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Cognition White Paper (PDF - 237KB)

Created on June 1, 2011

14 Submitted Comments on Cognition

This is an excellent set of recommendations on many levels. I am glad my peers were there to represent me. Brain-gene-behavior-environment interactions throughout development are critical, as are multidisciplinary "team" science projects. Large scale studies such as the National Children's Study will be informative. A general theme in the report seems to be of "standardization" across research groups, adopting the NIH toolbox, for example. While in theory, it would be good to make findings from multiple researchers more comparable, there is also a cost to using solely this kind of approach. That is, it seems we will always be left to the "lowest common denominator" as time goes on, and technology evolves. It is difficult to adopt newer cutting edge data acquisition if standardized procedures are "time-locked" to the year 2011. Thus, while standardization across investigation sites may in some cases be advantageous, we would not want to outweigh the importance of new innovation that can only come from creative new ways to think about the question of brain-gene-behavior-environment, which may have yet to come from the next generation of developmental cognitive neuroscientists.

Submitted by Anonymous Guest on June 1, 2011 at 6:35 PM

Scientific opportunity: Amelioration of cognitive disorders through targeted pharmacotherapy

The rich discussion of the NICHD Scientific Vision Workshop on Cognition, in which I was privileged to participate, and which is so ably summarized in this white paper, highlighted the neuroscientific progress in elucidating the molecular pathophysiology of cognitive disorders resulting from genetic conditions. (See the plenary addresses by Dr. Silva and Dr. State, and Scientific Opportunities #1 and #2 in the white paper.) The white paper highlights the opportunity to find potential "approaches to...intervention that are based on knowledge of the underlying pathophysiologic mechanisms."

In fact, the opportunity to test those approaches, not just to find potential approaches, is at hand. Dr. Silva and other researchers have initiated clinical trials of targeted pharmacotherapy for several genetic disorders, including neurofibromatosis, Fragile X syndrome, tuberous sclerosis, and Rett syndrome. The results of such trials, and trials in which pharmacotherapy is combined with educational-behavioral intervention, will also inform other key questions that are identified in the white paper, such as those related to sensitive periods of neurodevelopment and Brain x Environment interactions. If these trials or their successors are positive, they will represent a quantum leap toward fulfilling the mission of the NICHD, ensuring that "children...achieve their full from disease or disability."

The opportunity to identify potential approaches for targeted treatment of cognitive disorders is enormous, but in the next 10 years EKS NICHD can seize an even bolder opportunity - to develop and to test such treatments. That enterprise is already underway, and would benefit immeasurably from the attention and support of the Institute.

Submitted by Paul Wang on June 3, 2011 at 6:52 PM

Although 'nutritional profiles' were mentioned in the White Paper on Cognition as an example of preclinical risk and protective markers, the topic was not developed further. The topic of cerebral nutrition and fuel energetics was not mentioned, even though the brain consumes 25% of the circulating glucose on a minute-to-minute basis. Interruption of the brain's glucose supply leads to a cessation of cognition. The issue of alternate nutrient substrates for cerebral metabolism remains of interest, especially in the context of recurrent hypoglycemic attacks in children with type 1 diabetes. On a global basis, iron and iodine are the two most commonly encountered nutrient deficiencies, and both can exert pronounced effects on cognition, depending on the degree of the deficiency and the period of exposure. It is estimated that even mild degrees of iodine deficiency account for significant decrements in cognition as measured by IQ. It is important to delineate the window of vulnerability for this important nutrient and to ascertain if cognitive defects can be reversed by iodine supplementation during this window of opportunity. Lozoff has shown that iron deficiency in infancy affects brain development and function that lasts a lifetime. She has found that there is a relatively narrow window of time from birth to 18 months during which supplemental iron can reverse impairments of white matter and defective dopaminergic pathways of the brain. Without a reversal of this nutrient defiency during the window of opportunity in infancy, affected children fall further and further behind, first as school children, and then as adults unable to hold more than menial jobs. Elucidating the molecular basis of the developmental windows for the effect of iodine and iron on brain development and function would be of great interest, especially to ascertain if there are pathways that could be targeted outside the window of opportunity that would enable a reversal of cognitive defects. The effects of iodine and iron deficiency are well known. It would be of interest to ascertain the effects on brain development and cognition of other micronutrients, as well as essential fatty acids, and amino acids.

