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1. Baseline oxygen consumption decreases with cortical depth.

Author

Philipp Mächler, Natalie Fomin-Thunemann, Martin Thunemann, Marte Julie Sætra, Michèle Desjardins, Kıvılcım Kılıç, Layth N Amra, Emily A Martin, Ichun Anderson Chen, Ikbal Şencan-Eğilmez, Baoqiang Li, Payam Saisan, John X Jiang, Qun Cheng, Kimberly L Weldy, David A Boas, Richard B Buxton, Gaute T Einevoll, Anders M Dale, Sava Sakadžić, and Anna Devor

Subjects
Biology (General), QH301-705.5
Abstract

The cerebral cortex is organized in cortical layers that differ in their cellular density, composition, and wiring. Cortical laminar architecture is also readily revealed by staining for cytochrome oxidase-the last enzyme in the respiratory electron transport chain located in the inner mitochondrial membrane. It has been hypothesized that a high-density band of cytochrome oxidase in cortical layer IV reflects higher oxygen consumption under baseline (unstimulated) conditions. Here, we tested the above hypothesis using direct measurements of the partial pressure of O2 (pO2) in cortical tissue by means of 2-photon phosphorescence lifetime microscopy (2PLM). We revisited our previously developed method for extraction of the cerebral metabolic rate of O2 (CMRO2) based on 2-photon pO2 measurements around diving arterioles and applied this method to estimate baseline CMRO2 in awake mice across cortical layers. To our surprise, our results revealed a decrease in baseline CMRO2 from layer I to layer IV. This decrease of CMRO2 with cortical depth was paralleled by an increase in tissue oxygenation. Higher baseline oxygenation and cytochrome density in layer IV may serve as an O2 reserve during surges of neuronal activity or certain metabolically active brain states rather than reflecting baseline energy needs. Our study provides to our knowledge the first quantification of microscopically resolved CMRO2 across cortical layers as a step towards better understanding of brain energy metabolism.

Published
2022
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3. The potential for gas-free measurements of absolute oxygen metabolism during both baseline and activation states in the human brain

Author

Eulanca Y. Liu, Jia Guo, Aaron B. Simon, Frank Haist, David J. Dubowitz, and Richard B. Buxton

Subjects
Functional MRI, Blood oxygenation level dependent, Hypercapnia, Cerebral metabolism of oxygen, Oxygen extraction fraction, Cerebral blood flow, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Quantitative functional magnetic resonance imaging methods make it possible to measure cerebral oxygen metabolism (CMRO2) in the human brain. Current methods require the subject to breathe special gas mixtures (hypercapnia and hyperoxia). We tested a noninvasive suite of methods to measure absolute CMRO2 in both baseline and dynamic activation states without the use of special gases: arterial spin labeling (ASL) to measure baseline and activation cerebral blood flow (CBF), with concurrent measurement of the blood oxygenation level dependent (BOLD) signal as a dynamic change in tissue R2*; VSEAN to estimate baseline O2 extraction fraction (OEF) from a measurement of venous blood R2, which in combination with the baseline CBF measurement yields an estimate of baseline CMRO2; and FLAIR-GESSE to measure tissue R2′ to estimate the scaling parameter needed for calculating the change in CMRO2 in response to a stimulus with the calibrated BOLD method. Here we describe results for a study sample of 17 subjects (8 female, mean age = 25.3 years, range 21–31 years). The primary findings were that OEF values measured with the VSEAN method were in good agreement with previous PET findings, while estimates of the dynamic change in CMRO2 in response to a visual stimulus were in good agreement between the traditional hypercapnia calibration and calibration based on R2′. These results support the potential of gas-free methods for quantitative physiological measurements.

Published
2020
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6. Metabolic energetics underlying attractors in neural models

Author

Richard B. Buxton and Eric C. Wong

Abstract

Neural population modeling, including the role of neural attractors, is a promising tool for understanding many aspects of brain function. We propose a modeling framework to connect the abstract variables used in modeling to recent cellular level estimates of the bioenergetic costs of different aspects of neural activity, measured in ATP consumed per second per neuron. Based on recent work, an empirical reference for brain ATP use for the awake resting brain was estimated as ∼2×109ATP/s-neuron across several mammalian species. The energetics framework was applied to the Wilson-Cowan (WC) model of two interacting populations of neurons, one excitatory (E) and one inhibitory (I). Attractors were considered exhibiting steady-state behavior and limit cycle behavior, both of which end when the excitatory stimulus ends, and sustained activity that persists after the stimulus ends. The general finding was that the energy cost essentially follows the firing rate (average spikes/s) of theE-population, and firing rates of 8-10 spikes/s are in good agreement with the empirical reference value of ATP use. Self-sustained firing driven by recurrent excitation, though, involves higher firing rates and a higher energy cost. By considering a network in which each node is a WC model, we found that a combination of three nodes can serve as a circuit element that turns on when input passes a threshold and then persists after the input ends (an ‘on-switch’), with moderate overall ATP use. The proposed framework can serve as a guide for anchoring neural population models to plausible bioenergetics requirements.

