What aspect of the fMRI BOLD signal best reflects the underlying electrophysiology in human somatosensory cortex? (original) (raw)

Linear coupling between functional magnetic resonance imaging and evoked potential amplitude in human somatosensory cortex

Neuroscience, 2000

The interpretation of task-induced functional imaging of the brain is critically dependent on understanding the relationship between observed blood flow responses and the underlying neuronal changes. However, the exact nature of this neurovascular coupling relationship remains unknown. In particular, it is unclear whether blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) responses principally reflect neuronal synaptic activity. In order to address this issue directly in humans, we measured the increase in somatosensory evoked potential amplitude and fMRI BOLD changes to increases in intensity of median nerve electrical stimulation in five healthy non-anaesthetized subjects. We found that mean N20-P22 amplitudes increased significantly with stimulus intensity in all subjects, as did fMRI BOLD percentage signal intensity change. Moreover, the intensity of the BOLD signal was found to correlate linearly with evoked potential amplitude in four of the five subjects studied. This suggests that the BOLD response correlates with synchronized synaptic activity, which is the major energy consuming process of the cortex. ᭧

Intracortically Distributed Neurovascular Coupling Relationships within and between Human Somatosensory Cortices

Cerebral Cortex, 2006

The coupling of neuronal cellular activity to its blood supply is of critical importance to the physiology of the human brain and has been under discussion for more than a century. Linearity in this relationship has been demonstrated in some animal studies, but evidence is lacking in humans. In this study, we compared scalp evoked potentials and the functional magnetic resonance imaging (fMRI) blood oxygen level--dependent (BOLD) signal from healthy human volunteers with changes in the intensity of a somatosensory stimulus. By weighting the fMRI images according to the evoked potential amplitude at corresponding intensities, we tested for positive and negative covariation between these 2 data sets and the extent to which these were linear. Hemodynamic changes in primary somatosensory cortex covaried positively with neuronal activity in a predominantly linear manner, with a small quadratic contribution. Simultaneously, other cortical areas corresponding to the nonstimulated limbs were found to covary negatively and linearly in the hemispheres ipsilateral and contralateral to the stimulus. These concurrent and bilateral cortical dynamics, as well as the intraregional features of this neurovascular coupling, are both more complex than had been considered to date, with considerable implications.

Attention differentially modulates the coupling of fMRI BOLD and evoked potential signal amplitudes in the human somatosensory cortex

Experimental Brain Research, 2004

Blood oxygenation dependent contrast (BOLD) fMRI is used increasingly to probe "connectivity" based on temporal correlations between signals from different brain regions. This approach assumes that there is constant local coupling of neuronal activity to the associated BOLD response. Here we test the alternative hypothesis that there is not a fixed relationship between these by determining whether attention modulates apparent neurovascular coupling. Electrical stimulation of the median nerve was applied with and without a concurrent distractor task (serial subtraction). Increasing stimulation intensity increased discomfort ratings (p<0.001) and was associated with a significant increase in both somatosensory evoked potential (SEP) N20-P25 amplitude and BOLD fMRI response in the contralateral primary (SI) and bilaterally in the secondary somatosensory cortices. Attention to stimulation was reduced during distractor task performance and resulted in an overall trend for reduction in discomfort (p=0.056), which was significant at the highest stimulation level (p<0.05). A volume of interest analysis confined to SI confirmed a reduction in BOLD response with distraction (p<0.001). However, distraction did not measurably affect SEP magnitude. The quantitative relationship between the BOLD fMRI response and the local field potential measured by the early SEP response therefore varies with attentional context. This may be a consequence of differences in either local spatial or temporal signal summation for the two methods. Either interpretation suggests caution in assuming a simple, fixed relationship between local BOLD changes and related electrophysiological activity.

Circulatory basis of fMRI signals: relationship between changes in the hemodynamic parameters and BOLD signal intensity

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. D

Regional differences in the coupling of cerebral blood flow and oxygen metabolism changes in response to activation: implications for BOLD-fMRI

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 ...

