Historically, neuroscientists have had a range of tools to manipulate and observe neural circuits in the brain. These techniques, however, have often lacked the ability to isolate the contribution of specific neurons or types of neurons to the overall network. With optogenetics, researchers can now discretely control neuronal activity by using pulses of light to activate or inactivate specific populations of neurons. These tools are giving neuroscientists the potential to unlock many of the remaining mysteries of how individual groups of cells in the brain control perception and behavior.

The term optogenetics was first coined by one of its pioneers, Karl Deisseroth at Stanford. The technique, which recently won the 2010 Nature Methods method of the year award, makes use of a group of ion channels and other proteins discovered in bacteria and algae called “opsins.” These proteins are light sensitive and can therefore be activated by pulses of light of an appropriate wavelength. Depending on the opsin expressed, this will either excite or inhibit the neurons. The expression of opsins in mammalian neurons is achieved by inserting the encoding DNA into the target cells, which then produce the opsin proteins. The process of DNA addition is called transfection, and is typically accomplished by using a specially selected virus as a carrier to deliver the new DNA. Variants in the viral delivery and DNA coding sequence allow for specific subtypes of neurons to be targeted. Once opsins are expressed in the neurons, the firing rate can then be controlled in vivo by light from an implanted fiber-optic cable or through a small window in the skull.

This technique gives researchers enormous flexibility and control of the behavior of specific cell types in a given brain region. Spatial resolution comes from the location of the injection and the neural cell-type specificity of the viral vector. Temporal control is produced by the frequency of the delivered light pulses, which via the opsins drives the cells to fire at the same frequency as the pulses of light, or alternatively prevents them from firing at specific times.

For example, a group of neurons in a specific area of the brain could be transfected with an opsin that excites the cells, and then is activated at various frequencies to see how this changes the animal’s perception of a stimulus directed to this area of the brain. It can also be used to completely silence a set of neurons during specific behavioral tasks in order to determine the effect of those neurons on that behavior. With this level of precise control, many systems neuroscience questions that had imprecise answers previously can now be addressed by observing awake, behaving animals.

Some of the recent articles published using this technique have demonstrated new insights into previously vexing problems in neuroscience. For example, there has been a tremendous amount of debate about the mechanism of deep brain stimulation, or DBS, utilized to treat movement disorders resulting from Parkinson’s disease.

This treatment uses electrical stimulation targeted to a region of the brain involved in motor output and control, and its mechanism of action is not well understood. It has previously been difficult to assess whether this intervention affects the neurons nearby the electrode directly, the inputs to those neurons, or the targets of the output from these neurons in this circuit.

Researchers utilized a mouse model of Parkinson’s disease and optogenetics to dissect the circuits of the brain involved in the response to electrical stimulation of the targeted area. Their results suggest that rather than leading to a simple excitation or inhibition of the neurons in the targeted area, DBS is activating connections arising from another area, and that this activation is necessary for the effectiveness of the treatment.

Another recent article demonstrated the importance of a single type of neuron to cocaine addiction in mice, suggesting a target for future clinical interventions. Because this particular type of neuron represents only 1 percent of the cells in the investigated area (the Nucleus accumbens), they have been difficult to study up until now, and their function has been the subject of much debate in scientific literature. The precise genetic targeting of the opsins allowed for just this population of neurons to be manipulated during the experiment.

The implications of this new technology for the field of systems neuroscience are profound. Its potential is being realized as the technique is implemented more broadly and more difficult circuits and systems are teased apart. A better understanding of the circuits underlying psychiatric and neurological disorders will hopefully also lead to improved clinical treatments.

One question for the future is whether or not these new techniques may be directly used to treat some human disorders as well. For example, a future version of DBS might be coupled with optogenetics to provide more specific targeting of cells in the basal ganglia, directly affecting the firing patterns of the cells responsible for disrupted movement in Parkinson’s disease. In addition, research efforts in the past year have successfully demonstrated the feasibility of utilizing optogenetics in nonhuman primates. Use of this technology in humans, however, would combine the ethical dilemmas of gene therapy with those of brain-machine interfaces such as DBS. While the road to safe and efficacious use of this technology for treatment in humans is uncertain, it is already providing great benefits to scientists in understanding circuits and their complex regulation in the brain.

As Congress turns back this week to the continuing resolution to fund the government through the end of fiscal year 2011, it is important that we keep in mind the essential role of federal funding in facilitating scientific advances like optogenetics. The original project in Dr. Deisseroth’s laboratory, the first attempt to integrate the microbial opsins into mammalian cells, was funded by a grant awarded by the National Institutes of Mental Health and National Institutes of Health, as are many of the above-mentioned projects that followed. The first scientists describing the light-sensitive proteins in 1971 could not have predicted that their findings would lead to such a profound change in neuroscientific research. These discoveries are one of the best arguments for continuing to fund basic biological research as well as more translational research: We often don’t know where the breakthroughs are going to come from that will be the basis for the next generation of treatments for disease, or that will allow us to better understand the complex systems that make up our daily habits, thoughts, and decisions.

John A. Wolf, Ph.D., is a neuroscientist at the Center for Brain Injury and Repair in the Department of Neurosurgery at the University of Pennsylvania.

Nationwide, 68 percent of U.S. adults own their own homes, and about two-thirds have mortgages. Given recent market trends and financial instability, nearly 20 percent of homeowners owe more on their homes than their properties are currently worth. Studies by First American CoreLogic reveal that about 8.31 million properties were “underwater” at the end of 2008, up almost 10 percent from 7.63 million at the end of September.[1]

CoreLogic predicts about 2.16 million additional properties will sink “underwater” if home prices fall another 5 percent. The problem is the worst in California, Florida and Nevada (Reuters News, March 4, 2009).[2]

If the value of a home becomes less than the mortgage on it, a basic cost/benefit analysis of the tangibles might suggest walking away from the mortgage—even if one could afford to keep paying. Indeed, recent reports indicate that this phenomenon has been growing in frequency around the country. It may be no surprise that foreclosure rates rose 81 percent in 2008,[3] but that figure is only the latest of an uptrend that has been accelerating for over 50 years.[4] Yet the vast majority of homeowners choose to keep paying their “underwater” mortgages. Why?

Though behavioral scientists have been long aware of the importance of the irrational factors in human behavior—Freud wrote in 1937 about defense mechanisms and manifestations of unconscious conflict[5]—economic theories of personal financial decision making have assumed a rational “actor” driven by basic calculations built on dollars and cents.

In the last decade, these “intangible” drivers have finally come to the fore in the study of human “economic” decision-making. For example, the 2002 Nobel Prize in economics was awarded to Daniel Kahneman, a cognitive psychologist who elucidated the psychological asymmetry between risk-aversion and reward-seeking in economic decision making. Here, we re-examine one such “intangible” driver: the biology of social interactions, and assign it a proper place among the factors that make us keep our underwater mortgages and maintain other behaviors that are not accounted for by an individual’s rational cost and risk/benefit analyses.

Although quasi-financial but tangible consequences of walking away from an underwater mortgage, such as damage to credit rating and the logistic, legal, and accounting costs undoubtedly play a role in the decision to stay put, they alone may not account for all the forces that make the overwhelming majority of the underwater mortgage holders stay put. During a recent This American Life episode,[6] radio host Ira Glass interviewed a woman who continued to reside in an unmaintained condo building along with a handful of other owners despite there being 19 vacant units and having the financial means to cut her losses and leave. She replied, “I have an ability to pay… I will do my part to honor my word.” Another interviewee stated, “What would happen if everybody left??… If I leave and foreclose… then the people that are left, are left even more up a creek than they were before… it’s kind of like, we’re all in this together.” These statements suggest that the “social contract” rather than the tangible reward has been a decisive factor in the condo owners’ actions.[7]

In the past, the social contract was examined using traditional social science techniques based on surveys and subjective self-report. Recent progress in social neuroscience, building on advances in imaging technology, shines a new light on the biology underlying the social forces that influence our behavior.

One approach to identifying the effects of social interactions is to examine the effects of their absence, by studying the biology of social isolation. As Atul Gawande asserted in a recent piece in The New Yorker,[8] isolation is one of the most biologically deleterious states of human existence. According to recent neurobiological research, prolonged isolation is associated with diverse but uniformly negative medical and psychological outcomes, including reduced ability to recover from disease, obesity, depression and anxiety.[9],[10]

At the other end of the spectrum, a growing body of literature highlights the biological rewards of social cooperation. For example, dopamine release, the “feel-good” rush associated with drug addiction and euphoria, has been associated with reciprocity and cooperation among non-relatives.[11] In other words, from a biological standpoint, socially cooperative behaviors could be an end to themselves, as far as your unconscious brain is concerned.

Back to the underwater mortgages: Perhaps the reluctance of debtors to walk away from their financial commitments reflects a more fundamental (unconscious) need to remain attached to the social fabric? As the famous Polish anthropologist Bronislaw Malinowski noted in his classic Argonauts of the South Pacific, commerce itself is a highly social endeavor.[12] Malinowski studied the “Kula,” a symbolic system of shell exchange of the Massim tribes in the South Pacific islands during the First World War. His main finding was that the Kula was a social economy built on reciprocity. The material possessions (armshells and necklaces in this case) were simply a conduit for fostering positive reputations and meaningful social connections, activities that we now know to be directly reinforced by the release of the “feel good” neurotransmitters—i.e. dopamine.

A paper published in the journal Neuron last year explored the similarities between social approval and monetary reward on a neural level.[13] The researchers found that in both cases common pathways are activated (a “common currency” so to speak) and that there are likely reward pathways (in the medial pre-frontal cortex) uniquely activated by social approval that ultimately contribute to dopamine release. In other words, the brain is likely hard-wired to seek social approval through cooperative interactions.

Given the growing body of evidence of the biological necessity of human cooperation, the weakening of the unwritten social contract that links individual biology to mass behavior may lead to large scale unanticipated complications, such as those facing the United States today. The unexpected adverse effects of the complex and untested financial instruments such as credit-default swaps and collateralized debt obligations may be enabled by the anonymous marketplace in which they have been conceived.

The increasing distance between parties involved in financial transactions and the increasing number of intermediaries (often virtual and/or disembodied through technological advances) between a buyer and seller reduce accountability while breeding anonymity. It is likely that it is less costly for the brain to lose approval or experience isolation from a vaguely known virtual brokerage accountant than from the local banker who has mutual social connections. If biologically-driven self-regulation is extinguished, the only support left for the sustainable financial behaviors is external regulation and enforcement, which is inadequate—derivative trading being a recent and notable example—as there are never enough resources to enforce rules that society is not positively and instinctively motivated to uphold.

The ever-growing stream of financial scandals involving the breach of trust is an example. If the world’s equity value is determined largely by the trust in the underlying financial system of exchange, rather than intangible assets, the loss of the social contract could spell the end of the globalized financial markets as we know them. Though regulation has been offered as the panacea for corporate malfeasance, this may not be practical in the absence of self-regulation by social contract. What portion of the world’s daily financial and equity transactions is or can be actually audited? It is likely a minority.

We would like to propose a few practical steps for reinforcing the social contract despite rapid changes in financial markets and unfettered globalization. First, the relevance of neurobiology should be recognized by the financial and industrial policymakers. Second, since data processing and communications technology are the major drivers of complex financial markets and globalization, they may likewise be harnessed to correct resultant social damage. For example, reducing the number of intermediaries in, and restoring human interaction to, financial transactions—such as refinancing underwater mortgages—whether through webinars, Skype, or actual-human interaction, would help reestablish the social reward of holding up one’s end of the bargain. Imagine smart technology employed to visibly maintain the ties between all agents involved in derivative products, from the homeowner to the lender to the insurer, trader, banker, and ultimate tiers of investors. Further, investing financial systems with mechanisms to apportion tokens of social approval upon clients who uphold contracts may enhance their innate tendency to do so. Finally, independent research, applying the wide array of the deceptively “academic” basic social neuroscience data, to the problems on hand, should be encouraged through the established funding mechanisms, such as the National Institutes of Health or the Congressionally Directed Medical Research Programs, along the lines of “translational” research in molecular biology and other purely “medical” topics.

The main focus throughout all of these interventions is recognizing and using the existing instinctive prosocial individual behaviors to benefit society rather than expend societal resources on the self-destructive battle against human biology. It is true that contemporary society—mortgages and all—is a far cry from the environs in which humans evolved. However, turning away from fundamental neurobiological human drives, such as the need for social approval and cooperation, might ultimately sink us all.

