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Neuroethics Publications Center for Neuroscience & Society
5-1-2004
Neurocognitive Enhancement: what can we do and what should Neurocognitive Enhancement: what can we do and what should
we do? we do?
Martha J. Farah
University of Pennsylvania
, mfarah@psych.upenn.edu
Judy Illes
Stanford University
Robert Cook-Deegan
Duke University
Howard Gardner
Harvard University
Eric Kandel
Columbia University
See next page for additional authors
Follow this and additional works at: https://repository.upenn.edu/neuroethics_pubs
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Recommended Citation Recommended Citation
Farah, M. J., Illes, J., Cook-Deegan, R., Gardner, H., Kandel, E., King, P., Parens, E., Sahakian, B., & Wolpe, P.
R. (2004). Neurocognitive Enhancement: what can we do and what should we do?. Retrieved from
https://repository.upenn.edu/neuroethics_pubs/9
Postprint version. Published in
Nature Reviews Neuroscience
, Volume 5, Issue 5, May 2004, pages 421-425.
Publisher URL: http://dx.doi.org/doi:10.1038/nrn1390
This paper is posted at ScholarlyCommons. https://repository.upenn.edu/neuroethics_pubs/9
For more information, please contact repository@pobox.upenn.edu.
Neurocognitive Enhancement: what can we do and what should we do? Neurocognitive Enhancement: what can we do and what should we do?
Abstract Abstract
Our growing ability to alter brain function can be used to enhance the mental processes of normal
individuals as well as to treat mental dysfunction in people who are ill. The prospect of neurocognitive
enhancement raises many issues about what is safe, fair and otherwise morally acceptable. This article
resulted from a meeting on neurocognitive enhancement that was held by the authors. Our goal is to
review the state of the art in neurocognitive enhancement, its attendant social and ethical problems, and
the ways in which society can address these problems.
Keywords Keywords
WORKING-MEMORY, METHYLPHENIDATE, BRAIN, DRUGS
Disciplines Disciplines
Neurosciences
Comments Comments
Postprint version. Published in
Nature Reviews Neuroscience
, Volume 5, Issue 5, May 2004, pages
421-425.
Publisher URL: http://dx.doi.org/doi:10.1038/nrn1390
Author(s) Author(s)
Martha J. Farah, Judy Illes, Robert Cook-Deegan, Howard Gardner, Eric Kandel, Patricia King, Eric Parens,
Barbara Sahakian, and Paul Root Wolpe
This journal article is available at ScholarlyCommons: https://repository.upenn.edu/neuroethics_pubs/9
Science and Society
NEUROCOGNITIVE ENHANCEMENT: WHAT CAN WE DO
AND WHAT SHOULD WE DO?
Martha J. Farah, Judy Illes, Robert Cook-Deegan, Howard Gardner,
Eric Kandel, Patricia King, Eric Parens, Barbara Sahakian & Paul Root Wolpe
Our growing ability to alter brain function can be used to enhance the mental processes of
normal individuals as well as to treat mental dysfunction in people who are ill. The prospect of
neurocognitive enhancement raises many issues about what is safe, fair and otherwise morally
acceptable. This article resulted from a meeting on neurocognitive enhancement that was held
by the authors. Our goal is to review the state of the art in neurocognitive enhancement, its
attendant social and ethical problems, and the ways in which society can address these
problems.
Many are predicting that the twenty-first century will be the century of neuroscience.
Humanity's ability to alter its own brain function might well shape history as powerfully as the
development of metallurgy in the Iron Age, mechanization in the Industrial Revolution or
genetics in the second half of the twentieth century. This possibility calls for an examination of
the benefits and dangers of neuroscience-based technology, or 'neurotechnology', and
consideration of whether, when and how society might intervene to limit its uses.
At the turn of the century, neurotechnology spans a wide range of methods and stages of
development. Brain–machine interfaces that allow direct two-way interaction between neural
tissue and electronic transducers remain in the 'proof of concept' stage, but show substantial
promise
1
. Neurosurgery is increasingly considered as a treatment for mental illnesses and an
array of new procedures are under development, including the implantation of devices and
tissue
2
. Non-invasive transcranial magnetic stimulation (TMS) of targeted brain areas is the
basis of promising new treatments for depression and other psychopathology
3
.
