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Emerging Ethical Issues in Neuroscience. Nature

Emerging Ethical Issues in Neuroscience. Nature

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Emerging ethical issues in Martha J. Farah

There is growing public awareness of the ethical issues raised by progress in many areas of neuroscience. This commentary reviews the issues, which are triaged in terms of their novelty and their imminence, with an exploration of the relevant ethical principles in each case.

In less than a year, “neuroethics” has ical issues raised are similarly varied, and the possibility of safe mood enhancement. joined the vocabulary of most neurosci- include the rights to equal opportunity, The growth in sales of SSRIs clearly indi- entists. Exactly what the word signifies and freedom. cates that more people, with less severe may not be clear to most of us, however. depression, are using them. Has the Both the word and the field to which it Enhancement of normal function threshold for SSRI use dropped below the refers come largely from individuals out- If drugs and other forms of central ner- line separating the healthy from the sick? side neuroscience. Newspaper columnist vous system intervention can be used to This question is hard to answer for sever- William Safire gave the field its name, and improve the mood, cognition or behavior al reasons. First, the line between healthy http://www.nature.com/natureneuroscience defining statements of the issues are found of people with problems in these areas, and sick is a fuzzy and perhaps arbitrary in such sources as Brain Policy1 by bioethi- what might they do for normal individu- one. There is no simple discontinuity cist Robert Blank, Our Posthuman Future2 als? Some treatments can be viewed as between the characteristic mood of by historian Francis Fukuyama and a ‘normalizers’, which have little or no effect patients with diagnosable mood disorders cover story in The Economist magazine on systems that are already normal (for and the range of moods found in the gen- (May 23, 2002). them- instance, the mood stablizer lithium3) and eral population5. Second, diagnostic selves have been relatively scarce in pub- will not therefore figure in debates over thresholds are clearly moving downward lic discourse on neuroethics, perhaps enhancement. Other treatments can as a result of these very changes in treat- because many of the issues under discus- indeed make normal people ‘better than ment. For a given severity of illness, the sion seem far-fetched. Need we devote normal’. Pharmacological enhancement is better tolerated the treatment, the more serious attention now to the needs and arguably being practiced now in several likely patients are to present for diagnosis rights of humans with computer- psychological domains: enhancement of and the more likely are to diag- augmented brains? Probably not, given mood, cognition and vegetative functions, nose and treat. As a related point, other the current state of . Yet neu- including , appetite and sex. more common and less debilitating con- roscientists are just the people to guide the The enhancement potential of some ditions are also being treated with SSRIs, © Group 2002 Publishing discussion toward issues of current and psychiatric treatments is, in itself, noth- such as cyclic changes in women’s moods near-term priority. How does neuroethics, ing new. Until recently, however, psy- before menstruation6. Third, although as presented to us in the literature, relate chotropic medications had significant depression is usually a remitting-relaps- to the current state of neuroscience and risks and side effects that made them ing disease with typically years between its foreseeable future? Here I attempt to attractive only as an alternative to illness. episodes, patients today are likely to be triage the issues that have been raised, sep- With our growing understanding of neu- treated prophylactically with antidepres- arating those that are both new and rotransmission at a molecular level, it has sant medication for periods of 1–3 years, immediate from those that are not new or been possible to design more selective even when symptom free7. Thus there are are likely to arise only in the distant drugs with better side-effect profiles. In many people now on antidepressant med- future. Although all three categories addition, adjuvant therapy with other ication who are healthy, with only a vul- deserve our continued attention, the first drugs is increasingly used to counteract nerability to depression as opposed to poses the most immediate intellectual and the remaining side effects. For example, depression. These changes in psychiatric social challenges. the most troublesome side effect for users practice have resulted in many people Three broad issues survive the triage of selective seratonin reuptake inhibitors using SSRIs and other antidepressants for novelty and imminence: enhancement (SSRIs) is sexual dysfunction, which who would not have been prescribed these of normal function, court-ordered CNS responds well to the drug sildenafil (Via- drugs ten years ago. There is no reason to intervention and ‘brain-reading’. Each gra). Other drugs specifically developed predict their ranks will not continue to emerges from work in multiple areas of to counteract the sexual side effects of swell, and to include healthier and high- neuroscience, from molecular to cogni- SSRIs are in development and clinical tri- er-functioning people. tive neuroscience. The nature of the eth- als (Vernalis press release, May 22, 2002). What changes might healthy individ- The result of both new designer drugs and uals hope to experience through the use Martha Farah is at the Center for Cognitive adjuvant drugs is the same: increasingly of antidepressant medication? Mood Neuroscience, University of Pennsylvania, selective neurochemical alteration of our enhancement belongs on the docket of 3815 Walnut St., Philadelphia, Pennsylvania mental states and abilities. new and imminent bioethical issues in 19104-6196, USA. Peter Kramer’s book Listening to neuroscience only if current and foresee- e-mail: [email protected] Prozac4 first focused society’s attention on able medications can deliver pleasing

