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Proceedings 2004

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  1. Maria Antonietta Macrì, Girolamo Garreffa, Federico Giove, Manuela Guardati, Anna Ambrosini, Claudio Colonnese and Bruno Maraviglia.
    In vivo quantitative 1H MRS of cerebellum and evaluation of quantitation reproducibility by simulation of different levels of noise and spectral resolution. Magnetic Resonance Imaging 22(10):1385–1393, 2004.
    Abstract A quantitative analysis of cerebellar metabolites in normal subjects has been performed by proton MR spectroscopy (MRS) with relaxation time correction. Quantitation was carried out in seven healthy human subjects with the well-established LCModel program. The prior knowledge utilized for quantitation was obtained from solutions containing the major brain metabolites and MRS investigated under the same experimental conditions. The tissue water signal was used as an internal standard for the in vivo studies. Both in vitro (for the prior knowledge template) and in vivo data were acquired separately at 1.5 T by PRESS sequence (TR, 1500 ms; TE, 30 ms). The absolute concentration of main cerebellar metabolites was corrected for relaxation time effects. Different noise and line broadening conditions were considered and simulated in the spectral processing in order to evaluate the effect of spectral quality on the concentration estimates. A quantitative analysis of cerebellar metabolites in normal subjects has been performed by proton MR spectroscopy (MRS) with relaxation time correction. Quantitation was carried out in seven healthy human subjects with the well-established LCModel program. The prior knowledge utilized for quantitation was obtained from solutions containing the major brain metabolites and MRS investigated under the same experimental conditions. The tissue water signal was used as an internal standard for the in vivo studies. Both in vitro (for the prior knowledge template) and in vivo data were acquired separately at 1.5 T by PRESS sequence (TR, 1500 ms; TE, 30 ms). The absolute concentration of main cerebellar metabolites was corrected for relaxation time effects. Different noise and line broadening conditions were considered and simulated in the spectral processing in order to evaluate the effect of spectral quality on the concentration estimates.
    URL, DOI

  2. Adam D Liston, Afraim Salek-Haddadi, Stefan J Kiebel, Khalid Hamandi, Robert Turner and Louis Lemieux.
    The MR detection of neuronal depolarization during 3-Hz spike-and-wave complexes in generalized epilepsy. Magnetic Resonance Imaging 22(10):1441–1444, 2004.
    Abstract Previously, an analysis of activations observed in a patient with idiopathic generalized epilepsy using electroencephalogram-correlated functional magnetic resonance imaging (MRI) during runs of 3-Hz generalized spike?wave discharge (GSWD) was presented by Salek-Haddadi. Time-locked, bilateral, thalamic blood oxygenation level-dependent increases were reported to be accompanied by widespread, symmetric, cortical deactivation with a frontal maximum. In light of recent investigations into MRI detection of the magnetic field perturbations caused by neuronal current loops during depolarization, we revisited the analysis of the data of Salek-Haddadi as a preliminary search for a neuroelectric signal. We modeled the MRI response as the sum of a fast signal and a slower signal and demonstrated significant MRI activity at a time scale of the order of 30 ms associated with GSWDs. Further work is necessary before firm conclusions may be drawn about the nature of this signal. Previously, an analysis of activations observed in a patient with idiopathic generalized epilepsy using electroencephalogram-correlated functional magnetic resonance imaging (MRI) during runs of 3-Hz generalized spike?wave discharge (GSWD) was presented by Salek-Haddadi. Time-locked, bilateral, thalamic blood oxygenation level-dependent increases were reported to be accompanied by widespread, symmetric, cortical deactivation with a frontal maximum. In light of recent investigations into MRI detection of the magnetic field perturbations caused by neuronal current loops during depolarization, we revisited the analysis of the data of Salek-Haddadi as a preliminary search for a neuroelectric signal. We modeled the MRI response as the sum of a fast signal and a slower signal and demonstrated significant MRI activity at a time scale of the order of 30 ms associated with GSWDs. Further work is necessary before firm conclusions may be drawn about the nature of this signal.
    URL, DOI

