Impact of intravenous nicotine on BOLD signal response to photic stimulation

Functional magnetic resonance imaging (fMRI) is increasingly being applied in the study of brain effects of nicotine. In addition, because tobacco smoking is common, many subjects studied with fMRI for other reasons may have appreciable levels of nicotine in plasma and brain during scanning. However, there is concern that the vascular effects of nicotine may alter the coupling between blood oxygen level dependent (BOLD) signal and neuronal activity. The objective of this study was to test for evidence of alteration of BOLD signal response of occipital cortex, a region with a relatively low concentration of neuronal nicotine receptors, to photic stimulation during intravenous infusion of nicotine. Nine nicotine dependent healthy smokers were withdrawn from nicotine under controlled conditions and then scanned while receiving photic stimulation and successive intravenous infusions of saline and nicotine. No evidence for an effect of nicotine on BOLD signal response to photic stimulation was detected at the doses studied. This observation suggests that nicotine does not alter the coupling between BOLD signal and neuronal activity in the visual cortex.     

Effects of hypoglycemia on human brain activation measured with fMRI

Functional magnetic resonance imaging (fMRI) was used to measure the effects of acute hypoglycemia caused by passive sensory stimulation on brain activation. Visual stimulation was used to generate blood-oxygen-level-dependent (BOLD) contrast, which was monitored during hyperinsulinemic hypoglycemic and euglycemic clamp studies. Hypoglycemia (50 +/- 1 mg glucose/dl) decreased the fMRI signal relative to euglycemia in 10 healthy human subjects: the fractional signal change was reduced by 28 +/- 12% (P < .05). These changes were reversed when euglycemia was restored. These data provide a basis of comparison for studies that quantify hypoglycemia-related changes in fMRI activity during cognitive tasks based on visual stimuli and demonstrate that variations in blood glucose levels may modulate BOLD signals in the healthy brain.     

Percept-related activity in the human somatosensory system: functional magnetic resonance imaging studies

In this paper, we review blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies addressing the neural correlates of touch, thermosensation, pain and the mechanisms of their cognitive modulation in healthy human subjects. There is evidence that fMRI signal changes can be elicited in the parietal cortex by stimulation of single mechanoceptive afferent fibers at suprathreshold intensities for conscious perception. Positive linear relationships between the amplitude or the spatial extents of BOLD fMRI signal changes, stimulus intensity and the perceived touch or pain intensity have been described in different brain areas. Some recent fMRI studies addressed the role of cortical areas in somatosensory perception by comparing the time course of cortical activity evoked by different kinds of stimuli with the temporal features of touch, heat or pain perception. Moreover, parametric single-trial functional MRI designs have been adopted in order to disentangle subprocesses within the nociceptive system.

Available evidence suggest that studies that combine fMRI with psychophysical methods may provide a valuable approach for understanding complex perceptual mechanisms and top-down modulation of the somatosensory system by cognitive factors specifically related to selective attention and to anticipation. The brain networks underlying somatosensory perception are complex and highly distributed. A deeper understanding of perceptual-related brain mechanisms therefore requires new approaches suited to investigate the spatial and temporal dynamics of activation in different brain regions and their functional interaction.     

Sensitivity limitations of high-resolution perfusion-based human fMRI at 7 Tesla

The study of the brain's functional organization at laminar and columnar level of the cortex with blood oxygenation-level dependent (BOLD) functional MRI (fMRI) is affected by the contribution of large veins downstream from the microvascular response to brain activity. Blood volume- and especially perfusion-based techniques may reduce this problem because of their reduced sensitivity to venous effects, but may not allow the same spatial resolution because of smaller signal changes associated with brain activity. Here we investigated the practical resolution limits of perfusion-weighted fMRI in human visual stimulation experiments. For this purpose, we used a highly sensitive, single-shot perfusion labeling (SSPL) technique at 7 T and compared sensitivity to detect visual activation at low (2 mm, n = 10) and high (1 mm, n = 8) nominal isotropic spatial, and 3 s temporal, resolution with BOLD in 5½-minute-long experiments. Despite the smaller absolute signal change with activation, 2 mm resolution SSPL yielded comparable sensitivity to BOLD. This was attributed to a superior suppression of physiological noise with SSPL. However, at 1 mm nominal resolution, SSPL sensitivity fell on average at least 42% below that of BOLD, and detection of visual activation was compromised. This is explained by the fact that at high resolution, with both techniques, typically thermal noise rather than physiological noise dominates sensitivity. The observed sensitivity loss implies that to perform 1-mm resolution, perfusion weighted fMRI with a robustness similar to BOLD, scan times that are almost 3 times longer than the comparable BOLD experiment are required. This is in line with or slightly better than previous comparisons between perfusion-weighted fMRI and BOLD. The lower sensitivity has to be weighed against the spatial fidelity advantages of high-resolution perfusion-weighted fMRI.     