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results to healthy people. A handful of primarily on the basis of parent and teacher ing presynaptic release studies have assessed the effects of SSRIs questionnaire responses, it can be difficult (for example, existing cholinesterase on mood and personality in normal sub- to free the diagnostic process from the val- inhibitors such as donezipil) and postsy- jects over short periods of a few months ues and standards of the respondents. naptic effects (such as the class of drugs or less (for example, refs. 8, 9). The effects Whereas diagnostic ‘over-reach’ is a known as ). These drugs are are relatively selective, reducing self- reason that some arguably normal chil- currently considered treatments for reported negative affect (such as fear, hos- dren receive stimulants, many young dementia and so-called ‘mild cognitive tility) while leaving positive affect adults with no pretense at all to a diagno- impairment’, which is more severe than (, excitement) the same. The sis are using stimulants to enhance their normal age-related cognitive decline. No drugs also increase affiliative behavior in performance in college. Methylphenidate drug companies have yet targeted normal laboratory social interactions and coop- is considered by some to be the most memory for enhancement, but there is erative/competitive games played with widely used recreational drug on Ameri- reason to believe that some of the prod- confederates, for example decreasing the can campuses12. Students have often ucts under development would work for number of spoken commands and approached me after talks on the topic to that purpose as well. For example, treat- increasing the number of suggestions. In relate their own stories about Ritalin use ment of healthy human subjects with an one double-blind crossover design, sub- among their non-ADHD peers, for exam- improved performance on sev- jects not only were more cooperative in a ple recalling a hockey coach who always eral memory tests18. game, but showed real-world changes in reminded her team to take their Ritalin Advances in the of behavior as well: roommates found them before playing another school. sleep, appetite and sex are paving the way less submissive on citalopam, though no Loss of cholinergic neurons is respon- for better pharmacological control of more dominant or hostile9. Much more sible for many of the cognitive changes in these functions as well, with results that research is needed to clarify the effects of Alzheimer’s disease, including the pro- will be of interest to normal people. The http://www.nature.com/natureneuroscience SSRIs and other antidepressant agents on nounced impairment of memory. Drug drug modafinil (Provigil), approved for mood and behavior of normal subjects, therapies such as donepezil (Aricept) that the treatment of narcolepsy, can prolong but the evidence so far suggests subtle increase acetylcholine can slow or reverse alert wakefulness for days19. Its use by salutary effects. the loss of memory ability in the early healthy people is currently being explored Pharmacological manipulations of stages of the disease. Can this or other by the military20. The appeal of such a other neurotransmitter systems can alter treatments improve the memory of drug to average people who would like cognitive abilities, including attention and healthy individuals? Discussions of mem- more time in their lives is obvious, and memory. Attention, in the sense of sus- ory enhancement must take age into media coverage of modafinil has been tained effort and resistance to distraction, account. Although certain specialized extensive. Weight control is a societal pre- is primarily modulated by dopamine and pursuits could conceivably benefit from occupation, and Wallace Simpson’s quip norepinephrine. Stimulant medication, super-memory, the forgetting rates of that “a woman cannot be too rich or too such methylphenidate (Ritalin) and normal young humans seem to be opti- thin” sums up the likely attitude of most amphetamines (Adderol) affect both sys- mal for most purposes13. Empirically, people to a safe, long-term appetite sup- tems and are effective in treating attention prodigious memory is linked to difficul- pressant. There is currently a very limit- deficit hyperactivity disorder (ADHD). In ties with thinking and problem solving14, ed choice of medication for weight loss, © Group 2002 Nature Publishing normal individuals, these drugs induce and computationally, boosting the dura- and what is available is less effective than reliable changes in vigilance, response bility of individual memories decreases the Fenfluramine-Phenylpropanolanine time and higher cognitive functions, such the ability to generalize15. Memory combination, withdrawn from the mar- as novel problem-solving and planning10. enhancement is of more interest in mid- ket in 1997 due to severe adverse effects21. As it turns out, thousands of normal, dle age and beyond, when the normal However, findings that hormones such as healthy children and adults have discov- process of memory loss is first noticeable leptin, ghrelin and melanocortin are ered similar effects on their own. in healthy individuals16. Rejuvenation of involved in appetite control have given The question of whether and when to memory function in healthy older peo- pharmaceutical researchers new avenues treat ADHD medically is a complex and ple is a form of memory enhancement