From Molecules to Minds Challenges for the 21st Century: Workshop Summary (2008) / Chapter Skim
Currently Skimming:
Workshop Summary
Workshop Summary
Pages 1-30
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 1... ...
Forum on Neuroscience and Nervous System Disorders titled, "From Molecules to Mind: Challenges for the 21st Century." Their goals were significant: Each participant was asked to identify one or two "Grand Challenges" that could galvanize both the scientific community and the public around the possibilities for neuroscience in the 21st century. This idea of identifying Grand Challenges has a strong history in science.
|
From page 2... ...
Exploring that potential set of common goals, or Grand Challenges, was one of the major goals of the workshop. What Can We Achieve For a Grand Challenges exercise to work, it must ask questions that are both big and answerable.
|
From page 3... ...
The goals of a forum, and this workshop, are not to provide specific recommendations or arrive at consensus conclusions; rather, a forum seeks to highlight important issues and articulate the challenges facing a particular scientific field. Organized by an independently appointed planning committee, the workshop was organized so that representatives of all corners of the neuroscience world could provide updates on the latest advances in the field, and then discuss how they related to the concept of Grand Challenges.
|
From page 4... ...
Leshner and Olsen concluded the workshop by synthesizing the day's discussions into three overarching Grand Challenges that emerged during the workshop, which will be used to organize this workshop summary: • How does the brain work and produce mental activity? How does physical activity in the brain give rise to thought, emotion, and behavior?
|
From page 5... ...
, on the Grand Challenges list of the National Academy of Engineering (NRC, 2008) , and on the wish lists of at least a halfdozen major scientific fields, from genetics to computer science.
|
From page 6... ...
The classic approach, in place since the 1960s, has been simple: Define behaviors, identify neurons involved in those behaviors, determine the connectivity between those neurons, and then excite individual neurons to understand their role in influencing behavior. This approach is called "circuit dynamics," and it has been tremendously helpful to understanding how these simple neurological systems work.
|
From page 7... ...
The Golgi method works quite well, but comes with two major flaws that limit its use in studying complex connections among neurons in a single network. The first flaw is that the method stains everything the same color -- grey -- making it very difficult to study multiple neurons at once or to envision how different neurons link together.
|
From page 8... ...
As an added bonus, researchers attached this protein to a gene that glows when exposed to green light, allowing them to both identify and control individual neurons. Therefore, under green light researchers can view the neurons that make the protein, and by switching the light beam to blue, they can excite a neuron and investigate its effects.
|
From page 9... ...
"Brain functions are encoded in a distributed network in the brain," said Bin He, professor of biomedical engineering, electrical engineering, and neuroscience, University of Minnesota, so it is important to image brain connectivity and network dynamics not only beyond localized circuits, but throughout the entire network. Functional Magnetic Resonance Imaging Functional Magnetic Resonance Imaging (fMRI)
|
From page 10... ...
This is where computer science comes in. One example of using computational methods to link neural activity to psychological states was provided by Tom Mitchell, chair of the Machine Learning Department at Carnegie Mellon University, who described how, through the use of machine learning methods, a person's neural activity and reactions to words or pictures can be decoded via fMRI.
|
From page 11... ...
William Bialek, a professor at the Joseph Henry Laboratories of Physics and the Lewis-Sigler Institute of Integrative Genomics, Princeton University, described this series of spikes at the workshop as "the language in which the nervous system does its business." "Although much of the history of neuroscience is about understanding the responses of individual neurons," said Bialek, "in fact, almost all of our experiences are based on the activity of many, many neurons."
|
From page 12... ...
John Hopfield proposed just such a model of neural networks in 1982, and the model has been supported by the research in many ways. Bialek explained, for instance, that these networks have a tendency to fall into different "states," or general patterns of electrical spikes, which are more consistent than the individual firing of single neurons.
|
From page 13... ...
There was widespread support in the room for the importance of mapping the physical circuitry of the brain, but there was also a feeling that a physical map alone would not be sufficient to explain how it actually works. There were suggestions to focus on neural networks and the language of electrical activity in the brain, as well as efforts to drive agnostic data crunching to search for patterns that we cannot even imagine.
|
From page 14... ...
As summarized below in greater detail, many workshop participants -- including Hyman, Marder, and Michael Greenberg, chair of the Department of Neurobiology at Harvard Medical School -- chose to highlight the nature versus nurture question as one of the Grand Challenges of the field, but in so doing, they put a twist on the question, asking: How does the interplay of biology and experience shape our brains and make us who we are? The key word there is "interplay." "Interplay" suggests, and modern research in neuroscience demands, that there is a back and forth pattern between nature and nurture, a dynamic system that involves a continuous feedback loop shaping the physical structure of our brains.
|
From page 15... ...
