Elinor Ostrum

This year’s co-winner of the Nobel Economics Prize, Elinor Ostrum works on a topic familiar to many Institute social complexity scientists: the tragedy of the commons. While this is a fascinating issue from the standpoint of human social behavior, I wonder to what extent our brain’s own cognitive resources (taken as a whole) are subject to something similar as we shift our attention from one thing to another. Isn’t cognitive overload essentially a tragedy of the neural commons? And is the entire cognitive attentional machinery a means of trying to avoid tragedy of the neural commons?

I keep thinking back to the terrible fix that the pilots of Air France Flight 447 must have been in as they entered an area of extreme thunderstorm activity with multiple system failure warnings, degrading of the jet’s fly-by-wire system into a “safe” mode, and whatever else cropped up in the deadly minutes before disaster. The cockpit is potentially always a place for tragedy of the neural commons.

Poker and the brain

The Chronicle Review has an interesting article on Poker viewed through a kind of De Toqueville lens as integral the character of Americans. When I was in growing up in Pasadena as a Caltech faculty-brat Poker was a very important part of my socialization. My high school buddies and I played it with the intensity that I think some people ascribe more to chess–and we certainly weren’t playing for high stakes.

I’m wondering if Poker has yet made it to the fMRI literature? It would be interesting to visualize the neurobiological substrate of “folding”.
Loyal readers care to point me in the right direction?
Jim

Pharmacogenetics of response to treatment following traumatic brain injury.

Editor’s Note:
The below is a guest blog entry from Robert Lipsky who is joining the faculty of the Institute for Advanced Study while concurrently maintaining his current position as Director of Neurocience Research at Inova Fairfax Hospital. As readers know, I routinely ask new scientific staff at the Institute to talk a bit about their work…..

Background. Anxiety and mood disorders frequently occur following traumatic brain injury (TBI) and may influence cognitive and behavioral recovery. TBI involves both diffuse brain injury as well as frequent focal injuries to frontal and temporal structures, including the hippocampus and amygdala, areas that are associated with the neurobiology of anxiety. While there are anecdotal reports of response to selective serotonin reuptake inhibitors (SSRIs) in treating anxiety associated with TBI, no controlled trials have been conducted to establish SRSI efficacy in patients with anxiety following brain injury.

My major findings. I have been a co-principal investigator on two projects related to this proposed study: 1. An ancillary genetic study with a clinical effectiveness trial, Sequenced Treatment Alternatives to Relieve Depression (STAR*D), collected DNA from outpatients with non-psychotic major depressive disorder who received citalopram in the first treatment step in the trial. Participants were scored for treatment outcome and side effects. 2. An exploratory genetic study of individuals referred to the Walter Reed Army Medical Center and other collaborating military hospitals underwent a comprehensive TBI evaluation and were genotyped for polymorphisms in candidate genes involved in serotonin, dopamine, and glutamate neurotransmitter pathways. Comparison of mean differences among the genotype groups for several executive functioning measures was conducted. In the STAR*D study, a large population of patients with major depression (n = 4,000) treated with citalopram, we discovered and replicated an association of a reduction-of-function HTTLPR alleles to impaired SSRI treatment response. Furthermore, we found that side effects and treatment tolerability mediated this effect. We also identified a marker in the HTR2A serotonin receptor and a second marker in a glutamate receptor gene, GRIK4, that each predicted citalopram response in the same large patient cohort. In the TBI study, we determined that the e4 allele of the APOE gene (involved in neuronal plastic responses) predicted poorer memory performance while a variant of the naturally occurring Val158Met polymorphism of the catechol-O-methyltranseferase gene (COMT) gene, the Met 158 allele, which encodes an enzyme with reduced activity in metabolizing dopamine and norepinephrine, was associated with better performance on cognitive tests, supporting the idea that COMT Val158Met has a role in executive functioning, especially related to cognitive flexibility.