  3. Josef Pfeuffer, Christoph Juchem, Hellmut Merkle, Arno Nauerth and Nikos K Logothetis.
    High-field localized 1H NMR spectroscopy in the anesthetized and in the awake monkey. Magnetic Resonance Imaging 22(10):1361–1372, 2004.
    Abstract Localized cerebral in vivo 1H NMR spectroscopy (MRS) was performed in the anesthetized as well as the awake monkey using a novel vertical 7 T/60 cm MR system. The increased sensitivity and spectral dispersion gained at high field enabled the quantification of up to 16 metabolites in 0.1- to 1-ml volumes. Quantification was accomplished by using simulations of 18 metabolite spectra and a macromolecule (MM) background spectrum consisting of 12 components. Major cerebral metabolites (concentrations >3 mM) such as glutamate (Glu), N-acetylaspartate (NAA), creatine (Cr)/phosphocreatine (PCr) and myo-inositol (Ins) were identified with an error below 3%; most other metabolites were quantified with errors in the order of 10%. Metabolite ratios were 1.39:1 for total NAA, 1.38:1 for glutamate (Glu)/glutamine (Gln) and 0.09:1 for cholines (Cho) relative to total Cr. Taurine (Tau) was detectable at concentrations lower than 1 mM, while lactate (Lac) remained below the detection limit. The spectral dispersion was sufficient to separate metabolites of similar spectral patterns, such as Gln and Glu, N-acetylaspartylglutamate (NAAG) and NAA, and PCr?Cr. MRS in the awake monkey required the development and refinement of acquisition and correction strategies to minimize magnetic susceptibility artifacts induced by respiration and movement of the mouth or body. Periods with major motion artifacts were rejected, while a frequency/phase correction was performed on the remaining single spectra before averaging. In resting periods, both spectral amplitude and line width, that is, the voxel shim, were unaffected permitting reliable measurements. The corrected spectra obtained from the awake monkey afforded the reliable detection of 6?10 cerebral metabolites of 1-ml volumes. Localized cerebral in vivo 1H NMR spectroscopy (MRS) was performed in the anesthetized as well as the awake monkey using a novel vertical 7 T/60 cm MR system. The increased sensitivity and spectral dispersion gained at high field enabled the quantification of up to 16 metabolites in 0.1- to 1-ml volumes. Quantification was accomplished by using simulations of 18 metabolite spectra and a macromolecule (MM) background spectrum consisting of 12 components. Major cerebral metabolites (concentrations >3 mM) such as glutamate (Glu), N-acetylaspartate (NAA), creatine (Cr)/phosphocreatine (PCr) and myo-inositol (Ins) were identified with an error below 3%; most other metabolites were quantified with errors in the order of 10%. Metabolite ratios were 1.39:1 for total NAA, 1.38:1 for glutamate (Glu)/glutamine (Gln) and 0.09:1 for cholines (Cho) relative to total Cr. Taurine (Tau) was detectable at concentrations lower than 1 mM, while lactate (Lac) remained below the detection limit. The spectral dispersion was sufficient to separate metabolites of similar spectral patterns, such as Gln and Glu, N-acetylaspartylglutamate (NAAG) and NAA, and PCr?Cr. MRS in the awake monkey required the development and refinement of acquisition and correction strategies to minimize magnetic susceptibility artifacts induced by respiration and movement of the mouth or body. Periods with major motion artifacts were rejected, while a frequency/phase correction was performed on the remaining single spectra before averaging. In resting periods, both spectral amplitude and line width, that is, the voxel shim, were unaffected permitting reliable measurements. The corrected spectra obtained from the awake monkey afforded the reliable detection of 6?10 cerebral metabolites of 1-ml volumes.
    URL, DOI

  4. Fernando Lopes da Silva.
    Functional localization of brain sources using EEG and/or MEG data: volume conductor and source models. Magnetic Resonance Imaging 22(10):1533–1538, 2004.
    Abstract In this overview we examine the basic principles of properties of electroencephalogram and magnetoencephalogram and the corresponding models of sources and of the volume conductor. In particular we show how the dipolar model is anchored in neurophysiological findings and how the different conductivities of the brain and the tissue surrounding it can be estimated. Using these basic models as tools we show how the functional localization of the neural sources of rhythmic activities (alpha and mu rhythms and sleep spindles) and of epileptiform activities can be estimated and integrated with structural data of the brain obtained with MRI. In this overview we examine the basic principles of properties of electroencephalogram and magnetoencephalogram and the corresponding models of sources and of the volume conductor. In particular we show how the dipolar model is anchored in neurophysiological findings and how the different conductivities of the brain and the tissue surrounding it can be estimated. Using these basic models as tools we show how the functional localization of the neural sources of rhythmic activities (alpha and mu rhythms and sleep spindles) and of epileptiform activities can be estimated and integrated with structural data of the brain obtained with MRI.
    URL, DOI

  5. Christoph Juchem, Hellmut Merkle, Fritz Schick, Nikos K Logothetis and Josef Pfeuffer.
    Region and volume dependencies in spectral line width assessed by 1H 2D MR chemical shift imaging in the monkey brain at 7 T. Magnetic Resonance Imaging 22(10):1373–1383, 2004.
    Abstract High magnetic fields increase the sensitivity and spectral dispersion in magnetic resonance spectroscopy (MRS). In contrast, spectral peaks are broadened in vivo at higher field strength due to stronger susceptibility-induced effects. Strategies to minimize the spectral line width are therefore of critical importance. In the present study, 1H 2D chemical shift imaging at short echo times was performed in the macaque monkey brain at 7 T. Large brain coverage was obtained at high spatial resolution with voxel sizes down to 50 ?l being able to quantify up to nine metabolites in vivo with good reliability. Measured line widths of metabolites decreased from 14.2 to 7.6 Hz with voxel volumes of 3.14 ml to 50 ?l (at increased spatial resolution). The line width distribution of the metabolites (7.6±1.6 Hz, ranging from 5.5 to 10 Hz) was considerably smaller compared to that of water (10.6±2.4 Hz) and was also smaller than reported in 1H MRS at 7 T in the human brain. Our study showed that even in well-shimmed areas assumed to have minimal macroscopic susceptibility variations, spectral line widths are tissue-specific exhibiting considerable regional variation. Therefore, an overall improvement of a gross spectral line width ? directly correlated with improved spectral quality ? can only be achieved when voxel volumes are significantly reduced. Our line width optimization was sufficient to permit clear glutamate (Glu)?glutamine separation, yielding distinct Glu maps for brain areas including regions of greatly different Glu concentration (e.g., ventricles vs. surrounding tissue). High magnetic fields increase the sensitivity and spectral dispersion in magnetic resonance spectroscopy (MRS). In contrast, spectral peaks are broadened in vivo at higher field strength due to stronger susceptibility-induced effects. Strategies to minimize the spectral line width are therefore of critical importance. In the present study, 1H 2D chemical shift imaging at short echo times was performed in the macaque monkey brain at 7 T. Large brain coverage was obtained at high spatial resolution with voxel sizes down to 50 ?l being able to quantify up to nine metabolites in vivo with good reliability. Measured line widths of metabolites decreased from 14.2 to 7.6 Hz with voxel volumes of 3.14 ml to 50 ?l (at increased spatial resolution). The line width distribution of the metabolites (7.6±1.6 Hz, ranging from 5.5 to 10 Hz) was considerably smaller compared to that of water (10.6±2.4 Hz) and was also smaller than reported in 1H MRS at 7 T in the human brain. Our study showed that even in well-shimmed areas assumed to have minimal macroscopic susceptibility variations, spectral line widths are tissue-specific exhibiting considerable regional variation. Therefore, an overall improvement of a gross spectral line width ? directly correlated with improved spectral quality ? can only be achieved when voxel volumes are significantly reduced. Our line width optimization was sufficient to permit clear glutamate (Glu)?glutamine separation, yielding distinct Glu maps for brain areas including regions of greatly different Glu concentration (e.g., ventricles vs. surrounding tissue).
    URL, DOI

