BOLD Images Research Articles

Estimating the transfer function from neuronal activity to BOLD using simultaneous EEG-fMRI

Previous studies using combined electrical and hemodynamic measurements of brain activity, such as EEG and (BOLD) fMRI, have yielded discrepant results regarding the relationship between neuronal activity and the associated BOLD response. In particular, some studies suggest that this link, or transfer function, depends on the frequency content of neuronal activity, while others suggest that total neuronal power accounts for the changes in BOLD. Here we explored this dependency by comparing different frequency-dependent and -independent transfer functions, using simultaneous EEG-fMRI. Our results suggest that changes in BOLD are indeed associated with changes in the spectral profile of neuronal activity and that these changes do not arise from one specific spectral band. Instead they result from the dynamics of the various frequency components together, in particular, from the relative power between high and low frequencies. Understanding the nature of the link between neuronal activity and BOLD plays a crucial role in improving the interpretability of BOLD images as well as on the design of more robust and realistic models for the integration of EEG and fMRI.

Ultrafast bold fMRI using single-shot spin-echo echo planar imaging

The choice of imaging parameters for functional MRI can have an impact on the accuracy of functional localization by affecting the image quality and the degree of blood oxygenation-dependent (BOLD) contrast achieved. By improving sampling efficiency, parallel acquisition techniques such as sensitivity encoding (SENSE) have been used to shorten readout trains in single-shot (SS) echo planar imaging (EPI). This has been applied to susceptibility artifact reduction and improving spatial resolution. SENSE together with single-shot spin-echo (SS-SE) imaging may also reduce off-resonance artifacts. The goal of this work was to investigate the BOLD response of a SENSE-adapted SE-EPI on a three Tesla scanner. Whole-brain fMRI studies of seven healthy right hand-dominant volunteers were carried out in a three Tesla scanner. fMRI was performed using an SS-SE EPI sequence with SENSE. The data was processed using statistical parametric mapping. Both, group and individual subject data analyses were performed. Individual average percentage and maximal percentage signal changes attributed to the BOLD effect in M1 were calculated for all the subjects as a function of echo time. Corresponding activation maps and the sizes of the activated clusters were also calculated. Our results show that susceptibility artifacts were reduced with the use of SENSE; and the acquired BOLD images were free of the typical quadrature artifacts of SS-EPI. Such measures are crucial at high field strengths. SS SE-EPI with SENSE offers further benefits in this regard and is more specific for oxygenation changes in the microvasculature bed. Functional brain activity can be investigated with the help of single-shot spin echo EPI using SENSE at high magnetic fields.

A bilateral cortico-bulbar network associated with breath holding in humans, determined by functional magnetic resonance imaging

Few tasks are simpler to perform than a breath hold; however, the neural basis underlying this voluntary inhibitory behaviour, which must suppress spontaneous respiratory motor output, is unknown. Here, using blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI), we investigated the neural network responsible for volitional breath holding in 8 healthy humans. BOLD images of the whole brain (156 brain volumes, voxel resolution 3×3×3 mm) were acquired every 5.2 s. All breath holds were performed for 15 s at resting expiratory lung volume when respiratory musculature was presumed to be relaxed, which ensured that the protocol highlighted the inhibitory components underlying the breath hold. An experimental paradigm was designed to dissociate the time course of the whole-brain BOLD signal from the time course of the local, neural-related BOLD signal associated with the inhibitory task. We identified a bilateral network of cortical and subcortical structures including the insula, basal ganglia, frontal cortex, parietal cortex and thalamus, which are in common with response inhibition tasks, and in addition, activity within the pons. From these results we speculate that the pons has a role in integrating information from supra-brainstem structures, and in turn it exerts an inhibitory effect on medullary respiratory neurones to inhibit breathing during breath holding.

