Investigation of the neurovascular coupling in positive and negative BOLD responses in human brain at 7T (original) (raw)
Related papers
Vascular dynamics and BOLD fMRI: CBF level effects and analysis considerations
Neuroimage, 2006
Changes in the cerebral blood flow (CBF) baseline produce significant changes to the hemodynamic response. This work shows that increases in the baseline blood flow level produce blood oxygenation-level dependent (BOLD) and blood flow responses that are slower and lower in amplitude, while decreases in the baseline blood flow level produce faster and higher amplitude hemodynamic responses. This effect was characterized using a vascular model of the hemodynamic response that separated arterial blood flow response from the venous blood volume response and linked the input stimulus to the vascular response. The model predicted the baseline blood flow level effects to be dominated by changes in the arterial vasculature. Specifically, it predicted changes in the arterial blood flow time constant and venous blood volume time constant parameters of +294% and À24%, respectively, for a 27% increase in the baseline blood flow. The vascular model performance was compared to an empirical model of the hemodynamic response. The vascular and empirical hemodynamic models captured most of the baseline blood flow level effects observed and can be used to correct for these effects in fMRI data. While the empirical hemodynamic model is easy to implement, it did not incorporate any explicit physiological information. D
Multi-Echo Investigations of Positive and Negative CBF and Concomitant BOLD Changes
Unlike the positive blood oxygenation level-dependent (BOLD) response (PBR), commonly taken as an indication of an ‘activated’ brain region, the physiological origin of negative BOLD signal changes (i.e. a negative BOLD response, NBR), also referred to as ‘deactivation’ is still being debated. In this work, an attempt was made to gain a better understanding of the underlying mechanism by obtaining a comprehensive measure of the contributing cerebral blood flow (CBF) and its relationship to the NBR in the human visual cortex, in comparison to a simultaneously induced PBR in surrounding visual regions. To overcome the low signal-to-noise ratio (SNR) of CBF measurements, a newly developed multi-echo version of a center-out echo planar-imaging (EPI) readout was employed with pseudo-continuous arterial spin labeling (pCASL). It achieved very short echo and inter-echo times and facilitated a simultaneous detection of functional CBF and BOLD changes at 3 T with improved sensitivity. Evalua...
NeuroImage, 2000
In this study, the hemodynamic response and changes in oxidative metabolism during functional activation were measured using three functional magnetic resonance imaging (fMRI) techniques: the blood oxygenation level-dependent (BOLD) technique, flowsensitive alternating inversion recovery (FAIR), and bolus tracking (BT) of an MR contrast agent. With these three techniques we independently determined changes in BOLD signal, relative cerebral blood flow (rCBF), and cerebral blood volume (rCBV) associated with brain activation in eight healthy volunteers. In the motor cortex, the BOLD signal increased by 1.8 ؎ 0.5%, rCBF by 36.3 ؎ 8.2% (FAIR), and 35.1 ؎ 8.6% (BT), and rCBV by 19.4 ؎ 4.1% (BT) in response to simultaneous bilateral finger tapping. In the visual cortex, BOLD signal increased by 2.6 ؎ 0.5%, rCBF by 38.5% ؎ 7.6 (FAIR), and 36.9 ؎ 8.8% (BT), and rCBV by 18.8 ؎ 2.8% (BT) during flickering checkerboard stimulation. Comparing the experimentally measured rCBV with the calculated rCBV using Grubb's power-law relation, we conclude that the use of power-law relationship results in systematic underestimate of rCBV.
A method for determining venous contribution to BOLD contrast sensory activation
Magnetic Resonance Imaging, 2002
While BOLD contrast reflects haemodynamic changes within capillaries serving neural tissue, it also has a venous component. Studies that have determined the relation of large blood vessels to the activation map indicate that veins are the source of the largest response, and the most delayed in time. It would be informative if the location of these large veins could be extracted from the properties of the functional responses, since vessels are not visible in BOLD contrast images. The present study describes a method for investigating whether measures taken from the functional response can reliably predict vein location, or at least be useful in downweighting the venous contribution to the activation response, and illustrates this method using data from one subject. We combined fMRI at 3 Tesla with highresolution anatomical imaging and MR venography to test whether the intrinsic properties of activation time courses corresponded to tissue type. Measures were taken from a gamma fit to the functional response. Mean magnitude showed a significant effect of tissue type (P<0.001) where CSF > veins ≈ grey matter > white matter. Mean delays displayed the same ranking across tissue types (P<0.001), except that veins > grey matter. However, measures for all tissue types were distributed across an overlapping range. A logistic regression model correctly discriminated 72% of the veins from grey matter in the absence of independent information of macroscopic vessels (ROC=0.72). Whilst tissue classification was not perfect for this subject, weighting the T contrast by the predicted probabilities materially reduced the venous component to the activation map.