To smooth or not to smooth? ROC analysis of perfusion fMRI data

Blood oxygenation level dependent (BOLD) contrast has been widely used for visualizing regional neural activation. Temporal filtering and parameter estimation algorithms are generally used to account for the intrinsic temporal autocorrelation present in BOLD data. Arterial spin labeling perfusion imaging is an emerging methodology for visualizing regional brain function both at rest and during activation. Perfusion contrast manifests different noise properties compared with BOLD contrast, represented by the even distribution of noise power and spatial coherence across the frequency spectrum. Consequently, different strategies are expected to be employed in the statistical analysis of functional magnetic resonance imaging (fMRI) data based on perfusion contrast. In this study, the effect of different analysis methods upon signal detection efficacy, as assessed by receiver operator characteristic (ROC) measures, was examined for perfusion fMRI data. Simulated foci of neural activity of varying amplitude and spatial extent were added to resting perfusion data, and the accuracy of each analysis was evaluated by comparing the results with the known distribution of pseudo-activation. In contrast to the BOLD fMRI, temporal smoothing or filtering reduces the power of perfusion fMRI data analyses whereas spatial smoothing is beneficial to the efficacy of analyses.     

Quantification of venous blood signal contribution to BOLD functional activation in the auditory cortex at 3 T

Most modern techniques for functional magnetic resonance imaging (fMRI) rely on blood-oxygen-level-dependent (BOLD) contrast as the basic principle for detecting neuronal activation. However, the measured BOLD effect depends on a transfer function related to neurophysiological changes accompanying electrical neural activation. The spatial accuracy and extension of the region of interest are determined by vascular effect, which introduces incertitude on real neuronal activation maps. Our efforts have been directed towards the development of a new methodology that is capable of combining morphological, vascular and functional information; obtaining new insight regarding foci of activation; and distinguishing the nature of activation on a pixel-by-pixel basis. Six healthy volunteers were studied in a parametric auditory functional experiment at 3 T; activation maps were overlaid on a high-resolution brain venography obtained through a novel technique. The BOLD signal intensities of vascular and nonvascular activated voxels were analyzed and compared: it was shown that nonvascular active voxels have lower values for signal peak (P<10(-7)) and area (P<10(-8)) with respect to vascular voxels. The analysis showed how venous blood influenced the measured BOLD signals, supplying a technique to filter possible venous artifacts that potentially can lead to misinterpretation of fMRI results. This methodology, although validated in the auditory cortex activation, maintains a general applicability to any cortical fMRI study, as the basic concepts on which it relies on are not limited to this cortical region. The results obtained in this study can represent the basis for new methodologies and tools that are capable of adding further characterization to the BOLD signal properties.     

Dynamics and nonlinearities of the BOLD response at very short stimulus durations

In designing a functional imaging experiment or analyzing data, it is typically assumed that task duration and hemodynamic response are linearly related to each other. However, numerous human and animal studies have previously reported a deviation from linearity for short stimulus durations (<4 s). Here, we investigated nonlinearities of blood-oxygenation-level-dependent (BOLD) signals following visual stimulation of 5 to 1000 ms duration at two different luminance levels in human subjects. It was found that (a) a BOLD response to stimulus durations as short as 5 ms can be reliably detected; this stimulus duration is shorter than employed in any previous study investigating BOLD signal time courses; (b) the responses are more nonlinear than in any other previous study: the BOLD response to 1000 ms stimulation is only twice as large as the BOLD response to 5 ms stimulation although 200 times more photons were projected onto the retina; (c) the degree of nonlinearity depends on stimulus intensity; that is, nonlinearities have to be characterized not only by stimulus duration but also by stimulus features like luminance. These findings are especially of most practical importance in rapid event-related functional magnetic resonance imaging (fMRI) experimental designs. In addition, an 'initial dip' response--thought to be generated by a rapid increase in cerebral metabolic rate of oxygen metabolism (CMRO2) relative to cerebral blood flow--was observed and shown to colocalize well with the positive BOLD response. Highly intense stimulation, better tolerated by human subjects for short stimulus durations, causes early CMRO2 increase, and thus, the experimental design utilized in this study is better for detecting the initial dip than standard fMRI designs. These results and those from other groups suggest that short stimulation combined with appropriate experimental designs allows neuronal events and interactions to be examined by BOLD signal analysis, despite its slow evolution.     

