Saturday, September 21, 2013

Gary Marcus - A Map for the Future of Neuroscience?

Last week in The New Yorker, neuroscientist Gary Marcus (author of Kluge: The Haphazard Evolution of the Human Mind [2009] and co-editor of The Future of The Brain [2014]), wrote a brief review/overview of the fifty-eight-page report on the National Institutes of Health (NIH) vision for the future of neuroscience—the first substantive step in developing President Obama’s BRAIN Initiative.

The report identifies six "themes" that the authors of this preliminary report feel will still be relevant when the working group begin the broader scientific plan detailing a larger vision, timelines, and milestones.
1. Use appropriate experimental system and models. 
2. Cross boundaries in interdisciplinary collaborations.
3. Integrate spatial and temporal scales. 
4. Establish platforms for sharing data. 
5. Validate and disseminate technology. 
6. Consider ethical implications of neuroscience research.
From these six themes, they have identified nine research areas that the National Institutes of Mental Health (NIMH) wish to focus on:
1. Generate a Census of Cell Types.
2. Create Structural Maps of the Brain.
3. Develop New Large-Scale Network Recording Capabilities.
4. Develop A Suite of Tools for Circuit Manipulation.
5. Link Neuronal Activity to Behavior.
6. Integrate Theory, Modeling, Statistics, and Computation with Experimentation.
7. Delineate Mechanisms Underlying Human Imaging Technologies.
8. Create Mechanisms to Enable Collection of Human Data.
9. Disseminate Knowledge and Training.
The model proposed allows no real space for psychology and psychotherapy, which seems to be the point and which serves as a continuation of move to make the brain and neuroscience the singular focus of mental health care.

As Marcus points out, however, "Though some dream of eliminating psychology from the discussion altogether, no neuroscientist has ever shown that we can understand the mind without psychology and cognitive science."

It's an interesting review - and I have included two sections from the report, which is freely available at the links below (as a PDF document).

A Map for the Future of Neuroscience

Posted by Gary Marcus

On Monday, the National Institutes of Health released a fifty-eight-page report on the future of neuroscience—the first substantive step in developing President Obama’s BRAIN Initiative, which seeks to “revolutionize our understanding of the human mind and uncover new ways to treat, prevent, and cure brain disorders like Alzheimer’s, schizophrenia, autism, epilepsy, and traumatic brain injury.” Assembled by an advisory panel of fifteen scientists led by Cori Bargmann, of Rockefeller University, and William Newsome, of Stanford, the report assesses the state of neuroscience and offers a vision for the field’s future.

The core challenge, as the report puts it, is simply that “brains—even small ones—are dauntingly complex”:
Information flows in parallel through many different circuits at once; different components of a single functional circuit may be distributed across many brain structures and be spatially intermixed with the components of other circuits; feedback signals from higher levels constantly modulate the activity within any given circuit; and neuromodulatory chemicals can rapidly alter the effective wiring of any circuit.
To tackle the brain’s immense complexity, the report outlines nine goals for the initiative. No effort to study the brain is likely to succeed without devoting serious attention to all nine, which range from creating structural maps of its static, physical connections to developing new ways of recording continuous, dynamic activity as it perceives the world and directs action. A less flashy, equally critical goal is to create a “census” of the brain’s basic cell types, which neuroscientists haven’t yet established. (The committee also devotes attention to ethical questions that could arise, such as what should happen if neural enhancement—the use of engineering to alter the brain—becomes a realistic possibility.)

The most important goal, in my view, is buried in the middle of the list at No. 5, which seeks to link human behavior with the activity of neurons. This is more daunting than it seems: scientists have yet to even figure out how the relatively simple, three-hundred-and-two-neuron circuitry of the C. Elegans worm works, in part because there are so many possible interactions that can take place between sets of neurons. A human brain, by contrast, contains approximately eighty-six billion neurons.

To progress, we need to learn how to combine the insights of molecular biochemistry, which has come to dominate the lowest reaches of neuroscience, with the study of computation and cognition, which have moved to the forefront of fields such as cognitive psychology. (Though some dream of eliminating psychology from the discussion altogether, no neuroscientist has ever shown that we can understand the mind without psychology and cognitive science.) The key, emphasized in the report, is interdisciplinary work shared as openly as possible: “The most exciting approaches will bridge fields, linking experiment to theory, biology to engineering, tool development to experimental application, human neuroscience to non-human models, and more.”

Perhaps the least compelling aspect of the report is one of its justifications for why we should invest in neuroscience in the first place: “The BRAIN Initiative is likely to have practical economic benefits in the areas of artificial intelligence and ‘smart’ machines.” This seems unrealistic in the short- and perhaps even medium-term: we still know too little about the brain’s logical processes to mine them for intelligent machines. At least for now, advances in artificial intelligence tend to come from computer science (driven by its longstanding interest in practical tools for efficient information processing), and occasionally from psychology and linguistics (for their insights into the dynamics of thought and language). Only rarely do advances come from neuroscience. That may change someday, but it could take decades.

It would have been useful for the report to include more discussion of the Allen Institute for Brain Science, which has its own half-billion-dollar budget for neuroscience, provided by its founder, Paul Allen. Whereas the BRAIN Initiative is still only a proposal, the A.I.B.S. has, for the past decade, been building brain maps and sharing them freely. Because its recent proposal for a series of “brain observatories,” described last year in Nature, presaged Obama’s BRAIN Initiative in many ways, it arguably deserves more comment and analysis. (Full disclosure: I’m speaking at the Institute next week.)

But these are quibbles. There are plenty of reasons to invest in basic neuroscience, even if it takes decades for the field to produce significant advances in artificial intelligence. If the projects outlined in the new report deliver half of what they intend, they will revolutionize both science and medicine by giving us the first clear understanding of the circuits that underlie brain function. With those discoveries, we may see the first major advances in decades in the treatment of mental illnesses and brain injuries. More than that, we stand an excellent chance of gaining a significantly richer understanding of ourselves.

Gary Marcus is a professor of psychology at N.Y.U., the author of “Guitar Zero,” and a co-editor of the forthcoming book “The Future of The Brain: Essays by the World’s Leading Neuroscientists.”

Illustration by Nishant Choksi. 

The nine research areas identified below, in the Executive Summary of the new Interim Report, are the only types of research Thomas Insel and NIMH will fund going forward. I think this is unfortunate.

Below this section, I am including one other section that should be interesting to those working in this field, the vision and philosophy of the BRAIN Initiative.

Advisory Committee to the NIH Director - Interim Report

The BRAIN Initiative: Brain Research through Advancing Innovative Neurotechnologies

September 16, 2013


On April 2, 2013, President Obama launched the BRAIN Initiative to “accelerate the development and application of new technologies that will enable researchers to produce dynamic pictures of the brain that show how individual brain cells and complex neural circuits interact at the speed of thought.” In response to this Grand Challenge, NIH convened a working group of the Advisory Committee to the Director, NIH, to develop a rigorous plan for achieving this scientific vision. To ensure a swift start, the NIH Director asked the group to deliver an interim report identifying high priority research areas that should be considered for the BRAIN Initiative NIH funding in Fiscal Year 2014. These areas of priority are reflected in this report and, ultimately, will be incorporated into the working group’s broader scientific plan detailing a larger vision, timelines and milestones.

