore, a continued imperative for thoughtfulness and care at all points along the research to application trajectory, especially in the context of public understanding of neuroscience. While responsible science communication and accurate dissemination of findings are critical to ensure public support of and trust in neuroscience research (Illes et al. 2009), if the past predicts the future, early fears about the consequences of imaging research for our innermost sense of individuality can be calmed.
Where does the partnership between neuroimaging and neuroethics go from here? We predict that the coupling of technologies, such as neuroimaging with genetics-imaging genetics-is likely to propel neuroscience and medicine forward in the years to come, and the neuroethics discourse with it. Imaging genetics has emerged as a powerful and sensitive approach to the study of brain-relevant genetic polymorphisms with the potential to understand their impact on behavior (Bigos and Weinberger 2010). The combined technology has been applied, for example, to Alzheimer’s and Huntington’s disease with the goal of early prediction, improved disease tracking and advanced prevention strategies. It has been applied to improve the understanding of attention deficit hyperactivity disorder, depression, obsessive-compulsive disorder, anxiety, and schizophrenia, and to study emotional behavior (anxiety, response to fear) in healthy volunteers with different genotypes (Reiman 2007; Esslinger et al. 2009).
While imaging genetics remains a purely laboratory technique today, its potential integration into society requires careful reflection on how the knowledge may be constructed and interpreted by scientists, clinicians, patients, ethicists, and the lay public. The ethics challenges for genetics and neuroimaging have been explored at length separately, but the ethical space in which they overlap is just beginning to be explored. Tairyan and Illes (2009) suggested that the ethics issues at this juncture parallel the heightened discriminative power (the capacity to differentiate phenomena and distinguish them based on objective criteria) and cumulative power (the ability to gain greater information about the discriminated phenomena and by extension, associated ethics challenges) afforded by the powerful combination of technologies. In the new space, features of discriminative power concern better differentiation of disease, sometimes by ethnicity, and incidental findings. Features of clinical utility, prediction and intervention, and stigma and labeling share a common ground between discriminative and cumulative power. Privacy, autonomy, response sensitivity and attitudes, resource allocation for research and for health care, and commercialization, are features of cumulative power. The combined space also yields unique neuroethics considerations for science and society. These are characterized by new knowledge and new implications for health care, justice, and policy.
Ever-improving neurotechnologies and tools such as imaging, genetics, their combination or others to identify diseases and disease variants of the brain will bring the promise of personalized medicine to reality. Ethical issues related to the cost of health care and resource allocation notwithstanding, lives have already been changed through new knowledge about brain function, improved diagnosis of pathology, and movement toward tailored therapeutic interventions (Matthews et al. 2006; Monti et al. 2009).
The hope and promise has been and will be complicated, however, by direct-to-consumer marketing strategies adopted by an eager for profit sector both for clinical and non-clinical applications. The practical challenges of evidence for effectiveness, complexity of information, oversight and regulation, and tensions with traditional approaches to clinical practice described both for genetics (Conti 2010) and imaging (Illes et al. 2007; Lau and Illes 2009) will surely come into play. We are confident, however, that the type of forethought promulgated by neuroethics will pave the path by which benefits can reach people and patients, and will inform policy that sensibly and effectively mitigates risks.
The authors’ work is generously supported by CIHR/INMHA CNE #85177, the British Columbia Knowledge Development Fund, NIH/NIMH #9R01MH84282–04A1, Vancouver Coastal Research Institute. Sofia Lombera is currently at the London School of Economics. We thank Emily Borgelt for her input to this manuscript and the team and the National Core for Neuroethics for ongoing and insightful discussions about neuroimaging and neuroethics.
Abraham, A., Werning, M., Rakoczy, H., von Cramon, D.Y., and Schubotz, R.I. (2008). Minds, persons, and space: an fMRI investigation into the relational complexity of higher-order intentionality. Consciousness and Cognition, 17, 438–50.
Aggarwal, N.K. (2009). Neuroimaging, culture and forensic psychiatry. Journal of the American Academy of Psychiatry and the Law, 37, 239–44.
