The borders of human visual areas V1, V2, VP, V3, and V4 were precisely and noninvasively determined. Functional magnetic resonance images were recorded during phase-encoded retinal stimulation. This volume data set was then sampled with a cortical surface reconstruction, making it possible to calculate the local visual field sign (mirror image versus non-mirror image representation). This method automatically and objectively outlines area borders because adjacent areas often have the opposite field sign. Cortical magnification factor curves for striate and extrastriate cortical areas were determined, which showed that human visual areas have a greater emphasis on the center-of-gaze than their counterparts in monkeys. Retinotopically organized visual areas in humans extend anteriorly to overlap several areas previously shown to be activated by written words.

Neuronal activity causes local changes in cerebral blood flow, blood volume, and blood oxygenation. Magnetic resonance imaging (MRI) techniques sensitive to changes in cerebral blood flow and blood oxygenation were developed by high-speed echo planar imaging. These techniques were used to obtain completely noninvasive tomographic maps of human brain activity, by using visual and motor stimulus paradigms. Changes in blood oxygenation were detected by using a gradient echo (GE) imaging sequence sensitive to the paramagnetic state of deoxygenated hemoglobin. Blood flow changes were evaluated by a spin-echo inversion recovery (IR), tissue relaxation parameter Tl-sensitive pulse sequence. A series of images were acquired continuously with the same imaging pulse sequence (either GE or IR) during task activation. Cine display of subtraction images (activated minus baseline) directly demonstrates activity-induced changes in brain MR signal observed at a temporal resolution of seconds. During 8-Hz patterned-flash photic stimulation, a significant increase in signal intensity (paired t test; P < 0.001) of 1.8% ± 0.8% (GE) and 1.8% ± 0.9% (ID) was observed in the primary visual cortex (Vi) of seven normal volunteers. The mean rise-time constant of the signal change was 4.4 ± 2.2 s for the GE images and 8.9 ± 2.8 s for the IR images. The stimulation frequency dependence of visual activation agrees with previous positron emission tomography observations, with the largest MR signal response occurring at 8 Hz. Similar signal changes were observed within the human primary motor cortex (Ml) during a hand squeezing task and in animal models of increased blood flow by hypercapnia. By using intrinsic blood-tissue contrast, functional MRI opens a spatialtemporal window onto individual brain physiology. The brain possesses anatomically distinct processing regions. A complete understanding of brain function requires determination ofwhere these sites are located, what operations are performed, and how distributed processing is organized (1). Changes in neuronal activity are accompanied by focal changes in cerebral blood flow (CBF) (2), blood volume (CBV) (3,4), blood oxygenation (3,5), and metabolism (6, 7). These physiological changes can be used to produce functional maps of component mental operations.Conventional magnetic resonance imaging (MRI) examinations provide high spatial-resolution anatomic images primarily based on contrast derived from the tissue-relaxation parameters T1 and T2. Recently, several investigators have demonstrated in animals that brain tissue relaxation is influenced by the oxygenation state of hemoglobin (a T* effect, modulated by the local blood volume) (8-13) and intrinsic tissue perfusion (T1 effect) (14)(15)(16). High-speed MRI techniques sensitive to these relaxation phenomena can thus be used to generate tomographic images of brain activity (17).We report here completely noninvasive MRI of brain activity by techniques with intrinsic sensitivity to CBF and blood oxygenation state. Time-resolved...

