Author: Donald Doherty

  • Sex Matters But the Brain is Like Nothing Else

    My longtime friend and mentor Dr. Karl Pribram has often said to me that anything may be found in the brain. It seems that whatever the current trend is – hydraulics or computers, chaos theory or graph theory – some structure or function in the brain supports the idea in some way. It’s only a matter of time when quantum and/or optical hybrid computing machines are common and a larger audience will understand and perhaps embrace Karl’s holonomic hypothesis.

    Figure 1. The construction of a cortical anatomical network by diffusion tensor imaging. See text below for more information. From “Sex- and Brain Size–Related Small-World Structural Cortical Networks in Young Adults: A DTI Tractography Study“. By Chaogan Yan, Gaolang Gong, Jinhui Wang, Deyi Wang, Dongqiang Liu, Chaozhe Zhu, Zhang J. Chen, Alan Evans, Yufeng Zang and Yong He. Cerebral Cortex Volume 21, Number 2, February 2011.

    A currently popular topic is graph theory, which is certainly dear to my heart as core to Semantic Web technologies and forms the mathematical foundation of many other networking technologies and analyses. Naturally, graph theory is currently being used while investigating many different things including the central nervous system.

    The authors of the new paper “Sex- and Brain Size–Related Small-World Structural Cortical Networks in Young Adults: A DTI Tractography Study” (published February 2011 in Cerebral Cortex) hypothesized that there are sex and brain size related differences in the patterns of anatomical connectivity in the human brain. To test their hypothesis, the research team used diffusion tensor imaging (DTI) techniques on 72 healthy young human adults to construct interregional connectivity for each participant and calculate topological parameters using graph-theoretical approaches. They then investigated the association of interregional connectivity and topological parameters with sex and brain size.

    The research team derived the cerebral cortical network connectivity of each individual using a multi-stepped process, which is outlined visually in Figure 1 above. The structural image of a brain was first transformed into what is called diffusion tensor imaging native space (a). Next the image was segmented into grey matter, white matter, and cerebrospinal fluid (b; left image). The automated anatomical labeling template (b; right image) was applied to an individual’s segmented diffusion tensor imaging native space brain image (c). In parallel, each individual’s white matter fibers were reconstructed in the whole brain by using diffusion tensor imaging deterministic tractography (d).

    The result is a brain mapped into 39 cerebral cortical regions within each hemisphere and associated with a connection matrix weighted according to the number of fibers connecting the regions. At bottom (e) left is a connection matrix color coded for the fiber density between each pair of regions. At bottom middle and right are views of the brain showing connections as graphs with nodes placed at the center of mass for each of the 39 brain regions per hemisphere. Edge thicknesses are coded according to the number of fibers connecting the regions.

    Consistent with previous studies, the research team found that women’s brains were significantly smaller than those of men. The team found that the difference in brain size between males and females remained after correcting for height. Unfortunately, they didn’t report if the difference remains significant after correcting for overall body mass. Also consistent with previous research results is their finding that the anatomical networks of the human brain have “small-world network” characteristics with relatively greater local interconnectivity and an emphasis on the shorter connections between regions.

    This study goes beyond earlier studies by showing that females have greater local clustering in cortical anatomical networks as compared with males, suggesting higher local network efficiency in the female brain. They also found that brain size is significantly and negatively correlated with local clustering, suggesting that smaller human brains are more efficient in local information transfer. Interestingly, they found that the brain size effect on local efficiency was not significant in males.

    The brain is like many things. Probably because the brain is really completely unlike anything humans have ever built or understood. Put another way, Newtonian physics is an approximation (it’s “like”) relativity physics within a particular scale of time and space. The brain encompasses so much structural and functional complexity that there are a lot of things “like” in the brain. It is fun and sometimes even useful to say that a certain system in the brain is like a telephone switchboard, a computer, or a social network. However, we must keep in mind that the brain is really not the same as anything else we know.