The goals voiced in the charge from the President and from the NIH Director are bold and ambitious. The working group agreed that in its initial stages, the best way to enable these goals is to accelerate technology development, as reflected in the name of the BRAIN Initiative: “Brain Research through Advancing Innovative Neurotechnologies.” The focus is not on technology per se, but on the development and use of tools for acquiring fundamental insight about how the nervous system functions in health and disease. In addition, since this initiative is only one part of the NIH’s substantial investment in basic and translational neuroscience, these technologies were evaluated for their potential to accelerate and advance other areas of neuroscience as well.

In analyzing these goals and the current state of neuroscience, the working group identified the analysis of circuits of interacting neurons as being particularly rich in opportunity, with potential for revolutionary advances. Truly understanding a circuit requires identifying and characterizing the component cells, defining their synaptic connections with one another, observing their dynamic patterns of activity in vivo during behavior, and perturbing these patterns to test their significance. It also requires an understanding of the algorithms that govern information processing within a circuit, and between interacting circuits in the brain as a whole. With these considerations in mind, the working group consulted extensively with the scientific community to evaluate challenges and opportunities in the field. Over the past four months, the working group met seven times and held workshops with invited experts to discuss technologies in chemistry and molecular biology; electrophysiology and optics; structural neurobiology; computation, theory, and data analysis; and human neuroscience (a full list of speakers and topics can be found in Appendix A). Workshop discussions addressed the value of appropriate experimental systems, animal and human models, and behavioral analysis. Each workshop included opportunity for public comments, which were valuable for considering the perspectives of patient advocacy groups, physicians, and members of the lay public.

Although we emphasize that this is an interim report, which will develop with much additional advice before June 2014, certain themes have already emerged that should become core principles for the NIH BRAIN Initiative.
  1. Use appropriate experimental system and models. The goal is to understand the human brain, but many methods and ideas will be developed first in animal models. Experiments should take advantage of the unique strengths of diverse animal systems.
  2. Cross boundaries in interdisciplinary collaborations. No single researcher or discovery will crack the brain’s code. The most exciting approaches will bridge fields, linking experiment to theory, biology to engineering, tool development to experimental application, human neuroscience to non-human models, and more, in innovative ways.
  3. Integrate spatial and temporal scales. A unified view of the brain will cross spatial and temporal levels, recognizing that the nervous system consists of interacting molecules, cells, and circuits across the entire body, and important functions can occur in milliseconds, minutes, or take a lifetime.
  4. Establish platforms for sharing data. Public, integrated repositories for datasets and data analysis tools, with an emphasis on user accessibility and central maintenance, would have immense value.
  5. Validate and disseminate technology. New methods should be critically tested through iterative interaction between tool-makers and experimentalists. After validation, mechanisms must be developed to make new tools available to all.
  6. Consider ethical implications of neuroscience research. BRAIN Initiative research may raise important issues about neural enhancement, data privacy, and appropriate use of brain data in law, education and business. Involvement of the President’s Bioethics Commission and neuroethics scholars will be invaluable in promoting serious and sustained consideration of these important issues. BRAIN Initiative research should hew to the highest ethical and legal standards for research with human subjects and with non-human animals under applicable federal and local laws.
The following research areas are identified as high-priority research areas in FY 2014.

#1. Generate a Census of Cell Types. It is within reach to characterize all cell types in the nervous system, and to develop tools to record, mark, and manipulate these precisely defined neurons in vivo. We envision an integrated, systematic census of neuronal and glial cell types, and new genetic and non-genetic tools to deliver genes, proteins, and chemicals to cells of interest. Priority should be given to methods that can be applied to many animal species and even to humans.

#2. Create Structural Maps of the Brain. It is increasingly possible to map connected neurons in local circuits and distributed brain systems, enabling an understanding of the relationship between neuronal structure and function. We envision improved technologies—faster, less expensive, scalable—for anatomic reconstruction of neural circuits at all scales, such as molecular markers for synapses, trans-synaptic tracers for identifying circuit inputs and outputs, and electron microscopy for detailed reconstruction. The effort would begin in animal models, but some mapping techniques may be applied to the human brain, providing for the first time cellular-level information complementary to the Human Connectome Project.

#3. Develop New Large-Scale Network Recording Capabilities. We should seize the challenge of recording dynamic neuronal activity from complete neural networks, over long periods, in all areas of the brain. There are promising opportunities both for improving existing technologies and for developing entirely new technologies for neuronal recording, including methods based on electrodes, optics, molecular genetics, and nanoscience, and encompassing different facets of brain activity, in animals and in some cases in humans.

#4. Develop A Suite of Tools for Circuit Manipulation. By directly activating and inhibiting populations of neurons, neuroscience is progressing from observation to causation, and much more is possible. To enable the immense potential of circuit manipulation, a new generation of tools for optogenetics, pharmacogenetics, and biochemical and electromagnetic modulation should be developed for use in animals and eventually in human patients. Emphasis should be placed on achieving modulation of circuits in patterns that mimic natural activity.

#5. Link Neuronal Activity to Behavior. The clever use of virtual reality, machine learning, and miniaturized recording devices has the potential to dramatically increase our understanding of how neuronal activity underlies cognition and behavior. This path can be enabled by developing technologies to quantify and interpret animal behavior, at high temporal and spatial resolution, reliably, objectively, over long periods of time, under a broad set of conditions, and in combination with concurrent measurement and manipulation of neuronal activity.

#6. Integrate Theory, Modeling, Statistics, and Computation with Experimentation. Rigorous theory, modeling and statistics are advancing our understanding of complex, nonlinear brain functions where human intuition fails. New kinds of data are accruing at increasing rates, mandating new methods of data analysis and interpretation. To enable progress in theory and data analysis, we must foster collaborations between experimentalists and scientists from statistics, physics, mathematics, engineering and computer science.

#7. Delineate Mechanisms Underlying Human Imaging Technologies. We must improve spatial resolution and/or temporal sampling of human brain imaging techniques, and develop a better understanding of cellular mechanisms underlying commonly measured human brain signals (fMRI, Diffusion Weighted Imaging (DWI), EEG, MEG, PET)—for example, by linking fMRI signals to cellular-resolution population activity of neurons and glia contained within the imaged voxel, or by linking DWI connectivity information to axonal anatomy. Understanding these links will permit more effective use of clinical tools for manipulating circuit activity, such as deep brain stimulation and transcranial magnetic stimulation.

#8. Create Mechanisms to Enable Collection of Human Data. Humans who are undergoing diagnostic brain monitoring or receiving neurotechnology for clinical applications provide an extraordinary opportunity for scientific research. This setting enables research on human brain function, the mechanisms of human brain disorders, the effect of therapy, and the value of diagnostics. Meeting this opportunity requires closely integrated research teams including clinicians, engineers, and scientists, all performing according to the highest ethical standards of clinical care and research. New mechanisms are needed to maximize the collection of this priceless information and ensure that it benefits people with brain disorders.

