Publications by authors named "Mauro DiNuzzo"

Background: Functional Magnetic Resonance Imaging (fMRI) is based on the Blood Oxygenation Level Dependent contrast and has been exploited for the indirect study of the neuronal activity within both the brain and the spinal cord. However, the interpretation of spinal cord fMRI (scfMRI) is still controversial and its adoption is rather restricted because of technical limitations. Overcoming these limitations would have a beneficial effect for the assessment and follow-up of spinal injuries and neurodegenerative diseases.

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Functional magnetic resonance imaging time-series are conventionally processed by linear modelling the evoked response as the convolution of the experimental conditions with a stereotyped hemodynamic response function (HRF). However, the neural signal in response to a stimulus can vary according to task, brain region, and subject-specific conditions. Moreover, HRF shape has been suggested to carry physiological information.

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Despite extensive research on neuroimaging correlates of human brain aging, there is little mechanistic insight into how they are linked to loss of brain function. Previous studies on the role of cerebral blood flow (CBF) in supporting brain function have focused on delivery of nutrients, namely oxygen and glucose. However, CBF is required also to clear the byproducts of energy metabolism, namely CO and protons.

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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.

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Article Synopsis
  • Following a spinal cord injury (SCI), the extent of motor, sensory, and autonomic loss is linked to the damage of nervous tissue, but current imaging methods cannot fully capture the complexity of this damage.
  • A new technique, synchrotron X-ray phase-contrast tomography (SXPCT), provides high-resolution 3D imaging, allowing researchers to study neurovascular architecture and track changes in spinal cord tissues in mice during the acute and subacute phases post-SCI.
  • Findings showed that while SXPCT effectively visualized neuronal loss and blood-brain barrier breakdown, there was no significant additional loss of motor neurons between 30 minutes and 7 days after injury, indicating early tissue damage may not progress considerably in this time frame.
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Visuospatial attention is strongly lateralized, with the right hemisphere commonly exhibiting stronger activation and connectivity patterns than the left hemisphere during attentive processes. However, whether such asymmetry influences inter-hemispheric information transfer and behavioral performance is not known. Here we used a region of interest (ROI) and network-based approach to determine steady-state fMRI functional connectivity (FC) in the whole cerebral cortex during a leftward/rightward covert visuospatial attention task.

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Processing of incoming sensory stimulation triggers an increase of cerebral perfusion and blood oxygenation (neurovascular response) as well as an alteration of the metabolic neurochemical profile (neurometabolic response). Here, we show in human primary visual cortex (V1) that perceived and unperceived isoluminant chromatic flickering stimuli designed to have similar neurovascular responses as measured by blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) have markedly different neurometabolic responses as measured by proton functional magnetic resonance spectroscopy (1H-fMRS). In particular, a significant regional buildup of lactate, an index of aerobic glycolysis, and glutamate, an index of malate-aspartate shuttle, occurred in V1 only when the flickering was perceived, without any relation with other behavioral or physiological variables.

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Article Synopsis
  • Sleep is a crucial behavior found in many animal species, essential for maintaining performance and long-term brain health, but the fundamental reasons for its necessity remain unclear.
  • The article discusses potential mechanisms that make sleep restorative, like metabolic biosynthesis, fluid perfusion, and synaptic homeostasis.
  • Recent research explores the possibility of inducing or enhancing slow-wave activity (SWA) during wakefulness or sleep using noninvasive brain stimulation, which could lead to a better understanding and control of sleep's restorative functions.
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  • In the last 20 years, a direct correlation has been established between glucose metabolism in neurons and astrocytes and the rates of neurotransmitter cycles (glutamate/GABA-glutamine), but the mechanisms behind this relationship remain unclear.
  • Researchers propose a theoretical model examining how the compartmentalization of glycogen metabolism in astrocytes and the need for glucose in neurons account for this correlation, particularly focusing on a mechanism known as Glucose Sparing by Glycogenolysis (GSG).
  • The findings from the GSG model align well with experimental data across various species, suggesting that glycogen breakdown and glucose sparing are crucial for maintaining energy for neuronal activity, impacting brain function in both healthy and diseased states.
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In-scanner head motion represents a major confounding factor in functional connectivity studies and it raises particular concerns when motion correlates with the effect of interest. One such instance regards research focused on functional connectivity modulations induced by sustained cognitively demanding tasks. Indeed, cognitive engagement is generally associated with substantially lower in-scanner movement compared with unconstrained, or minimally constrained, conditions.

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Spontaneous oscillations of the blood oxygenation level-dependent (BOLD) signal are spatially synchronized within specific brain networks and are thought to reflect synchronized brain activity. Networks are modulated by the performance of a task, even if the exact features and degree of such modulations are still elusive. The presence of networks showing anticorrelated fluctuations lend initially to suppose that a competitive relationship between the default mode network (DMN) and task positive networks (TPNs) supports the efficiency of brain processing.

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Non-invasive imaging methods have become essential tools for understanding the central nervous system (CNS) in health and disease. In particular, magnetic resonance imaging (MRI) techniques provide information about the anatomy, microstructure, and function of the brain and spinal cord non-invasively. However, MRI is limited by its spatial resolution and signal specificity.

