Modeling the contribution of neuron-astrocyte cross talk to slow blood oxygenation level-dependent signal oscillations

A consistent and prominent feature of brain functional magnetic resonance imaging (fMRI) data is the presence of low-frequency (<0.1 Hz) fluctuations of the blood oxygenation level-dependent (BOLD) signal that are thought to reflect spontaneous neuronal activity. In this report we provide modeling evidence that cyclic physiological activation of astroglial cells produces similar BOLD oscillations through a mechanism mediated by intracellular Ca(2+) signaling. Specifically, neurotransmission induces pulses of Ca(2+) concentration in astrocytes, resulting in increased cerebral perfusion and neuroactive transmitter release by these cells (i.e., gliotransmission), which in turn stimulates neuronal activity. Noticeably, the level of neuron-astrocyte cross talk regulates the periodic behavior of the Ca(2+) wave-induced BOLD fluctuations. Our results suggest that the spontaneous ongoing activity of neuroglial networks is a potential source of the observed slow fMRI signal oscillations.     

Isolating the sources of widespread physiological fluctuations in functional near-infrared spectroscopy signals

Physiological fluctuations at low frequency (<0.1 Hz) are prominent in functional near-infrared spectroscopy (fNIRS) measurements in both resting state and functional task studies. In this study, we used the high spatial resolution and full brain coverage of functional magnetic resonance imaging (fMRI) to understand the origins and commonalities of these fluctuations. Specifically, we applied a newly developed method, regressor interpolation at progressive time delays, to analyze concurrently recorded fNIRS and fMRI data acquired both in a resting state study and in a finger tapping study. The method calculates the voxelwise correlations between blood oxygen level dependent (BOLD) fMRI and fNIRS signals with different time shifts and localizes the areas in the brain that highly correlate with the fNIRS signal recorded at the surface of the head. The results show the wide spatial distribution of this physiological fluctuation in BOLD data, both in task and resting states. The brain areas that are highly correlated with global physiological fluctuations observed by fNIRS have a pattern that resembles the venous system of the brain, indicating the blood fluctuation from veins on the brain surface might strongly contribute to the overall fNIRS signal.     

Pushing functional MRI spatial and temporal resolution further: High‐density receive arrays combined with shot‐selective 2D CAIPIRINHA for 3D echo‐planar imaging at 7 T

To be able to examine dynamic and detailed brain functions, the spatial and temporal resolution of 7 T MRI needs to improve. In this study, it was investigated whether submillimeter multishot 3D EPI fMRI scans, acquired with high‐density receive arrays, can benefit from a 2D CAIPIRINHA sampling pattern, in terms of noise amplification (g‐factor), temporal SNR and fMRI sensitivity. High‐density receive arrays were combined with a shot‐selective 2D CAIPIRINHA implementation for multishot 3D EPI sequences at 7 T. In this implementation, in contrast to conventional inclusion of extra k_z gradient blips, specific EPI shots are left out to create a CAIPIRINHA shift and reduction of scan time. First, the implementation of the CAIPIRINHA sequence was evaluated with a standard receive setup by acquiring submillimeter whole brain T₂*‐weighted anatomy images. Second, the CAIPIRINHA sequence was combined with high‐density receive arrays to push the temporal resolution of submillimeter 3D EPI fMRI scans of the visual cortex. Results show that the shot‐selective 2D CAIPIRINHA sequence enables a reduction in scan time for 0.5 mm isotropic 3D EPI T₂*‐weighted anatomy scans by a factor of 4 compared with earlier reports. The use of the 2D CAIPIRINHA implementation in combination with high‐density receive arrays, enhances the image quality of submillimeter 3D EPI scans of the visual cortex at high acceleration as compared to conventional SENSE. Both the g‐factor and temporal SNR improved, resulting in a method that is more sensitive to the fMRI signal. Using this method, it is possible to acquire submillimeter single volume 3D EPI scans of the visual cortex in a subsecond timeframe. Overall, high‐density receive arrays in combination with shot‐selective 2D CAIPIRINHA for 3D EPI scans prove to be valuable for reducing the scan time of submillimeter MRI acquisitions.     