Arthur Robinson Williams, M. A. (Bioethics), is a fourth-year medical student and Daniel D. Langleben, M.D. is an Associate Professor of Psychiatry, both at the University of Pennsylvania School of Medicine.

Sources

[1] First American CoreLogic, “First American CoreLogic’s Negative Equity Data Report,” December 11, 2008.

[2] Stempel, Johnathan, “One in Five US Mortgage Borrowers are Underwater,” Reuters, March 4, 2009.

[3] Christie, Les (2009), Foreclosures up a record 81% in 2008, “Filings continued to soar through the end of the year – and there’s no relief in sight for 2009,” CNNMoney.com, January 15, 2009.

[4] Elmer, Peter J. and Seelig, Steven A., “The Rising Long-Term Trend of Single-Family Mortgage Foreclosure Rates,” Working Paper, Federal Deposit Insurance Corporation, Division of Research and Statistics, 1998.

[5] Freud, A., “The Ego and the Mechanisms of Defence,” London: Hogarth Press and Institute of Psycho-Analysis, 1937.

[6] Glass, Ira., “Scenes From a Recession,” This American Life #377, Chicago Public Radio, March 27th, 2009.

[7] Rousseau, Jean-Jacques, “The Social Contract, or Principles of Political Right,” 1762.

[8] Gawande, Atul, “Hellhole,” The New Yorker, March 30th, 2009.

[9] Karelina, K, et al. “Social isolation alters neuroinflammatory response to stroke.” Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5895-900.

Wallace, DL, et al., “CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits,” Nat Neurosci. 2009 Feb;12(2):200-9.

[10] Fone KC, Porkess MV., “Behavioural and neurochemical effects of post-weaning social isolation in rodents-relevance to developmental neuropsychiatric disorders,” Neurosci Biobehav Rev. 2008 Aug;32(6):1087-102. Epub 2008 Mar 18.; Herzog, CJ, et al. “Chronic Social Instability Stress in Female Rats: A Potential Animal Model for Female Depression,” Neuroscience 159 (2009) 982–992.

[11] Rilling, J., D. Gutman, et al., (2002). “A neural basis for social cooperation,” Neuron 35(2): 395-405; Glocker, M., Langleben, DD, Ruparel, K, Loughead JW, Gur, RC, Sachser, N (2009), “Baby Schema in Infant Faces Induces Cuteness Perception and Motivation for Caretaking in Adults,” Ethology 115(3): 257-263.

[12] Malinowski, B., Argonauts of the Western Pacific (1922).

[13] Izuma, K; Saito, DN; Sadato, N., “Processing of Social and Monetary Rewards in the Human Striatum,” Elsevier Inc. Neuron (58), 284-294, 2008.

The equivalence concept-that training should produce soldiers with similar skill sets-provides commanders with flexibility in replacing one soldier with another as casualties and other exigencies of combat require. It is embodied in the “uniform” assigned to each new recruit, and illustrated in such films as Band of Brothers, in which soldiers come and go as barely distinguishable names and faces. Of course, as soon as basic training is over, distinctions are drawn over such matters as special training, assignments and, eventually rank. But the essential idea that the basic warfighter should be functionally similar to another remains salient in military theory.

But with more attention to the empirical applications of modern neuroscience, we can better understand the connections between predictors of success and individual variability in training and learning. As a result, equivalence may not be the key to preparing the modern soldier.

Although commanders have always intuitively recognized individual differences (as in the case of President Abraham Lincoln, who sought a general who would execute his war strategy), the application of 20th century psychological concepts like IQ and personality types formalized the idea that uniqueness could be exploited as well as screened out. Work assignments and military career paths could be guided by valid distinctions in capacity and potential. In the selection of certain individuals for high risk/high gain tasks, as in the case of special operations personnel, it is surely desirable to have as much psychological data as possible.

Yet with data comes the potential for bias, and genetic discrimination is a concept familiar in the civilian world. While he was a U.S. Senator, President Obama co-sponsored a bill that prohibits discrimination based on the results of DNA tests. But the use of such testing for positive purposes like employment opportunities might not be considered discriminatory, and in any case national security needs could trump conditions thought to be unacceptable in the civilian world. Those who take up arms in defense of a nation, whether volunteers or conscripts, are commonly understood to have ceded their liberties, and implicitly accept risks that are not necessarily shouldered by other citizens.

In the real world these extraordinary burdens of duty are not usually resented. Soldiers tend to embrace virtually any arrangement that might make them more likely to be of help to their comrades in arms. Imagine for example that there was an advance in understanding of brain chemistry that helped predict susceptibility to post-traumatic stress. Combat soldiers might well welcome such a screen if it meant avoiding operational failures that could result in harm to others in their unit, even if their own career opportunities were impaired as a result.

Already there are biomarkers for the ability to manage stress and neurological measures of post-traumatic stress. Indeed, many in and out of the military have called on the services to mandate a pre-deployment mental screening in order to establish a baseline of brain functioning on which to measure future changes. This information could also help screen candidates for certain jobs and missions and be incorporated into debriefing and post-operations examinations. Neural indicators of different learning and decision making styles could help in designing training regimens and duty assignments. Growing understanding of the neural basis of performance under conditions like sleep and nutrition deprivation and stress could identify interventions to ameliorate performance degradation, like pharmaceuticals for cognitive enhancement and improved delivery of nutrients to the brain. The new report advises the Army to monitor nonmilitary research on neuroscience elsewhere in government as well as in academia and industry.

In 2008 there was a complementary report on the potential for neuroscience to make greater contributions-and create novel challenges-for national security. Entitled “Emerging Cognitive Neuroscience and Related Technologies,” the committee (of which I was a member) urged close collaboration between the scientific and intelligence communities to keep track of rapid advances in neuroscience and neurotechnology. Organizers asked the committee to assess the current state of work for trends worth trackeding, to assess the rate of innovation, and to pay special attention to selected countries. The committee’s key finding addressed the need for intelligence collection and analysis to emphasize science and technology, to obtain intelligence professionals with advanced scientific training, and to increase collaboration with the academic community. Its key recommendation was that the intelligence community use a more centralized indication and warning system concerning non-U.S. neuroscience potential. This new report broadens the conversation to include the uniformed military as well as the intelligence community.

Although the applications of neuroscience can easily be hyped, the implications are so great that we should expect the national security establishment to follow these developments with great interest in the years ahead.

Jonathan D. Moreno, Ph.D., is the David and Lyn Silfen University Professor of Ethics and Professor of Medical Ethics and of the History and Sociology of Science at the University of Pennsylvania, and the Editor-in-Chief of Science Progress.

For some time, the dialogue between conservatives and progressives on this issue has consisted of ad hominem charges. Consider John Derbyshire, writing recently at The Corner: “There is terrific social and political pressure on researchers, publishers, and commentators to put forward the most nurturist possible interpretation of every finding.” Some of the better-grounded discussions were able to delve into the empirical, methodological, and value-based assumptions as well as the statistical minutiae behind each side’s claims. (See William Saletan’s earnest, yet flawed, series on race and intelligence published last year in Slate and Stephen Metcalf’s critique of it.) Even though the connection between genes and IQ was subject to numerous caveats, the conservative genetic explanations for race and intelligence never really disappeared. This was due to the reductive appeal of genetic explanations for anything and the unfortunate persistence of educational inequalities.

For many years, it seemed the scientific jury was out and there was enough conflicting evidence to support any ideological bias. (This debate even makes for some strange ideological bedfellows, as it is easy, from the progressive vantage point, to agree with Leon Kass’s criticism of the Bell Curve. In this case, he is actually right about genetic explanations reducing the quality of human ability to mere quantity and the danger it poses to society by reinforcing prejudices.)

Fortunately, there has been a raft of scientific evidence in recent years demonstrating that environment matters much more than genes when it comes to an individual’s brain development and intellectual achievement. More importantly, this evidence has been making its way into the popular press and non-fiction, thus bringing digestible coherence to non-genetic explanations for intelligence. University of Michigan psychologist Richard Nisbett’s new book, Intelligence and How to Get It explains in rich yet accessible detail how myriad environmental stimuli can affect a person’s intelligence and educational achievement. This may seem obvious to many people, but the specific findings put forward by Nisbett and his colleagues demonstrate how policies, educational techniques, or environmental adjustments can improve the achievement of everyone from preschoolers mastering their ABCs to high schoolers taking the SATs. These findings are much more robust than the population-wide blanket correlations of the Bell Curve, which are used to advance the case for conservative “throw-in-the-towel” non-policies.

One of the best explanations Nisbett provides has to do with elucidating the concept of heritability, which many science popularizers misinterpret as the end-all-be-all calculation of nature versus nurture. In reality, heritability is about populations and the variability of the environment for the population being studied. Jim Holt draws attention to this in his review of Nisbett’s book in the New York Times:

Even if genes play some role in determining I.Q. differences within a population, which Nisbett grants, that implies nothing about average differences between populations. The classic example is corn seed planted on two plots of land, one with rich soil and the other with poor soil. Within each plot, differences in the height of the corn plants are completely genetic. Yet the average difference between the two plots is entirely environmental.

These claims are supported by research conducted by Eric Turkheimer of the University of Virginia, who has found that on measures of intelligence, middle-class and wealthy households are very similar; therefore differences within those groups are due more to genes. Poor households can vary widely, thus intelligence differences within that group are due more to the environment.

In a laudatory op-ed, the New York Times’ Nicholas Kristof runs off a list of Nisbett’s best recommendations about raising individual intellectual achievement: “Praise effort more than achievement, teach delayed gratification, limit reprimands and use praise to stimulate curiosity” —and collective intelligence. He goes on: “Professor Nisbett strongly advocates intensive early childhood education because of its proven ability to raise I.Q. and improve long-term outcomes…[and] suggests putting less money into Head Start, which has a mixed record, and more into these intensive childhood programs.” The Center for American Progress supports Head Start, but our education team feels it must be coordinated with high-quality state-supported early childhood programs and other federal and state programs for young children.

In a recent paper published in Proceedings of the National Academy of Sciences, Gary Evans and Michelle Schamberg from Cornell University find that poverty affects the physical and psychological health of poor teens through stress and inadequate nutrition. (The Washington Post and Wired.com both covered the study.) With stress in particular, they were able to associate biological markers such as blood pressure and stress hormones with a decrease in working memory capacity. We employ working memory temporarily for remembering things like a phone number that we are about to dial. In their experiment, Evans and Schamber found that poor teenagers could remember an average of 8.5 items; better-off children could remember an average of 9.44 items. This is a significant difference and the differences remained when they controlled for variables such as parenting styles, maternal education level, birth weight, and parent marital status. The only time the differences were eliminated was when the stress indicators were controlled for.

Science Progress board member and University of Pennsylvania neuroscientist Martha Farah explained to me that greater cognitive stimulation in childhood creates more connections between neurons and that a more nurturing environment prevents abnormal development of the hippocampus, the region of the brain associated with forming long-term memories. These effects of stress on the brain are supported not just by hormonal and behavioral differences, but also by differences in brain shape, as evidenced by fMRI studies, and differences in brain electrical activity, as evidenced in event related potential, or ERP, studies, even when behavioral differences are absent. As detailed in Nisbett’s book, more qualitative social science research has shed light on the actual stress-inducing experiences of children who live in poor households, which can include more residential moving, greater neighborhood turmoil and disruption, or the lower levels of parental nurturance that result from parental stress. Farah mentions in the Washington Post article that for children, factors also include “having fewer trips to museums, having fewer toys, having parents who don’t…read to them or talk to them.”

Finally, it is only fair to mention that there has been some reluctance among progressive social scientists to focus on more than just the political and social aspects of educational achievement and poverty. The fear was that once scientists start to study the immediate environments or the neurobiology of poor people, it could be misconstrued as “blaming the victim” or, even worse, social Darwinism. However, when environmental and biological studies are done right, we see how they shed light on combining a top-down socio-political approach with a bottom-up bio-behavioral approach. This combined approach lies at the heart of evidence-based pragmatic progressivism. Already, the Obama administration has made a commitment of $10 billion to early childhood education, aimed at closing the achievement gap in public schools. The administration’s policy provides large-scale support for educators, community leaders, and parents who want to create a more supportive environment for their children so that they can succeed. Indeed, the science of the mind can further bolster the human-level empirical foundations for society-level public policies. From there, we can figure out how our educational system can both enhance our children’s abilities and point them in a successful direction, regardless of what those abilities might be.

