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 BRIDGING THE GAP BETWEEN NEUROIMAGING AND NEURONAL PHYSIOLOGY

2011 ◽  
Vol 21 (2) ◽  
pp. 97 ◽  
Author(s):  
Dae-Shik Kim ◽  
Kamil Ugurbil
Keyword(s):  
Functional Mri ◽  
Functional Neuroimaging ◽  
Explanatory Power ◽  
Blood Oxygenation ◽  
Functional Magnetic Resonance ◽  
Neural Correlate ◽  
Neuroimaging Data ◽  
Oxygenation Level ◽  
Spatial Specificity ◽  
Neuronal Physiology

Despite the fact that blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) studies have become ubiquitous and are of ever increasing importance for clinical and basic neurosciences, the fundamental relationships between BOLD and the underlying neuronal physiology are not understood. This raises severe concerns about the validity of BOLD contrast per se, and the conceptual frameworks currently employed in interpreting cognitive neuroimaging data. In order to expand the explanatory power of functional MRI data, several crucial questions will have to be addressed. The two most important questions are: First, what is the ultimate spatial resolution of fMRI?, secondly, what is the "neural correlate" of functional MRI? This article attempts to compile a series of results from our and other laboratories, suggesting that both the questions of "spatial specificity" and "neural correlate" might be within the reach of a tentative solution, thus finally bridging the gap between functional neuroimaging and neuronal physiology.

scholarly journals Separating vascular and neuronal effects of age on fMRI BOLD signals

2020 ◽  
Vol 376 (1815) ◽  
pp. 20190631 ◽  
Author(s):  
Kamen A. Tsvetanov ◽  
Richard N. A. Henson ◽  
James B. Rowe
Keyword(s):  
Neuronal Activity ◽  
Functional Neuroimaging ◽  
Well Being ◽  
Blood Oxygenation ◽  
Vascular Effects ◽  
Accurate Identification ◽  
Form Complex ◽  
Bold Fmri ◽  
Oxygenation Level ◽  
Neurovascular Interactions

Accurate identification of brain function is necessary to understand the neurobiology of cognitive ageing, and thereby promote well-being across the lifespan. A common tool used to investigate neurocognitive ageing is functional magnetic resonance imaging (fMRI). However, although fMRI data are often interpreted in terms of neuronal activity, the blood oxygenation level-dependent (BOLD) signal measured by fMRI includes contributions of both vascular and neuronal factors, which change differentially with age. While some studies investigate vascular ageing factors, the results of these studies are not well known within the field of neurocognitive ageing and therefore vascular confounds in neurocognitive fMRI studies are common. Despite over 10 000 BOLD-fMRI papers on ageing, fewer than 20 have applied techniques to correct for vascular effects. However, neurovascular ageing is not only a confound in fMRI, but an important feature in its own right, to be assessed alongside measures of neuronal ageing. We review current approaches to dissociate neuronal and vascular components of BOLD-fMRI of regional activity and functional connectivity. We highlight emerging evidence that vascular mechanisms in the brain do not simply control blood flow to support the metabolic needs of neurons, but form complex neurovascular interactions that influence neuronal function in health and disease. This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.

scholarly journals Assessment of single-vessel cerebral blood velocity by phase contrast fMRI

PLoS Biology ◽  
2021 ◽  
Vol 19 (9) ◽  
pp. e3000923
Author(s):  
Xuming Chen ◽  
Yuanyuan Jiang ◽  
Sangcheon Choi ◽  
Rolf Pohmann ◽  
Klaus Scheffler ◽  
...  
Keyword(s):  
High Resolution ◽  
High Field ◽  
Phase Contrast ◽  
Cerebral Blood Volume ◽  
Blood Velocity ◽  
Blood Oxygenation ◽  
Single Vessel ◽  
Oxygenation Level ◽  
Cerebral Blood Velocity ◽  
Human Brains

