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At least 109 records · Page 6

atonal regulates neurite arborization but does not act as a proneural gene in the Drosophila brain

Drosophila atonal (ato) is the proneural gene of the chordotonal organs (CHOs) in the peripheral nervous system (PNS) and the larval and adult photoreceptor organs. Here, we show that ato is expressed at multiple stages during the development of a lineage of central brain neurons that innervate the optic lobes and are required for eclosion. A novel fate mapping approach shows that ato is expressed in the embryonic precursors of these neurons and that its expression is reactivated in third instar larvae (L3). In contrast to its function in the PNS, ato does not act as a proneural gene in the embryonic brain. Instead, ato performs a novel function, regulating arborization during larval and pupal development by interacting with Notch.

NASA Discipline Developmental Biology↗

Using light and X-ray scattering to untangle complex neuronal orientations and validate diffusion MRI

Disentangling human brain connectivity requires an accurate description of nerve fiber trajectories, unveiled via detailed mapping of axonal orientations. However, this is challenging because axons can cross one another on a micrometer scale. Diffusion magnetic resonance imaging (dMRI) can be used to infer axonal connectivity because it is sensitive to axonal alignment, but it has limited spatial resolution and specificity. Scattered light imaging (SLI) and small-angle X-ray scattering (SAXS) reveal axonal orientations with microscopic resolution and high specificity, respectively. Here, we apply both scattering techniques on the same samples and cross-validate them, laying the groundwork for ground-truth axonal orientation imaging and validating dMRI. We evaluate brain regions that include unidirectional and crossing fibers in human and vervet monkey brain sections. SLI and SAXS quantitatively agree regarding in-plane fiber orientations including crossings, while dMRI agrees in the majority of voxels with small discrepancies. We further use SAXS and dMRI to confirm theoretical predictions regarding SLI determination of through-plane fiber orientations. Scattered light and X-ray imaging can provide quantitative micrometer 3D fiber orientations with high resolution and specificity, facilitating detailed investigations of complex fiber architecture in the animal and human brain.

59 BASIC BIOLOGICAL SCIENCES↗

AutoAtlas: Neural Network for 3D Unsupervised Partitioning and Representation Learning

Here we present a novel neural network architecture called AutoAtlas for fully unsupervised partitioning and representation learning of 3D brain Magnetic Resonance Imaging (MRI) volumes. AutoAtlas consists of two neural network components: one neural network to perform multi-label partitioning based on local texture in the volume, and a second neural network to compress the information contained within each partition. We train both of these components simultaneously by optimizing a loss function that is designed to promote accurate reconstruction of each partition, while encouraging spatially smooth and contiguous partitioning, and discouraging relatively small partitions. We show that the partitions adapt to the subject specific structural variations of brain tissue while consistently appearing at similar spatial locations across subjects. AutoAtlas also produces very low dimensional features that represent local texture of each partition. We demonstrate prediction of metadata associated with each subject using the derived feature representations and compare the results to prediction using features derived from FreeSurfer anatomical parcellation. Since our features are intrinsically linked to distinct partitions, we can then map values of interest, such as partition-specific feature importance scores onto the brain for visualization.

42 ENGINEERING↗

Synchronization, non-linear dynamics and low-frequency fluctuations: Analogy between spontaneous brain activity and networked single-transistor chaotic oscillators

In this paper, the topographical relationship between functional connectivity (intended as inter-regional synchronization), spectral and non-linear dynamical properties across cortical areas of the healthy human brain is considered. Based upon functional MRI acquisitions of spontaneous activity during wakeful idleness, node degree maps are determined by thresholding the temporal correlation coefficient among all voxel pairs. In addition, for individual voxel time-series, the relative amplitude of low-frequency fluctuations and the correlation dimension (D{sub 2}), determined with respect to Fourier amplitude and value distribution matched surrogate data, are measured. Across cortical areas, high node degree is associated with a shift towards lower frequency activity and, compared to surrogate data, clearer saturation to a lower correlation dimension, suggesting presence of non-linear structure. An attempt to recapitulate this relationship in a network of single-transistor oscillators is made, based on a diffusive ring (n = 90) with added long-distance links defining four extended hub regions. Similarly to the brain data, it is found that oscillators in the hub regions generate signals with larger low-frequency cycle amplitude fluctuations and clearer saturation to a lower correlation dimension compared to surrogates. The effect emerges more markedly close to criticality. The homology observed between the two systems despite profound differences in scale, coupling mechanism and dynamics appears noteworthy. These experimental results motivate further investigation into the heterogeneity of cortical non-linear dynamics in relation to connectivity and underline the ability for small networks of single-transistor oscillators to recreate collective phenomena arising in much more complex biological systems, potentially representing a future platform for modelling disease-related changes.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

