Spatial relationship between neuronal activity and BOLD functional MRI (original) (raw)
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Journal of Neuroscience, 2011
The relationship between blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signal and the underlying neural electrical activity in humans is a topic of intense interest to systems neuroscience. This relationship has generally been assumed to be invariant regardless of the brain region and the cognitive task being studied. We critically evaluated these assumptions by comparing the BOLD-fMRI response with local field potential (LFP) measurements during visually cued common noun and verb generation in 11 humans in whom 1210 subdural electrodes were implanted. As expected, power in the mid-gamma band (60 -120 Hz) correlated positively (r 2 ϭ 0.16, p Ͻ 10 Ϫ16 ) and power in the beta band (13-30 Hz) correlated negatively (r 2 ϭ 0.09, p Ͻ 10 Ϫ16 ) with the BOLD signal change. Beta and mid-gamma band activity independently explain different components of the observed BOLD signal. Importantly, we found that the location (i.e., lobe) of the recording site modulates the relationship between the electrocorticographic (ECoG) signal and the observed fMRI response (p Ͻ , while the type of language task does not. Across all brain regions, ECoG activity in the gamma and beta bands explains 22% of the fMRI response, but if the lobar location is considered, 28% of the variance can be explained. Further evaluation of this relationship at the level of individual gyri provides additional evidence of differences in the BOLD-LFP relationship by cortical locus. This spatial variability in the relationship between the fMRI signal and neural activity carries implications for modeling of the hemodynamic response function, an essential step for interregional fMRI comparisons.
Calibrating BOLD fMRI Activations with Neurovascular and Anatomical Constraints
2013
Abstract Functional magnetic resonance imaging signals, in addition to reflecting neuronal response, also contain physiological variances. These factors may introduce variability into blood oxygen level–dependent (BOLD) activation results, particularly in different population groups. In this study, we hypothesized that the amplitude as well as the spatial extent of BOLD activation could be improved after minimizing the variance caused by the neurovascular and anatomical factors.
Bridging the Gap Between Neuroimaging and Neuronal Physiology
Image Analysis & Stereology, 2011
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…
NeuroImage, 2008
Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, but quantitative interpretation of the BOLD response is problematic. The BOLD response is primarily driven by cerebral blood flow (CBF) changes, but is moderated by M, a scaling parameter reflecting baseline deoxyhemoglobin, and n, the ratio of fractional changes in CBF to cerebral metabolic rate of oxygen consumption (CMRO(2)). We compared M and n between cortical (visual cortex, VC) and subcortical (lentiform nuclei, LN) regions using a quantitative approach based on calibrating the BOLD response with a hypercapnia experiment. Although M was similar in both regions (~5.8%), differences in n (2.21+/-0.03 in VC and 1.58+/-0.03 in LN; Cohen d=1.71) produced substantially weaker (~3.7x) subcortical than cortical BOLD responses relative to CMRO(2) changes. Because of this strong sensitivity to n, BOLD response amplitudes cannot ...
Enhanced fMRI Response Detection and Reduced Latency through Spatial Analysis of BOLD Signals
2008
In conventional functional magnetic resonance imaging (fMRI) analysis, activation is often inferred by examining only the intensity modulation of blood-oxygen-level dependent (BOLD) signal of each voxel in isolation or in small, local clusters. However, as has been recently demonstrated, activation can in fact be detected by examining the spatial modulation of the BOLD distribution within a region of interest (ROI). In this paper, we propose and demonstrate with real fMRI data that analyzing such spatial changes can enhance the effect size of fMRI response detection over using intensity information alone. Furthermore, we show that such spatial changes consistently and significantly antecede mean intensity changes in multiple ROIs. We hence foresee spatial analysis of BOLD distribution to be a promising direction to explore in complementing pure intensity-based approaches.