Michael Rugnetta is a research assistant with the Progressive Bioethics Initiative at the Center for American Progress.

Part of the appeal of this research is that it often involves investigation of how the brain responds to familiar emotional stimuli and social conditions. Yet questions persist about what fMRI can really tell us about how the brain works, and the research has implications for a variety of issues ranging from brain-reading devices to the ethical use of brain enhancement technologies.

Importantly, fMRI is no longer just a medical or academic tool used to diagnose disease or learn about basic cognitive functions in the brain. It is now widely viewed, and many would say mistakenly, as a potential way to solve problems in court and in the interrogation room—by helping discern what individuals are thinking. How we balance the inherent technological drawbacks of fMRI research and the ethical minefields of its application with the potential for profound discoveries about how the mind works promises to be a point of great contention in the future.

fMRI research focused on the relationship between mental states and behavior abounds. A recent study demonstrated that lonely or socially isolated individuals, when shown images of people in pleasant settings, had much lower activation in a reward center of the brain, the ventral striatum, than non-lonely people. And Science recently published an article showing the activation of brain reward centers in subjects witnessing the misfortune of an envied competitor and activation in punishment centers when they saw an envied competitor with a valuable object. The study argued that brain regions responding to feelings of envy and schadenfreude are also those that respond to, respectively, physical pain (envy hurts) and reward/pleasure (schadenfreude feels good).

The most common form of fMRI measures the “blood oxygen level dependent,” or BOLD, signal in the brain, which results from the differing flow of oxygenated and deoxygenated blood through the brain. Brain areas that receive oxygenated versus deoxygenated blood are detected by the MRI scanner because the blood protein hemoglobin has different magnetic properties when it carries oxygen compared to when it does not. Why is it important to know which brain areas are receiving more oxygenated blood than others? Because in a process called the hemodynamic response, blood supplies oxygen to active, “thinking” neurons at a greater rate than to inactive neurons. Using complex statistical methods, researchers can evaluate which areas of brain are consistently receiving more oxygenated blood (a high BOLD signal), therefore revealing which areas of the brain are “active” during the specific thoughts or sensory experiences induced by researchers.

But lately some have challenged the validity of fMRI as a tool for drawing these connections between thoughts/experiences and brain activation. Massachusetts Institute of Technology graduate student Ed Vul recently published a paper called “Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition.” In it, he argues that a large proportion of fMRI studies in fact utilize spurious and biased statistical processes, resulting in impossibly high correlations between assessments of individual emotional or personality differences and associated brain region activation.

How to Read the Numbers

fMRI is a decidedly indirect measure of brain activity, as it does not measure “thinking” processes or even neural changes directly, but merely oxygenated blood flow. Scientists have even discovered that blood flow through astrocytes, glial cells that are thought to play a largely supportive role in the brain, are the main source of the fMRI signal, not neurons. In other words, the BOLD signal may not be the unquestionably valid representation of cognitive processes that researchers sometimes claim it is.

The dominant methodology utilized in fMRI research involves scouring the brain for statistically significant correlations between the BOLD signal and a specific emotion, behavior, or disease state—envy, loneliness, “right-handedness,” schizophrenia, etc. Researchers divide the brain into tiny three-dimensional pixels called “voxels” and examine them for significant increases in oxygenated blood flow correlated with the stimuli. Those areas that show significant correlations are plotted onto a structural image of the brain as a functional map of the brain-behavior association.

In his paper, Vul highlights a number of issues with fMRI studies, most prominently the existence of misleadingly high, or “voodoo,” correlations between brain signal and individual behavioral differences, like personality and emotion. He claims that these spuriously high correlations are the result of a non-independence error. He explained this error to science writer Jonah Lehrer in Scientific American:

When researchers want to determine which parts of the brain are correlated with certain aspect of behavior, they must somehow choose a subset of thousands of voxels [to study]. One tempting strategy is to choose voxels that show a high correlation with this behavior. So far this strategy is fine.

The problem arises when researchers then go on to provide their readers with a quantitative measure of the correlation magnitude measured just within the voxels they have pre-selected for having a high correlation. This two-step procedure is circular: it chooses voxels that have a high correlation, and then estimates a high average correlation. This practice inflates the correlation measurement because it selects those voxels that have benefited from chance, as well as any real underlying correlation, pushing up the numbers.

In other words, Vul argues that when researchers select voxels that exhibit a high correlation between oxygenated blood flow and response to stimuli, they are choosing both voxels that have a high correlation due to chance along with those that really do exhibit the correlation. The non-independence error results when researchers use these high-correlation voxels to estimate high average correlation across the whole brain. That is, the analysis (Does the brain have a high average correlation with a specific individual difference?) is not independent of the initial selection criteria (Which voxels exhibit a high correlation with a specific individual difference?).

The paper’s criticism of fMRI studies and their “voodoo correlations” went over well with many in traditional media as well as in the blogosphere. Several writers claimed that Vul’s work finally revealed that the whole field of fMRI was based on false foundations. Sharon Begley of Newsweek wrote that “psychiatrists and social psychologists [are] enamored [by] fMRI and other brain imaging toys . . . like so many researchers in the social sciences, they have physics envy, and think that the illusory precision and solidity of neuroimaging can give their field some rigor.”

In response to Vul’s claims, brain researchers Matthew D. Lieberman and Elliot T. Berkman from the University of California, Los Angeles, and Tor D. Wager from Columbia University published a detailed reply. They wrote that the non-independence error that Vul claims is the cause of spuriously high correlations in a number of studies actually does not occur. In a subsequent interview with Lehrer, Professor Lieberman responded to Vul’s charge of non-independence, explaining that fMRI researchers are not interested in how the whole brain correlates with a measure of individual difference. Instead they are interested in which specific areas, or “voxels,” in the brain show a significant difference in blood flow in response to stimuli:

[Vul suggests] that we might be interested in whether a psychology or a sociology course is harder and assess this [question] by comparing the grades of students who took both courses. In a comparison of all students, we find no difference in scores. But what if we began by selecting only students who scored higher in psychology than sociology and then statistically compared those? If we used the results of that analysis to draw a general inference about the two courses, this [strategy] would be a non-independence error, because the selection of the sample to test is not independent of the criterion being tested. This [practice] would massively bias the results.

Although Vul is absolutely right that this would be a major error, he’s not describing what we actually do [in social fMRI]. Vul’s example assumes that the question that we are interested in is how the entire brain correlates with a personality measure or responds differently to two tasks. Staying with the grades examples, what social neuroscientists are really doing, however, is something closer to asking, “Across all colleges in the country, are there colleges where psychology grades are higher than sociology grades?” In other words, the question is not what the average difference is across all schools, but rather which schools show a difference. There is nothing inappropriate about asking this question or about describing the results found in those schools where a significant effect emerges.

With whole-brain analyses in fMRI, we’re doing the same thing. We are interested in where significant effects are occurring in the brain and when we find them we describe the results in terms of means, correlations, and so on. We are not cherry-picking regions and then claiming these represent the effects for the whole brain.

Vul responded with a rebuttal of his own to the rebuttal above, claiming that his criticism of the non-independence error still applies, so the debate continues. But we should neither blindly accept Vul’s critiques nor Lieberman, Berkman, and Wager’s responses—fMRI is neither a perfect technology, nor is it fundamentally flawed.

fMRI in Court

The utility of this sort of brain research has policy implications because the results of this work might end up in court. Skeptics of the validity of fMRI have expressed their worries about the recent news that for the first time, defense attorneys submitted results from an fMRI lie-detection test as evidence in a trial—although the evidence was withdrawn in late March by the lawyers. No Lie MRI, a private company, scanned the defendant in the juvenile sex-abuse case and claimed that its test revealed that the abuse did not in fact happen because the defendant’s claim of innocence did not show neural patterns consistent with a lie. No Lie MRI uses fMRI to measure changes in blood blow to the ventrolateral area of the prefrontal cortex, a section of the brain in which several studies have identified activity during lying.

Studies on fMRI lie detection have identified lying with accuracies of 76 percent to over 90 percent. However, many people are suspicious of the reliability of this new technology, and are apprehensive about using it in court. Ed Vul said in a comment in Wired: “I don’t think [fMRI lie detection] can be either reliable or practical. It is very easy to corrupt fMRI data. The biggest difficulty is that it’s very easy to make fMRI data unusable by moving a little, holding your breath, or even thinking about a bunch of random stuff. So far as I can tell, there are many more reliable ways to corrupt data from an MRI machine than a classic polygraph machine.”

Hank Greely, Director of the Center for Law and the Biosciences at Stanford University, has also expressed skepticism about admitting such a young and poorly understood technology. He told Wired that “having studied all the published papers on fMRI-based lie detection, I personally wouldn’t put any weight on it in any individual case. We just don’t know enough about its accuracy in realistic situations.”

Concerns about the use of an untested technology like fMRI lie detection to determine the fate of individuals in our legal system are understandable and appropriate. Before we even consider using MRI lie detection in the courts, randomized studies with hundreds of participants must reveal the unequivocal reliability of the techniques. And this has not happened…yet.

However, with respect to Vul’s critiques of the validity of brain imaging in social neuroscience, the mainstream press and the bloggers should not necessarily trash a well-established and useful tool in both medical research and clinical medicine. fMRI studies, though by no means perfect, have provided remarkable and valuable insight into the important and often nebulous connections between the brain and mind, revealing the extent to which our emotional and social lives emerge from specific biological processes.

As brain science continues to advance, it is vital for researchers and the public alike to step back and rigorously examine the basic techniques and assumptions of fMRI, whether the technology is used in social neuroscience, lie detection, or elsewhere. We don’t want to base our science policy, medical judgment, or court decisions on data that is not fully understood, or perhaps even fundamentally flawed. Nevertheless, the proper response to the Vul study and the development of fMRI lie detection technologies is not to throw up our hands in despair, but to respond with reasoned and thoughtful rebuttals like those outlined earlier, firmly committing ourselves to the improvement of imaging techniques, data interpretation, and experimental design through the continued support of neuroscience research.

Justin Masterman is an intern with the Progressive Bioethics Initiative at the Center for American Progress.

One set of questions has to do with the use of brain scanning technologies to identify deception. Although brain researchers largely doubt the validity of such applications of, for example, functional magnetic resonance imaging, or fMRI, investigations of these uses of neuroimaging are ongoing and are stimulating a growing scientific literature. Another, and arguably more promising, approach is the artificial induction of brain chemicals associated with trust, like oxytocin. It has been theorized that stimulating the production of this naturally occurring hormone would be an alternative to more indirect ways of developing emotional bonds with interrogation subjects.

The use of these kinds of technologies would obviously raise disquieting associations with abuses uncovered by the Church Committee nearly 25 years ago, including clandestine experiments with hallucinogens. At the request of the Defense Intelligence Agency, a National Research Council committee (of which I was a member), reported on the implications of cognitive neuroscience last summer.

There is no national security exception to the rules governing human experiments. So unless authorities held that the normal rules don’t apply to suspected terrorists (a theory I have speculated about elsewhere), even experimental forays in this area would require intensive prior review and—hold onto your hats—informed consent. Ironically, the notorious LSD “experiments” of the cold war-era themselves contributed to an atmosphere that led to the current rules. The scandal has even been associated with the decay of the CIA’s human intelligence capacity and the failure to detect the events of 9/11.

There is no evidence that any such practices have taken place in recent years, but it would make sense for well-informed interrogators to note the provocative possibilities of the new neurotechnologies for their craft, if not now, then someday. Are there circumstances in which relatively benign but invasive techniques may be used for the sake of national security? The cause of public education in these matters could be advanced were the Senate to raise the issue before another generation of revelations cripples intelligence capacity and undermines public trust—with or without oxytocin.

In an interesting move, the Associated Press picked up the Commentary feature in this week’s online edition of Nature on healthy people enhancing their brain power with pharmaceuticals (which is presently available without a subscription). The authors (who again include Farah) “propose actions that will help society accept the benefits of enhancement, given appropriate research and evolved regulation.” They go on: “Prescription drugs are regulated as such not for their enhancing properties but primarily for considerations of safety and potential abuse. Still, cognitive enhancement has much to offer individuals and society, and a proper societal response will involve making enhancements available while managing their risks.”