Aron, A., Fisher, H., Mashek, D.J., Strong, G., Li, H., and Brown, L.L (2005). Reward, motivation, and emotion systems associated with early-stage intense romantic love. Journal of Neurophysiology, 94, 327–37.
Bigos, K.L. and Weinberger, D.R. (2010). Imaging genetics – days of future past. Neuroimage [Epub 18 January 2010].
Cho, M.K., Magnus, D., Caplan, A.L., McGee, D., and the Ethics of Genomics Group. (1999). Ethical considerations in synthesizing a minimal genome. Science, 286, 208–90.
Conti, R., Veenstra, D.L., Armstrong, K., Lesko, L.J., and Grosse, S.D. (2010). Personalized medicine and genomics: challenges and opportunities in assessing effectiveness, cost-effectiveness, and future research priorities. Medical Decision Making, 30, 328–40.
Eisenberger, N.I., Lieberman, M.D., and Williams, K.D. (2003). Does rejection hurt? An fMRI study of social exclusion. Science, 302, 290–2.
Esslinger, C., Walter, H., Kirsch, P., et al. (2009). Neural mechanisms of a genome-wide supported psychosis variant. Science, 324, 605.
Farah, M.J. (2005). Neuroethics: the practical and the philosophical. Trends in Cognitive Sciences, 9, 34–40.
Farah, M.J. and Wolpe, P.R. (2004). Monitoring and manipulating brain function: new neuroscience technologies and their ethical implications. Hastings Center Report, 34, 35–45.
Fenton, A., Meynell, L., and Baylis, F. (2009). Ethical challenges and interpretive difficulties with non-clinical applications of pediatric fMRI. The American Journal of Bioethics, 9, 3–13.
Fins, J.J., Illes, J., Bernat, J.L., Hirsch, J., Laureys, S., and Murphy, E. (2008). Neuroimaging and disorders of consciousness: envisioning an ethical research agenda. American Journal of Bioethics, 8, 3–12.
Fisher, H., Aron, A., and Brown, L.L. (2005). Romantic love: An fMRI study of a neural mechanism for mate choice. The Journal of Comparative Neurology, 493, 58–62.
Garnett, A., Piwowar, H.A., Rasmussen, E.M., and Illes, J. (2010). Formulating MEDLINE queries for article retrieval based on PubMed exemplars. Nature Precedings [Online]. 10 March. Available from: http://precedings.nature.com/documents/4270/version/1. [Accessed: 10 March 2010]
Glannon, W. (2006). Neuroethics. Bioethics, 20, 37–52.
Greely, H.T. and Illes, J. (2007). Neuroscience-based lie detection: The urgent need for regulation. American Journal of Law and Medicine, 33, 377–431.
Greicius, M.D., Srivastava, G., Reiss, A.L., and Menon, V. (2004). Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI. Proceedings of the National Academy of Sciences USA, 101, 4637–42.
Hall, W., Capps, B., and Carter, A. (2008). The use of depot naltroxone under legal coercion: the case for caution. Addiction, 103, 1922–4.
Harris, S., Kaplan, J.T., Curiel, A., Bookheimer, S.Y., Iacoboni, M., and Cohen, M.S. (2009). The neural correlates of religious and nonreligious belief. PLoS ONE, 4, e0007272.
Illes, J., Kirschen, M.P., and Gabrieli, J.D. (2003). From neuroimaging to neuroethics. Nature Neuroscience, 5, 205.
Illes, J. (2007). Empirical neuroethics. Can brain imaging visualize human thought? Why is neuroethics interested in such a possibility? EMBO Reports, 8, S57–60.
Illes, J. and Racine, E. (2005). Imaging or imagining? A neuroethics challenge informed by genetics. American Journal of Bioethics, 5, 5–18.
Illes, J., Moser, M.A., McCormick, J.B., et al. (2009). Neurotalk: improving the communication of neuroscience research. Nature Reviews Neuroscience, 11, 61–9.
