Some science-related strategic challenges (excerpt)

A report for the UK Government Office for Science

Ariel Research Services February 2013
Written by Michael Reilly +44 (0)7986599791 michael@arielresearchservices.com www.arielresearchservices.com
Prospero and Ariel by Steering for North 2012 All rights reserved

This report has been commissioned by the UK Government Office for Science. The views expressed in this report are not those of the UK Government and do not represent its policies.

Created by Ariel Research Services 4. Neuroscience from genes to cognition, from molecule to mind Summary

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Neuroscience, the study of the brain and the nervous system, could be the most revolutionary and far-reaching area of scientific research of the 21st century. The most important application so far has been to the analysis and treatment of neurological disorders but some of the other early applications of neuroscience are rudimentary and controversial. There are risks of policy mis-steps in the regulation of the neuroscience application and principles will have to be carefully formulated. Through new pedagogies, it could have a key role in treating learning difficulties and enhancing cognition. Security applications are already being explored, particularly in the US, and it is expected to be a force multiplier. Neuroeconomics, a rich inter-disciplinary convergence between biology, psychology and economics is likely to have implications for policymaking. The physiology and the activity of the brain resemble that of a complex network and it may be resistant to meaningful simulation. Invasive experiments on mice and monkeys have been crucial to the rapid development of neuroscience since the latter half of the 20th century and experts argue they will still be necessary. The phenomenal rise of fMRI has meant that non-invasive experiments using humans have become widespread. Although fMRI is a crude instrument, it could be improved in the future. Optogenetics, which is currently exciting neuroscientists, illustrates the profound societal opportunities of neuroscience but also the threats it represents to some social norms. New connections In 1906 a brilliant Spanish anatomist Santiago Ramn y Cajal produced evidence for the neuron doctrine (Ramn y Cajal, 1967). Cajal found that the brain is made of discrete cells, neurons, which act as elementary signalling units. The number of neurons and their connectivity is what distinguishes the cognitive ability of species. Around the 1960s it was becoming apparent that the brain filters and transforms sensory information, according to its physiology, and that these transformations are critical for perception (Kandel & Squire, 2000). Neuroscience, the study of the brain and the nervous system, could be the most revolutionary and far-reaching area of scientific research of the 21st century (Taylor, 2012). The fundamental questions of how the brain perceives, thinks, acts and remembers have been invigorated by a remarkable integration of molecular and cell biology and psychology. Once at the periphery, neuroscience has become an inter-disciplinary field that is now central to both. Its scope ranges from genes to cognition, from molecules to mind (Kandel & Squire, 2000). Measured in terms of publication and citation, neuroscience and its related disciplines have been the fastest growing areas of scientific research for the last decade (University of Washington, 2012). The most important application so far has been in the analysis and treatment of neurological disorders (Kandel & Squire, 2000). Slower progress has been made with psychiatric disorders partly because they are also modulated by environment factors.

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Figure 4.1, New connections in science research, 2004. Source: (University of Washington, 2012). Orange circles represent fields, with larger, darker circles indicating larger field size as measured by an eigenfactor score. Blue arrows represent citation flow between fields. An arrow from field A to field B indicates citation traffic from A to B, with larger, darker arrows indicating higher citation volume. Fuzzy thinking But some of the other early applications of neuroscience are rudimentary and controversial. Professor Dan Ariely argues that using functional magnetic resonance imaging (fMRI) to assess products and services at the ideas stage may be commercially useful while others dismiss it as marketing hype (Ariel & Berns, 2010). Neuroimaging has also been introduced as evidence in courts of law even to the extent in the US of helping to assess culpability of criminal behaviour (Royal Society, 2011). There are risks of policy mis-steps in the regulation of the neuroscience application. In France, neuroscientists helped convince the French Parliament to revise its rules on bioethics and ban commercial use of neuroimaging but were unable to resist politicians 3