#9. Disseminate Knowledge and Training. Progress would be dramatically accelerated by the rapid dissemination of skills across the community. To enable the broadest possible impact of newly developed methods, and their rigorous application, support should be provided for training—for example, summer courses and course modules in computational neuroscience, statistics, imaging, electrophysiology, and optogenetics—and for educating non-neuroscientists in neuroscience.

Although these FY 2014 research priorities are presented as nine individual recommendations, the overarching vision is to combine these approaches into a single, integrated science of cells, circuits, brain and behavior. For example, there is immense added value if recordings from neuronal populations are conducted in identified cell types whose anatomical connections are established in the same study. Such an experiment is currently an exceptional tour de force; with new technology, it could become routine. In another example, neuronal populations recorded during complex behavior might be immediately retested with circuit manipulation techniques to determine their causal role in generating the behavior. Theory and modeling could be woven into successive stages of ongoing experiments, enabling effective bridges to be built from single cells to connectivity maps, population dynamics, and behavior. Facilitating this vision of integrated, seamless inquiry across levels is the initial goal of the BRAIN Initiative, to be explored and refined before the final report in June 2014.
* * * * *


On April 2, 2013, the White House proposed a major national project to unlock the mysteries of the brain—the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. The President called on scientists to “get a dynamic picture of the brain in action and better understand how we think and how we learn and how we remember.” In response to the President’s call to action, the Director of the National Institutes of Health created this Working Group to “catalyze an interdisciplinary effort of unprecedented scope” to discover the patterns of neural activity and underlying circuit mechanisms that mediate mental and behavioral processes, including perception, memory, learning, planning, emotion, and complex thought:
“By exploring these patterns of activity, both spatially and temporally, and utilizing simpler systems to learn how circuits function, we can generate a more comprehensive understanding of how the brain produces complex thoughts and behaviors. This knowledge will be an essential guide to progress in diagnosing, treating, and potentially curing the neurological diseases and disorders that devastate so many lives.”
— Charge to the NIH BRAIN Working Group, April 2013
This ambitious “American Project”, articulated eloquently by President Obama in a White House announcement, can only be achieved through innovative, multidisciplinary investigation at all levels of nervous system function—behavioral, electrophysiological, anatomical, cellular and molecular. In parallel, advances in theory, computation, and analytics will be essential to understand and manage the large quantities of new data that will soon flow from neuroscience laboratories.

Over the past five months, we have reviewed the state of the field and identified key research opportunities. In this initial report we recommend specific goals to guide the BRAIN Initiative in Fiscal Year 2014. Our final report, to follow in June 2014 will define the vision more sharply, make longer term recommendations, and suggest benchmarks for evaluating progress toward the goals.

The Goal of the BRAIN Initiative

Our charge is to understand the circuits and patterns of neural activity that give rise to mental experience and behavior. To achieve this goal for any circuit requires an integrated view of its component cell types, their local and long-range synaptic connections, their electrical and chemical activity over time, and the functional consequences of that activity at the levels of circuits, the brain, and behavior. Combining these elements is at present immensely difficult even for one circuit, yet we must also weave together the many interlocking circuits in a single brain. As the President said in his White House press conference, this is indeed a “grand challenge for the 21st century.”

As for any field and any era, progress toward these scientific goals is limited, to a large extent, by the experiments that are technically possible. But we are now within a period of rapid—perhaps revolutionary—technological innovation that could vastly accelerate progress toward an integrated understanding of neural circuits and activity. Thus for this interim report, our planning effort embraces a substantial technology emphasis, as reflected in the name of the working group: “Brain Research through Advancing Innovative Neurotechnologies.” Our focus is not on technology per se, but on the development and use of tools for acquiring fundamental insight about how the nervous system functions in health and disease. We have considered how mature technologies can be applied to neuroscience in novel ways, how new technologies of obvious relevance can be rapidly developed and integrated into regular neuroscience practice, and what longer term investments should be made in ‘blue sky’ technologies with higher risk but potentially high payoff. As the BRAIN Initiative progresses, these technologies should increasingly be used to shed light on the healthy brain and on tragic human brain disorders.

Developing these novel technologies will require intense, iterative collaboration between neuroscientists and colleagues in the biological, physical, engineering, mathematical, and statistical and behavioral sciences. Essential partners should come from the private sector as well: corporate expertise in microelectronics, optics, wireless communication, and organization and mining of ‘big data’ sets can radically accelerate the BRAIN Initiative. Finally, clinicians will be essential partners to translate new tools and knowledge into diagnostics and therapies. The new technical and conceptual approaches to be created as part of the BRAIN Initiative will exert maximal impact if accompanied by specific plans for implementation, validation and dissemination to a larger community. Catalyzing the necessary collaborations and delivering reliable tools and resources to neuroscience laboratories should be major, overarching themes of the BRAIN Initiative.

Foundational Concepts: Neural Coding, Neural Circuit Dynamics and Neuromodulation
Neural coding and neural circuit dynamics are conceptual foundations upon which to base a mechanistic understanding of the brain. At the microscopic scale, the brain consists of vast networks of neurons that are wired together with synaptic connections to form neural circuits. In an active brain, each neuron can have electrical and chemical activity that is different from that of its neighbors; thus some neurons can play specialized roles in different tasks. Yet the activity of each neuron also depends on that of the others in the circuit, through the synaptic connections that define the circuit’s architecture. Synaptic connections can change strength as a result of recent activity in the circuit, meaning that circuit architecture is constantly modified by experience. A thinking brain can therefore be viewed as an immensely complex pattern of activity distributed across multiple, ever-changing circuits.

Neural coding refers to how information about the environment, the individual’s needs, motivational states, and previous experience are represented in the electrical and chemical activity of the neurons in the circuit. In a familiar example, the neural code for color vision begins with just three basic detectors in the eye—the cone photoreceptors. Circuits in our brains combine patterns of cone activation with other inputs to discriminate over a million different colors. More sophisticated, and poorly understood, neural codes enable us to recognize instantly the voice of a friend or the dramatic light of a Rembrandt painting. Elucidating the nature of complex neural codes and the logic that underlies them is one goal of the BRAIN Initiative.

As different neurons become silent or active in a thinking brain, the pattern of activity shifts in space and time across different circuits and brain regions. These shifting patterns define what is known as neural circuit dynamics. A key to understanding how the brain works is to determine how the neural dynamics across these vast networks process information relevant to behavior. For example, what is the form of neural dynamics in a circuit that makes a decision? What are the dynamically changing patterns of activity for speaking a sentence or imagining a future action? To probe the mechanics of the brain more deeply, we must learn how the biophysical properties of neurons and the architecture of circuits shape dynamic patterns of neural activity and how these patterns interact with incoming sensory information, memory, and outgoing motor commands. In the same way that the basic electrophysiological properties of single neurons are common across brain areas and species, it is likely that many fundamental forms of neural dynamics will generalize as well. One goal of the BRAIN Initiative is the identification and characterization of universal forms of neural circuit dynamics, likely represented by dynamical motifs such as attractors, sequence generation, oscillation, persistent activity, synchrony-based computation, and others yet to be discovered.