to explore for drug development. Men contentious one for many reasons, most of with broad appeal. Indeed, memory- without erectile dysfunction have discov- which are not related to enhancement. enhancing nutritional supplements are a ered sildenafil (Viagra) and created a new However, as with affective disorders, it is billion-dollar industry (Nutrition Busi- market for the drug as an enhancer of sex- difficult to locate a discontinuity between ness Journal, 1998), despite little evidence ual performance. Although a prescription normal attentional functioning and ADHD concerning efficacy. Ginkgo biloba, the medication, sildenafil is easily obtained (NIH consensus statement, 1998). To the most popular of the memory-enhancing for such purposes after completing a short extent that we intervene too ‘high up’ the supplements, was recently found to be diagnostic questionnaire on the internet22. continuum, we are practicing enhance- equivalent to placebo17. Pharmaceutical companies are pursuing ment. According to most experts, pharma- How close are we to more specific and drugs that more selectively target the cological enhancement of children’s effective memory enhancement for neural bases of sexual function, which attention is routine in some communi- healthy older adults? Many drug compa- would have fewer cardiovascular side ties11. Parents who are eager to give their nies are now directing enormous research effects than sildenafil. children every edge in school may press efforts to the development of memory- In sum, enhancement is not just a the- their pediatricians for medication, and boosting drugs (Neuroinvestment, Sep- oretical possibility. Enhancement of teachers often welcome the greater order- tember 2001). The candidate drugs target mood, cognition and vegetative functions liness in a classroom of attentive children. various stages in the molecular cascade in healthy people is now a fact of life, and Because ADHD in children is diagnosed that underlies memory formation, includ- the only uncertainties concern the speed

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with which new and more appealing cants their SAT prep books or Stanley sake of avoiding the indirect coercion of enhancement methods will become avail- Kaplan classes. Psychopharmacological individuals who do not wish to partake. able and attract more users. enhancement can therefore be seen as fit- The idea of self-enhancement through ting in with an array of practices that are manipulations of brain function feels Ethical issues in enhancement already accepted and widespread. wrong or dangerous to many people. Yet Most of us would love to go through life One variant of the ‘no , no gain’ the root cause of that feeling is difficult to cheerful and svelte, focusing like a laser objection is specific to our emotional lives. find. Perhaps it is a misleading feeling, beam at work and enjoying rapturous sex Many people hold the belief that one can- which we will get over once we have dis- each night. Yet most of us also feel uneasy not experience the beauty and joy of life cussed the issue of enhancement thor- about the idea of achieving these things unless one is also acquainted with life’s oughly and rationally. Or perhaps further through drugs. With the necessary tech- pain. In the words of Nietzsche, “If you discussion will reveal the cause of our nology at or near hand, it is important to take away my devils, you will take away reflexive worry. examine the reasons for this unease (for a my angels too.” As an empirical claim, more detailed discussion of enhancement supporting evidence is so far lacking. Court-ordered CNS intervention in other domains, see ref. 23). Objections Anecdotal reports of generalized emo- Another controversial use of our current to enhancement can be divided into two tional blunting notwithstanding, the small psychopharmacopia is to improve the broad categories: problems for the indi- literature on short-term SSRI effects in behavior of others when that behavior is vidual user and problems for society if use normal subjects suggests no change in medically unremarkable but socially becomes widespread. either direction on positive affect, only a undesirable. Rehabilitation has long been The first problem that springs to selective decrease in negative affect. In any intertwined with punishment in our mind for many people is the possibility case, even if emotional blunting were a criminal system. Successful reha- of serious side effects for the individual, side effect of current mood enhancers, it bilitation benefits both the offender and http://www.nature.com/natureneuroscience including long-term or delayed effects is not a basis for rejecting mood enhance- society, insofar as it reduces repeat offens- that might evade current FDA safe- ment in general. There is no a-priori rea- es. It may be offered as an option or as a guards. Perhaps a youth spent scaling the son that newer medications would have mandatory component of a sentence. Fur- heights of academic and job success the same effect. thermore, court-ordered therapy or reha- thanks to enhancement by Ritalin will be Other objections stem from potential bilitation is not confined to medically followed by a middle age of premature harm to society. One worry is that diagnosed illnesses. Judges may require memory loss and cognitive decline. By enhancement will not be fairly distrib- healthy individuals to undergo such inter- and large, a concern with long-term or uted. It is likely that the wealthy and priv- ventions as parenting classes or anger hidden side effects is not unique to ileged will have the choice of self- management therapy. enhancement but applies to therapeutic enhancement and the less privileged will , aggression, impulse control treatments as well. Its special salience in not. Is this what at the root of our and even