scholarly journals Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity

2020 ◽  
Vol 376 (1815) ◽  
pp. 20190622
Author(s):  
Anusha Mishra ◽  
Catherine N. Hall ◽  
Clare Howarth ◽  
Ralph D. Freeman
Keyword(s):  
Blood Flow ◽  
Neuronal Activity ◽  
Vascular Function ◽  
Functional Neuroimaging ◽  
Cell Types ◽  
Human Cognition ◽  
Measured Signal ◽  
Bold Signal ◽  
Theme Issue ◽  
Non Invasive

Functional neuroimaging using MRI relies on measurements of blood oxygen level-dependent (BOLD) signals from which inferences are made about the underlying neuronal activity. This is possible because neuronal activity elicits increases in blood flow via neurovascular coupling, which gives rise to the BOLD signal. Hence, an accurate interpretation of what BOLD signals mean in terms of neural activity depends on a full understanding of the mechanisms that underlie the measured signal, including neurovascular and neurometabolic coupling, the contribution of different cell types to local signalling, and regional differences in these mechanisms. Furthermore, the contributions of systemic functions to cerebral blood flow may vary with ageing, disease and arousal states, with regard to both neuronal and vascular function. In addition, recent developments in non-invasive imaging technology, such as high-field fMRI, and comparative inter-species analysis, allow connections between non-invasive data and mechanistic knowledge gained from invasive cellular-level studies. Considered together, these factors have immense potential to improve BOLD signal interpretation and bring us closer to the ultimate purpose of decoding the mechanisms of human cognition. This theme issue covers a range of recent advances in these topics, providing a multidisciplinary scientific and technical framework for future work in the neurovascular and cognitive sciences. This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity'.

scholarly journals More than just summed neuronal activity: how multiple cell types shape the BOLD response

2020 ◽  
Vol 376 (1815) ◽  
pp. 20190630 ◽  
Author(s):  
Clare Howarth ◽  
Anusha Mishra ◽  
Catherine N. Hall
Keyword(s):  
Neuronal Activity ◽  
Functional Neuroimaging ◽  
Cell Types ◽  
Blood Oxygen Level Dependent ◽  
Inhibitory Neurons ◽  
Human Cognition ◽  
Projection Neurons ◽  
Bold Signal ◽  
Bold Response ◽  
Biological Phenomena

Functional neuroimaging techniques are widely applied to investigations of human cognition and disease. The most commonly used among these is blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. The BOLD signal occurs because neural activity induces an increase in local blood supply to support the increased metabolism that occurs during activity. This supply usually outmatches demand, resulting in an increase in oxygenated blood in an active brain region, and a corresponding decrease in deoxygenated blood, which generates the BOLD signal. Hence, the BOLD response is shaped by an integration of local oxygen use, through metabolism, and supply, in the blood. To understand what information is carried in BOLD signals, we must understand how several cell types in the brain—local excitatory neurons, inhibitory neurons, astrocytes and vascular cells (pericytes, vascular smooth muscle and endothelial cells), and their modulation by ascending projection neurons—contribute to both metabolism and haemodynamic changes. Here, we review the contributions of each cell type to the regulation of cerebral blood flow and metabolism, and discuss situations where a simplified interpretation of the BOLD response as reporting local excitatory activity may misrepresent important biological phenomena, for example with regards to arousal states, ageing and neurological disease. This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.

scholarly journals Cytochrome P450 eicosanoids and cerebral vascular function

2011 ◽  
Vol 13 ◽  
Author(s):  
John D. Imig ◽  
Alexis N. Simpkins ◽  
Marija Renic ◽  
David R. Harder
Keyword(s):  
Blood Flow ◽  
Cytochrome P450 ◽  
Vascular Function ◽  
Therapeutic Targets ◽  
Vascular Diseases ◽  
Cell Types ◽  
Cellular Mechanisms ◽  
Molecular Therapeutic ◽  
Molecular Therapeutic Targets ◽  
Cerebral Vascular