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Since the introduction of functional magnetic resonance imaging (fMRI), several computational approaches have been developed to examine the effect of the morphology and arrangement of blood vessels on the blood oxygenation-level dependent (BOLD) signal in the brain. In the present work, we implemented the original Ogawa's model using a numerical simulation based on the finite element method (FEM) instead of the analytical models. In literature, there are different works using analytical methods to analyse the transverse relaxation rate ( ), which BOLD signal is related to, modelling the vascular system with simple and canonical geometries such as an infinite cylinder model (ICM) or a set of cylinders.

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A fundamental understanding of glycogen structure, concentration, polydispersity and turnover is critical to qualify the role of glycogen in the brain. These molecular and metabolic features are under the control of neuronal activity through the interdependent action of neuromodulatory tone, ionic homeostasis and availability of metabolic substrates, all variables that concur to define the state of the system. In this chapter, we briefly describe how glycogen responds to selected behavioral, nutritional, environmental, hormonal, developmental and pathological conditions.

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Phasic changes in eye's pupil diameter have been repeatedly observed during cognitive, emotional and behavioral activity in mammals. Although pupil diameter is known to be associated with noradrenergic firing in the pontine Locus Coeruleus (LC), thus far the causal chain coupling spontaneous pupil dynamics to specific cortical brain networks remains unknown. In the present study, we acquired steady-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) data combined with eye-tracking pupillometry from fifteen healthy subjects that were trained to maintain a constant attentional load.

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Astrocytic glycogen is the sole glucose reserve of the brain. Both glycogen and glucose are necessary for basic neurophysiology and in turn for higher brain functions. In spite of low concentration, turnover and stimulation-induced degradation, any interference with normal glycogen metabolism in the brain severely affects neuronal excitability and disrupts memory formation.

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Purpose Of Review: The goal of the present paper is to review current literature supporting the occurrence of fundamental changes in brain energy metabolism during the transition from wakefulness to sleep.

Recent Findings: Latest research in the field indicates that glucose utilization and the concentrations of several brain metabolites consistently change across the sleep-wake cycle. Lactate, a product of glycolysis that is involved in synaptic plasticity, has emerged as a good biomarker of brain state.

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Brain activity at rest is characterized by widely distributed and spatially specific patterns of synchronized low-frequency blood-oxygenation level-dependent (BOLD) fluctuations, which correspond to physiologically relevant brain networks. This network behaviour is known to persist also during task execution, yet the details underlying task-associated modulations of within- and between-network connectivity are largely unknown. In this study we exploited a multi-parametric and multi-scale approach to investigate how low-frequency fluctuations adapt to a sustained n-back working memory task.

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Subtle semantic deficits can be observed in Alzheimer's disease (AD) patients even in the early stages of the illness. In this work, we tested the hypothesis that the semantic control network is deregulated in mild AD patients. We assessed the integrity of the semantic control system using resting-state functional magnetic resonance imaging in a cohort of patients with mild AD (n = 38; mean mini-mental state examination = 20.

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Brain activity during wakefulness is associated with high metabolic rates that are believed to support information processing and memory encoding. In spite of loss of consciousness, sleep still carries a substantial energy cost. Experimental evidence supports a cerebral metabolic shift taking place during sleep that suppresses aerobic glycolysis, a hallmark of environment-oriented waking behavior and synaptic plasticity.

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Time-domain analysis of blood-oxygenation level-dependent (BOLD) signals allows the identification of clusters of voxels responding to photic stimulation in primary visual cortex (V1). However, the characterization of information encoding into temporal properties of the BOLD signals of an activated cluster is poorly investigated. Here, we used Shannon entropy to determine spatial and temporal information encoding in the BOLD signal within the most strongly activated area of the human visual cortex during a hemifield photic stimulation.

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Supercompensated brain glycogen levels may contribute to the development of hypoglycemia-associated autonomic failure (HAAF) following recurrent hypoglycemia (RH) by providing energy for the brain during subsequent periods of hypoglycemia. To assess the role of glycogen supercompensation in the generation of HAAF, we estimated the level of brain glycogen following RH and acute hypoglycemia (AH). After undergoing 3 hyperinsulinemic, euglycemic and 3 hyperinsulinemic, hypoglycemic clamps (RH) on separate occasions at least 1 month apart, five healthy volunteers received [1-C]glucose intravenously over 80+ h while maintaining euglycemia.

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Brain activity involves essential functional and metabolic interactions between neurons and astrocytes. The importance of astrocytic functions to neuronal signaling is supported by many experiments reporting high rates of energy consumption and oxidative metabolism in these glial cells. In the brain, almost all energy is consumed by the Na/K ATPase, which hydrolyzes 1 ATP to move 3 Na outside and 2 K inside the cells.

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Glycogen provides an important glucose reservoir in the brain since the concentration of glucosyl units stored in glycogen is several fold higher than free glucose available in brain tissue. We have previously reported 3-4 µmol/g brain glycogen content using in vivo (13)C magnetic resonance spectroscopy (MRS) in conjunction with [1-(13)C]glucose administration in healthy humans, while higher levels were reported in the rodent brain. Due to the slow turnover of bulk brain glycogen in humans, complete turnover of the glycogen pool, estimated to take 3-5 days, was not observed in these prior studies.

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