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. Increasing prescriptions for Ritalin
Methylphenidate
Increasing prescriptions for Ritalin
Farah 2005 TICS

5. Modafinil Modafinil improves planning in healthy volunteers
Improvement
Modafinil improves planning in healthy volunteers

6. Modafinil
100mg

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 enhancement in healthy people

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

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 enhancement Conclusions
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:

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. Forensic neuroimaging: violent offenders
Criminal psychopaths show different patterns of emotional-related activity compared to non-criminal control subjects (Kiehl, Biol Psychiatry 2001)
Areas of less activation
Areas of more activation
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 (3):

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

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:
Turner DC, Sahakian BJ (2006) Ethical questions in functional neuroimaging and cognitive enhancement. Poiesis and Praxis, doi: /s
Turner DC, Sahakian BJ (2006) The neuroethics of cognitive enhancement. BioSocieties, 1:
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.
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