MMINi-DASS - Large-scale brain circuit construction and simulation for interconnectivity prediction

Event Abstract Back to Event MMINi-DASS - Large-scale brain circuit construction and simulation for interconnectivity prediction Venkateswaran Nagarajan1*, Karthik Srinivasan1, Ashutosh Mohan1, Vijay Daniel1, Vijay R1, Harish Chandran1 and Vignesh J1 1 Waran Research Foundation, India The MMINi-DASS framework[1,2] starts off with an arbitrary biological neural network which is statistically correct for a given brain region and a set of desired dynamics in the form of fMRI BOLD images. The constructed network is then simulated using computationally efficient and realistic models on a custom-made and event-driven simulator. Some models have been designed exclusively for the project while others are optimized implementations of existing models. The dynamics obtained from the simulation are then analyzed during run-time and compared with the desired dynamics by a Simulated Annealing Optimization engine. This then makes changes to the structure of the constructed network and invokes the simulation again, thus starting another loop. Evidently, the most interesting aspect of the MMINi-DASS project is the possibility of gaining structural, biophysical, biochemical and electrical knowledge from merely knowledge of the dynamics of a region initially. Since the simulation is large-scale while also being detailed, the simulator is optimized for handling the large number of generated events efficiently. A Linux-based MPI (Message Passing Interface) cluster is setup. To handle the large amount of data generated, dedicated database architecture is used. The whole system including the API (Application Programming Interface), simulator and analyzer are generic and are based on XML specifications. This eliminates the need to rebuild or reconfigure the system each time the logic for circuit building, models or analysis is modified. A change in the XML specifications automatically ripples throughout the system. Among the most important problems for neuronal network simulations on a cluster are scalability, performance evaluation and improvement. The MMINi-DASS project uses a custom-made Performance Evaluator. This, while measuring the performance and resource utilization during run-time, also provides pointers to how performance scaling can be made linear with respect to problem size and architectural scaling within the current context and limitations. In the context of neuronal simulations, performance evaluation packages like HPL don’t provide accurate estimates. Thus, efforts are underway to use the BENSIM benchmarking package developed in-house for a realistic estimate of efficiency of both the implementation and the architecture. tn_Figure 1 Figure 1

Abnormal connections in the supraspinal bladder control network in women with urge urinary incontinence

The regions of the supraspinal network that controls urinary bladder behavior are well known, but little is known about their interconnections. We tested the feasibility of using physiophysiological interaction to explore the effective connections of the network and to seek disease-related differences in connectivity. This was a secondary analysis of fMRI data obtained from women aged 26–85 years, 11 with urge urinary incontinence and 10 with normal bladder function. In each subject, fMRI BOLD images were obtained during a period with full bladder and strong bladder sensation (without detrusor overactivity) while repeatedly infusing and withdrawing a small amount of liquid in and out of the bladder. Regions of interest included right insula (RI) and anterior cingulate gyrus (ACG), both consistently involved in bladder control. Other regions effectively connected to them were identified by significant correlation between their fMRI signal and the interaction RI × ACG. Among normal subjects, many regions involved in bladder control were effectively connected with RI/ACG, including frontotemporal and sensorimotor cortex, forebrain, midbrain and pontine regions. The sign of the correlation with RI × ACG was near-uniformly positive, perhaps suggesting mainly inhibitory connections. Among urge-incontinent subjects, the effective connectivity was shifted to a parieto-temporal complex, while the sign of the correlation was predominantly negative, perhaps consistent with excitation (recruitment) of accessory pathways in an attempt to maintain bladder control. Thus, physiophysiological interaction yields potentially important information about the connectivity of the bladder control network and its changes in disease.

Magnetic Resonance Imaging Protocol Optimization for Detection of Endometriotic Lesions

transmit-receive extremity RF coil; previous medical history and investigation indicated compartment syndrome was suspected in the anterior tibialis region. High resolution T1-weighted SPGR images were acquired prior to functional imaging. Mid-calf axial BOLD images were acquired using a Gradient Echo sequence with an EPI readout (∝=70o, TE/TR=35/250ms, FOV 24cm, 64x64 matrix). 3072 contiguous images were acquired over 12.8 minutes at a rate of 4 per second (4Hz). Data acquisition was performed prior to and immediately following 30 minutes of intense exercise. BOLD data obtained from muscle regions of interest (ROIs; soleus, gastrocnemius, anterior tibialis) were spatially aligned with anatomical slices and Fourier transformed into frequency spectra using in-house programs written in Matlab (The Mathworks, Natick MA).