The eicosanoids 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs), which are generated from the metabolism of arachidonic acid by cytochrome P450 (CYP) enzymes, possess a wide array of biological actions, including the regulation of blood flow to organs. 20-HETE and EETs are generated in various cell types in the brain and cerebral blood vessels, and contribute significantly to cerebral blood flow autoregulation and the coupling of regional brain blood flow to neuronal activity (neurovascular coupling). Investigations are beginning to unravel the molecular and cellular mechanisms by which these CYP eicosanoids regulate cerebral vascular function and the changes that occur in pathological states. Intriguingly, 20-HETE and the soluble epoxide hydrolase (sEH) enzyme that regulates EET levels have been explored as molecular therapeutic targets for cerebral vascular diseases. Inhibition of 20-HETE, or increasing EET levels by inhibiting the sEH enzyme, decreases cerebral damage following stroke. The improved outcome following cerebral ischaemia is a consequence of improving cerebral vascular structure or function and protecting neurons from cell death. Thus, the CYP eicosanoids are key regulators of cerebral vascular function and novel therapeutic targets for cardiovascular diseases and neurological disorders.

The use of cerebral blood flow as an index of neuronal activity in functional neuroimaging: experimental and pathophysiological considerations

2000 ◽  
Vol 20 (3-4) ◽  
pp. 215-224 ◽  
Author(s):  
Willy Gsell ◽  
Christelle De Sadeleer ◽  
Yannick Marchalant ◽  
Eric T. MacKenzie ◽  
Pascale Schumann ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Neuronal Activity ◽  
Functional Neuroimaging

scholarly journals Pharmacological Uncoupling of Activation Induced Increases in CBF and CMRO2

2009 ◽  
Vol 30 (2) ◽  
pp. 311-322 ◽  
Author(s):  
Christoph Leithner ◽  
Georg Royl ◽  
Nikolas Offenhauser ◽  
Martina Füchtemeier ◽  
Matthias Kohl-Bareis ◽  
...  
Keyword(s):  
Blood Flow ◽  
Somatosensory Cortex ◽  
Neuronal Activity ◽  
Functional Neuroimaging ◽  
Neuronal Activation ◽  
Cranial Window ◽  
Flow Response ◽  
Blood Flow Increase ◽  
Rat Somatosensory Cortex ◽  
Hb Concentration

Neurovascular coupling provides the basis for many functional neuroimaging techniques. Nitric oxide (NO), adenosine, cyclooxygenase, CYP450 epoxygenase, and potassium are involved in dilating arterioles during neuronal activation. We combined inhibition of NO synthase, cyclooxygenase, adenosine receptors, CYP450 epoxygenase, and inward rectifier potassium (Kir) channels to test whether these pathways could explain the blood flow response to neuronal activation. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) of the somatosensory cortex were measured during forepaw stimulation in 24 rats using a laser Doppler/spectroscopy probe through a cranial window. Combined inhibition reduced CBF responses by two-thirds, somatosensory evoked potentials and activation-induced CMRO2 increases remained unchanged, and deoxy-hemoglobin (deoxy-Hb) response was abrogated. This shows that in the rat somatosensory cortex, one-third of the physiological blood flow increase is sufficient to prevent microcirculatory increase of deoxy-Hb concentration during neuronal activity. The large physiological CBF response is not necessary to support small changes in CMRO2. We speculate that the CBF response safeguards substrate delivery during functional activation with a considerable ‘safety factor’. Reduction of the CBF response in pathological states may abolish the BOLD–fMRI signal, without affecting underlying neuronal activity.

scholarly journals Time-dependent spatial specificity of high-resolution fMRI: insights into mesoscopic neurovascular coupling

2020 ◽  
Vol 376 (1815) ◽  
pp. 20190623
Author(s):  
Mitsuhiro Fukuda ◽  
Alexander J. Poplawsky ◽  
Seong-Gi Kim
Keyword(s):  
High Resolution ◽  
Neuronal Activity ◽  
Cerebral Blood Volume ◽  
Functional Neuroimaging ◽  
Neurovascular Coupling ◽  
Blood Oxygenation ◽  
Non Invasive ◽  
True Location ◽  
Oxygenation Level ◽  
Spatial Specificity

