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  • Neuroinformatics
  • eScholarship - University of California

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Toronov, V; Webb, AG; Choi, JH; Wolf, M; +3 Authors
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    Authors: Kubby, Joel;

    Our ability to see fine detail at depth in tissues is limited by scattering and other refractive characteristics of the tissue. For fixed tissue, we can limit scattering with a variety of clearing protocols. This allows us to see deeper but not necessarily clearer. Refractive aberrations caused by the bulk index of refraction of the tissue and its variations continue to limit our ability to see fine detail. Refractive aberrations are made up of spherical and other Zernike modes, which can be significant at depth. Spherical aberration that is common across the imaging field can be corrected using an objective correcting collar, although this can require manual intervention. Other aberrations may vary across the imaging field and can only be effectively corrected using adaptive optics. Adaptive optics can also correct other aberrations simultaneously with the spherical aberration, eliminating manual intervention and speeding imaging. We use an adaptive optics two-photon microscope to examine the impact of the spherical and higher order aberrations on imaging and contrast the effect of compensating only for spherical aberration against compensating for the first 22 Zernike aberrations in two tissue types. Increase in image intensity by 1.6×1.6× and reduction of root mean square error by 3×3× are demonstrated.

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    Authors: Kubby, Joel;

    Optical sectioning of biological tissues has become the method of choice for three-dimensional histological analyses. This is particularly important in the brain were neurons can extend processes over large distances and often whole brain tracing of neuronal processes is desirable. To allow deeper optical penetration, which in fixed tissue is limited by scattering and refractive index mismatching, tissue-clearing procedures such as CLARITY have been developed. CLARITY processed brains have a nearly uniform refractive index and three-dimensional reconstructions at cellular resolution have been published. However, when imaging in deep layers at submicron resolution some limitations caused by residual refractive index mismatching become apparent, as the resulting wavefront aberrations distort the microscopic image. The wavefront can be corrected with adaptive optics. Here, we investigate the wavefront aberrations at different depths in CLARITY processed mouse brains and demonstrate the potential of adaptive optics to enable higher resolution and a better signal-to-noise ratio. Our adaptive optics system achieves high-speed measurement and correction of the wavefront with an open-loop control using a wave front sensor and a deformable mirror. Using adaptive optics enhanced microscopy, we demonstrate improved image quality wavefront, point spread function, and signal to noise in the cortex of YFP-H mice.

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    Authors: London, Edythe D;

    Aims. This review aims to present and interpret evidence that methamphetamine dependence is associated with disorder of brain function that is required for top-down control of behavior. Approach. Presented here are findings from brain imaging studies of human research participants with histories of chronic methamphetamine abuse in the context of functional consequences and implications for treatment of their dependence on methamphetamine. Findings. Brain imaging studies have revealed differences in the brains of research participants who have used methamphetamine chronically and then abstained from taking the drug, compared with healthy control subjects. These abnormalities are prominent in cortical and limbic systems, and include deficits in markers of dopaminergic and serotonergic neurotransmitter systems, differences in glucose metabolism, and deficits in gray matter. These abnormalities accompany cognitive deficits, including evidence of impaired inhibitory control. Conclusion. Cortical deficits in abstinent methamphetamine abusers can affect a wide range of functions that can be important for success in maintaining drug abstinence. These include but are not limited to modulation of responses to environmental stimuli as well as internal triggers that can lead to craving and relapse. Potential therapies may combine behavioral approaches with medications that can improve cognitive control.

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    Authors: Kim, HS; Sasaki, JY;
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    Authors: London, E D; Berman, S M; Voytek, B; Simon, S L; +9 Authors

    Background: Methamphetamine (MA) abusers have cognitive deficits, abnormal metabolic activity and structural deficits in limbic and paralimbic cortices, and reduced hippocampal volume. The links between cognitive impairment and these cerebral abnormalities are not established. Methods: We assessed cerebral glucose metabolism with [F-18]fluorodeoxyglucose positron emission tomography in 17 abstinent (4 to 7 days) methamphetamine users and 16 control subjects performing an auditory vigilance task and obtained structural magnetic resonance brain scans. Regional brain radioactivity served as a marker for relative glucose metabolism. Error rates on the task were related to regional radioactivity and hippocampal morphology Results. Methamphetamine users bad higher error rate than control subjects on the vigilance task. The groups showed different relationships between error rates and relative activity), in the anterior and middle cingulate gyrus and the insula. Whereas the MA user group showed negative correlations involving these regions, the control group showed positive correlations involving the cingulate cortex. Across groups, hippocampal metabolic and structural measures were negatively correlated with error rates. Conclusions: Dysfunction in the cingulate and insular cortices of recently abstinent MA abusers contribute to impaired vigilance and other cognitive functions requiring sustained attention. Hippocampal integrity predicts task performance in methamphetamine users as well as control subjects.