Quantitative functional imaging of the brain: towards mapping neuronal activity by BOLD fMRI
NMR in Biomedicine, 2001
Quantitative magnetic resonance imaging (MRI) and spectroscopy (MRS) measurements of energy metabolism (i.e. cerebral metabolic rate of oxygen consumption, CMR O2 ), blood circulation (i.e. cerebral blood flow, CBF, and volume, CBV), and functional MRI (fMRI) signal over a wide range of neuronal activity and pharmacological treatments are used to interpret the neurophysiologic basis of blood oxygenation level dependent (BOLD) image-contrast at 7 T in glutamatergic neurons of rat cerebral cortex. Multi-modal MRI and MRS measurements of CMR O2 , CBF, CBV and BOLD signal (both gradient-echo and spin-echo) are used to interpret the neuroenergetic basis of BOLD image-contrast. Since each parameter that can influence the BOLD image-contrast is measured quantitatively and separately, multi-modal measurements of changes in CMR O2 , CBF, CBV, BOLD fMRI signal allow calibration and validation of the BOLD image-contrast. Good agreement between changes in CMR O2 calculated from BOLD theory and measured by 13 C MRS, reveals that BOLD fMRI signal-changes at 7 T are closely linked with alterations in neuronal glucose oxidation, both for activation and deactivation paradigms. To determine the neurochemical basis of BOLD, pharmacological treatment with lamotrigine, which is a neuronal voltagedependent Na channel blocker and neurotransmitter glutamate release inhibitor, is used in a rat forepaw stimulation model. Attenuation of the functional changes in CBF and BOLD with lamotrigine reveals that the fMRI signal is associated with release of glutamate from neurons, which is consistent with a link between neurotransmitter cycling and energy metabolism. Comparisons of CMR O2 and CBF over a wide dynamic range of neuronal activity provide insight into the regulation of energy metabolism and oxygen delivery in the cerebral cortex. The current results reveal the energetic and physiologic components of the BOLD fMRI signal and indicate the required steps towards mapping neuronal activity quantitatively by fMRI at steady-state. Consequences of these results from rat brain for similar calibrated BOLD fMRI studies in the human brain are discussed. Abbreviations used: BOLD, blood-oxygenation level dependent; CBF, cerebral blood flow; CBV, cerebral blood volume; CMR glc , cerebral metabolic rate for glucose consumption; CMR glc(ox) , cerebral metabolic rate for glucose oxidation; CMR O2 , cerebral metabolic rate for oxygen consumption; D, effective mass transfer coefficient for oxygen in the capillary bed; DANTE, delays alternating with nutations for tailored excitation; EPI, echo planar imaging; FLASH, fast low-angle shot; fMRI, functional MRI; ICED PEPSI, in vivo carbon edited detection with proton echo planar spectroscopic imaging; MRI, magnetic resonance imaging;
Spatio-temporal point-spread function of fMRI signal in human gray matter at 7 Tesla
NeuroImage, 2007
This study investigated the spatio-temporal properties of blood-oxygenation level-dependent (BOLD) functional MRI (fMRI) signals in gray matter (GM), excluding the confounding, inaccurate contributions of large blood vessels. Specifically, we quantified the spatial specificity of the BOLD response, and we investigated whether this specificity varies as a function of time from stimulus onset. fMRI was performed at 7 Tesla, where mapping signals of parenchymal origin are easily detected. Two abutting visual stimuli were adjusted to elicit responses centered on a flat GM region in V1. fMRI signals were sampled in high-resolution orthogonal to the retinotopic boundary between the representations of the stimuli. Signals from macro-vessels were masked out. Principal component analysis revealed that the first component in space accounted for 96.2±1.6% of the variance over time. The spatial profile of this time-invariant response was fitted with a model consisting of the convolution of a step function and a Gaussian point-spread-function. The mean fullwidth at half-maximal-height of the fitted point-spread-function was 2.34±0.20 mm. Based on simulations of confounding effects, we estimate that BOLD point-spread-function in human GM is smaller than 2 mm. A detailed time-point to time-point analysis revealed that the estimated pointspread-function obtained during the 3rd (1.52 mm) and 4th (1.99 mm) seconds of stimulation were narrower than the mean estimated point-spread-function obtained from the 5th second on (2.42±0.15 mm, mean ± SD). The position of the edge of the responding region was offset (1.72±0.07 mm) from the boundary of the stimulated region, indicating a spatial non-linearity. In conclusion, the point-spread-function of the hyper-oxygenated BOLD response in human GM is narrower than that reported at 1.5 Tesla, where macro-vessels dominate the mapping signals. The initial phase of this response is more spatially specific than later phases. Data acquisition methods that suppress macro-vascular signals should increase the spatial specificity of BOLD fMRI. The choice of optimal stimulus duration represents a trade-off between the spatial specificity and the overhead associated with short stimulus duration.