独立分量分析在功能磁共振成像信号功能活动区检测中的应用

主要讨论独立分量分析(ICA)在功能磁共振成像(fMRI)信号功能区检测中的应用。fMRI利用血氧水平依赖(BOLD)效应成像，根据大脑神经元兴奋后局部血氧饱和度增高的原理间接显示神经元活动。假设fMRI信号中包含反映血氧饱和度事件相关的信号、生理噪声和仪器产生的随机噪声等独立分量，首先对fMRI信号进行去噪、配准等预处理，然后利用fastlCA算法对独立分量进行分离，有效抑制噪声对功能区检测的影响，利用相关原理检测出fMRI信号的功能活动区。     

Enhanced sensitivity with fast three-dimensional blood-oxygen-level-dependent functional MRI: comparison of SENSE-PRESTO and 2D-EPI at 3 T

A major impetus in functional MRI development is to enhance sensitivity to changes in neural activity. One way to improve sensitivity is to enhance contrast to noise ratio, for instance by increasing field strength or the number of receiving coils. If these parameters are fixed, there is still the possibility to optimize scans by altering speed or signal strength [signal-to-noise ratio (SNR)]. We here demonstrate a very fast whole-brain scan, by combining a three-dimensional (3D)-PRESTO (principle of echo shifting with a train of observations) pulse sequence with a commercial eight-channel head coil and sensitivity encoding (SENSE). 3D-PRESTO uses time optimally by means of echo shifting. Moreover, 3D scans can accommodate SENSE in two directions, reducing scan time proportionally. The present PRESTO-SENSE sequence achieves full brain coverage within 500 ms. We compared this with a two-dimensional (2D) echo planar imaging (EPI) scan with identical brain coverage on 10 volunteers. Resting-state temporal SNR in the blood-oxygen-level-dependent (BOLD) frequency range and T-statistics for thumb movement and visual checkerboard activations were compared. Results show improved temporal SNR across the brain for PRESTO-SENSE compared with EPI. The percentage signal change and relative standard deviation of the noise were smaller for PRESTO-SENSE. Sensitivity for brain activation, as reflected by T-values, was consistently higher for PRESTO, and this seemed to be mainly due to the increased number of observations within a fixed time period. We conclude that PRESTO accelerated with SENSE in two directions can be more sensitive to BOLD signal changes than the widely used 2D-EPI, when a fixed amount of time is available for functional MRI scanning.     

Theoretical optimization of multi-echo fMRI data acquisition

Simulations are used to optimize multi-echo fMRI data acquisition for detection of BOLD signal changes in this study. Optimal sequence design (echo times and sampling period (receiver bandwidth)) and the variation in sensitivity between tissues with different baseline T*(2) are investigated, taking into account the effects of physiological noise and non-exponential signal decay. In the case of a single echo, for normally distributed, uncorrelated noise, the results indicate that the sampling period should be made as long as possible (so as to produce an acceptable level of image distortion), up to a maximum sampling period of 3T*(2), (i.e. optimum TE = 1.5T*(2)). Combining the signal from multiple echoes using weighted summation improves the contrast-to-noise ratio (CNR), at a reduced optimum echo interval. If the BOLD effect causes a constant change in relaxation rate, DeltaR*(2), independent of the tissue R*(2), then a multi-echo acquisition causes considerable variation in sensitivity to BOLD signal changes with tissue T*(2), so that if the sequence is optimized for a target tissue T*(2) it will be more sensitive to BOLD signal changes in tissues with shorter T*(2) values. Fitting for DeltaR*(2) reduces the CNR, and when using this approach, the shortest echo time interval should be used, down to a limit of about 0.3T*(2), and as many echoes as possible within the constraints of TR or hardware limitations should be collected. It is also shown that the optimal sequence will remain optimum or close to optimum irrespective of whether there are physiological noise contributions.     

Combined diffusion weighting and CSF suppression in functional MRI

In this study, EPI pulse sequences with diffusion weighting for reduction of contributions from large vessels and inversion pulses in order to minimize the effects of CSF pulsations and CSF partial volume effects were developed for BOLD contrast investigations in functional MR imaging. One inversion recovery echo-planar imaging (IR-EPI) pulse sequence and one IR-EPI with additional diffusion weighting (DW-IR-EPI) were developed and compared to a standard gradient-echo EPI sequence in a cortical stimulation experiment in nine healthy volunteers. Stimulation of motor cortex was performed using a semi-complex finger-tapping paradigm in seven periods of alternating rest and stimulation. Comparison between the three pulse sequences was made by measuring the activated volume in each subject, as well as by calculating the relative signal increase during stimulation. Due to different baseline signal-to-noise levels in the images generated by the three pulse sequences, artificial noise was added so that the comparative investigation could be performed independently of the noise level. The activated volume was 128 +/- 73 pixels (mean +/- SD) using the standard EPI pulse sequence, 31 +/- 12 pixels using IR-EPI and 15 +/- 13 pixels when DW-IR-EPI was employed. The relative signal increase was 5.7 +/- 1.1% using standard EPI, 11.5 +/- 3.1% using IR-EPI and 9.9 +/- 2.4% using DW-IR-EPI. The activated volume obtained with the addition of extra noise, i.e. at equal S/N, was 70 +/- 50 pixels using the standard EPI, and when using IR-EPI, the activated volume was 28 +/- 13 pixels. At equal S/N, the signal increase was 7.3 +/- 1.4% using standard EPI and 12.0 +/- 3.6% using IR-EPI. In BOLD contrast imaging, a combination of diffusion weighting and inversion recovery appeared to reduce false activation caused by CSF pulsation and blood flow in large vessels.     