High-resolution functional magnetic resonance imaging (fMRI) is becoming increasingly popular because of the growing availability of ultra-high magnetic fields which are capable of improving sensitivity and spatial resolution. However, it is debatable whether increased spatial resolutions for haemodynamic-based techniques, like fMRI, can accurately detect the true location of neuronal activity. We have addressed this issue in functional columns and layers of animals with haemoglobin-based optical imaging and different fMRI contrasts, such as blood oxygenation level-dependent, cerebral blood flow and cerebral blood volume fMRI. In this review, we describe empirical evidence primarily from our own studies on how well these fMRI signals are spatially specific to the neuronally active site and discuss insights into neurovascular coupling at the mesoscale. This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.

scholarly journals Quantitative relations between transient BOLD responses, cortical energetics, and impulse firing in different cortical regions

2019 ◽  
Vol 122 (3) ◽  
pp. 1226-1237 ◽  
Author(s):  
M. R. Bennett ◽  
L. Farnell ◽  
W. G. Gibson
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Neuronal Activity ◽  
Blood Oxygen Level Dependent ◽  
Blood Oxygen ◽  
Bold Signal ◽  
Oxygen Level ◽  
Blood Oxygen Level ◽  
Baseline Activity ◽  
Input Activity

The blood oxygen level-dependent (BOLD) functional magnetic resonance imaging signal arises as a consequence of changes in blood flow (cerebral blood flow) and oxygen usage (cerebral metabolic rate of oxygen) that in turn are modulated by changes in neuronal activity. Much attention has been given to both theoretical and experimental aspects of the energetics but not to the neuronal activity. Here we use our previous theory relating the steady-state BOLD signal to neuronal activity and amalgamate it with the standard dynamic causal model (DCM, Friston) theory to produce a quantitative model relating the time-dependent BOLD signal to the underlying neuronal activity. Unlike existing treatments, this new theory incorporates a nonzero baseline activity in a completely consistent way and is thus able to account for both positive and negative BOLD signals. It can reproduce a wide variety of experimental BOLD signals reported in the literature solely by adjusting the neuronal input activity. In this way it provides support for the claim that the main features of the signals, including poststimulus undershoot and overshoot, are principally a result of changes in neuronal activity. NEW & NOTEWORTHY A previous model relating the steady-state blood oxygen level-dependent (BOLD) signal to neuronal activity, both above and below baseline, is extended to account for transient BOLD signals. This allows for a detailed investigation of the role neuronal activity can play in such signals and also encompasses poststimulus undershoot and overshoot. A wide variety of experimental BOLD signals are reproduced solely by adjusting the neuronal input activity, including recent results regarding the BOLD signal in patients with schizophrenia.

scholarly journals Hemodynamic Changes after Visual Stimulation and Breath Holding Provide Evidence for an Uncoupling of Cerebral Blood Flow and Volume from Oxygen Metabolism

2008 ◽  
Vol 29 (1) ◽  
pp. 176-185 ◽  
Author(s):  
Manus J Donahue ◽  
Robert D Stevens ◽  
Michiel de Boorder ◽  
James J Pekar ◽  
Jeroen Hendrikse ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Blood Volume ◽  
Visual Stimulation ◽  
Functional Neuroimaging ◽  
Oxygen Metabolism ◽  
Blood Oxygenation ◽  
Breath Holding ◽  
Breath Hold ◽  
Bold Signal

Functional neuroimaging is most commonly performed using the blood-oxygenation-level-dependent (BOLD) approach, which is sensitive to changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and the cerebral metabolic rate of oxygen (CMRO2). However, the precise mechanism by which neuronal activity elicits a hemodynamic response remains controversial. Here, visual stimulation (14 secs flashing checkerboard) and breath-hold (4 secs exhale + 14 secs breath hold) experiments were performed in alternating sequence on healthy volunteers using BOLD, CBV-weighted, and CBF-weighted fMRI. After visual stimulation, the BOLD signal persisted for 33 ± 5 secs (n = 9) and was biphasic with a negative component (undershoot), whereas CBV and CBF returned to baseline without an undershoot at 20 ± 5 and 20 ± 3 secs, respectively. After breath hold, the BOLD signal returned to baseline (23 ±7 secs) at the same time ( P < 0.05) as CBV (21 ± 6 secs) and CBF (18 ±3 secs), without a poststimulus undershoot. These data suggest that the BOLD undershoot after visual activation reflects a persistent increase in CMRO2. These observations support the view that CBV and CBF responses elicited by neuronal activation are not necessarily coupled to local tissue metabolism.

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