  • The Database of Odor Responses (DoOR): a Functional Atlas of All Available Odor Responses

    Odors are recognized by a large family of odor receptors. Each receptor cell expresses one or a few receptor proteins, which give that cell a specific odor response profile. This profile can be represented by a mathematical function.

    When we smell, most chemicals stimulate more than 1 odor receptor cell type. The result is that each odor elicits an activity pattern across an array of odor receptor cells. Population coding enables the brain to recognize and remember thousands or maybe millions of different odors with a limited number of receptor types (approximately 350 in humans and about 60 in fruit flies).

    The recent paper “Integrating Heterogeneous Odor Response Data into a Common Response Model: A DoOR to the Complete Olfactome” (published September 2010 in Chemical Senses) reports on the creation of a functional atlas of odor responses for not only odor receptors but also the olfactory glomeruli of the fruit fly.

    The project is important for two reasons:

    • The functional atlas represents a consensus data set combining all available data that can serve as a standard reference for the sense of smell in fruit flies. Since the odor response profiles are based on many studies they are statistically more reliable than any single study.
    • The computer software tools test an approach for mapping different data sets onto each other.

    The team developed a software platform that allows the extraction of odor response profiles across chemicals for individual receptors or the extraction of the entire combinatorial response pattern elicited by a given chemical. The software is an open source R-package and can be downloaded from the DoOR website. The download also includes the fruit fly data.

    Note: R-packages are written in the R programming language and and must be run in the R software environment for statistical computing and graphics. The software is all open source and freely available through the R Project for Statistical Computing website.

  • NIF: Better Literature Search

    Over the past couple of days we’ve looked at the data aggregating capabilities of the Neuroscience Information Framework (NIF). What about literature search? Is there any reason you should move from PubMed or Google Scholar to NIF?

    Figure 1. NIF literature search results for “barrel cortex.” NIF provides four tabs on the literature search results page.

    NIF provides the results of a standard PubMed search under the PubMed tab. In addition, NIF provides Open Access Literature, Neuronal Morphology, and Neuroscience Literature tabs. The Open Access Literature tab provides a convenient way to go directly to relevant articles that are freely available over the Internet. The Neuronal Morphology tab provides quick access to papers associated with digitally reconstructed neurons available through NeuroMorpho.org. The Neuroscience Literature tab lists papers returned based on a full text search using your search words. This could arguably the most valuable additional literature search service that NIF provides.

    Unfortunately the majority of papers are still published in journals that are not open access. Because of legal restrictions, NIF is only able to provide full text search services on a subset of papers that include those published in open access journals and those published in the Journal of Neuroscience. NIF provides a complete list of journals searched here.

    There is a large literature surrounding the amyloid beta protein. Recent evidence suggests that amyloid beta 42 is particularly important in Alzheimer’s disease. What if we only want papers that used amyloid beta 42 in their research? I decided to run a quick test of the full text search capabilities by typing the following “amyloid beta 42” into the NIF home page search box and clicking on the search icon. That didn’t even kick off a search but took me to a blank NEUROLEX page (under neurons and brain regions). The same thing happened when I typed in “amyloid-beta 42” but “abeta42” worked.

    Note: All of the variants above worked when I typed them into the search box returned by the initial search from home page (like at top left in Figure 1 above). Surprisingly, searches for “amyloid beta 42” and “amyloid-beta 42” each resulted in zero hits under “Neuroscience Literature.”

    A search for “abeta42” returned 161 papers under Neuroscience Literature. I checked all the articles in the first three pages and the last page and they all included abeta42 in the title or the abstract so I’m not sure if we’ve located additional articles that, for example, may have only mentioned the 42 amino acid peptide in its methods section. Also, it doesn’t look like synonyms are being used in the search.

    Other related blog posts:

    NIF: When You’re Looking for Neuroscience Resources Including Data

    NIF: Neurons, Models, and Grants