Simultaneous multi‐slice (SMS) acquisition enhances the sensitivity of hemodynamic mapping using gas challenges

Hemodynamic mapping using gas inhalation has received increasing interest in recent years. Cerebrovascular reactivity (CVR), which reflects the ability of the brain vasculature to dilate in response to a vasoactive stimulus, can be measured by CO₂ inhalation with continuous acquisition of blood oxygen level‐dependent (BOLD) magnetic resonance images. Cerebral blood volume (CBV) can be measured by O₂ inhalation. These hemodynamic mapping methods are appealing because of their absence of gadolinium contrast agent, their ability to assess both baseline perfusion and vascular reserve, and their utility in calibrating the functional magnetic resonance imaging (fMRI) signal. However, like other functional and physiological indices, a major drawback of these measurements is their poor sensitivity and reliability. Simultaneous multi‐slice echo planar imaging (SMS EPI) is a fast imaging technology that allows the excitation and acquisition of multiple two‐dimensional slices simultaneously, and has been shown to enhance the sensitivity of several MRI applications. To our knowledge, the benefit of SMS in gas inhalation imaging has not been investigated. In this work, we compared the sensitivity of CO₂ and O₂ inhalation data collected using SMS factor 2 (SMS2) and SMS factor 3 (SMS3) with those collected using conventional EPI (SMS1). We showed that the sensitivity of SMS scans was significantly (p = 0.01) higher than that of conventional EPI, although no difference was found between SMS2 and SMS3 (p = 0.3). On a voxel‐wise level, approximately 20–30% of voxels in the brain showed a significant enhancement in sensitivity when using SMS compared with conventional EPI, with other voxels showing an increase, but not reaching statistical significance. When using SMS, the scan duration can be reduced by half, whilst maintaining the sensitivity of conventional EPI. The availability of a sensitive acquisition technique can further enhance the potential of gas inhalation MRI in clinical applications.     

Resting state networks in human cervical spinal cord observed with fMRI

It has been reported that spontaneous fluctuations of blood oxygen level dependent (BOLD) signals can be detected in human brain and constitute resting state networks. It has not been reported whether resting state networks also exist in human spinal cord. In the present study, we investigate spontaneous BOLD signal changes in human cervical spinal cord during resting state. fMRI data were analyzed with independent component analysis and SPM software package. Acceptable reproducibility of spatial maps of BOLD signal changes was found across sessions, with the highest correlation values ranging from 0.18 to 0.44. The dominant frequency of signal changes from independent components with the highest correlation values was approximately the frequency range of the respiratory circle. Activities of spinal motor neurons innervating the scalenes were considered as a major factor in the production of BOLD signal fluctuations were observed in this study. Our findings suggest that BOLD fMRI can be applied to study the features of low-frequency rhythmic activities and corresponding mechanisms in the spinal cord during resting state.     

Temporal resolving power of perfusion- and BOLD-based event-related functional MRI