Michael Rugnetta reported on the success of the first meeting of the Neuroethics Society in November, and AAAS, which hosted the event, now has full coverage posted. The focus is on military and national security applications of neuroscience, an issue Jonathan Moreno (who sat on a panel at the meeting) tackled in a recent feature, “Intelligence on the Brain.”

The most famous patient in neuroscience research, Henry Molaison–formerly known to only as H.M.–passed away last week. In order to treat debilitating seizures, he underwent surgery to remove the site of the problem, the hippocampus, and subsequently lost all ability to form new episodal memories. NYT has a full report, and ScienceBloggers Jake Young, Mo, and Omnibrain offer thoughtful reflections on the man who helped scientists understand how human memory works. (Hat tip to Alta Charo.)

Across the nation, in hospitals, clinics, and doctor’s offices both military and civilian, health care providers are facing unprecedented challenges in dealing with these weapons’ results. Among the most puzzling is a set of injuries widely considered a medical “signature” of this conflict, and one that raises clinical and scientific questions thus far unanswered.

This is the combination of traumatic brain injury and post-traumatic stress disorder. TBI is a force to the head that damages the brain and impairs its function, with the extent and kind of harm depending on the exact location and scope of the injury. PTSD is a terrifying and often disabling anxiety disorder caused by the experience of violent trauma.

Any blast powerful enough to cause TBI is also powerful enough to cause PTSD, so a high—though unknown—percentage of the many exposed to blasts suffer from both. The scientific literature finds that “anywhere form 20% to 60%” of blast victims have PTSD, says Maxine Krengel, PhD, clinical neuropsychologist at the Department of Veterans Affairs Poly Trauma Network Site in Boston. “It’s huge.” The circumstances of the “event itself” indicate TBI, Krengel says. For example, “did the somebody have a loss of consciousness? If so, for how long?” At least mild TBI is therefore also very common.

Many Questions

A major clinical challenge is that the symptoms of the two conditions overlap—although the conditions are very different in their natures—making diagnosis often “very, very tricky,” Krengel says. TBI causes physiological damage to brain tissue that can result in cognitive deficits and reduced emotional control, among many other problems. PTSD is a learned connection between a traumatic event and a set of responses, which can include nightmares, flashbacks, and constant anxiety and can lead sufferers to alcohol, drugs, and even suicide. But the two conditions share many markers, including sleep disruption, irritability, personality changes, difficulty concentrating and remembering, depression, and more.

To add to the complication, the presence of one condition can interfere with the treatment of the other. And to make things even more uncertain, the type and extent of the brain damage caused by the compression wave of a blast appears to differ considerably from the injuries that form the basis of current scientific understanding of TBI.

“Most of the TBI research has been done in survivors of either motor vehicle accidents or sports injuries—a quarterback [who] gets knocked unconscious” or a driver who hits his head against the steering wheel, says Matthew Friedman, MD, PhD, Executive Director of the National Center on PTSD and professor of psychiatry at Dartmouth medical school. “But the real question that a lot of people are raising is, given the tremendous impact of an explosion, can it really compare to the impact of even a 350 pound defensive end knocking you to the ground? Even though that’s pretty bad, is it anything to compare to a bomb blowing up your Humvee and killing the person sitting beside you?”

Beyond a difference in strength of the impact, Krengel adds, the percussive wave of an explosion acts differently on tissue than an ordinary blow. “The blast impacts the air-filled cavities in the body, every air-filled cavity,” she says. “It’s different in different areas and also depending on how close you are to the blast.”

What is known about the impact of blasts on the brain essentially comes from animal models. “But in the animal literature there is a difference in what the connectivity looks like”—in other words, how the brain’s parts work together—“in blast injury versus traumatic brain injury, that we are typically used to seeing,” Krengel says.

“And then the second piece is that so many of these people have had more than one blast injury,” Friedman continues. So the crucial but as yet unresolved scientific question, he says, is “How generalizable is the sports injury or motor vehicle accident to what is coming into Walter Reed or VA hospitals these days?”

Figuring Out How to Help

The point is not just to study the problems with more science, but to find the best ways of helping suffering human beings, Friedman and Krengel emphasize. “We have two fabulous treatments for PTSD,” says Friedman. “These are evidence-based treatments and…vigorous review recently by the Institute of Medicine has verified their effectiveness.” One treatment, cognitive behavioral therapy, uses systematic, Socratic challenges to thinking about the traumatic experience to help patients restructure their thinking. The other, exposure therapy, breaks the Pavlovian connection between the event and the response with guided confrontation with the troubling memories. Beyond that, several medications help control the symptoms, though they do not resolve the basic issues. If medication is used alone, the symptoms return when treatment ends. Successful psychotherapy, however, permanently frees people from the terrors of PTSD. Which type of psychotherapy works better in a given case depends on the individual, but, Friedman says, in tests of otherwise normal individuals, both overall “perform extremely well and equally well.”

There are no drugs approved for TBI, although some appear to provide some benefit. They are not, however, the same drugs useful for PTSD.

But blast victims very often also have some degree of TBI, and depending where and how it damaged the brain, TBI can reduce the effectiveness of either or both of the two best PTSD treatments. Cognitive damage can impair the intellectual resources needed for cognitive behavioral therapy. The loss of emotional inhibition caused by brain injury can make a person unable to tolerate the emotional stress involved in exposure therapy. Mild TBI very often resolves over time, potentially allowing psychotherapy to work, but clinicians do not consider waiting a sound option because, as Friedman says, “six months is a long time to suffer.”

An additional potential complication is that a damaged brain may not tolerate medications very well. There are no drugs approved for TBI, although some appear to provide some benefit. They are not, however, the same drugs useful for PTSD.

A number of studies and proposals are underway, many of them sponsored by the VA or the Department of Defense, Krengel says, noting that, “The VA system is developing treatment modules or manuals to treat the pain issues, the PTSD, the depression.” Whether sufficient resources have been devoted to studying these conditions is a matter of opinion. But, Friedman notes, “It’s probably going to be a few years until we have definitive data. What I can tell you is that we understand the challenge and research is ongoing.”

Until the big questions get answered, “the challenge is to figure out what to do for these folks. We have some good stuff on PTSD, other [work] on TBI. The question is how applicable, how useful is it going to be for this more complicated situation. Can we utilize what works in the less-complicated cases and how much are we going to have to improvise?” At present, clinicians are improvising ad hoc modifications to treatments to make them more usable by individuals with impairments, while waiting for research to provide more answers.

Is It Enough?

Beyond these questions of basic knowledge and treatment are large issues of access to appropriate care. Although the VA maintains a number of specialized polytrauma centers in various parts of the country for dealing with complicated cases, for an unknown but undoubtedly large number of veterans distances can be large and waiting times long. People with mild TBI and PTSD can be “quite ambulatory and they’re going to walk into primary care clinics, psychiatric clinics” throughout the nation, Friedman says. They often show up with vague symptoms such as headaches or sleep disturbances. Many providers lack even the understanding of the conditions found in more specialized facilities. That’s why, he says, primary care doctors and mental health providers across the country need to be educated about these conditions and told that “anyone who has been in uniform should be asked about the different kinds of exposures they’ve had.”

For now, though, untold numbers of service members and veterans who have experienced blasts are suffering, often without knowing why. And PTSD can strike months or years after a traumatic experience. “You might be in a blast and you have to immediately go back to your job,” Krengel says. “You can sort of keep it together while you’re busy, busy, busy, but after you’re home for a while, people say, ‘Wait, I’m not functioning the way I should be.’”

The experience of a blast may therefore be a time bomb that goes off long after the traumatic event. Unless and until researchers and clinicians answer the crucial questions and effective care is readily available from military, veteran, and civilian providers, it should surprise no one that many who served in today’s wars continue to feel their effects long after the conflicts end.

Washington, D.C. science journalist Beryl Lieff Benderly contributes the monthly “Taken for Granted” column on labor force and early career issues to the website of Science magazine and articles to other major magazines and websites.

flickr.com/lizhenry

Originally, the Neuroethics Society expected 50—maybe 80—people to show up for its First Annual Meeting. But over 200 neuroethics devotees assembled last week at the American Academy for the Advancement of Science in Washington, D.C. for the two-day series of presentations, discussions, and poster sessions.

Neuroethics is the subfield of bioethics that studies the ethical, legal, social, cultural, and policy issues that arise from our ability to understand and manipulate the brain through basic, applied, and clinical neuroscience.

Several members of the Science Progress advisory board either spearheaded the effort to get this conference together or participated in the meeting’s discussion panels. Martha Farah led a session on the up-and-coming neurotechnology industry featuring Zach Lynch. Hank Greeley discussed the legal and ethical controversies surrounding neuroscience-based lie-detection technologies. Paul Root Wolpe moderated an unexpectedly agreeable discussion between two neuro-partisans on the ever-prescient issue of brain enhancement. Science Progress Editor-in-Chief Jonathan Moreno spoke on a panel about the ethics of deep brain stimulation research and also led a panel on neuroscience research and the use of neurotechnology by the military and intelligence communities.

The success of the meeting is a clear sign that neuroethics has come a long way in a short period of time. Although not the first person to use the term, New York Times columnist William Safire coined “neuroethics” in its contemporary sense. Safire and others refined the term at the 2002 conference, “Neuroethics: Mapping the Field,” convened by the Dana Foundation. According to its website, the Neuroethics Society itself was founded in May of 2006 after a small meeting in Asilomar, California. Shortly thereafter, in October of 2006, the Society aligned with the International Neuroethics Network in an effort to broaden its scope. Harvard University’s Steve Hyman currently serves as the society’s president.

In these few short years, websites such as neuroethics.upenn.edu, the Neuroethics and Law Blog, and journals such as Neuroethics and AJOB-Neuroscience have sprouted up, adding intellectual heft and scope to the field. In fact, it is the breadth of the field that has made neuroethics so popular. The community sees itself as a big tent and incorporates scholars from the humanities, hard sciences, and social sciences, along with doctors, lawyers, businesspeople, and policy professionals. Indeed, the program agenda from last week’s meeting is a testament to the community’s commitment to breadth, diversity, and interdisciplinary.

The society’s will expand its impact with activities like the First Annual Penn Neuroscience Bootcamp on August 2-12, 2009 at the University of Pennsylvania. The Bootcamp will introduce the methods and findings of neuroscience research to educators, economists, businesspeople, policy professionals, along with anyone else whose work requires them to “understand, predict, or influence human behavior.”

Neuroscience is becoming increasingly relevant in our everyday lives. fMRI brain scan images already flood the science sections—and advertising space—in newspapers and magazines. In order to properly separate the reality of advances in brain technology from the hype, consumers, citizens, and professionals have to get educated on the science and engaged in the ethical conversation.

For more details on the Penn Neuroscience Bootcamp, including application instructions, check out the program website.

In July 2008 a committee of the United States Senate revealed that, beginning in 2002, Guantanamo Bay interrogators had based their methods partly on a chart that appeared in a 1957 paper prepared by an Air Force social scientist. The chart represented a summary of the types of coercive measures used by Chinese Communist interrogators against American P.O.W.’s during the Korean War, causing them to make a number of false confessions of U.S. war crimes. These measures fell under headings that included “sleep deprivation,” “prolonged constraint,” and “exposure.” At the time, consternation about the effectiveness of the Chinese methods led to vague but deep-seated fears of “brain washing.”

The irony that information gleaned from circumstances involving the torture of American soldiers over 50 years ago could be used against detainees in the war on terror was not lost on opponents of the Bush administration’s policies. Yet this incident is but the tip of the iceberg of a much larger set of questions for 21^st century neural and behavioral science and their role in national intelligence operations, and for an increasingly globalized scientific community.

The American intelligence establishment’s infamous Cold War forays into various experiments with hallucinogens and other mind-altering processes can be attributed in part to worries that Eastern bloc Communist governments were both ahead of the intelligence game and less likely to respect ethical constraints than the West. One scenario was that an American nuclear physicist with a high security clearance attending a conference abroad could be invited to an apparently innocent meal and made “indiscreet” with LSD. The CIA’s MKUltra and other top-secret experimental programs were among the excesses that were revealed by government investigations in the mid-1970s.