parenting behavior have been the case of enhancement may reflect an unease with enhancement? Probably not, studied for several decades, and we are underlying wariness of ‘free lunches’. given that our society is already full of increasingly able to manipulate the rele- There is one respect in which enhance- such inequities. No one would seek to vant neural systems in animals by drugs ment might deserve extra scrutiny for prohibit private schools, personal train- and other interventions. Some of this work © Group 2002 Nature Publishing hidden costs, which is suggested by evo- ers or cosmetic surgery on the grounds has been successfully generalized to lutionary considerations. We understand that they are inequitably distributed. humans. For example, impulsive little about the design constraints that Besides, consider a scenario in which the has been linked to seratonergic abnormal- were being satisfied in the process of cre- entire populace is given full and equal ities in patient24, criminal25 and healthy ating a modern . Therefore access to Ritalin, Prozac and other community populations26. Accordingly, we do not know which ‘limitations’ are enhancers. If our qualms about enhance- SSRIs have been tried as a treatment for there for a reason. As already men- ment were linked to equal opportunity, aggressive behavior, and found to be help- tioned, normal forgetting rates seem to then this should set our minds at ease, but ful27. For example, in three double-blind be optimal for information retrieval. more than likely it does not. studies, fluoxetine (compared against A concern unique to enhancement is Another social problem with enhance- placebo) reduced aggression in patients the moral objection to, in effect, gain ment is that widespread enhancement will with personality disorder25,28,29. without pain. Most people in our society raise our standards of normalcy. This in How close do our current practices feel there is to earning one’s happi- turn will put individuals who choose not come to directly altering brain function ness, success, and so on. When wealthy to enhance at a disadvantage, in effect a under the rubric of court-ordered reha- parents make their teenage children take form of indirect coercion. Even the bilitation? For any person deemed a threat summer jobs to earn their spending enhancement of mood, which at first to self or others, including criminal money, they are applying this principle glance lacks a competitive function, seems offenders, judges routinely order compli- in a way that most of us would find rea- to be associated with increased social abil- ance with medication. Although the ethi- sonable. However, our judgments often ity8, which does confer an advantage in cal issues raised by involuntary treatment deviate from this principle. Although we many walks of life. Such coercion may are far from trivial, there is nevertheless recognize the value of earning life’s already be felt by parents whose children broad consensus in favor of applying rec- rewards, our lives are full of shortcuts to attend schools with high rates of Ritalin ognized treatments in such cases. A more looking and feeling better. We do not dis- use. Clearly coercion is not a good thing. controversial use is sentencing sexual approve of people who dislike vegetables Yet it would seem at least as much of an offenders to pharmacological treatments improving their health by taking vitamin infringement on personal freedom to aimed at reducing their sex drive. Several pills. Nor do we begrudge college appli- restrict access to safe enhancements for the states in the US have enacted laws that

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either allow or require sex offenders to many people’s intuitions raise a flag here. cannot reliably place most patients in a take the synthetic hormone medroxy- And if not here, then at the thought of diagnostic category, this limitation does progesterone acetate, which lowers serum more permanent interventions such as not rule out occasional revelations about testosterone and significantly decreases implanted stimulators or to an individual. Even though most patients’ recidivism30. Other pharmacological achieve the same goals. scans will be impossible to classify with approaches involving seratonin are being What moral intuition triggers this flag? certainty, other individual scans will devi- explored in research studies30. Primarily an intuition about individual ate enough from the normal pattern to The issue of diagnostic creep is also freedom, of a kind that we have not pre- constitute a ‘positive’ finding. One such relevant here. Many behavioral tendencies viously denied even to prisoners: the free- example comes from studies of drug crav- that the layman would consider ‘bad’ but dom to think one’s own thoughts and ing. Drug-free cocaine addicts experience not medical illnesses have acquired diag- have one’s own personality. In anger man- a craving state when shown pictures of nostic codes in the Diagnostic Statistical agement class, a person is free to think, drug paraphernalia, which results in reli- Manual of the American Psychiatric Asso- “This is stupid. No way am I going to use able group differences in PET activation ciation31. These diagnoses include drug these methods.” In contrast, the mecha- of the amygdala, anterior cingulate and abuse, compulsive shoplifting and sexual nism by which Prozac curbs impulsive orbitofrontal cortex34. Although some of attraction to children. Alvin violence cannot be accepted or resisted in the individual scans in the patient group Poussaint has even suggested that racism the same way. Offering CNS interventions are indistinguishable from normal, oth- is a psychiatric illness and should be treat- in the context of a choice, with conven- ers clearly differ from normal. In one lab- ed by therapy (The New York