Submitted by Gilman Grave on June 8, 2011 at 4:33 PM

I favor these recommendations. However, the broad vision which encompasses these individual selections is diminished by lacking specific reference to Global application of this vision. NICHD has gained recognition for having a significant global vision directed to both relatively static and rapidly changing resouce poor populations. Specifically extending the Vision Globally accelerates the acquisition of knowlege applicable both to to these populations and to the United States. I hope NICHD will expand its unique role as a Global leader in evidence-based research.

Submitted by Michael Hambidge on June 9, 2011 at 10:07 AM

The emphasis on the genetic underpinnings is understandable, but the paper has nothing to say about the crucial role of accurate phenotyping if a genetic approach is to be successful. The field needs clearer evidence on the development and interconnections of cognitive abilities and how to measure them. The complexity of the gene-cognition relations coupled with insufficiently precise characterization of cognitive abilities (especially over development) is a serious obstacle to progress. NICHD should support research on individual differences (not just disabilities-these need to be understood as a continuum) in cognitive development. The accurate phenotype is essential.

Submitted by Charles Guest on June 10, 2011 at 8:31 AM

I find it both intriguing and worrisome that the pendulum has swung so far toward the "rare variant" story. I think it is very important not to close doors on anything that has generated (and keeps generating) interesting information. Whereas rare variants are important for generating diversity (and we really do not know much yet about what they do for "extreme" traits at the other end of the continuum-e.g., where does intellectual greatness come from?), common variants are important for maintaining diversity and they have proven to be a consistent and significant source of individual differences in cognition. Thus, putting all the weight of genetic research on rare variants appears a little... shortsighted.
Another shortcoming here is the lack of discussion of secondary genetic mechanisms, e.g., epigenetic mechanisms. The report talks a lot about intervention, but it does not focus enough on the possible underlying mechanisms that can capture the impact of the intervention. The gap in the discussion on "translating" behavior interventions into biological changes, thus, stimulating research on the biological maintenance of behavioral change, seems important to close.

Submitted by Elena Grigorenko on June 10, 2011 at 11:48 AM

I applaud the visionary thinking of the panel that put this document together. Clearly, a lot of effort went in to considering what is on the horizon of research on cognitive development. I hope we don't lose sight of the fact that we have much more to learn about typical cognitive development and this is an important consideration for all research done on disorders of any kind. We may find that some of these investigations into disordered development are jumping the gun if the phenomenon and tasks being studied are not yet well-mapped-out in the normative realm.

Submitted by Amy Needham on June 10, 2011 at 12:17 PM

The White Paper on Cognition largely omits consideration of economic and social research on cognition and its relationship to child development. It also fails to discuss the potential for supporting work that would facilitate integrative research to capture important interrelations between neurobiology and genetics with recent innovative research and data in economic and psychological science. The NIA-supported Health and Retirement Study has recently introduced genetic, biomarker and cognitive measures which are linked to the rich longitudinal survey data on economic, family and health information. This investment in data that crosses disciplinary domains provides a crucial input for the development of new, interdisciplinary research in aging. It equally important for NICHD to aggressively support the collection of similar longitudinal data beginning at conception. As with the HRS, designing such data requires serious and sustained interaction between researchers in the social, economic and psychological sciences with those in the biological sciences. The ability to think and reason-what psychologists call fluid intelligence-is a critical input into the ability of individuals to acquire knowledge and skills through parental nurture, formal education, learning on the job and, outside of work, in a wide variety of consumption, production and leisure activities in the family and community. Psychologists refer to this constellation of acquired knowledge and skills as crystallized intelligence while economists refer to it as human capital. Although the psychological theory of fluid and crystallized intelligence and the economic theory of human capital originated in the middle of the last century, it is only in the past decade that economists and psychologists have become aware of the parallels between these core theoretical frameworks and the potential gains from creating new, integrated theory. Ongoing joint research by economists and psychologists has shown that parental and societal investments in early childhood are critical determinants of later success and, importantly, that it is difficult and very costly to make up for failures to invest at early ages. Future research offers great scope for further integration of heretofore separate lines of research by utilizing genetic data, imaging techniques from neuroscience (including neuroeconomics) and other relevant scientific theories, methods and data.

