Alberto Vazquez | University of Pittsburgh (original) (raw)

Papers by Alberto Vazquez

Research paper thumbnail of Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies

Implantable biosensors are valuable scientific tools for basic neuroscience research and clinical... more Implantable biosensors are valuable scientific tools for basic neuroscience research and clinical applications. Neurotechnologies provide direct readouts of neurological signal and neurochemical processes. These tools are generally most valuable when performance capacities extend over months and years to facilitate the study of memory, plasticity, and behavior or to monitor patients’ conditions. These needs have generated a variety of device designs from microelectrodes for fast scan cyclic voltammetry (FSCV) and electrophysiology to microdialysis probes for sampling and detecting various neurochemicals. Regardless of the technology used, the breaching of the blood–brain barrier (BBB) to insert devices triggers a cascade of biochemical pathways resulting in complex molecular and cellular responses to implanted devices. Molecular and cellular changes in the microenvironment surrounding an implant include the introduction of mechanical strain, activation of glial cells, loss of perfusion, secondary metabolic injury, and neuronal degeneration. Changes to the tissue microenvironment surrounding the device can dramatically impact electrochemical and electrophysiological signal sensitivity and stability over time. This review summarizes the magnitude, variability, and time course of the dynamic molecular and cellular level neural tissue responses induced by state-of-the-art implantable devices. Studies show that insertion injuries and foreign body response can impact signal quality across all implanted central nervous system (CNS) sensors to varying degrees over both acute (seconds to minutes) and chronic periods (weeks to months). Understanding the underlying biological processes behind the brain tissue response to the devices at the cellular and molecular level leads to a variety of intervention strategies for improving signal sensitivity and longevity.

Research paper thumbnail of Photoelectric artefact from optogenetics and imaging on microelectrodes and bioelectronics: New Challenges and Opportunities

Bioelectronics, electronic technologies that interface with biological systems, are experiencing ... more Bioelectronics, electronic technologies that interface with biological systems, are experiencing rapid growth in terms of technology development and applications, especially in neuroscience and neuroprosthetic research. The parallel growth with optogenetics and in vivo multi-photon microscopy has also begun to generate great enthusiasm for simultaneous applications with bioelectronic technologies. However, emerging research showing artefact contaminated data highlight the need for understanding the fundamental physical principles that critically impact experimental results and complicate their interpretation. This review covers four major topics: (1) material dependent properties of the photoelectric effect (conductor, semiconductor, organic, photoelectric work function (band gap)); (2) optic dependent properties of the photoelectric effect (single photon, multiphoton, entangled biphoton, intensity, wavelength, coherence); (3) strategies and limitations for avoiding/minimizing photoelectric effects; and (4) advantages of and applications for light-based bioelectronics (photo-bioelectronics).

Research paper thumbnail of Two-photon imaging of chronically implanted neural electrodes: Sealing methods and new insights.

Background: Two-photon microscopy has enabled the visualization of dynamic tissue changes to inju... more Background: Two-photon microscopy has enabled the visualization of dynamic tissue changes to injuryand disease in vivo. While this technique has provided powerful new information, in vivo two-photonchronic imaging around tethered cortical implants, such as microelectrodes or neural probes, presentunique challenges.New method: A number of strategies are described to prepare a cranial window to longitudinally observethe impact of neural probes on brain tissue and vasculature for up to 3 months.Results: It was found that silastic sealants limit cell infiltration into the craniotomy, thereby limiting lightscattering and preserving window clarity over time. In contrast, low concentration hydrogel sealantsfailed to prevent cell infiltration and their use at high concentration displaced brain tissue and disruptedprobe performance.Comparison with existing method(s): The use of silastic sealants allows for a suitable imaging window forlong term chronic experiments and revealed new insights regarding the dynamic leukocyte responsearound implants and the nature of chronic BBB leakage in the sub-dural space.Conclusion: The presented method provides a valuable tool for evaluating the chronic inflammatoryresponse and the performance of emerging implantable neural technologies.