Current approaches to high-field functional MRI (fMRI) provide 2 means to map hemodynamics at the level of single vessels in the brain. One is through changes in deoxyhemoglobin in venules, i.e., blood oxygenation level–dependent (BOLD) fMRI, while the second is through changes in arteriole diameter, i.e., cerebral blood volume (CBV) fMRI. Here, we introduce cerebral blood flow–related velocity-based fMRI, denoted CBFv-fMRI, which uses high-resolution phase contrast (PC) MRI to form velocity measurements of flow. We use CBFv-fMRI in measure changes in blood velocity in single penetrating microvessels across rat parietal cortex. In contrast to the venule-dominated BOLD and arteriole-dominated CBV fMRI signals, CBFv-fMRI is comparable from both arterioles and venules. A single fMRI platform is used to map changes in blood pO2 (BOLD), volume (CBV), and velocity (CBFv). This combined high-resolution single-vessel fMRI mapping scheme enables vessel-specific hemodynamic mapping in animal models of normal and diseased states and further has translational potential to map vascular dementia in diseased or injured human brains with ultra–high-field fMRI.

scholarly journals Modelling the depth-dependent VASO and BOLD responses in human primary visual cortex

2021 ◽  
Author(s):  
Atena Akbari ◽  
Saskia Bollmann ◽  
Tonima Ali ◽  
Markus Barth
Keyword(s):  
Visual Cortex ◽  
Blood Volume ◽  
Primary Visual Cortex ◽  
Cerebral Blood Volume ◽  
Blood Oxygenation ◽  
Physiological Variables ◽  
Oxygenation Level ◽  
Signal Specificity ◽  
Experimental Findings ◽  
Spatial Specificity

Functional magnetic resonance imaging (fMRI) using blood-oxygenation-level-dependent (BOLD) contrast is a common method for studying human brain function non-invasively. Gradient-echo (GRE) BOLD is highly sensitive to the blood oxygenation change in blood vessels; however, the signal specificity can be degraded due to signal leakage from the activated lower layers to the superficial layers in depth-dependent (also called laminar or layer-specific) fMRI. Alternatively, physiological variables such as cerebral blood volume using VAscular-Space-Occupancy (VASO) measurements have shown higher spatial specificity compared to BOLD. To better understand the physiological mechanisms (e.g., blood volume and oxygenation change) and to interpret the measured depth-dependent responses we need models that reflect vascular properties at this scale. For this purpose, we adapted a cortical vascular model previously developed to predict the layer-specific BOLD signal change in human primary visual cortex to also predict layer-specific VASO response. To evaluate the model, we compared the predictions with experimental results of simultaneous VASO and BOLD measurements in a group of healthy participants. Fitting the model to our experimental findings provided an estimate of CBV change in different vascular compartments upon neural activity. We found that stimulus-evoked CBV changes mainly occur in intracortical arteries as well as small arterioles and capillaries and that the contribution from venules is small for a long stimulus (~30 sec). Our results confirm the notion that VASO contrast is less susceptible to large vessel effects compared to BOLD.

scholarly journals A dynamical model of the laminar BOLD response

2019 ◽  
Author(s):  
Martin Havlicek ◽  
Kamil Uludag
Keyword(s):  
High Resolution ◽  
Blood Volume ◽  
Neuronal Activity ◽  
Cerebral Blood Volume ◽  
Local Maximum ◽  
Mass Conservation ◽  
Physiological Parameters ◽  
Blood Oxygenation ◽  
Bold Signal ◽  
Bold Response