My aims and future plans. A goal of this study is to identify genetic components of behaviors following TBI. For example, decreased serotonin metabolism has been strongly implicated in controlling different behaviors in humans such as anxiety-related intolerance and impaired impulse control. In addition, because TBI results in the uncontrolled release of neurotransmitters, including glutamate and dopamine, both of these neurotransmitters are neurotoxic at high concentrations. Delineating the molecular mechanism of neurotoxicity acting through glutamate receptors (NMDA, NR1, NR2A-D; AMPA, GluR1-4) and dopamine receptors (D2) may provide sites of pharmacological intervention in protecting neurons from excitotoxic cell death. Envisioned is a randomized placebo controlled clinical trial of TBI patients treated with citalopram (estimated at 200 participants). Participants will be rated for improvement at weeks 3, 6, and 9 for possible dosage adjustment. Candidate genes and markers will be selected based on prior genetic linkage/association findings or neurobiological evidence from animal studies.

Relevance. The study is appropriate because a better understanding of the influence of genetic variation in response to treatment may aide in improving treatment regimens. It is likely that the future of patient care may rely on individualized therapies, where pre-treatment genotyping will be an essential part in the decision-making process to provide appropriate care and management of TBI patients.

Understanding cities with agents

Dear Jim,

Thanks for inviting me to write a guest entry on your blog about my research interests and background. It is actually quite strange writing on someone else’s blog rather than my own. Since starting at the Department of Computational Social Science in August, I have been overwhelmed with how friendly and supportive everyone has been.

Prior to arriving at GMU, I spent several years at the Centre for Advanced Spatial Analysis (CASA) at University College London, both as a PhD student and as a research fellow. My PhD was carried out under the supervision of Professors Mike Batty and Paul Longley and sponsored by the Greater London Authority (GLA) Economics unit. It focused on integrating geographical information systems (GIS) and agent-based models thus providing the ability to link agents to actual ‘real’ world places and explored general questions about residential location and spatial interaction. Specifically how agents locate and interact with their surrounding environment, along with how competition for land results in distinct spatial patterns emerging. This has subsequently led me to develop my research interests in agent-based modeling (ABM) of cities.

Cities are extremely important as they provide habitats for over half of the world’s population and this percentage is expected to increase further in future decades. This increase will cause many problems such as sprawl, congestion and segregation; along with environmental effects associated with land use and land cover change. However, understanding such systems is extremely complex because of the many different factors and activities that are seen within cities all of which operate at different temporal and spatial scales. As Professor Sir Alan Wilson writes, understanding cities represents “one of the major scientific challenges of our time.”

I believe that a greater understanding of cities can be gained through the use of agent-based models: from the split second decisions involving local movements such as people walking, to the development of land over months and years, the migration of peoples over decades, to the rise and fall of cultures and civilizations over eons. These processes all that have at their core people (in some shape or form), thus understanding the reasoning on which individual decisions are made may therefore help us better understand the effects of such growth. However, there are several challenges which need to be addressed ranging from validation of such models to the communication of models. More recently I have been exploring how one can take advantage of advances in digital data, 3D modeling environments and virtual worlds such as Second Life for the creation and outreach of agent-based models.

http://vimeo.com/moogaloop.swf?clip_id=4429002&server=vimeo.com&show_title=0&show_byline=1&show_portrait=0&color=00ADEF&fullscreen=1

These broad research interests have been the foundation of the graduate course that I am currently teaching this semester entitled “Agent-based Modeling of Urban Systems” which explores many aspects of urban systems from the micro-movement of pedestrians to residential dynamics. Next semester I will be teaching two classes. The first is “Spatial Agent-Based Models of Human-Environment Interactions” which explores how one can link socio economic and environmental models, along with GIS to study topics in areas such as agriculture, forestry, human/non human populations. The second course “Land-Use Modeling Techniques and Applications” focuses on a variety of land-use change models including cellular automata and agent-based models, along with exploring the drivers of change.

I am finding it great to be among a group of faculty, staff and students who are interested and extremely knowledgeable about ABM from a variety of backgrounds and I am looking forward to developing further links with people at GMU in the future.

Sincerely,

Andrew Crooks

Geo-engineering response to Climate Change: the opposition

Over at Science Progress, a very well written skeptical response by Joronen and Oksanen to those who are advocating large-scale geo-engineering as a response to climate change. Even if it’s a Plan B. My problem with the skeptics is this: given the high stakes, it seems better to have a Plan B than not. I have yet to hear of an alternative Plan B for run-away global warming.