Abstract Functional magnetic resonance imaging (fMRI) techniques in which the blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) response to a neural stimulus are measured, can be used to estimate the fractional increase in the cerebral metabolic rate of oxygen consumption (CMRO2) that accompanies evoked neural activity. A measure of neurovascular coupling is obtained from the ratio of fractional \{CBF\} and \{CMRO2\} responses, defined as n, with the implicit assumption that relative rather than absolute changes in \{CBF\} and \{CMRO2\} adequately characterise the flow-metabolism response to neural activity. The coupling parameter n is important in terms of its effect on the \{BOLD\} response, and as potential insight into the flow-metabolism relationship in both normal and pathological brain function. In 10 healthy human subjects, \{BOLD\} and \{CBF\} responses were measured to test the effect of baseline perfusion (modulated by a hypercapnia challenge) on the coupling parameter n during graded visual stimulation. A dual-echo pulsed arterial spin labelling (PASL) sequence provided absolute quantification of \{CBF\} in baseline and active states as well as relative \{BOLD\} signal changes, which were used to estimate \{CMRO2\} responses to the graded visual stimulus. The absolute \{CBF\} response to the visual stimuli were constant across different baseline \{CBF\} levels, meaning the fractional \{CBF\} responses were reduced at the hyperperfused baseline state. For the graded visual stimuli, values of n were significantly reduced during hypercapnia induced hyperperfusion. Assuming the evoked neural responses to the visual stimuli are the same for both baseline \{CBF\} states, this result has implications for fMRI studies that aim to measure neurovascular coupling using relative changes in CBF. The coupling parameter n is sensitive to baseline CBF, which would confound its interpretation in fMRI studies where there may be significant differences in baseline perfusion between groups. The absolute change in CBF, as opposed to the change relative to baseline, may more closely match the underlying increase in neural activity in response to a stimulus.
NeuroImage, 2006
Spatial specificity of functional magnetic resonance imaging (fMRI) signals to sub-millimeter functional architecture remains controversial. To investigate this issue, high-resolution fMRI in response to visual stimulus was obtained in isoflurane-anesthetized cats at 9.4 T using conventional gradient-echo (GE) and spin-echo (SE) techniques; blood oxygenation-level dependent (BOLD) and cerebral blood volume (CBV)-weighted data were acquired without and with injection of 10 mg Fe/kg monocrystalline iron oxide nanoparticles (MION), respectively. Studies after MION injection at two SE times show that the T 2 V contribution to SE fMRI is minimal. GE and SE BOLD changes were spread across the cortical layers. GE and SE CBV-weighted fMRI responses peaked at the middle cortical layer, which has the highest experimentally-determined microvascular volume; full-width at halfmaximum was <1.0 mm. Parenchymal sensitivity of GE CBV-weighted fMRI was¨3 times higher than that of SE CBV-weighted fMRI and 1.5 times higher than that of BOLD fMRI. It is well known that GE CBV-weighted fMRI detects a volume change in vessels of all sizes, while SE CBV-weighted fMRI is heavily weighted toward microvascular changes. Peak CBV change of 10% at the middle of the cortex in GE measurements was 1.8 times higher than that in SE measurements, indicating that CBV changes occur predominantly for vasculature connecting the intracortical vessels and capillaries. Our data supports the notion of laminar-dependent CBV regulation at a sub-millimeter scale. D
Dynamic and static contributions of the cerebrovasculature to the resting-state BOLD signal
2014
Functional magnetic resonance imaging (fMRI) in the resting state, particularly fMRI based on the blood-oxygenation level-dependent (BOLD) signal, has been extensively used to measure functional connectivity in the brain. However, the mechanisms of vascular regulation that underlie the BOLD fluctuations during rest are still poorly understood. In this work, using dual-echo pseudo-continuous arterial spin labeling and MR angiography (MRA), we assess the spatiotemporal contribution of cerebral blood flow (CBF) to the resting-state BOLD signals and explore how the coupling of these signals is associated with regional vasculature. Using a general linear model analysis, we found that statistically significant coupling between resting-state BOLD and CBF fluctuations is highly variable across the brain, but the coupling is strongest within the major nodes of established resting-state networks, including the default-mode, visual, and task-positive networks. Moreover, by exploiting MRA-derived large vessel (macrovascular) volume fraction, we found that the degree of BOLD-CBF coupling significantly decreased as the ratio of large vessels to tissue volume increased. These findings suggest that the portion of resting-state BOLD fluctuations at the sites of medium-to-small vessels (more proximal to local neuronal activity) is more closely regulated by dynamic regulations in CBF, and that this CBF regulation decreases closer to large veins, which are more distal to neuronal activity.