  6. Nikos K Logothetis and Josef Pfeuffer.
    On the nature of the BOLD fMRI contrast mechanism. Magnetic Resonance Imaging 22(10):1517–1531, 2004.
    Abstract Since its development about 15 years ago, functional magnetic resonance imaging (fMRI) has become the leading research tool for mapping brain activity. The technique works by detecting the levels of oxygen in the blood, point by point, throughout the brain. In other words, it relies on a surrogate signal, resulting from changes in oxygenation, blood volume and flow, and does not directly measure neural activity. Although a relationship between changes in brain activity and blood flow has long been speculated, indirectly examined and suggested and surely anticipated and expected, the neural basis of the fMRI signal was only recently demonstrated directly in experiments using combined imaging and intracortical recordings. In the present paper, we discuss the results obtained from such combined experiments. We also discuss our current knowledge of the extracellularly measured signals of the neural processes that they represent and of the structural and functional neurovascular coupling, which links such processes with the hemodynamic changes that offer the surrogate signal that we use to map brain activity. We conclude by considering applications of invasive MRI, including injections of paramagnetic tracers for the study of connectivity in the living animal and simultaneous imaging and electrical microstimulation. Since its development about 15 years ago, functional magnetic resonance imaging (fMRI) has become the leading research tool for mapping brain activity. The technique works by detecting the levels of oxygen in the blood, point by point, throughout the brain. In other words, it relies on a surrogate signal, resulting from changes in oxygenation, blood volume and flow, and does not directly measure neural activity. Although a relationship between changes in brain activity and blood flow has long been speculated, indirectly examined and suggested and surely anticipated and expected, the neural basis of the fMRI signal was only recently demonstrated directly in experiments using combined imaging and intracortical recordings. In the present paper, we discuss the results obtained from such combined experiments. We also discuss our current knowledge of the extracellularly measured signals of the neural processes that they represent and of the structural and functional neurovascular coupling, which links such processes with the hemodynamic changes that offer the surrogate signal that we use to map brain activity. We conclude by considering applications of invasive MRI, including injections of paramagnetic tracers for the study of connectivity in the living animal and simultaneous imaging and electrical microstimulation.
    URL, DOI

  7. Fabio Babiloni, Donetella Mattia, Claudio Babiloni, Laura Astolfi, Serenella Salinari, Alessandra Basilisco, Paolo Maria Rossini, Maria Grazia Marciani and Febo Cincotti.
    Multimodal integration of EEG, MEG and fMRI data for the solution of the neuroimage puzzle. Magnetic Resonance Imaging 22(10):1471–1476, 2004.
    Abstract In this paper, advanced methods for the modeling of human cortical activity from combined high-resolution electroencephalography (EEG), magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) data are presented. These methods include a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from magnetic resonance images, multidipole source model and regularized linear inverse source estimates of cortical current density. Determination of the priors in the resolution of the linear inverse problem was performed with the use of information from the hemodynamic responses of the cortical areas as revealed by block-designed (strength of activated voxels) fMRI. Examples of the application of these methods to the estimation of the time varying cortical current density activity in selected region of interest (ROI) are presented for movement-related high-resolution EEG data. In this paper, advanced methods for the modeling of human cortical activity from combined high-resolution electroencephalography (EEG), magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) data are presented. These methods include a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from magnetic resonance images, multidipole source model and regularized linear inverse source estimates of cortical current density. Determination of the priors in the resolution of the linear inverse problem was performed with the use of information from the hemodynamic responses of the cortical areas as revealed by block-designed (strength of activated voxels) fMRI. Examples of the application of these methods to the estimation of the time varying cortical current density activity in selected region of interest (ROI) are presented for movement-related high-resolution EEG data.
    URL, DOI

