Doctoral Dissertation

My dissertation, entitled “Comparative topological analysis of neuronal arbors via sequence representation and alignment”, is focused on applying bioinformatic approaches to neuronal morphology to enable new discoveries and increase understanding about how morphology and neuron function interrelate.

Alignment and cluster analysis of neuronal tree sequences

Alignment of neurons represented as sequences of branching points can be used to detect clusters of similar neurons which can then be investigated for their stereotypical branching patterns. We use a modified sequence alignment procedure to produce pairwise similarity values between two neuronal sequences and then, after embedding the neurites (axons, dendrites, or apical dendrites) into a consistent abstract space, we found clusters in the space. By overlaying those clusters with known cell classes we found significant associations. There were strong associations by cell type, brain region, and species, indicating that neuronal branching patterns are indicative of neuronal type and function.

Recycle your plastic gift and credit cards

Between gifts cards, credit cards, and old health insurance cards, I’ve got a far bit of plastic in my drawer. It finally dawned on me to just look it up online, and lo and behold, someone is recycling them. Earthworks System, LLC takes the cards, grinds them up, and then creates new PVC sheets (that’s what they’re made of) so new cards can be made.

Send your cards to

Earthworks System, LLC
33200 Bainbridge Road, Suite E
Solon, OH 44139

Based on “Can I recycle plastic gift cards?” at Mother Nature Network.

 

Fed whistleblower and regulatory capture (Story in BoingBoing)

The story: Fed whistleblower secretly recorded 46 hours of regulatory capture inside Goldman Sachs

From the piece:

The Fed had vowed to reform this culture, and Segarra was supposed to be part of that mission. But once she reported for work at the Fed department at Goldman Sachs (Fed regulators actually work at desks inside the banks they’re regulating), she discovered a culture rotten with cowardice and capture, where her boss’s idea of a really stern rebuke for lying in official filings was to mildly mention that there appeared to be some irregularities in the compliance regime, then trailing off ineffectually.

We know this because of the recordings, which were edited into a documentary by This American Life that aired yesterday. It’s an absolutely riveting and essential hour of audio (MP3), and the accompanying package by Pro Publica is likewise essential reading.

Congress and/or President Obama could do something about this, not overnight, but given some prioritization. The problem of course is that they are bought as well. Some folks need to go to jail, but in any case we need electoral reform so that we can actually have a government willing to take on this sort of corruption.

IBM’s TrueNorth – The first neuromorphic chip

IBM has recently released details of a neuromorphic chip named TrueNorth via their website, the press, and a research report in the journal Science. The research team, headed by Dharmendra Modha as part of the DARPA SyNAPSE Program, developed a chip containing a million “programmable spiking neurons” and 256 million synapses. The chips use 5.4 billion transistors on 4096 “neurosynaptic cores” which each has its memory (in the form of connection routing and timing delays) close to its “neuronal” processing units.

The United States is an Oligarchy

A group at Princeton recently completed a study (to be published this Fall of 2014) that shows pretty definitively that over the 80’s and 90’s (the period studied), the United States government has represented wealthy interests and ignored the broader public interest.

The study is entitled Testing Theories of American Politics: Elites, Interest Groups, and Average Citizens (see original pdf preprint), and it looks at the correlations between policy preferences of particular groups and policy outcomes. The authors looked at preferences of wealthy citizens, average citizens, wealthy/commercial organizations, and public organizations without a commercial interest. While often it appears that the federal government is acting on behalf of the people, the data and analysis strongly suggest that is only because of how often the preferences of the average citizen aligns with the preferences of the wealthy interests.

This story was covered by multiple sources back in April. Here’s an article at the BBC. It was also covered by The Young Turks, an online news network that has spent a large amount of time on the issue of corruption and money in politics:

How does a cat land on its feet?

