Neuroethical issues in cognitive enhancement and neuroimaging

1. Neuroethical issues in cognitive enhancement and neuroimaging Barbara Sahakian FMedSci Professor of Clinical Neuropsychology Department of Psychiatry, School of Clinical Medicine and Behavioral and Clinical Neuroscience Institute (Jointly Funded by the Medical Research Council and Wellcome Trust) and Danielle Turner

2. Cognitive Enhancers • Many drugs have enormous potential to improve the quality of life for numerous individuals and to benefit society. • Developments in pharmacogenomics will make it possible to target subgroups of individuals with safe and effective cognitive enhancers. • It is important that we are not complacent about the harms that many agents can cause, particularly with long-term use and in the developing brain. • It is imperative to use experimental psychology paradigms to screen drugs to ensure the safest possible use of current and future psychotropic drugs.

3. Neuroethics The study of the ethical, legal and social questions that arise when scientific findings about the brain are carried into medical practice, legal interpretations and health and social policy The Dana Foundation Marcus, 2002

4. Methylphenidate Increasing prescriptions for Ritalin Farah 2005 TICS

5. Modafinil Improvement Modafinil improves planning in healthy volunteers

6. 100mg Modafinil

7. Action of methylphenidate, modafinil, and atomoxetine Methylphenidate (Ritalin) increases synaptic concentration of Dopamine and Noradrenaline by blocking their reuptake. Modafinil(Provigil) action is unclear; Possibilities include: indirect mediation of ACh and/or Adrenergic alpha –1 receptor activity. Appears to effect hypothalamic orexin and histamine, and has a small effect on dopamine transporter activity. Atomoxetine (Strattera) is a relatively selective noradrenaline reuptake inhibitor (SNRI). Stimulated vigilance Calm wakefulness Stahl SM (2002) J Clin Psychiatry

8. Novel cognitive enhancers “40 potential cognitive enhancers are currently in clinical development” - NeuroInvestment Ampakines improve cognition in healthy aged volunteers

9. Ampakines enhance the AMPA receptor’s response to glutamate

10. The “Rights” and “Wrongs” of cognitive enhancementin healthy people

11. ‘RIGHTS’ Potential benefits In addition to scientific and clinical advances • Shift workers, air traffic control … • School pupils • Normalisation – removal of unfair disparity in society (if people can be helped they should be) • Increase performance (both pleasurable and competitive activities) • Military

12. Military uses of cognitive enhancers

13. ‘WRONGS’ Potential harms • There could be long-term side-effects, especially in the developing brain • We run the risk of becoming a homogeneous society • There could be greater inequality, with access dependent on wealth • Our perception of ourselves could change (mechanistic beings) and we will not be able to take credit for our achievements • Virtues such as motivation and working hard could become outdated (students will just take a drug) • You could be “over-enhanced” e.g. plagued by unwanted memories • People could be coerced into taking cognitive enhancers (24/7 society) or even forced …

15. Cognitive enhancementConclusions • Pharmacological enhancement is one solution to improving society. However, we would not want to preclude other solutions, for example, extra help in the classroom, smaller classes, greater consideration for life/work balance etc. • Currently cognitive enhancers (in particular pharmaceuticals like modafinil and methylphenidate) have the potential to provide important clinical benefits and further development in this area is worthy of pursuit • Pharmacogenomics will make it possible to target individuals with safe and effective cognitive enhancers • Scientists need to work together with social scientists, philosophers, ethicists, policy makers and the general public to actively discuss the ethical and moral consequences of cognitive enhancement • This will go some way to ensuring that technological advances are put to maximal benefit and minimal harm

16. ‘Brain reading’: Ethics of neuroimaging • Growing public perception of neuroimaging as “hard” science, complementary to the “soft” science of psychological evaluation • However this new technology should be applied cautiously – Neuroimaging is not evidence for causation. Example: criminal psychopaths appear to “rehabilitate” well with behavioural therapy, yet have higher rates of reoffending than would be predicted by their therapists. This may be because they can manipulate or “dupe” people, but could they “dupe” a brain scan? News Feature, Nature 2001 vol 410: 296-298

17. Examples of possible applications of neuroimaging • Neuroimaging of emotion in healthy volunteers • Unconscious biases • Neural correlates of morality • Deception and lie detection • Forensic neuroimaging in violent offenders • Psychopathy and affective processing • Self-control: imaging inhibition

18. Unconscious racial biases In White subjects, amygdala activation in response to Black faces correlates with unconscious measures of bias (IAT response latencies) ….but not with score on Modern Racism Scale, measuring how “racist” they perceive themselves. (Phelps et al J Cogn Neurosci 2000) Would it be ethical to screen job applicants, judges, lawyers, teachers, doctors ... for discriminatory biases?