  8. Josef Pfeuffer, Hellmut Merkle, Michael Beyerlein, Thomas Steudel and Nikos K Logothetis.
    Anatomical and functional MR imaging in the macaque monkey using a vertical large-bore 7 Tesla setup. Magnetic Resonance Imaging 22(10):1343–1359, 2004.
    Abstract Functional magnetic resonance imaging (MRI) in the nonhuman primate promises to provide a much desired link between brain research in humans and the large body of systems neuroscience work in animals. We present here a novel high field, large-bore, vertical MR system (7 T/60 cm, 300 MHz), which was optimized for neuroscientific research in macaque monkeys. A strong magnetic field was applied to increase sensitivity and spatial resolution for both MRI and spectroscopy. Anatomical imaging with voxel sizes as small as 75?150?300 ?m3 and with high contrast-to-noise ratios permitted the visualization of the characteristic lamination of some neocortical areas, e.g., Baillarger lines. Relaxation times were determined for different structures: at 7 T, T1 was 2.01/1.84/1.54 s in GM/GM-V1/WM, T2 was 59.1/54.4 ms in GM/WM and T2* was 29 ms. At 4.7 T, T1 was 25% shorter, T2 and T2* 18% longer compared to 7T. Spatiotemporally resolved blood-oxygen-level-dependent (BOLD) signal changes yielded robust activations and deactivations (negative BOLD), with average amplitudes of 4.1% and ?2.4%, respectively. Finally, the first high-resolution (500 ?m in-plane) images of cerebral blood flow in the anesthetized monkey are presented. On functional activation we observed flow increases of up to 38% (59 to 81 ml/100 g/min) in the primary visual cortex, V1. Compared to BOLD maps, functional CBF maps were found to be localized entirely within the gray matter, providing unequivocal evidence for high spatial specificity. The exquisite sensitivity of the system and the increased specificity of the hemodynamic signals promise further insights into the relationship of the latter to the underlying physiological activity. Functional magnetic resonance imaging (MRI) in the nonhuman primate promises to provide a much desired link between brain research in humans and the large body of systems neuroscience work in animals. We present here a novel high field, large-bore, vertical MR system (7 T/60 cm, 300 MHz), which was optimized for neuroscientific research in macaque monkeys. A strong magnetic field was applied to increase sensitivity and spatial resolution for both MRI and spectroscopy. Anatomical imaging with voxel sizes as small as 75?150?300 ?m3 and with high contrast-to-noise ratios permitted the visualization of the characteristic lamination of some neocortical areas, e.g., Baillarger lines. Relaxation times were determined for different structures: at 7 T, T1 was 2.01/1.84/1.54 s in GM/GM-V1/WM, T2 was 59.1/54.4 ms in GM/WM and T2* was 29 ms. At 4.7 T, T1 was 25% shorter, T2 and T2* 18% longer compared to 7T. Spatiotemporally resolved blood-oxygen-level-dependent (BOLD) signal changes yielded robust activations and deactivations (negative BOLD), with average amplitudes of 4.1% and ?2.4%, respectively. Finally, the first high-resolution (500 ?m in-plane) images of cerebral blood flow in the anesthetized monkey are presented. On functional activation we observed flow increases of up to 38% (59 to 81 ml/100 g/min) in the primary visual cortex, V1. Compared to BOLD maps, functional CBF maps were found to be localized entirely within the gray matter, providing unequivocal evidence for high spatial specificity. The exquisite sensitivity of the system and the increased specificity of the hemodynamic signals promise further insights into the relationship of the latter to the underlying physiological activity.
    URL, DOI

  9. Iole Indovina and Emiliano Macaluso.
    Occipital–parietal interactions during shifts of exogenous visuospatial attention: trial-dependent changes of effective connectivity. Magnetic Resonance Imaging 22(10):1477–1486, 2004.
    Abstract We studied neural interactions between brain areas involved in exogenous (stimulus-driven) control of visuospatial attention. With event-related functional magnetic resonance imaging (fMRI), we investigated changes of connectivity during shifts of spatial attention from an attended location to a previously unattended target location. Using a 3-T scanner, fMRI data were acquired from three healthy volunteers. According to a central visual cue, participants directed endogenous spatial attention to the left or the right visual hemifield for blocks of 56 s. Peripheral visual targets were presented unpredictably in either the attended hemifield (valid trials, 80%) or in the unattended hemifield (invalid trials, 20%) and participants performed a two-alternative forced-choice discrimination task with the target, irrespective of cue validity. In accordance with previous results, we found that the temporal?parietal junction (TPJ) mediates the shift of spatial attention toward stimuli presented at the unattended side (i.e., invalid trials). We critically studied the interaction between occipital areas responding to the visual stimuli and other brain regions in order to find regions functionally coupled with the occipital cortex during invalid trials. We found that the coupling between occipital areas processing visual stimuli and the TPJ selectively increased during invalid trials. Our results highlight how changes of connectivity between brain areas can describe attentional processes such as stimulus-driven shifts of spatial attention. We studied neural interactions between brain areas involved in exogenous (stimulus-driven) control of visuospatial attention. With event-related functional magnetic resonance imaging (fMRI), we investigated changes of connectivity during shifts of spatial attention from an attended location to a previously unattended target location. Using a 3-T scanner, fMRI data were acquired from three healthy volunteers. According to a central visual cue, participants directed endogenous spatial attention to the left or the right visual hemifield for blocks of 56 s. Peripheral visual targets were presented unpredictably in either the attended hemifield (valid trials, 80%) or in the unattended hemifield (invalid trials, 20%) and participants performed a two-alternative forced-choice discrimination task with the target, irrespective of cue validity. In accordance with previous results, we found that the temporal?parietal junction (TPJ) mediates the shift of spatial attention toward stimuli presented at the unattended side (i.e., invalid trials). We critically studied the interaction between occipital areas responding to the visual stimuli and other brain regions in order to find regions functionally coupled with the occipital cortex during invalid trials. We found that the coupling between occipital areas processing visual stimuli and the TPJ selectively increased during invalid trials. Our results highlight how changes of connectivity between brain areas can describe attentional processes such as stimulus-driven shifts of spatial attention.
    URL, DOI

