The influence of brain tissue anisotropy on human EEG and MEG.

The influence of gray and white matter tissue anisotropy on the human electroencephalogram (EEG) and magnetoencephalogram (MEG) was examined with a high resolution finite element model of the head of an adult male subject. The conductivity tensor data for gray and white matter were estimated from magnetic resonance diffusion tensor imaging. Simulations were carried out with single dipoles or small extended sources in the cortical gray matter. The inclusion of anisotropic volume conduction in the brain was found to have a minor influence on the topology of EEG and MEG (and hence source localization). We found a major influence on the amplitude of EEG and MEG (and hence source strength estimation) due to the change in conductivity and the inclusion of anisotropy. We expect that inclusion of tissue anisotropy information will improve source estimation procedures.

Functional neuroanatomy of biological motion perception in humans.

We used whole brain functional MRI to investigate the neural network specifically engaged in the recognition of "biological motion" defined by point-lights attached to the major joints and head of a human walker. To examine the specificity of brain regions responsive to biological motion, brain activations obtained during a "walker vs. non-walker" discrimination task were compared with those elicited by two other tasks: (i) non-rigid motion (NRM), involving the discrimination of overall motion direction in the same "point-lights" display, and (ii) face-gender discrimination, involving the discrimination of gender in briefly presented photographs of men and women. Brain activity specific to "biological motion" recognition arose in the lateral cerebellum and in a region in the lateral occipital cortex presumably corresponding to the area KO previously shown to be particularly sensitive to kinetic contours. Additional areas significantly activated during the biological motion recognition task involved both, dorsal and ventral extrastriate cortical regions. In the ventral regions both face-gender discrimination and biological motion recognition elicited activation in the lingual and fusiform gyri and in the Brodmann areas 22 and 38 in superior temporal sulcus (STS). Along the dorsal pathway, both biological motion recognition and non-rigid direction discrimination gave rise to strong responses in several known motion sensitive areas. These included Brodmann areas 19/37, the inferior (Brodmann Area 39), and superior parietal lobule (Brodmann Area 7). Thus, we conjecture that, whereas face (and form) stimuli activate primarily the ventral system and motion stimuli primarily the dorsal system, recognition of biological motion stimuli may activate both systems as well as their confluence in STS. This hypothesis is consistent with our findings in stroke patients, with unilateral brain lesions involving at least one of these areas, who, although correctly reporting the direction of the point-light walker, fail on the biological motion task.

Conductivity tensor mapping of the human brain using diffusion tensor MRI.

Knowledge of the electrical conductivity properties of excitable tissues is essential for relating the electromagnetic fields generated by the tissue to the underlying electrophysiological currents. Efforts to characterize these endogenous currents from measurements of the associated electromagnetic fields would significantly benefit from the ability to measure the electrical conductivity properties of the tissue noninvasively. Here, using an effective medium approach, we show how the electrical conductivity tensor of tissue can be quantitatively inferred from the water self-diffusion tensor as measured by diffusion tensor magnetic resonance imaging. The effective medium model indicates a strong linear relationship between the conductivity and diffusion tensor eigenvalues (respectively, final sigma and d) in agreement with theoretical bounds and experimental measurements presented here (final sigma/d approximately 0.844 +/- 0.0545 S small middle dots/mm(3), r(2) = 0.945). The extension to other biological transport phenomena is also discussed.

Influence of EEG electrodes on the BOLD fMRI signal.

Measurement of the EEG during fMRI scanning can give rise to image distortions due to magnetic susceptibility, eddy currents or chemical shift artifacts caused by certain types of EEG electrodes, cream, leads, or amplifiers. Two different creams were tested using MRS and T2* measurements, and we found that the one with higher water content was superior. This study introduces an index that quantifies the influence of EEG equipment on the BOLD fMRI signal. This index can also be used more generally to measure the changes in the fMRI signal due to the presence of any type of device inside (or outside) of the field of view (e.g., with fMRI and diffuse optical tomography, infrared imaging, transcranial magnetic stimulation, ultrasound imaging, etc.). Quantitative noise measurements are hampered by the normal variability of functional activation within the same subject and by the different slice profiles obtained when inserting a subject multiple times inside a MR imaging system. Our measurements account for these problems by using a matched filtering of cortical surface maps of functional activations. The results demonstrate that the BOLD signal is not influenced by the presence of EEG electrodes when using a properly constructed MRI compatible recording cap.