Published
2023
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9. Thermodynamic limitations on brain oxygen metabolism: physiological implications

Author

Richard B. Buxton

Abstract

A recent hypothesis is that maintaining the brain tissue ratio of O2to CO2is critical for preserving the entropy increase available from oxidative metabolism of glucose, with a fall of that available entropy leading to a reduction of the phosphorylation potential and impairment of brain energy metabolism. The hypothesis suggests that physiological responses under different conditions can be understood as preserving tissue O2/CO2. To test this idea, a mathematical model of O2and CO2transport was used to calculate how well different physiological responses maintain tissue O2/CO2, showing good agreement with reported experimental measurements for increased neural activity, hypercapnia and hypoxia. The results highlight the importance of thinking about brain blood flow as a way to modulate tissue O2/CO2, rather than simply in terms of O2delivery to the capillary bed. The hypoxia modeling focused on humans at high altitude, including acclimatized lowlanders and adapted populations, with a primary finding that decreasing CO2by increasing ventilation rate is much more effective for preserving tissue O2/CO2than increasing blood hemoglobin content. The modeling provides a new framework and perspective for understanding how blood flow and other physiological factors support energy metabolism in the brain under a wide range of conditions.Key points summaryRecent thermodynamic modeling suggests that preserving the O2/CO2ratio in brain tissue is critical for preserving the entropy change available from the oxidative metabolism of glucose and the phosphorylation potential underlying energy metabolism.The hypothesis tested is that normal physiological responses (notably blood flow changes) often act to preserve this ratio under changing conditions.Using a detailed model to calculate tissue O2/CO2we found good agreement with the predictions of the hypothesis and reported experimental results during hypoxia, hypercapnia and increased oxygen metabolic rate in response to increased neural activity.For the hypoxia modeling we considered high altitude acclimatization and adaptation in humans, showing the critical role of reducing CO2in preserving tissue O2/CO2.The tissue O2/CO2hypothesis provides a useful perspective for understanding the function of observed physiological responses under different conditions in terms of preserving brain energy metabolism, although the mechanisms underlying these functions are not well understood.

Published
2023
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25. Cell type specificity of neurovascular coupling in cerebral cortex

Author

Hana Uhlirova, Kıvılcım Kılıç, Peifang Tian, Martin Thunemann, Michèle Desjardins, Payam A Saisan, Sava Sakadžić, Torbjørn V Ness, Celine Mateo, Qun Cheng, Kimberly L Weldy, Florence Razoux, Matthieu Vandenberghe, Jonathan A Cremonesi, Christopher GL Ferri, Krystal Nizar, Vishnu B Sridhar, Tyler C Steed, Maxim Abashin, Yeshaiahu Fainman, Eliezer Masliah, Srdjan Djurovic, Ole A Andreassen, Gabriel A Silva, David A Boas, David Kleinfeld, Richard B Buxton, Gaute T Einevoll, Anders M Dale, and Anna Devor

Subjects
2-photon microscopy, optogenetic, dilation, constriction, NPY, Medicine, Science, Biology (General), QH301-705.5
Abstract

Identification of the cellular players and molecular messengers that communicate neuronal activity to the vasculature driving cerebral hemodynamics is important for (1) the basic understanding of cerebrovascular regulation and (2) interpretation of functional Magnetic Resonance Imaging (fMRI) signals. Using a combination of optogenetic stimulation and 2-photon imaging in mice, we demonstrate that selective activation of cortical excitation and inhibition elicits distinct vascular responses and identify the vasoconstrictive mechanism as Neuropeptide Y (NPY) acting on Y1 receptors. The latter implies that task-related negative Blood Oxygenation Level Dependent (BOLD) fMRI signals in the cerebral cortex under normal physiological conditions may be mainly driven by the NPY-positive inhibitory neurons. Further, the NPY-Y1 pathway may offer a potential therapeutic target in cerebrovascular disease.

Published
2016
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26. Hemodynamic latency is associated with reduced intelligence across the lifespan: an fMRI DCM study of aging, cerebrovascular integrity, and cognitive ability

Author

Pamela K. Douglas, Karl J. Friston, Mahtash Esfandiari, Mirella Díaz-Santos, Susan Y. Bookheimer, Ariana Anderson, Spencer Frei, Bianca H. Dang, Usha Nookala, Patrick D. Lyden, Robert M. Bilder, Pashmeen Kaur, and Richard B. Buxton

Subjects
Aging, Neurology, Cerebrovascular, Haemodynamic response, Intelligence, Medical Physiology, Hemodynamics, Disease, Type 2 diabetes, Cardiovascular, Vascular dementia, Cognition, 0302 clinical medicine, Risk Factors, 80 and over, Aged, 80 and over, Brain Mapping, General Neuroscience, fMRI, 05 social sciences, Brain, Middle Aged, Magnetic Resonance Imaging, Heart Disease, Cardiology, Cognitive Sciences, Anatomy, Adult, medicine.medical_specialty, Histology, Adolescent, Longevity, Article, 050105 experimental psychology, Young Adult, 03 medical and health sciences, Clinical Research, Internal medicine, Behavioral and Social Science, Acquired Cognitive Impairment, medicine, Humans, 0501 psychology and cognitive sciences, Cognitive skill, Aged, Neurology & Neurosurgery, Hemodynamic response function, business.industry, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), medicine.disease, Brain Disorders, Cerebrovascular Disorders, Dynamic causal modeling, Dementia, business, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Changes in neurovascular coupling are associated with both Alzheimer's disease and vascular dementia in later life, but this may be confounded by cerebrovascular risk. We hypothesized that hemodynamic latency would be associated with reduced cognitive functioning across the lifespan, holding constant demographic and cerebrovascular risk. In 387 adults aged 18-85 (mean = 48.82), dynamic causal modeling was used to estimate the hemodynamic response function in the left and right V1 and V3-ventral regions of the visual cortex in response to a simple checkerboard block design stimulus with minimal cognitive demands. The hemodynamic latency (transit time) in the visual cortex was used to predict general cognitive ability (Full-Scale IQ), controlling for demographic variables (age, race, education, socioeconomic status) and cerebrovascular risk factors (hypertension, alcohol use, smoking, high cholesterol, BMI, type 2 diabetes, cardiac disorders). Increased hemodynamic latency in the visual cortex predicted reduced cognitive function (p