Accompanying this rapid flow of information that drives cognition, perception, and action are slower modulatory influences associated with arousal, emotion, motivation, physiological needs, and circadian states. In some cases, these slower influences are associated with specialized neuromodulatory chemicals like serotonin and neuropeptides, often produced deep in the brain or even in peripheral tissues, that can act locally or globally to change the flow of information across other brain circuits. In effect, neuromodulatory modifications of synaptic efficacy can ‘rewire’ a circuit to produce different dynamic patterns of activity at different points in time. The BRAIN Initiative should strive for a deeper understanding of these powerful but elusive regulators of mood and behavior.

Why Now?

This is a propitious moment for a sustained national effort to unlock the secrets of the brain. The reason lies in the technological and conceptual revolution that is underway in modern neuroscience. New molecular, genetic and cellular tools are generating exquisite insights into the remarkably diverse neuronal cell types that exist within our brains, the basic ‘parts list’ of our neural circuits. Novel anatomical techniques are providing remarkable new opportunities for tracing the interconnections between brain regions and individual neurons, revealing basic brain circuit maps in unprecedented detail. Innovative electrical and optical recording tools are allowing us to measure the intricate patterns of electrical activity that exist within those circuits across a broad array of behaviors ranging from decision-making to memory to sleep. Only a short time ago, we were restricted to studying the brain’s electrical activity one nerve cell at a time; now we can record from hundreds of nerve cells, allowing us to analyze the cooperative activity of nerve cells as they operate in intact circuits; we look toward a future in which we can measure even richer patterns of brain activity, involving millions of nerve cells at any instant. Furthermore, newly invented genetic and chemically based techniques are giving us the power to modify activity in those circuits with great precision, creating extraordinary opportunities for deciphering the information-carrying codes in patterned electrical activity, and in the longer term, creating a foundation for novel therapeutic treatments for disease.

With these increasingly powerful techniques come new data sets of massive size and complexity. Reconstructing neural circuits and their dynamic activity in fine detail will require image analysis at a formidable scale as well as simultaneous activity measurements from thousands of neurons. The age of ‘big data’ for the brain is upon us. Thus, neuroscientists are seeking increasingly close collaborations with experts in computation, statistics and theory in order to mine and understand the secrets embedded in their data. These startling new technologies, many of which did not exist 10 years ago, force us to reconceive what it means to be an experimental neuroscientist today.

The challenge that now faces neuroscience lies in integrating these diverse experimental approaches and scaling them up to the level of circuits and systems. Previously, we could study the brain at very high resolution by examining individual genes, molecules, synapses, and neurons, or we could study large brain areas at low resolution with whole-brain imaging. Continued progress at both of these levels is essential, but our unique new opportunity is to study the critical intermediate level as well—the thousands and millions of neurons that make up a functional circuit. Remarkable new discoveries are possible at this intermediate level, for here we expect to observe the circuits, codes, dynamics, and information processing strategies that enable a collection of nerve cells to generate a complex, organized behavior.

The Brain and Behavior

The purpose of the brain is to generate adaptive behavior—predicting, interpreting, and responding to a complex world. As foreshadowed in the preceding section, some of the most riveting questions in neuroscience revolve around the relationship between neural circuit structure, neural dynamics, and complex behavior. Objectively measureable behavior is an indispensable anchor for the field of neuroscience—it defines the set of phenomena that we ultimately seek to explain. We benefit in this respect from the rich traditions of experimental psychology, psychophysics and neuroethology, but new innovation is needed in the analysis of behavior. Dobzhansky once said that “Nothing in biology makes sense except in the light of evolution,” and it is no exaggeration to say that nothing in neuroscience makes sense except in the light of behavior. Thus a primary theme of the BRAIN Initiative should be to illuminate how the tens of billions of neurons in the central nervous system interact to produce behavior.

In advanced organisms our concept of ‘behavior’ must be extended to include sophisticated internal cognitive processes, in addition to externally observable actions. This point is dramatized by the story of Jean-Dominique Bauby, a French magazine editor who was left in a ‘locked-in’ condition by a brainstem stroke. Bauby was robbed of all voluntary movement except the ability to blink his left eye. Using the one behavior left to him, he wrote The Diving Bell and the Butterfly, an astounding memoir of the rich internal mental life that he continued to experience after his stroke:

“My diving bell becomes less oppressive, and my mind takes flight like a butterfly. There is so much to do. You can wander off into space or in time, set out for Tierra del Fuego or for King Midas’s court. You can visit the woman you love, slide down beside her and stroke her still-sleeping face. You can build castles in Spain, steal the Golden Fleece, discover Atlantis, realize your childhood dreams and adult ambitions.”
Mental life can flourish within the nervous system, even if the behavioral link to the observable world is tenuous. Thus the BRAIN Initiative should focus on internal cognitive processes and mental states in addition to overt behavior. Accordingly, a preferred experimental emphasis should be on whole animals (typically behaving animals) with a secondary emphasis on reduced circuits that maintain important connections and integrative properties.

Measuring internal cognitive processes in animals is challenging, but rigorous methods have been developed to assess perception, memory, attention, decision-making, reward prediction, and many other examples. Although we must be constantly on guard against facile anthropomorphism, the continuity of brain structure and organization across species provides confidence that some cognitive processes analogous to ours are likely to exist in the brains of animals other than humans. Improving the behavioral analysis of these cognitive processes, both in experimental animals and in humans, should be a central goal of the BRAIN Initiative.

Strategies and Experimental Systems

Ultimately, the goal of the Brain Initiative is to understand how the human brain produces cognition and behavior, and specific recommendations of this report involve human neuroscience. However, human brains are complicated and difficult to access experimentally both for ethical and practical reasons. To reach our goal of understanding the human brain, it is therefore vital that we also investigate simpler animal brains as model systems—some with behaviors as comparable as possible to humans, but some with nervous systems that are more experimentally tractable. We cannot satisfy all requirements with a single animal model; a range of experimental systems, from simple to complex, will be needed to make progress. Fortunately, many basic principles of neural organization and function are conserved across animal species, so that progress in understanding simple systems can accelerate understanding of more complex systems.

In both animals and humans, we should enumerate and describe the brain’s component parts—the different types of neurons and glia—and we should map their precise anatomical connections to obtain an accurate circuit diagram. We should measure the dynamic activity of the cells in a circuit under a variety of conditions and across a range of behaviors, and we should manipulate this activity to test causal hypotheses about how circuit activity influences behavior. Finally, we will require computationally powerful ways to analyze and understand the mechanisms by which dynamic patterns of activity in neural circuits give rise to behavior. These individual elements are clear; the challenge is how to accelerate, facilitate and combine them for maximum impact.