Spatial specificity of BOLD versus cerebral blood volume fMRI for mapping cortical organization
Journal of Cerebral Blood Flow & Metabolism, 2007
Intravascular contrast agents are used in functional magnetic resonance imaging to obtain cerebral blood volume (CBV) maps of cortical activity. Cerebral blood volume imaging with MION (monocrystalline-iron-oxide-nanoparticles) increases the sensitivity of functional imaging compared with the blood oxygenation level-dependent (BOLD) signal . It therefore represents an attractive method for obtaining detailed maps of cortical organization . However, it remains to be determined how the spatial profile of CBV maps of cortical activity derived with MION compares with the profile of BOLD activation maps under a variety of different stimulation conditions. We used several stimulation paradigms to compare the spatial specificity of CBV versus BOLD activation maps in macaque area V1 at 4.7 T. We observed that: (1) CBV modulation is relatively stronger in deep cortical layers compared with BOLD, in agreement with studies in cats and rodents and surprisingly, under large surround stimulation conditions, CBV maps extend along the cortical surface to cover large ( > 10 mm) regions of the cortex that are devoid of significant BOLD modulation. We conclude that the spatial profiles of BOLD and CBV activity maps do not coregister across all stimulus conditions, and therefore do not necessarily represent equivalent transforms of the neural response. Cerebral blood volume maps should be interpreted with care, in the context of the particular experimental paradigm applied.
All that glitters is not BOLD: inconsistencies in functional MRI
Scientific Reports, 2014
The blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal is a widely-accepted marker of brain activity. The acquisition parameters (APs) of fMRI aim at maximizing the signals related to neuronal activity while minimizing unrelated signal fluctuations. Currently, a diverse set of APs is used to acquire BOLD fMRI data. Here we demonstrate that some fMRI responses are alarmingly inconsistent across APs, ranging from positive to negative, or disappearing entirely, under identical stimulus conditions. These discrepancies, resulting from non-BOLD effects masquerading as BOLD signals, have remained largely unnoticed because studies rarely employ more than one set of APs. We identified and characterized non-BOLD responses in several brain areas, including posterior cingulate cortex and precuneus, as well as AP-dependence of both the signal time courses and of seed-based functional networks, noticing that AP manipulation can inform about the origin of the measured signals.
Clinical Neurophysiology, 2003
The interpretation of task-induced functional imaging of the brain is critically dependent on understanding the relationship between observed haemodynamic responses and the underlying neural changes. However, the precise nature of this neurovascular coupling relationship remains unknown. In particular, it is unclear which measure of functional magnetic resonance imaging blood oxygen level dependent (fMRI BOLD) activity is the best correlate of neural activity. We measured the somatosensory evoked potential (SEP) amplitude at the scalp, and fMRI BOLD signal to increases in intensity of contralateral median nerve electrical stimulation in healthy non-anaesthetised subjects. We compared correlation analyses between SEP amplitude and both peak voxel fMRI BOLD percentage signal change and mean voxel fMRI BOLD percentage signal change across a somatosensory cluster, and we also performed a voxel-by-voxel correlation between fMRI BOLD activity and SEP amplitude. We found that fMRI BOLD changes in primary somatosensory cortex correlate significantly with SEP amplitudes, suggesting a linear neurovascular coupling relationship under the conditions investigated. We also found that mean changes across a cluster correlate less well with SEP amplitude than peak voxel levels. This suggests that the area of haemodynamic activity correlating with SEP amplitude is smaller than the entire cluster observed. (S.J. Boniface).