Comparison of hemodynamic response nonlinearity across primary cortical areas
NeuroImage, 2004
Blood oxygenation level dependent (BOLD) response, which is measured by functional magnetic resonance imaging (fMRI), is known to be a combination of various vascular parameters, among which deoxy-hemoglobin is argued to be a major contributor. Functional near infrared spectroscopy (fNIRS), though being limited in its spatial resolution, provides a promising tool to study cortical activations, due to its specificity of independent measurement of blood parameters (Oxy, De-oxy and Total Hemoglobin), high temporal resolution and ease of use. To study the close relationship between these imaging modalities, a finger tapping task with stimulus durations (2, 4, 8 & 16 sec) with variable inter-stimulation intervals was chosen to compare spatio-temporal properties and non-linearity of BOLD signal with HbO, HbR and HBT signal. This helped determine what parameter (HbO, HbR and HbT) BOLD signals correlate to most and how factors like neural adaptation that cause non-linearity can affect the hemodynamic behavior. It investigates the non-linearity in HbO, HbR and HbT concentrations as compared to BOLD signal obtained using simultaneous fNIRS and fMRI measurement. Investigating non-linearity in hemodynamic response could provide a better understanding of neuronal function by modeling neural adaptation. The paper also discusses a method to model the neural adaptation and hemodynamic response.
NeuroImage, 2013
The blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI) depends on the evoked changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO 2) in response to changes in neural activity. This response is strongly modulated by the CBF/CMRO 2 coupling relationship with activation, defined as n, the ratio of the fractional changes. The reliability of the BOLD signal as a quantitative reflection of underlying physiological changes depends on the stability of n in response to different stimuli. The effect of visual stimulus contrast on this coupling ratio was tested in 9 healthy human subjects, measuring CBF and BOLD responses to a flickering checkerboard at four visual contrast levels. The theory of the BOLD effect makes a robust prediction-independent of details of the model-that if the CBF/CMRO 2 coupling ratio n remains constant, then the response ratio between the lowest and highest contrast levels should be higher for the BOLD response than the CBF response because of the ceiling effect on the BOLD response. Instead, this response ratio was significantly lower for the BOLD response (BOLD response: 0.23 ± 0.13, mean ± SD; CBF response: 0.42 ± 0.18; p=0.0054). This data is consistent with a reduced dynamic range (strongest/ weakest response ratio) of the CMRO 2 response (~1.7-fold) compared to the CBF response (~2.4fold) as luminance contrast increases, corresponding to an increase of n from 1.7 at the lowest contrast level to 2.3 at the highest contrast level. The implication of these results for fMRI studies is that the magnitude of the BOLD response does not accurately reflect the magnitude of underlying physiological processes. Keywords visual contrast; functional magnetic resonance imaging (fMRI); cerebral blood flow (CBF); cerebral metabolic rate of oxygen consumption (CMRO 2); blood oxygen level dependent (BOLD) effect; arterial spin labeling (ASL); visual cortex
Arterial impulse model for the BOLD response to brief neural activation
NeuroImage, 2016
The blood oxygen level dependent (BOLD) signal evoked by brief neural stimulation, the hemodynamic response function (HRF), is a critical feature of neurovascular coupling. The HRF is directly related to local transient changes in oxygen supplied by cerebral blood flow (CBF) and oxygen demand, the cerebral metabolic rate of oxygen (CMRO 2). Previous efforts to explain the HRF have relied upon the hypothesis that CBF produces a non-linear venous dilation within the cortical parenchyma. Instead, the observed dynamics correspond to prompt arterial dilation without venous volume change. This work develops an alternative biomechanical model for the BOLD response based on the hypothesis that prompt upstream dilation creates an arterial flow impulse amenable to linear description. This flow model is coupled to a continuum description of oxygen transport. Measurements using high-resolution fMRI demonstrate the efficacy of the model. The model predicts substantial spatial variations of the oxygen saturation along the length of capillaries and veins, and fits the varied gamut of measured HRFs by the combined effects of corresponding CBF and CMRO 2 responses. Three interesting relationships among the hemodynamic parameters are predicted. First, there is an offset linear correlation with approximately unity slope between CBF and CMRO 2 responses. Second, the HRF undershoot is strongly correlated to the corresponding CBF undershoot. Third, late-time-CMRO 2 response can contribute to a slow recovery to baseline, lengthening the HRF undershoot. The model provides a powerful mathematical framework to understand the dynamics of neurovascular and neurometabolic responses that form the BOLD HRF.