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    Authors: Fischer, Jason Thomas;

    Perceiving objects' positions is one of the fundamental purposes of vision and is crucial to day-to-day life. Much work has been devoted to finding and characterizing spatial maps in the brain, but we still know strikingly little about how these maps support perceptual localization. The experiments in this thesis employ a combination of functional brain imaging and visual psychophysics, drawing on a body of behavioral literature on spatial perception and visual attention, to ask how position coding in the brain adapts to support the demands of the task at hand.The experiments in Chapter 2 ask how and where perceived object positions are represented in the brain. Perceived position depends on many factors such as attention, frame of reference, adaptation, and motion. At what stage of visual processing is this information integrated into the brain's retinotopic maps? By measuring variability in perceived position alongside variability in the multivariate pattern of neural responses in a host of visual areas, we identify a percept-centered reference frame in high-level object-, face-, scene-, and motion-selective regions.The experiments in Chapter 3 ask how the visual system achieves improved spatial resolution with focused attention. Attention is known to boost the amplitude of neural responses, but it might also sharpen position tuning at the neural population level, making the activations produced by adjacent objects more distinct within the cortex. Employing a combined imaging and modeling approach, we find that attention narrows the spatial spread of the fMRI BOLD response in early visual cortical areas, including V1. This narrowed population position tuning is an efficient means of achieving visual resolution improvements.The experiments in Chapter 4 ask how the brain suppresses distracting visual input in order to limit its negative impact on performance. During a selective attention task, we measure the BOLD response in the pulvinar nucleus of the thalamus, an area whose damage appears to lead to distractor filtering deficits. We find that while attended items are represented with high spatial and featural precision in the pulvinar, ignored items are gated out, leaving no discernable trace in the pattern of response in the pulvinar. These results suggest that the spatial maps in the pulvinar may serve as an interface in which distracting visual input is filtered out.Collectively, the findings presented here speak to a remarkable flexibility in the way the brain represents spatial information. The brain's visual maps adapt on a moment-by-moment basis to support the demands of the task at hand.

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    Authors: Meyerhoff, Dieter; Durazzo, Timothy C;

    This book focuses on "what to know" and "how to apply" information, prioritizing novel principles and delineating cutting-edge assessment, phenotyping and treatment tools.

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    Authors: Ye, Hu;

    Positron Emission Tomography (PET) is a functional medical imaging tool that enables the visualization of radio-labeled biologically active molecules (tracer) distributed inside a living body. PET is also combined with other modalities such as CT and MRI with either software or hardware methods to gain synergy. However numerous technical and biological issues remain to be addressed to improve the utility of PET in multimodal imaging for both clinical and preclinical applications. Patient movement during the PET/CT dynamic scan is one of the major problems in clinical study and automated MRI template-based volume of interest (VOI) analysis is one of the key issues in preclinical brain studies for PET. PET/CT is an imaging system that combines PET and CT, in which CT not only provides structure information but also aids attenuation correction for PET. This multimodal medical imaging has become prevalence in clinical diagnosis. However, head movements occurring during PET/CT dynamic scans can create large artifacts in CT-based attenuation corrected PET due to mismatches between CT and PET images. We have thus developed an automated movement correction (MC) procedure for PET/CT dynamic brain scans. MC method was first validated in a Hoffman phantom study and further evaluated with patient FDDNP (a tracer that binds beta-amyloid and tau-protein depositions in tissue) and FDG (a glucose analogue) scans. Results showed that the use of MC for PET/CT dynamic scan significantly improved image quality and allowed more accurate tracer quantitative analysis.To accurately analyze longitudinal FDG preclinical PET brain scans, especially to quantitate image values in small brain structures, an automated MRI template-based volume of interest (VOI) analysis method has been established. The method was applied to longitudinal rat brain FDG PET images to evaluate regional cerebral metabolic change that could not be done without such a template-based analysis methodology. A 6-month study in normal young adult rats showed stable FDG uptake in sensorimotor cortex and lateral prefrontal cortex, a linear decline of relative FDG uptake in striatum, hippocampus and medial prefrontal cortex, while a linear increase in the relative FDG uptake was observed in cerebellum and brain stem. This linear progressive change in regional brain metabolism is first elucidated in normal young adult rats. The method was also applied to rat brain FDG PET images to evaluate the acute and long-term effects of chemotherapy on regional cerebral metabolism.