Research paper thumbnail of Contrast mechanisms and acquisition methods in functional MRI

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2004

Functional brain imaging using MRI (functional MRI or fMRI) has become a valuable tool for studyi... more Functional brain imaging using MRI (functional MRI or fMRI) has become a valuable tool for studying function/structure relationships in the human brain in both normal and clinical populations. This paper describes the physiological changes associated with brain activity, including changes in blood flow, volume, and oxygenation. The latter of these, known as blood oxygenation level dependent (BOLD) contrast, is the most common approach for functional MRI, but it is related to brain activity via a variety of complex mechanisms. Here we describe a physiological and fluid mechanical model that can explain the shape and behavior seen in the BOLD response and may allow for improved quantification of the measured response. We also describe basic acquisition methods used in BOLD fMRI and associated artifacts. Finally, we briefly introduce approaches to acquired alternate contrast mechanisms in fMRI.

Research paper thumbnail of Nonlinear Aspects of the BOLD Response in Functional MRI

NeuroImage, 1998

Functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) contr... more Functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) contrast has progressed rapidly and is commonly used to study function in many regions of the human brain. This paper introduces a method for characterizing the linear or nonlinear properties of the hemodynamic response. Such characterization is essential for accurate prediction of time-course behavior. Linearity of the BOLD response was examined in the primary visual cortex for manipulations of the stimulus amplitude and duration. Stimuli of 1, 2, 4, and 8 s duration (80% contrast) and 10, 20, 40, and 80% contrast (4 s duration) were used to test the hemodynamic response. Superposition of the obtained responses was performed to determine if the BOLD response is nonlinear. The nonlinear characteristics of the BOLD response were assessed using a Laplacian linear system model cascaded with a broadening function. Discrepancies between the model and the observed response provide an indirect measure of the nonlinearity of the response. The Laplacian linear system remained constant within subjects so the broadening function can be used to absorb nonlinearities in the response. The results show that visual stimulation under 4 s in duration and less than 40% contrast yield strong nonlinear responses. 1998 Academic Press

Research paper thumbnail of Biomechanical Model of Brain Vasculature

The vascular compartment plays a very important role in the response observed during a BOLD (bloo... more The vascular compartment plays a very important role in the response observed during a BOLD (blood oxygenation level-dependent) contrast experiment. Principally, it contains the contrast agent that makes us sensitive to chages in metabolic demand (which is related to ...

Research paper thumbnail of The dynamics of the blood oxygenation response in functional magnetic resonance imaging

UMI, ProQuest ® Dissertations & Theses. The world's most comprehensive collectio... more UMI, ProQuest ® Dissertations & Theses. The world's most comprehensive collection of dissertations and theses. Learn more... ProQuest, The dynamics of the blood oxygenation response in functional magnetic resonance imaging. ...

Research paper thumbnail of Temporal BOLD Characteristics and Non-Linearity

S St ta ar rt t o of f E Ev ve en nt t S Sl lo ow we er r N Ne eg ga at ti iv ve e R Re es sp po ... more S St ta ar rt t o of f E Ev ve en nt t S Sl lo ow we er r N Ne eg ga at ti iv ve e R Re es sp po on ns se e R Ri is se e a an nd d

Research paper thumbnail of Time-invariant properties of the {BOLD} response

Research paper thumbnail of A study of the time-invariant properties of the BOLD response

Research paper thumbnail of Non-linear temporal aspects of the BOLD response in fMRI

Research paper thumbnail of Assessing the quantification of CMRO2 from blood oxygen measurements

Research paper thumbnail of An agent-based Collaboratory

Collaboration for distributed groups can be supported by intelligent agents in charge of several ... more Collaboration for distributed groups can be supported by intelligent agents in charge of several functionalities, partly addressed by Computer Supported Co-operative Work (CSCW) and Knowledge Management Systems. Collaboratories are special type of systems covering the needs of research communities. We describe here an agent-based architecture and a real collaboratory implementation that is a natural evolution of a set of recommender

Research paper thumbnail of VALORACIÓN DEL SISTEMA TRADICIONAL DE PRODUCCIÓN CAPRINA A PARTIR DE MECANISMOS DE DIFERENCIACIÓN, EL CASO DEL "CHIVITO CRIOLLO DEL NORTE NEUQUINO