Examining the regional and cerebral depth-dependent BOLD cerebrovascular reactivity response at 7T
NeuroImage, 2015
Changes in cerebral blood flow (CBF) in response to hypercapnia induced changes in vascular tone, known as cerebrovascular reactivity (CVR), can be measured using the Blood Oxygenation Level Dependent (BOLD) MR contrast. We examine regional differences in the BOLD-CVR response to a progressively increasing hypercapnic stimulus as well as regional BOLD characteristics for the return to baseline normocapnia. CVR across 9 subjects was highest in the cerebral lobes and deep grey matter. Peak CVR in these regions was measured at 3.6±1.6 mmHg above baseline end-tidal CO2. White matter CVR was generally reduced compared to that of the grey matter (peak white matter CVR was ~48% lower). A positive relationship between the end-tidal CO2 value at which peak CVR was measured and white matter depth is observed. Furthermore, the time required for the BOLD signal to return to baseline after cessation of the hypercapnic stimulus, was also related to white matter depth; the return, expressed as a t...
NeuroImage, 2015
In a recent study on healthy subjects, spatially inhomogeneous fMRI responses to intermittent photic stimulation (IPS) were observed. Preliminary results from Arrigoni et al. (2013) and Maggioni et al.(2013) showed a complex pattern of positive and negative BOLD changes , involving both striate and extra-striate visual cortexes during IPS. In addition to the positive BOLD response (PBR) in the primary visual cortex, two symmetric regions with significant NBR were detected, located in the inferior portion of the lateral occipital cortex (LOC)(Larsson and Heeger, 2006). The NBRs to IPS are more extended and exhibit higher amplitude compared to previously described visual NBRs (Shmuel et al., 2002; Bressler et al., 2007; Goense et al., 2012). A further difference versus previous studies concerns the location of the NBRs. The spatial extension of these NBRs and their high amplitude, which was comparable to the PBR one, increased the interest towards the underlying neuronal, metabolic and vascular mechanisms. Despite many efforts made towards a better comprehension of the negative BOLD phenomenon, its origin is still under discussion. Some studies suggested that the NBR could be related to a hemodynamic
NeuroImage, 2004
The blood-oxygen-level-dependent (BOLD) signal measured in the brain with functional magnetic resonance imaging (fMRI) during an activation experiment often exhibits pronounced transients at the beginning and end of the stimulus. Such transients could be a reflection of transients in the underlying neural activity, or they could result from transients in cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO 2 ), or cerebral blood volume (CBV). These transients were investigated using an arterial spin labeling (ASL) method that allows simultaneous measurements of BOLD and CBF responses. Responses to a finger-tapping task (40-s stimulus, 80-s rest) were measured in primary motor area (M1) and supplementary motor area (SMA) in five healthy volunteers. In SMA, the average BOLD response was pronounced near the beginning and end of the stimulus, while in M1, the BOLD response was nearly flat. However, CBF responses in the two regions were rather similar, and did not exhibit the same transient features as the BOLD response in SMA. Because this suggests a hemodynamic rather than a neural origin for the transients of the BOLD response in SMA, we used a generalization of the balloon model to test the degree of hemodynamic transients required to produce the measured curves. Both data sets could be approximated with modest differences in the shapes of the CMRO 2 and CBV responses. This study illustrates the utility and the limitations of using theoretical models combined with ASL techniques to understand the dynamics of the BOLD response. D
NeuroImage, 2004
Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) is widely used as a tool for functional brain mapping. During brain activation, increases in the regional blood flow lead to an increase in blood oxygenation and a decrease in paramagnetic deoxygenated hemoglobin (deoxy-Hb), causing an increase in the MR signal intensity at the site of brain activation. However, not a few studies using fMRI have failed to detect activation of areas that ought to have been activated. We assigned BOLD-positive (an increase in the signal intensity), BOLD-negative (a decrease in the signal intensity), and BOLD-silent (no change) brain activation to respective circulatory conditions through a description of fMRI signals as a function of the concentration of oxygenated Hb (oxy-Hb) and deoxy-Hb obtained with near-infrared optical imaging (NIOI). Using this model, we explain the sensory motor paradox in terms of BOLDpositive, BOLD-negative, and BOLD-silent brain activation.