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    Authors: Fischer, Jason Thomas;

    Perceiving objects' positions is one of the fundamental purposes of vision and is crucial to day-to-day life. Much work has been devoted to finding and characterizing spatial maps in the brain, but we still know strikingly little about how these maps support perceptual localization. The experiments in this thesis employ a combination of functional brain imaging and visual psychophysics, drawing on a body of behavioral literature on spatial perception and visual attention, to ask how position coding in the brain adapts to support the demands of the task at hand.The experiments in Chapter 2 ask how and where perceived object positions are represented in the brain. Perceived position depends on many factors such as attention, frame of reference, adaptation, and motion. At what stage of visual processing is this information integrated into the brain's retinotopic maps? By measuring variability in perceived position alongside variability in the multivariate pattern of neural responses in a host of visual areas, we identify a percept-centered reference frame in high-level object-, face-, scene-, and motion-selective regions.The experiments in Chapter 3 ask how the visual system achieves improved spatial resolution with focused attention. Attention is known to boost the amplitude of neural responses, but it might also sharpen position tuning at the neural population level, making the activations produced by adjacent objects more distinct within the cortex. Employing a combined imaging and modeling approach, we find that attention narrows the spatial spread of the fMRI BOLD response in early visual cortical areas, including V1. This narrowed population position tuning is an efficient means of achieving visual resolution improvements.The experiments in Chapter 4 ask how the brain suppresses distracting visual input in order to limit its negative impact on performance. During a selective attention task, we measure the BOLD response in the pulvinar nucleus of the thalamus, an area whose damage appears to lead to distractor filtering deficits. We find that while attended items are represented with high spatial and featural precision in the pulvinar, ignored items are gated out, leaving no discernable trace in the pattern of response in the pulvinar. These results suggest that the spatial maps in the pulvinar may serve as an interface in which distracting visual input is filtered out.Collectively, the findings presented here speak to a remarkable flexibility in the way the brain represents spatial information. The brain's visual maps adapt on a moment-by-moment basis to support the demands of the task at hand.

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    Authors: Toronov, V; Webb, AG; Choi, JH; Wolf, M; +3 Authors
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    Authors: Kubby, Joel;

    Our ability to see fine detail at depth in tissues is limited by scattering and other refractive characteristics of the tissue. For fixed tissue, we can limit scattering with a variety of clearing protocols. This allows us to see deeper but not necessarily clearer. Refractive aberrations caused by the bulk index of refraction of the tissue and its variations continue to limit our ability to see fine detail. Refractive aberrations are made up of spherical and other Zernike modes, which can be significant at depth. Spherical aberration that is common across the imaging field can be corrected using an objective correcting collar, although this can require manual intervention. Other aberrations may vary across the imaging field and can only be effectively corrected using adaptive optics. Adaptive optics can also correct other aberrations simultaneously with the spherical aberration, eliminating manual intervention and speeding imaging. We use an adaptive optics two-photon microscope to examine the impact of the spherical and higher order aberrations on imaging and contrast the effect of compensating only for spherical aberration against compensating for the first 22 Zernike aberrations in two tissue types. Increase in image intensity by 1.6×1.6× and reduction of root mean square error by 3×3× are demonstrated.

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    Authors: Kubby, Joel;

    Optical sectioning of biological tissues has become the method of choice for three-dimensional histological analyses. This is particularly important in the brain were neurons can extend processes over large distances and often whole brain tracing of neuronal processes is desirable. To allow deeper optical penetration, which in fixed tissue is limited by scattering and refractive index mismatching, tissue-clearing procedures such as CLARITY have been developed. CLARITY processed brains have a nearly uniform refractive index and three-dimensional reconstructions at cellular resolution have been published. However, when imaging in deep layers at submicron resolution some limitations caused by residual refractive index mismatching become apparent, as the resulting wavefront aberrations distort the microscopic image. The wavefront can be corrected with adaptive optics. Here, we investigate the wavefront aberrations at different depths in CLARITY processed mouse brains and demonstrate the potential of adaptive optics to enable higher resolution and a better signal-to-noise ratio. Our adaptive optics system achieves high-speed measurement and correction of the wavefront with an open-loop control using a wave front sensor and a deformable mirror. Using adaptive optics enhanced microscopy, we demonstrate improved image quality wavefront, point spread function, and signal to noise in the cortex of YFP-H mice.