19. Neural correlates of morality Areas shown are those activated by moral versus non-moral unpleasant visual stimuli. Differential activation was also seen in moral vs. neutral conditions. (Moll et al J Neurosci 2002) How would we interpret someone’s scan that does not show this pattern of activation. Are they immoral? Amoral?

20. Deception and lie detection Differential patterns of activation observed for Truth (T), spontaneous-isolated lies (SI) and memorized scenarios (MS). This may be evidence for neural correlates of different types of lying. Ganis et al, Cerebral Cortex 2003 Can we tell when someone is lying? Can we tell if someone has a false memory?

21. Areas of less activation Areas of more activation Forensic neuroimaging: violent offenders Criminal psychopaths show different patterns of emotional-related activity compared to non-criminal control subjects (Kiehl, Biol Psychiatry 2001) Will this change our diagnosis of “psychopathy” to a brain scan rather than observed behaviour? Would we incarcerate “brainscan-psychopaths” before they commit a crime?

22. Behaviour prediction: imaging inhibition In noncriminal male subjects, sexual arousal in response to erotic films produced activation in limbic and paralimbic regions (compared to viewing neutral films), but attempted inhibition of arousal was restricted to activation of right superior frontal gyrus and anterior cingulate. Beauregard et al, J Neurosci 2001 If scanning shows a lack of inhibitory ability, are you likely to commit a sexual crime? If one’s brain cannot inhibit arousal, is one responsible for impulsive actions? Should one be required to register with authorities or accept treatment?

23. Neuroethical questions • Should we enhance cognition in healthy people and if so, under what conditions (e.g. shift workers, military personnel etc)? • Should we limit access to cognitive enhancing drugs? Fairness? Possible harms on the developing brain? • Should we attempt to predict behaviour (e.g. the film Minority Report)? What impact will this have on our legal system? • What is the risk/benefit ratio to individuals and society of using available neurotechnology? How should we address error of measurement? • Who should have access to this neurotechnology? • What are the implications of developments in pharmacogenomics?

24. Pharmacogenomics Should people who do not experience harms be allowed to take illicit drugs? Who should have access to your “gene chip”? Roiser et al. Am J Psychiatry 2005 162(3):609-612

25. Conclusion: Active discourse is needed between scientists and ethicists, policymakers, and the general public to address these complicated ethical questions raised by new neurotechnology

26. Neuroethics Society http://www.neuroethicssociety.org/

27. Key references • Farah MJ, Illes J, Cook-Deegan R, Gardner H, Kandel E, King P, Parens E, Sahakian BJ, Wolpe PR (2004) Neurocognitive enhancement: what can we do and what should we do? Nature Reviews Neuroscience 5: 421-425 • Turner DC, Sahakian BJ (2006) Ethical questions in functional neuroimaging and cognitive enhancement. Poiesis and Praxis, doi: 10.1007/s10202-005-0020-1 • Turner DC, Sahakian BJ (2006) The neuroethics of cognitive enhancement. BioSocieties, 1: 113-123 • Turner DC, Sahakian BJ (2006) The cognition-enhanced classroom. Better Humans, (Eds P. Miller & J. Wilsdon), Demos • Duka T, Turner DC, Sahakian BJ (2005). Experimental Psychology and research into brain science, addiction and drugs. Foresight Review. http://www.foresight.gov.uk/Brain_Science_Addiction_and_Drugs/Reports_and_Publications/ScienceReviews/Index.htm See also: • Illes, J. (Ed) (2006) Neuroethics: Defining the issues in the theory, practice and policy, Oxford University Press • Entire issue Brain and Cognition 50, 2002 particularly: Wolpe, Canli and Amin