Journal of Magnetic Resonance Imaging, 2013
Purpose: To quantify the amplitude and temporal aspects of the blood oxygenation level-dependent (BOLD) response to an auditory stimulus during normocapnia and hypercapnia in healthy subjects in order to establish which BOLD parameters are best suited to infer the cerebrovascular reactivity (CVR) in the middle cerebral artery (MCA) territory. Materials and Methods: Twenty healthy volunteers (mean age: 23.6 6 3.7 years, 11 women) were subjected to a functional paradigm composed of five epochs of auditory stimulus (3 sec) intercalated by six intervals of rest (21 sec). Two levels of hypercapnia were achieved by a combination of air and CO 2 while the end-tidal CO 2 (ETCO 2 ) was continually measured. An autoregressive method was applied to analyze four parameters of the BOLD signal: onset-time, time-to-peak, full-width-at-halfmaximum (FWHM), and amplitude. Results: BOLD onset time (P < 0.001) and full-width at half-maximum (FWHM) (P < 0.05) increased linearly, while BOLD amplitude decreased (P < 0.001) linearly with increasing levels of hypercapnia. Test-retest for reproducibility in five subjects revealed excellent concordance for onset time and amplitude. The robust linear dependence of BOLD onset time, FWHM, and amplitude to hypercapnia suggest future application of this protocol in clinical studies aimed at evaluating CVR of the MCA territory.
Development of BOLD signal hemodynamic responses in the human brain
NeuroImage, 2012
If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
BOLD signal sign and transient vessels volume variation
Magnetic Resonance Imaging, 2003
The purpose of this work was to investigate the relation between BOLD signal sign and transient vessels volume variation induced by apnea. This stimulus consisting of breath holding after inspiration is able to induce a light slowing down in venous blood flow like in a sort of Valsalva maneuver. We observed diffuse negative BOLD responding areas at cortical level and a stronger negative response in correspondence of the main sinuses. These phenomena seem to be unrelated to a specific neural activity, appearing to be expressions of a mechanical variation in the hemodynamics. Our study suggests that particular care must be considered in the interpretation of fMRI findings, especially when patients with vascular-related cerebral diseases are involved.
Stimulus-evoked changes in cerebral vessel diameter: A study in healthy humans
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2017
The high metabolic demand of neuronal tissue, coupled with its relatively low energy storage capacity, requires that increases in neuronal activation are quickly matched with increased blood flow to ensure efficient supply of oxygen and nutrients to the tissue. For this to occur, dilation of nearby arterioles must be coordinated with the dilation of larger upstream feeding arteries. As it stands, the exact spatial extent of such dilation in humans is unknown. Using non-invasive time-of-flight magnetic resonance angiography in healthy participants, we developed an automatic methodology for reconstructing cerebral arterial vessels and quantifying their diameter on a voxel-by-voxel basis. Specifically, we isolated the posterior cerebral artery (PCA) supplying each occipital lobe and quantified its vasodilation induced by visual stimulation. Stimulus-induced changes were strongest (∼30%) near primary visual cortex and progressively decreased in a non-linear fashion as a function of dist...