Coupling between simultaneously recorded BOLD response and neuronal activity in the rat somatosensory cortex

NeuroImage, 2008

Understanding the link between the hemodynamic response and the underlying neuronal activity is important for interpreting functional magnetic resonance (fMRI) signals in human and animal studies. Simultaneous electrophysiological and functional imaging measurements provide a knowledge of information processing and communication in the brain with high spatial and temporal resolution. In this study, a range of neural and blood oxygenation level-dependent (BOLD) responses were elicited in the rat somatosensory cortex by changing the type of anesthesia (urethane or alpha-chloralose) and the electrical forepaw stimulus frequency (1-15 Hz). Duration of the stimulus was 30 s. Electrical local field potential and BOLD fMRI responses were recorded simultaneously. Under urethane anesthesia, integrated neural activity and BOLD responses increased with increasing stimulus frequency up to 11 Hz, after which both responses plateaued. In contrast, in alpha-chloralose-anesthetized rats both responses were measurable only at 1 and 3 Hz. Although neuronal and BOLD responses were nonlinear as a function of frequency over the 1 to 15 Hz stimulation range under both anesthetics, tight neuralhemodynamic coupling was observed independently of the anesthetic agent. Anesthetic agents influence neuronal activity in a different manner, but the relationship of neuronal activity and BOLD response remains the same.

Variability of the Relationship between Electrophysiology and BOLD-fMRI across Cortical Regions in Humans

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.

Negative BOLD signal changes in ipsilateral primary somatosensory cortex are associated with perfusion decreases and behavioral evidence for functional inhibition

NeuroImage, 2012

We used functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) to study the negative blood oxygenation level dependent (BOLD) signal and its underlying blood flow changes in healthy human subjects. This was combined with psychophysiological measurements to test that the negative BOLD signal is associated with functional inhibition. Electrical stimulation of the median nerve at 7 Hz evoked robust negative BOLD signals in the primary somatosensory cortex (SI) ipsilateral to stimulation, and positive BOLD signals in contralateral SI. The negative BOLD signal in ipsilateral SI was accompanied by commensurate decreases in relative regional cerebral blood flow (rCBF). Conjunction analysis of the fMRI and PET data revealed a region in the ipsilateral postcentral gyrus showing overlap of negative BOLD signals and relative rCBF decreases. The current perception threshold (CPT) at the ipsilateral finger during concomitant stimulation of the contralateral median nerve increased significantly, suggesting augmented functional inhibition. Since the CPT in the ipsilateral hallux did not significantly change in response to median nerve stimulation, it is more likely that the CPTincrease for the finger is due to functional inhibition (Kastrup et al., 2008) than to changes in selective attention. In conclusion, our data provide evidence that stimulus-induced reductions in relative rCBF may underlie the negative BOLD signal, which in turn may reflect increments in functional inhibition.

Imaging of prolonged BOLD response in the somatosensory cortex of the rat

NMR in Biomedicine, 2015

Blood oxygenation level-dependent (BOLD) functional MRI is a widely employed methodology in experimental and clinical neuroscience, although its nature is not fully understood. To gain insights into BOLD mechanisms and take advantage of the new functional methods, it is of interest to investigate prolonged paradigms of activation suitable for long experimental protocols and to observe any long-term modifications induced by these functional challenges. While different types of sustained stimulation paradigm have been explored in human studies, the BOLD response is typically limited to a few minutes in animal models, due to fatigue, anesthesia effects and physiological instability. In the present study, the rat forepaw was electrically stimulated for 2 h, which resulted in a prolonged and localized cortical BOLD response over that period. The stimulation paradigm, including an inter-stimulus interval (ISI) of 10 s, that is 25% of the total time, was applied at constant or variable frequency over 2 h. The steady-state level of the BOLD response was reached after 15-20 min of stimulation and was maintained until the end of the stimulation. On average, no substantial loss in activated volume was observed at the end of the stimulation, but less variability in the fraction of remaining activated volume and higher steady-state BOLD amplitude were observed when stimulation frequency was varied between 2 and 3 Hz every 5 min. We conclude that the combination of ISI and variable stimulus frequency reproducibly results in robust, prolonged and localized BOLD activation.

Evoked local field potentials can explain temporal variation in blood oxygenation level-dependent responses in rat somatosensory cortex

NMR in Biomedicine, 2010

The aim of this study was to explain the temporal variations between subjects in the blood oxygenation leveldependent (BOLD) response. Somatosensory responses were elicited with the electrical forepaw stimulus at a frequency of 10 Hz in urethane-anesthetized rats, and functional magnetic resonance imaging (fMRI) with BOLD contrast and local field potential (LFP) measurements were performed simultaneously. BOLD fMRI activation was evaluated by two different models, one based on the stimulus paradigm (the block model) and the other on the simultaneously measured evoked LFP responses. In the initial analysis, the LFP model captured the BOLD activation in the primary somatosensory cortex in all cases, and the block model in 10 of 12 rats. A statistical comparison of the two models revealed that the LFP-derived model was able to explain additional BOLD variation over the block model in the somatosensory cortex in nine of 12 rats. These results suggest that there is more information regarding neuronal activity in the BOLD signal than can be exploited using the block model alone. Furthermore, the hemodynamic coupling remains unchanged in the case of temporally variable BOLD signals.