Resting-state functional MRI of the nose as a novel investigational window into the nervous system.

Besides being responsible for olfaction and air intake, the nose contains abundant vasculature and autonomic nervous system innervations, and it is a cerebrospinal fluid clearance site. Therefore, the nose is an attractive target for functional MRI (fMRI). Yet, nose fMRI has not been possible so far due to signal losses originating from nasal air-tissue interfaces.

Medial prefrontal cortex neurotransmitter abnormalities in posttraumatic stress disorder with and without comorbidity to major depression.

Posttraumatic stress disorder (PTSD) is a chronic psychiatric condition that follows exposure to a traumatic stressor. Though previous in vivo proton (H) MRS) research conducted at 4 T or lower has identified alterations in glutamate metabolism associated with PTSD predisposition and/or progression, no prior investigations have been conducted at higher field strength. In addition, earlier studies have not extensively addressed the impact of psychiatric comorbidities such as major depressive disorder (MDD) on PTSD-associated H-MRS-visible brain metabolite abnormalities.

Acute Management of Moderate to Severe Traumatic Brain Injury.

The focus of this article is on the acute management of traumatic brain injury. The article focuses on the classification of traumatic brain injury, general acute management of traumatic brain injury, the role of the physiatrist on this team, and lastly, behavioral and family considerations in the acute care setting. The article includes a focus on physiologic systems, strategies for the management of various aspects of brain injury, and consideration of factors associated with the continuum of care.

In vivo neuropil density from anatomical MRI and machine learning.

Brain energy budgets specify metabolic costs emerging from underlying mechanisms of cellular and synaptic activities. While current bottom-up energy budgets use prototypical values of cellular density and synaptic density, predicting metabolism from a person's individualized neuropil density would be ideal. We hypothesize that in vivo neuropil density can be derived from magnetic resonance imaging (MRI) data, consisting of longitudinal relaxation (T1) MRI for gray/white matter distinction and diffusion MRI for tissue cellularity (apparent diffusion coefficient, ADC) and axon directionality (fractional anisotropy, FA).

Deficits in brain glucose transport among younger adults with obesity.

Objective: Obesity is associated with alterations in eating behavior and neurocognitive function. In this study, we investigate the effect of obesity on brain energy utilization, including brain glucose transport and metabolism.

Methods: A total of 11 lean participants and 7 young healthy participants with obesity (mean age, 27 years) underwent magnetic resonance spectroscopy scanning coupled with a hyperglycemic clamp (target, ~180 mg/dL) using [1-C] glucose to measure brain glucose uptake and metabolism, as well as peripheral markers of insulin resistance.

Slow closure of Earth's carbon cycle.

Carbon near the Earth's surface cycles between the production and consumption of organic carbon; the former sequesters carbon dioxide while the latter releases it. Microbes attempt to close the loop, but the longer organic matter survives, the slower microbial degradation becomes. This aging effect leaves observable quantitative signatures: Organic matter decays at rates that are inversely proportional to its age, while microbial populations and concentrations of organic carbon in ocean sediments decrease at distinct powers of age.

Brain energy metabolism: A roadmap for future research.

Although we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well as during development, aging, and disease. The focus is on unknowns in metabolism of major brain substrates and associated transporters, the roles of insulin and of lipid droplets, the emerging role of metabolism in microglia, mysteries about the major brain cofactor and signaling molecule NAD, as well as unsolved problems underlying brain metabolism in pathologies such as traumatic brain injury, epilepsy, and metabolic downregulation during hibernation.

Magnetic Resonance Spectroscopy Spectral Registration Using Deep Learning.

Background: Deep learning-based methods have been successfully applied to MRI image registration. However, there is a lack of deep learning-based registration methods for magnetic resonance spectroscopy (MRS) spectral registration (SR).

Purpose: To investigate a convolutional neural network-based SR (CNN-SR) approach for simultaneous frequency-and-phase correction (FPC) of single-voxel Meshcher-Garwood point-resolved spectroscopy (MEGA-PRESS) MRS data.

The impact of metabolism on the adaptation of organisms to environmental change.

Since Jacob and Monod's discovery of the lac operon ∼1960, the explanations offered for most metabolic adaptations have been genetic. The focus has been on the adaptive changes in gene expression that occur, which are often referred to as "metabolic reprogramming." The contributions metabolism makes to adaptation have been largely ignored.