AbstractHigh-resolution functional magnetic resonance imaging (fMRI) using blood oxygenation dependent level-dependent (BOLD) signal is an increasingly popular tool to non-invasively examine neuronal processes at the mesoscopic level. However, as the BOLD signal stems from hemodynamic changes, its temporal and spatial properties do not match those of the underlying neuronal activity. In particular, the laminar BOLD response (LBR), commonly measured with gradient-echo (GE) MRI sequence, is confounded by non-local changes in deoxygenated hemoglobin and cerebral blood volume propagated within intracortical ascending veins, leading to a unidirectional blurring of the neuronal activity distribution towards the cortical surface. Here, we present a new cortical depth-dependent model of the BOLD response based on the principle of mass conservation, which takes the effect of ascending (and pial) veins on the cortical BOLD responses explicitly into account. It can be used to dynamically model cortical depth profiles of the BOLD signal as a function of various baseline- and activity-related physiological parameters for any spatiotemporal distribution of neuronal changes. We demonstrate that the commonly observed spatial increase of LBR is mainly due to baseline blood volume increase towards the surface. In contrast, an occasionally observed local maximum in the LBR (i.e. the so-called “bump”) is mainly due to spatially inhomogeneous neuronal changes rather than locally higher baseline blood volume. In addition, we show that the GE-BOLD signal laminar point-spread functions, representing the signal leakage towards the surface, depend on several physiological parameters and on the level of neuronal activity. Furthermore, even in the case of simultaneous neuronal changes at each depth, inter-laminar delays of LBR transients are present due to the ascending vein. In summary, the model provides a conceptual framework for the biophysical interpretation of common experimental observations in high-resolution fMRI data. In the future, the model will allow for deconvolution of the spatiotemporal hemodynamic bias of the LBR and provide an estimate of the underlying laminar excitatory and inhibitory neuronal activity.

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 Physiological origin for the BOLD poststimulus undershoot in human brain: Vascular compliance versus oxygen metabolism

2011 ◽  
Vol 31 (7) ◽  
pp. 1599-1611 ◽  
Author(s):  
Jun Hua ◽  
Robert D Stevens ◽  
Alan J Huang ◽  
James J Pekar ◽  
Peter CM van Zijl
Keyword(s):  
Cerebral Blood Volume ◽  
Visual Stimulation ◽  
Oxygen Metabolism ◽  
Blood Oxygenation ◽  
Biophysical Model ◽  
Breath Hold ◽  
Signal Recovery ◽  
Vascular Compliance ◽  
Oxygenation Level ◽  
Bold Undershoot

The poststimulus blood oxygenation level-dependent (BOLD) undershoot has been attributed to two main plausible origins: delayed vascular compliance based on delayed cerebral blood volume (CBV) recovery and a sustained increased oxygen metabolism after stimulus cessation. To investigate these contributions, multimodal functional magnetic resonance imaging was employed to monitor responses of BOLD, cerebral blood flow (CBF), total CBV, and arterial CBV (CBVa) in human visual cortex after brief breath hold and visual stimulation. In visual experiments, after stimulus cessation, CBVa was restored to baseline in 7.9 ± 3.4 seconds, and CBF and CBV in 14.8 ± 5.0 seconds and 16.1 ± 5.8 seconds, respectively, all significantly faster than BOLD signal recovery after undershoot (28.1 ± 5.5 seconds). During the BOLD undershoot, postarterial CBV (CBVpa, capillaries and venules) was slightly elevated (2.4 ± 1.8%), and cerebral metabolic rate of oxygen ( CMRO2) was above baseline (10.6 ± 7.4%). Following breath hold, however, CBF, CBV, CBVa and BOLD signals all returned to baseline in ∼20 seconds. No significant BOLD undershoot, and residual CBVpa dilation were observed, and CMRO2 did not substantially differ from baseline. These data suggest that both delayed CBVpa recovery and enduring increased oxidative metabolism impact the BOLD undershoot. Using a biophysical model, their relative contributions were estimated to be 19.7 ± 15.9% and 78.7 ± 18.6%, respectively.

scholarly journals Multimodal Measurements of Blood Plasma and Red Blood Cell Volumes during Functional Brain Activation

2008 ◽  
Vol 29 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Peter Herman ◽  
Basavaraju G Sanganahalli ◽  
Fahmeed Hyder
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Blood Plasma ◽  
Cerebral Blood Volume ◽  
Superparamagnetic Iron Oxide ◽  
Blood Oxygenation ◽  
Mri Contrast Agent ◽  
Resonance Imaging ◽  
Doppler Flowmetry ◽  
Oxygenation Level