Spatiotemporal brain imaging of visual-evoked activity using interleaved EEG and fMRI recordings.

Combined analysis of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) has the potential to provide higher spatiotemporal resolution than either method alone. In some situations, in which the activity of interest cannot be reliably reproduced (e.g., epilepsy, learning, sleep states), accurate combined analysis requires simultaneous acquisition of EEG and fMRI. Simultaneous measurements ensure that the EEG and fMRI recordings reflect the exact same brain activity state. We took advantage of the spatial filtering properties of the bipolar montage to allow recording of very short (125--250 ms) visual-evoked potentials (VEPs) during fMRI. These EEG and fMRI measurements are of sufficient quality to allow source localization of the cortical generators. In addition, our source localization approach provides a combined EEG/fMRI analysis that does not require any manual selection of fMRI activations or placement of source dipoles. The source of the VEP was found to be located in the occipital cortex. Separate analysis of EEG and fMRI data demonstrated good spatial overlap of the observed activated sites. As expected, the combined EEG/fMRI analysis provided better spatiotemporal resolution than either approach alone. The resulting spatiotemporal movie allows for the millisecond-to-millisecond display of changes in cortical activity caused by visual stimulation. These data reveal two peaks in activity corresponding to the N75 and the P100 components. This type of simultaneous acquisition and analysis allows for the accurate characterization of the location and timing of neurophysiological activity in the human brain.

High microvascular blood volume is associated with high glucose uptake and tumor angiogenesis in human gliomas.

The purpose of this investigation was to elucidate the association between microvascular blood volume and glucose uptake and to link these measures with tumor angiogenesis. We demonstrate a regionally specific correlation between tumor relative microvascular blood volume (CBV), determined in vivo with functional magnetic resonance imaging techniques, and tumor glucose uptake determined with fluorodeoxyglucose positron emission tomography. Regions of maximum glucose uptake were well matched with maximum CBV across all patients (n = 21; r = 0.572; P = 0.023). High-grade gliomas showed significantly elevated CBV and glucose uptake compared with low-grade gliomas, (P = 0.009 and 0.008, respectively). Correlations between CBV and glucose uptake were then determined on a voxel-by-voxel basis within each patient's glioma. Correlation indices varied widely, but in 16 of 21 cases of human glioma, CBV and glucose uptake were correlated (r > 0.150). These measures were well correlated in all cases when comparing healthy brain tissue in these same patients. Tumor vascularity, as determined immunohistochemically and morphometrically on clinical samples, revealed statistically significant relationships with functional imaging characteristics in vivo. Regional heterogeneities in glucose uptake were well matched with functional magnetic resonance imaging CBV maps. Our findings support the concept that there is an association of microvascular density and tumor energy metabolism in most human gliomas. In addition, the findings are likely to have important clinical applications in the initial evaluation, treatment, and longitudinal monitoring of patients with malignant gliomas.

Dynamic statistical parametric mapping: combining fMRI and MEG for high-resolution imaging of cortical activity.

Functional magnetic resonance imaging (fMRI) can provide maps of brain activation with millimeter spatial resolution but is limited in its temporal resolution to the order of seconds. Here, we describe a technique that combines structural and functional MRI with magnetoencephalography (MEG) to obtain spatiotemporal maps of human brain activity with millisecond temporal resolution. This new technique was used to obtain dynamic statistical parametric maps of cortical activity during semantic processing of visually presented words. An initial wave of activity was found to spread rapidly from occipital visual cortex to temporal, parietal, and frontal areas within 185 ms, with a high degree of temporal overlap between different areas. Repetition effects were observed in many of the same areas following this initial wave of activation, providing evidence for the involvement of feedback mechanisms in repetition priming.