人脑初级视皮层内事件相关型视觉刺激fMRI BOLD响应特性初步研究

基于脑血氧水平依赖(BOLD)对比的功能磁共振成像（fMRI）方法是研究脑功能活动的一种重要的无损伤探测手段，BOLD的机制及它与脑神经活动关系一直是国际上十分活跃的研究领域，尤其是在实验研究方面. 视觉刺激所引起的脑的初级视皮层(V1) 的BOLD响应的时间特性已有较多的研究，但是在这些研究中，有的结论认为BOLD对视觉刺激的响应是线性的，有的结论却是相反的. 我们采用事件关联型核磁共振功能成像（ER-fMRI）方法，研究不同的短暂视觉刺激持续时间下的BOLD响应，得到了视觉刺激下的脑激活图. 同时找出了视觉刺激时间分别是1、2、3、4、5和6 s的V1区的BOLD响应曲线，并初步显示出BOLD响应与刺激持续时间的线性关系.     

Steady-state activation in somatosensory cortex after changes in stimulus rate during median nerve stimulation

Passive electrical stimulation activates various human somatosensory cortical systems including the contralateral primary somatosensory area (SI), bilateral secondary somatosensory area (SII) and bilateral insula. The effect of stimulation frequency on blood oxygenation level-dependent (BOLD) activity remains unclear. We acquired 3-T functional magnetic resonance imaging (fMRI) in eight healthy volunteers during electrical median nerve stimulation at frequencies of 1, 3 and 10 Hz. During stimulation BOLD signal changes showed activation in the contralateral SI, bilateral SII and bilateral insula. Results of fMRI analysis showed that these areas were progressively active with the increase of rate of stimulation. As a major finding, the contralateral SI showed an increase of peak of BOLD activation from 1 to 3 Hz but reached a plateau during 10-Hz stimulation. Our finding is of interest for basic research and for clinical applications in subjects unable to perform cognitive tasks in the fMRI scanner.     

Measurement and characterization of the human spinal cord SEEP response using event-related spinal fMRI

Although event-related fMRI is able to reliably detect brief changes in brain activity and is now widely used throughout systems and cognitive neuroscience, there have been no previous reports of event-related spinal cord fMRI. This is likely attributable to the various technical challenges associated with spinal fMRI (e.g., imaging a suitable length of the cord, reducing image artifacts from the vertebrae and intervertebral discs, and dealing with physiological noise from spinal cord motion). However, with many of these issues now resolved, the largest remaining impediment for event-related spinal fMRI is a deprived understanding of the spinal cord fMRI signal time course. Therefore, in this study, we used a proton density-weighted HASTE sequence, with functional contrast based on signal enhancement by extravascular water protons (SEEP), and a motion-compensating GLM analysis to (i) characterize the SEEP response function in the human cervical spinal cord and (ii) demonstrate the feasibility of event-related spinal fMRI. This was achieved by applying very brief (1 s) epochs of 22°C thermal stimulation to the palm of the hand and measuring the impulse response function. Our results suggest that the spinal cord SEEP response (time to peak ≈8 s; FWHM ≈4 s; and probably lacking pre- and poststimulus undershoots) is slower than previous estimates of SEEP or BOLD responses in the brain, but faster than previously reported spinal cord BOLD responses. Finally, by detecting and mapping consistent signal-intensity changes within and across subjects, and validating these regions with a block-designed experiment, this study represents the first successful demonstration of event-related spinal fMRI.     