Functional magnetic resonance imaging (fMRI) based on both perfusion and blood oxygenation level-dependent (BOLD) contrasts has been widely applied in spatiotemporal mapping of the human brain function. Temporal resolving power of fMRI is limited by the smoothed hemodynamic response function dispersed from the neuronal activity. In this study, temporal modulation transfer functions were utilized to quantify the resolving powers of perfusion and BOLD fMR signals in time domain. The impulse response function was determined using brief visual stimulations and event-related image acquisition schemes. An important feature of arterial spin labeling techniques is that quantitative perfusion and BOLD signals could be simultaneously acquired. This simultaneous BOLD response may arise from signals that are more proximal to capillary beds, and its temporal resolution may be different from that of the typical BOLD response. Therefore, we assessed and compared the temporal resolving capabilities of perfusion, simultaneous BOLD, and the typical BOLD response obtained from the gradient echo EPI pulse sequence. Full-width-at-half-maximums of perfusion and simultaneous BOLD measurements were significantly smaller than that of BOLD ones (4.3+/- 0.6 s vs 5.5 +/- 0.9 s, p<0.02 and 4.7 +/- 1.3 s vs 5.5 +/- 0.9 s, p<0.01, respectively). The corresponding temporal resolving powers of perfusion and simultaneous BOLD signals were statistically better than that of BOLD signals (0.23 +/- 0.03 Hz vs 0.17 +/- 0.02 Hz, p<0.01 and 0.21 +/- 0.04 Hz vs 0.17 +/- 0.02 Hz, p<0.01, respectively). Our results showed that the typical BOLD response was significantly smoothed from the perfusion response, thus resulting in a degraded temporal resolving power. However, results from the simultaneous BOLD and perfusion measurements were not significantly different. Biophysical implications of the experimental outcomes were further investigated using a computer simulation based on the Balloon model. By fitting the measured data into the model, an apparently longer transit time was obtained for the typical BOLD signal (1.7 s), comparing to that for the simultaneous BOLD one (1.2 s). Therefore, the simultaneous BOLD signal was regarded as less susceptible to the variations from local draining veins. Combining the simulation result with the significantly discrepant resolving powers between the two BOLD signals, we speculated that the blurred effects from large vessels played a predominant role that further reduced the temporal resolution of the BOLD-based fMRI from the perfusion response.     

Increased blood oxygen level-dependent (BOLD) sensitivity in the mouse somatosensory cortex during electrical forepaw stimulation using a cryogenic radiofrequency probe

Functional MRI (fMRI) based on the blood oxygen level‐dependent (BOLD) contrast is widely used in preclinical neuroscience. The small dimensions of rodent brain place high demands on spatial resolution, and hence on the sensitivity of the fMRI experiment. This work investigates the performance of a 400‐MHz cryogenic quadrature transceive radiofrequency probe (CryoProbe) with respect to the enhancement of the BOLD sensitivity. For this purpose, BOLD fMRI experiments were performed in mice during electrical forepaw stimulation using the CryoProbe and a conventional room temperature surface coil of comparable dimensions. Image signal‐to‐noise ratio (SNR) and temporal SNR were evaluated as quality measures for individual images and for fMRI time series of images, resulting in gains (mean ± standard deviation) with factors of 3.1 ± 0.7 and 1.8 ± 1.0 when comparing the CryoProbe and room temperature coil. The CryoProbe thermal shield temperature did not affect the noise characteristics, with temporal noise levels being 63 ± 16% of the corresponding room temperature value. However, a significant effect on BOLD amplitudes was found, which was attributed to temperature‐dependent baseline cerebral blood volumes. Defined local thermal conditions were found to be a critical parameter for achieving an optimal and reproducible fMRI signal. In summary, the CryoProbe represents an attractive alternative for the enhancement of image SNR, temporal SNR and BOLD sensitivity in mouse fMRI experiments. Copyright © 2010 John Wiley & Sons, Ltd.     

Blood oxygenation level‐dependent functional MRI signal turbulence caused by ultrahigh spatial resolution: numerical simulation and theoretical explanation

High‐spatial‐resolution functional MRI (fMRI) can enhance image contrast and improve spatial specificity for brain activity mapping. As the voxel size is reduced, an irregular magnetic fieldmap will emerge as a result of less local averaging, and will lead to abnormal fMRI signal evolution with respect to the image acquisition TE. In this article, we report this signal turbulence phenomenon observed in simulations of ultrahigh‐spatial‐resolution blood oxygenation level‐dependent (BOLD) fMRI (voxel size of less than 50 × 50 × 50 µm³). We present a four‐level coarse‐to‐fine multiresolution BOLD fMRI signal simulation. Based on the statistical histogram of an intravoxel fieldmap, we reformulate the intravoxel dephasing summation (a form of Riemann sum) into a new formula that is a discrete Fourier transformation of the intravoxel fieldmap histogram (a form of Lebesgue sum). We interpret the BOLD signal formation by relating its magnitude (phase) to the even (odd) symmetry of the fieldmap histogram. Based on multiresolution BOLD signal simulation, we find that the signal turbulence mainly emerges at the vessel boundary, and that there are only a few voxels (less than 10%) in an ultrahigh‐resolution image that reveal turbulence in the form of sparse point noise. Our simulation also shows that, for typical human brain imaging of the cerebral cortex with millimeter resolution, TE < 30 ms and B₀ = 3 T, we are unlikely to observe BOLD signal turbulence. Overall, the main causes of voxel signal turbulence include a high spatial resolution, high field, long TE and large vessel. Copyright © 2012 John Wiley & Sons, Ltd.     