A quantitative comparison of simultaneous BOLD fMRI and NIRS recordings during functional brain activation

Near-infrared spectroscopy (NIRS) has been used to noninvasively monitor adult human brain function in a wide variety of tasks. While rough spatial correspondences with maps generated from functional magnetic resonance imaging (fMRI) have been found in such experiments, the amplitude correspondences between the two recording modalities have not been fully characterized. To do so, we simultaneously acquired NIRS and blood-oxygenation level-dependent (BOLD) fMRI data and compared Delta(1/BOLD) (approximately R(2)(*)) to changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations derived from the NIRS data from subjects performing a simple motor task. We expected the correlation with deoxyhemoglobin to be strongest, due to the causal relation between changes in deoxyhemoglobin concentrations and BOLD signal. Instead we found highly variable correlations, suggesting the need to account for individual subject differences in our NIRS calculations. We argue that the variability resulted from systematic errors associated with each of the signals, including: (1) partial volume errors due to focal concentration changes, (2) wavelength dependence of this partial volume effect, (3) tissue model errors, and (4) possible spatial incongruence between oxy- and deoxyhemoglobin concentration changes. After such effects were accounted for, strong correlations were found between fMRI changes and all optical measures, with oxyhemoglobin providing the strongest correlation. Importantly, this finding held even when including scalp, skull, and inactive brain tissue in the average BOLD signal. This may reflect, at least in part, the superior contrast-to-noise ratio for oxyhemoglobin relative to deoxyhemoglobin (from optical measurements), rather than physiology related to BOLD signal interpretation.

Non-NASA Center↗

SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.

60 APPLIED LIFE SCIENCES↗

High-resolution imaging of Hg/Se aggregates in the brain of small Indian mongoose, a wild terrestrial species: insights into intracellular Hg detoxification

Human activities result in the emission of 2000 metric tons of mercury compounds annually. Mercury (Hg) biomagnification has been characterized in marine mammals and predatory fish; however, little is known about mercury accumulation in brains of wild terrestrial species. Elevated Hg content, of 1.27 μg/g wet wt.—found in the brain of wild small Indian mongoose, prompted us to use synchrotron X-ray fluorescence imaging for simultaneous, quantitative mapping of biologically relevant and neurotoxic elements with high spatial resolution. X-ray fluorescence combined with immunohistochemistry revealed ~0.5–1.9 micron Hg-rich aggregates in cells of the choroid plexus and astrocytes of the subventricular wall in the mongoose brain. Hg content within aggregates correlated with selenium. Hg aggregates did not co-localize with lysosomes. The low Hg density inside aggregates indicated diffuse Hg binding to a Se-containing biomolecule, rather than much denser HgSe nanoparticles proposed to form in other species. Our data show the susceptibility of the small Indian mongoose population to Hg pollution and highlight the vulnerability of the brain as an organ targeted by mercury. Data also provide evidence on the adaptation in the form of a Se-based detoxification mechanism sequestering Hg into intracellular aggregates.

36 MATERIALS SCIENCE↗

Does Preinterventional Flat-Panel Computer Tomography Pooled Blood Volume Mapping Predict Final Infarct Volume After Mechanical Thrombectomy in Acute Cerebral Artery Occlusion?