Magnetic resonance (MR) diffusion tensor imaging (DTI) can resolve the white matter fiber orientation within a voxel provided that the fibers are strongly aligned. However, a given voxel may contain a distribution of fiber orientations due to, for example, intravoxel fiber crossing. The present study sought to test whether a geodesic, high b-value diffusion gradient sampling scheme could resolve multiple fiber orientations within a single voxel. In regions of fiber crossing the diffusion signal exhibited multiple local maxima/minima as a function of diffusion gradient orientation, indicating the presence of multiple intravoxel fiber orientations. The multimodality of the observed diffusion signal precluded the standard tensor reconstruction, so instead the diffusion signal was modeled as arising from a discrete mixture of Gaussian diffusion processes in slow exchange, and the underlying mixture of tensors was solved for using a gradient descent scheme. The multitensor reconstruction resolved multiple intravoxel fiber populations corresponding to known fiber anatomy.Magn Key words: diffusion; diffusion-weighted MRI (DWI); diffusion tensor imaging (DTI); white matter; tractographyTissues with regularly ordered microstructure, such as skeletal muscle, spine, tongue, heart, and cerebral white matter, exhibit anisotropic water diffusion due to the alignment of the diffusion compartments in the tissue (1-7). The direction of preferred diffusion, and hence the direction of preferred orientation in the tissue, can be resolved with a method called magnetic resonance (MR) diffusion tensor imaging (DTI) (7), which measures the apparent water self-diffusion tensor under the assumption of Gaussian diffusion. Based on the eigenstructure of the measured diffusion tensor, it is possible to infer the orientation of the diffusion compartments within the voxel so that, for example, the major eigenvector of the diffusion tensor parallels the mean fiber orientation (7), and the minor eigenvector parallels the normal to the mean plane of fiber dispersion (8).The tensor model is incapable, however, of resolving multiple fiber orientations within an individual voxel. This shortcoming of the tensor model stems from the fact that the tensor possesses only a single orientational maximum, i.e., the major eigenvalue of the diffusion tensor (9,10). At the millimeter-scale resolution typical of DTI, the volume of cerebral white matter containing such intravoxel orientational heterogeneity (IVOH) may be considerable given the widespread divergence and convergence of fascicles (11-13). The abundance of IVOH at the millimeter scale can be further appreciated by considering the ubiquity of oblate (pancake-shaped) diffusion tensors in DTI, a hypothesized indicator of IVOH (3,4,8).Given the obstacle that IVOH (particularly fiber crossing (14 -16)) poses to white matter tractography algorithms (14 -20), we sought to determine whether high angular resolution, high b-value diffusion gradient sampling could resolve such intravoxel heterogeneity (9). H...

Using noninvasive functional magnetic resonance imaging (fMRI) technique, we analyzed the responses in human area MT with regard to visual motion, color, and luminance contrast sensitivity, and retinotopy. As in previous PET studies, we found that area MT responded selectively to moving (compared to stationary) stimuli. The location of human MT in the present fMRI results is consistent with that of MT in earlier PET and anatomical studies. In addition we found that area MT has a much higher contrast sensitivity than that in several other areas, including primary visual cortex (V1). Functional MRI half-amplitudes in V1 and MT occurred at approximately 15% and 1% luminance contrast, respectively. High sensitivity to contrast and motion in MT have been closely associated with magnocellular stream specialization in nonhuman primates. Human psychophysics indicates that visual motion appears to diminish when moving color-varying stimuli are equated in luminance. Electrophysiological results from macaque MT suggest that the human percept could be due to decreases in firing of area MT cells at equiluminance. We show here that fMRI activity in human MT does in fact decrease at and near individually measured equiluminance. Tests with visuotopically restricted stimuli in each hemifield produced spatial variations in fMRI activity consistent with retinotopy in human homologs of macaque areas V1, V2, V3, and VP. Such activity in area MT appeared much less retinotopic, as in macaque. However, it was possible to measure the interhemispheric spread of fMRI activity in human MT (half amplitude activation across the vertical meridian = approximately 15 degrees).

Knowledge of regional cerebral hemodynamics has widespread application for both physiological research and clinical assessment because of the well-established interrelation between physiological function, energy metabolism, and localized blood supply. A magnetic resonance technique was developed for quantitative imaging of cerebral hemodynamics, allowing for measurement of regional cerebral blood volume during resting and activated cognitive states. This technique was used to generate the first functional magnetic resonance maps of human task activation, by using a visual stimulus paradigm. During photic stimulation, localized increases in blood volume (32 +/- 10 percent, n = 7 subjects) were detected in the primary visual cortex. Center-of-mass coordinates and linear extents of brain activation within the plane of the calcarine fissure are reported.

Knowledge of regional hemodynamics has widespread application for both physiological research and clinical assessment. Here we review the use of MR contrast agents to measure tissue perfusion. Two primary mechanisms of image contrast are discussed: relaxivity and susceptibility effects. Relaxivity effects result from dipolar enhancement of T1 and T2 rates. Because tissue T1 rates are intrinsically smaller, the dominant effect is shortening of T1 relaxation times. The second mechanism of image contrast is the variation in tissue magnetic field produced by heterogeneous distribution of high magnetic susceptibility agents. Quantitation of tissue perfusion requires a detailed understanding of the relation between contrast agent concentration and associated MR signal changes. Studies to date show a linear relationship between contrast agent concentration and rate change in most organs. The exact nature of this relationship in the dynamic setting of rapid contrast agent passage through the microcirculatory bed is less well established. If this relationship is known, tracer kinetic modeling can be used to calculate regional blood flow and blood volume. Data are presented which indicate that this approach is feasible, and suggest the potential of contrast-enhanced NMR for high resolution in vivo mapping of both physiology and anatomy.

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.

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.