Solving Big Questions: HHMI Bulletin September 2005:

HHMI Bulletin September 2005: Solving Big Questions: "Janelia Farm will pursue two basic, and intertwined, goals: identifying the general principles that allow neural circuits to process information and developing imaging technologies and computational methods for image analysis. "

Misfolded Proteins

Google Image Result for http://www.bu.edu/dbin/anatneuro/assets/images/pics/lab/fmri.jpg: "Accumulation of misfolded proteins is a feature of aging and appears to be accelerated in many neurodegenerative disorders. Protein misfolding can result from defects in the chaperone system or may arise due to mutations or oxidative damage. Recent data indicates that the misfolded proteins play an active role in cellular toxicity. "

BOLD fMRI vs electrophysiological

Google Image Result for http://www.bu.edu/dbin/anatneuro/assets/images/pics/lab/fmri.jpg: "While BOLD-based neuroimaging studies have provided unprecedented amount of insights into the workings of the human brain in vivo, the explanatory power of BOLD fMRI is currently limited since there is a fundamental gap in our understanding of the linkage between the observed BOLD contrast and the underlying neuronal physiology. In particular, the extent to which the magnitude and spatial scale of the BOLD signal correlates with neuronal physiology remains elusive. To this end, a small but increasing body of results suggests a predominantly linear coupling between BOLD and neuronal activity. For example, a recent study by Ogawa et al demonstrated a linear relationship between somatosensory evoked potentials and BOLD signals for brief stimulation durations. Rees et al. and Heeger et al. demonstrated a linear correlation between BOLD contrast in humans and suprathreshold spiking rate averaged over a cortical area in monkeys during the stimulation with nearly identical stimuli. A similarly linear relationship was observed also in anesthetized monkeys by Logothetis et al. in which single unit responses were acquired simultaneously with BOLD signals for the first time inside the MRI scanner. While the these results suggest that the fundamental coupling between BOLD and the underlying neuronal activity is approximately linear, important questions remain about the spatial scale over which the presumed linear coupling between BOLD and neuronal activity remains valid. Is the hypothesized linear coupling between BOLD and neuronal activity invariant across the different spatial scales of the cortical architecture? Can we assume a universal linearity from the spatial scale of entire cortical areas (several millimeters to centimeters) to individual cortical columns (sub-millimeter)?"

DTI: Diffusion Tensor Imaging

Google Image Result for http://www.bu.edu/dbin/anatneuro/assets/images/pics/lab/fmri.jpg: "Diffusion Tensor Imaging (DTI) is a powerful MRI technique that enables us to translate the self-diffusion, or microscopic motion of water molecules in tissue into a MRI measure of tissue integrity and structure. Namely, the spatial characteristic of water diffusion highly depends on the barriers imposed on the water molecule motion, those barriers being the elements of tissue such as cell membranes, myelin sheath, intracellular microorganelles and others. Specifically, in white matter, water self diffusion is restricted, or hindered mostly by the intracellular axonal space, and by the interstitial, extracellular space among the well-packed axons in the fiber tract. By taking several diffusion weighted images in several dimensions, one can reconstruct the so-called diffusion tensor for each image unit, or pixel. The diffusion tensor gives a three dimensional representation of the preferred direction of diffusion, in the shape of the 3D ellipsoid. This ellipsoid can be characterized by six parameters; diffusion constants along the longest, middle, and shortest axes ( λ1, λ2, and λ3, called principal axes) and the direction of the three principal axes. Once the diffusion ellipsoid is fully characterized at each pixel of the brain images, local fiber structure can be derived. For example, if λ1 >> λ2 ≥ λ3 (diffusion is anisotropic), it suggests the existence of dense and aligned fibers within the each pixel, whereas isotropic diffusion (λ1 ≈ λ2 ≈ λ3) suggests sparse or unaligned fibers. When diffusion is anisotropic, the direction of λ1 indicates the direction of the fibers. Recently, such DTI techniques in combination with 3-D fiber reconstruction algorithm was used to generate spectacular images of the axonal connectivity pattern in vivo both in humans, rodents, and recently also in cats."