Published
2020
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27. A novel nonlinear analysis of blood flow dynamics applied to the human lung

Author

Richard B. Buxton, G. Kim Prisk, and Susan R. Hopkins

Subjects
Physiology, Physiology (medical), Altitude, Hypertension, Pulmonary, Innovative Methodology, Humans, Pulmonary Edema, Spin Labels, Disease Susceptibility, Altitude Sickness, Hypoxia, Lung
Abstract

The spatial/temporal dynamics of blood flow in the human lung can be measured noninvasively with magnetic resonance imaging (MRI) using arterial spin labeling (ASL). We report a novel data analysis method using nonlinear prediction to identify dynamic interactions between blood flow units (image voxels), potentially providing a probe of underlying vascular control mechanisms. The approach first estimates the linear relationship (predictability) of one voxel time series with another using correlation analysis, and after removing the linear component, it estimates the nonlinear relationship with a numerical mutual information approach. Dimensionless global metrics for linear prediction (F(L)) and nonlinear prediction (F(NL)) represent the average amplitude of fluctuations in one voxel estimated by another voxel, as a percentage of the global average voxel flow. A proof-of-principle test of this approach analyzed experimental data from a study of high-altitude pulmonary edema (HAPE), providing two groups exhibiting known differences in vascular reactivity. Subjects were mountaineers divided into HAPE-susceptible (S, n = 4) and HAPE-resistant (R, n = 5) groups based on prior history at high altitudes. Dynamic ASL measurements in the lung in normoxia (N, [Formula: see text] = 0.21) and hypoxia (H, [Formula: see text] = 0.13 ± 0.01) were compared. The nonlinear prediction metric F(NL) decreased with hypoxia [7.4 ± 1.3 (N) vs. 6.3 ± 0.7 (H), P = 0.03] and was significantly different between groups [7.4 ± 1.2 (R) vs. 6.2 ± 14.1 (S), P = 0.03]. This proof-of-principle test demonstrates that this nonlinear analysis approach applied to ASL data is sensitive to physiological effects even in small subject cohorts, and it potentially can be used in a wide range of studies in health and disease in the lung and other organs. NEW & NOTEWORTHY Pulmonary blood flow varies both spatially and temporally. We describe a novel technique to uncover nonlinear interactions in dynamic images of pulmonary blood flow measured using MRI, based on mutual information between the flow fluctuations in different imaging voxels. In a proof-of-principle study, we show that the proposed metric of nonlinear interactions was sufficiently sensitive to detect a difference between small cohorts of subjects susceptible to high-altitude pulmonary edema (HAPE) and subjects resistant to HAPE.

Published
2022

33. Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer:a multicentre pooled analysis of 5161 patients

Author

Christina Yau, Marie Osdoit, Marieke van der Noordaa, Sonal Shad, Jane Wei, Diane de Croze, Anne-Sophie Hamy, Marick Laé, Fabien Reyal, Gabe S Sonke, Tessa G Steenbruggen, Maartje van Seijen, Jelle Wesseling, Miguel Martín, Maria del Monte-Millán, Sara López-Tarruella, Judy C Boughey, Matthew P Goetz, Tanya Hoskin, Rebekah Gould, Vicente Valero, Stephen B Edge, Jean E Abraham, John M S Bartlett, Carlos Caldas, Janet Dunn, Helena Earl, Larry Hayward, Louise Hiller, Elena Provenzano, Stephen-John Sammut, Jeremy S Thomas, David Cameron, Ashley Graham, Peter Hall, Lorna Mackintosh, Fang Fan, Andrew K Godwin, Kelsey Schwensen, Priyanka Sharma, Angela M DeMichele, Kimberly Cole, Lajos Pusztai, Mi-Ok Kim, Laura J van 't Veer, Laura J Esserman, W Fraser Symmans, Kathi Adamson, Kathy S. Albain, Adam L. Asare, Smita M. Asare, Ron Balassanian, Heather Beckwith, Scott M. Berry, Donald A. Berry, Judy C. Boughey, Meredith B. Buxton, Yunn-Yi Chen, Beiyun Chen, A. Jo Chien, Stephen Y. Chui, Amy S. Clark, Julia L. Clennell, Brian Datnow, Angela M. DeMichele, Xiuzhen Duan, Kirsten K. Edmiston, Anthony D. Elias, Erin D. Ellis, Laura L. Esserman, David M. Euhus, Oluwole Fadare, Michael D Feldman, Andres Forero-Torres, Barbara B. Haley, Hyo S. Han, Shuko Harada, Patricia Haugen, Teresa Helsten, Gillian L. Hirst, Nola M. Hylton, Claudine Isaacs, Kathleen Kemmer, Qamar J. Khan, Laila Khazai, Molly E. Klein, Gregor Krings, Julie E. Lang, Lauren G. LeBeau, Brian Leyland-Jones, Minetta C. Liu, Shelly Lo, Janice Lu, Anthony Magliocco, Jeffrey B. Matthews, Michelle E. Melisko, Paulette Mhawech-Fauceglia, Stacy L. Moulder, Rashmi K. Murthy, Rita Nanda, Donald W. Northfelt, Idris T. Ocal, Olufunmilayo Olopade, Stefan Pambuccian, Melissa Paoloni, John W. Park, Barbara A. Parker, Jane Perlmutter, Garry Peterson, Mara Rendi, Hope S. Rugo, Sunati Sahoo, Sharon Sams, Ashish Sanil, Husain Sattar, Richard B. Schwab, Ruby Singhrao, Katherine Steeg, Erica Stringer-Reasor, W. Fraser Symmans, Ossama Tawfik, Debasish Tripathy, Megan L. Troxell, Laura J. van't Veer, Sara J. Venters, Tuyethoa Vinh, Rebecca K. Viscusi, Anne M. Wallace, Shi Wei, Amy Wilson, Douglas Yee, Jay C. Zeck, and Pathology