As an alternative to functional magnetic resonance imaging (fMRI) with blood oxygenation level dependent (BOLD) contrast, cerebral blood volume (CBV)-weighted fMRI with intravascular contrast agents in animal models have become popular. In this study, dynamic measurements of CBV were performed by magnetic resonance imaging (MRI) and laser-Doppler flowmetry (LDF) in α-chloralose anesthetized rats during forepaw stimulation. All recordings were localized to the contralateral primary somatosensory cortex as revealed by BOLD at 11.7 T. Ultra-small superparamagnetic iron oxide (15mg/kg)—a plasma-borne MRI contrast agent with a half-life of several hours in blood circulation—was used to quantify changes in magnetic field inhomogeneity in blood plasma. The LDF backscattered laser light (805 nm), which reflects the amount of red blood cells, was used to measure alterations in the non-plasma compartment. Dynamic and layer-specific comparisons of the two CBV signals during functional hyperemia revealed excellent correlations (> 0.86). These results suggest that CBV measurements from either compartment may be used to reflect dynamic changes in total CBV. Furthermore, by assuming steady-state mass balance and negligible counter flow, these results indicate that volume hematocrit is not appreciably affected during functional activation.

The importance of the negative blood-oxygenation-level-dependent (BOLD) response in the somatosensory cortex

2015 ◽  
Vol 26 (6) ◽  
pp. 647-653 ◽  
Author(s):  
Carsten M. Klingner ◽  
Stefan Brodoehl ◽  
Otto W. Witte
Keyword(s):  
Somatosensory Cortex ◽  
Neuronal Activity ◽  
Brain Regions ◽  
Blood Oxygenation Level Dependent ◽  
Blood Oxygenation ◽  
Bold Response ◽  
Functional Importance ◽  
Blood Oxygenation Level ◽  
Oxygenation Level

AbstractIn recent years, multiple studies have shown task-induced negative blood-oxygenation-level-dependent responses (NBRs) in multiple brain regions in humans and animals. Converging evidence suggests that task-induced NBRs can be interpreted in terms of decreased neuronal activity. However, the vascular and metabolic dynamics and functional importance of the NBR are highly debated. Here, we review studies investigating the origin and functional importance of the NBR, with special attention to the somatosensory cortex.

scholarly journals A studyforrest extension, MEG recordings while watching the audio-visual movie "Forrest Gump"

2021 ◽  
Author(s):  
Xingyu Liu ◽  
Yuxuan Dai ◽  
Hailun Xie ◽  
Zonglei Zhen
Keyword(s):  
Neuronal Activity ◽  
Brain Function ◽  
Ecological Validity ◽  
Blood Oxygenation ◽  
Free Access ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Oxygenation Level ◽  
The Brain ◽  
The Magnetic Field

Naturalistic stimuli, such as movies, are being increasingly used to map brain function because of their high ecological validity. The pioneering studyforrest and other naturalistic neuroimaging projects have provided free access to multiple movie-watching functional magnetic resonance imaging (fMRI) datasets to prompt the community for naturalistic experimental paradigms. However, sluggish blood-oxygenation-level-dependent fMRI signals are incapable of resolving neuronal activity with the temporal resolution at which it unfolds. Instead, magnetoencephalography (MEG) measures changes in the magnetic field produced by neuronal activity and is able to capture rich dynamics of the brain at the millisecond level while watching naturalistic movies. Herein, we present the first public prolonged MEG dataset collected from 11 participants while watching the 2 h long audio-visual movie "Forrest Gump". Minimally preprocessed data was also provided to facilitate the use. As a studyforrest extension, we envision that this dataset, together with fMRI data from the studyforrest project, will serve as a foundation for exploring the neural dynamics of various cognitive functions in real-world contexts.

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