  10. Elia Formisano, Fabrizio Esposito, Francesco Di Salle and Rainer Goebel.
    Cortex-based independent component analysis of fMRI time series. Magnetic Resonance Imaging 22(10):1493–1504, 2004.
    Abstract The cerebral cortex is the main target of analysis in many functional magnetic resonance imaging (fMRI) studies. Since only about 20% of the voxels of a typical fMRI data set lie within the cortex, statistical analysis can be restricted to the subset of the voxels obtained after cortex segmentation. While such restriction does not influence conventional univariate statistical tests, it may have a substantial effect on the performance of multivariate methods.Here, we describe a novel approach for data-driven analysis of single-subject fMRI time series that combines techniques for the segmentation and reconstruction of the cortical surface of the brain and the spatial independent component analysis (sICA) of the functional time courses (TCs). We use the mesh of the white matter/gray matter boundary, automatically reconstructed from high-spatial-resolution anatomical MR images, to limit the sICA decomposition of a coregistered functional time series to those voxels which are within a specified region with respect to the cortical sheet (cortex-based ICA, or cbICA). We illustrate our analysis method in the context of fMRI blocked and event-related experimental designs and in an fMRI experiment with perceptually ambiguous stimulation, in which an a priori specification of the stimulation protocol is not possible.A comparison between cbICA and conventional hypothesis-driven statistical methods shows that cortical surface maps and component TCs blindly obtained with cbICA reliably reflect task-related spatiotemporal activation patterns. Furthermore, the advantages of using cbICA when the specification of a temporal model of the expected hemodynamic response is not straightforward are illustrated and discussed. A comparison between cbICA and anatomically unconstrained ICA reveals that ? beside reducing computational demand ? the cortex-based approach improves the fitting of the ICA model in the gray matter voxels, the separation of cortical components and the estimation of their TCs, particularly in the case of fMRI data sets with a complex spatiotemporal statistical structure. The cerebral cortex is the main target of analysis in many functional magnetic resonance imaging (fMRI) studies. Since only about 20% of the voxels of a typical fMRI data set lie within the cortex, statistical analysis can be restricted to the subset of the voxels obtained after cortex segmentation. While such restriction does not influence conventional univariate statistical tests, it may have a substantial effect on the performance of multivariate methods.Here, we describe a novel approach for data-driven analysis of single-subject fMRI time series that combines techniques for the segmentation and reconstruction of the cortical surface of the brain and the spatial independent component analysis (sICA) of the functional time courses (TCs). We use the mesh of the white matter/gray matter boundary, automatically reconstructed from high-spatial-resolution anatomical MR images, to limit the sICA decomposition of a coregistered functional time series to those voxels which are within a specified region with respect to the cortical sheet (cortex-based ICA, or cbICA). We illustrate our analysis method in the context of fMRI blocked and event-related experimental designs and in an fMRI experiment with perceptually ambiguous stimulation, in which an a priori specification of the stimulation protocol is not possible.A comparison between cbICA and conventional hypothesis-driven statistical methods shows that cortical surface maps and component TCs blindly obtained with cbICA reliably reflect task-related spatiotemporal activation patterns. Furthermore, the advantages of using cbICA when the specification of a temporal model of the expected hemodynamic response is not straightforward are illustrated and discussed. A comparison between cbICA and anatomically unconstrained ICA reveals that ? beside reducing computational demand ? the cortex-based approach improves the fitting of the ICA model in the gray matter voxels, the separation of cortical components and the estimation of their TCs, particularly in the case of fMRI data sets with a complex spatiotemporal statistical structure.
    URL, DOI