Subjects
Adult, Neoplasm, Residual, Adolescent, Receptor, ErbB-2, Oncology and Carcinogenesis, Breast Neoplasms, RC0254, Young Adult, ErbB-2, Clinical Research, Breast Cancer, 80 and over, Humans, Chemotherapy, Oncology & Carcinogenesis, Adjuvant, Aged, Cancer, Aged, 80 and over, Evaluation of treatments and therapeutic interventions, Middle Aged, Neoadjuvant Therapy, Oncology, Chemotherapy, Adjuvant, Residual, 6.1 Pharmaceuticals, Neoplasm, Female, I-SPY 2 Trial Consortium, Patient Safety, Receptor
Abstract

Background: Previous studies have independently validated the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. We used results from several independent cohorts in a pooled patient-level analysis to evaluate the relationship of RCB with long-term prognosis across different phenotypic subtypes of breast cancer, to assess generalisability in a broad range of practice settings. Methods: In this pooled analysis, 12 institutes and trials in Europe and the USA were identified by personal communications with site investigators. We obtained participant-level RCB results, and data on clinical and pathological stage, tumour subtype and grade, and treatment and follow-up in November, 2019, from patients (aged ≥18 years) with primary stage I–III breast cancer treated with neoadjuvant chemotherapy followed by surgery. We assessed the association between the continuous RCB score and the primary study outcome, event-free survival, using mixed-effects Cox models with the incorporation of random RCB and cohort effects to account for between-study heterogeneity, and stratification to account for differences in baseline hazard across cancer subtypes defined by hormone receptor status and HER2 status. The association was further evaluated within each breast cancer subtype in multivariable analyses incorporating random RCB and cohort effects and adjustments for age and pretreatment clinical T category, nodal status, and tumour grade. Kaplan-Meier estimates of event-free survival at 3, 5, and 10 years were computed for each RCB class within each subtype. Findings: We analysed participant-level data from 5161 patients treated with neoadjuvant chemotherapy between Sept 12, 1994, and Feb 11, 2019. Median age was 49 years (IQR 20–80). 1164 event-free survival events occurred during follow-up (median follow-up 56 months [IQR 0–186]). RCB score was prognostic within each breast cancer subtype, with higher RCB score significantly associated with worse event-free survival. The univariable hazard ratio (HR) associated with one unit increase in RCB ranged from 1·55 (95% CI 1·41–1·71) for hormone receptor-positive, HER2-negative patients to 2·16 (1·79–2·61) for the hormone receptor-negative, HER2-positive group (with or without HER2-targeted therapy; p

Published
2022
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39. Microscopic Quantification of Oxygen Consumption across Cortical Layers

Author

Anna Devor, Marte J. Sætra, Kimberly L. Weldy, Anders M. Dale, Gaute T. Einevoll, Martin Thunemann, Bin E. Li, Natalie Fomin-Thunemann, Payam A. Saisan, Qun Cheng, Kıvılcım Kılıç, Richard B. Buxton, Ikbal Sencan, David A. Boas, P. Mächler, Sava Sakadzic, and Michèle Desjardins

Subjects
Blood-oxygen-level dependent, Cytochrome, biology, Chemistry, chemistry.chemical_element, Oxygenation, Oxygen, Respiratory electron transport chain, medicine.anatomical_structure, Cerebral cortex, biology.protein, medicine, Biophysics, Premovement neuronal activity, Cytochrome c oxidase
Abstract

The cerebral cortex is organized in cortical layers that differ in their cellular density, composition, and wiring. Cortical laminar architecture is also readily revealed by staining for cytochrome oxidase – the last enzyme in the respiratory electron transport chain located in the inner mitochondrial membrane. It has been hypothesized that a high-density band of cytochrome oxidase in cortical layer IV reflects higher oxygen consumption under baseline (unstimulated) conditions. Here, we tested the above hypothesis using direct measurements of the partial pressure of O 2 (pO 2 ) in cortical tissue by means of 2-photon phosphorescence lifetime microscopy (2PLM). We revisited our previously developed method for extraction of the cerebral metabolic rate of O 2 (CMRO 2 ) based on 2-photon pO 2 measurements around diving arterioles and applied this method to estimate baseline CMRO 2 in awake mice across cortical layers. To our surprise, our results revealed a decrease in baseline CMRO 2 from layer I to layer IV . This decrease of CMRO 2 with cortical depth was paralleled by an increase in tissue oxygenation. Higher baseline oxygenation and cytochrome density in layer IV may serve as an O 2 reserve during surges of neuronal activity or certain metabolically active brain states rather than baseline energy needs. Our study provides the first quantification of microscopically resolved CMRO 2 across cortical layers as a step towards informed interpretation and modeling of cortical-layer-specific Blood Oxygen Level Dependent (BOLD) fMRI signals.