En este trabajo comentaremos la experiencia realizada en la provincia de Neuquén (Patagonia, Arge... more En este trabajo comentaremos la experiencia realizada en la provincia de Neuquén (Patagonia, Argentina) sobre la valorización del sistema de producción criancero trashumante. Como hipótesis se sostiene que los mecanismos de diferenciación como la denominación de origen (DO), son eficaces para la promoción del desarrollo, la valorización territorial y la inserción en el mercado de los productos de sistema tradicionales. Este mecanismo reúne las cualidades propias del producto de un territorio particular, con el saber-hacer de un grupo social, amalgamados a lo largo de la historia. El proceso iniciado en 2005 es continuación de estudios previos sobre los recursos genéticos locales, la raza caprina "Criolla Neuquina"; y sobre las estrategias sociales y productivas de las familias crianceras. En una primera etapa se analizó la pertinencia de los mecanismos de diferenciación existentes vinculados a los productos agroalimentarios. Posteriormente, se construyó la visión compartid...

Research paper thumbnail of Changes in arterial oxygen tension with evoked stimulation in the rat somato-sensory cortex: implication for quantitative fMRI

Research paper thumbnail of Molsidomine in the treatment of acute heart failure

American Heart Journal, 1985

Research paper thumbnail of Two-photon imaging of chronically implanted neural electrodes: Sealing methods and new insights

Journal of neuroscience methods, Jan 23, 2015

Two-photon microscopy has enabled the visualization of dynamic tissue changes to injury and disea... more Two-photon microscopy has enabled the visualization of dynamic tissue changes to injury and disease in vivo. While this technique has provided powerful new information, in vivo two-photon chronic imaging around tethered cortical implants, such as microelectrodes or neural probes, present unique challenges. A number of strategies are described to prepare a cranial window to longitudinally observe the impact of neural probes on brain tissue and vasculature for up to 3 months. It was found that silastic sealants limit cell infiltration into the craniotomy, thereby limiting light scattering and preserving window clarity over time. In contrast, low concentration hydrogel sealants failed to prevent cell infiltration and their use at high concentration displaced brain tissue and disrupted probe performance. The use of silastic sealants allows for a suitable imaging window for long term chronic experiments and revealed new insights regarding the dynamic leukocyte response around implants an...

Research paper thumbnail of Microglia Vascular Movie

Research paper thumbnail of Photoelectric artefact from optogenetics and imaging on microelectrodes and bioelectronics: new challenges and opportunities

J. Mater. Chem. B, 2015

Bioelectronics, electronic technologies that interface with biological systems, are experiencing ... more Bioelectronics, electronic technologies that interface with biological systems, are experiencing rapid growth in terms of technology development and applications, especially in neuroscience and neuroprosthetic research. The parallel growth with optogenetics and in vivo multi-photon microscopy has also begun to generate great enthusiasm for simultaneous applications with bioelectronic technologies. However, emerging research showing artefact contaminated data highlight the need for understanding the fundamental physical principles that critically impact experimental results and complicate their interpretation. This review covers four major topics: (1) material dependent properties of the photoelectric effect (conductor, semiconductor, organic, photoelectric work function (band gap)); (2) optic dependent properties of the photoelectric effect (single photon, multiphoton, entangled biphoton, intensity, wavelength, coherence); (3) strategies and limitations for avoiding/minimizing photoelectric effects; and (4) advantages of and applications for light-based bioelectronics (photo-bioelectronics).

Research paper thumbnail of Cerebral oxygen delivery and consumption during evoked neural activity

Frontiers in neuroenergetics, 2010

Increases in neural activity evoke increases in the delivery and consumption of oxygen. Beyond ob... more Increases in neural activity evoke increases in the delivery and consumption of oxygen. Beyond observations of cerebral tissue and blood oxygen, the role and properties of cerebral oxygen delivery and consumption during changes in brain function are not well understood. This work overviews the current knowledge of functional oxygen delivery and consumption and introduces recent and preliminary findings to explore the mechanisms by which oxygen is delivered to tissue as well as the temporal dynamics of oxygen metabolism. Vascular oxygen tension measurements have shown that a relatively large amount of oxygen exits pial arterioles prior to capillaries. Additionally, increases in cerebral blood flow (CBF) induced by evoked neural activation are accompanied by arterial vasodilation and also by increases in arteriolar oxygenation. This increase contributes not only to the down-stream delivery of oxygen to tissue, but also to delivery of additional oxygen to extra-vascular spaces surround...