Neurovascular coupling is optimized to compensate for the increase in proton production from nonoxidative glycolysis and glycogenolysis during brain activation and maintain homeostasis of pH, pCO, and pO.

During transient brain activation cerebral blood flow (CBF) increases substantially more than cerebral metabolic rate of oxygen consumption (CMRO) resulting in blood hyperoxygenation, the basis of BOLD-fMRI contrast. Explanations for the high CBF versus CMRO slope, termed neurovascular coupling (NVC) constant, focused on maintenance of tissue oxygenation to support mitochondrial ATP production. However, paradoxically the brain has a 3-fold lower oxygen extraction fraction (OEF) than other organs with high energy requirements, like heart and muscle during exercise.

Measurement of neuro-energetics and neurotransmission in the rat olfactory bulb using H and H-[C] NMR spectroscopy.

The olfactory bulb (OB) plays a fundamental role in the sense of smell and has been implicated in several pathologies, including Alzheimer's disease. Despite its importance, high metabolic activity and unique laminar architecture, the OB is not frequently studied using MRS methods, likely due to the small size and challenging location. Here we present a detailed metabolic characterization of OB metabolism, in terms of both static metabolite concentrations using H MRS and metabolic fluxes associated with neuro-energetics and neurotransmission by tracing the dynamic C flow from intravenously administered [1,6-C]-glucose, [2-C]-glucose and [2-C]-acetate to downstream metabolites, including [4-C]-glutamate, [4-C]-glutamine and [2-C]-GABA.

A tribute to Leif Hertz: The historical context of his pioneering studies of the roles of astrocytes in brain energy metabolism, neurotransmission, cognitive functions, and pharmacology identifies important, unresolved topics for future studies.

Leif Hertz, M.D., D.

In vivo calibration of genetically encoded metabolite biosensors must account for metabolite metabolism during calibration and cellular volume.

Isotopic assays of brain glucose utilization rates have been used for more than four decades to establish relationships between energetics, functional activity, and neurotransmitter cycling. Limitations of these methods include the relatively long time (1-60 min) for the determination of labeled metabolite levels and the lack of cellular resolution. Identification and quantification of fuels for neurons and astrocytes that support activation and higher brain functions are a major, unresolved issues.

The early days of ex vivo H, C, and P nuclear magnetic resonance in the laboratory of Dr. Robert G. Shulman from 1975 to 1995.

This paper provides a brief description of the early use of ex vivo nuclear magnetic resonance (NMR) studies of tissue and tissue extracts performed in the laboratory of Dr. Robert G. Shulman from 1975 through 1995 at Bell Laboratories, then later at Yale University.

Presence or absence of stabilizing Earth system feedbacks on different time scales.

The question of how Earth's climate is stabilized on geologic time scales is important for understanding Earth's history, long-term consequences of anthropogenic climate change, and planetary habitability. Here, we quantify the typical amplitude of past global temperature fluctuations on time scales from hundreds to tens of millions of years and use it to assess the presence or absence of long-term stabilizing feedbacks in the climate system. On time scales between 4 and 400 ka, fluctuations fail to grow with time scale, suggesting that stabilizing mechanisms like the hypothesized "weathering feedback" have exerted dominant control in this regime.

Overexpression of UCP3 decreases mitochondrial efficiency in mouse skeletal muscle in vivo.

Uncoupling protein-3 (UCP3) is a mitochondrial transmembrane protein highly expressed in the muscle that has been implicated in regulating the efficiency of mitochondrial oxidative phosphorylation. Increasing UCP3 expression in skeletal muscle enhances proton leak across the inner mitochondrial membrane and increases oxygen consumption in isolated mitochondria, but its precise function in vivo has yet to be fully elucidated. To examine whether muscle-specific overexpression of UCP3 modulates muscle mitochondrial oxidation in vivo, rates of ATP synthesis were assessed by P magnetic resonance spectroscopy (MRS), and rates of mitochondrial oxidative metabolism were measured by assessing the rate of [2- C]acetate incorporation into muscle [4- C]-, [3- C]-glutamate, and [4- C]-glutamine by high-resolution C/ H MRS.

A 3D atlas of functional human brain energetic connectome based on neuropil distribution.