Studying the Typical Brain Should Accelerate Understanding of Brain Disorders

While the primary goal of the BRAIN Initiative is an understanding of normal brain function, we expect this work to provide an essential foundation for understanding neurological and psychiatric disorders. The burden of brain disorders is enormous. All of us are touched, directly or indirectly, by the ravages of degenerative diseases like Alzheimer’s and Parkinson’s, thought disorders like schizophrenia, mood and anxiety disorders like depression and post-traumatic stress disorder, and developmental disorders like autism spectrum disorders. Brain disorders limit personal independence and place enormous demands on family and society. The knowledge gained in the BRAIN initiative offers the possibility of reducing this burden.

There is reason to think that many disorders result in part from circuit dysfunction. Epilepsy is best understood as a circuit disease, where instability in neuronal communication leads to uncontrolled excitation and seizures. We currently stabilize patients by treating them chronically with potent drugs, but pinpointing abnormal circuits with new technologies could aid in the prediction of seizures and the development of more precise, localized treatments to stabilize activity. Like epilepsy, mood disorders and thought disorders are episodic, with an unstable waxing and waning of symptoms over days or years. The ability of many affected individuals to function normally at some times, and the absence of massive loss of brain cells, suggests that there may be no immovable obstacle to recovery of stable cognitive or emotional processing -- the circuitry for information flow exists, but it is not always regulated correctly. Unfortunately, there has not been a fundamentally new class of drugs for psychiatric disorders since the 1970s, largely because we understand neither how the circuits work nor how the drugs act on them. There are some clues, however. For example, the drugs we have for depression—most of which affect the neurotransmitters dopamine, serotonin, and norepinephrine—appear to act in part by modulating the flow of information between subcortical and cortical brain areas. A greater understanding of these circuits and their regulation could advance our ability to diagnose and treat thought and mood disorders.

Similarly, a better understanding of brain circuits has the potential to provide new paths to the treatment of neurological disorders. The neurodegenerative disorder Parkinson’s disease is caused by the loss of dopaminergic neurons; like many neurodegenerative disorders, it manifests itself at the level of single cells. Nonetheless, those dopaminergic neurons are circuit elements. Changing the flow of information through the damaged circuits of Parkinson’s disease patients with deep brain stimulation can dramatically improve their motor symptoms, even after most dopaminergic neurons are lost. We anticipate that refined knowledge of motor circuits will make deep brain stimulation more efficacious, and enable its use for other motor disorders. For other neurodegenerative disorders like Alzheimer’s disease and motor neuron diseases, it may also be possible to deliver a therapeutic benefit by mimicking the circuit effect of a permanently lost population of cells. But first those circuit effects must be discovered, and interventional tools for delivering the appropriate circuit-level effect must be designed and built.

We also envision new ways to repair physical damage to the brain. Stroke, traumatic brain injury and spinal cord injury result in the loss of sight or memory, paralysis, or the inability to communicate. By tapping into existing brain circuits with new stimulators and sensors, it may be possible to re-establish damaged brain pathways, or allow control of prosthetic limbs with brain signals. Such implantable devices may sound like science fiction, but they are already in development in a few patients. Their success is limited by our fragmentary understanding of the brain’s codes and instructions; there is great potential for human benefit from knowing more about the brain.

The Deliverables of the BRAIN Initiative

The BRAIN Initiative will deliver transformative scientific tools and methods that should accelerate all of basic neuroscience, translational neuroscience, and direct disease studies, as well as biology beyond neuroscience. It will deliver a foundation of knowledge about the function of the normal brain, its cellular components, the wiring of its circuits, its patterns of electrical activity at local and global scales, the causes and effects of those activity patterns, and the expression of brain activity in behavior. Through the interaction of experiment and theory, the BRAIN Initiative should elucidate the computational logic as well as the specific mechanisms of brain function at different spatial and temporal scales, defining the connections between molecules, neurons, circuits, activity, and behavior.

This new knowledge of the normal brain should form a foundation for more advanced translational research into brain disease mechanisms, diagnoses, and therapies. It should serve our colleagues in medicine, biotechnology, engineering, and the pharmaceutical and medical device industries, providing fundamental knowledge needed to ameliorate the vast human burden of brain disorders.
In addition to accelerating biomedical knowledge and treatment of disease, the BRAIN Initiative is likely to have practical economic benefits in the areas of artificial intelligence and ‘smart’ machines. Our brains can rapidly solve problems in vision, speech and motor coordination that the most powerful supercomputers cannot approach. As we learn more about the principles employed by the brain to solve these problems, new computing devices may be devised based on the cognitive architectures found in brains. Information companies are already investing in brain-inspired algorithms to enhance speech recognition, text search and language translation; the economic value of neurotech industries could someday rival that of biotech.

Finally, we hope through the BRAIN Initiative to also create a culture of neuroscience research that emphasizes worldwide collaboration, open sharing of results and tools, mutual education across disciplines, and the added value that comes from having many minds address the same questions from different angles.

Bringing Embodied Cognition to the Clinical Domain (Giovanni Ottoboni)

In this new paper from Frontiers in Psychology: Cognition, Giovanni Ottoboni advocates for an interdisciplinary approach that would combine embodied cognition with clinical psychotherapy. While his argument is solid and useful, he fails to acknowledge the wide body of literature and approaches already working in that realm.

Peter Levine's Somatic Experiencing (Waking the Tiger: Healing Trauma: The Innate Capacity to Transform Overwhelming Experiences, 1997; and In an Unspoken Voice: How the Body Releases Trauma and Restores Goodness, 2010, among others) and Pat Ogden's Sensorimotor Psychotherapy (Trauma and the Body: A Sensorimotor Approach to Psychotherapy, 2006) are two of the best known and clinically supported models.

Going back even further, there was Wilhelm Reich and his body-centered psychoanalytic approach (Character Analysis, 1933), out of which Alexander Lowen developed his own particular model, called Bioenergetics (Bioenergetics: The Revolutionary Therapy That Uses the Language of the Body to Heal the Problems of the Mind).

Anyway, there is more history to this idea than presented here, but this is still an interesting article.

Grounding clinical and cognitive scientists in an interdisciplinary discussion

Giovanni Ottoboni [1,2]
1. Department of Psychology, University of Bologna, Bologna, Italy
2. Centro di Psicologia e Psicoterapia Funzionale Integrata, Trieste, Italy
In most clinical approaches the body receives little attention. In cognitive science, in contrast, the embodied and grounded perspective, which emphasizes the importance of the body, has been intensively explored over the last decade. The present article aims to engage theorists of embodied cognition and clinical experts in a discussion encouraging them to consider the insights that may arise from each other’s approaches. In a review of the cognitive and clinical literature substantial overlap is revealed between cognitive and clinical domains.