Quantitative evaluation of activation state in functional brain imaging

Neuronal activity can evoke the hemodynamic change that gives rise to the observed functional magnetic resonance imaging (fMRI) signal. These increases are also regulated by the resting blood volume fraction (V (0)) associated with regional vasculature. The activation locus detected by means of the change in the blood-oxygen-level-dependent (BOLD) signal intensity thereby may deviate from the actual active site due to varied vascular density in the cortex. Furthermore, conventional detection techniques evaluate the statistical significance of the hemodynamic observations. In this sense, the significance level relies not only upon the intensity of the BOLD signal change, but also upon the spatially inhomogeneous fMRI noise distribution that complicates the expression of the results. In this paper, we propose a quantitative strategy for the calibration of activation states to address these challenging problems. The quantitative assessment is based on the estimated neuronal efficacy parameter [Formula: see text] of the hemodynamic model in a voxel-by-voxel way. It is partly immune to the inhomogeneous fMRI noise by virtue of the strength of the optimization strategy. Moreover, it is easy to incorporate regional vascular information into the activation detection procedure. By combining MR angiography images, this approach can remove large vessel contamination in fMRI signals, and provide more accurate functional localization than classical statistical techniques for clinical applications. It is also helpful to investigate the nonlinear nature of the coupling between synaptic activity and the evoked BOLD response. The proposed method might be considered as a potentially useful complement to existing statistical approaches.     

Brain imaging of acupuncture: comparing superficial with deep needling

The difference between superficial and deep needling at acupuncture points has yet to be mapped with functional magnetic resonance imaging (fMRI). Using a 3T MRI, echo planar imaging data were acquired for 17 right-handed healthy volunteer participants. Two fMRI scans of acupuncture needling were taken in random order in a block design, one for superficial and one for deep needling on the right hand at the acupuncture point LI-4 (Hegu), with the participant blind to the order. For both scans needle stimulation was used. Brain image analysis tools were used to explore within-group and between-group differences in the blood oxygen level dependent (BOLD) responses. The study demonstrated marked similarities in BOLD signal responses between superficial and deep needling, with no significant differences in either activations (increases in BOLD signal) or deactivations (decreases in BOLD signal) above the voxel Z score of 2.3 with corrected cluster significance of P=0.05. For both types of needling, deactivations predominated over activations. These fMRI data suggest that acupuncture needle stimulation at two different depths of needling, superficial and deep, do not elicit significantly different BOLD responses. This data is consistent with the equivalent therapeutic outcomes that are claimed by proponents of Japanese and Chinese styles of acupuncture that utilise superficial and deep needling, respectively.     

Continuous noninvasive monitoring of transcutaneous blood gases for a stable and persistent BOLD contrast in fMRI studies in the rat

The physiological status of anesthetized rats greatly influences blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). Monitoring of physiological parameters, particularly partial pressure of carbon dioxide (pCO(2)) levels in the blood, is therefore an important part in the design and performance of reliable fMRI experiments. In this paper, the use of a transcutaneous blood gas analyzing system in rats as a completely noninvasive and MR-compatible method is demonstrated. It was successfully used to monitor continuously pCO(2) values, as an effective alternative to more invasive methods, such as analysis of repetitive arterial blood samples or endtidal capnography. In addition, the transcutaneous pCO(2) of rats anesthetized for long periods was studied using different anesthetic substances and experimental protocols. On-line monitoring of pCO(2) values permitted experimental conditions to be established in which the animals remained normocapnic and during which a robust and consistent BOLD contrast could be observed upon somatosensory forepaw stimulation. A transcutaneous pCO(2) threshold level was defined for the reliable detection of a stimulus-dependent BOLD response.     

