A dynamical model of the laminar 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.

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

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2019.0623 ◽

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’.

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Simultaneous acquisition of cerebral blood volume-, blood flow-, and blood oxygenation-weighted MRI signals at ultra-high magnetic field

Magnetic Resonance in Medicine ◽

10.1002/mrm.25431 ◽

2014 ◽

Vol 74 (2) ◽

pp. 513-517 ◽

Cited By ~ 6

Author(s):

Steffen N. Krieger ◽

Laurentius Huber ◽

Benedikt A. Poser ◽

Robert Turner ◽

Gary F. Egan

Keyword(s):

Magnetic Field ◽

Blood Flow ◽

Blood Volume ◽

High Magnetic Field ◽

Cerebral Blood Volume ◽

Blood Oxygenation ◽

Simultaneous Acquisition ◽

Volume Blood ◽

Volume Blood Flow

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DETECTION OF Ca2+-DEPENDENT NEURONAL ACTIVITY SIMULTANEOUSLY WITH DYNAMIC CHANGES IN CEREBRAL BLOOD VOLUME AND TISSUE OXYGENATION FROM THE LIVE RAT BRAIN

Journal of Innovative Optical Health Sciences ◽

10.1142/s1793545809000498 ◽

2009 ◽

Vol 02 (02) ◽

pp. 189-200 ◽

Cited By ~ 2

Author(s):

CONGWU DU ◽

ZHONGCHI LUO ◽

MEI YU ◽

HELENE BENVENISTE ◽

MELISSA TULLY ◽

...

Keyword(s):

Rat Brain ◽

Blood Volume ◽

Neuronal Activity ◽

Cerebral Blood Volume ◽

Tissue Oxygenation ◽

Simultaneous Detection ◽

Fluorescence Emission ◽

High Temporal Resolution ◽

Functional Changes ◽

The Brain

We present a catheter-based optical diffusion and fluorescence (ODF) probe to study the functional changes of the brain in vivo. This ODF probe enables the simultaneous detection of the multi-wavelength absorbance and fluorescence emission from the living rat brain. Our previous studies, including a transient stroke experiment of the rat brain as well as the brain response to cocaine, have established the feasibility of simultaneously determining changes in cerebral blood volume (CBV), tissue oxygenation ( S t O 2) and intracellular calcium ([ Ca 2+]i, using the fluorescence indicator Rhod2). Here, we present our preliminary results of somatosensory response to electrical forepaw stimulation obtained from the rat cortical brain by using the ODF probe, which indicate that the probe could track brain activation by directly detecting [ Ca 2+]i along with separately distinguishing CBV and S t O 2 in real time. The changes of CBV, S t O 2 and [ Ca 2+]i are comparable with the blood-oxygen-level-dependent (BOLD) response to the stimulation obtained using functional magnetic resonance imaging (fMRI). However, the high temporal resolution of the optical methodology is advanced, thus providing a new modality for brain functional studies to understand the hemodynamic changes that underlie the neuronal activity.

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

Reviews in the Neurosciences ◽

10.1515/revneuro-2015-0002 ◽

2015 ◽

Vol 26 (6) ◽

pp. 647-653 ◽

Cited By ~ 8

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.

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Quantitative Assessment of the Balance between Oxygen Delivery and Consumption in the Rat Brain after Transient Ischemia with T2-BOLD Magnetic Resonance Imaging

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200203000-00003 ◽

2002 ◽

Vol 22 (3) ◽

pp. 262-270 ◽

Cited By ~ 23

Author(s):

Mikko I. Kettunen ◽

Olli H. J. Gröhn ◽

M. Johanna Silvennoinen ◽

Markku Penttonen ◽

Risto A. Kauppinen

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Carotid Artery ◽

Rat Brain ◽

Blood Volume ◽

Common Carotid Artery ◽

Cerebral Blood Volume ◽

Blood Oxygenation ◽

Resonance Imaging ◽

Transient Ischemia

The balance between oxygen consumption and delivery in the rat brain after exposure to transient ischemia was quantitatively studied with single-spin echo T2-BOLD (blood oxygenation level–dependent) magnetic resonance imaging at 4.7 T. The rats were exposed to graded common carotid artery occlusions using a modification of the four-vessel model of Pulsinelli. T2, diffusion, and cerebral blood volume were quantified with magnetic resonance imaging, and CBF was measured with the hydrogen clearance method. A transient common carotid artery occlusion below the CBF value of approximately 20 mL·100 g−1·min−1 was needed to yield a T2 increase of 4.6 ± 1.2 milliseconds (approximately 9% of cerebral T2) and 6.8 ± 1.7 milliseconds (approximately 13% of cerebral T2) after 7 and 15 minutes of ischemia, respectively. Increases in CBF of 103 ± 75% and in cerebral blood volume of 29 ± 20% were detected in the reperfusion phase. These hemodynamic changes alone could account for only approximately one third of the T2 increase in luxury perfusion, suggesting that a substantial increase in blood oxygen saturation (resulting from reduced oxygen extraction by the brain) is needed to explain the magnetic resonance imaging observation.

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Simultaneous Blood Oxygenation Level-Dependent and Cerebral Blood Flow Functional Magnetic Resonance Imaging during Forepaw Stimulation in the Rat

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199908000-00006 ◽

1999 ◽

Vol 19 (8) ◽

pp. 871-879 ◽

Cited By ~ 204

Author(s):

Afonso C. Silva ◽

Sang-Pil Lee ◽

Guang Yang ◽

Costantino Iadecola ◽

Seong-Gi Kim

Keyword(s):

Correlation Coefficient ◽

Cerebral Blood Volume ◽

Blood Oxygenation Level Dependent ◽

Blood Oxygenation ◽

Single Shot ◽

Bold Signal ◽

Doppler Flowmetry ◽

Blood Oxygenation Level ◽

Oxygenation Level ◽

Signal Changes

The blood oxygenation level-dependent (BOLD) contrast mechanism can be modeled as a complex interplay between CBF, cerebral blood volume (CBV), and CMRO2. Positive BOLD signal changes are presumably caused by CBF changes in excess of increases in CMRO2. Because this uncoupling between CBF and CMRO2 may not always be present, the magnitude of BOLD changes may not be a good index of CBF changes. In this study, the relation between BOLD and CBF was investigated further. Continuous arterial spin labeling was combined with a single-shot, multislice echo-planar imaging to enable simultaneous measurements of BOLD and CBF changes in a well-established model of functional brain activation, the electrical forepaw stimulation of a-chloralose-anesthetized rats. The paradigm consisted of two 18- to 30-second stimulation periods separated by a 1-minute resting interval. Stimulation parameters were optimized by laser Doppler flowmetry. For the same cross-correlation threshold, the BOLD and CBF active maps were centered within the size of one pixel (470 µm). However, the BOLD map was significantly larger than the CBF map. Measurements taken from 15 rats at 9.4 T using a 10-millisecond echo-time showed 3.7 ± 1.7% BOLD and 125.67 ± 81.7% CBF increases in the contralateral somatosensory cortex during the first stimulation, and 2.6 ± 1.2% BOLD and 79.3 ± 43.6% CBF increases during the second stimulation. The correlation coefficient between BOLD and CBF changes was 0.89. The overall temporal correlation coefficient between BOLD and CBF time-courses was 0.97. These results show that under the experimental conditions of the current study, the BOLD signal changes follow the changes in CBF.

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