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wishes for it to be used in the context of court expertise (Ouillier, 2012). Policy-makers would do well to anticipate applications in advance because decisions could be difficult; and principles-based regulation may be necessary to prevent innovation being stifled by blunt prohibition. A force multiplier The gradual application of neuroscience to policy belies its extraordinary potential. Although learning outcomes are also modulated by environmental factors, in education and lifelong learning, neuroscience research has provided new insights into the enduring plasticity of the brain and the transience of skill. Through new pedagogies, it could have a key role in treating learning difficulties and enhancing cognition (Royal Society, 2011). Security applications are already being explored, particularly in the US. A National Academy of Science report in 2009 urged a more systematic monitoring of research breakthroughs so as to anticipate applications where investment may confer significant military advantage (National Research Council, 2009). Cognitive neuroscience has been identified as an area that could lead to improvements in soldier performance. A deeper understanding of individual variability could, by enabling a better allocation of personnel to tasks based on their attitude to and appetite for risk, become a force multiplier. There is interest in its applicability to the efficacy of training, pharmacological cognitive enhancement, as well as post-traumatic stress disorder (PTSD) and post-blast care. The report also recommends investment into key technologies such as brain-machine interfaces. Neuroeconomics Neuroscience has also become recently intertwined with economics through the study of decision-making and economic behaviour. This rich inter-disciplinary convergence between biology, psychology and economics is likely to have implications for policymaking. One of the early breakthroughs in neuroeconomics has been a deepening in the understanding of reinforcement learning where an agent has to make choices through trial and error. In this decision-making framework, prediction errors update and guide the agent towards options that maximise reward. Following on from single-neuron recording experiments in monkeys, it has subsequently been discovered that dopamine-mediated prediction error is used as a teaching signal to learn expected action values and to favour optimal choice in humans (Dolan, 2008). For humans especially, there can also be other potential outcomes to a decision such as another more uncertain though potentially more valuable reward. There is evidence that this exploit-explore dilemma is mediated by activity in distinct parts of the brain: orbital prefrontal cortex activity covaries with exploitative actions and anterior frontopolar cortex activity covaries with exploratory actions (Daw, et al., 2006). Neuroeconomics insights are leading to a more theoretical understanding of decisionmaking. If key economic variables such as a disposition to explore or exploit, a propensity to discount future rewards, or sensitivity to variance in outcomes, are under modulatory neurotransmitter control then it raises the prospect of more precise pharmacological interventions to treat aberrant decision-making (Dolan, 2008). But it also presents socially awkward - though potentially game-changing - opportunities to enhance sub-optimal 4

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decision-making through selection, training and pharmacology. Neuroscience could load categorisations of human computational cognition with meanings that invite dangerous interpretations. Brain activity If only neuroeconomics were advanced enough to help decision-makers allocate resources to future research. Despite the achievements of neuroscience, the brain represents an exemplar of the messiness of the real. Two hugely ambitious neuroscience projects in the US and in Europe have been launched recently to generate and synthesise new knowledge. The US project, announced by President Obama in his 2013 State of the Union address, is likely to follow the successful approach of the Human Genome Project by mapping brain activity (Markoff, 2013). The European Union Human Brain Project, on the other hand, a 10 year 1.2bn flagship science project, intends to simulate the brain using supercomputers, an undertaking that some neuroscience experts consider foolhardy at current levels of knowledge (Waldrop, 2012). The physiology and the activity of the brain resemble that of a complex network, which may resistant to meaningful simulation (Marcus, 2013). It is, thus, important to take stock of the inadequacies of current knowledge. There are many important questions in neuroscience that it will be difficult to answer with the limitations of existing methods (Brain Mind Forum, 2012). But an instrumental challenge Some reporting of the Human Brain Project has erroneously claimed that computer simulation may lessen the need for invasive experiments on animals such as mice and monkeys (Waldrop, 2012). Such experiments have been crucial to the rapid development of neuroscience since the latter half of the 20th century and experts argue they will still be necessary. Professor Colin Blakemore, a renowned neuroscientist, and an outspoken advocate of the need for experiments with animals to improve scientific knowledge of the human nervous system, faced years of attacks by animal rights activists (McKie, 2003). The phenomenal rise of fMRI has meant that non-invasive experiments using humans have become widespread. Using blood as a proxy for the measurement of neuron activity, fMRI is a crude instrument. The technique could be improved by switching to superconducting quantum interference devices to measure directly the electrical activity of neurons, or, failing this, using stronger magnets and molecular enablers like parahydrogen that generate a better signal (Smith, 2012). More powerful statistical analysis may improve the low signal-tonoise ratio of fMRI while a systematic accumulation of reference datasets could benefit comparative research (Smith, 2012). Optogenetics shines a light Neuroscientists are currently very excited by optogenetics. By genetically engineering neurons to be sensitive to light and then employing implanted optical fibres to stimulate and control their expression, experiments have been able to discover with greater precision how complex brain networks affect behaviour in mice (Schoonover & Rabinowitz, 2011). The application of this new knowledge to human neurological and psychiatric disorders could refine imprecise pharmacological interventions and invasive deep brain stimulation. The 5