Comparison of “silent” clustered and sparse temporal fMRI acquisitions in tonal and speech perception tasks

In the functional imaging of auditory cortical functions, long silent periods between the data acquisitions prevent interferences between scanner noise and the auditory stimulus processing. Recent fMRI studies have shown that sparse temporal acquisition designs are advantageous over continuous scanning protocols on physiological, perceptual, and cognitive levels. Sparse temporal acquisition schemes (STA) which use a single volume acquisition after each trial imply the advantage of auditory stimulation devoid of ambient scanner noise but have the drawback of a reduced statistical power. To alleviate this effect, STA schemes have been extended to clustered-sparse temporal acquisition (CTA) designs which record several subsequent BOLD contrast images in rapid succession. In the present study, we collected data from 13 healthy volunteers performing a speech and a tonal discrimination task using both a CTA and STA scheme to carry out a systematic evaluation of these acquisition protocols. By statistical modeling of the fMRI data sets, we revealed stronger effect sizes for the STA protocol regardless of the task, reflecting the better signal-to-noise-ratio of MR images acquired with this scheme. In contrast, we demonstrate higher statistical power for the use of a CTA protocol. Accordingly, in the context of standard fMRI analysis, the CTA protocol clearly outperformed the STA scheme at the level of single-subject analysis and fixed-effects group analysis. Our results clearly suggest that it is advantageous to acquire several sample points per trial if one wants to use the benefit of "silent" fMRI. Furthermore, our data demonstrate the feasibility of the clustered acquisition of subsequent imaging volumes along the T1-decay.

Measurement of activation-related changes in cerebral blood volume: VASO with single-shot HASTE acquisition

Object The recently developed vascular space occupancy (VASO) fMRI technique is gaining popularity as it facilitates the measurement of cerebral blood volume (CBV) changes concomitant with brain activation, without the use of contrast agents. Thus far, VASO fMRI has only been used in conjunction with a GE-EPI (gradient-echo echo planar imaging) sequence, which is proceeded by an inversion recovery (IR) experiment to selectively null the blood signal. The use of GE-EPI has potential disadvantages: (a) the non-zero TE may lead to BOLD contamination and (b) images suffer from the EPI-typical inhomogeneity artefacts.Materials and methods Here, we propose the use of VASO based on an IR-HASTE (inversion recovery half-Fourier acquisition single-shot turbo spin echo) sequence.Results Results from a visual stimulation study (n = 8) show a 43% higher functional contrast-to-noise (CNR) of HASTE compared to EPI, with a strongly increased count of active voxels at the same significance threshold. Sensitivity to inflow effects was investigated and found to be similar for both methods.Conclusion As HASTE VASO yields essentially artefact-free images, it appears to be the method of choice for measuring relative CBV changes with VASO.

Changes of brain activity in the aged SAMP mouse

This study investigates characteristics of aging in the central nervous system of the senescence accelerated prone mice (SAMP8). We examined 3 and 10-months old senescence-accelerated-prone mice (SAMP8) for functional and molecular changes in their brains, specifically in the hippocampus and somatosensory cortex. There was no statistically significant increase in the apoptosis indicators as revealed by Western Blotting for BAD and TUNEL experiments. However, the functional magnetic resonance imaging showed an increase in the area of BOLD images from the 3-month old to the 10-months old SAMP mice upon the application of tail stimulus. These results demonstrated a lack of neuronal deaths but an increase in the activated brain area with age.

Network analysis of single-subject fMRI during a finger opposition task

The analysis of functional magnetic resonance imaging (fMRI) data has typically relied on univariate methods to identify areas of brain activity related to cognitive and behavioral task performance. We investigated the ability of multivariate network analysis using a modified form of principal component analysis, the Scaled Subprofile Model (SSM), applied to single-subject fMRI data to identify patterns of interactions among brain regions over time during an anatomically well-characterized simple motor task. We hypothesized that each subject would exhibit correlated patterns of brain activation in several regions known to participate in the regulation of movement including the contralateral motor cortex and the ipsilateral cerebellum. EPI BOLD images were acquired in six healthy participants as they performed a visually and auditorally paced finger opposition task. SSM analysis was applied to the fMR time series on a single-subject basis. Linear combinations of the major principal components that predicted the expected hemodynamic response to the order of experimental conditions were identified for each participant. These combinations of SSM patterns were highly associated with the expected hemodynamic response, an indicator of local neuronal activity, in each participant (0.84 ≤ R 2 ≤ 0.97, all P's < 0.0001). As predicted, the combined pattern in each subject was characterized most prominently by relatively increased activations in contralateral sensorimotor cortex and ipsilateral cerebellum. Additionally, all subjects showed areas of relatively decreased activation in the ipsilateral sensorimotor cortex and contralateral cerebellum. The application of network analysis methods, such as SSM, to single-subject fMRI data can identify patterns of task-specific, functionally interacting brain areas in individual subjects. This approach may help identify individual differences in the task-related functional connectivity, track changes in task-related patterns of activity within or between fMRI sessions, and provide a method to identify individual differences in response to treatment.

