Neuroethical issues in cognitive enhancement and neuroimaging

Barbara Sahakian FMedSciProfessor 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

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.

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 FoundationMarcus, 2002

Neuroethics

Ritalin abuse scoring high on college illegal drug circuit January 8, 2001 Web posted at: 2:55 PM EST (1955 GMT)

From Linda Ciampa CNN Medical Correspondent

(CNN) -- There's a popular drug on the streets with nicknames such as "Vitamin R" and "R-Ball" that's making its way into the college scene. But it's not for kicks -- students use this drug to improve concentration and study longer. The drug is Ritalin, a mild stimulant commonly prescribed for young children to treat attention deficit/hyperactivity disorder, or ADHD. But on U.S college campuses, students are popping Ritalin without a doctor's prescription -- which is illegal -- before taking on all-night study sessions or to boost alertness during an important test. "People find this drug enticing because they can get their academic work done quicker or do more in a shorter period of time," said Dr. Eric Heiligenstein, of the University of Wisconsin. "So for students who have put off work or are not very strong academically, we find some are using it to kind of counteract or remedy their problems."

Increasing prescriptions for Ritalin

Farah 2005 TICS

Methylphenidate

Modafinil

Number of moves

Mea

n at

tem

pts

take

n to

cor

rect

ly s

olve

pro

blem

0.8

1.0

1.2

1.4

1.6

1.8

PlaceboLowHigh

1 2 3 4 5 6

* * **

P=0.002

Modafinil improves planning in healthy volunteers

Impr

ovem

ent

Posted on Thu, May. 20, 2004

American sprinter takes two-year ban White won't run in 2004 Olympics

American sprinter Kelli White accepted a

two-year drug ban Wednesday, costing her a trip to the Athens Olympics and every medal she won during the past four years.

White tested positive for the stimulant modafinil at last year's world championships and U.S. nationals.

Buy Your prescription drugs without the need for prescription or consultation. Order MODAFINIL online without the hassle of a pharmacy or drugstore membership. Prescriptions are discretely packed and shipped at no additional cost. All transactions are 100% secure and full confidentiality is offered. We honour customer service and are here for You 24 hours a day, 7 days a week.

Save up to 85% in medicine costs at our Discount Online Pharmacy

No prescription required at this Internet pharmacy

Over 2000 brand name & generic products at our Discount Online Pharmacy

NO CONTROLLED DRUGS/ HABIT FORMING DRUGS

Order MODAFINIL within minutes at our online Internet pharmacy

No embarrassment, no appointments

Best quality of prescription MODAFINIL available at our Discount Online Pharmacy

Over 10,000 extremely satisfied customers

No membership fees required at our Internet pharmacy

MODAFI NI L Also known as : Alertec, Provigil

Buy MODAFINIL online without a prior prescription

Manufacturer: Cephalon

Strength Price US$

10mg Tabs 30 $69.00

Information: Used to treat excessive daytime sleepiness associated with narcolepsy

100mg

Modafinil

Stahl SM (2002) J Clin Psychiatry

Calm wakefulness

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.

Stimulated vigilance

Atomoxetine (Strattera) is a relatively selective noradrenaline reuptake inhibitor (SNRI).

“40 potential cognitive enhancers are currently in clinical development”

- NeuroInvestment

Novel cognitive enhancers

Ampakines improve cognition in healthy aged volunteers

Ampakines enhance the AMPA receptor’s response to glutamate

The “Rights” and “Wrongs” of cognitive enhancement

in healthy people

– Shift workers, air traffic control …– School pupils

• Normalisation – removal of unfair disparity in society (if people can be helped they should be)

‘RIGHTS’Potential benefits

•Increase performance (both pleasurable and competitive activities)

– Military

In addition to scientific and clinical

advances

“ Eliminating the need for sleep during an operation, while maintaining the high level of both cognitive and physical performance of the individual, will create a fundamental change in war fighting and force employment. Such a capability has the potential to disrupt enemy OPTEMPO [operations tempo], increase the effectiveness of small footprint military forces and shorten the duration of conflict.”

Research and Development organisation for the US Department of Defence

Military uses of cognitive enhancers

• 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 …

‘WRONGS’Potential harms

Tuesday, 11 February, 2003, 22:01 GMT US inmate faces deadly drugs cure

Taking drugs may mean the prisoners can be executed

By Susannah Price BBC correspondent in New York

A United States federal appeals court has ruled that mentally ill prisoners can be forced to take drugs even if it makes them sane enough to be executed.

The US Supreme Court prohibits the execution of the mentally ill but says inmates can be forced to take anti-psychotic medication in some cases.

Las t U p d a ted : W ed n esd ay , 7 J an u a ry , 2 0 0 4 , 0 8 : 2 4 G M T

E - m a il th is to a fr ien d P r in tab le v e rs ion

M en ta lly ill m a n ex ecu ted in U S

T h e s ta te o f A rk a n sa s h a s e x e cu te d a m a n w ith a se v e re m e n ta l illn e ss .

C h ar les S in g le to n , 4 4 , w as fo rc ib ly g iv en an ti- p s y ch o tic d ru g s w h ich m ad e h im lu c id en o u g h u n d er co u r t g u id e lin es to b e p u t to d ea th .

A d iag n o s ed s ch iz o p h ren ic , h e w as g iv en a le th a l in j ectio n in th e s ta te 's d ea th ch am b er in V a rn er fo r k illin g g ro cery s to re w o rk er M ary Lo u Y o rk in 1 9 7 9 .

S in g le ton 's law y ers a t tem p ted to s top h is m ed ica t ion

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

‘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

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

Unconscious racial biasesIn 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?

Neural correlates of moralityAreas 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?

Deception and lie detectionDifferential 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?

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?

Behaviour prediction: imaging inhibitionIn 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?

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?

Pharmacogenomics

L a s t U p d a t e d : F r id a y , 4 M a r c h , 2 0 0 5 , 0 0 : 3 4 G M T

E - m a il t h is t o a f r ie n d P r in t a b le v e r s io n

E c s ta s y u s e ' l in k ' t o d e p r e s s io n

H e a v y e c s ta s y u s e is l in k e d to a n in c r e a s e in d e p r e s s iv e s y m p to m s in s o m e p e o p le , a s tu d y s u g g e s ts .

A C a m b r id g e U n iv e r s it y t e a m s tu d ie d 1 2 4 p e o p le a n d fo u n d th o s e w ith a c e r ta in g e n e t ic m a k e - u p s h o w e d g r e a te r s ig n s o f d e p r e s s io n a f te r u s in g th e d r u g .

T h e s c ie n t is t s , w r it in g in th e A m e r ic a n J o u r n a l o f P s y c h ia t r y , s a id it c o u ld s h o w h o w v u ln e r a b le e c s ta s y u s e r s a r e t o lo n g -te r m p s y c h ia t r ic p r o b le m s .

T h e s t u d y lo o k e d a t p e o p le w h o r e g u la r ly u s e e c s t a s y

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

Conclusion:

Active discourse is needed between scientists and

ethicists, policymakers, and the general public to address these complicated ethical questions

raised by new neurotechnology

Neuroethics Societyhttp://www.neuroethicssociety.org/

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