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.

Spatiotemporal activity of a cortical network for processing visual motion revealed by MEG and fMRI.

A sudden change in the direction of motion is a particularly salient and relevant feature of visual information. Extensive research has identified cortical areas responsive to visual motion and characterized their sensitivity to different features of motion, such as directional specificity. However, relatively little is known about responses to sudden changes in direction. Electrophysiological data from animals and functional imaging data from humans suggest a number of brain areas responsive to motion, presumably working as a network. Temporal patterns of activity allow the same network to process information in different ways. The present study in humans sought to determine which motion-sensitive areas are involved in processing changes in the direction of motion and to characterize the temporal patterns of processing within this network of brain regions. To accomplish this, we used both magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). The fMRI data were used as supplementary information in the localization of MEG sources. The change in the direction of visual motion was found to activate a number of areas, each displaying a different temporal behavior. The fMRI revealed motion-related activity in areas MT+ (the human homologue of monkey middle temporal area and possibly also other motion sensitive areas next to MT), a region near the posterior end of the superior temporal sulcus (pSTS), V3A, and V1/V2. The MEG data suggested additional frontal sources. An equivalent dipole model for the generators of MEG signals indicated activity in MT+, starting at 130 ms and peaking at 170 ms after the reversal of the direction of motion, and then again at approximately 260 ms. Frontal activity began 0-20 ms later than in MT+, and peaked approximately 180 ms. Both pSTS and FEF+ showed long-duration activity continuing over the latency range of 200-400 ms. MEG responses in the region of V3A and V1/V2 were relatively small, and peaked at longer latencies than the initial peak in MT+. These data revealed characteristic patterns of activity in this cortical network for processing sudden changes in the direction of visual motion.

Visual evoked potential (VEP) measured by simultaneous 64-channel EEG and 3T fMRI.

We present the first simultaneous measurements of evoked potentials (EPs) and fMRI hemodynamic responses to visual stimulation. Visual evoked potentials (VEPs) were recorded both inside and outside the static 3T magnetic field, and during fMRI examination. We designed, constructed, and tested a non-magnetic 64-channel EEG recording cap. By using a large number of EEG channels it is possible to design a spatial filter capable of removing the artifact noise present when recording EEG/EPs within a strong magnetic field. We show that the designed spatial filter is capable of recovering the ballistocardiogram-contaminated original EEG signal. Isopotential plots of the electrode array recordings at the peak of the VEP response (approximately 100ms) correspond well with simultaneous fMRI observed activated areas of primary and secondary visual cortices.

Language dominance determined by whole brain functional MRI in patients with brain lesions.

BACKGROUND: Functional MRI (fMRI) is of potential value in determining hemisphere dominance for language in epileptic patients. OBJECTIVE: To develop and validate an fMRI-based method of determining language dominance for patients with a wide range of potentially operable brain lesions in addition to epilepsy. METHODS: Initially, a within-subjects design was used with 19 healthy volunteers (11 strongly right-handed, 8 left-handed) to determine the relative lateralizing usefulness of three different language tasks in fMRI. An automated, hemispheric analysis of laterality was used to analyze whole brain fMRI data sets. To evaluate the clinical usefulness of this method, we compared fMRI-determined laterality with laterality determined by Wada testing or electrocortical stimulation mapping, or both, in 23 consecutive patients undergoing presurgical evaluation of language dominance. RESULTS: Only the verb generation task was reliably lateralizing. fMRI, using the verb generation task and an automated hemispheric analysis method, was concordant with invasive measures in 22 of 23 patients (12 Wada, 11 cortical stimulation). For the single patient who was discordant, in whom a tumor involved one-third of the left hemisphere, fMRI became concordant when the tumor and its reflection in the right hemisphere were excluded from laterality analysis. No significant negative correlation was obtained between lesion size and strength of laterality for the patients with lesions involving the dominant hemisphere. CONCLUSION: This fMRI method shows potential for evaluating language dominance in patients with a variety of brain lesions.