Submitted by Robert Willis on June 10, 2011 at 12:40 PM

The authors identify integration as an over-arching theme and invoke team science as a promising approach in a number of their stated Scientific Opportunities. There are (at least) two broad areas of interest to economists as potential members of those teams. First, while many of the Scientific Opportunities seemed clinical and driven by the discipline's justifiable interest in pathology, community-based approaches may be effective. Second, Scientific Opportunity #8 is of particular interest to economists who worry about the economic outcomes for children who do not obtain levels of human capital necessary to be "successful" in the 21st Century. (1) A recent JAMA comment (Teutsch and Fielding, June 1, 2011) noted that focusing on individual clinical interventions fails to identify cost effective community-level behavioral interventions (e.g., public health programs that reduce smoking rates are more cost effective than individual interventions in reducing lung cancer). There are likely analogs in the cognitive health area (e.g., Preventing Fetal Alcohol Syndrome). A "science team" that included economists and behavioral public health practitioners would help to identify those kinds of opportunities and design appropriate policy, particularly if coupled with the kinds of database sharing noted in the White Paper. (2) One big reason for economists' interest in children's cognitive development is concern about what happens when children grow up and enter the labor force. Longitudinal tracking of cognitive development into the pre-teen years and high school years would be particularly important in addressing educational (and other) approaches that might help children better navigate that fraught time between childhood and adulthood. Scientific Opportunity #4 notes these "sensitive periods". Economists familiar with the methodologies and data used to study trends in educational attainment and labor market outcomes and opportunities could contribute to science teams engaged in this inquiry. Investigations into behavioral economics topics like risk-taking and patience have shed some light on behaviors that teens engage in that negatively affect their economic outcomes. These behaviors seem directly related to cognitive development during "sensitive periods". The economic research in this area, to my knowledge is new and sparse and would clearly benefit from multidisciplinary collaboration.

Submitted by Kate Krause on June 10, 2011 at 1:43 PM

As a participant in the Cognition workshop, I was especially pleased that some attention was devoted to the need to focus on typical cognitive development. Scientific Opportunity 4 is critical...a continued focus on normal cognitive development with technologies that integrate multiple levels of analysis: genetic, brain, and (importantly) behavioral. Behavioral science research is essential for understanding normal developmental trajectories in cognitive processes and the normal variations in these trajectories.

Submitted by Martha Ann Bell on June 10, 2011 at 3:35 PM

There has been a lot of exciting research in economics over the last ten years on developing frameworks for modeling the life-cycle development of cognitive and noncognitive skills and using the frameworks to study how the development is affected by parental and societal investments. That research also studies when investments in children are optimally made. This is a very active area of research in economics that has been growing in importance. For example, Nobel laureate James Heckman has written numerous papers in recent years on these topics that develop new methodologies and employ fairly sophisticated statistical modeling (e.g. dynamic factor models). Some of the work is collaborative with psychologists. The research along these lines has already led to a better understanding of the reasons for the observed skill differences between groups (e.g. by race, gender) and how skill gaps evolve over the life-cycle and are ultimately are translated into educational attainment and earnings gaps. A major reason that cognitive differences that develop during childhood are important is that they translate into differences in adult educational attainment and earnings capacities that then persist throughout the lifetime and cannot easily be remedied at a later time. I think the White paper would benefit from more consideration of the economic approach to modeling the determinants of skill development and how this development can be affected by public policies (such as the introduction of subsidies to allow children from lower income backgrounds to attend higher quality child care centers).

Submitted by Petra Todd on June 10, 2011 at 3:52 PM

I congratulate the team of scholars who produced this white paper, and echo their views that the study of cognition is a critical component of a research program on healthy function. I note that this emphasis should include a thorough understanding of normal cognition, and not just the disorders and treatments of cognition. The research directions identified here are meritorious; however, I was disappointed not to see more emphasis on basic behavioral research, including research on the emergence of cognitive competencies from developmental or comparative/animal-model perspectives. Cognition is a manifestation of neurobiology, and thus it is important to keep momentum in the area of cognitive neuroscience. But humans are not unique as neurobiological creatures. As experimental methods have developed to allow unprecedented comparability in testing methods and data across species, the time is right to expand our studies of cognition as it is manifest across organisms, so as to enhance our understanding of cognition's role in behavior at every level of analysis (e.g., chemical, neural, computational, behavioral, social). In this way, cognitive theory and its application can be grounded in fundamental knowledge about the behavior of our species and other cognitive organisms.