Perhaps loyal readers can better inform me?

Jim

Francis Collins: somewhere between Varmus and Zerhouni

From today’s New York Times profile of new NIH director Francis Collins:

Dr. Collins’s predecessor, Dr. Elias A. Zerhouni, drove a silver Mercedes sports car to work and wore expensive suits, and those choices — along with a natural reserve and the unpopularity of President George W. Bush, who appointed him — meant he was never entirely embraced by the thousands of rumpled scientists who make up the core of the health institutes’ staff.

That he was a brilliant scientist and had highly developed organizational skills never won him plaudits outside of the agency’s top leaders, many of whom praised Dr. Zerhouni effusively.

By contrast, Dr. Zerhouni’s predecessor, Dr. Harold Varmus, rode a bicycle to work, wore khakis and was beloved.

With his high-end motorcycle, Dr. Collins seems to be splitting the difference between his predecessors. But he is distinctly in Dr. Varmus’s camp on clothing, and he has promised to be far more open than either. He has held town-hall-style meetings with staff members, reporters and outsiders. And neither of his predecessors was given to meeting reporters at the nearby greasy spoon

Cox Lab Moves to Krasnow Institute

Dear Jim,



Many thanks for the opportunity to contribute to your blog. My research group and I are very excited to be moving our laboratory from the Prince William Campus to the beautiful new facilities at the Krasnow Institute for Advanced Study this Fall. Prior to joining the Department of Molecular and Microbiology at George Mason in Fall 2004, I completed my PhD in the laboratory of Dr. Haifan Lin at Duke University where my research focused on the molecular mechanisms governing stem cell regulation. I next went on to complete postdoctoral training as a Jane Coffin Childs Fellow in the laboratory of Dr. Yuh-Nung Jan at UCSF where my research focused on investigating the molecular and regulatory mechanisms governing class-specific dendrite morphogenesis.



Presently, my research laboratory is focused on a number of key areas of inquiry including the mechanisms by which the size, shape and complexity of dendritic arbors is achieved and subsequently regulated, how the boundaries of neuronal receptive fields are specified and refined, how dendrites function in mediating recognition between synaptic partners, and how dendritic fields are established, maintained and remodeled during development.



To investigate these questions, we use Drosophila genetics to dissect the molecular mechanisms mediating class specific dendrite morphogenesis. The Drosophila peripheral nervous system (PNS) serves as a molecular, genetic, morphological and physiological model system in which to investigate these processes. Specifically, our group is focused on the roles of transcriptional, cytoskeletal, cell surface receptor, and RNAi (siRNA/miRNA) regulatory mechanisms governing class-specific dendrite morphogenesis as they relate to dendritic field specification and dendritic tiling. We have also recently published a paper describing novel methods for the isolation and transcriptional expression profiling of class-specific neurons as a tool to investigate these processes.



Apart from my research program, I am currently the Graduate Program Director for the Biosciences PhD and M.S. Biology degree programs at Mason and am delighted to take on the role as Director for the new Confocal Imaging Core of the Krasnow Institute (C.I.C.K.I.).



I am particularly anxious to establish new collaborations with other Krasnow Investigators in the areas of high-resolution cellular imaging and neuroinformatics and look forward to interacting with all the faculty, students, and staff in the Neuroscience program.



Sincerely,



Dan Cox

Hard times for California

These are very hard times for my native state, but this Guardian piece (hat tip Slate) sees better times ahead. I hope so.

I do think that the troubles can be traced back to when the (in)famous Proposition 13 was passed. The first of several financially consequential initiatives (a result of California’s constitutional affection for direct democratic decision making), it lead to the State becoming overly dependent upon economic growth for the delivery of basic services.

Curating

So I wasn’t aware that as an institute director (and according the the NY Times), I’m a curator of scientists–but apparently I am. Here’s hoping that I have good taste in science.

Money quote:

The word “curate,” lofty and once rarely spoken outside exhibition corridors or British parishes, has become a fashionable code word among the aesthetically minded, who seem to paste it onto any activity that involves culling and selecting.