Laminar specificity in monkey V1 using high-resolution SE-fMRI

The lamination of mammalian neocortex is widely used as reference for describing a wide range of anatomical and physiological data. Its value lies in the observation that in all examined species, cortical afferents, intrinsic cells and projection neurons organize themselves with respect to the laminae. The comprehension of the computations, carried out by the neocortical microcircuits, critically relies on the study of the interlaminar connectivity patterns and the intralaminar physiological processes in vivo. High-resolution functional neuroimaging, enabling the visualization of activity in individual cortical laminae or columns, may greatly contribute in such studies. Yet, the BOLD effect, as measured with the commonly used GE-EPI, contains contributions from both macroscopic venous blood vessels and capillaries. The low density of the cortical veins limits the effective spatial specificity of the fMRI signal and yields maps that are weighted toward the macrovasculature, which thus can be significantly different from the actual site of increased neuronal activity. Spin-echo (SE) sequences yielding apparent T2-weighted BOLD images have been shown to improve spatial specificity by increasing the sensitivity of the signal to spins of the parenchyma, particularly at high magnetic fields. Here we used SE-fMRI at 4.7 T to examine the specificity and resolution of functional maps obtained by stimulating the primary visual cortex of monkeys. Cortical layers could be clearly visualized, and functional activity was predominantly localized in cortical layer IV/Duvernoy layer 3. The choice of sequence parameters influences the fMRI signal, as the SE-EPI is by nature sensitive to T2* in addition to its T2 dependency. Using parameters that limit T2* effects yielded higher specificity and better visualization of the cortical laminae. Because the demands of high-spatial resolution using SE severely decreases temporal resolution, we used a stimulus protocol that allows sampling at higher effective temporal resolution. This way, it was possible to acquire high-spatial and high-temporal resolution SE-fMRI data.

The BOLD response during Stroop task-like inhibition paradigms: Effects of task difficulty and task-relevant modality

Previous studies of the Stroop task propose two key mediators: the prefrontal and cingulate cortices but hints exist of functional specialization within these regions. This study aimed to examine the effect of task modality upon the prefrontal and cingulate response by examining the response to colour, number, and shape Stroop tasks whilst BOLD fMRI images were acquired on a Siemens 3 T MRI scanner. Behavioural analyses indicated facilitation and interference effects and a noticeable effect of task difficulty. Some modular effects of modality were observed in the prefrontal cortex that survived exclusion of task difficulty related activations. No effect of task-relevant information was observed in the anterior cingulate. Future comparisons of the mediation of selective attention need to consider the effects of task context and task difficulty.

Magnetic Resonance Imaging Characteristics of a Gliosarcoma

In this case report, we define THE MR characteristics of a gliosarcoma surgically removed from the left cerebral hemisphere of a 67-year-old man who presented with right hemiparesis and headache. The tumor was located in the gray-white matter interface abutting the dural surface. It showed slightly high signal on T2-weighted images with hemorrhagic and necrotic components and irregular ring-like enhancement on post-contrast T1-weighted images. Apparent diffusion coefficient of the tumor was measured as 1.09 × 10−3 cm2/s. Tumoral and peritumoral cerebral blood volume (rCBV) ratios were calculated as 8.4 and 2.2, and choline/creatine ratios were 1.78 and 1.11 respectively. The tumor primarily compromised the secondary motor area and affected the left primary motor area on BOLD images. Although MR characteristics of gliosarcoma did not allow an exact differential diagnosis, they were very useful in surgical planning to decrease post-treatment morbidity.

Simultaneous EEG–fMRI acquisition: how far is it from being a standardized technique?