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    Authors: London, Edythe D;

    Aims. This review aims to present and interpret evidence that methamphetamine dependence is associated with disorder of brain function that is required for top-down control of behavior. Approach. Presented here are findings from brain imaging studies of human research participants with histories of chronic methamphetamine abuse in the context of functional consequences and implications for treatment of their dependence on methamphetamine. Findings. Brain imaging studies have revealed differences in the brains of research participants who have used methamphetamine chronically and then abstained from taking the drug, compared with healthy control subjects. These abnormalities are prominent in cortical and limbic systems, and include deficits in markers of dopaminergic and serotonergic neurotransmitter systems, differences in glucose metabolism, and deficits in gray matter. These abnormalities accompany cognitive deficits, including evidence of impaired inhibitory control. Conclusion. Cortical deficits in abstinent methamphetamine abusers can affect a wide range of functions that can be important for success in maintaining drug abstinence. These include but are not limited to modulation of responses to environmental stimuli as well as internal triggers that can lead to craving and relapse. Potential therapies may combine behavioral approaches with medications that can improve cognitive control.

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    Authors: Kim, HS; Sasaki, JY;
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    Authors: London, E D; Berman, S M; Voytek, B; Simon, S L; +9 Authors

    Background: Methamphetamine (MA) abusers have cognitive deficits, abnormal metabolic activity and structural deficits in limbic and paralimbic cortices, and reduced hippocampal volume. The links between cognitive impairment and these cerebral abnormalities are not established. Methods: We assessed cerebral glucose metabolism with [F-18]fluorodeoxyglucose positron emission tomography in 17 abstinent (4 to 7 days) methamphetamine users and 16 control subjects performing an auditory vigilance task and obtained structural magnetic resonance brain scans. Regional brain radioactivity served as a marker for relative glucose metabolism. Error rates on the task were related to regional radioactivity and hippocampal morphology Results. Methamphetamine users bad higher error rate than control subjects on the vigilance task. The groups showed different relationships between error rates and relative activity), in the anterior and middle cingulate gyrus and the insula. Whereas the MA user group showed negative correlations involving these regions, the control group showed positive correlations involving the cingulate cortex. Across groups, hippocampal metabolic and structural measures were negatively correlated with error rates. Conclusions: Dysfunction in the cingulate and insular cortices of recently abstinent MA abusers contribute to impaired vigilance and other cognitive functions requiring sustained attention. Hippocampal integrity predicts task performance in methamphetamine users as well as control subjects.

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    Authors: Fischer, Jason Thomas;

    Perceiving objects' positions is one of the fundamental purposes of vision and is crucial to day-to-day life. Much work has been devoted to finding and characterizing spatial maps in the brain, but we still know strikingly little about how these maps support perceptual localization. The experiments in this thesis employ a combination of functional brain imaging and visual psychophysics, drawing on a body of behavioral literature on spatial perception and visual attention, to ask how position coding in the brain adapts to support the demands of the task at hand.The experiments in Chapter 2 ask how and where perceived object positions are represented in the brain. Perceived position depends on many factors such as attention, frame of reference, adaptation, and motion. At what stage of visual processing is this information integrated into the brain's retinotopic maps? By measuring variability in perceived position alongside variability in the multivariate pattern of neural responses in a host of visual areas, we identify a percept-centered reference frame in high-level object-, face-, scene-, and motion-selective regions.The experiments in Chapter 3 ask how the visual system achieves improved spatial resolution with focused attention. Attention is known to boost the amplitude of neural responses, but it might also sharpen position tuning at the neural population level, making the activations produced by adjacent objects more distinct within the cortex. Employing a combined imaging and modeling approach, we find that attention narrows the spatial spread of the fMRI BOLD response in early visual cortical areas, including V1. This narrowed population position tuning is an efficient means of achieving visual resolution improvements.The experiments in Chapter 4 ask how the brain suppresses distracting visual input in order to limit its negative impact on performance. During a selective attention task, we measure the BOLD response in the pulvinar nucleus of the thalamus, an area whose damage appears to lead to distractor filtering deficits. We find that while attended items are represented with high spatial and featural precision in the pulvinar, ignored items are gated out, leaving no discernable trace in the pattern of response in the pulvinar. These results suggest that the spatial maps in the pulvinar may serve as an interface in which distracting visual input is filtered out.Collectively, the findings presented here speak to a remarkable flexibility in the way the brain represents spatial information. The brain's visual maps adapt on a moment-by-moment basis to support the demands of the task at hand.