Published
2021
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40. Awake Mouse Imaging: From Two-Photon Microscopy to Blood Oxygen Level–Dependent Functional Magnetic Resonance Imaging

Author

Dominic Holland, Payam A. Saisan, Qun Cheng, Anders M. Dale, Anna Devor, Kimberly L. Weldy, Joseph B. Mandeville, David Kleinfeld, Michèle Desjardins, Andrew K. Dunn, Richard B. Buxton, Takaki Komiyama, Miriam Scadeng, Christopher G. L. Ferri, Kıvılcım Kılıç, Eric C. Wong, Martin Thunemann, Sava Sakadžić, Celine Mateo, David A. Boas, Robert Bussell, Baoqiang Li, Jonathan A. Cremonesi, and Thomas T. Liu

Subjects
genetic structures, Haemodynamic response, Cognitive Neuroscience, Neuroimaging, Article, 050105 experimental psychology, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Wakefulness, Biological Psychiatry, Blood-oxygen-level dependent, medicine.diagnostic_test, business.industry, Optical Imaging, 05 social sciences, Magnetic resonance imaging, Laser Speckle Imaging, Somatosensory Cortex, Blood flow, Magnetic Resonance Imaging, Optogenetics, Cerebral blood flow, Models, Animal, Neurology (clinical), Functional magnetic resonance imaging, business, 030217 neurology & neurosurgery, Biomedical engineering
Abstract

Background Functional magnetic resonance imaging (fMRI) in awake behaving mice is well positioned to bridge the detailed cellular-level view of brain activity, which has become available owing to recent advances in microscopic optical imaging and genetics, to the macroscopic scale of human noninvasive observables. However, though microscopic (e.g., two-photon imaging) studies in behaving mice have become a reality in many laboratories, awake mouse fMRI remains a challenge. Owing to variability in behavior among animals, performing all types of measurements within the same subject is highly desirable and can lead to higher scientific rigor. Methods We demonstrated blood oxygenation level–dependent fMRI in awake mice implanted with long-term cranial windows that allowed optical access for microscopic imaging modalities and optogenetic stimulation. We started with two-photon imaging of single-vessel diameter changes (n = 1). Next, we implemented intrinsic optical imaging of blood oxygenation and flow combined with laser speckle imaging of blood flow obtaining a mesoscopic picture of the hemodynamic response (n = 16). Then we obtained corresponding blood oxygenation level–dependent fMRI data (n = 5). All measurements could be performed in the same mice in response to identical sensory and optogenetic stimuli. Results The cranial window did not deteriorate the quality of fMRI and allowed alternation between imaging modalities in each subject. Conclusions This report provides a proof of feasibility for multiscale imaging approaches in awake mice. In the future, this protocol could be extended to include complex cognitive behaviors translatable to humans, such as sensory discrimination or attention.

Published
2019
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41. Corrigendum: Variability of the coupling of blood flow and oxygen metabolism responses in the brain: a problem for interpreting BOLD studies but potentially a new window on the underlying neural activity

Author

Richard B Buxton, Valerie E. M. Griffeth, Aaron B Simon, Farshad eMoradi, and Amir eShmuel

Subjects
fMRI, inhibition, cerebral blood flow, BOLD, cerebral metabolic rate of oxygen, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published
2014
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42. Variability of the coupling of blood flow and oxygen metabolism responses in the brain: a problem for interpreting BOLD studies but potentially a new window on the underlying neural activity

Author

Richard B Buxton, Valerie E. M. Griffeth, Aaron B. Simon, and Farshad eMoradi

Subjects
functional magnetic resonance imaging (fMRI), blood oxygenation level dependent (BOLD), cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), inhibitory/excitatory neural activity, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Recent studies from our group and others using quantitative fMRI methods have found that variations of the coupling ratio of blood flow (CBF) and oxygen metabolism (CMRO2) responses to a stimulus have a strong effect on the BOLD response. Across a number of studies an empirical pattern is emerging in the way CBF and CMRO2 changes are coupled to neural activation: if the stimulus is modulated to create a stronger response (e.g., increasing stimulus contrast), CBF is modulated more than CMRO2; on the other hand, if the brain state is altered such that the response to the same stimulus is increased (e.g., modulating attention, adaptation or excitability), CMRO2 is modulated more than CBF. Because CBF and CMRO2 changes conflict in producing BOLD signal changes, this finding has an important implication for conventional BOLD-fMRI studies: the BOLD response exaggerates the effects of stimulus variation but is only weakly sensitive to modulations of the brain state that alter the response to a standard stimulus. A speculative hypothesis is that variability of the coupling ratio of the CBF and CMRO2 responses reflects different proportions of inhibitory and excitatory evoked activity, potentially providing a new window on neural activity.

Published
2014
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43. A Suite of Neurophotonic Tools to Underpin the Contribution of Internal Brain States in fMRI

Author

Hana Uhlirova, Anna Devor, Massimo Vergassola, Celine Mateo, Sava Sakadžić, David A. Boas, Michèle Desjardins, Martin Thunemann, Kıvılcım Kılıç, Richard B. Buxton, Ikbal Sencan, Mohammad A. Yaseen, Laura D. Lewis, David Kleinfeld, Xin Yu, Andreas A. Linninger, Thomas Broggini, Martin Lauritzen, Bruce R. Rosen, Philipp Mächler, Natalie Fomin-Thunemann, Jonathan R. Polimeni, and Patrick R. Doran

Subjects
0303 health sciences, Future studies, medicine.diagnostic_test, Computer science, Brain maturation, Biomedical Engineering, Medicine (miscellaneous), Bioengineering, 02 engineering and technology, Longitudinal imaging, 021001 nanoscience & nanotechnology, Neuromodulation (medicine), Article, Biomaterials, 03 medical and health sciences, Optical imaging, Brain state, Cerebral blood flow, medicine, 0210 nano-technology, Functional magnetic resonance imaging, Neuroscience, 030304 developmental biology
Abstract

Recent developments in optical microscopy, applicable for large-scale and longitudinal imaging of cortical activity in behaving animals, open unprecedented opportunities to gain a deeper understanding of neurovascular and neurometabolic coupling during different brain states. Future studies will leverage these tools to deliver foundational knowledge about brain state-dependent regulation of cerebral blood flow and metabolism, as well as regulation as a function of brain maturation and aging. This knowledge is of critical importance to interpret hemodynamic signals observed with functional magnetic resonance imaging (fMRI).