Times, tional therapies and incarceration as alter- oratory, at least half of recently detoxified August 26, 1999). The ‘medical model’ of natives, mitigates this worry but does not cocaine users could be identified by dif- condemnable behavior has been criticized eliminate it. Sentencing alternatives are ferential amygdala response to drug-relat- when used to excuse, not simply explain, rarely appealing options, introducing ed versus non-drug-related pictures (A.R. 32 http://www.nature.com/natureneuroscience behavior . In the future, the model’s implicit coercion. Childress, personal ). impact may be less friendly to offenders, Drug use is not unique in this respect; by subjecting more of them to involun- ‘Brain reading’ other stimuli to which individuals are tary regimens of psychotropic medication. Mind reading is the stuff of fic- strongly attracted evoke activity in similar Court-ordered CNS intervention has tion, and the current capabilities of neu- circuits. For instance, subjects aroused by not been highlighted in recent discus- roscience fall far short of such a feat. Even sexually explicit videos activate many of sions of neuroethics, but deserves greater a major leap in the signal-to-noise ratio the same limbic system areas35. Further- attention for three reasons. First, some of functional brain imaging would simply more, the conscious attempt to suppress of the relevant are already leave us with gigabytes of more accurate arousal may also engender a distinct pat- available, for example SSRIs to reduce physiological data whose psychological tern of brain activation36, suggesting an violent behavior. Second, the practice of meaning would be obscure. Nevertheless, advantage of such scans over more requiring nonpharmacological treatment the accomplishments of the field to date peripheral measures capable of revealing aimed at changing the behavior of include neural correlates of many psy- sexual preferences. healthy offenders is well established. And chological traits and states. Furthermore, The significance of such results for if this, in itself, does not put us on the the demand for ‘scientific’ measures of individuals is not in their use for classi- © Group 2002 Nature Publishing slippery slope toward court-ordered personality, veracity, attitudes and behav- fication or diagnosis, because of the CNS modification of healthy offenders, ioral dispositions in our society ensures ambiguity of most people’s scans, but in then the third fact surely does, namely that, ready or not, these measures will the information they reveal about some the use of antiadrogen treatment with have an increasing role in our lives. fraction of the subjects (the size of which convicted sex offenders. Most of our knowledge of individual varies from study to study) whose scans variation in mental and neural function fall clearly outside the normal range. of court-ordered intervention comes from biological and Although subject cooperation is required Court-ordered CNS intervention need not concerns patterns of brain activity in for such scans, because of the need to simply subjugate an individual’s interests mental disorders. This work has impor- remain still and focus on the visually to those of society, in the style of Soviet tant future clinical implications, especially presented stimuli, the subject need not psychiatry or A Clockwork Orange. Such in a field in which the major diagnostic know the scan’s purpose. uses do not challenge our moral intuitions categories remain syndromal, that is, Many recent studies have sought neu- or social policies; they are clear violations defined in terms of clusters of signs and roimaging correlates of the dimensions of of an individual’s freedom and human symptoms. The current state of the art in personality found in classic theories of dignity. The harder questions arise when functional does not earn it normal personality, such as extraversion we consider uses of neuroscience in the a place in psychiatric diagnosis. In gen- and neuroticism (see ref. 37 for a review criminal justice system for genuinely ther- eral, abnormalities that characterize par- of the social and ethical issues). These apeutic purposes. For example, a judge’s ticular illnesses can be demonstrated studies use small groups of subjects, but order to attend anger management class when small groups of patients are com- at least a small fraction of the subjects can or a parenting support group is intended pared to control subjects, but are not be classified by visual inspection of the to help the offender, in addition to what- diagnostic at the individual patient level. scans (T. Canli, personal communica- ever society gains from having fewer hot- Nevertheless, diagnostic imaging is cur- tion). Other socially relevant characteris- heads and abusive parents among us. rently the goal of many research groups, tics such as racial group identity and Substituting medications that improve with encouraging results for some disor- unconscious racial attitudes also have anger management or parenting skills ren- ders, such as ADHD33. neural correlates that can be measured in ders the effect no less therapeutic. Yet Although current imaging methods small groups of subjects. For example, a