A perfect example of science and fun! Ever wonder how a cat is able to flip over so quickly and ensure it lands on its feet? Some super slow-motion capture and some careful handling of cats (none harmed in the making of the video) provides a look:

Wolf PAC Petition Calling for a Constitutional Amendment

We have a problem of corruption here in the United States (see other posts in this section) with multiple causes and manifestations. Money in politics is one major driver, which over our history has led to greater concentration of power which has in turn made money in politics an even bigger problem. Two-party politics, public apathy, and gerrymandering all play a role as well. Many groups are attempting to address it. Several organizations are taking on the problem, including the Mayday PAC (led by Lawrence Lessig), Public Citizen, Move to Amend, Represent.Us, and Wolf PAC, among others. The following is a brief overview connecting the dots to a call for an Article V convention (made possible by the US Constitution).

Particularly in Congress/at the federal level, money has massively corrupted our government such that just about every issue you might care about is dominated by not just special interests, but moneyed corporate interests. Representatives spend more than half their time raising money rather than dealing with the issues (whether that be spending time with other reps, studying the issues, or hearing from constituents). While an increase in voter participation would be a huge help, the money will continue to flow and …

Mining Tree Patterns Poster

PDF of Poster

Neuronal morphology plays a major role in the electrophysiological and connectivity characteristics of neurons, and thus in neuron and network function.

Various morphometrics have been applied in studying neurons; however, the structural patterns of the tree-like dendrites and axons have yet to be fully explored. These patterns may reflect strategies that achieve functional properties such as dendritic compartmentalization, space filling, and targeting of various spatial distributions of synapses.

To address these issues we analyzed thousands of neurons, made available via NeuroMorpho.Org, in terms of structural patterns by representing their arbors (axons, dendrites, apical dendrites) as gene-like sequences. We compared neurons by arborization type within and between cell classes using sequence analysis techniques. Sequence domains can be used in conjunction with functional studies to further elucidate the structure-function relationship.

Neuronal Morphology Background

Morphology is the study of the physical shape of things for the purposes of understanding the processes involved in forming an object and/or the purpose/function of the object. We know that neurons are involved in converting environmental stimuli into electrochemical signals, processing that information, producing consciousness, and enabling behavior. Through studies of morphology, often in conjunction with electrophysiology, gene and protein expression, and other properties of neurons, neuroscientists have learned much about what specifically neurons do and how their various individual functions contribute to more emergent phenomena vital to brain function. The first chapter of my dissertation (and the book chapter “Measuring and Modeling Morphology: How Dendrites Take Shape“, of Springer textbook Computational Systems Neurobiology) discusses many of the relationships between morphology, function, and other neuronal properties, along with the major approaches (old and new) used in making the discoveries.

After discussing the relevance of morphology in neuroscience, the chapter begins with an description of morphological metrics and the relationships between morphological and electrophysiological features. An review of molecular pathways involved in neuronal development and plasticity follows. Having provided the context of molecular pathways and electrophysiological function, the chapter describes a diverse set of studies using simulations at various levels of …

Stem cells used to treat a brain disease

While this latest research is a proof of concept, it’s a pretty impressive and important one. Scientists started out putting stem cells into mouse brains that were genetically modified to produce less myelin, essentially an electrical insulator of neuronal connections, and thus have various cognitive and motor deficits (abstract). Similar problems plague people through various demyelination diseases of the central nervous system (CNS), like multiple sclerosis, or of the peripheral nervous system (PNS), like Guillain-Barré syndrome. New cell growth was detected in the mouse brains, with a great proportion of the new cells being oligodendrocytes which are the cells responsible for covering neuronal connections with myelin (in the CNS). Substantial additional myelination was also observed with no clear negative effects.

Following these results the scientists ran a case study (abstract) on 4 boys with the genetic disorder Pelizaeus-Merzbacher disease which produces defective oligodendrocytes. The scientists injected stems cells, along with immunosuppression drugs, into the boys and saw substantial improvement in myelination near the implantation sites with no apparent adverse effects. Future studies will involve more patients and hopefully will lead to treatments of a number of highly debilitating diseases.