  11. Laura Astolfi, Febo Cincotti, Donatella Mattia, Serenella Salinari, Claudio Babiloni, Alessandra Basilisco, Paolo Maria Rossini, Lei Ding, Ying Ni, Bin He, Maria Grazia Marciani and Fabio Babiloni.
    Estimation of the effective and functional human cortical connectivity with structural equation modeling and directed transfer function applied to high-resolution EEG. Magnetic Resonance Imaging 22(10):1457–1470, 2004.
    Abstract Different brain imaging devices are presently available to provide images of the human functional cortical activity, based on hemodynamic, metabolic or electromagnetic measurements. However, static images of brain regions activated during particular tasks do not convey the information of how these regions are interconnected. The concept of brain connectivity plays a central role in the neuroscience, and different definitions of connectivity, functional and effective, have been adopted in literature. While the functional connectivity is defined as the temporal coherence among the activities of different brain areas, the effective connectivity is defined as the simplest brain circuit that would produce the same temporal relationship as observed experimentally among cortical sites. The structural equation modeling (SEM) is the most used method to estimate effective connectivity in neuroscience, and its typical application is on data related to brain hemodynamic behavior tested by functional magnetic resonance imaging (fMRI), whereas the directed transfer function (DTF) method is a frequency-domain approach based on both a multivariate autoregressive (MVAR) modeling of time series and on the concept of Granger causality.This study presents advanced methods for the estimation of cortical connectivity by applying SEM and DTF on the cortical signals estimated from high-resolution electroencephalography (EEG) recordings, since these signals exhibit a higher spatial resolution than conventional cerebral electromagnetic measures. To estimate correctly the cortical signals, we used a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from individual MRI, a distributed source model and a regularized linear inverse source estimates of cortical current density. Before the application of SEM and DTF methodology to the cortical waveforms estimated from high-resolution EEG data, we performed a simulation study, in which different main factors (signal-to-noise ratio, SNR, and simulated cortical activity duration, LENGTH) were systematically manipulated in the generation of test signals, and the errors in the estimated connectivity were evaluated by the analysis of variance (ANOVA). The statistical analysis returned that during simulations, both SEM and DTF estimators were able to correctly estimate the imposed connectivity patterns under reasonable operative conditions, that is, when data exhibit an SNR of at least 3 and a LENGTH of at least 75 s of nonconsecutive EEG recordings at 64 Hz of sampling rate.Hence, effective and functional connectivity patterns of cortical activity can be effectively estimated under general conditions met in any practical EEG recordings, by combining high-resolution EEG techniques and linear inverse estimation with SEM or DTF methods. We conclude that the estimation of cortical connectivity can be performed not only with hemodynamic measurements, but also with EEG signals treated with advanced computational techniques. Different brain imaging devices are presently available to provide images of the human functional cortical activity, based on hemodynamic, metabolic or electromagnetic measurements. However, static images of brain regions activated during particular tasks do not convey the information of how these regions are interconnected. The concept of brain connectivity plays a central role in the neuroscience, and different definitions of connectivity, functional and effective, have been adopted in literature. While the functional connectivity is defined as the temporal coherence among the activities of different brain areas, the effective connectivity is defined as the simplest brain circuit that would produce the same temporal relationship as observed experimentally among cortical sites. The structural equation modeling (SEM) is the most used method to estimate effective connectivity in neuroscience, and its typical application is on data related to brain hemodynamic behavior tested by functional magnetic resonance imaging (fMRI), whereas the directed transfer function (DTF) method is a frequency-domain approach based on both a multivariate autoregressive (MVAR) modeling of time series and on the concept of Granger causality.This study presents advanced methods for the estimation of cortical connectivity by applying SEM and DTF on the cortical signals estimated from high-resolution electroencephalography (EEG) recordings, since these signals exhibit a higher spatial resolution than conventional cerebral electromagnetic measures. To estimate correctly the cortical signals, we used a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from individual MRI, a distributed source model and a regularized linear inverse source estimates of cortical current density. Before the application of SEM and DTF methodology to the cortical waveforms estimated from high-resolution EEG data, we performed a simulation study, in which different main factors (signal-to-noise ratio, SNR, and simulated cortical activity duration, LENGTH) were systematically manipulated in the generation of test signals, and the errors in the estimated connectivity were evaluated by the analysis of variance (ANOVA). The statistical analysis returned that during simulations, both SEM and DTF estimators were able to correctly estimate the imposed connectivity patterns under reasonable operative conditions, that is, when data exhibit an SNR of at least 3 and a LENGTH of at least 75 s of nonconsecutive EEG recordings at 64 Hz of sampling rate.Hence, effective and functional connectivity patterns of cortical activity can be effectively estimated under general conditions met in any practical EEG recordings, by combining high-resolution EEG techniques and linear inverse estimation with SEM or DTF methods. We conclude that the estimation of cortical connectivity can be performed not only with hemodynamic measurements, but also with EEG signals treated with advanced computational techniques.
    URL, DOI

  12. Federico Giove, Girolamo Garreffa, Giovanni Giulietti, Silvia Mangia, Claudio Colonnese and Bruno Maraviglia.
    Issues about the fMRI of the human spinal cord. Magnetic Resonance Imaging 22(10):1505–1516, 2004.
    Abstract Noninvasive functional studies on human spinal cord by means of magnetic resonance imaging (MRI) are gaining attention because of the promising applications in the study of healthy and injured central nervous system. The findings obtained are generally consistent with the anatomic knowledge based on invasive methods, but the origin and specificity of functional contrast is still debated. In this paper, a review of current knowledge and major issues about functional MRI (fMRI) in the human spinal cord is presented, with emphasis on the main methodological and technical problems and on forthcoming applications as clinical tool. Noninvasive functional studies on human spinal cord by means of magnetic resonance imaging (MRI) are gaining attention because of the promising applications in the study of healthy and injured central nervous system. The findings obtained are generally consistent with the anatomic knowledge based on invasive methods, but the origin and specificity of functional contrast is still debated. In this paper, a review of current knowledge and major issues about functional MRI (fMRI) in the human spinal cord is presented, with emphasis on the main methodological and technical problems and on forthcoming applications as clinical tool.
    URL, DOI

  13. Carlo Adolfo Porro, Fausta Lui, Patrizia Facchin, Marta Maieron and Patrizia Baraldi.
    Percept-related activity in the human somatosensory system: functional magnetic resonance imaging studies. Magnetic Resonance Imaging 22(10):1539–1548, 2004.
    Abstract 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. 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.
    URL, DOI