Research paper thumbnail of Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies

Implantable biosensors are valuable scientific tools for basic neuroscience research and clinical... more Implantable biosensors are valuable scientific tools for basic neuroscience research and clinical applications. Neurotechnologies provide direct readouts of neurological signal and neurochemical processes. These tools are generally most valuable when performance capacities extend over months and years to facilitate the study of memory, plasticity, and behavior or to monitor patients’ conditions. These needs have generated a variety of device designs from microelectrodes for fast scan cyclic voltammetry (FSCV) and electrophysiology to microdialysis probes for sampling and detecting various neurochemicals. Regardless of the technology used, the breaching of the blood–brain barrier (BBB) to insert devices triggers a cascade of biochemical pathways resulting in complex molecular and cellular responses to implanted devices. Molecular and cellular changes in the microenvironment surrounding an implant include the introduction of mechanical strain, activation of glial cells, loss of perfusion, secondary metabolic injury, and neuronal degeneration. Changes to the tissue microenvironment surrounding the device can dramatically impact electrochemical and electrophysiological signal sensitivity and stability over time. This review summarizes the magnitude, variability, and time course of the dynamic molecular and cellular level neural tissue responses induced by state-of-the-art implantable devices. Studies show that insertion injuries and foreign body response can impact signal quality across all implanted central nervous system (CNS) sensors to varying degrees over both acute (seconds to minutes) and chronic periods (weeks to months). Understanding the underlying biological processes behind the brain tissue response to the devices at the cellular and molecular level leads to a variety of intervention strategies for improving signal sensitivity and longevity.

Research paper thumbnail of Photoelectric artefact from optogenetics and imaging on microelectrodes and bioelectronics: New Challenges and Opportunities

Bioelectronics, electronic technologies that interface with biological systems, are experiencing ... more Bioelectronics, electronic technologies that interface with biological systems, are experiencing rapid growth in terms of technology development and applications, especially in neuroscience and neuroprosthetic research. The parallel growth with optogenetics and in vivo multi-photon microscopy has also begun to generate great enthusiasm for simultaneous applications with bioelectronic technologies. However, emerging research showing artefact contaminated data highlight the need for understanding the fundamental physical principles that critically impact experimental results and complicate their interpretation. This review covers four major topics: (1) material dependent properties of the photoelectric effect (conductor, semiconductor, organic, photoelectric work function (band gap)); (2) optic dependent properties of the photoelectric effect (single photon, multiphoton, entangled biphoton, intensity, wavelength, coherence); (3) strategies and limitations for avoiding/minimizing photoelectric effects; and (4) advantages of and applications for light-based bioelectronics (photo-bioelectronics).

Research paper thumbnail of Two-photon imaging of chronically implanted neural electrodes: Sealing methods and new insights.

Background: Two-photon microscopy has enabled the visualization of dynamic tissue changes to inju... more Background: Two-photon microscopy has enabled the visualization of dynamic tissue changes to injuryand disease in vivo. While this technique has provided powerful new information, in vivo two-photonchronic imaging around tethered cortical implants, such as microelectrodes or neural probes, presentunique challenges.New method: A number of strategies are described to prepare a cranial window to longitudinally observethe impact of neural probes on brain tissue and vasculature for up to 3 months.Results: It was found that silastic sealants limit cell infiltration into the craniotomy, thereby limiting lightscattering and preserving window clarity over time. In contrast, low concentration hydrogel sealantsfailed to prevent cell infiltration and their use at high concentration displaced brain tissue and disruptedprobe performance.Comparison with existing method(s): The use of silastic sealants allows for a suitable imaging window forlong term chronic experiments and revealed new insights regarding the dynamic leukocyte responsearound implants and the nature of chronic BBB leakage in the sub-dural space.Conclusion: The presented method provides a valuable tool for evaluating the chronic inflammatoryresponse and the performance of emerging implantable neural technologies.