PurposeDecreased cerebral blood volume is known to be a predictor for final infarct volume in acute cerebral artery occlusion. To evaluate the predictability of final infarct volume in patients with acute occlusion of the middle cerebral artery (MCA) or the distal internal carotid artery (ICA) and successful endovascular recanalization, pooled blood volume (PBV) was measured using flat-panel detector computed tomography (FPD CT).Materials and MethodsTwenty patients with acute unilateral occlusion of the MCA or distal ACI without demarcated infarction, as proven by CT at admission, and successful Thrombolysis in cerebral infarction score (TICI 2b or 3) endovascular thrombectomy were included. Cerebral PBV maps were acquired from each patient immediately before endovascular thrombectomy. Twenty-four hours after recanalization, each patient underwent multislice CT to visualize final infarct volume. Extent of the areas of decreased PBV was compared with the final infarct volume proven by follow-up CT the next day.ResultsIn 15 of 20 patients, areas of distinct PBV decrease corresponded to final infarct volume. In 5 patients, areas of decreased PBV overestimated final extension of ischemia probably due to inappropriate timing of data acquisition and misery perfusion.ConclusionPBV mapping using FPD CT is a promising tool to predict areas of irrecoverable brain parenchyma in acute thromboembolic stroke. Further validation is necessary before routine use for decision making for interventional thrombectomy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-D-18C-05: Variable Bolus Arterial Spin Labeling MRI for Accurate Cerebral Blood Flow and Arterial Transit Time Mapping

Purpose: Arterial spin labeling (ASL) is an MRI perfusion imaging method from which quantitative cerebral blood flow (CBF) maps can be calculated. Acquisition with variable post-labeling delays (PLD) and variable TRs allows for arterial transit time (ATT) mapping and leads to more accurate CBF quantification with a scan time saving of 48%. In addition, T1 and M0 maps can be obtained without a separate scan. In order to accurately estimate ATT and T1 of brain tissue from the ASL data, variable labeling durations were invented, entitled variable-bolus ASL. Methods: All images were collected on a healthy subject with a 3T Siemens Skyra scanner. Variable-bolus Psuedo-continuous ASL (PCASL) images were collected with 7 TI times ranging 100-4300ms in increments of 700ms with TR ranging 1000-5200ms. All boluses were 1600ms when the TI allowed, otherwise the bolus duration was 100ms shorter than the TI. All TI times were interleaved to reduce sensitivity to motion. Voxel-wise T1 and M0 maps were estimated using a linear least squares fitting routine from the average singal from each TI time. Then pairwise subtraction of each label/control pair and averaging for each TI time was performed. CBF and ATT maps were created using the standard model by Buxton et al. with a nonlinear fitting routine using the T1 tissue map. Results: CBF maps insensitive to ATT were produced along with ATT maps. Both maps show patterns and averages consistent with literature. The T1 map also shows typical T1 contrast. Conclusion: It has been demonstrated that variablebolus ASL produces CBF maps free from the errors due to ATT and tissue T1 variations and provides M0, T1, and ATT maps which have potential utility. This is accomplished with a single scan in a feasible scan time (under 6 minutes) with low sensivity to motion.

60 APPLIED LIFE SCIENCES↗

A review of MRI evaluation of demyelination in cuprizone murine model

The cuprizone mouse model of non-autoimmune demyelination reproduces some phenomena of multiple sclerosis and is appropriate for validation and specification of a new method of non-invasive diagnostics. In the review new data which are collected using the new MRI method are compared with one or more conventional MRI tools. Also the paper reviewed the validation of MRI approaches using histological or immunohistochemical methods. Luxol fast blue histological staining and myelin basic protein immunostaining is widespread. To improve the accuracy of non-invasive conventional MRI, multimodal scanning could be applied. The new quantitative MRI method of fast mapping of the macromolecular proton fraction is a reliable biomarker of myelin in the brain and can be used for research of demyelination in animals. To date, a validation of MPF method on the CPZ mouse model of demyelination is not performed, although this method is probably the best way to evaluate demyelination using MRI.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