Published
2021
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46. Production of light-flavor hadrons in pp collisions at root s=7 and root s=13 Tev

Author

Acharya, S. Acosta, F. T. Adam, J. Adamova, D. Adler, A. and Adolfsson, J. Aggarwal, M. M. Rinella, G. Aglieri and Agnello, M. Agrawal, N. Ahammed, Z. Ahn, S. U. Aiola, S. and Akindinov, A. Al-Turany, M. Alam, S. N. Albuquerque, D. S. D. Aleksandrov, D. Alessandro, B. Alfanda, H. M. and Alfaro Molina, R. Ali, Y. Alici, A. Alkin, A. Alme, J. and Alt, T. Altenkamper, L. Altsybeev, I. Anaam, M. N. and Andrei, C. Andreou, D. Andrews, H. A. Andronic, A. and Angeletti, M. Anguelov, V. Anson, C. Anticic, T. and Antinori, F. Antonioli, P. Anwar, R. Apadula, N. and Aphecetche, L. Appelshaeuser, H. Arcelli, S. Arnaldi, R. and Arratia, M. Arsene, I. C. Arslandok, M. Augustinus, A. and Averbeck, R. Azmi, M. D. Badala, A. Baek, Y. W. and Bagnasco, S. Bailhache, R. Bala, R. Baldisseri, A. Ball, M. Baral, R. C. Barbano, A. M. Barbera, R. Barile, F. and Barioglio, L. Barnafoeldi, G. G. Barnby, L. S. Barret, V. Bartalini, P. Barth, K. Bartsch, E. Bastid, N. and Basu, S. Batigne, G. Batyunya, B. Batzing, P. C. Bazo Alba, J. L. Bearden, I. G. Beck, H. Bedda, C. Behera, N. K. Belikov, I. Bellini, F. Bello Martinez, H. Bellwied, R. Beltran, L. G. E. Belyaev, V. Bencedi, G. Beole, S. and Bercuci, A. Berdnikov, Y. Berenyi, D. Bertens, R. A. and Berzano, D. Betev, L. Bhaduri, P. P. Bhasin, A. Bhat, I. R. Bhatt, H. Bhattacharjee, B. Bhom, J. Bianchi, A. and Bianchi, L. Bianchi, N. Bielcik, J. Bielcikova, J. and Bilandzic, A. Biro, G. Biswas, R. Biswas, S. Blair, J. T. Blau, D. Blume, C. Boca, G. Bock, F. Bogdanov, A. and Boldizsar, L. Bolozdynya, A. Bombara, M. Bonomi, G. and Bonora, M. Borel, H. Borissov, A. Borri, M. Botta, E. and Bourjau, C. Bratrud, L. Braun-Munzinger, P. Bregant, M. and Broker, T. A. Broz, M. Brucken, E. J. Bruna, E. and Bruno, G. E. Budnikov, D. Buesching, H. Bufalino, S. and Buhler, P. Buncic, P. Busch, O. Buthelezi, Z. Butt, J. B. Buxton, J. T. Cabala, J. Caffarri, D. Caines, H. and Caliva, A. Calvo Villar, E. Camacho, R. S. Camerini, P. and Capon, A. A. 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Zhu, Y. and Zichichi, A. Zimmermann, M. B. Zinovjev, G. Zmeskal, J. and ALICE Collaboration

Subjects
High Energy Physics::Experiment, Nuclear Experiment
Abstract

The production of pi(+/-), K-+/-, K-S(0), K*(892)(0), p, phi(1020), Lambda, Xi(-), Omega(-), and their antiparticles was measured in inelastic proton-proton (pp) collisions at a center-of-mass energy of root s = 13 TeV at midrapidity (vertical bar y vertical bar < 0.5) as a function of transverse momentum (P-T) using the ALICE detector at the CERN LHC. Furthermore, the single-particle p(T) distributions of K-S(0), Lambda, and (Lambda) over bar in inelastic pp collisions at root s = 7 TeV are reported here for the first time. The p(T) distributions are studied at midrapidity within the transverse momentum range 0