For another review …

“The China Study” by T. Colin Campbell and Thomas M. Campbell II

Full Title: “The China Study: The Most Comprehensive Study of Nutrition Ever Conducted And the Startling Implications for Diet, Weight Loss, And Long-term Health”
First published in September 2001

While this book has had its critics, and while I am not fully convinced by every single one of Campbell’s arguments, the scientific knowledge presented and the perspectives on diet, nutrition, and the interaction with agribusiness, science, and government make for a compelling and worthwhile read. Moreover, while criticism on specific points may be valid, Campbell is open and honest about the fact that some of the evidence is only suggestive, but his argument is that when all of it (the strong, weak, and in between evidence) is brought together the clear conclusion is that a whole-foods, plant-based diet is the way to be healthy physically and mentally throughout life. This is a somewhat more strict and specific formulation of Michael Pollan’s “Eat food. Not too much. Mostly plants.” One major difference though is that Campbell suggests that you can actually eat plenty as long as it is healthy, as studies have shown that vegetarians generally consume more calories but are healthier (with regards to a host of particular diseases discussed in the …

PHD Comics: The Neurobiology of Writing

For a good laugh, or perhaps a sigh of recognition and resignation, see Jorge Cham’s take on the writing process of (I assume) a student.

Does this fit with your experience?

Literally see a fish brain in action!

For those not already familiar with the Janelia Farm Research Campus of the Howard Hughes Medical Institute, if you follow great and exciting advances in neuroscience you will hear about work out of them frequently. Nikita Vladimirov (first author) and colleagues, including Jeremy Freeman and Misha Ahrens, just published a methods paper in Nature Methods describing a method for viewing functional activity of individual neurons in the whole brain of a “fictively” behaving zebrafish. Zebrafish are transparent and scientists have mapped their genome, making them a particularly valuable model organism. This new method, which involves a sort of virtual reality (moving light bars simulating movement) for the fish, along with expression of a calcium indicator which fluoresces when the neuron is active, was used to produce a very cool video:

One of the big challenges here was to avoid any of the scanning light that causes the signaling molecule to fluoresce from hitting the fish’s retina. Their solution was to scan simultaneously with two beams from different directions and along different planes, cutting off the beams when they would otherwise hit the retina and disrupt behavior.

Check out another take on this work over at

Preview of “Automata”

When one ponders the possibilities of the future of robotics and “artificial” intelligence (perhaps more properly “synthetic intelligence” once we’ve actually got it figured out), one usually looks to hard science fiction books. Isaac Asimov in particular comes to mind.

A few movies have done an ok job, including the interesting but also very flawed “I, Robot” with Will Smith and Bridget Moynahan, and Terminator: Salvation…. Both were at least decent movies, but neither felt particularly realistic and both tried to pull on our emotions in fairly obvious ways that felt anything but organic… more

Publications


Gillette TA, Ascoli GA (2015) Topological characterization of neuronal arbor morphology via sequence representation: I – Motif analysis. BMC Bioinformatics, 16.
Summary | PDF

Gillette TA, Hosseini P, Ascoli GA (2015) Topological characterization of neuronal arbor morphology via sequence representation: II – Global alignmentBMC Bioinformatics, 16.
Summary | PDF

Polavaram S, Gillette TA, Parekh R, Ascoli GA (2014) Statistical analysis and data mining of digital reconstructions of dendritic morphologies. Frontiers in Neuroanatomy, 8:138.

Gillette TA, Brown KM, Ascoli GA (2011) The DIADEM Metric: Comparing multiple reconstructions of the same neuronNeuroinformatics, 9:233-45.
Summary

Gillette TA, Brown KM, Svoboda K, Liu Y, Ascoli GA (2011) DIADEMchallenge.Org: A compendium of resources fostering the contiuous development of automated neuronal reconstruction. Neuroinformatics, 9:2-3.