On the leading edge of neurotechnology is psychopharmacology. Our ability to achieve specific
psychological changes by targeted neurochemical interventions, which began through a
process of serendipity and trial and error in the mid-twentieth century, is evolving into the
science of rational drug design. The psychopharmacopia of the early twenty-first century
encompasses both familiar, and in some cases highly effective, drugs, and a new generation of
more selective drugs that target the specific molecular events that underlie cognition and
emotion
4
. For the most part, these drugs are used to treat neurological and psychiatric
illnesses, and there is relatively little controversy surrounding this use. However,
psychopharmacology is also increasingly used for 'enhancement' — that is, for improving the
psychological function of individuals who are not ill.
The enhancement of normal neurocognitive function by pharmacological means is already a
fact of life for many people in our society, from elementary school children to ageing baby
boomers. In some school districts in the United States the proportion of boys taking
methylphenidate exceeds the highest estimates of the prevalence of attention deficit–
hyperactivity disorder (ADHD)
5
, implying that normal childhood boisterousness and
distractibility are being targeted for pharmacological intervention. The use of prescription
stimulants (such as methylphenidate and dextroamphetamine) as study aids by high school
and college students who do not have ADHD has recently drawn attention, and might include
as many as 16% of the students on some campuses
6
. Sales of nutritional supplements that
promise improved memory in middle age and beyond have reached a billion dollars annually in
the United States alone
7
, despite mixed evidence of effectiveness
8
. In contrast to the other
neurotechnologies mentioned earlier, whose potential use for enhancement is still
hypothetical, pharmacological enhancement has already begun.
What can we do?
Many aspects of psychological function are potential targets for pharmacological enhancement,
including memory, executive function, mood, appetite, libido and sleep
9, 10
. We will use the
first two of these, memory and executive function, as examples to show the state of the art in
psychopharmaceutical enhancement, the ethical issues raised by such enhancement and the
policy implications of these ethical issues. A brief review of the state of the art in
neurocognitive enhancement is offered here; additional information is freely available to
readers of this article at www.nyas.org/ebrief/neuroethics and in recent articles by Rose
11
,
Lynch
12
and Hall
7
.
Memory enhancement. Memory enhancement is of interest primarily to older adults. The
ability to encode new memories declines measurably from the third decade of life onwards,
and by the fourth decade the decline can become noticeable and bothersome to normal
healthy individuals
13
. Memory difficulties in middle or old age are not necessarily a harbinger
of future dementia but can be part of the normal pattern of cognitive ageing, which does not
make it any less inconvenient when we misplace our glasses or forget the name of a recent
acquaintance. What can current and imminent neurotechnologies offer us by way of help?
The changes that underlie normal age-related declines in memory probably differ from those
that underlie Alzheimer's disease, indicating that the optimal pharmacological approaches to
therapy and enhancement might also differ. Although donepezil, a cholinesterase inhibitor that
is used to treat Alzheimer's disease, did enhance performance in one study of healthy middle-
aged pilots after flight simulator training
14
, drug companies are looking elsewhere for
pharmacological approaches to memory enhancement in normal individuals. Recent advances
in the molecular biology of memory have presented drug designers with many entry points
through which to influence the specific processes of memory formation, potentially redressing
the changes that underlie both normal and pathological declines in memory. Most of the
candidate drugs fall into one of two categories: those that target the initial induction of long-
term potentiation and those that target the later stages of memory consolidation. In the first
category are drugs that modulate AMPA (
-amino-3-hydroxy-5-methyl-4-isoxazole propionic
acid) receptors to facilitate depolarization, including Cortex Pharmaceuticals' Ampakines
12
. In
the second category are drugs that increase CREB (the cAMP response element-binding
protein), a molecule that in turn activates genes to produce proteins that strengthen the
synapse. One such drug is the molecule MEM1414, which is being tested by Memory
Pharmaceuticals
7
(a company co-founded by one of the authors (E.K)).
The pursuit of mastery over our own memories includes erasing undesirable memories as well
as retaining desirable ones. Traumatic events can cause lifelong suffering by the intrusive
memories of post-traumatic stress disorder (PTSD), and methods are being sought to prevent
the consolidation of such memories by pharmacological intervention immediately after the
trauma
15
. Drugs whose primary purpose is to block memories are also being developed by the
pharmaceutical industry
7
. Extending these methods beyond the victims of trauma, to anyone
who wishes to avoid remembering an unpleasant event, is another way in which the neural
bases of memory could be altered to enhance normal function.