Simultaneous EEG-fMRI is a powerful tool to study spontaneous and evoked brain activity because of the complementary advantages of the two techniques in terms of temporal and spatial resolution. In recent years, a significant number of scientific works have been published on this subject. However, many technical problems related to the intrinsic incompatibility of EEG and MRI methods are still not fully solved. Furthermore, simultaneous acquisition of EEG and event-related fMRI requires precise synchronization of all devices involved in the experimental setup. Thus, timing issue must be carefully considered in order to avoid significant methodological errors. The aim of the present work is to highlight and discuss some of technical and methodological open issues associated with the combined use of EEG and fMRI. These issues are presented in the context of preliminary data regarding simultaneous acquisition of event-related evoked potentials and BOLD images during a visual odd-ball paradigm.

Functional MRI changes before and after onset of reported emotions

The social nature of emotion is evident in the importance of facial and vocal displays in emotion-related behavior. This is the first brain-imaging study to use simulated face-to-face social interactions to evoke emotional responses and to compare valence-related activations before and after subjective onset of emotional response. Videotapes were prepared with actresses who described happy or unhappy experiences. Functional magnetic resonance imaging (fMRI) at 1.5 T was used to acquire BOLD images in 21 healthy young adults before, after, and during viewing of the happy and sad tapes. Subjects pushed buttons to indicate the onset of subjective emotional responses. Group data were analyzed by a bootstrap randomization method after anatomical normalization. Significant activation was detected in frontal and sensory regions prior to the reported onset of emotional response, and this activity showed a marked decrease after the report of conscious emotional experience. Significant differences between happy and sad conditions were evident in multiple brain regions both before and after the reported onset of emotional response, including the middle and superior temporal gyri, the middle frontal gyrus, the caudate, and the hippocampus. Socially relevant emotional stimulation is feasible and evokes robust responses. The neural correlates of the evoked emotion are multiple, widely distributed, and inclusive of areas important in many cognitive tasks. Positive and negative emotional responses include activation of common and distinctive brain regions.

A method for determining venous contribution to BOLD contrast sensory activation

While BOLD contrast reflects hemodynamic changes within capillaries serving neural tissue, it also has a venous component. Studies that have determined the relation of large blood vessels to the activation map indicate that veins are the source of the largest response, and the most delayed in time. It would be informative if the location of these large veins could be extracted from the properties of the functional responses, since vessels are not visible in BOLD contrast images. The present study describes a method for investigating whether measures taken from the functional response can reliably predict vein location, or at least be useful in down-weighting the venous contribution to the activation response, and illustrates this method using data from one subject. We combined fMRI at 3 Tesla with high-resolution anatomic imaging and MR venography to test whether the intrinsic properties of activation time courses corresponded to tissue type. Measures were taken from a gamma fit to the functional response. Mean magnitude showed a significant effect of tissue type ( p < 0.001) where CSF > veins ≈ gray matter > white matter. Mean delays displayed the same ranking across tissue types ( p < 0.001), except that veins > gray matter. However, measures for all tissue types were distributed across an overlapping range. A logistic regression model correctly discriminated 72% of the veins from gray matter in the absence of independent information of macroscopic vessels (ROC = 0.72). While tissue classification was not perfect for this subject, weighting the T contrast by the predicted probabilities materially reduced the venous component to the activation map.

Comparison of Spike-Triggered Functional MRI BOLD Activation and EEG Dipole Model Localization

We studied six patients with localization-related epilepsy, frequent interictal epileptiform discharges, and positive spike-triggered blood oxygen level-dependent functional MRI (BOLD-fMRI) findings. EEG source analysis solutions based on 64-channel EEG recorded in a separate session outside the scanner were obtained using dipole models and compared to the BOLD localization. The BOLD and structural images were coregistered, allowing the measurement of distances between the generator models and BOLD activation(s) and structural lesion when present. In all cases dipole models could be found that explained a sufficient amount of the data and that were anatomically concordant with the BOLD localization. In the five cases with structural abnormality visible on T1 scans, the BOLD activation overlapped or was in close proximity to the abnormaility. The overall mean distance between the main moving dipole and the center of the nearest BOLD activation was 3.5 and 2.2 cm for the negative and positive peaks, respectively, including one case of a deep BOLD activation, in which the distance was 5 cm. In conclusion, the degree of agreement between the BOLD and EEG source localization indicates that the combination of these two noninvasive techniques offers the possibility of advancing the study of the generators of epileptiform electrical activity.