Research paper thumbnail of Contrast mechanisms and acquisition methods in functional MRI

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2004

Functional brain imaging using MRI (functional MRI or fMRI) has become a valuable tool for studyi... more Functional brain imaging using MRI (functional MRI or fMRI) has become a valuable tool for studying function/structure relationships in the human brain in both normal and clinical populations. This paper describes the physiological changes associated with brain activity, including changes in blood flow, volume, and oxygenation. The latter of these, known as blood oxygenation level dependent (BOLD) contrast, is the most common approach for functional MRI, but it is related to brain activity via a variety of complex mechanisms. Here we describe a physiological and fluid mechanical model that can explain the shape and behavior seen in the BOLD response and may allow for improved quantification of the measured response. We also describe basic acquisition methods used in BOLD fMRI and associated artifacts. Finally, we briefly introduce approaches to acquired alternate contrast mechanisms in fMRI.

Research paper thumbnail of Nonlinear Aspects of the BOLD Response in Functional MRI

NeuroImage, 1998

Functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) contr... more Functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) contrast has progressed rapidly and is commonly used to study function in many regions of the human brain. This paper introduces a method for characterizing the linear or nonlinear properties of the hemodynamic response. Such characterization is essential for accurate prediction of time-course behavior. Linearity of the BOLD response was examined in the primary visual cortex for manipulations of the stimulus amplitude and duration. Stimuli of 1, 2, 4, and 8 s duration (80% contrast) and 10, 20, 40, and 80% contrast (4 s duration) were used to test the hemodynamic response. Superposition of the obtained responses was performed to determine if the BOLD response is nonlinear. The nonlinear characteristics of the BOLD response were assessed using a Laplacian linear system model cascaded with a broadening function. Discrepancies between the model and the observed response provide an indirect measure of the nonlinearity of the response. The Laplacian linear system remained constant within subjects so the broadening function can be used to absorb nonlinearities in the response. The results show that visual stimulation under 4 s in duration and less than 40% contrast yield strong nonlinear responses. 1998 Academic Press

Research paper thumbnail of Biomechanical Model of Brain Vasculature

The vascular compartment plays a very important role in the response observed during a BOLD (bloo... more The vascular compartment plays a very important role in the response observed during a BOLD (blood oxygenation level-dependent) contrast experiment. Principally, it contains the contrast agent that makes us sensitive to chages in metabolic demand (which is related to ...

Research paper thumbnail of The dynamics of the blood oxygenation response in functional magnetic resonance imaging

UMI, ProQuest ® Dissertations & Theses. The world's most comprehensive collectio... more UMI, ProQuest ® Dissertations & Theses. The world's most comprehensive collection of dissertations and theses. Learn more... ProQuest, The dynamics of the blood oxygenation response in functional magnetic resonance imaging. ...

Research paper thumbnail of Temporal BOLD Characteristics and Non-Linearity

S St ta ar rt t o of f E Ev ve en nt t S Sl lo ow we er r N Ne eg ga at ti iv ve e R Re es sp po ... more S St ta ar rt t o of f E Ev ve en nt t S Sl lo ow we er r N Ne eg ga at ti iv ve e R Re es sp po on ns se e R Ri is se e a an nd d

Research paper thumbnail of Time-invariant properties of the {BOLD} response

Research paper thumbnail of A study of the time-invariant properties of the BOLD response

Research paper thumbnail of Non-linear temporal aspects of the BOLD response in fMRI

Research paper thumbnail of Assessing the quantification of CMRO2 from blood oxygen measurements

Research paper thumbnail of An agent-based Collaboratory

Collaboration for distributed groups can be supported by intelligent agents in charge of several ... more Collaboration for distributed groups can be supported by intelligent agents in charge of several functionalities, partly addressed by Computer Supported Co-operative Work (CSCW) and Knowledge Management Systems. Collaboratories are special type of systems covering the needs of research communities. We describe here an agent-based architecture and a real collaboratory implementation that is a natural evolution of a set of recommender

Research paper thumbnail of VALORACIÓN DEL SISTEMA TRADICIONAL DE PRODUCCIÓN CAPRINA A PARTIR DE MECANISMOS DE DIFERENCIACIÓN, EL CASO DEL "CHIVITO CRIOLLO DEL NORTE NEUQUINO