Enhancement of executive function. Executive function refers to abilities that enable
flexible, task-appropriate responses in the face of irrelevant competing inputs or more habitual
but inappropriate response patterns. These include the overlapping constructs of attention,
working memory and inhibitory control. Drugs that target the dopamine and noradrenaline
neurotransmitter systems are effective at improving deficient executive function, for example
in ADHD, and have recently been shown to improve normal executive function as well
16, 17
.
For example, one of the authors (B.J.S.) found that healthy young volunteers performed the
Tower of London problem-solving task more accurately after being given methylphenidate
than after being given a placebo when the task was novel
16
. Methylphenidate also increased
accuracy in a complex spatial working memory task, and this was accompanied by a reduction
in the activation of areas of the brain that are related to working memory, as shown by
positron emission tomography (PET)
17
. For the latter task, the amount of benefit was inversely
proportional to the volunteers' working memory capacity as assessed by a different working
memory task, digit span, with little or no benefit to those with the highest digit span
performances. This is of interest in discussions of enhancement, because it indicates that, for
this medication and this cognitive ability at least, those with lower levels of performance are
more likely to benefit from enhancement than those with higher levels. Indeed, it is possible
that some drugs would compress the normal range of performance in both directions. One of
the authors (M.J.F.) found that the dopamine agonist bromocriptine improved performance on
various executive function tasks for individuals with lower- than-average working memory
capacity, but lowered the performance of those with the highest working memory capacities
18
.
Whether enhancement can boost the performance of already high-performing individuals must
be determined empirically for each drug and for each type of cognitive ability.
Newer drugs might improve executive function in different ways, influencing different
underlying processes and interacting in different ways with individual differences (for example,
in working memory capacity) and states (such as restedness). The newest potential
neurocognitive enhancer is the drug modafinil, which is approved for the treatment of
narcolepsy and is increasingly prescribed off-label for other purposes
19
. One of the authors
(B.J.S.) found that it increases performance among healthy young adults on a set of executive
function tasks that differs partly from those that are influenced by methylphenidate, with its
effects resulting at least in part from an improved ability to inhibit impulsive responses
20
.
What should we do?
Ethical problems and policy solutions. Neurocognitive enhancement raises ethical issues
for many different constituencies. These include academic and industry scientists who are
developing enhancers, and physicians who will be the gatekeepers to them, at least initially.
Also included are individuals who must choose to use or not to use neurocognitive enhancers
themselves, and parents who must choose to give them or not to give them to their children.
With the advent of widespread neurocognitive enhancement, employers and educators will
also face new challenges in the management and evaluation of people who might be
unenhanced or enhanced (for example, decisions to recommend enhancement, to prefer
natural over enhanced performance or vice versa, and to request disclosure of enhancement).
Regulatory agencies might find their responsibilities expanding into considerations of 'lifestyle'
benefits and the definition of acceptable risk in exchange for such benefits. Finally, legislators
and the public will need to decide whether current regulatory frameworks are adequate for the
regulation of neurocognitive enhancement, or whether new laws must be written and new
agencies commissioned.
To focus our discussion, we will dispense with some ethical issues that are important but not
specific to neurocognitive enhancement. The first such issue is research ethics. Research on
neurocognitive enhancement, as opposed to therapy, raises special considerations mainly
insofar as the potential benefits can be viewed as smaller, and acceptable levels of risk to
research subjects would be accordingly lower. This consideration is largely academic for those
neurocognitive enhancers that come to market first as therapies for recognized medical
conditions, which includes all of the substances that are now available for enhancement,
although this might not be true in the future. Another important ethical issue concerns the use
of neurocognitive enhancement in the criminal justice system, in which a large proportion of
offenders fall in the lower range of cognitive ability in general
21
and executive inhibitory
control in particular
22
. Although neurocognitive enhancement brings with it the potential for
subtle coercion in the office or classroom, 'neurocorrection' is more explicitly coercive and
raises special issues of privacy and liberty that will not be discussed here. Finally, the ethical
problems that are involved in parental decision-making on behalf of minor children are
complex and enter into the ethics of neurocognitive enhancement in school children, but will
not be discussed here.