Some believe that the United States continues to pay the price for these excesses—or, perhaps, for their revelation—even to the extent of blaming intelligence failures prior to the 9/11 attacks on the resultant weakening of the CIA’s covert operations capacity. What does seem indisputable is that the American intelligence community’s internal expertise on matters of the brain and behavior is not what it was in the 1950s. Some of the world’s top scientists were then deeply engaged advisors to military and civilian intelligence agencies, including Harvard University psychologist Henry Murray and Harvard/Massachusetts General Hospital’s Henry Beecher, continuing relationships that began during World War II. Whether or not that expertise actually improved performance of national security activities or not is another question.

Upgrading anthropology capacity

Nevertheless, there are some indications that American security officials are concerned that U.S. intelligence capacity has been somewhat degraded in recent years by a failure to integrate the best and most up-to-date academic work in fields like anthropology and cognitive science. Cultural insensitivity is often cited as one of the reasons for the early failure of the occupation of Iraq. Soldiers have often had to learn the nuances of communication with locals themselves. Sometimes failures to make intentions clear, as for example in passing through checkpoints, may have had tragic consequences due to cultural variations in the meaning of seemingly simple hand gestures for “proceed” and “halt.”

U.S. Secretary of Defense Robert Gates, formerly president of Texas A&M University who has served as deputy director of the CIA, recently announced a new initiative called the Minerva Consortium. Minerva is intended to provide a group of universities with funding to assist the Department of Defense in areas such as Chinese military and technology studies, perspectives on terrorism in Iraq and elsewhere, religious and ideological studies, and “new disciplines” including history, anthropology, sociology, and evolutionary psychology. In an April 14, 2008 speech the secretary also elaborated at length on the history of complicated relationships between the defense establishment and academic anthropology. With candor that surprised some, Gates noted that, “Understanding the traditions, motivations, and languages of other parts of the world has not always been a strong suit of the United States. It was a problem during the Cold War, and remains a problem.” He associated these difficulties with a tension that has persisted between the American military and academia since the Vietnam War era.

As the American military establishment reaches out anew to the university system, what will be the reaction? Although Gates urged rapprochement and cited several institutions that have created special programs for injured veterans who might not otherwise qualify for admission, this is a far cry from the kinds of close relationships that characterized the World War II and post-war era. In an era in which federal funding for medical science has in real terms diminished, American academic research leaders have more motivation than patriotism alone to take an interest in a lucrative new government funding source for the generally under-supported “soft” social sciences.

Neuroscience and National Intelligence

Neuroscientists cite evidence that cultural differences may extend even to the way that members of different groups process information, and that these differences are measurable. If it is true that scientific understanding of culture and group dynamics has deepened in the past half century, necessitating renewed interest on the part of security officials, how much more must that be the case for the scientific study of the brain and its functions. Neuroscience conferences now rival the world’s largest medical meetings, bringing together a wide range of disciplines, from psycholinguists to electron microscopists. Even taking into account the hyperbole that seems to accompany much modern science, it’s a good bet that our basic understanding of the brain and its functions is on an impressive growth path.

Smart defense planners are well aware of the buzz about the brain. During the summer of 2008 a U.S. National Research Council committee of which I was a member issued a report on “Emerging Cognitive Neuroscience and Related Technologies.” The bland title belies the fact that this was, I believe, the first time that the American intelligence community sought systematic and rather public advice on the future of brain research from a group of scientists and academics. Just before being named to this committee I published a book that included a reconstructed history of national security interest in the brain (Mind Wars: Brain Research and National Defense, 2006), so I found this turn of events particularly intriguing.

I cannot speak for my colleagues on the committee, but I think we all found the charge compelling, which was in part to “review the current state of today’s work in neurophysiology and cognitive/neural science, select the manners in which this work could be of interest to security professionals, and trends for future warfighting applications that may warrant continued analysis and tracking by the intelligence community.” We were to have special sensitivity to work that might be done in selected other countries.

Over about a year and a half, the committee’s deliberations congealed around several themes reflected in the final report. In each case the national intelligence implications were paramount: Could new devices overcome challenges to the detection of psychological states and intentions, so that deliberate deception could be identified far more reliably than with traditional “lie detectors”? In what directions might neurologically active drugs take us, perhaps as tools for cognitive enhancement that exceeds normalcy? What if computational biology leads to intelligent machines, or aids in creating human-machine systems that combine and leverage the abilities of both? What are the prospects for acquiring intelligence on cognitive neuroscience developments that might be accomplished by our competitors and adversaries? How will culture and ethics influence both the hypotheses that other countries might find of interest and their willingness to engage in human experiments? Readers should of course consult the report itself for details; none of it is classified. Predictions of specific technical breakthroughs are kept to a minimum, and where disagreements arose among committee members, as for example over the genuine prospects for advances in lie detection, they are duly recorded.

As important as any of the report’s particular findings or recommendations is the fact that it lays a predicate for a series of critical social questions that we must face even if the more extravagant expectations for emerging neuroscience are not realized. For some we may rely on familiar territory, like risk-benefit assessments for clinical research involving implants or more powerful magnets. As advances in imaging and computing establish more reliable correlations between neural activity and behavior, privacy limits may stretch. Governments may have to amend international conventions to establish whether interrogations of prisoners may include investigation of psychological states through real-time measurements of neural function and spatial localization. As the report notes, unethical applications of neuroscience should be at the forefront of our concern.

Professional and Political Ethics

The environment of modern science is far more public and transparent than ever before. Simultaneously, the role of applied science in the manner and methods of political violence (for non-state as well as state actors), seems to be accelerating. Scientists are therefore under far more pressure to assess what “professional ethics” means as they participate in addressing great societal and political challenges. Perhaps only nuclear physicists have previously faced such scrutiny, though biologists, too, have in the past several years been drawn into relatively novel problems like those involving publications concerning biological weapons.

Moreover, in the 21^st century the community of science is less localized than ever. Modern communications and publication technologies make data sharing vastly more efficient. Obstacles to international collegial exchange have largely fallen, with the significant exceptions of government control of web access or the granting of visas. In an abstract sense the culture of science has always resisted political boundaries, a cosmopolitanism that has long earned the suspicion of jealous dictators like Hitler and Stalin. But now a globalized scientific community is a functional reality. Inevitably, that community will be obliged to assess its cultural role and political responsibilities in a far more focused fashion than has previously been the case.

Jonathan D. Moreno, Ph.D., is the David and Lyn Silfen University Professor of Ethics and Professor of Medical Ethics and of the History and Sociology of Science at the University of Pennsylvania, and the Editor in Chief of Science Progress.

SOURCE: BBC

Eddie Adcock plays his banjo while undergoing deep brain stimulation.

Deep brain stimulation is an experimental technique in which electrodes are implanted into the thalamus to correct the effects of neurodegenration or brain injury. Scientists have used the process to treat essential tremor since 1997 and Parkinson’s disease since 2002. The Neurophilosophy blog reports that doctors have recently used the technique to monitor brain surgery in real time—and in tempo.

Neurosurgeons had their patient, the legendary bluegrass musician Eddie Adcock, play his banjo while he was undergoing deep brain stimulation. According to Neurophilospohy:

Adcock is suffering from essential tremor, a progressive neurological condition characterized by tremors in the arms which appear during voluntary movements and which are thought to occur as a result of degeneration of cerebellar Purkinje cells.

Due to his tremor, Adcock could no longer play the banjo with his characteristic fast-picking style. As the surgeons stimulated Adcock’s brain with electrodes, his banjo-playing became more nimble. By observing the quality of Adcock’s strumming, the surgeons were able to fine-tune the therapy by finding the most effective positions for the electrodes.

The surgery was performed at Vanderbilt University Medical Center in Nashville, Tennessee and video footage of the surgery is available on the BBC’s website, which explains that the electrodes are powered by a pacemaker in Adcock’s chest.

A review article in Nature Medicine (subscription) from earlier this year notes that scientists and clinicians are still unsure about how DBS actually works. It might facilitate, impede, or “overwrite” the information passing through the stimulated neurons. There is some evidence from studies of essential tremor that DBS increases production of the neuromodulator adenosine. This makes neurons less active, reducing the tremor. The charges must administered continuously by the pacemaker, otherwise the tremors resume.

So far only the first assertion has been confirmed by neuroscience. Katherine Rankin, a University of California, San Francisco investigator, combined fMRI and a test on the awareness of social inference. She found that the right parahippocampal gyrus, previously associated with spacial context, is also involved with the ability to perceive the verbal and visual cues of sarcasm; or, in other words, with social context. Patients with damage to that region lose the capacity to sense social nuances.

As a New York Times piece on the Rankin study notes, understanding someone else’s point of view, even when sarcastically expressed, is tantamount to the appreciation that there are minds and subjectivities other than one’s own, and to ability to relate to them. When this ability is impaired it’s particularly disturbing to family and friends because a crucial element of the relationship with that person has been lost.

Actually the area identified by UCSF study only accounts for perceiving sarcasm, not for a teen’s ability to generate it. I was just being sarcastic.

At the governmental level, there are a host of questions about safety, privacy, social and political coercion, access to technology and therapy, and the direction of government-funded neuroscience research. Informing these policy questions is “neuroethics”—the field of bioethics that studies the values and principles involved in researching and manipulating the brain. Neruoethics also considers how individuals should conceptualize the brain as an integral part of the human person, especially as individuals attempt to alter or enhance their brains and nervous systems.

Safety

One of the major reasons drugs or devices that affect the brain might seem more dangerous than those that affect other parts of the body is because the brain is a complex system. Tampering with it can be alarming because the mind is inextricably linked to conceptions of who we are as individuals. This makes the side effects of trying to alter or enhance the brain loom large.

For example, although Ritalin has proven to be quite helpful for children, researchers still do not understand its long-term effects, such as whether it might speed up cognitive decline in old age. Memory-enhancement drugs like Donepezil might also prevent those who take them from properly understanding, integrating, and relating information. In fact, it is precisely because of these side effects that the clinical neuroscience community is moving away from drug-based approaches to brain enhancement, which work by trial and error, and is focusing instead on brain stimulation technologies, which deliberately target specific areas of the brain. Regardless of therapy, the FDA must regulate brain enhancement technologies in order to make sure that the benefits outweigh the risks. The analysis that guided the FDA’s July 2005 approval of technology for vagus nerve stimulation for the treatment of depression was insufficient. The technology did not confer a statistically significant benefit, and was approved because the Agency deemed it harmless—but safety alone is an insufficient criterion for therapeutic approval. The FDA needs to be more critical in its evaluation of future enhancement technologies.

Privacy and Mind Reading

Experiments that employ brain-imaging technologies have given scientists a new vision of the brain and its operations—in some cases allowing researchers to build computer programs that understand what people are thinking.

Scientists employ a variety of techniques that allow them to non-invasively peer into the heads of study participants. The most common of these is functional magnetic resonance imaging, or fMRI, which allows observation of oxygen levels in the brain that are associated with neural activity. Other techniques include event-related potentials (ERP), which can detect and average electrical impulses across larger areas of the brain and produce readings on the millisecond scale; and transcranial magnetic stimulation (TMS), which uses strong magnetic impulses to stimulate or inactivate small targeted areas of the brain for research or therapeutic purposes.

Already, fMRI experiments can tell researchers the intentions of a subject presented with the option to add or subtract two numbers. The ERP technique can reveal whether a subject has seen an object before, or—to a certain extent—whether a subject is lying. Scientists at the University of Pennsylvania have even derived an algorithm from fMRI observations of subjects that can tell the difference between a lying brain and a truth-telling brain. There is even evidence that fMRI can decode the brain’s visual cortex and tell us what a subject is looking at. The ethical questions that follow some of these technologies raise serious issues in the legal realm. Could an fMRI scan become admissible in court as evidence of malicious intentions? More ominously, does this so-called “brain-reading” portend a future where the inside of a person’s head is no longer sacrosanct? Could the government exploit this technology for national security purposes? If so, what does that mean for the freedom of human thought?

Although much of this research is benign, aimed simply at better understanding the brain or possibly helping to cure brain disorders, some of the more controversial forms of research—such as memory and lie-detection—have been funded by the Department of Defense through DARPA, and are intended for national security purposes. Since fMRI machines are large and expensive and the scans take time, DARPA has been developing more portable lie and memory-detectors by using wireless near-infrared technology to scan brains from a distance in airports or other secure areas.