Published
2021

47. First measurement of quarkonium polarization in nuclear collisions at the LHC

Author

Acharya, S. Adamova, D. Adler, A. Adolfsson, J. and Aggarwal, M. M. Rinella, G. Aglieri Agnello, M. Agrawal, N. and Ahammed, Z. Ahmad, S. Ahn, S. U. Akbar, Z. and Akindinov, A. Al-Turany, M. Alam, S. N. Albuquerque, D. S. D. Aleksandrov, D. Alessandro, B. Alfanda, H. M. Alfaro Molina, R. Ali, B. Ali, Y. Alici, A. Alizadehvandchali, N. Alkin, A. Alme, J. Alt, T. Altenkamper, L. and Altsybeev, I. Anaam, M. N. Andrei, C. Andreou, D. and Andrews, H. A. Andronic, A. Angeletti, M. Anguelov, V. and Anson, C. Anticic, T. Antinori, F. Antonioli, P. Anwar, R. Apadula, N. Aphecetche, L. Appelshaeuser, H. Arcelli, S. Arnaldi, R. Arratia, M. Arsene, I. C. Arslandok, M. and Augustinus, A. Averbeck, R. Aziz, S. Azmi, M. D. and Badala, A. Baek, Y. W. Bagnasco, S. Bai, X. Bailhache, R. Bala, R. Baldisseri, A. Ball, M. Balouza, S. and Banerjee, D. Barbera, R. Barioglio, L. Barnafoldi, G. G. and Barnby, L. S. Barret, V. Bartalini, P. Bartels, C. and Barth, K. Bartsch, E. Baruffaldi, F. Bastid, N. Basu, S. and Batigne, G. Batyunya, B. Bauri, D. Bazo Alba, J. L. and Bearden, I. G. Beattie, C. Bedda, C. Behera, N. K. and Belikov, I. Hechavarria, A. D. C. Bell Bellini, F. Bellwied, R. Belyaev, V. Bencedi, G. Beole, S. Bercuci, A. and Berdnikov, Y. Berenyi, D. Bertens, R. A. Berzano, D. and Besoiu, M. G. Betev, L. Bhasin, A. Bhat, I. R. Bhat, M. A. Bhatt, H. Bhattacharjee, B. Bianchi, A. Bianchi, L. and Bianchi, N. Bielcik, J. Bielcikova, J. Bilandzic, A. and Biro, G. Biswas, R. Biswas, S. Blair, J. T. Blau, D. and Blume, C. Boca, G. Bock, F. Bogdanov, A. Boi, S. and Bok, J. Boldizsar, L. Bolozdynya, A. Bombara, M. Bonomi, G. Borel, H. Borissov, A. Bossi, H. Botta, E. and Bratrud, L. Braun-Munzinger, P. Bregant, M. Broz, M. and Brucken, J. Bruna, E. Bruno, G. E. Buckland, M. D. and Budnikov, D. Buesching, H. Bufalino, S. Bugnon, O. and Buhler, P. Buncic, P. Buthelezi, Z. Butt, J. B. Buxton, J. T. Bysiak, S. A. Caffarri, D. Caliva, A. Calvo Villar, E. Camacho, J. M. M. Camacho, R. 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Subjects
High Energy Physics::Experiment, Nuclear Experiment
Abstract

The polarization of inclusive J/psi and Upsilon(1S) produced in Pb-Pb collisions at root s(NN) = 5.02 TeV at the LHC is measured with the ALICE detector. The study is carried out by reconstructing the quarkonium through its decay to muon pairs in the rapidity region 2.5 < y < 4 and measuring the polar and azimuthal angular distributions of the muons. The polarization parameters lambda(theta), lambda(phi) and lambda(theta phi) are measured in the helicity and Collins-Soper reference frames, in the transverse momentum interval 2 < p(T) < 10 GeV/c and p(T) < 15 GeV/c for the J/psi and Upsilon(1S), respectively. The polarization parameters for the J/psi are found to be compatible with zero, within a maximum of about two standard deviations at low p(T), for both reference frames and over the whole p(T) range. The values are compared with the corresponding results obtained for pp collisions at root s = 7 and 8 TeV in a similar kinematic region by the ALICE and LHCb experiments. Although with much larger uncertainties, the polarization parameters for Upsilon(1S) production in Pb-Pb collisions are also consistent with zero. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Published
2021

48. Centrality dependence of J/psi and psi(2S) production and nuclear modification in p-Pb collisions at sNN=8.16 TeV

Author

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Zinovjev, G. Zmeskal, J. and ALICE Collaboration

Abstract

The inclusive production of the J/ and psi (2S) charmonium states is studied as a function of centrality in p-Pb collisions at a centre-of-mass energy per nucleon pair sNN = 8.16 TeV at the LHC. The measurement is performed in the dimuon decay channel with the ALICE apparatus in the centre-of-mass rapidity intervals -4.46 < y(cms)< -2.96 (Pb-going direction) and 2.03 < y(cms)< 3.53 (p-going direction), down to zero transverse momentum (p(T)). The J/psi and psi (2S) production cross sections are evaluated as a function of the collision centrality, estimated through the energy deposited in the zero degree calorimeter located in the Pb-going direction. The p(T)-differential J/psi production cross section is measured at backward and forward rapidity for several centrality classes, together with the corresponding average < p(T)> and ” open=”pT2 values. The nuclear effects affecting the production of both charmonium states are studied using the nuclear modification factor. In the p-going direction, a suppression of the production of both charmonium states is observed, which seems to increase from peripheral to central collisions. In the Pb-going direction, however, the centrality dependence is different for the two states: the nuclear modification factor of the J/psi increases from below unity in peripheral collisions to above unity in central collisions, while for the psi (2S) it stays below or consistent with unity for all centralities with no significant centrality dependence. The results are compared with measurements in p-Pb collisions at sNN = 5.02 TeV and no significant dependence on the energy of the collision is observed. Finally, the results are compared with theoretical models implementing various nuclear matter effects.