Cited by
Recent applications of UHF-MRI in the study of human brain function and structure: a review
NMR in biomedicine, 2015
The increased availability of ultra-high-field (UHF) MRI has led to its application in a wide range of neuroimaging studies, which are showing promise in transforming fundamental approaches to human neuroscience. This review presents recent work on structural and functional brain imaging, at 7 T and higher field strengths. After a short outline of the effects of high field strength on MR images, the rapidly expanding literature on UHF applications of blood-oxygenation-level-dependent-based functional MRI is reviewed. Structural imaging is then discussed, divided into sections on imaging weighted by relaxation time, including quantitative relaxation time mapping, phase imaging and quantitative susceptibility mapping, angiography, diffusion-weighted imaging, and finally magnetization-transfer imaging. The final section discusses studies using the high spatial resolution available at UHF to identify explicit links between structure and function. Copyright © 2015 John Wiley & Sons, Ltd.
Journal of Cerebral Blood Flow & Metabolism
Negative blood oxygenation–level dependent (BOLD) signal observed during task execution in functional magnetic resonance imaging (fMRI) can be caused by different mechanisms, such as a blood-stealing effect or neuronal deactivation. Electrophysiological recordings showed that neuronal deactivation underlies the negative BOLD observed in the occipital lobe during visual stimulation. In this study, the metabolic demand of such a response was studied by measuring local metabolite concentration changes during a visual checkerboard stimulation using functional magnetic resonance spectroscopy (fMRS) at 7 Tesla. The results showed increases of glutamate and lactate concentrations during the positive BOLD response, consistent with previous fMRS studies. In contrast, during the negative BOLD response, decreasing concentrations of glutamate, lactate and gamma-aminobutyric acid (GABA) were found, suggesting a reduction of glycolytic and oxidative metabolic demand below the baseline. Additional...
Identification of negative BOLD responses using windkessel models
Alongside positive BOLD responses (PBR), a variety of negative BOLD responses (NBR) with distinct underlying mechanisms also occur. We identify five mechanisms of NBR: i) local/lateral/contralateral inhibition (LCI), ii) neuronal disruption of network activity (NDA), iii) altered balance of neuro-metabolic/vascular couplings (ANC), iv) arterial blood stealing (ABS), and v) venous blood backpressure (VBB). Detecting and classifying these mechanisms from BOLD signals is pivotal in understanding normal/pathological brain functions. This requires models and parameters with anatomical/functional interpretation that furnish the understanding of how these mechanisms are fingerprinted by their BOLD responses. Here, we used a windkessel model with viscoelastic compliance as well as dynamics of both neuronal and tissue/blood O2 to investigate the generation, detection, classification and interpretation of the BOLD hemodynamic response functions (HRF) of above mechanisms. Firstly, we evaluated...
Frontiers in Systems Neuroscience
Background: Compression of myofascial trigger points (MTrPs) in muscles is reported to reduce chronic musculoskeletal pain. Although the prefrontal cortex (PFC) is implicated in development of chronic pain, the mechanisms of how MTrP compression at low back regions affects PFC activity remain under debate. In this study, we investigated effects of MTrP compression on brain hemodynamics and EEG oscillation in subjects with chronic low back pain. Methods: The study was a prospective, randomized, parallel-group trial and an observer and subject-blinded clinical trial. Thirty-two subjects with chronic low back pain were divided into two groups: subjects with compression at MTrPs (n = 16) or those with non-MTrPs (n = 16). Compression at MTrP or non-MTrP for 30 s was applied five times, and hemodynamic activity (near-infrared spectroscopy; NIRS) and EEGs were simultaneously recorded during the experiment. Results: The results indicated that compression at MTrPs significantly (1) reduced subjective pain (P < 0.05) and increased the pressure pain threshold (P < 0.05), (2) decreased the NIRS hemodynamic activity in the frontal polar area (pPFC) (P < 0.05), and (3) increased the current source density (CSD) of EEG theta oscillation in the anterior part of the PFC (P < 0.05). CSD of EEG theta oscillation was negatively correlated with NIRS hemodynamic activity in the pPFC (P < 0.05). Furthermore, functional connectivity in theta bands between the medial pPFC and insula cortex was significantly decreased
Human Brain Mapping, 2016
Although the occurrence of concomitant positive BOLD responses (PBRs) and negative BOLD responses (NBRs) to visual stimuli is increasingly investigated in neuroscience, it still lacks a definite explanation. Multimodal imaging represents a powerful tool to study the determinants of negative BOLD responses: the integration of functional Magnetic Resonance Imaging (fMRI) and electroencephalographic (EEG) recordings is especially useful, since it can give information on the neurovascular coupling underlying this complex phenomenon. In the present study, the brain response to intermittent photic stimulation (IPS) was investigated in a group of healthy subjects using simultaneous EEG-fMRI, with the main objective to study the electrophysiological mechanisms associated with the intense NBRs elicited by IPS in extrastriate visual cortex. The EEG analysis showed that IPS induced a desynchronization of the basal rhythm, followed by the instauration of a novel rhythm driven by the visual stimulation. The most interesting results emerged from the EEG-informed fMRI analysis, which suggested a relationship between the neuronal rhythms at 10 and 12 Hz and the BOLD dynamics in extra-striate visual cortex. These findings support the hypothesis that NBRs to visual stimuli may be neuronal in origin rather than reflecting pure vascular phenomena.