Failure to direct detect magnetic field dephasing corresponding to ERP generation

Functional magnetic resonance imaging (fMRI) has become the method of choice for mapping brain activity in human subjects and detects changes in regional blood oxygenation and volume associated with local changes in neuronal activity. While imaging based on blood oxygenation level dependent (BOLD) contrast has good spatial resolution and sensitivity, the hemodynamic signal develops relatively slowly and is only indirectly related to neuronal activity. An alternative approach termed magnetic source magnetic resonance imaging (msMRI) is based on the premise that neural activity may be mapped by magnetic resonance imaging (MRI) with greater temporal resolution by detecting the local magnetic field perturbations associated with local neuronal electric currents. We used a hybrid ms/BOLD MRI method to investigate whether msMRI could detect signal changes that occur simultaneously at the time of the production of well-defined event-related potentials, the P300 and N170, in regions that previously have been identified as generators of these electrical signals. Robust BOLD activations occurred after some seconds, but we were unable to detect any significant changes in the T2*-weighted signal in these locations that correlated temporally with the timings of the evoked response potentials (ERPs).     

Activation mapping as a percentage of local excitation: fMRI stability within scans, between scans and across field strengths

Functional magnetic resonance imaging (fMRI) does not typically yield highly reproducible maps of brain activation. Maps can vary significantly even with constant scanning parameters and consistent task performance conditions (Liu et al., Magn. Reson. Med., 2004, 52:751-760). Reproducibility is even more of a problem when comparing fMRI signal magnitude and spatial extent of activation across scans involving different task performance levels, scan durations, pulse sequences or magnetic field strengths. In this report, the consistency of fMRI was reexamined by considering the relative spatial and temporal distribution of fMRI blood oxygen level dependent (BOLD) activation signals separately from the absolute magnitude of the activation signal in each brain area. Subjects repeatedly performed the same simple motor task but under a variety of imaging conditions, using both spiral and standard echo-planar pulse sequences and at 1.5- and 4.0-T magnetic field strengths. The results demonstrate that the absolute amplitude of BOLD statistical activation signals varied significantly across time and scanning conditions, but the relative spatial pattern of BOLD activation was highly reproducible across all conditions. Analysis of realistic simulated fMRI data sets indicates that stability of relative activation patterns could provide a useful tool for assessing the accuracy of fMRI maps.     

A comparison of Gamma and Gaussian dynamic convolution models of the fMRI BOLD response

Blood oxygenation level-dependent (BOLD) contrast-based functional magnetic resonance imaging (fMRI) has been widely utilized to detect brain neural activities and great efforts are now stressed on the hemodynamic processes of different brain regions activated by a stimulus. The focus of this paper is the comparison of Gamma and Gaussian dynamic convolution models of the fMRI BOLD response. The convolutions are between the perfusion function of the neural response to a stimulus and a Gaussian or Gamma function. The parameters of the two models are estimated by a nonlinear least-squares optimal algorithm for the fMRI data of eight subjects collected in a visual stimulus experiment. The results show that the Gaussian model is better than the Gamma model in fitting the data. The model parameters are different in the left and right occipital regions, which indicate that the dynamic processes seem different in various cerebral functional regions.     

Origins of intersubject variability of blood oxygenation level dependent and arterial spin labeling fMRI: implications for quantification of brain activity

Accurate localization of brain activity using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been challenged because of the large BOLD signal within distal veins. Arterial spin labeling (ASL) techniques offer greater sensitivity to the microvasculature but possess low temporal resolution and limited brain coverage. In this study, we show that the physiological origins of BOLD and ASL depend on whether percent change or statistical significance is being considered. For BOLD and ASL fMRI data collected during a simple unilateral hand movement task, we found that in the area of the contralateral motor cortex the centre of gravity (CoG) of the intersubject coefficient of variation (CV) of BOLD fMRI was near the brain surface for percent change in signal, whereas the CoG of the intersubject CV for Z-score was in close proximity of sites of brain activity for both BOLD and ASL. These findings suggest that intersubject variability of BOLD percent change is vascular in origin, whereas the origin of inter-subject variability of Z-score is neuronal for both BOLD and ASL. For longer duration tasks (12 s or greater), however, there was a significant correlation between BOLD and ASL percent change, which was not evident for short duration tasks (6 s). These findings suggest that analyses directly comparing percent change in BOLD signal between pre-defined regions of interest using short duration stimuli, as for example in event-related designs, may be heavily weighted by large-vessel responses rather than neuronal responses.     