Gillette TA, Ascoli GA. Measuring and Modeling Morphology: How Dendrites Take Shape. In Le Novere N. (Ed.), “Computational Systems Neurobiology”, pp. 387-428, Springer (2012).
Summary

Theodore C Dumas, Todd A Gillette, Deveroux Ferguson et al. (2010) Anti-glucocorticoid gene therapy reverses the impairing effects of elevated corticosterone on spatial memory, hippocampal neuronal excitability, …

Neurotechnology Panel at Potomac Policy Institute

A SEMINAR ON “NEUROTECHNOLOGY: ENHANCING THE HUMAN BRAIN AND RESHAPING SOCIETY”

From the Potomac Institute for Policy Studies:

The Potomac Institute for Policy Studies held a seminar on “Neurotechnology: Enhancing the Human Brain and Reshaping Society” on June 30th, 2014. Neuro-enhancements can maximize our physical, cognitive, innovative, and technological potential as a society. The panelists in attendance included Dr. Amy Kruse (Vice President, Intific), Dr. Jonathan D. Moreno (Professor, University of Pennsylvania), Dr. Gerry Yonas (Mind Research Network, University of New Mexico), and Congressman Chaka Fattah (D-PA). The panelists drew from their experience in industry, government, and academia to discuss current neuro-enhancements, the future of the field, and policy solutions. The speakers emphasized the further enhancement and development of neurotechnology with the support from both the private and public sector.

View the entire summary of the event. Video recordings of the talks and panel discussion are available as well.

Spurious Correlations

There are many tricks one can do with statistics to make an argument, and true to the old saying many statistical reports are lies of one sort or another (more so in the political arena than in the scientific arena, but statistic are often tricky to understand so the problem is universal). However there is another sort of “lie” that we all need to be aware of, and that is the lie of the spurious correlation. Tyler Vigen has created a humorous but insightful website dedicated to this phenomenon.

We often say “correlation is not causation”, but sometimes two things can be correlated and have exactly nothing to do with one another. This can give rise to superstition, or, as Tyler points out in his video at the bottom, it can be an opportunity to act as scientists and consider whether or not there is a reasonable chance that a causal mechanisms exists for the correlation.

Radio Lab did a show related to these ideas called “Stochasticity”, addressing the phenomenon of amazing coincidences and whether they really are as amazing as they seem and what the chances really are. After all, it is the seemingly amazing events which …

Cleaning Up a Broken Compact Fluorescent Lightbulb (CFL)

Twice in one week to people I know? Yep, it’s time for a PSA. No need to freak out, but that powdery stuff in compact fluorescent light bulbs IS hazardous (it contains mercury).

Here’s the EPA’s how-to: http://www2.epa.gov/cfl/cleaning-broken-cfl

(originally shared via Google+ on May 21, 2014)

“Dance of the Photons” by Anton Zeilinger

Full Title: “Dance of the Photons: From Einstein to Quantum Teleportation”

This book was substantially enlightening and yet amazingly frustrating at the same time. Zeilinger begins simply enough with the standard story of Alice and Bob (the physicists’ personification of observer A and B), but he turns them into curious undergraduates. They are the medium through which the reader discovers the quantum world after being given an experimental opportunity by their physics professor and his postdoctoral student. The ground is covered and recovered, sometimes providing useful insight and other times being overly pedantic and annoying. Some parts are so dumbed down it may seem insulting, and this also makes the story take a long time to get through. On the plus side you learn quite a bit about polarization, Bell’s inequality, and a number of other quantum topics.

A bit over half way through the book Zeilinger transitions away from Alice and Bob and toward even more recent experiments with quantum teleportation. Here still many parts are well explained and without too many rereads you should have a fair conception of what is going on. Unfortunately some claims are completely opaque and claims are made with no basis. That is not to …

“Reamde” by Neal Stephenson

“Reamde” is a story centering on the inventor of an immensely popular and successful massively multiplayer online role playing game (MMORPG), his niece, and a slew of other associated characters dealing with a variety of threads including in-world MMORPG dynamics and sociology, international (primarily American and Chinese) real and virtual-world financial and criminal activities, terrorism, and a clever computer virus that ties (almost) all of them together. This book has quite a lot going on and does not head in any one clear direction.