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    Authors: Meyerhoff, Dieter; Durazzo, Timothy C;

    This book focuses on "what to know" and "how to apply" information, prioritizing novel principles and delineating cutting-edge assessment, phenotyping and treatment tools.

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    Authors: Ye, Hu;

    Positron Emission Tomography (PET) is a functional medical imaging tool that enables the visualization of radio-labeled biologically active molecules (tracer) distributed inside a living body. PET is also combined with other modalities such as CT and MRI with either software or hardware methods to gain synergy. However numerous technical and biological issues remain to be addressed to improve the utility of PET in multimodal imaging for both clinical and preclinical applications. Patient movement during the PET/CT dynamic scan is one of the major problems in clinical study and automated MRI template-based volume of interest (VOI) analysis is one of the key issues in preclinical brain studies for PET. PET/CT is an imaging system that combines PET and CT, in which CT not only provides structure information but also aids attenuation correction for PET. This multimodal medical imaging has become prevalence in clinical diagnosis. However, head movements occurring during PET/CT dynamic scans can create large artifacts in CT-based attenuation corrected PET due to mismatches between CT and PET images. We have thus developed an automated movement correction (MC) procedure for PET/CT dynamic brain scans. MC method was first validated in a Hoffman phantom study and further evaluated with patient FDDNP (a tracer that binds beta-amyloid and tau-protein depositions in tissue) and FDG (a glucose analogue) scans. Results showed that the use of MC for PET/CT dynamic scan significantly improved image quality and allowed more accurate tracer quantitative analysis.To accurately analyze longitudinal FDG preclinical PET brain scans, especially to quantitate image values in small brain structures, an automated MRI template-based volume of interest (VOI) analysis method has been established. The method was applied to longitudinal rat brain FDG PET images to evaluate regional cerebral metabolic change that could not be done without such a template-based analysis methodology. A 6-month study in normal young adult rats showed stable FDG uptake in sensorimotor cortex and lateral prefrontal cortex, a linear decline of relative FDG uptake in striatum, hippocampus and medial prefrontal cortex, while a linear increase in the relative FDG uptake was observed in cerebellum and brain stem. This linear progressive change in regional brain metabolism is first elucidated in normal young adult rats. The method was also applied to rat brain FDG PET images to evaluate the acute and long-term effects of chemotherapy on regional cerebral metabolism.

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    Authors: Fischer, Jason Thomas;

    Perceiving objects' positions is one of the fundamental purposes of vision and is crucial to day-to-day life. Much work has been devoted to finding and characterizing spatial maps in the brain, but we still know strikingly little about how these maps support perceptual localization. The experiments in this thesis employ a combination of functional brain imaging and visual psychophysics, drawing on a body of behavioral literature on spatial perception and visual attention, to ask how position coding in the brain adapts to support the demands of the task at hand.The experiments in Chapter 2 ask how and where perceived object positions are represented in the brain. Perceived position depends on many factors such as attention, frame of reference, adaptation, and motion. At what stage of visual processing is this information integrated into the brain's retinotopic maps? By measuring variability in perceived position alongside variability in the multivariate pattern of neural responses in a host of visual areas, we identify a percept-centered reference frame in high-level object-, face-, scene-, and motion-selective regions.The experiments in Chapter 3 ask how the visual system achieves improved spatial resolution with focused attention. Attention is known to boost the amplitude of neural responses, but it might also sharpen position tuning at the neural population level, making the activations produced by adjacent objects more distinct within the cortex. Employing a combined imaging and modeling approach, we find that attention narrows the spatial spread of the fMRI BOLD response in early visual cortical areas, including V1. This narrowed population position tuning is an efficient means of achieving visual resolution improvements.The experiments in Chapter 4 ask how the brain suppresses distracting visual input in order to limit its negative impact on performance. During a selective attention task, we measure the BOLD response in the pulvinar nucleus of the thalamus, an area whose damage appears to lead to distractor filtering deficits. We find that while attended items are represented with high spatial and featural precision in the pulvinar, ignored items are gated out, leaving no discernable trace in the pattern of response in the pulvinar. These results suggest that the spatial maps in the pulvinar may serve as an interface in which distracting visual input is filtered out.Collectively, the findings presented here speak to a remarkable flexibility in the way the brain represents spatial information. The brain's visual maps adapt on a moment-by-moment basis to support the demands of the task at hand.

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