  14. Robert V Mulkern, Nan-kuei Chen, Koichi Oshio, Lawrence P Panych, Frank J Rybicki and Giulio Gambarota.
    Fast spectroscopic imaging strategies for potential applications in fMRI. Magnetic Resonance Imaging 22(10):1395–1405, 2004.
    Abstract Technical aspects of two general fast spectroscopic imaging (SI) strategies, one based on gradient echo trains and the other on spin echo trains, are reviewed within the context of potential applications in the field of functional magnetic resonance imaging (fMRI). Fast spectroscopic imaging of water may prove useful for identifying mechanisms underlying the blood oxygenation level dependence (BOLD) of the water signal during brain activation studies. Reasonably rapid mapping of changes in proton signals from brain metabolites, like lactate, creatine or even neurotransmitter associated metabolites like GABA, is substantially more challenging but technically feasible particularly as higher field strengths become available. Fast spectroscopic methods directed towards the 31P signals from phosphocreatine (PCr) and adenosine tri-phosphates (ATP) are also technically feasible and may prove useful for studying cerebral energetics within fMRI contexts. Technical aspects of two general fast spectroscopic imaging (SI) strategies, one based on gradient echo trains and the other on spin echo trains, are reviewed within the context of potential applications in the field of functional magnetic resonance imaging (fMRI). Fast spectroscopic imaging of water may prove useful for identifying mechanisms underlying the blood oxygenation level dependence (BOLD) of the water signal during brain activation studies. Reasonably rapid mapping of changes in proton signals from brain metabolites, like lactate, creatine or even neurotransmitter associated metabolites like GABA, is substantially more challenging but technically feasible particularly as higher field strengths become available. Fast spectroscopic methods directed towards the 31P signals from phosphocreatine (PCr) and adenosine tri-phosphates (ATP) are also technically feasible and may prove useful for studying cerebral energetics within fMRI contexts.
    URL, DOI

  15. Kerry L Shannon, Rosa T Branca, Gigi Galiana, Silvia Cenzano, Louis-Serge Bouchard, Winston Soboyejo and Warren S Warren.
    Simultaneous acquisition of multiple orders of intermolecular multiple-quantum coherence images in vivo. Magnetic Resonance Imaging 22(10):1407–1412, 2004.
    Abstract Until recently, NMR imaging with intermolecular multiple-quantum coherences (iMQCs) has been based on the acquisition of a single echo. In vivo studies of iMQC image contrast would greatly benefit from a method that could acquire several orders of quantum coherence during the same acquisition. This would enable comparison of the image contrast for various orders and eliminate image coregistration problems between scans. It has previously been demonstrated that multiple orders of iMQC images can be simultaneously acquired of a simple phantom. Here, we examine the technique and its effect on biological tissue, both in vivo and in vitro. First, we establish the effectiveness of the iMQC sequence in vivo using earthworms as specimens. We then further show that the multi-CRAZED sequence enhances detection of next generation (nanoparticle) contrast agents on excised tumor tissue. Until recently, NMR imaging with intermolecular multiple-quantum coherences (iMQCs) has been based on the acquisition of a single echo. In vivo studies of iMQC image contrast would greatly benefit from a method that could acquire several orders of quantum coherence during the same acquisition. This would enable comparison of the image contrast for various orders and eliminate image coregistration problems between scans. It has previously been demonstrated that multiple orders of iMQC images can be simultaneously acquired of a simple phantom. Here, we examine the technique and its effect on biological tissue, both in vivo and in vitro. First, we establish the effectiveness of the iMQC sequence in vivo using earthworms as specimens. We then further show that the multi-CRAZED sequence enhances detection of next generation (nanoparticle) contrast agents on excised tumor tissue.
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  16. Daniel Konn, Sean Leach, Penny Gowland and Richard Bowtell.
    Initial attempts at directly detecting alpha wave activity in the brain using MRI. Magnetic Resonance Imaging 22(10):1413–1427, 2004.
    Abstract The ?direct detection? of neuronal activity by MRI could offer improved spatial and temporal resolution compared to the blood oxygenation level-dependent (BOLD) effect. Here we describe initial attempts to use MRI to detect directly the neuronal currents resulting from spontaneous alpha wave activity, which have previously been shown to generate the largest extracranial magnetic fields. Experiments were successfully carried out on four subjects at 3 T. A single slice was imaged at a rate of 25 images per second under two conditions. The first (in darkness with eyes-closed) was chosen to promote alpha wave activity, while the second (eyes-open viewing a visual stimulus) was chosen to suppress it. The fluctuations of the phase and magnitude of the resulting MR image data were frequency analysed, and tested for the signature of both alpha wave activity and neuronal activity evoked by the visual stimulus.Regions were found that consistently showed elevated power in fluctuations of the phase of the MR signal, in the frequency range of alpha waves, during the eyes-closed condition. It was conservatively assumed that if oscillations occurred at the same frequency in the magnitude signal from the same region or at the same frequency in the phase or magnitude signal from other regions overlying large vessels or cerebrospinal fluid (CSF), then the phase changes were not due to neuronal activity related to alpha waves. Using these criteria the data obtained were consistent with direct detection of alpha wave activity in three of the four volunteers. No significant MR signal fluctuations due to evoked activity were identified. The ?direct detection? of neuronal activity by MRI could offer improved spatial and temporal resolution compared to the blood oxygenation level-dependent (BOLD) effect. Here we describe initial attempts to use MRI to detect directly the neuronal currents resulting from spontaneous alpha wave activity, which have previously been shown to generate the largest extracranial magnetic fields. Experiments were successfully carried out on four subjects at 3 T. A single slice was imaged at a rate of 25 images per second under two conditions. The first (in darkness with eyes-closed) was chosen to promote alpha wave activity, while the second (eyes-open viewing a visual stimulus) was chosen to suppress it. The fluctuations of the phase and magnitude of the resulting MR image data were frequency analysed, and tested for the signature of both alpha wave activity and neuronal activity evoked by the visual stimulus.Regions were found that consistently showed elevated power in fluctuations of the phase of the MR signal, in the frequency range of alpha waves, during the eyes-closed condition. It was conservatively assumed that if oscillations occurred at the same frequency in the magnitude signal from the same region or at the same frequency in the phase or magnitude signal from other regions overlying large vessels or cerebrospinal fluid (CSF), then the phase changes were not due to neuronal activity related to alpha waves. Using these criteria the data obtained were consistent with direct detection of alpha wave activity in three of the four volunteers. No significant MR signal fluctuations due to evoked activity were identified.
    URL, DOI