Published
2021

49. First measurement of the vertical bar t vertical bar-dependence of coherent J/psi photonuclear production

Author

Acharya, S. Acosta, F. T. Adam, J. Adamova, D. Adler, A. and Adolfsson, J. Aggarwal, M. M. Rinella, G. Aglieri and Agnello, M. Agrawal, N. Ahammed, Z. Ahn, S. U. Aiola, S. and Akindinov, A. Al-Turany, M. Alam, S. N. Albuquerque, D. S. D. Aleksandrov, D. Alessandro, B. Alfanda, H. M. and Alfaro Molina, R. Ali, Y. Alici, A. Alkin, A. Alme, J. and Alt, T. Altenkamper, L. Altsybeev, I. Anaam, M. N. and Andrei, C. Andreou, D. Andrews, H. A. Andronic, A. and Angeletti, M. Anguelov, V. Anson, C. Anticic, T. and Antinori, F. Antonioli, P. Anwar, R. Apadula, N. and Aphecetche, L. Appelshaeuser, H. Arcelli, S. Arnaldi, R. and Arratia, M. Arsene, I. C. Arslandok, M. Augustinus, A. and Averbeck, R. Azmi, M. D. Badala, A. Baek, Y. W. and Bagnasco, S. Bailhache, R. Bala, R. Baldisseri, A. Ball, M. Baral, R. C. Barbano, A. M. Barbera, R. Barile, F. and Barioglio, L. Barnafoeldi, G. G. Barnby, L. S. Barret, V. Bartalini, P. Barth, K. Bartsch, E. Bastid, N. and Basu, S. Batigne, G. Batyunya, B. 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Zhu, Y. and Zichichi, A. Zimmermann, M. B. Zinovjev, G. Zmeskal, J. and ALICE Collaboration

Subjects
High Energy Physics::Phenomenology, High Energy Physics::Experiment, Nuclear Experiment
Abstract

The first measurement of the cross section for coherent J/Psi photoproduction as a function of vertical bar t vertical bar, the square of the momentum transferred between the incoming and outgoing target nucleus, is presented. The data were measured with the ALICE detector in ultra-peripheral Pb-Pbcollisions at a centre-of-mass energy per nucleon pair root s(NN) = 5.02 TeV with the J/Psi produced in the central rapidity region vertical bar y vertical bar < 0.8, which corresponds to the small Bjorken-xrange (0.3 - 1.4) x 10(-3). The measured vertical bar t vertical bar-dependence is not described by computations based only on the Pb nuclear form factor, while the photonuclear cross section is better reproduced by models including shadowing according to the leading-twist approximation, or gluon-saturation effects from the impact-parameter dependent Balitsky-Kovchegov equation. These new results are therefore a valid tool to constrain the relevant model parameters and to investigate the transverse gluonic structure at very low Bjorken- x. (C) 2021 The Author(s). Published by Elsevier B.V.

Published
2021

50. Lambda K femtoscopy in Pb-Pb collisions at root s(NN)=2.76 TeV

Author

Acharya, S. Adamova, D. Adler, A. Adolfsson, J. and Aggarwal, M. M. Rinella, G. Aglieri Agnello, M. Agrawal, N. and Ahammed, Z. Ahmad, S. Ahn, S. U. Akbar, Z. and Akindinov, A. Al-Turany, M. Alam, S. N. Albuquerque, D. S. D. Aleksandrov, D. Alessandro, B. Alfanda, H. M. Molina, R. Alfaro Ali, B. Ali, Y. Alici, A. Alkin, A. Alme, J. Alt, T. Altenkamper, L. Altsybeev, I Anaam, M. N. and Andrei, C. Andreou, D. Andronic, A. Angeletti, M. and Anguelov, V Anson, C. Antinori, F. Antonioli, P. and Apadula, N. Aphecetche, L. Appelshauser, H. Arcelli, S. and Arnaldi, R. Arratia, M. Arsene, I. C. Arslandok, M. and Augustinus, A. Averbeck, R. Aziz, S. Azmi, M. D. Badala, A. Baek, Y. W. Bagnasco, S. Bai, X. Bailhache, R. and Bala, R. Balbino, A. Baldisseri, A. Ball, M. Balouza, S. and Banerjee, D. Barbera, R. Barioglio, L. Barnafoldi, G. G. and Barnby, L. S. Barret, V Bartalini, P. Bartels, C. and Barth, K. Bartsch, E. Baruffaldi, F. Bastid, N. Basu, S. and Batigne, G. Batyunya, B. Bauri, D. 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Abstract

The first measurements of the scattering parameters of Lambda K pairs in all three charge combinations (Lambda K+, Lambda K-, and Lambda K-S(0)) are presented. The results are achieved through a femtoscopic analysis of Lambda K correlations in Pb-Pb collisions at root s(NN) = 2.76 TeV recorded by ALICE at the Large Hadron Collider. The femtoscopic correlations result from strong final-state interactions and are fit with a parametrization allowing for both the characterization of the pair emission source and the measurement of the scattering parameters for the particle pairs. Extensive studies with the THERMINATOR 2 event generator provide a good description of the nonfemtoscopic background, which results mainly from collective effects, with unprecedented precision. Furthermore, together with HIJING simulations, this model is used to account for contributions from residual correlations induced by feed-down from particle decays. The extracted scattering parameters indicate that the strong force is repulsive in the Lambda K+ interaction and attractive in the Lambda K- interaction. The data hint that the Lambda K-S(0) interaction is attractive; however, the uncertainty of the result does not permit such a decisive conclusion. The results suggest an effect arising either from different quark-antiquark interactions between the pairs (s (s) over bar in Lambda K+ and u (u) over bar in Lambda K-) or from different net strangeness for each system (S = 0 for Lambda K+, and S = -2 for Lambda K-). Finally, the Lambda K systems exhibit source radii larger than expected from extrapolation from identical particle femtoscopic studies. This effect is interpreted as resulting from the separation in space-time of the single-particle Lambda and K source distributions.

Published
2021

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