Government and Social Coercion

As a result of DARPA’s Augmented Cognition (AugCog) project, U.S. soldiers may eventually carry equipment that integrates directly with their brains. Despite the program’s recent completion, its aims live on in other brain research initiatives. One project monitors soldiers’ brains as they rapidly scan intelligence photos: as many as 10 to 20 a second. Computers can then assess the fluctuations in their attention levels and determine whether the soldier’s brain finds the image relevant before the soldier is even consciously aware of the image. The computer can then store the relevant images for later viewing. Similar technology could also operate in a soldier’s binoculars and induce increased attention in the soldier when his visual system detects a relevant stimulus—again, all before he is even aware of the stimulus and consciously attends to it. Commanders can also assess the stress levels of soldiers in the field and shift tasks to other soldiers so that work is distributed for maximum efficiency. Electrocardiogram (ECG) and electroencephalogram (EEG) sensors in soldiers’ helmets could monitor vitals—or computer chips might even be implanted directly in a soldier’s brain.

Today pharmaceuticals like Adderall can enhance cognition, and others, like Prozac, can enhance mood. Drugs such as Provigil can even keep us awake for extended periods of time. Of course, their stated medical purpose is to help those with neuropsychological disorders—attention deficit disorder, depression, and narcolepsy, respectively. Nevertheless, ambitious college students, academics, and professionals are taking Adderall and Ritalin for enhancement purposes, either through off-label prescriptions or—as is the case with up to 25% of students at some colleges—without prescriptions. The journal Nature recently released the results from a survey of 1,400 of its readers. It found that one-in-five respondents had used drugs for non-medical reasons to enhance focus, concentration, or memory. Of those users, 62% have taken methylphenidate (Ritalin) and 44% have taken modafinil (Provigil).

One perspective is that these pharmaceutical forms of self-improvement should come out of the shadows so that individuals can exercise their freedom to alter their capabilities without stigma. The opposing viewpoint is that these drugs pose a significant problem because the usage and acceptance of brain-enhancement by society at large will pressure even the most enhancement-resistant citizens to finally give in or be left behind in the cognitive dust. And although many people may shudder at the notion of required enhancement in order to keep a job or stay in school, it would be equally coercive to forbid enhancements for all just to protect those who might choose not to take them. Even assuming that brain enhancement is safe and effective, access to cognitive enhancement technologies will likely be distributed no better than current healthcare technologies; but again, this is not necessarily a reason to forbid brain enhancement for all. But if brain-boosting drugs were to further contribute to social stratification, it might provide a rationale for government subsidies for those enhancements through existing healthcare frameworks.

Because school and workplace are obvious situations where required enhancement would raise serious ethical questions, it is likely that the first policies will be formed at the local level with school boards, employers, contractors, unions, and local governments. Will these policies require, forbid, or simply allow pharmaceutical enhancement in these contexts, or will it be some nuanced mixture? Already Connecticut has a statute that prohibits “any school personnel from recommending the use of psychotropic drugs for any child.” The state also has another statute that prohibits children from being taken into state or court custody because their parents or guardians refuse to administer psychotropic drugs to the child.

Most importantly, policies must be sensitive to special populations within society that might be subjected to certain kinds of brain enhancement or brain manipulation coercively: these groups include military personnel, prisoners and detainees, and criminal suspects and witnesses. The military has an obvious interest in enhancing the capabilities of soldiers so they are able to fight for long periods of time without sleeping, and remain alert and attentive. Pharmaceuticals might also make soldiers less sensitive to psychological trauma. This could prevent many soldiers from suffering post-traumatic stress disorder—an obvious benefit. But another conceivable effect of limiting the psychological impacts of warfare might also make military personnel less risk averse or less empathic—effectively turning them into guiltless killing machines. Are these the kind of soldiers that America wants returning from the battlefield? Are these the kind of soldiers that America even wants on the battlefield in the first place?

Coercive brain alteration also raises ethical concerns for the treatment of convicted criminals. Some courts have taken it upon themselves to mete out so-called “therapeutic justice”: both to sex offenders by requiring them to take androgens, to reduce sex drive, and also to violent criminals by requiring them to take drugs known as selective-serotonin reuptake inhibitors (SSRIs), like Prozac, to reduce their impulsiveness.

In the criminal justice system, issues of privacy and coercion merge when considering drugs like oxytoic, which can compel detainees, witnesses, or suspects to tell the truth or act friendlier to their interrogators. This is different from peering into a person’s brain, since the subject is aware that he or she is actively giving up the information—but is it still free will when that will is bent by a drug? Are there circumstances in which authorities should be allowed to slip coercive drugs to detainees without their knowledge?

Limitations of the Technology and Policies for Advancement

These brain-imaging studies have significant limitations with the current technology. For instance, fMRIs only look at the increase in blood oxygen levels associated with brain activity and not the activity itself. Also, in order for experiments to provide us with relevant information, they must be carried out with highly specific designs: conditions must have discreet variables so that precise differences in each metal state are discernible. Complicating this is the fact that some regions of the brain have multiple functions.

The most relevant policy consideration regarding brain imaging is to fund the advancement of the neuroimaging apparatuses. In order to improve these imaging technologies and develop smaller, less expensive imaging machines, biological and physical scientists need to work together to determine how to unlock clear, real-time images from the brain’s electrochemical signals. This kind of research is difficult, given the current structure of scientific funding in this country, which assigns physical science research to the National Science Foundation and biological science research to the National Institutes of Health. Since neuroimaging lies at the intersection of both agencies’ jurisdictions, more joint-funding mechanisms—or even a restructuring of both agencies into one—would make sense.

Another consideration for science-funding policy is that private companies will conduct certain kinds of research that they will not publish or leave open for review. Advertising agencies have already entered into the field of neuromarketing; fMRI research probing how the brain responds to advertisements. Private companies such as Cephos and the aptly named No Lie MRI have also begun to offer fMRI lie-detection services. However, their clients have largely been married couples who suspect each other of cheating. Private companies may conduct less-than-thorough studies and make unsubstantiated claims about neurological research; appropriate oversight will be necessary to protect public interests and health.

Conclusion

Neuroscience research will continue to progress. Whether the research is done by the government or by private companies, in the U.S. or abroad, someone will fund it. Regardless of where the brain-enhancing drugs are made, they will eventually make it into the hands of the people who are willing to pay for them. Funding, marketing, and regulation will shape the impact of neuroscience research on society. These forces will determine what kinds of research are carried out, the purpose of that research, and subjects on which it will be performed. They will determine what institutions or corporations will get access to the technology and innovations that result from that research. Finally, these forces will determine which citizens will have access to the products of neuroscience. Therefore, public policies must ensure rigorous research standards, protect privacy, prevent coercion, and an aim for an equitable distribution of benefits.

Michael Rugnetta is a Fellows Assistant at the Center for American Progress.

Because mind reading and near-flawless detection of deception would avoid many of the limitations of conventional lie detectors, national security agencies and the courts stand to significantly benefit from this technology. Investment in this research by the Pentagon and by private companies highlights interest in its development.

In the most common form of fMRI research, scientists focus their observations on oxygen in the brain, because the magnetic properties of hemoglobin change when it carries oxygen. The fMRI scanner transmits information on the rate of oxygen-carrying blood flow in the brain to a computer, where software translates data into a representation of the brain. This is not a picture of the brain, but rather a map of blood flow in the brain. With this information, researchers can correlate increases in blood flow during controlled activities with various brain functions. Experiments built on this technology can determine with accuracy whether or not a subject under observation is making truthful statements.

Most ethical and policy concerns do not require immediate attention, given the present state of this technology.

Some cognitive researchers predict a startling increase in the accuracy of this technology, making the detection of deception nearly flawless. If that ever happens, concerns arise about forensic applications. For example, some worry that a machine of such accuracy will challenge the “province of juries.” National security interests would almost certainly harness such technology for both interrogations and interviews. And will this extend to regular penetration of civilian thought? Fortunately, most ethical and policy concerns do not require immediate attention, given the present state of this technology, especially considering that national security and court use hinges on the ability to accurately scan individual subjects. To remove “background noise” from a scan, researchers establish a baseline and subtract this recording from experimentally obtained data. This works well for groups but poorly for individual analysis; distinguishing signal from background noise on an individual level proves difficult.[1]

Generating a representation of this neural activity presents additional problems. For example, current techniques measure changes in neural activity on the order of seconds, where most neural processes occur on the order of milliseconds. Additionally, when software translates data into images, smoothing and magnification to ensure a view of high-order brain functions reduces resolution.[2]

There are other limits to fMRI. Few studies investigate variance between scans of individuals of differing age, sex, race, fitness level, cultural background, or account for the prevalence of mental disorder and other characteristics that might have a significant effect on the data gathered in experiments. Researchers also face the challenge of testing fMRI for detecting deception in settings more realistic than the lab. Lying in court generally entails both rehearsal and reasoning. In this setting, suspects feel emotional pressure and stress as they try to deliver a convincing story. Lab studies don’t replicate that kind of pressure.

fMRI lie detection likely falls under the existing policy for polygraph use. State law and federal law differ with regard to lie detection through polygraph, and will probably differ with regard to fMRI lie detection. Federal law seems more permissive of polygraph in courts, whereas 27 states and DC entirely prohibit its use.[3] Until recently, a 1923 court precedent, called the Frye Standard, arising out of Frye v. United States, set the general acceptance of a technology or scientific development as the standard for admission in court.

Although national security interest in fMRI extends to interrogation, screening job candidates and employees seems the most practical application.

Today, Rule 702 of the Federal Rules of Evidence supplements this criterion, explaining, “if scientific, technical, or other specialized knowledge will assist the trier of fact to understand the evidence or to determine a fact at issue, a witness qualified as an expert by knowledge, skill, experience, training, or education may testify thereto in the form of an opinion or otherwise.”[4] This rule allows judges to determine whether the science has been tested, subjected to peer review, the known or suspected rate of error, and whether or not the scientific community generally accepts the technology.[5] Under the Frye Standard, courts prohibited polygraph use, however, after Rule 702, exclusions of polygraph tests no longer presented a foregone conclusion. If fMRI scans for lie detection reach 99 percent or better accuracy, standard use in courts seems possible. So what happens then?

It is clear that regulation of fMRIs for lie detection parallels, in some ways, regulation of polygraphs. For example, implementation in courts requires evaluation under Rule 702, including the general acceptance of efficacy, something which has yet to occur. Despite these similarities, fMRI brings up many new issues associated with both its potential accuracy and invasion of privacy. Jurors without knowledge of error rates and competing evidence will likely give undue credibility to an fMRI reading. The difference between perceived accuracy and actual accuracy jeopardizes the likelihood of an “impartial jury,” as guaranteed under the Sixth Amendment. As neuroscience scholar and neuroethicist Judy Illes explains, “The sheer complexity of neuroscience research poses challenges for integration of knowledge and meaningful interpretation of data.”[6] The most challenging problem at this time, she argues, is that, “with dynamic images in hand, we may forget the limits of how the images were produced, including variability in research designs, statistical treatment of the data, and resolution.”[7]

There are other constitutional issues. The courts will have to determine whether fMRI lie detection constitutes an unreasonable search or seizure under the Fourth Amendment, and high-accuracy lie detection likely carries implications on the Fifth Amendment clause on self-incrimination.

Specific issues arise with the use of fMRI in the context of national security. For example, would this technology be applied in interrogations as an acceptable alternative to currently controversial techniques? At least one former intelligence officer has stated that it has been used in the “war on terror.”[8] However, applying fMRI in this context still seems to invite debate on questions of international law. Although national security interest in fMRI extends to interrogation, screening job candidates and employees seems the most practical application. National security agencies are among the largest users of polygraphs at present, despite their flaws, so a promising technology like fMRI surely opens new doors.

The Employee Polygraph Protection Act prohibits the administration of polygraph to civil employees, except in the case of ongoing investigations. However, this act does not apply to government employees, specifically exempting those working in national security with access to sensitive information. So just as national security agencies legally use polygraphs, legal application of fMRI seems possible.

Even if researchers overcome the technical problems in brain-scanning lie detection, other practical issues make implementation of fMRI challenging. For instance, the size of an fMRI machine and the necessary subject cooperation present serious problems—a person must lie prone inside a giant magnet and hold perfectly still for the device to function properly. Portable fMRI machines or long-range fMRI scanners might quell these issues, but such developments require significant scientific leaps. Gathering any significant valid data from a scan also requires an immobile subject. Even moving one’s tongue during a scan compromises the validity of results. At this point in time, the cost and inconvenience of using this technology makes its reliable use unrealistic, even if its accuracy is incredibly high, except in the most pressing of matters.