Measuring brain hemodynamic changes in a songbird: responses to hypercapnia measured with functional MRI and near-infrared spectroscopy

Songbirds have been evolved into models of choice for the study of the cerebral underpinnings of vocal communication. Nevertheless, there is still a need for in vivo methods allowing the real-time monitoring of brain activity. Functional Magnetic Resonance Imaging (fMRI) has been applied in anesthetized intact songbirds. It relies on blood oxygen level-dependent (BOLD) contrast revealing hemodynamic changes. Non-invasive near-infrared spectroscopy (NIRS) is based on the weak absorption of near-infrared light by biological tissues. Time-resolved femtosecond white laser NIRS is a new probing method using real-time spectral measurements which give access to the local variation of absorbing chromophores such as hemoglobins. In this study, we test the efficiency of our time-resolved NIRS device in monitoring physiological hemodynamic brain responses in a songbird, the zebra finch (Taeniopygia guttata), using a hypercapnia event (7% inhaled CO(2)). The results are compared to those obtained using BOLD fMRI. The NIRS measurements clearly demonstrate that during hypercapnia the blood oxygen saturation level increases (increase in local concentration of oxyhemoglobin, decrease in deoxyhemoglobin concentration and total hemoglobin concentration). Our results provide the first correlation in songbirds of the variations in total hemoglobin and oxygen saturation level obtained from NIRS with local BOLD signal variations.     

Quantitative functional imaging of the brain: towards mapping neuronal activity by BOLD fMRI.

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 voltage-dependent 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.     

Neurometabolic coupling in cerebral cortex reflects synaptic more than spiking activity

In noninvasive neuroimaging, neural activity is inferred from local fluctuations in deoxyhemoglobin. A fundamental question of functional magnetic resonance imaging (fMRI) is whether the inferred neural activity is driven primarily by synaptic or spiking activity. The answer is critical for the interpretation of the blood oxygen level-dependent (BOLD) signal in fMRI. Here, we have used well-established visual-system circuitry to create a stimulus that elicits synaptic activity without associated spike discharge. In colocalized recordings of neural and metabolic activity in cat primary visual cortex, we observed strong coupling between local field potentials (LFPs) and changes in tissue oxygen concentration in the absence of spikes. These results imply that the BOLD signal is more closely coupled to synaptic activity.     

Quantitative study of changes in oxidative metabolism during visual stimulation using absolute relaxation rates

In the context of quantitative functional MRI (fMRI), deoxyhemoglobin (dHb) content is the essential physiological parameter for calibrating the blood oxygenation level-dependent (BOLD) signal. In studies on humans, the baseline dHb content or its equivalent has been evaluated indirectly by means of carbon dioxide breathing as a physiological reference condition. In this study with normal volunteers, quantitative mapping of baseline dHb content was performed in a direct manner by measuring the reversible contribution of the effective transverse relaxation rate. The BOLD signal change in the visual cortex during 8 Hz flicker visual stimulation was calibrated based on the quantitative map of baseline dHb content. The calibrated relaxation rate change that represents the stimulation-induced fractional change of dHb content decreased by 14% within the activated visual cortex. Simultaneous measurement of cerebral blood flow (CBF) with BOLD showed an increase of 59%. From the calibrated relaxation rate and CBF changes, the cerebral metabolic rate of oxygen (CMRO2) was calculated to increase by 19-28% within the activated visual cortex. The ratio of the CBF increase to the CMRO2 increase was 2-3:1, which agreed well with results of similar quantitative fMRI studies for humans. The method proposed here for quantitative evaluation of the BOLD signal may be applicable not only to fMRI for normal human subjects, but also to physiologically altered or diseased states, because it requires no physiological perturbation.     

Independent component-cross correlation-sequential epoch (ICS) analysis of high field fMRI time series: direct visualization of dual representation of the primary motor cortex in human

A new technique for functional magnetic resonance imaging (fMRI) time series analysis is presented. The technique referred to here as independent component-cross correlation-sequential epoch (ICS) analysis is a hybrid technique of two standard methodologies of biological signal analysis, namely, data driven methods, represented by independent component analysis, and hypothesis driven methods, represented by a general linear model. The technique successfully identified four functionally discrete areas within the primary sensorimotor cortex (SMI) in normal human subjects based on blood oxygenation level dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) time series performed on a high field (3.0 T) system. Each of the four areas identified corresponded to the four physiological subdivisions of SMI, recognized in primates to be essential for voluntary hand motion, namely, 4 anterior (MI-4a) and 4 posterior (MI-4p) of the primary motor cortex, and 3a and the 'classical' (Brodmann areas 1, 2, and 3b) primary sensory cortex, respectively. ICS analysis appears to be a highly reliable and versatile technique for fMRI time series analysis.