Neural systems underlying learning and representation of global motion.

We demonstrate performance-related changes in cortical and cerebellar activity. The largest learning-dependent changes were observed in the anterior lateral cerebellum, where the extent and intensity of activation correlated inversely with psychophysical performance. After learning had occurred (a few minutes), the cerebellar activation almost disappeared; however, it was restored when the subjects were presented with a novel, untrained direction of motion for which psychophysical performance also reverted to chance level. Similar reductions in the extent and intensity of brain activations in relation to learning occurred in the superior colliculus, anterior cingulate, and parts of the extrastriate cortex. The motion direction-sensitive middle temporal visual complex was a notable exception, where there was an expansion of the cortical territory activated by the trained stimulus. Together, these results indicate that the learning and representation of visual motion discrimination are mediated by different, but probably interacting, neuronal subsystems.

Spatiotemporal imaging of human brain activity using functional MRI constrained magnetoencephalography data: Monte Carlo simulations.

The goal of our research is to develop an experimental and analytical framework for spatiotemporal imaging of human brain function. Preliminary studies suggest that noninvasive spatiotemporal maps of cerebral activity can be produced by combining the high spatial resolution (millimeters) of functional MRI (fMRI) with the high temporal resolution (milliseconds) of electroencephalography (EEG) and magnetoencephalography (MEG). Although MEG and EEG are sensitive to millisecond changes in mental activity, the ability to resolve source localization and timing is limited by the ill-posed "inverse" problem. We conducted Monte Carlo simulations to evaluate the use of MRI constraints in a linear estimation inverse procedure, where fMRI weighting, cortical location and orientation, and sensor noise statistics were realistically incorporated. An error metric was computed to quantify the effects of fMRI invisible ("missing") sources, "extra" fMRI sources, and cortical orientation errors. Our simulation results demonstrate that prior anatomical and functional information from MRI can be used to regularize the EEG/MEG inverse problem, giving an improved solution with high spatial and temporal resolution. An fMRI weighting of approximately 90% was determined to provide the best compromise between separation of activity from correctly localized sources and minimization of error caused by missing sources. The accuracy of the estimate was relatively independent of the number and extent of the sources, allowing for incorporation of physiologically realistic multiple distributed sources. This linear estimation method provides an operator-independent approach for combining information from fMRI, MEG, and EEG and represents a significant advance over traditional dipole modeling.

Location of language in the cortex: a comparison between functional MR imaging and electrocortical stimulation.

PURPOSE: To determine the accuracy of functional MR imaging in locating language areas for planning surgical resection. METHODS: Intraoperative photographs were digitized and overlaid on functional MR language maps. The sensitivity and specificity of functional MR imaging for identifying language areas were determined for five different language tasks by comparing functional MR areas of language activation with results of electrocortical stimulation. A match was considered to occur if an activated area contacted overlapped, or surrounded a language tag. The borders of the activation areas were extended by 1 and 2 cm to determine whether the number of matches changed. Language and nonlanguage tag matches were tabulated separately. RESULTS: Sensitivity/specificity for all patients and all language tasks ranged from 81%/53% for areas that touched to 92%/0% for areas separated by 2 cm. Individual language tasks were not as sensitive as a battery of language tasks combined. Location of language areas varied among subjects for a given task and among tasks for a given subject. CONCLUSION: Functional MR imaging should be considered a useful presurgical planning tool for mapping cortical language areas, because it is sensitive, it provides increased time for planning before surgery, and it is noninvasive.

Characterization of cerebral blood oxygenation and flow changes during prolonged brain activation.

The behavior of cerebral blood flow and oxygenation during prolonged brain activation was studied using magnetic resonance imaging (MRI) sensitized to flow and oxygenation changes, as well as positron emission tomography sensitized to flow. Neuronal habituation effects and hemodynamic changes were evaluated across tasks and cortical regions. Nine types of activation stimuli or tasks, including motor activation, vibrotactile stimulation, and several types of visual stimulation, were used. Both flow and oxygenation were evaluated in separate time course series as well as simultaneously using two different MRI methods. In most cases, the activation-induced increase in flow and oxygenation remained elevated for the entire stimulation duration. These results suggest that both flow rate and oxygenation consumption rate remain constant during the entire time that primary cortical neurons are activated by a task or a stimulus.

Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder.

BACKGROUND: The new technique of functional magnetic resonance imaging was used to investigate the mediating neuroanatomy of obsessive-compulsive disorder symptoms. METHODS: Ten patients with obsessive-compulsive disorder and 5 normal subjects were studied via functional magnetic resonance imaging during control and provoked conditions. Data analysis entailed parametric and nonparametric statistical mapping. RESULTS: Statistical maps (nonparametric; P < 10(-3)) showed activation for 70% or more of patients with obsessive-compulsive disorder in medial orbitofrontal, lateral frontal, anterior temporal, anterior cingulate, and insular cortex, as well as caudate, lenticulate, and amygdala. No normal subjects exhibited activation in any brain region. CONCLUSIONS: Results of functional magnetic resonance imaging were consistent with past studies of obsessive-compulsive disorder that used other functional neuroimaging modalities. However, paralimbic and limbic activations were more prominent in the present study.

Changes in cortical activity during mental rotation. A mapping study using functional MRI.

Mental imagery is an important cognitive method for problem solving, and the mental rotation of complex objects, as originally described by Shepard and Metzler (1971), is among the best studied mental imagery tasks. Functional MRI was used to observe focal changes in blood flow in the brains of 10 healthy volunteers performing a mental rotation task. On each trial, subjects viewed a pair of perspective drawings of three-dimensional shapes, mentally rotated one into congruence with the other, and then determined whether the two forms were identical or mirror-images. The control task, which we have called the 'comparison' condition, was identical except that both members of each pair appeared at the same orientation, and hence the same encoding, comparison and decision processes were used but mental rotation was not required. These tasks were interleaved with a baseline 'fixation' condition, in which the subjects viewed a crosshair. Technically adequate studies were obtained in eight of the 10 subjects. Areas of increased signal were identified according to sulcal landmarks and are described in terms of the Brodmann's area (BA) definitions that correspond according to the atlas of Talaraich and Tournoux. When the rotation task was contrasted with the comparison condition, all subjects showed consistent foci of activation in BAs 7a and 7b (sometimes spreading to BA 40): 88% had increased signal in middle frontal gyrus (BA 8) and 75% showed extrastriate activation, including particularly BAs 39 and 19, in a position consistent with area V5/human MT as localized by functional and histological assays. In more than half of the subjects, hand somatosensory cortex (3-1-2) was engaged, and in 50% of subjects there was elevated signal in BA 18. In frontal cortex, activation was above threshold in half the subjects in BAs 9 and/or 46 (dorsolateral prefrontal cortex). Some (four out of eight) subjects also showed signal increases in BAs 44 and/or 46. Premotor cortex (BA 6) was active in half of the subjects during the rotation task. There was little evidence for lateralization of the cortical activity or of engagement of motor cortex. These data are consistent with the hypothesis that mental rotation engages cortical areas involved in tracking moving objects and encoding spatial relations, as well as the more general understanding that mental imagery engages the same, or similar, neural imagery as direct perception.

Functional magnetic resonance imaging shows localized brain activation during serial transcranial stimulation in man.

Area and depth penetration of transcranial stimulation methods such as transcranial electrical stimulation (TES) are poorly defined. We investigated the feasibility of a simultaneous TES and fMRI measurement. The aim was to compare the signal intensity changes measured using BOLD fMRI during sequential finger movement with the signal response during artificial transcranial stimulation. Tes induced contralateral finger contractions and in T2* weighted images a transient signal increase was observed in the area underlying the electrodes. Compared with the signal obtained during sequential finger movements, the area activated by TES was more localized, signal amplitude, was smaller and there was no post-stimulus undershoot. These data indicate that TES induces a local blood flow increase associated with a drop in the concentration of deoxyhaemoglobin.