Of Neal Stephenson’s works I have read Snow Crash, The Diamond Age, and Cryptonomicon. I would not recommend each of these books to everyone, but I would recommend all of them to most. Each had very interesting ideas wrapped in a generally compelling plot. Reamde contains some compelling ideas, but at a bit over 1000 pages it would have communicated those ideas and the plot much more satisfactorily in half the words. It is a shame too, because there were a few characters I came to like and a lot of what happened both in the first quarter and in the last quarter made for a great read. In fact I’d love to see a movie made …

“Survivor’s Quest” (Star Wars) by Timothy Zahn

Survivor’s Quest is a story in the Star Wars universe focused on an expedition by a combination of parties including the Empire (what remains of it), the New Republic (represented by Luke Skywalker and his wife and fellow jedi Mara Jade), and other alien cultures with their own territorial and historical reasons to be involved. The target of the expedition is a lost exploration and colony ship sent off in the days of the old Republic (with Anakin Skywalker and Obi-wan Kenobi initially present) meant to travel outside of the galaxy. The following includes some very minor spoilers.

Zahn is always a great writer, but some of his characters and plots don’t always live up to expectations. I have never found that to be the case when he is writing in the Star Wars universe. He takes characters old and new and breathes life into them. Here he focuses more on Mara Jade than in past stories, but nonetheless gives us the perspective of a number of characters, including Luke Skywalker, and several members of the new imperial 501st (also known as Empire of the Hand). The mystery and suspense is wonderful, even more so given the backdrop of Outbound Flight. …

“On Intelligence” by Jeff Hawkins

This book is surprisingly good in its ability to reach both the lay reader (for at least the first half) and the reader familiar with neuroscience. Articles since its publications provide much greater detail and are very useful for those interested in going deeper, but On Intelligence serves very well as an introduction to the concepts. The ideas expressed in On Intelligence are important both for scientific advancement and for philosophical consideration. While one could argue that perhaps there are other forms of intelligence or ways to produce intelligence, Hawkins does a good job in arguing what intelligence is in terms of mammalian brains and what the basic neocortical unit does. While Hawkins brings these ideas together in an orderly framework, he does give credit to the many neuroscientists responsible for the various components and underlying ideas that make it possible. These ideas as a whole until recently have not been sufficiently discussed in the neuroscience community in my opinion, and I believe they will aid (and in fact already have aided) greatly in advancing our understanding of the brain and creating real “artificial” intelligence that isn’t actually artificial at all.

The balance between addressing the expert and lay audiences did at …

Analyzing Neuronal Morphology with Gene Sequencing Approaches

Analysis of neuronal morphology has until recently been limited to small data sets due to the amount of time necessary to generate a digitized representation of a neuron’s structure.

Recent efforts to curate data from many different labs working in parallel on vastly differing topics has led to the NeuroMorpho.Org database which currently provides access and metadata for over 10,000 neurons from a variety of species, cell types, brain regions, and experimental conditions.

Quantitative Measuring of Neuronal Reconstructions – The DIADEM Metric

Summary: This post summarizes some recent efforts in the fields of neuroscience and computer vision to improve neuronal reconstructions, particularly the DIADEM metric, a measure used to evaluate reconstructions produced by algorithms.

Citations:

Gillette TA, Brown KM, Ascoli GA. The DIADEM Metric: Comparing multiple reconstructions of the same neuron. Neuroinformatics, 9:233-245 (2011).

Gillette TA, Brown KM, Svoboda K, Liu Y, Ascoli GA. DIADEMchallenge.Org: A Compendium of Resources Fostering the Continuous Development of Automated Neuronal Reconstruction. Neuroinformatics, 9:303–304 (2011).