EEG-Linked functional magnetic resonance imaging in epilepsy and cognitive neurophysiology.

The ability to trigger functional magnetic resonance imaging (fMRI) acquisitions related to the occurrence of EEG-based physiologic transients has changed the field of fMRI into a more dynamically based technique. By knowing the temporal relationship between focal increases in neuronal firing rates and the provoked focal increase in blood flow, investigators are able to maximize the fMR-linked images that show where the activity originates. Our mastery of recording EEG inside the bore of a MR scanner has also allowed us to develop cognitive paradigms that record not only the fMR BOLD images, but also the evoked potentials (EPs). The EPs can subsequently be subjected to localization paradigms that can be compared to the localization seen on the BOLD images. These two techniques will most probably be complimentary. BOLD responses are dependent on a focal increase in metabolic demand while the EPs may or may not be related to energy demand increases. Additionally, recording EPs require that the source or sources of that potential come from an area that is able to generate far-field potentials. These potentials are related to the laminar organization of the neuronal population generating that potential. As best we know the BOLD response does not depend on any inherent laminar neuronal organization. Therefore, by merging these two recording methods, it is likely that we will gain a more detailed understanding of not only the areas involved in certain physiologic events, e.g. focal epilepsy or cognitive processing, but also on the sequencing of the activation of the various participating regions.

Comparison of matched BOLD and FAIR 4.0T-fMRI with [15O]water PET brain volumes

Valid comparisons of functional activation volumes from fMRI and PET require accurate registration, matched spatial resolution, and if possible matched noise. We coregistered 4.0T-fMRI and PET volumes, using a series of linear and nonlinear transformations applied to the PET volumes. Because of the limited number of fMRI slices that were available, PET volumes were transformed to the fMRI space. Since 4.0T-fMRI and 4.0T-MRI volumes have significant spatial distortion due to magnet inhomogeneities, high resolution 1.5T-MRI volumes were nonlinearly transformed to 4.0T-MRI volumes as part of the transformation chain. The smoothing effects of these registration transformations were measured, in order to match the spatial resolution of the coregistered fMRI and PET volumes. Spatial resolution of the transformed PET volumes in the fMRI space was degraded by up to 60% due to the transformation process. Due to both the image acquisition characteristics and the coregistration process, the transformed PET volumes had a spatial resolution that was lower than that of tMRI. Therefore, significant smoothing of fMRI volumes was necessary to match their spatial resolution with that of the transformed PET volumes. Matching the spatial resolution of the fMRI volumes to those of the transformed PET volumes was achieved by matching the shape of their point spread functions. In order to do this, Gaussian kernels were employed to smooth the fMRI volumes. We were unable to simultaneously match the resolution and noise of fMRI and PET signals in the motor cortex. Activation maps derived from transformed PET and smoothed fMRI volumes were compared. Contralateral motor cortex was active in all modalities but there were large variations in the size of the activated region and its signal to noise ratio across BOLD, FAIR, and PET images within each subject. Nevertheless, the relative CBF changes measured by FAIR were consistent with those determined by PET.

Functional magnetic resonance imaging in macaque cortex.

The ability to use fMRI in a monkey model would bridge the gap between the fMRI demonstration of cerebral activation in humans and the cumulative wealth of monkey data on the functional organization of the brain from single electrode mapping, radioisotope and histology studies. We report a new technique for fMRI in an awake co-operative rhesus macaque (Macaca mulatta) in a conventional clinical 1.5T MR scanner and present the first fMRI images from a macaque. Good resolution, signal-to-noise ratio and BOLD response (2.6-4.6%) have been achieved using the manufacturer's standard volume knee coil. T1 values of macaque gray and white matter (1490 ms, 1010 ms respectively) are higher than human brain, whereas T2 values are lower (55 ms, 48 ms respectively). An MR-compatible design for restraining the monkey is also described, along with a suitable EPI sequence for BOLD images, optimized for monkey T2, with voxel sizes from 29 to 61 microl, and MPRAGE sequence for anatomical studies with 0.8 mm isotropic resolution, optimized for monkey T1.