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study in which four black and four white cal processes. For now, however, this is not which defined brain death as “the irre- subjects viewed photographs of black and the case, and there is a risk that juries, versible cessation of all functions of the white faces found significant differences judges, parole boards, the immigration entire brain, including the brain stem.” in response to ingroup and outgroup service and so on will weight such mea- This definition has, in turn, been found faces38. A correlational study of uncon- sures too heavily in their decision-making. wanting41. With our growing under- scious attitudes found that white subjects standing of mind–brain relationships, and with more negative evaluations of black Long-standing issues in neuroethics our ability to assess them with function- faces had more of an increase in amygdala The emerging field of neuroethics is con- al neuroimaging, a narrower focus on the activity to pictures of unfamiliar black cerned with a broad array of issues status of higher brain functions seems than white faces39. beyond the three just discussed. Some are indicated1,42. However, any such move One of the most sought-after uses of familiar, though by no means settled. Oth- will raise profound questions about per- ‘brain reading’ is the detection of decep- ers remain hypothetical, pending future sonhood and the brain. tion. In the wake of the 9-11 tragedy, developments in neuroscience, but are Informed for research partic- there is renewed interest in detection fairly certain to materialize within many ipation or for treatment43 is another issue for security purposes, to screen individ- readers’ lifetimes. In both cases, bioethi- that is special in neuroscience, because in uals for their attitudes and allegiances, as cists, policy makers and society in gener- many cases the subjects or patients in well as for traditional forensic purposes. al will benefit from having the perspective question have brain disorders that affect The company Brain Fingerprinting Lab- of informed neuroscientists included in their decision-making ability. The ethics oratories is already marketing a system their discussions. of is a related issue, not least that uses scalp-recorded ERPs to detect The familiar issues can themselves be because thousands of patients ostensibly so-called ‘guilty knowledge’, such as divided into those that relate to neuro- consented to the destructive and unproven familiarity with certain people, objects or science and to other biomedical method of prefrontal leucotomy44. http://www.nature.com/natureneuroscience scenes. Research seeking more neu- as well, and those uniquely related to our Although relatively rare today, psy- roanatomically specific measures of growing understanding of brain function. chosurgery continues to be practiced as a deception using fMRI is underway40. Common biomedical issues are exempli- last resort for patients from fied by questions such as the following. refractory depression, obsessive-compul- Ethical issues in brain reading How safe are the new methods of neuro- sive disorder (OCD) and anxiety disor- One problem posed by these develop- science, such as transcranial magnetic ders. The most common procedures are ments concerns privacy. As with any test- stimulation or high-field MRI, and who cingulotomy, stereotactic subcaudate trac- ing method that reveals information should decide? What is the appropriate totomy, anterior capsulotomy and limbic about an individual (such as genetic test- course of action when an incidental neu- leucotomy, all of which disrupt the inter- ing for breast cancer risk), it may not rological abnormality is found in the connecting pathways of the limbic system always be in the person’s best interest to course of research data collection? What and the prefrontal cortex45,46. According have that information available to others. considerations should guide the develop- to one recent review, at least one third of However, there is an added dimension of ment of therapies for diseases such as depressed patients experience improve- ethical significance when the information Parkinson’s based on fetal tissue or embry- ment as a result of these operations, with concerns the kinds of personal traits and onic stem cells? How should promising just under one third of OCD and anxiety © Group 2002 Nature Publishing states that neuroimaging may reveal. The new therapies be rationed? When and why patients improving45. This could be con- goal, in some cases already partially real- should predictive testing be offered for sidered a favorable record with patients ized, involves breaching the privacy of a future neurological or neuropsychiatric ill- who have failed to benefit from multiple person’s own mind. ness when no cure is available, as with other treatments. Should we therefore Another, more immediate problem Alzheimer’s and Huntington’s diseases? approve of psychosurgery as a less-than- concerns the way that brain scans are These are difficult questions, on which last resort? interpreted outside the neuroimaging reasonable people can disagree. They are Our notions of responsibility and community. Physiological measures, espe- also questions with a history in , blame, which guide our legal as well as cially brain-based measures, possess an which offers helpful general principles and personal ethics, seem at odds with deter- illusory accuracy and objectivity as per- precedents. ministic views of human behavior. ceived by the general public. One com- Other ethical issues arise exclusively in Whether we are moved by the ‘Twinkie mentator, in proposing the use of Brain neuroscience because of the particular defense’ (the apocryphal defense of a Fingerprinting as a screening tool at air- subject matter of the field. The brain is the murderer based on his loss of control ports, wrote “Although people lie…brain- organ of the mind, consciousness and self- caused by junk-food consumption) or the waves do not” (www.skirsh.com). Brain- hood. Although the issues in this catego- ‘abuse excuse’ depends on how we recon- based measures do, in principle, have an ry are not new, they are evolving as the cile common-sense notions of advantage as indices of psychological traits field evolves and in some cases develop- with mechanistic views of the causation and states. Measures of brain function are ing new wrinkles. of behavior. Although the perceived con- one causal step closer to