MO-DE-BRA-06: MrRSCAL: A Radiological Simulation Tool for Resident Education

Purpose: The goal of this project was to create a readily accessible, comprehensive-yet-flexible interactive MRI simulation tool for use in training and education of radiology residents in particular. This tool was developed to take the place of an MR scanner in laboratory activities, as magnet time has become scarce while hospitals are optimizing clinical scheduling for improved throughput. Methods: MrRSCAL (Magnetic resonance Resident Simulation Console for Active Learning) was programmed and coded using Matlab on a Mac workstation utilizing OS X platform. MR-based brain images were obtained from one of the co-authors and processed to generate parametric maps. Scanner sounds are also generated via mp3 convolution of a single MR gradient slew with a time-profile of gradient waveforms. Results: MrRSCAL facilitates the simulation of multiple MR sequences with the ability to alter MR parameters via an intuitive GUI control panel. The application allows the user to gain real-time understanding of image transformation when varying these said parameters by examining the resulting images. Lab procedures can be loaded and displayed for more directed study. The panel is also configurable, providing a simple interface for elementary labs or a full array of controls for the expert user. Conclusion: Our introduction of MrRSCAL, which is readily available to users with a current laptop or workstation, allows for individual or group study of MR image acquisition with immediate educational feedback as the MR parameters are manipulated. MrRSCAL can be used at any time and any place once installed, offering a new tool for reviewing relaxometric and artifact principles when studying for boards or investigating properties of a pulse sequence. This tool promises to be extremely useful in conveying traditionally difficult and abstract concepts involved with MR to the radiology resident and other medical professionals at large.

60 APPLIED LIFE SCIENCES↗

SU-E-QI-06: Design and Initial Validation of a Precise Capillary Phantom to Test Perfusion Systems

Purpose: To design a precise perfusion phantom mimicking capillaries of the brain vasculature which could be used to test various perfusion protocols and algorithms which generate perfusion maps. Methods: A perfusion phantom was designed in Solidworks and built using additive manufacturing. The phantom was an overall cylindrical shape of diameter and height 20mm and containing capillaries of 200μm or 300μm which were parallel and in contact making up the inside volume where flow was allowed. We created a flow loop using a peristaltic pump and contrast agent was injected manually. Digital Subtraction Angiographic images and low contrast images with cone beam CT were acquired after the contrast was injected. These images were analyzed by our own code in LabVIEW software and Time-Density Curve, MTT and TTP was calculated. Results: Perfused area was visible in the cone beam CT images; however, individual capillaries were not distinguishable. The Time-Density Curve acquired was accurate, sensitive and repeatable. The parameters MTT, and TTP offered by the phantom were very sensitive to slight changes in the TDC shape. Conclusion: We have created a robust calibrating model for evaluation of existing perfusion data analysis systems. This approach is extremely sensitive to changes in the flow due to the high temporal resolution and could be used as a golden standard to assist developers in calibrating and testing of imaging perfusion systems and software algorithms. Supported by NIH Grant: 2R01EB002873 and an equipment grant from Toshiba Medical Systems Corporation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

The PRP Effect Following Callosotomy: Residual Interference Despite Uncoupling of Lateralized Response Codes

A callosotomy patient was tested in two dual-task experiments requiring successive speeded responses to lateralized stimuli. In accord with the recent findings of Pashler, O'Brien, Luck, Hillyard, Mangun, and Gazzaniga (in press), the patient showed a robust psychological refractory period effect (PRP) responses on Task 2 were inversely related to the stimulus-onset asynchrony (SOA). However, three aspects of our data indicated that the processing limitations for the patient were different than those observed with control subjects. First, the split-brain patient did not show an increase in reaction time when the two tasks required responses from a common output system (i.e., both manual responses) in comparison to when different output systems were used (i.e., manual-vocal). Second, inconsistent stimulus-response mappings for the two tasks greatly inflated response latencies for the control subjects, but had minimal effect on the performance of the split-brain patient. Third, the consistency manipulation was underadditive with SOA for only the patient, suggesting a later bottleneck in processing following callosotomy than was observed for the control subjects. It is proposed that sectioning the corpus callosum eliminates interference resulting from competing stimulus response codes. Nonetheless, dual-task interference persists for the split-brain subject because a subcortical gate constrains when selected responses can be implemented.