Functional MR imaging assessment of a non-responsive brain injured patient.

Functional magnetic resonance imaging (fMRI) was requested to assist in the evaluation of a comatose 38-year-old woman who had sustained multiple cerebral contusions from a motor vehicle accident. Previous electrophysiologic studies suggested absence of thalamocortical processing in response to median nerve stimulation. Whole-brain fMRI was performed utilizing visual, somatosensory, and auditory stimulation paradigms. Results demonstrated intact task-correlated sensory and cognitive blood oxygen level dependent (BOLD) hemodynamic response to stimuli. Electrodiagnostic studies were repeated and evoked potentials indicated supratentorial recovery in the cerebrum. At 3-months post trauma the patient had recovered many cognitive & sensorimotor functions, accurately reflecting the prognostic fMRI evaluation. These results indicate that fMRI examinations may provide a useful evaluation for brain function in non-responsive brain trauma patients.     

Synchronized detection of minute electrical currents with MRI using Lorentz effect imaging

The blood oxygenation level-dependent (BOLD) effect is the most commonly used contrast mechanism in functional magnetic resonance imaging (fMRI), due to its relatively high spatial resolution and sensitivity. However, the ability of BOLD fMRI to accurately localize neuronal activation in space and time is limited by the inherent hemodynamic modulation. There is hence a need to develop alternative MRI methods that can directly image neuroelectric activity, thereby achieving both a high temporal resolution and spatial specificity as compared to conventional BOLD fMRI. In this paper, we extend the Lorentz effect imaging technique, which can detect spatially incoherent yet temporally synchronized minute electrical activity in a strong magnetic field, and demonstrate its feasibility for imaging randomly oriented electrical currents on the order of microamperes with a temporal resolution on the order of milliseconds in gel phantoms. This constitutes a promising step towards its application to direct imaging of neuroelectric activity in vivo, which has the same order of current density and temporal synchrony.     

Identification of activated regions during a language task

Functional magnetic resonance imaging (fMRI) techniques are based on the assumption that changes in neural activity are accompanied by modulation in the blood-oxygenation-level-dependent (BOLD) signal. In addition to conventional increases in BOLD signals, sustained negative BOLD signal changes are occasionally observed in many fMRI experiments, which show regions of cortex that seem to respond in antiphase with primary stimulus. The existence of this so-called negative BOLD response (NBR) has been observed and investigated in many functional studies. Several theoretical mechanisms have been proposed to account for it, but its origin has never been fully explained. In this study, the variability of fMRI activation, including the sources of the negative BOLD signal, during phonological and semantic language tasks, was investigated in six right-handed healthy subjects. We found significant activations in the brain regions, mainly in the left hemisphere, involved in the language stimuli [prominent in the inferior frontal gyrus, approximately Brodmann Areas (BA)7, BA44, BA45 and BA47, and in the precuneus]. Moreover, we observed activations in motor regions [precentral gyrus and supplementary motor area (SMA)], a result that suggests a specific role of these areas (particularly the SMA) in language processing. Functional analysis have also shown that certain brain regions, including the posterior cingulate cortex and the anterior cingulate cortex, have consistently greater activity during resting states compared to states of performing cognitive tasks. In our study, we observed diffuse NBR at the cortical level and a stronger negative response in correspondence to the main sinuses. These phenomena seem to be unrelated to a specific neural activity, appearing to be expressions of a mechanical variation in hemodynamics. We discussed about the importance of these responses that are anticorrelated with the stimulus. Our data suggest that particular care must be considered in the interpretation of fMRI findings, especially in the case of presurgical studies.     

Influence of speech stimuli intensity on the activation of auditory cortex investigated with functional magnetic resonance imaging.

Understanding the impact of variations in the acoustic signal is critical for the development of auditory and language fMRI as an experimental tool. We describe the dependence of the BOLD signal and speech intelligibility on the intensity of auditory stimuli. Eighteen subjects were imaged on a 1.5-T MRI scanner. Speech stimuli were English monosyllabic words played at five intensity levels. Intrasubject reproducibility was measured on one subject by presenting the stimulus five times at the same intensity level. Intelligibility was measured during data acquisition as subjects signaled when hearing two targets. Each functional trial consisted of four cycles (30 s off-30 s on). Five oblique slices covering primary and association auditory areas were imaged. Activated voxels were identified by cross-correlation analysis and their percent signal change (delta S) was measured. Intersubject differences in activation extent, asymmetry, and dependence on intensity were striking. Volume of activation was significantly greater in the left than in the right hemisphere. Intrasubject reproducibility for delta S was higher than for volume of activation. delta S and intelligibility showed a similar dependence on intensity suggesting that not only intensity but also intelligibility affect the fMRI signal.     