En este trabajo comentaremos la experiencia realizada en la provincia de Neuquén (Patagonia, Arge... more En este trabajo comentaremos la experiencia realizada en la provincia de Neuquén (Patagonia, Argentina) sobre la valorización del sistema de producción criancero trashumante. Como hipótesis se sostiene que los mecanismos de diferenciación como la denominación de origen (DO), son eficaces para la promoción del desarrollo, la valorización territorial y la inserción en el mercado de los productos de sistema tradicionales. Este mecanismo reúne las cualidades propias del producto de un territorio particular, con el saber-hacer de un grupo social, amalgamados a lo largo de la historia. El proceso iniciado en 2005 es continuación de estudios previos sobre los recursos genéticos locales, la raza caprina "Criolla Neuquina"; y sobre las estrategias sociales y productivas de las familias crianceras. En una primera etapa se analizó la pertinencia de los mecanismos de diferenciación existentes vinculados a los productos agroalimentarios. Posteriormente, se construyó la visión compartid...

Research paper thumbnail of Changes in arterial oxygen tension with evoked stimulation in the rat somato-sensory cortex: implication for quantitative fMRI

Research paper thumbnail of Molsidomine in the treatment of acute heart failure

American Heart Journal, 1985

Research paper thumbnail of Two-photon imaging of chronically implanted neural electrodes: Sealing methods and new insights

Journal of neuroscience methods, Jan 23, 2015

Two-photon microscopy has enabled the visualization of dynamic tissue changes to injury and disea... more Two-photon microscopy has enabled the visualization of dynamic tissue changes to injury and disease in vivo. While this technique has provided powerful new information, in vivo two-photon chronic imaging around tethered cortical implants, such as microelectrodes or neural probes, present unique challenges. A number of strategies are described to prepare a cranial window to longitudinally observe the impact of neural probes on brain tissue and vasculature for up to 3 months. It was found that silastic sealants limit cell infiltration into the craniotomy, thereby limiting light scattering and preserving window clarity over time. In contrast, low concentration hydrogel sealants failed to prevent cell infiltration and their use at high concentration displaced brain tissue and disrupted probe performance. The use of silastic sealants allows for a suitable imaging window for long term chronic experiments and revealed new insights regarding the dynamic leukocyte response around implants an...

Research paper thumbnail of Microglia Vascular Movie

Research paper thumbnail of Photoelectric artefact from optogenetics and imaging on microelectrodes and bioelectronics: new challenges and opportunities

J. Mater. Chem. B, 2015

Bioelectronics, electronic technologies that interface with biological systems, are experiencing ... more Bioelectronics, electronic technologies that interface with biological systems, are experiencing rapid growth in terms of technology development and applications, especially in neuroscience and neuroprosthetic research. The parallel growth with optogenetics and in vivo multi-photon microscopy has also begun to generate great enthusiasm for simultaneous applications with bioelectronic technologies. However, emerging research showing artefact contaminated data highlight the need for understanding the fundamental physical principles that critically impact experimental results and complicate their interpretation. This review covers four major topics: (1) material dependent properties of the photoelectric effect (conductor, semiconductor, organic, photoelectric work function (band gap)); (2) optic dependent properties of the photoelectric effect (single photon, multiphoton, entangled biphoton, intensity, wavelength, coherence); (3) strategies and limitations for avoiding/minimizing photoelectric effects; and (4) advantages of and applications for light-based bioelectronics (photo-bioelectronics).

Research paper thumbnail of Cerebral oxygen delivery and consumption during evoked neural activity

Frontiers in neuroenergetics, 2010

Increases in neural activity evoke increases in the delivery and consumption of oxygen. Beyond ob... more Increases in neural activity evoke increases in the delivery and consumption of oxygen. Beyond observations of cerebral tissue and blood oxygen, the role and properties of cerebral oxygen delivery and consumption during changes in brain function are not well understood. This work overviews the current knowledge of functional oxygen delivery and consumption and introduces recent and preliminary findings to explore the mechanisms by which oxygen is delivered to tissue as well as the temporal dynamics of oxygen metabolism. Vascular oxygen tension measurements have shown that a relatively large amount of oxygen exits pial arterioles prior to capillaries. Additionally, increases in cerebral blood flow (CBF) induced by evoked neural activation are accompanied by arterial vasodilation and also by increases in arteriolar oxygenation. This increase contributes not only to the down-stream delivery of oxygen to tissue, but also to delivery of additional oxygen to extra-vascular spaces surround...