these traits and The definition of death is one such flict between free will and determinism states than the behavioral or even periph- issue. Until the 1960s, the generally does not hinge on the particulars of any eral autonomic signs that form the basis accepted criterion for death was perma- specific deterministic account, progress in of more familiar measures, from respons- nent cessation of respiration and circula- cognitive and es on personality questionnaires to poly- tion. The Harvard criteria for death, certainly increases the salience of the graph tracings. Imaging may therefore, published in 1968, shifted the focus to deterministic view. The abstraction that one day, provide the most sensitive and brain function. This definition was refined all human behavior is explainable in terms specific measures available of psychologi- by a presidential commission in 1981, of the laws of physics does not encroach

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much on our intuitions about a defen- sion in the early days of recombinant DNA 19. Lagarde, D., Batejat, D., Van Beers, P., dant’s responsibility for his actions. In research, neuroscientists have paid rela- Sarafian, D. & Pradella, S. Interest of modafinil, a new psychostimulant, during a contrast, a detailed account of the mech- tively little attention to the social implica- sixty-hour sleep deprivation experiment. anisms linking childhood abuse to dimin- tions of their field. The time is now ripe Fund. Clin. Pharmacol. 9, 1–9 (1995). ished impulse control seems much more for examination of these implications, 20. Caldwell, J., Caldwell, J., Smythe, N. & Hall, K. likely to temper our intuitions about among scientists themselves and in dialog A double-blind, placebo-controlled responsibility and blame. As the neuro- with policy makers and the public. investigation of the efficacy of modafinil for sustaining the alertness and performance of science of intentional behavior continues aviators: a helicopter simulator study. to develop, it will challenge our ways of 1. Blank, R. H. Brain Policy: How the New 150, 272–282 (2000). Neuroscience Will Change Our Lives and Our 21. Campbell, M. L. & Mathys, M. L. thinking about responsibility and blame. Politics (Georgetown Univ. Press, Washington, Pharmacologic options for the treatment of DC, 1999). obesity. Am. J. Health System Pharmacol. 58, Neuroethical questions on the horizon 2. Fukuyama, F. Our Posthuman Future (Farrar, 1301–1308 (2001). The future will bring new ways of enhanc- Straus & Giroux, New York, 2002). 22. Armstrong, K., Schwartz, J. & Asch, D. Direct ing, controlling and ‘reading’ the brain. 3. Shastry, B. On the functions of lithium: the sale of sildenafil (Viagra) to consumers over The current ability of TMS to improve mood stabilizer. Bioessays 19, 199–200 (1997). the internet. New Engl. J. Med. 341, 1389–1392 cognition and mood47 by the activation 4. Kramer, P. D. Listening to Prozac (Penguin, (1999). or inhibition of specific brain areas may New York, 1993). 23. Parens, E. Enhancing Human Traits: Ethical 5. Flett, G. L., Vrendenburg, K. & Krames, L. The and Social Implications (Georgetown Univ. be refined in the service of enhancement Press, Washington, DC, 1998). or control. In the more distant future, continuity of depression in clinical and nonclinical samples. Psychol. Bull. 121, 24. Coccaro, E. F., Kavoussi, R. J. & Hauger, R. L. similar extensions of deep brain stimula- 395–416 (1997). Serotonin function and antiaggressive tion techniques can be envisioned, and 6. Redmond, G. Mood disorders in the female responsive to fluoxetine: a pilot study. Biol. genetic manipulations of targeted neural patient. Int. J. Fertility Women’s Med. 42, Psychiatry 42, 546–552 (1997). http://www.nature.com/natureneuroscience systems and neurosurgery could perma- 67–72 (1997). 25. Cherek, D. R., Lane, S. D., Pietras, C. J. & 7. Berman, R. M., Belanoff, J. K., Charney, D. S. Steinberg, J. L. Effects of chronic paroxetine nently modify brain function. Nanotech- administration on measures of aggressive and nology and neural prostheses might & Schatzberg, A. F. in Neurobiology of Mental Illness (eds. Charney, D. S., Nestler, E. J. & impulsive responses of adult males with a history eventually create a breed of enhanced Bunney, B. S.) 419–432 (Oxford University of conduct disorder. Psychopharmacology 159, human . Such possibilities may Press, New York, 1999). 266–274 (2002). sound like science fiction in 2002, but 8. Knutson, B. et al. Selective alteration of 26. Manuck, S. B. et al. Aggression, impulsivity, and central nervous system seretonergic consider that space travel and test tube personality and social behavior by serotonergic intervention. Am. J. Psychiatry responsivity in a nonpatient sample. babies were once just science fiction and 155, 373–379 (1998). Neuropsychopharmacology 19, 287–299 seemed every bit as far-fetched in the (1998). 9. Tse, W. S. & Bond, A. J. Serotonergic decades before they became reality. intervention affects both social dominance 27. Walsh, M.-T. & Dinan, T. G. Selective In addition to altering brain function, and affiliative behaviour. Psychopharmacology serotonin reuptake inhibitors and violence: a 161, 324–330 (2002). review of the available evidence. Acta our ability to monitor and interpret it Psychiatry Scand. 104, 84–91 (2001). could one day achieve equally fantastic 10. Elliott, R. et al. Effects of methylphenidate on spatial working memory and planning in 28. Coccaro, E. F. & Kavoussi, R. J. Fluoxetine and results. After all, twenty years ago it would healthy young adults. Psychopharmacology impulsive aggressive behavior in personality- have seemed implausible that neuroscien- 131, 196–206 (1997). disordered subjects. Arch. Gen. Psychiatry 54, © Group 2002 Nature Publishing 1081–1088 (1997). tists would have even candidate brain 11. Diller, L. H. The run on Ritalin: Attention indices of truth versus lie40, veridical versus deficit disorder and stimulant treatment in the 29. Salzman, C. et al. Effect of fluoxetine on anger 48 1990s. Hastings Center Report 26, 12–14 in symptomatic volunteers with borderline false memory , the likelihood of future (1996). personality disorder. J. Clin. Psychopharmacol. violent crime49, styles of moral reason- 15, 23–29 (1995). 