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technology illustrates the profound societal opportunities of neuroscience but also the threats it represents to some social norms. On the one hand, identifying complex brain circuits in humans that explain disorders may reduce the considerable stigma of neurological and psychiatric disorders. On the other, the pioneer of optogenetics, Professor Gero Miesenbock, has been caricatured as a comic character in Japan as a brilliant, but evil, scientist whose skull has been replaced with a plexi-glass dome so that his thoughts can be controlled with light (Fielden, 2012).

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References Ariel, D. & Berns, G., 2010. Neuromarketing: the hope and hype of neuroimaging in business. Nature Neuroscience, Volume 11, pp. 284-292. Brain Mind Forum, 2012. The Key Questions for brain sceince and society to address, London: Brain Mind Forum. Daw, N. et al., 2006. Cortical substrates for exploratory decisions in humans. Nature, Volume 441, pp. 876-879. Dolan, R., 2008. State of science review: neuroeconomics, London: Governemnt Office for Science. Fielden, T., 2012. Switching on a light in the brain. [Online] Available at: http://www.bbc.co.uk/news/science-environment-20513292 Kandel, E. & Squire, L., 2000. Neuroscience: breaking down scientific to the study of brain and mind. Science, Volume 290, pp. 1113-1120. Marcus, G., 2013. We are not yet ready to simulate the brain. [Online] Available at: http://www.ft.com/cms/s/0/b70cc5d6-6b00-11e2-9670-00144feab49a.html Markoff, J., 2013. Project seeks build map of human brain. [Online] Available at: http://www.nytimes.com/2013/02/18/science/project-seeks-to-build-map-ofhuman-brain.html?ref=science McKie, R., 2003. Scientist who stood up to terrorism and mob hate faces his toughest test. [Online] Available at: http://www.guardian.co.uk/uk/2003/sep/14/animalwelfare.science National Research Council, 2009. Opportunities in Neuroscience for Future Army Applications, Washington D.C.: National Academies Press. Ouillier, O., 2012. Clear up this fuzzy thinking on brain scans. [Online] Available at: http://www.nature.com/news/clear-up-this-fuzzy-thinking-on-brain-scans1.10127 Ramn y Cajal, S., 1967. Nobel Lectures: Physiology or Medicine (1901-1921). Amsterdam: Elsevier. Royal Society, 2011. Brain Waves Module 2: implications for education and lifelong learning, London: Royal Society. Royal Society, 2011. Brain Waves Module 4: Neuoroscience and the law, London: Royal Society. Schoonover, C. & Rabinowitz, A., 2011. Control desk for the neural switchboard. [Online] Available at: http://www.nytimes.com/2011/05/17/science/17optics.html?pagewanted=all&_r=0 Smith, K., 2012. fMRI 2.0. Nature, Volume 484, pp. 24-26.

Created by Ariel Research Services Taylor, K., 2012. The Brain Supremacy. [Online] Available at: http://www.huffingtonpost.com/kathleen-taylor/neuroscienceresearch_b_1909556.html University of Washington, 2012. Maps of science. [Online] Available at: http://www.eigenfactor.org/map/maps.php

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Waldrop, M., 2012. Computer modelling: brain in a box. Nature, Volume 482, pp. 456-458.