Kapogiannis, D., Barbey, A.K., Su, M., Zamboni, G., Krueger, F., and Grafman, J. (2009). Cognitive and neural foundations of religious belief. Proceedings of the National Academy of Science, 106, 4876–81.
King, J.A., Tenney, J., Rossi, V., Colamussi, L., and Burdick, S (2003). Neural substrates underlying impulsivity. Annals of the New York Academy of Science, 1008, 160–69.
Knauff, M., Famgmeier, T., Ruff, C.C., and Sloutsky, V. (2006). FMRI evidence for a three-stage model of deductive reasoning. Journal of Cognitive Neuroscience, 18, 320–34.
Lau, P.W. and Illes, J. (2009). The gray zones of privatized imaging. American Journal of Bioethics, 9, 21–2.
Laureys, S., Owen, A., and Schiff, N. (2009). Coma science: clinical and ethical implications. Preface. Progress in Brain Research, 277, xiii-xiv.
Lawrence, E.J., Shaw, P., Giampietro, V.P, Surguladze, S., Brammer, M.J, and David, A.S. (2006). The role of ‘shared representations’ in social perception and empathy: an fMRI study. Neuroimage, 29, 1173–84.
Marcus, S. (2002). Neuroethics: Mapping the Field. New York: The Dana Foundation Press.
Matthews, P.M., Honey, G.D., and Bullmore, E.T. (2006). Applications of fMRI in translational medicine and clinical practice. Nature Reviews Neuroscience, 7, 732–44.
Meegan, D.V. (2008). Neuroimaging techniques for memory detection: scientific, ethical and legal issues. American Journal of Bioethics, 8, 9–20.
Miller, G. (2009). fMRI evidence used in murder sentencing. Science Insider, [Internet] 23 November. Available at: http://news.sciencemag.org/scienceinsider/2009/11/fmri-evidence-u.html) [Accessed 9 March 2010]
Moll, J., de Oliveira-Souza, R., Garrido, G.J., et al. (2009). The self as a moral agent: linking the neural bases of social agency and moral sensitivity. A Social Neuroscience, 2, 336–52.
Monti, M.M., Coleman, M.R., and Owen, A.M. (2009). Neuroimaging and the vegetative state: Resolving the behavioral assessment dilemma. Annals of the New York Academy of Science, 1157, 81–9.
President’s Council on Bioethics (2004). Reproduction and responsibility: the regulation of new biotechnologies. Washington, DC: National Academies Press.
Reiman, E.M. (2007). Linking brain imaging and genomics in the study of Alzheimer’s disease and aging. Annals of the New York Academy of Sciences, 1097, 94–113.
Roskies A. (2002). Neuroethics for the new millennium. Neuron, 34, 21–3.
Rothenberg, K. and Terry, S.F. (2002). Human genetics. Before it’s too late – addressing fear of genetic discrimination. Science, 297, 196–7.
Soon, C.S., Brass, M., Heinze, H.J., and Haynes, J.D. (2008). Unconscious determinants of free decisions in the human brain. Nature Neuroscience, 11, 543–5.
Tairyan, K. and Illes, J. (2009). Imaging genetics and the power of combined technologies: a perspective from neuroethics. Neuroscience, 164, 7–15.
Thompson, P.B. and Hannah, W. (2008). Food and agricultural biotechnology: a summary and analysis of ethical concerns. Advances in Biochemical Engineering Biotechnology, 111, 229–64.
Vogeley, K., May, M., Ritzl, A., Falkai, P., Zilles, K., and Fink, G.R. (2004). Neural correlates of first-person perspective as one constituent of human self-consciousness. Journal of Cognitive Neuroscience, 16, 327–37.
Volkow, N.D., Fowler, J.S., and Wang, G.J. (2004). The addicted human brain viewed in the light of imaging studies: brain circuits and treatment strategies. Neuropharmacology, 47, 3–13.
Williams, A. (1992). Cost-effectiveness analysis: is it ethical? Journal of Medical Ethics, 18, 7–11.
Yang, T.T., Menon, V., Eliez, S., et al. (2002). Amygdalar activation associated with positive and negative facial expressions. Neuroreport, 13, 1737–41.