Ivry, Richard B.↗

Irregular activity arises as a natural consequence of synaptic inhibition

Irregular neuronal activity is observed in a variety of brain regions and states. This work illustrates a novel mechanism by which irregular activity naturally emerges in two-cell neuronal networks featuring coupling by synaptic inhibition. We introduce a one-dimensional map that captures the irregular activity occurring in our simulations of conductance-based differential equations and mathematically analyze the instability of fixed points corresponding to synchronous and antiphase spiking for this map. We find that the irregular solutions that arise exhibit expansion, contraction, and folding in phase space, as expected in chaotic dynamics. Our analysis shows that these features are produced from the interplay of synaptic inhibition with sodium, potassium, and leak currents in a conductance-based framework and provides precise conditions on parameters that ensure that irregular activity will occur. In particular, the temporal details of spiking dynamics must be present for a model to exhibit this irregularity mechanism and must be considered analytically to capture these effects.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Modular Spiking Neural Circuits for Mapping Long Short-Term Memory on a Neurosynaptic Processor

Due to the distributed and asynchronous nature of neural computation through low-energy spikes, brain-inspired hardware systems offer high energy efficiency and massive parallelism. One such platform is the IBM TrueNorth neurosynaptic system. Recently, TrueNorth compatible representation learning algorithms have emerged, achieving close to the state-of-the-art performance in various data sets. However, its application in temporal sequence processing models, such as recurrent neural networks (RNNs), is still only at the proof of concept level. There is an inherent difficulty in capturing temporal dynamics of an RNN using spiking neurons, which is only exasperated by the hardware constraints in connectivity and synaptic weight resolution. This paper presents a design flow that overcomes these difficulties and maps a special case of recurrent networks called long short-term memory (LSTM) onto a spike-based platform. The framework utilizes various approximation techniques, such as activation discretization, weight quantization, and scaling and rounding, spiking neural circuits that implement the complex gating mechanisms, and a store-and-release technique to enable neuron synchronization and faithful storage. While the presented techniques can be applied to map LSTM to any spiking neural network (SNN) simulator/emulator, here we choose the TrueNorth chip as the target platform by adhering to its hardware constraints. Three LSTM applications, parity check, extended Reber grammar, and question classification, are evaluated. The tradeoffs among accuracy, performance, and energy tradeoffs achieved on TrueNorth are demonstrated. Finally, this is compared with the performance on an SNN platform without hardware constraints, which represents the upper bound of the achievable accuracy.

97 MATHEMATICS AND COMPUTING↗

Deep learning as a tool for neural data analysis: Speech classification and cross-frequency coupling in human sensorimotor cortex

A fundamental challenge in neuroscience is to understand what structure in the world is represented in spatially distributed patterns of neural activity from multiple single-trial measurements. This is often accomplished by learning a simple, linear transformations between neural features and features of the sensory stimuli or motor task. While successful in some early sensory processing areas, linear mappings are unlikely to be ideal tools for elucidating nonlinear, hierarchical representations of higher-order brain areas during complex tasks, such as the production of speech by humans. Here, we apply deep networks to predict produced speech syllables from a dataset of high gamma cortical surface electric potentials recorded from human sensorimotor cortex. We find that deep networks had higher decoding prediction accuracy compared to baseline models. Having established that deep networks extract more task relevant information from neural data sets relative to linear models (i.e., higher predictive accuracy), we next sought to demonstrate their utility as a data analysis tool for neuroscience. We first show that deep network's confusions revealed hierarchical latent structure in the neural data, which recapitulated the underlying articulatory nature of speech motor control. We next broadened the frequency features beyond high-gamma and identified a novel high-gamma-to-beta coupling during speech production. Finally, we used deep networks to compare task-relevant information in different neural frequency bands, and found that the high-gamma band contains the vast majority of information relevant for the speech prediction task, with little-to-no additional contribution from lower-frequency amplitudes. Together, these results demonstrate the utility of deep networks as a data analysis tool for basic and applied neuroscience.

60 APPLIED LIFE SCIENCES↗