Vision

Google Image Result for http://www.bu.edu/dbin/anatneuro/assets/images/pics/lab/fmri.jpg: "Like in other primates, human visual areas are clustered along two "streams" diverging from the occipital pole: the ventro-temporal "what or perception" stream and the dorsal "where or action" stream. While the areas in the dorsal stream are tuned for visual stimuli and tasks related to stimulus location and/or action, the ventral stream consists of a web of exquisitely category selective areas. For example, a region in the lateral occipital cortex (LOC) extending anteriorly into the temporal cortex responds strongly to a variety of complex shaped objects such as polygonal figures, chairs, and gloves, etc. Furthermore, in the so called fusiform face area (FFA; located within the fusiform gyrus, cells are tuned to faces and facial stimuli (e.g., front-view photographs of faces and line drawings of faces, etc.) in a way comparable to the receptive field properties of face-selective neurons in primate inferotemporal cortex (IT). Further down the temporal cortex, in the so called parahippocampal place area (PPA), maximum functional response can be obtained using scenic or place type of stimuli. The description of highly specialized areas such as FFA and PPA raises the question how many category-selective regions of cortex exist in the human visual system, and, more generally, how the ventral temporal cortex is organized. Hypotheses range from the assumption that there are a few specialized processing modules, i.e., for faces, places, letters and human body parts up to the proposal of widely distributed and overlapping cortical object representations. Effects of category-related expertise and, more recently, different category-related resolution needs have also been proposed to explain the topology of the human what-pathway. Further insights into the question how objects are represented in ventral visual cortex might come from functional imaging studies investigating within-category responses, for example, by comparing responses to single object images, such as two different faces or two different houses (Kriegeskorte et al., personal communication). It has also been proposed that the eccentricity gradient observed in early visual areas continues into ventral visual cortex (Malach et al., 2002). For example, regions selective to faces (FFA) overlap with the representation of the fovea, while regions that are selective to houses (PPA) overlap with a peripheral visual representation located in the collateral sulcus."

BOLD fMRI

Google Image Result for http://www.bu.edu/dbin/anatneuro/assets/images/pics/lab/fmri.jpg

" Laboratory of Brain Imaging







This laboratory uses high field MRI to investigate cortical plasticity, face representation in the cortex, and axonal connectivity. Members of the lab are also involved in the development of new MRI applications, and the verification of existing techniques using single unit recording and optical imaging. We are particularly interested in developing novel multimodal imaging techniques to simultaneously map the structure, function, and connectivity of various cortical functions in the mammalian brains. Few examples of our research enterprise are listed below:

Use of BOLD fMRI for mapping the detailed layout of the cortical functional architecture in vivo:

The BOLD technique is based on the use of deoxyhemoglobin as nature's own intravascular paramagnetic contrast agent. When placed in a magnetic field, deoxyhemoglobin alters the magnetic field in its vicinity, particularly when it is compartmentalized as it is within red blood cells and vasculature. The effect increases as the concentration of deoxyhemoglobin increases. At concentrations found in venous blood vessels, a detectable local distortion of the magnetic field surrounding the red blood cells and surrounding blood vessel is produced. This affects the magnetic resonance behavior of the water proton nuclei within and surrounding the vessels, which in turn result in decreases in the transverse relaxation times (T2 and T2*. During the activation of the brain, this process is reduced: increase in neuronal and metabolic activity results in a reduction of the relative deoxyhemoglobin concentration due to an increase of blood flow (and hence increased supply of fresh oxyhemoglobin) that follows. Consequently, in conventional BOLD fMRI, brain "activity" can be measured as an increase in T2 or T2* weighted MR signals. Since its introduction about 10 years ago, BOLD fMRI was successfully applied Ð among numerous other examples - to precisely localize the cognitive, motor, and perceptual function of the human cortex cerebri."