Neurovascular coupling in the developing neonatal brain at rest
Human Brain Mapping
The neonatal brain is an extremely dynamic organization undergoing essential development in terms of connectivity and function. Several functional imaging investigations of the developing brain have found neurovascular coupling (NVC) patterns that contrast with those observed in adults. These discrepancies are partly due to that NVC is still developing in the neonatal brain. To characterize the vascular response to spontaneous neuronal activations, a multiscale multimodal noninvasive approach combining simultaneous electrical, hemodynamic, and metabolic recordings has been developed for preterm infants. Our results demonstrate that the immature vascular network does not adopt a unique strategy to respond to spontaneous cortical activations. NVC takes on different forms in the same preterm infant during the same recording session in response to very similar types of neural activation. This includes (a) positive stereotyped hemodynamic responses (increases in HbO, decreases in HbR together with increases in rCBF and rCMRO2), (b) negative hemodynamic responses (increases in HbR, decreases in HbO together with decreases in rCBF and rCMRO2), and (c) Increases and decreases in both HbO-HbR and rCMRO2 together with no changes in rCBF. Age-related NVC maturation is demonstrated in preterm infants, which can contribute to a better understanding/prevention of cerebral hemodynamic risks in these infants.
Hemodynamic modeling of aspirin effects on BOLD responses at 7T
2020
Aspirin is considered a potential confound for functional magnetic resonance imaging (fMRI) studies. This is because aspirin affects the synthesis of prostaglandin, a vasoactive mediator centrally involved in neurovascular coupling, a process that underlies the blood oxygenated level dependent (BOLD) response. Aspirin-induced changes in BOLD signal are a potential confound for fMRI studies of patients (e.g. with cardiovascular conditions or stroke) who receive low-dose aspirin prophylactically and are compared to healthy controls that do not take aspirin. To examine the severity of this potential confound, we combined high field (7 Tesla) MRI during a simple hand movement task with a biophysically informed hemodynamic model. Comparing elderly volunteers with vs. without aspirin medication, we tested for putative effects of low-dose chronic aspirin on the BOLD response. Specifically, we fitted hemodynamic models to BOLD signal time courses from 14 regions of the human motor system an...
Human Brain Mapping, 2020
Calibrated functional magnetic resonance imaging can remove unwanted sources of signal variability in the blood oxygenation level-dependent (BOLD) response. This is achieved by scaling, using information from a perfusion-sensitive scan during a purely vascular challenge, typically induced by a gas manipulation or a breath-hold task. In this work, we seek for a validation of the use of the resting-state fluctuation amplitude (RSFA) as a scaling factor to remove vascular contributions from the BOLD response. Given the peculiarity of depth-dependent vascularization in gray matter, BOLD and vascular space occupancy (VASO) data were acquired at submillimeter resolution and averaged across cortical laminae. RSFA from the primary motor cortex was, thus, compared to the amplitude of hypercapnia-induced signal changes (tSD hc) and with the M factor of the Davis model on a laminar level. High linear correlations were observed for RSFA and tSD hc (R 2 = 0.92 ± 0.06) and somewhat reduced for RSFA and M (R 2 = 0.62 ± 0.19). Laminar profiles of RSFAnormalized BOLD signal changes yielded good agreement with corresponding VASO profiles. Overall, this suggests that RSFA contains strong vascular components and is also modulated by baseline quantities contained in the M factor. We
Molecular Brain, 2021
The neurotransmitter serotonin, involved in the regulation of pain and emotion, is critically regulated by the 5‐HT1A autoreceptor and the serotonin transporter (5-HTT). Polymorphisms of these genes affect mood and endogenous pain modulation, both demonstrated to be altered in fibromyalgia subjects (FMS). Here, we tested the effects of genetic variants of the 5‐HT1A receptor (CC/G-carriers) and 5-HTT (high/intermediate/low expression) on mood, pain sensitivity, cerebral processing of evoked pain (functional MRI) and concentrations of GABA and glutamate (MR spectroscopy) in rostral anterior cingulate cortex (rACC) and thalamus in FMS and healthy controls (HC). Interactions between serotonin-relevant genes were found in affective characteristics, with genetically inferred high serotonergic signalling (5-HT1A CC/5-HTThigh genotypes) being more favourable across groups. Additionally, 5‐HT1A CC homozygotes displayed higher pain thresholds than G-carriers in HC but not in FMS. Cerebral pr...