The human brain is energetically expensive, yet the key factors governing its heterogeneous energy distributions across cortical regions to support its diversity of functions remain unexplored. Here, we built up a 3D digital cortical energy atlas based on the energetic costs of all neuropil activities into a high-resolution stereological map of the human cortex with cellular and synaptic densities derived, respectively, from ex vivo histological staining and in vivo PET imaging. The atlas was validated with PET-measured glucose oxidation at the voxel level.

Mechanistic stoichiometric relationship between the rates of neurotransmission and neuronal glucose oxidation: Reevaluation of and alternatives to the pseudo-malate-aspartate shuttle model.

The ~1:1 stoichiometry between the rates of neuronal glucose oxidation (CMR) and glutamate (Glu)/γ-aminobutyric acid (GABA)-glutamine (Gln) neurotransmitter (NT) cycling between neurons and astrocytes (V) has been firmly established. However, the mechanistic basis for this relationship is not fully understood, and this knowledge is critical for the interpretation of metabolic and brain imaging studies in normal and diseased brain. The pseudo-malate-aspartate shuttle (pseudo-MAS) model established the requirement for glycolytic metabolism in cultured glutamatergic neurons to produce NADH that is shuttled into mitochondria to support conversion of extracellular Gln (i.

A Phenotypic Screen Identifies Potent DPP9 Inhibitors Capable of Killing HIV-1 Infected Cells.

Although current antiretroviral therapy can control HIV-1 replication and prevent disease progression, it is not curative. Identifying mechanisms that can lead to eradication of persistent viral reservoirs in people living with HIV-1 (PLWH) remains an outstanding challenge to achieving cure. Utilizing a phenotypic screen, we identified a novel chemical class capable of killing HIV-1 infected peripheral blood mononuclear cells.

Choroid plexus tissue perfusion and blood to CSF barrier function in rats measured with continuous arterial spin labeling.

The choroid plexus (ChP) of the cerebral ventricles is a source of cerebrospinal fluid (CSF) production and also plays a key role in immune surveillance at the level of blood-to-CSF-barrier (BCSFB). In this study, we quantify ChP blood perfusion and BCSFB mediated water exchange from arterial blood into ventricular CSF using non-invasive continuous arterial spin labelling magnetic resonance imaging (CASL-MRI). Systemic administration of anti-diuretic hormone (vasopressin) was used to validate BCSFB water flow as a metric of choroidal CSF secretory function.

Rate-induced collapse in evolutionary systems.

Recent work has highlighted the possibility of 'rate-induced tipping', in which a system undergoes an abrupt transition when a perturbation exceeds a critical rate of change. Here, we argue that this is widely applicable to evolutionary systems: collapse, or extinction, may occur when external changes occur too fast for evolutionary adaptation to keep up. To bridge existing theoretical frameworks, we develop a minimal evolutionary-ecological model showing that rate-induced extinction and the established notion of 'evolutionary rescue' are fundamentally two sides of the same coin: the failure of one implies the other, and vice versa.

Olfactory Changes After Military Deployment Are Associated With Emotional Distress but Not With Mild Traumatic Brain Injury History.

Objective: The aim of the study was to identify the impact of mild traumatic brain injury history and current emotional status on olfactory functioning.

Design: This was a cross-sectional study of 49 predominantly male, military veterans, reservists, and active duty service members with Operations Enduring Freedom, Iraqi Freedom, and New Dawn deployments and varying mild traumatic brain injury histories.

Results: Those with a positive history of mild traumatic brain injury (n = 32) endorsed significantly higher rates of self-reported olfactory disturbance.

Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans.

Background: Trauma and chronic stress are believed to induce and exacerbate psychopathology by disrupting glutamate synaptic strength. However, in human methods to estimate synaptic strength are limited. In this study, we established a novel putative biomarker of glutamatergic synaptic strength, termed energy-per-cycle (EPC).

From a Demand-Based to a Supply-Limited Framework of Brain Metabolism.

What defines the rate of energy use by the brain, as well as per neurons of different sizes in different structures and animals, is one fundamental aspect of neuroscience for which much has been theorized, but very little data are available. The prevalent theories and models consider that energy supply from the vascular system to different brain regions is adjusted both dynamically and in the course of development and evolution to meet the of neuronal activity. In this perspective, we offer an alternative view: that regional rates of energy use might be mostly constrained by , given the properties of the brain capillary network, the highly stable rate of oxygen delivery to the whole brain under physiological conditions, and homeostatic constraints.