But the technology has to make significant strides before any of these issues become pressing. Improvements in fMRI brain scans stand to benefit medical treatments as well—imaging brain tumors, for example—and have applications outside of national security and the legal system. The reservations and cautions expressed here are not reasons to inhibit the development of this technology, but are rather encouragement to continue.

Michael Peroski is an undergraduate majoring in biochemistry and philosophy at Allegheny College.

Notes

[1] Pearson, Helen. “Lure of Lie Detectors Spook Ethicists.” Nature 441 (2006): 918-919.

[2] Yousuf, Sameer. “The Legal and Ethical Implications of fMRI Lie Detectors.” Unpublished thesis (2007).

[3] Ford, Elizabeth B. “Lie Detection: Historical, Neuropsychiatric, and Legal Dimensions.” International Journal of Law and Psychiatry 29 (2006): 159-177.

[4] “Federal Rules of Evidence.” Cornell Law School. 18 Feb. 2008. http://www.law.cornell.edu/rules/fre/rules.htm

[5] Ford (2006); Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 US 579 (1993)

[6] Illes, Judy and Racine, Eric. “Imaging or Imagining? A Neuroethics Challenge Informed by Genetics.” The American Journal of Bioethics 5 (2005): 5-17.

[7] Illes and Racine (2005).

[8] “High Tech Interrogations Might Promote Abuse,”  Penn State Live,  March 17,  2008, available at  http://live.psu.edu/story/29457; JH Marks, “Interrogational Neuroimaging in Counterterrorism: A No-Brainer or a Human Rights Hazard?” The American Journal of Law and Medicine 33 (2007): 483-500.

• 20 percent of respondents report using medications to increase memory retention, concentration or focus.
• 60 percent of those who admitted non-medical use of cognitive-enhancing drugs used Ritalin.
• 44 percent of the admitting respondents used Provigil, known generically as modafinil.
• 15 percent admitted use beta-blockers.
• 9 out 10 respondents said they used the drugs to improve concentration and attention.

Science Progress advisory board member Martha Farah expressed concern about the ethical use of brain-enhancing drugs during a Seed Magazine-sponsored briefing on the Hill last month:

If higher productivity can come in a harmless pill, Farah wondered if workers might find themselves saying one day, “I want this job, but I don’t want to have to take a drug to get it.”

If Wired’s coverage is any indication, her concerns may already be manifest in some workplaces. In a recent edition of the magazine’s Mr. Know-It-All column, a reader asks the following question:

One of my coworkers, a rising star at the firm, is using unprescribed modafinil to work crazy hours. Our boss has started getting on my case for not being as productive. Should I tell him about my coworker’s pharmaceutical enhancement? Or should I start taking modafinil, too?

The question of what sort of social or governmental rules will govern such ethical choices about brain enhancement remains unanswered, but it’s obvious that deliberations have already begun.

Joined by author Jonah Leher and Science Progress Editor-in-Chief Jonathan Moreno at the Seed Magazine-sponsored briefing, Farah began by explaining that 20th-century advances in neuroscience came primarily in the fields of basic scientific research and medicine. Shifting to real-world applications, she said that 21st-century neuroscience has already brought and will bring more non-medical applications of this research, and these developments have already altered the way we can manage human capabilities. “Neuroscience has rappelled down from the ivory tower and eloped from the hospital ward,” she said, explaining that for any sphere, “in which it is important to understand, assess, predict, control, or improve human behavior, neuroscience can help.”

But the fundamental ethical question at the heart of developing brain enhancement technologies is the role of doctors. Most neuroscience research is tied to biomedical practice and infrastructure, and enhancement changes the nature of this establishment when producing non-medical applications. Farah explained that with advances in the field, the mission of medical groups is up for debate. She said that doctors must ask: “Are we in the business of just healing people and fixing the sick, or are we in the business of enhancing people and improving their lives?”

She identified two major approaches to altering and understanding the brain: drugs and devices, and some of the policy considerations related to each. The tradition of using chemicals to alter mental states or enhance mental performance goes back thousands of years, but some current non-medical applications of psychopharmacology that raise ethical questions include stimulants that improve attention or reduce the need for sleep. Farah cited a research study indicating that up to 25 percent of students on some college campuses use prescription stimulants like Adderall or Ritalin, originally designed to treat attention deficit hyperactivity disorder, for non-medical purposes. With the drugs, students can work or study additional hours without sleeping, potentially leveraging that time as an educational advantage. But she noted, “the students I teach did not wait to read about this study”–rather, the social pressure to succeed and the ready availability of the controlled substances incentivizes using the stimulants to increase their productivity.

Modafinil, marketed as Provigil, is a prescription drug with growing popularity that confers an even more powerful enhancement: it allows people who take it to function for days on end without the need for sleep, and without any short-term side effects. In addition to raising the same ethical questions about advantages in productivity in competitive fields associated with stimulants, Moreno pointed out that the Air Force already prescribes Provigil to pilots in order to allow them to carry out long missions without the need for rest. Both also questioned the impact these technologies have on personal freedom. If higher productivity can come in a harmless pill, Farah wondered if workers might find themselves saying one day, “I want this job, but I don’t want to have to take a drug to get it.” Addressing military applications specifically, Moreno pointed out that citizens in military service were going to have to accept more and more interventions to improve their performance and abilities, but he warned that “we need to think about what these young soldiers are going to tolerate.”

Farah explained several other pharmaceuticals that raise significant ethical and policy questions. Courts, she said, already have the authority to prescribe anti-androgen treatments that inhibit sex drive for sex crime offenders, raising the specter of Clockwork Orange-like state control over the bodies of prisoners. Many drug companies, she said, are working to bring drugs to market that combat the natural memory loss effects of aging. Propranolol, a beta-blocker that can dampen memory formation and retention, is currently used to treat post-traumatic stress disorder in soldiers. Considered through a different lens, the drug could ease the psychological burden of killing enemy soliders in combat. Moreno asked, “Are guilt-free soldiers the kind the United States wants to have?”

The pharmacological applications of neuroscientific research that Farah outlined are all real and commercially available. In shifting her discussion to devices, she was careful to stay with real applications, because the topic, “can easily get into science fiction.” The two primary categories of device applications are machines that stimulate or augment brain function, or machines that image and observe brain function. The former class includes Transcranial Magnetic Stimulation devices, which use magnetic pulses to activate specific areas of the brain and trigger a response. Portable TMS machines have battlefield applications: the direct brain stimulation can heighten awareness and alertness in demanding situations.

Neuromarketing is the burgeoning field of brain imaging applied to the development of effective corporate messaging. “A large number of Fortune 500 companies are paying neuromarketing firms to vet their advertising,” Farah said. For example, a Boston-based ad firm showed test subjects a series of potential images for use in marketing Jack Daniels whiskey, narrowing the most effective photos by observing the brain response of young men in an MRI machine.

Perhaps one of the most sensational fields of imaging research includes experiments that apply fMRI technology for lie detection. Farah explained the process by which researchers train computer algorithms to associate certain brain responses of study subjects with true and false statements, and then attempt to use the machines to determine the truthfulness of subsequent statements. While highly structured experiments have produced positive results, she registered her own skepticism “that this is ever going to transfer from the laboratory to any high-stakes purposes.”

One imaging application with high-stakes applications that could make it out of the lab allows researchers to associate personality characteristics with patterns of brain function. This allows scientists to predict extraversion, unconscious racial attitudes, or educational abilities without the usual pencil-and-paper tests–and without subjects necessarily knowing what researchers are looking for. The technology, already accurate, raises privacy concerns for job screening and discrimination.

Farah closed by pointing out that most neuroscience research is jointly funded by private enterprise and the federal government. Because private companies realize the potential of capitalizing on these technologies, the government should address future concerns about its responsible use by exerting ownership and control while it still maintains significant financial involvement, ensuring that its benefits are not inequitably distributed. “It’s going to happen anyway, and we ought to own it,” she said.

Using functional magnetic resonance (fMRI) scanners to record a person’s brain activity while they looked at thousands of pictures, researchers created a model to predict the mental activity patterns elicited by looking at specific images. Then individual subjects were asked to look at a set of novel images and the computer was able to identify which images they were looking at with a significant amount of accuracy. According to the report (subscription) published in Nature, “Results suggest that it may soon be possible to reconstruct a picture of a person’s visual experience from measurements of brain activity alone.”

While such mind-reading and dream re-creation may be a still be in the world of science fiction, the results are a big step forward in demonstrating the huge amount of information available in fMRI signals, which could go a long way in helping understand how the brain works.

The study consisted of two stages and only two subjects, both volunteers from the research team. The first stage involved showing the subjects 1,750 grayscale pictures of “natural” images–houses, trees, plants, animals–and recording their mental activity with fMRI scanners. The imaging data and mental activity patterns were then used to create a predictive model of activity in the visual areas of the brain. In the second stage, the researchers tested the model by showing subjects 120 new images. The model attempted to identify which image the subjects were focused on by comparing the measured mental activity against predicted activity. Based on the 120 possible images in the experimental set, the probability of guessing an image correctly each time is 0.8 percent. The model identified the correct image 92 percent and 72 percent of the time for each subject.

Any potential “visual decoder” would need to handle a larger set of images. So to test the capabilities of their model, researchers increased the set size to 1,000 new images and found that identification performance dropped only slightly. Extrapolating from these results, the scientists believe that identification accuracy would remain above ten percent even up to a set size a hundred times greater than the amount of pictures indexed by Google (880 million images). This amount of accuracy happens to be significantly above chance, demonstrating the potential of this model. The researchers even tested the performance of their model over time, bringing one of the subjects back after two months and achieving 82 percent correct identification.

Media outlets who covered the study choose to focus on the possible applications of the technology and the ethical questions it raises:

• Brandon Keim of Wired lays out the ethical dilemmas of the study. He writes about the possibility of such technology invading mental privacy, as well as how it could be used in the courtroom.

• Nikhil Swaminathan at Scientific American spoke to John-Dylan Haynes, a neuroscientist at the Max-Planck Institute, who said the predictive model used in the study is currently limited to sensory inputs and that high-level mental functions such as memories and emotions are still a bit far from being codified into a mathematical model.

• James Randerson at the Guardian outlines the study and highlights the futuristic potential of visualizing dreams and memories and helping understand the mental state of coma patients.

• Emily Singer at Technology Review points out a growing trend: the use of technology to analyze and study the brain’s neural processing pathways.

• Science Progress Editor-in-Chief Jonathan Moreno raises ethical and policymaking questions about the growing interest of Federal defense agencies in neuroscience in his book, Mind Wars. Case in point, this study was partially funded by the National Defense Science and Engineering Fellowship, whose website explains the purpose of these grants is “a means of increasing the number of U.S. citizens and nationals trained in science and engineering disciplines of military importance.”

Image: flickr.com/tico_bassie

Pinker reminds us that a diversity of cognitive systems both set the conditions for how we respond to uncertainty and how we learn. Applied to the social and political world, these observations suggest that in a culture devoted to participatory democracy and knowledge acquisition, we should foster self-corrective inquiry. We may be predisposed to learn about the objects in our world in certain ways, but we are nevertheless born prepared to learn. Pinker points out that this receptivity to education remains constant across all human beings in spite of our diverse patterns of DNA.

According to Pinker’s realism, we are anchored to a world of adaptation, wit, and social discourse. The growth of knowledge and science is grounded in noting an object, fixing reference to it or “tagging” it, and then engaging in the process of coming to understand the object in our world.

First and foremost, a formal education should teach us how to properly apply the categories that we are born to impose on what we sense.

In his conception, language is one mental organ among others that interacts with other senses such as our conception of space and time, our assessments of risk and probability, and our categorization of objects. Because these other intricate mental processes depend on interacting with other people in our social space, we see more clearly that minds must be unencumbered by tyrannical restraints, and that they should be nurtured and emboldened by wise policies that foster debate and discovery. Particularity democracy requires an understanding of the active mind. But the most essential policy would be one that supports these intellectual capabilities through education, beginning early in life.

First and foremost, a formal education should teach us how to properly apply the categories that we are born to impose on what we sense. As William James observed over a hundred years ago, we need to learn how to make our nervous system our ally instead of our enemy. An educational policy that sets this goal would represent a renewal of the progressive approach to learning.