Almost all fields, particularly in biology, are greatly benefited by having a large data set. Morphological reconstructions of neurons obviously benefit the study of neuronal morphology, but also the related fields of neuron growth, neuron function with regards to drug and/or dysfunction, connectomics, among many others. Until recently reconstructions were generated and analyzed for a particular study, occasionally being reused when another lab requested it or for a follow-up study. NeuroMorpho.Org helped to change this by bringing together reconstructions from labs around the world doing a variety of experiments. Now will over 10,000 reconstructions there are many questions that can be asked that could not be before so many were brought together.

Nonetheless, 10,000 is not so many when one considers the vast diversity of …

Presentation of Integrated Information Theory at Mind Guild July 8, 2014

The monthly Mind Guild will meet again Tuesday July 8th in the Conference Room (222) of the Krasnow Institute for Advanced Study. In the next several meetings the Guild will attempt to cover several of the current approaches to understanding consciousness and dealing with the “hard problem” as described by philosopher David Chalmers. Chalmers’ own views will be covered in a later meeting, however the upcoming meeting will focus on two perspectives on Integrated Information Theory (IIT).

Initially proposed by Giulio Tononi of the University of Wisconsin, IIT has reached its 3rd iteration. The core underlying idea is that subjective experience is intrinsic to information, and that consciousness experience can be defined as the irreducible integrated information of a network. Physicist Max Tegmark took expanded upon the idea to explore IIT with regards to physical systems generally in the paper “Consciousness as a State of Matter” (see a video of Tegmark lecturing about his recent paper). In the meeting this concepts will be explained and explored in greater detail.

Previous topics covered in the Mind Guild have included philosopher John Searle’s views, the thalamocortical loop theory …

SfN Neuroscience 2014- Annual Meeting Washington, DC Nov.16-20

Society for Neuroscience’s annual meeting is being held in Washington DC this year. SfN is an unmatched venue for sharing great science. Attendees can take advantage of countless opportunities to share and learn about emerging and unpublished findings, explore career paths and professional development opportunities, and discuss hot topics in scientific publishing, academia, advocacy, public education, and more.

‘Mental Floss’ Project Brings Artists and Scientists Together

Mason faculty and students create an interpretive 3-D sculpture called “Mental Floss.” The sculpture depicts 13 different neurons that are located in the hippocampus, the region of the brain responsible for processing autobiographical memories.

“Our goal for this project was to provoke viewers to ponder not only how intricate and complex the inner fabric of the brain appears, but also how beautiful and awe-inspiring it can be, providing a bridge between rational thought and emotions,” says Ascoli.

Anti-glucocorticoid Gene Therapy Reverses the Impairing Effects of Elevated Corticosterone

Full Title: Anti-glucocorticoid gene therapy reverses the impairing effects of elevated corticosterone on spatial memory, hippocampal neuronal excitability, and synaptic plasticity

Abstract:

Moderate release of the major stress hormones, glucocorticoids (GCs), improves hippocampal function and memory. In contrast, excessive or prolonged elevations produce impairments. Enzymatic degradation and reformation of GCs help to maintain optimal levels within target tissues, including the brain. We hypothesized that expressing a GC-degrading enzyme in hippocampal neurons would attenuate the negative impact of an excessive elevation in GC levels on synaptic physiology and spatial memory. We tested this by expressing 11-beta-hydroxysteroid dehydrogenase (type II) in dentate gyrus granule cells during a 3 d GC treatment followed by examination of synaptic responses in hippocampal slices or spatial performance in the Morris water maze. In adrenalectomized rats with basal GC replacement, additional GC treatments for 3 d reduced synaptic strength and promoted the expression of long-term depression at medial perforant path synapses, increased granule cell and CA1 pyramidal cell excitability, and impaired spatial reference memory (without influencing learning). Expression of 11-beta-hydroxysteroid dehydrogenase (type II), mostly in mature dentate gyrus granule cells, reversed the effects of high GC levels on granule cell and pyramidal cell excitability, perforant path synaptic plasticity, …

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