LayNii: A software suite for layer-fMRI
NeuroImage, 2021
High-resolution fMRI in the sub-millimeter regime allows researchers to resolve brain activity across cortical layers and columns non-invasively. While these highresolution data make it possible to address novel questions of directional information flow within and across brain circuits, the corresponding data analyses are challenged by MRI artifacts, including image blurring, image distortions, low SNR, and restricted coverage. These challenges often result in insufficient spatial accuracy of conventional analysis pipelines. Here we introduce a new software suite that is specifically designed for layer-specific functional MRI: LayNii. This toolbox is a collection of command-line executable programs written in C/C ++ and is distributed opensource and as pre-compiled binaries for Linux, Windows, and macOS. LayNii is designed for layer-fMRI data that suffer from SNR and coverage constraints and thus cannot be straightforwardly analyzed in alternative software packages. Some of the most popular programs of LayNii contain 'layerification' and columnarization in the native voxel space of functional data as well as many other layer-fMRI specific analysis tasks: layer-specific smoothing, model-based vein mitigation of GE-BOLD data, quality assessment of artifact dominated sub-millimeter fMRI, as well as analyses of VASO data.
Causal connectivity from right DLPFC to IPL in schizophrenia patients: a pilot study
Schizophrenia, 2022
Abnormal function and connectivity of the fronto-parietal network (FPN) have been documented in patients with schizophrenia, but studies are correlational. We applied repetitive transcranial magnetic stimulation (rTMS) to the dorso-lateral prefrontal cortex (DLPFC) and observed causal connectivity to the inferior parietal lobe (IPL). We hypothesized that patients with schizophrenia would have lower activation and slower reaction in the IPL following DLPFC stimulation. Thirteen patients with schizophrenia (SZ) and fourteen healthy controls subjects (HC) underwent rTMS at 10 Hz to the right DLPFC. Simultaneously, we measured brain activation in the IPL, represented as oxygenized hemoglobin (HbO) levels, using functional near-infrared spectroscopy (fNIRS). rTMS consisted of 20 trains of impulses at 10 Hz for 3 seconds, and 60 seconds waiting time. Using NIRSLab software, GLM was applied to estimate both hemodynamic response function (HRF) and its derivative. Following TMS to the DLPFC,...
Journal of Cerebral Blood Flow & Metabolism, 2018
Dynamic metabolic changes were investigated by functional magnetic resonance spectroscopy (fMRS) during sustained stimulation of human primary visual cortex. Two established paradigms, consisting of either a full-field or a small-circle flickering checkerboard, were employed to generate wide-spread areas of positive or negative blood oxygenation level-dependent (BOLD) responses, respectively. Compared to baseline, the glutamate concentration increased by 5.3% ( p = 0.007) during activation and decreased by −3.8% ( p = 0.017) during deactivation. These changes were positively correlated with the amplitude of the BOLD response ( R = 0.60, p = 0.002) and probably reflect changes of tricarboxylic acid cycle activity. During deactivation, the glucose concentration decreased by −7.9% ( p = 0.025) presumably suggesting increased consumption or reduced glucose supply. Other findings included an increased concentration of glutathione (4.2%, p = 0.023) during deactivation and a negative corre...