Ultimately, we will reap innumerable dividends from these policies because they act as an investment in an Enlightenment culture, a culture in which participation in the polity, not by the few but by many, is a normative goal; and a culture in which that participation is nurtured early on by harnessing our innate tendency to organize the objects in our world in a shared social space of comprehension and meaning. An investment in that kind of culture is an investment in the Enlightenment tradition on which this nation was founded by minds like Franklin and Jefferson—and from which this nation continues to progress by minds like Pinker.

Pinker is in the long tradition that dates back to Plato through the classical rationalists of the 17^th century (e.g. Descartes, Leibniz); the primary focus is a recognition of the innateness of the human mind. Language is always the paradigmatic example, a la Chomsky in the 20^th century: Without innate syntax wired into our brain biology, there would be no language acquisition. Pinker falls squarely within that tradition and is a staunch defender of its scientific validity.

But Pinker is also more than that. What makes this latest work important is that Pinker debunks extreme forms of rationalism within linguistics that endorse linguistic imperialism, claiming that language is all of human thought. The Stuff of Thought moderates this view of linguistic dominance. Pinker rightly notes, as many others have argued, that human thought is larger than just language acquisition. Language is a key to the vastness of the human mind, but it is nevertheless one among many other cognitive resources.

Pinker makes sure to emphasize that these cognitive systems connect us to the world, rather than separate us from events to which we are trying to adapt.

Similarly, the mind is far from the blank slate envisioned in classical empiricism. Chomsky and now Pinker are surely right about this. However, unlike Chomsky—and Jerry Fodor for that matter—Pinker is frankly empirical, but from a rationalistic perspective. Pinker’s view of the mind is close to that of Immanuel Kant. He argues throughout that our concepts of space, time, and causation are fundamental features of the mind. As Pinker puts it, “Kant was surely right that our minds ‘cleave the air’ with the concepts of space, time and causality” (p 253).

Pinker notes that there is abundant evidence of diverse forms of classifying tendencies that humans possess which set the foundations for our problem-solving abilities and then become expanded and extended through usage. We possess certain core concepts such as animacy and agency (the detection of the beliefs and desires of others), in addition to our senses of space, time, probability, and language—and together, these give rise to our worldview. In addition, these cognitive abilities are intertwined and utilized in even the most mundane everyday activities.

Pinker has always been enthusiastic about biology and ties language and other cognitive predilections to our biology, our evolution, and to our diverse forms of adaptation. The cognitive milieu, in addition to the cultural one, sets the context for human expression. Thus evolution does not hang on one cognitive feature, but provides us with a large toolbox of diverse kinds of cognitive abilities. Our responses to complex environments reflect the cognitive architecture and evolution that underlie our adaptation and organization of action.

Pinker makes sure to emphasize that these cognitive systems connect us to the world, rather than separate us from events to which we are trying to adapt. Moreover, our cognitive resources are tied to the fact that we are inherently social. The social milieu and the transactions between us reflect the mental machinations of our species.

We are also taxonomic animals. We categorize things, and we come prepared to discern events from a core orientation and perspective. The use of metaphor in our cognitive arsenal in categorizing events is fundamental to our semantic lexicon. Pinker engages the school of linguistics that emphasizes metaphor as the heart of human cognitive systems and he acknowledges the diverse roles that metaphor plays in our cognitive arsenal. They are, as Pinker rightly notes, “not simply literary garnishes but aids to reason” (p 253). Yet he also tweaks George Lakoff, the leading exponent of this school, for going “a wee bit too far” (p 247) when Lakoff claims that all thought is embedded in metaphor.

Understanding more fully the dynamic role categorization and metaphor play in our understanding of the world further emphasizes the necessity of cultivating each citizen’s awareness of how they comprehend the world.

Jay Schulkin is a Research Professor in the Department of Physiology and Biophysics and the Department of Neuroscience at Georgetown University.

This may seem like a novel and revelatory application of cutting-edge scientific research to real-world issues, but just because the research took place in a lab and uses expensive brain-imaging equipment, doesn’t mean that it’s sound science.

Last Wednesday, a group of seventeen cognitive neuroscientists wrote a letter to the editor pointing out that the study was not peer reviewed and that many of the findings were not as clear cut as the Op-Ed made them out to be. They note that multiple mental states can activate any given brain region. Case-in-point: positive emotions also arouse the amygdala—not just anxiety.

In order to arrive at a sound conclusion about the brain regions activated for given mental states, researchers must design experiments with carefully controlled variables, large sample sizes, and lots of repetition. That’s why the most solid brain imaging data cover attention and memory, whereas sexier topics like politics, religion, and consumer choice do not lend themselves to the pithy and reliable conclusions that make for good headlines. That being said, brain imaging has shown legitimate promise with regard to these other topics, and is certainly worth exploring.

In addition to the lack of peer-review, the researchers also did not release enough details of the experiments to demonstrate why they arrived at their conclusions. Wired Science raises questions about whether the data could have been skewed by a few subjects—after all, the study was only made up of 10 men and 10 women. They also chide the Op-Ed for making “sweeping generalizations.” Mind Hacks and Brainethics also leveled some testy criticisms.

A fair-minded critique comes from Martha Farah, Director of the Center for Cognitive Neuroscience at the University of Pennsylvania (full disclosure: Farah is a member of the Science Progress Advisory Board). Farah is both skeptical and optimistic about the findings. She casts aside simple criticisms such as “brain imaging can be used to show anything,” and “it doesn’t apply to real world situations like politics.” She goes with a more penetrating criticism about how different emotions can be associated with the same brain region and how the data was split up along many different lines —gender, early in the scan vs. late in the scan, favorable rating of candidates vs. unfavorable, still photos of candidates vs. videos. According to Farah, this makes it a lot easier to find interpretable patterns and construct “just so” stories. Ultimately, Farah thinks that Iacoboni et al. may have found some “useful information about voter attitudes,” but the findings need a more rigorous verification analysis.

Finally, Farah notes that the real issue is how brain imaging gets manipulated by marketing and research companies to attract customers regardless of the information conveyed. A high tech measurement like a brain scan—as opposed to a survey—appears more “scientific” or “objective.” But that isn’t necessarily so.

David Goldston gave a recent talk at the University of Connecticut on the political polarization of scientific evidence, the difference between science policy debates and debates over scientific evidence, and the proper role for scientists to take if they want to inform politicians accurately, honestly, and effectively. Former Staff Director of the House Committee on Science and Technology under Sherwood Boehlert (R-NY), Goldston appeared today on WAMU’s Kojo Nnamdi Show.

Time magazine has a powerful and thoughtful first-person account of erasing a patient’s bad memory. This is not about medications and therapies that may come about in the future or are currently under development. This is about a real case of immediate memory erasure that happened a number of years ago. The substance employed is called propofol and its usage raises issues about the ethics of informed consent and the nature of personhood vs brain chemistry.

Imagine walking into a doctor’s office where an advanced brain scanning system can detect cellular-level changes that signal the onset of Alzheimer’s disease, years before any physical or mental symptoms manifest. You and your loved ones’ quality of life could then be extended by decades with a treatment plan personalized to your specific case. Today, brain imaging technologies such as this are only just beginning to illuminate the causes of brain-related illnesses. But a wide chasm must still be crossed if we are to develop effective treatments for the nearly 100 million Americans and 2 billion people worldwide that currently suffer from brain illnesses such as Alzheimer’s.

The annual national economic burden of brain-related disorders has reached over $1 trillion (see chart) and is growing alarmingly due to an aging population. While research into the brain and brain-related illnesses is moving forward more rapidly than any other science today, our understanding of how the brain works still has many gaps and our ability to repair damage remains limited. Critical unmet medical needs exist in almost every area of brain and nervous system disorders, including Alzheimer’s disease, addiction, anxiety, autism, depression, epilepsy, multiple sclerosis, obesity, Parkinson’s disease, pain, sensory disorders, spinal cord injury, stroke, schizophrenia, sleep disorders, and traumatic brain injury.

SOURCE: Neuroinsights, Office of Nat’l Drug Policy, Nat’l Institute of Diabetes, Alz Assoc., Duke University, American Psych. Association, Harvard, Nat’l Sleep Found., American Stroke Assoc., Prevent Blindness America, CDC, Journal of Clinical Psych, Epilepsy Foundation, Cost of Brain Disorders Europe

Investigation into the mechanisms and functions of the brain will lead to vastly improved understanding of brain disease and injuries, human cognition and behavior, and will give us an unprecedented ability to treat and heal those in need, as well as begin to reduce this growing burden on our economy. But all of this won’t happen on its own.

Emerging neurotech companies developing drugs, medical devices, or diagnostics for the brain and nervous system face more difficult investment requirements, research and development challenges, and regulatory milestones than other healthcare sectors. This additional complexity results in higher costs and longer time to market for many neurotech treatments. For example, it costs nearly $100 million more and takes two years longer to bring a neuropharmaceutical treatment to market than the average drug.

It is critical that the progressive traditions of American science and technology, especially our longstanding focus on the legal and ethical implications of new scientific discoveries, carry special weight as this new science matures.While some companies can get private funding to bring low-risk drugs to market, few risk-averse private investors will fund research into potentially more powerful treatments leveraging novel approaches like gene therapy for Alzheimer’s or neurostimulation for mental illnesses. Today, the potential for innovative treatments has never been higher—but brain researchers and neurotech entrepreneurs require additional support if they are to bring their ideas out of the labs and into patients’ lives.

A targeted, coordinated national effort is needed to support the development of neurotechnology across the board. It is vitally important that public infrastructure be developed to ensure that today’s neurotechnology discoveries quickly become tools to improve the human condition. Government must become a partner with the private sector to encourage the translation of brain research into treatments.

In an effort to improve national coordination and accelerate neurotech innovation, the Neurotechnology Industry Organization is spearheading the National Neurotechnology Initiative. The NNTI calls for establishing a National Neurotechnology Coordinating Office within the Department of Health and Human Services to help agencies plan joint and complementary research strategies and to serve as the unified voice of federal neurotechnology efforts. The new initiative also seeks to create an advisory panel of experts from industry, academic institutions, and non-profit organizations to inform the new office on issues including research and development priorities, technology transfer, commercial applications, and ethical, legal, and social issues.

The NNTI legislation, which is currently being evaluated by healthcare policymakers on Capitol Hill, includes $200 million in new federal funding for the first fiscal year. This funding would flow to the National Institutes of Health, the Food and Drug Administration and several other agencies to jumpstart new research, prepare the regulatory ground for consideration of new neurotechnology tools, and examine the ethical, legal, and social implications of this new field.

Under our proposal, the National Institutes of Health would receive funds to coordinate research and move that research out of government labs and into young innovative companies developing the next generation of neurotech treatments. The FDA would be able to hire neuroscience-related staff and develop workshops to create more robust neurotech standards to ensure the increased timeliness and safety of the neurotechnology review process.

Like previous successful models of coordinated federal investment initiatives, including the Human Genome Project and the National Nanotechnology Initiative, the National Neurotechnology Initiative will lead to a cascade of investment, discovery, applications, and benefits that can only be imagined today. At the same time, a federal research effort can help ensure the responsible development of neurotechnology by establishing ethical guidelines and policy for research, development, and applications.

By taking these steps Congress can ensure that the United States remains at the forefront of the race to uncover the workings of the mind. Huge economic payoffs will accrue to new and emerging centers of neurotechnology excellence around our nation, among them the San Francisco Bay area, Boston, San Diego, Seattle and Greater New York. The growth of strong neurotech regions will have long-lasting implications for employment, infrastructure development, and regional competitiveness.

Today the United States leads the world in neurotechnology R and D and commercialization, but the United Kingdom, China, Sweden, Japan, and Germany are all developing their own centers of neurotechnology excellence. The global expansion of knowledge in this new scientific arena is good for the United States and good for humanity. Yet it is critical that the progressive traditions of American science and technology, especially our longstanding focus on the legal and ethical implications of new scientific discoveries, carry special weight as this new science matures.

Neurotechnology applications have the potential to transform highly specialized areas of medicine, computing, and defense, and will also affect the everyday lives of Americans. How this plays out, and the benefits or consequences of these new tools, will depend on the U.S. government taking a leadership role in neurotechnology R and D. As Congress weighs our legislative proposals, we invite the broader scientific community to examine our proposal and support this important cross-disciplinary initiative.

Zack Lynch is Executive Director of the Neurotechnology Industry Organization.