Full Citation: 
Ottoboni G. (2013, Sep 19). Grounding clinical and cognitive scientists in an interdisciplinary discussion. Frontiers in Psychology: Cognition, 4:630. doi: 10.3389/fpsyg.2013.00630
The interpretations academics and professionals offer for psychological disorders are not unanimous. Traditional therapeutic approaches explain that psychological disorders arise from irrational beliefs and illogical thought patterns or from unresolved emotional conflicts (e.g., Zeig, 1997; Sutker and Adams, 2001). Within these perspectives, an even wider range of treatments is offered. Some treatment options are targeted at changing learned behaviors, others are aimed at reshaping old attachment styles, others work on memories arising from relations occurring within the original family system, and others involve medical psychosomatic concepts. Few approaches to clinical treatment, however, are able to provide a comprehensive and integrated theoretical account of all human expressions (Palmer and Woolfe, 2000).

Alongside such views, the connection between the body (and bodily states), cognition and emotion is theoretically accepted (Van Oudenhove and Cuypers, 2010). According to some therapeutic approaches (Totton, 2003), and even in some early works in psychodynamic theory – later studied in depth by other psychoanalysts such as Perrin (2010) – the body plays an important causal role in the development of mental disorders. From a more body-oriented perspective it is argued that the body is included in all processes involved in self-awareness (Segal et al., 2002). Röhricht and colleagues (Röhricht and Priebe, 2006; Röhricht et al., 2013) provide congruent evidence. For example, the authors specifically report on the positive effects of the bodily therapy in two separate groups of schizophrenic and depressed patients. They showed that the negative, depressive symptoms decreased more than in controls. The authors also report that bodily techniques are effective for treatment of mental disorders among patients who do not respond to traditional talking therapies, e.g., somatoform disorders/medically unexplained syndromes, post-traumatic stress disorder (PTSD), anorexia nervosa, and chronic schizophrenia (Röhricht and Priebe, 2006; Röhricht, 2009). Also for medical practice, a number of clinical studies support that bodily therapies have positive impacts in pathological conditions (Moyer et al., 2004; Tsao, 2007).

One of the approaches that is presently attracting the attention of researchers and professionals by claiming a full integration between the bodily and the psychological aspects is the Mindfulness approach. Mindfulness is described as “a process of regulating [clients’] attention in order to bring a quality of non-elaborative awareness to current experience and a quality of relating to one’s experience within an orientation of curiosity, experiential openness, and acceptance” (Bishop et al., 2004, p. 234). In recent years, a number of studies have investigated the both the psychological and the physical modulations that can be achieved when people reach certain states of mindful awareness (Grossman et al., 2004; Michalak et al., 2010). Mindfulness techniques have been used to enhance self-observation from inner and outer perspectives. The mindfulness approach represents a third-wave for many clinical and non-clinical treatments because it prepares people to respond functionally and consciously to their environment (e.g., Boyle, 2011).

In recent years, the connection between what is expressed and conveyed by the body and cognitive, functional and emotional expressions has received renewed interest from a wide range of neuroscientists. Damasio (2005) approached the mind-body link directly by proposing that somatic markers are intimately related to thinking and decision-making. In a similar manner, other scholars have suggested the existence of a gut–brain/brain–gut axes (Mayer, 2011). Gut microbes appear able to transmit information directly to the central nervous system (CNS), communicating many of the changes that occur in the gut. Through this communication pathway, the CNS can identify the presence of pathogens in the gut lumen and activate appropriate response mechanisms. It seems that the level of intestinal microbiota and inflammation markers have a role, as for example, in the depression states (Bested et al., 2013; Rawdin et al., 2013).

From a cognitive perspective, the body–mind coupling has been at the center of scientific discussion in neuroscience for many years. In the middle of the last century, Yarbus (1967) described the importance of the muscular eye movement for vision and visual attention. Similarly, Liberman et al. (1967) proposed that language comprehension is inseparable from language production. More recently, a group of neurons was discovered in the monkey premotor cortex (di Pellegrino et al., 1992). The neurons able to produce electrophysiological spikes that have a similar pattern regardless of whether the monkey is executing an action or observing the same action but performed by the experimenter (i.e., grasping some monkey food). The double-firing property has led to this group of neurons to be termed Mirror Neurons (Gallese et al., 1996). When evidence of a similar system was reported in humans (Mukamel et al., 2010), the connection between body and mind entered centrally in the domain of psychology. The mirror neuron network serves as an automatic and involuntary system that is strengthened by links, such as motor expertise, between the action observer and the action performer (Castiello et al., 2009). Dysfunctions within this reverberating network are also considered to be a basis of empathic deficits associated with autistic spectrum disorder (Williams, 2008). In last years, the human mirror neuron system network has been found to respond to various stimuli, including action words (D’Ausilio et al., 2009) and pain-related stimuli. Avenanti et al. (2005) reported higher levels of activation in the brain area that principally controls hand movements when participants watched a video clip of a needle piercing a person’s hand than when participants watched a neutral video in a control condition. However, in some cases, the mirror neuron network has been used to explain even the mechanisms of empathic and emotional resonance that come into play in therapeutic settings (Berrol, 2006; Gallese et al., 2007; Schermer, 2010), as well as cultural, social, and psychodynamic interactions (Vanderwert et al., 2012).

With the growing evidence for the influence of the body in the control of cognitive processes, a new perspective (e.g., Varela et al., 1991; Borghi and Pecher, 2012), known as Embodied Cognition (EC) has developed. Recently, theorists have argued that mind-body influences are related to bodily states as well as to the physical and bodily experiences people have (Fischer, 2012). Along this vein, Barsalou (2008) suggested that the use of the concept of grounding is preferable to embodiment because the former includes concepts relating to simulation that are able to occur even when the action actor and the action observer do not share the same action motor control. This would be the case if a patient suffering apraxic were to engage in conversation about a pen. The patient would be able to name and describe the pen and provide relevant information about it, such as where it can usually be found, but would not be able to perform actions with the pen, such as write with the pen. In this way, aside from the boundaries of the body, the concept of grounding relies more on the effectiveness with which physical experiences interact with cognitive processes (e.g., Symes et al., 2008; Eder and Hommel, 2013).

Aside from the growing scientific and clinical evidence supporting the grounded body–mind interconnection, what appears missing from both fields is a proper translational process that integrates the scientific and clinical domains. Regarding clinical psychology, the opinions of academics and professionals differ greatly: there are cases in which grounding the therapeutic process in bodily terms using movements, posture, and physiological indexes is neglected or it is used only metaphorically (Sensky et al., 2007). There are examples of professionals who commit to theater, yoga, and dance the bodily healing aspect. Such a process of devolution is necessary when it is not possible to theoretically integrate such aspects into the existing theory (Palmer and Woolfe, 2000). On the other hand, there are health care professionals who are accustomed to working only with the physicality of the body and who find themselves unprepared for dealing with emotional and psychological aspects that arise during treatment.

One relatively new clinical approach that integrates bodily and psychological aspects is the Neo-Functionalism (NF) approach (Rispoli, 2008; Ottoboni and Iacono, 2013). The NF approach was developed from the body-centered perspectives. The involvement of the body within the therapeutic setting has generated two kinds of advantages: it provides the clients with the opportunity to communicate their psychological states directly without limits and it provides the therapist with the opportunity to get deeply in touch with the clients’ emotions and expressions. According to this view, indeed, the body conveys and communicates the individual’s psychological states as it receives feedback from outcomes of physical actions. Body movements and facial expressions, as well as the contextual information have been indicated as influencing psychological states and activities, such as memory, predisposition, and decision-making (Strack et al., 1988; Hatfield et al., 1992; Craig, 2002; Dijkstra et al., 2007) and pain perception (Avenanti et al., 2005).