All this seems to point the finger toward experience, but of course, the system really works as a complete feedback loop. "We used to think .
|
From page 16... ...
One intriguing study has shown that temporal-difference learning algorithms, which enable robots successfully to learn control strategies such as how to fly helicopters autonomously, can be used to predict the neural activity of dopamine-based systems in the human brain that are involved in reward-based learning (Schultz et al., 1997; Seymour et al., 2004; Doya, 2008)
|
From page 17... ...
Huge Clinical Importance Multiple participants at the workshop -- including Nora Volkow, director of the National Institute on Drug Abuse; Joseph Takahashi, investigator of the Howard Hughes Medical Institute and Northwestern University; Lichtman; and Coyle -- highlighted the role of genetics in shaping the brain as one of the fundamental challenges for neuroscience, both for its basic scientific interest and for its practical applications: Understanding how genes and experience come together to impact the brain could significantly alter how we think about treating neurological disease. Many of the most common neurological and mental health disorders -- schizophrenia, bipolar disorder, autism, Parkinson's disease, multiple sclerosis, Alzheimer's disease -- are complex genetic disorders that are influenced by environmental factors.
|
From page 18... ...
These mice, which have obvious cognitive deficits, regain mental function when treated; Silva has advanced the study into human clinical trials. The applications of this vein of study extend beyond developmental disorders.
|
From page 19... ...
" are phenomenally interesting, and have many practical corollaries. But workshop participants, including Timothy Coetzee, executive director of Fast Forward of the National Multiple Sclerosis Society, also recognized that their research aims to have an immediate impact on easing the suffering of those facing neurological disease.
|
From page 20... ...
Starting at Square One For many neurological disorders, we are really at square one in understanding how a particular disease works, and what avenues we should explore for treatment, let alone having a better understanding of what life style adjustments could be made to avoid or minimize the onset of agingrelated complications. Many participants, including Greenberg and Steven Dekosky, chair of the Department of Neurology at the University of Pittsburgh, expressed a desire for a better core understanding of the physical morphology of neurological disease, as well as the physical morphology of aging.
|
From page 21... ...
Greenberg explained research showing how parts of the genome are involved in the process of synapse development, synaptic pruning, and the balance between exciting and inhibiting individual synapses. Another emerging idea is that it is not just a genetic mutation that knocks out function, but subtle mutations that affect the level of expression of the genes and greatly impact disease and normal function.
|
From page 22... ...
This is the core charge of neuroscientists, and drives many of the Grand Challenges identified during the workshop.
|
From page 23... ...
that this field will move even faster and further than it has in the last 10 years, if that is possible." CHALLENGES AND TECHNICAL LIMITATIONS Many barriers that have impeded researchers from addressing the questions highlighted in the Grand Challenges workshop have disappeared over recent years, remarked Leshner. Advances in imaging technology, new techniques such as those similar to the Brainbow, and neuronal "light switches" have laid the groundwork for researchers to explore the brain as never before.
|
From page 24... ...
As mentioned earlier, one of neuroscience's great strengths is also its greatest weakness: It is not a single "science" at all, but an interdisciplinary field drawing on biology, chemistry, computer science, genetics, and others. "It is a very large continuum .
|
From page 25... ...
This likely will require an agreement on a common unit of analysis, which is the most reduced unit for the cognitive and most complex for the molecular neuroscience approaches. Montague, Hyman, and others argued for the need for more concrete and quantitative definitions of behavior-understanding behavior derived from an agnostic approach to the problem, rather than one driven by our preconceived ideas about how the brain functions." New Technological Requirements Despite tremendous advances in the past few years, many workshop participants highlighted the need for additional technical advances to drive the field forward.
|
From page 26... ...
Understanding how the brain works -- really understanding, on a core physiological level -- would have tremendous benefits for society. But it would also raise significant moral, ethical, and practical considerations, which neuroscience must address carefully as it moves forward.
|
From page 27... ...
The overarching point was that neuroscience stands on the cusp of huge advances, and those huge achievements raise major issues that the field has never considered before. "The time is really now to start thinking about what that means and how we want to .
|
From page 28... ...
The progress of the past in combination with new tools and techniques has positioned neuroscience on the cusp of even greater transformational progress in our understanding of the brain and how its activities result in mental activity. On the Cusp Neuroscience is on the cusp of exciting breakthroughs that take advantage of the convergence of scientific knowledge and technologies, like Brainbows, neuronal light switches, and computer learning technologies have made it possible to answer questions such as the following: • How does the brain work and produce mental activity?
|
From page 29... ...
. -- Eve Marder
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.