50 51 12. Babcock, Q. & Byrne, T. Student perceptions ing , the intention to cooperate , and of methylphenidate abuse at a public liberal 30. Grossman, L. S., Martis, B. & Fichtner, C. G. Are even the specific content of thoughts (visu- arts college. J. Am. College Health 49, 143–5 sex offenders treatable? A research overview. alizing houses versus faces)52. What might (2000). Psychiatric Services 50, 349–361 (1999). we have in another twenty years, or fifty? 13. Anderson, J. The Adaptive Characteristics of 31. Diagnostic and Statistical Manual of Mental Thought (Erlbaum, Hillsdale, New Jersey, Disorders IV-R (American Psychiatric Assoc., Our track record for predicting the rate of 1990). Washington, DC, 1994). scientific progress has not been impressive. 14. Luria, A. R. The Mind of a Mnemonist 32. Morse, S. J. Hooked on hype: addiction and has yet to achieve the (Harvard Univ. Press, Cambridge, responsibility. Law Philos. 19, 3–49, (2000). Massachusetts, 1968). promise that seemed imminent ten or fif- 33. Dougherty, D. D et al. Dopamine transporter teen years ago, whereas the cloning of 15. McClelland, J. L., McNaughton, B. L. & density in patients with attention deficit mammals took the world by surprise. O’Reilly, R. C. Why there are complementary hyperacivity disorder. Lancet 354, 2132–2133 learning systems in the hippocampus and (1999). One need not project very far into the neocortex: Insights from the successes and future to see the increasing role of neuro- failures of connectionist models of learning 34. Childress, A. R. et al. Limbic activation during and memory. Psychol. Rev. 102, 419–457 cue-induced cocaine craving. Am. J. Psychiatry science in our lives, and the social and eth- (1995). 156, 11–18 (1999). ical concerns it will bring. Like the field of 16. Craik, F. I. M. & Salthouse, T. A. The 35. Garavan, H. et al. Cue-induced cocaine genetics, neuroscience concerns the bio- Handbook of Aging and Cognition (Erlbaum, craving: neuroanatomical specificity for drug logical foundations of who we are, of our Hillsdale, New Jersey, 1992). users and drug stimuli. Am. J. Psychiatry 157, ‘essence’. The relationship of self to brain 17. Solomon, P., Adams, F., Silver, A., Zimmer, J. 1789–1798 (2000). is, if anything, more direct than that of self & DeVeaux, R. Ginkgo for memory 36. Beauregard M., Levesque J., & Bourgouin P. enhancement: a randomized controlled trial. to genome, and neural interventions are Neural correlates of conscious self-regulation JAMA 288, 835–840 (2002). of emotion. J. Neurosci. 21, 1–6 (2001). more easily accomplished than genetic 18. Ingvar, M. et al. Enhancement by an ampakine 37. Canli, T. & Amin, Z. Neuroimaging of emotion interventions. Yet compared to molecular of memory encoding in humans. Exp. Neurol. and personality: Scientific evidence and ethical geneticists, who instigated public discus- 146, 553–559 (1997). considerations. Brain Cogn. (in press).

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38. Hart, A., Whalen, P., McInerney, S., Fischer, affect decision-making capacity. New Engl. Jl regions distinguish true from false? Proc. Natl. H. & Rauch, S. Differential response in the Med. 340, 1430–1434 (1999). Acad. Sci. USA 98, 4805–4810 (2001). human amygdala to racial outgroup versus 44. Valenstein, E. S. Great and Desperate Cures: ingroup face stimuli. Neuroreport 11, 49. Raine, A. et al. Reduced prefrontal and 2351–2355 (2000). The Rise and Decline of Psychosurgery and increased subcortical brain functioning Other Radical Treatments for Mental Illness assessed using positron emission tomography 39. Phelps, E. et al. Performance on indirect (Basic, New York, 1986). measures of race evaluation predicts amygdala in predatory and affective murderers. Behav. activation. J. Cogn. Neurosci. 12, 729–738 45. Mahli, G. S. & Sachdev, P. Novel physical Sci. Law 16, 319–332 (1998). (2000). treatments for the management of neuropsychiatric disorders. J. Psychosom. Res. 50. Greene, J. et al. An fMRI investigation of 40. Langleben, D. D. et al. Brain activity during 53, 709–719 (2002). emotional engagement in moral judgement. simulated deception: an event-related Science 293, 2105–2108 (2001). functional magnetic resonance study. 46. Ovsview, F. & Frim, D. M. Neurosurgery for Neuroimage 15, 727–732 (2002). psychiatric disorders. J. Neurol. Neurosurg. 51. McCabe, K., Houser, D., Ryan, L., Smith, V. & Psychiatry 63, 701–705 (1997). 41. Truog, R. D. Is it time to abandon brain death? Trouard, T. A functional imagng study of Hastings Center Report 27, 29–37 (1997). 47. George, M., Wasserman, E. & Post, R. cooperation in two-person reciprocal exchange. Proc. Natl. Acad. Sci. USA 98, 42. Churchland, P. The Engine of Reason, the Seat Transcranial magnetic stimulation: A 11832–11835 (2001) of the Soul: A Philosophical Journey into the neuropsychiatric tool for the 21st century. J. Brain (MIT Press, Cambridge, Massachusettts, Clin. Neurosci. 8, 373–382 52. O’Craven, K. M. & Kanwisher, N. Mental 1995). (1996). imagery of faces and places activates 43. Capron, A. M. Ethical and human rights issues 48. Cabeza, R., Rao, S. M., Wagner, A. D., Mayer, corresponding stimulus-specific brain regions. in research on mental disorders that may A. R. & Schacter, D. L. Can medial temporal J. Cogn. Neurosci. 12, 1013–1023 (2000). http://www.nature.com/natureneuroscience © Group 2002 Nature Publishing

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