In the process of clinical evaluation and treatment, NF considers all life experiences people have had according to the experiences’ grounded and embodied aspects. The core concept of the NF approach relies on a discrete group of life instances whose experiences affect cognitive functioning and expressions (Rispoli, 2008; Ottoboni and Iacono, 2013). They are claimed to be universal and are called Basic Experiences of the Self (BEsS) to denote the strict connection between two concepts, the Self and grounded experiences. Indeed, the connection between behaviors (independently of their sane or deviant forms), the neurological background (intact or damaged), the social context (read social experiences) and the development of the Self has recently arisen a number of interesting debates within the scientific community (see, for example, Blanke and Metzinger, 2009; Brugger et al., 2013; Reed and McIntosh, 2013).

The way individuals experience each Basic Experience of the Self (BES) produces cognitive, emotional, physiological, and postural-related outcomes. Each time the same BES is experienced the individual stores a memory of the outcomes of the experience, matches them with past experiences and uses them to create expectations for the future (see Logan, 2002; see also Mancia, 2006 for a psychodynamic perspective). If the BES is experienced positively, memories are formed and are made available later for dealing with novel situations. In contrast, if the response to the BES is maladaptive, it may generate a sense of inability to deal with novel situations (Rispoli, 2008; Ottoboni and Iacono, 2013). Each BES may be experienced several times during the lifespan. The averaged mode in which each BES is experienced determines the manner in which memories of the BES are stored. The account that only the repeated outcomes of the same BES can modulate the behavior highlights that such a grounding process of memory development is not a point-to-point process; it required time either to form the maladaptive responses or to develop positive responses. Hence, if a large number of BEsS are experienced negatively, the individual’s responses to environmental demands will be poor because of a low level of resilience (Rothschild, 2000); indeed, the higher the functioning, the more adaptive the responses.

The NF interpretation of the word functioning is the same that grounding theory provides: each bodily expression (i.e., function) comprehends cognitive, emotional, postural, and physiological features (see also Hatfield et al., 1992). In line with this view, a depressed demeanor expresses a number of cognitive, physiological, and emotional features as well as bodily postures that must all be taken into account during therapeutic treatment (e.g., Michalak et al., 2009). By considering human expression as complex in nature, the NF therapist is able to find the most appropriate manner for interacting with the client. If one manner of expression is inappropriate, another manner may be pursued, and, as suggested by Röhricht (2009) in referring to body-centered techniques, unexpected results can be achieved. Let us consider, for example, a person suffering ruminations. The patient may be very careful and skilled at identifying appropriate verbal responses to the therapist’s requests. In such cases the therapeutic process could be made difficult. A way to achieve treatment results in such cases would be for the therapist to use the physical channel. The therapist must thus work on the client’s body (Ottoboni and Iacono, 2013) with calm and wide hand-on massages. Indeed, the focus of this therapeutic technique would be to calm the patient’s thoughts and let the therapeutic process to begin.

The healing outcomes are achieved by helping the client to re-experience the BEsS that were not positively experienced in the past. The process is intensive because, by using a grounding approach, the therapists tend to re-create the same physical and emotional conditions the patient experienced when the trauma begun. Mental thoughts, verbal expressions and body-related experiences are used in a combined fashion. The clients could, for example, be asked to lie down on the ground as they did in childhood, to wander in the room and express their feeling during the walk, or to vocalize with pre-verbal utterances the psychophysical sensations that therapeutic hand-on messages have made emerge. To repeat, these techniques are mainly used to make the patients emotionally regress to the specific moment of their past, because, in this way, the client may discharge the old memories and form new ones from the experience just-lived (Rispoli, 2008; Ottoboni and Iacono, 2013).

The change in the patient that the NF therapist aims to achieve concerns the attempt to reconstruct the harmonious organization of the Self as it was in the womb. Even if such a concept could be criticized for not accounting for the gestational period, the fetus could potentially experience problems and disease, premonitory of future functioning. I personally consider that the harmonious state indicates a general and natural state toward which everybody is inclined to experience. Using a Mindfulness concept, it could be claimed that such a harmonious state is the state of acceptance of internal and external changes (Grossman et al., 2004). This state involves a calm and relaxed state of mind.


A growing number of studies have shown that human cognition, emotions, and behaviors have embodied features, or as Barsalou (2008) has preferred to describe, grounded features.

However, this knowledge still remains in the research domain and is rarely applied in clinical practice. An attempt to translate grounded evidence in clinical practice has been introduced in a recent paper. Bedford (2012) theorizes that the visual component of perception can cure a number of medical symptoms by affecting the immune system. Vision, however, is controlled and modulated (Rizzolatti et al., 1994) by the motor system, as in the case of visual awareness studies demonstrating that the motor plan moderates perceptions of plan-congruent objects (Symes et al., 2008), or the reaching of a target in absence of visual awareness (Binsted et al., 2007). Interestingly, the visual information concerning the body is integrated and combined in several areas in the brain with information coming from the other senses too (see Blanke, 2012 for a review). As soon as the visually based information, mainly defining a map-like representation of body (e.g., Tessari et al., 2010), are integrated with kinesthetic and vestibular information, a body-based sense of self takes place (Blanke and Metzinger, 2009).

In sum, it appears that the approaches that effectively integrate cognitive and motor aspects of human behavior are few in number. One such approach is the NF approach (Rispoli, 2008; Ottoboni and Iacono, 2013). By working simultaneously on imagery-related techniques, verbal and bodily techniques (such as hand-on massages or body movements), the NF approach accounts for all aspects of human expression from a grounded perspective. During treatment, past experiences, which generate actual psychological states, are recalled and experienced again physically within a clinical setting.

However, the grounded assumptions, as well as the grounded techniques, must be tested thoroughly. As this review demonstrates, embodied cognition and grounded clinical approaches are still far from integrated with each other. Research exploring the effects of grounded therapeutic approaches should be a priority for scientists interested in understanding human behavior and its therapeutic treatments.

Scientific evidence suggests that embodied cognition could be very useful for achieving such an aim. Equally, studies dealing with embodied cognition could take advantage of what is known in clinical settings.

Conflict of Interest Statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The author would like to thank Valerie Womble, Jonathan Rolison, and Anna Borghi for the critical discussion during the various stages of this manuscript. The author would also like to acknowledge the EU FP7 project ROSSI (No. 216125) for the initial economic support provided for personal assistance to the author.

References are available at the Frontiers site.

Among Its Many Benefits, Resveratrol May Inhibit Rheumatoid Arthritis

In this new study, the researchers looked at the ability of resveratrol to suppress T cell activity, which may seem like a bad thing since T cells are a powerful part of the immune system. However, when T cells are activated in large quantities, there is a corresponding increase in cytokines, a large group of cell messengers and cell regulators that includes several involved in immune response, including the inflammatory response.