  17. Girolamo Garreffa, Marta Bianciardi, Gisela E Hagberg, Emiliano Macaluso, Maria Grazia Marciani, Bruno Maraviglia, Manuel Abbafati, Marco Carnì, Ivo Bruni and Luigi Bianchi.
    Simultaneous EEG–fMRI acquisition: how far is it from being a standardized technique?. Magnetic Resonance Imaging 22(10):1445–1455, 2004.
    Abstract 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. 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.
    URL, DOI

  18. Giovanni Battista Ricci, Diego De Carli, Claudio Colonnese, Giancarlo Di Gennaro, Pier Paolo Quarato, Gianpaolo Cantore, Vincenzo Esposito, Girolamo Garreffa and Bruno Maraviglia.
    Hemodynamic response (BOLD/fMRI) in focal epilepsy with reference to benzodiazepine effect. Magnetic Resonance Imaging 22(10):1487–1492, 2004.
    Abstract We studied a new procedure of BOLD/fMRI acquisition in epilepsy. They use the benzodiazepine effect to achieve a more reliable baseline for statistical analysis. The method works only in the MR domain without EEG correlation. It compares the EPI images during interictal epileptic discharges and the images ?inactivated? by benzodiazepine.The results in five out of eight patients show that this procedure in comparison with the EEG/fMRI method gives a net improvement of spatial definition of BOLD areas. These preliminary results seem to confirm the hypothesis that the better BOLD/fMRI procedure in epilepsy is to make use of physical features of MR that, unlike EEG, is not influenced by the distance of intercerebral sources and consequently allows a more complete and undistorted display of BOLD areas. We studied a new procedure of BOLD/fMRI acquisition in epilepsy. They use the benzodiazepine effect to achieve a more reliable baseline for statistical analysis. The method works only in the MR domain without EEG correlation. It compares the EPI images during interictal epileptic discharges and the images ?inactivated? by benzodiazepine.The results in five out of eight patients show that this procedure in comparison with the EEG/fMRI method gives a net improvement of spatial definition of BOLD areas. These preliminary results seem to confirm the hypothesis that the better BOLD/fMRI procedure in epilepsy is to make use of physical features of MR that, unlike EEG, is not influenced by the distance of intercerebral sources and consequently allows a more complete and undistorted display of BOLD areas.
    URL, DOI

  19. Marta Bianciardi, Francesco Di Russo, Teresa Aprile, Bruno Maraviglia and Gisela E Hagberg.
    Combination of BOLD-fMRI and VEP recordings for spin-echo MRI detection of primary magnetic effects caused by neuronal currents. Magnetic Resonance Imaging 22(10):1429–1440, 2004.
    Abstract In the present paper, for the first time, the feasibility to detect primary magnetic field changes caused by neuronal activity in vivo by spin-echo (SE) magnetic resonance imaging (MRI) is investigated. The detection of effects more directly linked to brain activity than secondary hemodynamic?metabolic changes would enable the study of brain function with improved specificity. However, the detection of neuronal currents by MRI is hampered by such accompanying hemodynamic changes. Therefore, SE image acquisition, rather than gradient-echo (GE) image acquisition, was preferred in the present work since the detection of primary neuronal and not blood oxygenation level-dependent (BOLD)-related effects may be facilitated by this approach. First of all, a precise spatiotemporal synchronization of image acquisition with the neuronal event had to be performed to avoid refocusing of the dephasing phenomenon during the course of the SE sequence. At this aim, we propose the combined use of visual evoked potential (VEP) recordings and BOLD-fMRI measurements prior to SE MRI scanning. Moreover, we exemplify by theory and experimentation how the control of artefactual signal changes due to BOLD and movement effects may be further improved by the experimental design. Finally, results from a pilot study using the proposed combination of VEP recordings and MRI techniques are reported, suggesting the feasibility of this method. In the present paper, for the first time, the feasibility to detect primary magnetic field changes caused by neuronal activity in vivo by spin-echo (SE) magnetic resonance imaging (MRI) is investigated. The detection of effects more directly linked to brain activity than secondary hemodynamic?metabolic changes would enable the study of brain function with improved specificity. However, the detection of neuronal currents by MRI is hampered by such accompanying hemodynamic changes. Therefore, SE image acquisition, rather than gradient-echo (GE) image acquisition, was preferred in the present work since the detection of primary neuronal and not blood oxygenation level-dependent (BOLD)-related effects may be facilitated by this approach. First of all, a precise spatiotemporal synchronization of image acquisition with the neuronal event had to be performed to avoid refocusing of the dephasing phenomenon during the course of the SE sequence. At this aim, we propose the combined use of visual evoked potential (VEP) recordings and BOLD-fMRI measurements prior to SE MRI scanning. Moreover, we exemplify by theory and experimentation how the control of artefactual signal changes due to BOLD and movement effects may be further improved by the experimental design. Finally, results from a pilot study using the proposed combination of VEP recordings and MRI techniques are reported, suggesting the feasibility of this method.
    URL, DOI