Submitted by David Washburn on June 10, 2011 at 4:07 PM

Cross-Cutting Issue: cognitive, developmental origins of health and disease, plasticity, behavior

While the identification numerous genetic variants have theoretically opened an unprecedented opportunity to understand genetic contributions to the etiology of diseases and cognitive processes, with the present research infrastructure, it is improbable that this coffer of knowledge will be used productively to develop diagnosis tools and treatments in the next decade.

The Vision: Creation of an NICHD or NIH supported national center for the generation of novel lines of animals, over- or under-expressing different combination of genes associated with risk for disease and cognitive deficits, that can be made available to investigators world-wide. The central goal is to identify combinations of multiple "at risk" genetic variants, based on our present knowledge from GWAS and CNV studies, which contribute to the development of diseases and cognitive deficits. This effort can be incorporated to presently funded projects that are generating different strains of GFP-reporter mice, and strains of inducible cre- or flp-recombinase mice targeting different cell types during development.

The potential outcomes during the coming decade:
* Identify signaling, cellular and functional networks that constitute the biological mechanisms underlying deficits

* Identify the role of development and GXE interactions in cognitive deficits and disease using inducible recombinant systems

* Identify combination of genes that are highly penetrant and associated with behavioral deficits/disease, and subsequently test a combination of these variants for predictive value for different diseases associated with cognitive deficits (i.e. schizophrenia, bipolar disorder, autism spectrum and ADHD)

* Develop diagnostic kits based on gene variants (SNPs) associated with disease or cognitive deficits

* Based on the identified combination of variants that are highly penetrant, develop iPS cells (from patients and/or animal models) that can be propagated and differentiated to screen for novel drug targets

The Good News: We already have all the technologies, but simply have not combined them, to study the effects of multiple gene variants on disease and cognition. Presently available: mice/fish harboring targeted mutations, cre- and flp- recomb mice, shRNAs for knockdown, rodent test for behavior and cognition studies, and electrophys/imaging techniques to identify net

Submitted by Andres Buonanno on June 10, 2011 at 4:51 PM

This white paper presents promising research directions focused largely on intellectual infrastructure and new techniques (e.g., genomics) for improving the developmental trajectory of cognition. It is important to note that economics and the emerging method of decision neuroscience
(sometimes called "neuroeconomics") can play a central role in the study of cognition too. Economists come to the study of cognition indirectly, from an emphasis on what factors influence human choices and whether changing those factors improves the quality of choices as people judge them. Starting in the 1980s an approach called "behavioral economics" emerged which proposes theories about how limits on computational power, willpower, and self-interest affect choice. This approach to economics is now increasingly popular and is well-rooted in cognition. The behavioral approach is also bearing fruit in applied fields such as finance (helping to explain mistakes investors make and aggregate phenomena such as price bubbles) and the study of regulation (in the form of "nudge" proposals to help people make better decisions with minimal unintended consequences). The economic approach to cognition can also be useful for psychology on its own terms. What economic theories are best at is using simple formal
modeling to generate insights and predictions. Since mathematics is little used in psychology, some insights may come from economic theories of traditional psychology topics such as overconfidence, the effect of salience and attention, misperceptions of randomness, and naivete or prejudice in judging other people's traits and actions. In neuroscience,
the central contribution of the neuroeconomic approach so far has been the use of experimental paradigms and mathematical tools (such as Bayesian generative models of optimal exploration among different choices) to design tasks. These tools typically permit the behavior people exhibit to reveal a numerical value of a hidden variable, like a neutrally-computed
valuation or degree of conflict. These values fluctuate from
trial-to-trial systematically and, when correlated with brain activity such as fMRI BOLD signal or EEG field potentials, typically yield very clean and precise conclusions about how the brain is computing the underlying value. The good statistical quality of these conclusions substantially avoids the well-known danger of data mining and drawing "false positive" reverse inference conclusions from simpler analyses.

Submitted by Camerer Colin on June 10, 2011 at 8:51 PM

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Last Reviewed: 06/04/2012