Quantification of the power changes in BOLD signals using Welch spectrum method during different single-hand motor imageries

Motor imagery is an experimental paradigm implemented in cognitive neuroscience and cognitive psychology. To investigate the asymmetry of the strength of cortical functional activity due to different single-hand motor imageries, functional magnetic resonance imaging (fMRI) data from right handed normal subjects were recorded and analyzed during both left-hand and right-hand motor imagery processes. Then the average power of blood oxygenation level-dependent (BOLD) signals in temporal domain was calculated using the developed tool that combines Welch power spectrum and the integral of power spectrum approach of BOLD signal changes during motor imagery. Power change analysis results indicated that cortical activity exhibited a stronger power in the precentral gyrus and medial frontal gyrus with left-hand motor imagery tasks compared with that from right-hand motor imagery tasks. These observations suggest that right handed normal subjects mobilize more cortical nerve cells for left-hand motor imagery. Our findings also suggest that the approach based on power differences of BOLD signals is a suitable quantitative analysis tool for quantification of asymmetry of brain activity intensity during motor imagery tasks.     

Integration of EEG source imaging and fMRI during continuous viewing of natural movies

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are noninvasive neuroimaging tools which can be used to measure brain activity with excellent temporal and spatial resolution, respectively. By combining the neural and hemodynamic recordings from these modalities, we can gain better insight into how and where the brain processes complex stimuli, which may be especially useful in patients with different neural diseases. However, due to their vastly different spatial and temporal resolutions, the integration of EEG and fMRI recordings is not always straightforward. One fundamental obstacle has been that paradigms used for EEG experiments usually rely on event-related paradigms, while fMRI is not limited in this regard. Therefore, here we ask whether one can reliably localize stimulus-driven EEG activity using the continuously varying feature intensities occurring in natural movie stimuli presented over relatively long periods of time. Specifically, we asked whether stimulus-driven aspects in the EEG signal would be co-localized with the corresponding stimulus-driven BOLD signal during free viewing of a movie. Secondly, we wanted to integrate the EEG signal directly with the BOLD signal, by estimating the underlying impulse response function (IRF) that relates the BOLD signal to the underlying current density in the primary visual area (V1). We made sequential fMRI and 64-channel EEG recordings in seven subjects who passively watched 2-min-long segments of a James Bond movie. To analyze EEG data in this natural setting, we developed a method based on independent component analysis (ICA) to reject EEG artifacts due to blinks, subject movement, etc., in a way unbiased by human judgment. We then calculated the EEG source strength of this artifact-free data at each time point of the movie within the entire brain volume using low-resolution electromagnetic tomography (LORETA). This provided for every voxel in the brain (i.e., in 3D space) an estimate of the current density at every time point. We then carried out a correlation between the time series of visual contrast changes in the movie with that of EEG voxels. We found the most significant correlations in visual area V1, just as seen in previous fMRI studies (Bartels A, Zeki, S, Logothetis NK. Natural vision reveals regional specialization to local motion and to contrast-invariant, global flow in the human brain. Cereb Cortex 2008;18(3):705–717), but on the time scale of milliseconds rather than of seconds. To obtain an estimate of how the EEG signal relates to the BOLD signal, we calculated the IRF between the BOLD signal and the estimated current density in area V1. We found that this IRF was very similar to that observed using combined intracortical recordings and fMRI experiments in nonhuman primates. Taken together, these findings open a new approach to noninvasive mapping of the brain. It allows, firstly, the localization of feature-selective brain areas during natural viewing conditions with the temporal resolution of EEG. Secondly, it provides a tool to assess EEG/BOLD transfer functions during processing of more natural stimuli. This is especially useful in combined EEG/fMRI experiments, where one can now potentially study neural-hemodynamic relationships across the whole brain volume in a noninvasive manner.