Peter B Littlewood - US grants

The three-day workshop "Physical, Engineering and Biological Limits to Brain Measurements" hosted by the University of Chicago on May 29-31, 2014 will bring together researchers from physics, computational science, biology, and network theory to discuss the foundations of brain science and recent methodological developments in the field. The meeting is inspired in part by ongoing discussions surrounding the BRAIN initiative about the development of new technologies and tools that will help us understand how the brain works and make transformative progress in engineering and medicine. An important part of the discussion will be how to substantially improve the spatial and temporal resolution, miniaturization, numbers of probes or actuators, etc. in brain related experiments. One of the questions that will be discussed is the fundamental limits set by physics (e.g. electrical, optical and wireless methods cannot violate Maxwell's equations), engineering and material science, and from biology (e.g. one cannot over-heat the brain by dissipating too much power). The meeting will bring together practicing experts to have a systematic discussion about these limits, resulting in a written document that can be broadly disseminated to help different parties in understanding the issues, to delineate possible/impossible boundaries and to point to areas requiring further research. This is a small, focused meeting with approximately 30 participants, with a single session attended by the whole group over the meeting period. The meeting will constitute sequential discussions of the different frequency ranges of the Maxwell's equation (EEG/MEG at low frequencies, MRI, wired/wireless, optical, and x-ray), with additional segments on electron microscopy, on a general framework spanning the frequency ranges, and statistics/inverse problems. Young scientists will have the opportunity to interact with the senior investigators in the field.

TECHNICAL
While computational modelling can transform the way we understand, and ultimately design and manufacture materials, such methods have not yet become pervasive. Modelling of materials requires a diversity of methods, each tailored according to the problem, and ranging from atomistic methods requiring "chemical accuracy" (i.e. sub kT per atom), through approximate quantum methods, MD, mesoscale and continuum. Handshaking across scales is necessary so that, for example, atomistic calculations quantitatively inform methods at the mesoscale. Experimental and computational data are needed to validate codes, to data-mine for high throughput property prediction, and for top-down model discovery.

There are international efforts in all these areas, and there are already many collaborations in particular topical areas. However, there are opportunities for larger partnerships that support methods development, validation and verification, training, data management, as well as other areas, which will benefit from bringing together distinct strengths in the EU and US.

The workshop will address three application areas with different needs in simulation tools, often determined by the length- and time-scales of the relevant science. Energy Materials and Critical materials often require quantum methods at the nanoscale; Soft and Bio-Materials require atomistic, molecular, or coarse-grained dynamics; and Structural Materials often focusses from mesoscale through the continuum.

NON TECHNICAL
The US-EU Materials Theory and Computation Workshop will explore and report on potential areas of collaboration between the EU and US scientific communities on topics relevant to the US Materials Genome Initiative (MGI). Advancing the MGI vision by decreasing the time to market of important materials discoveries and technologies would be an economic benefit to the US, EU and world.

The success of the BRAIN initiative will depend on widespread access to the technological advancements, computational tools, and data sets created by the initiative. However, there are no existing mechanisms for providing national access to the increasingly technologically and computationally oriented investigations of the brain. The barriers to entry are both financial and structural: not only is technologically intensive neuroscience costly, it requires an investment in physics, engineering and computer science beyond the scope of individual laboratories. This prevents the community's efficient utilization of current technological capabilities and limits the questions and hypotheses that will drive the next generation of innovation. Thus there is a need to counteract the widening gap between the small fraction of laboratories developing and utilizing the most recent technology and the remaining majority of neuroscientists. The successful removal of the gap will require a sophisticated national clearing house to ensure that the correct physics, engineering, and computer science tools are vetted and freely accessible for measurements of brain structure and functions. Successful accomplishment of these goals will require an iterative process whereby specific needs of the neuroscience community will be identified and either paired with the appropriate scientific, technological and computational resources or pipelined for potential future innovation. The model for the operation of this project will be a user facility, housed at Argonne National Laboratory (ANL), and leveraging the existing resources of their science facilities. This award provides funding for seed grants for infrastructure development, conferences, education, and outreach.

The team will enlist the Physics of Living Systems community, most specifically the young scientists therein, to join the neuroscience research effort by connecting to the graduate research network led by the NSF Physics Frontier Center for Theoretical Biological Physics. In order to engage and train a broad community, several annual conferences will be held that will cover a broad range of topics in imaging and quantitative neuroscience. The team will augment the program run by the UC Neuroscience Institute to teach Neuroscience to local 7th/4th graders. Almost all of the students in the target schools are African American and live in the local South Side community. ANL will partner with this endeavor by support through its own educational programs, but for the first time broaching the technology of neuroscience.

Emerging technologies to map whole brains at the synaptic level will soon produce complete maps of neural anatomy, but activity is only indirectly related to circuits, leaving large gaps in how we use anatomical maps to infer activity. Before facing the exabyte scales of whole brains, it is necessary to develop methods to infer activity from anatomy in smaller, simpler, but still complete model systems. Neural cell cultures (in vitro) are highly simplified systems that show complex dynamical activity, can be monitored in terms of spatial activity, and can have parameters tuned by chemistry. Critically, cultures are small, complete networks where every physical connection can be mapped and activity monitored at the single cell level. Thus, interpretations on how the physical wiring and activity in neural networks are correlated will not be confounded by artifacts or limitations encountered by other experimental methods that utilize living animals or brain tissue (e.g. living brain slices have thousands of severed connections.).

As well as a substrate on which to develop methods later to be applied to whole brains, neural cell cultures are of interest as model systems in their own right. In a separate development far from neuroscience, research on 'active matter' - the interactions of autonomous agents - has suggested new principles about how quiescent states become active, and potentially synchronize. This project aims to bring together the novel theoretical perspective with simplified but biologically relevant experiments, using the latest tools of cell culture, neural recording, and connectomics. The goal of the project is to produce an explicit physical model where the three key elements of neuronal systems are joined up: functional recording from a 2D neural cell network; connectivity measurement through serial electron microscopy; explicit theoretical modelling of the dynamics of the neural system. The fundamental question is: Can one infer activity from anatomy?

This research focuses on dynamical transitions between neural states, including synchrony. Epilepsy is a disease of synchrony and one of the co-investigators has his principal research activity in clinical investigations of pediatric epilepsy. There is little fundamental understanding about the (temporal) transition to seizure and we hope that understanding in a model system a (parameter driven) transition could be useful. Model systems are important in biology and physics. We hope that establishing a framework to analyze neural cell cultures will help normalize investigations which would otherwise be disconnected. The PIs will work with the electron microscopy program at Chicago State, a historically minority serving university. CSU students will be engaged in data analysis both as a component of their training in microscopy techniques and as full partners in the research.

The PIs specifically ask: What does it mean to have a balanced network that can spontaneously fire without complete synchrony? Can one control the transitions from one generic dynamical phase to another? Is there emergent spatial and temporal scaling at such a transition? Are there qualitative differences between networks with long- and short-range correlations? This work is intended to build a framework that can be applied in the future to the growing number of published connectomic datasets derived from different brain regions and other ex vivo experimental platforms such as living brain slices/organoids and inform the analysis of large scale connectomics in whole brains.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.