In this study, the use of the term cytokine refers to immunomodulating agents, such as interleukins (specifically: IL-2, IL-4, IL-5) and interferons (IFNy). They found that resveratrol (through a series of processes) increases the expression of Sirt1, and the activation of Sirt1 decreases the expression of various immunomodulating chemicals, which reduces inflammation. Additionally, when Sirt1 is inhibited, cells become less responsive to insulin, so it likely plays a role in the development of diabetes.

There is a potential downside to this, as well. It's possible that for some people whose immune systems are compromised there would a greater vulnerability to disease with the down-regulation of T cells and immune system agents.

The wider implication of this study is that resveratrol may be a useful treatment to prevent diabetes and possibly, as well, to treat autoimmune disorders, such as rheumatoid arthritis or lupus.

I'm just posting the abstract, but you can read the whole article at the link in the title.

Resveratrol Inhibits CD4+ T Cell Activation by Enhancing the Expression and Activity of Sirt1

Ting Zou, Yi Yang, Fei Xia, Anfei Huang, Xiaoming Gao, Deyu Fang, Sidong Xiong, Jinping Zhang


Resveratrol, a natural polyphenol compound, has broad effects on critical events, including inflammation, oxidation, cancer and aging. However, the function and molecular mechanisms of resveratrol on T cell activation are controversial. In the present study, we found that resveratrol significantly inhibits the activation and cytokine production of T cells in vitro and in vivo. Sirt1 expression was up-regulated in resveratrol-treated T cells. Once Sirt1 was down-regulated in the T cells, the resveratrol-induced inhibition of T cell activation noticeably diminished. The acetylation of c-Jun decreased and its translocation was impeded in the resveratrol-treated T cells. The incidence and severity of collagen-induced arthritis in the resveratrol-treated mice were considerably reduced.
Full Citation: 
Zou T, Yang Y, Xia F, Huang A, Gao X, et al. (2013, Sep 20). Resveratrol Inhibits CD4+ T Cell Activation by Enhancing the Expression and Activity of Sirt1. PLoS ONE, 8(9): e75139. doi:10.1371/journal.pone.0075139

Friday, September 20, 2013

Targeted Brain Stimulation Provokes Feelings of Bliss

I wonder how long it's going to take for the first implant based on this discovery to hit the FDA approval cycle? I'm sure people would line up to have a little implant (in their anterior-dorsal insula) that would allow them to press a button and experience instant bliss - like really good ecstasy without the hangover. It's the magic pill everyone has been searching for.

This article comes from Christian Jarrett at the BPS Research Digest.

Targeted brain stimulation provokes feelings of bliss

Posted by Christian Jarrett | BPS Research Digest

It's hard to fathom how our subjective lives can be rooted in the spongy flesh of brain matter. Yet the reality of the brain-mind link was made stark half way through the last century by the Canadian neurosurgeon Wilder Penfield. Before conducting neurosurgery on epilepsy patients he stimulated parts of their brains directly with an electrode, triggering in them subjective sensations that varied according to the source of stimulation.

In a new case study, a team of Swiss and French neurologists followed a similar strategy during brain surgery with a 23-year-old female patient. She has temporal lobe epilepsy and experiences "ecstatic auras" before seizure onset. During these periods she has "intense feelings of bliss and well-being", a floating sensation in her stomach, enhanced senses and time appears to contract.

Fabienne Picard and his colleagues stimulated different parts of the woman's temporal lobes with electrodes to try to find the precise source of her epileptic seizures. In fact none of their stimulations caused her to have a seizure. However they did observe some intriguing subjective experiences in the woman. When they stimulated her anterior-dorsal insula - a brain region implicated in many functions, including representing the internal state of the body - she experienced the same feelings of bliss and ecstasy that she reports prior to a seizure. "I feel really well with a very pleasant funny sensation of floating and a sweet shiver in my arms," she said. Such sensations were not triggered by stimulation in any other part of her temporal lobe.

Prior research has shown that stimulation of other brain regions, including the amygdala and other parts of the insula, can evoke pleasant memories and pleasant sensory experiences, but the researchers said theirs is the first ever account of neurostimulation leading to feelings of bliss or ecstasy. It complements brain imaging research that has found correlations between anterior insula activity and feelings of intense love and joy, and also oneness with God.

It's important not to be lulled into thinking this case study has helped identify the brain's "pleasure centre". Many parts of the brain are involved in motivation and hedonic experience. Stimulation of the nucleus accumbens, part of the brain's so-called "reward pathway", is being explored as a treatment for depression (although it has not been linked with the sensations of bliss reported here). Research also shows that rats will press a lever for hundreds of hours so as to receive stimulation of the nucleus accumbens, but it's thought this stimulation may trigger wanting and craving rather than pleasure per se. Activity in orbitofrontal cortex (at the front and bottom of the brain) has been associated with enjoyment of food and other sensory pleasures.

With that caveat aside, this case study makes a useful contribution. "Our findings, if reproduced in future studies, should aid in the understanding of the brain mechanisms causing feelings of happiness/bliss, whether they are elicited externally (for example, by highly positive emotional stimuli) or internally (for example, by religious or deep meditative states, or by seizures)," the researchers said.

Picard, F, Scavarda, D. and Bartolomei, F. (2013, Sep 3). Induction of a sense of bliss by electrical stimulation of the anterior insula. Cortex, online first. DOI: 10.1016/j.cortex.2013.08.013

Post written by Christian Jarrett (@psych_writer) for the BPS Research Digest.

Shrink Rap Radio #369 – A Biopsychological Model to Guide Psychotherapy with Robert Moss

This is an interesting podcast from Shrink Rap Radio. Robert Moss developed a model he calls clinical biopsychology, explained in his 2001 book, Clinical Biopsychology in Theory and Practice, that offers treatment for mood disorders and relationship issues. Moss offers several papers at his site that can be read online or downloaded (see below).

Shrink Rap Radio #369 – A Biopsychological Model to Guide Psychotherapy with Robert Moss

Posted on September 19, 2013
Robert A. Moss

Robert A. Moss, Ph.D., ABN, ABPP, is a clinical psychologist who works with Bon Secours St. Francis Hospital in Greenville, SC. While teaching neuropsychology in 1984 he developed a theory that the cortical column is the binary unit (bit) involved in all cortical processing and memory storage. Based on this theory, the Clinical Biopsychological approach to therapy was developed and continued to guide his work while in full-time private practice for over 20 years. As of 2006 the neuroscience field provided sufficient evidence to make the brain model publishable in a refereed journal, with a detailed description of its application to psychotherapy being published this year. One aspect of treatment, Emotional Restructuring, is a single session approach to address influential relationship negative emotional memories. Bob is board certified in clinical psychology and neuropsychology and is a former associate professor in clinical psychology. He has authored 43 professional articles and has presented at a number of professional meetings.
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A psychiatric podcast by David Van Nuys, Ph.D.
copyright 2013: David Van Nuys, Ph.D.

Online papers from Robert Moss: