An MRI time course of 512 echo-planar images (EPI) in resting human brain obtained every 250 ms reveals fluctuations in signal intensity in each pixel that have a physiologic origin. Regions of the sensorimotor cortex that were activated secondary to hand movement were identified using functional MRI methodology (FMRI). Time courses of low frequency (< 0.1 Hz) fluctuations in resting brain were observed to have a high degree of temporal correlation (P < 10(-3)) within these regions and also with time courses in several other regions that can be associated with motor function. It is concluded that correlation of low frequency fluctuations, which may arise from fluctuations in blood oxygenation or flow, is a manifestation of functional connectivity of the brain.

Functional magnetic resonance imaging (FMRI) is a new, noninvasive imaging tool thought to measure changes related to regional cerebral blood flow (rCBF). Previous FMRI studies have demonstrated functional changes within the primary cerebral cortex in response to simple activation tasks, but it is unknown whether FMRI can also detect changes within the nonprimary cortex in response to complex mental activities. We therefore scanned six right-handed healthy subjects while they performed self-paced simple and complex finger movements with the right and left hands. Some subjects also performed the tasks at a fixed rate (2 Hz) or imagined performing the complex task. Functional changes occurred (1) in the contralateral primary motor cortex during simple, self-paced movements; (2) in the contralateral (and occasionally ipsilateral) primary motor cortex, the supplementary motor area (SMA), the premotor cortex of both hemispheres, and the contralateral somatosensory cortex during complex, self-paced movements; (3) with less intensity during paced movements, presumably due to the slower movement rates associated with the paced (relative to self-paced) condition; and (4) in the SMA and, to a lesser degree, the premotor cortex during imagined complex movements. These preliminary results are consistent with hierarchical models of voluntary motor control.

Magnetic resonance imaging methods recently demonstrated regional cerebral signal changes in response to limb movement and visual stimulation, attributed to blood flow enhancement. We studied 5 normal subjects scanned while listening to auditory stimuli including nonspeech noise, meaningless speech sounds, single words, and narrative text. Imaged regions included the lateral aspects of both hemispheres. Signal changes in the superior temporal gyrus and superior temporal sulcus were observed bilaterally in all subjects. Speech stimuli were associated with significantly more widespread signal changes than was the noise stimulus, while no consistent differences were observed between responses to different speech stimuli. Considerable intersubject variability in the topography of signal changes was observed. These observations confirm the utility of magnetic resonance imaging in the study of human brain structure-function relationships and emphasize the role of the superior temporal gyrus in perception of acoustic-phonetic features of speech, rather than processing of semantic features.

Conceptual reasoning deficits are common in patients with multiple sclerosis (MS) and are typically associated with focal lesions involving the frontal lobes. In this study, we predicted that MS patients with frontal white matter lesions (MS-F) would be more impaired on a standard conceptual reasoning task (Wisconsin Card Sorting Test; WCST) than patients with minimal frontal lesions (MS-NF), even if the total cerebral lesion area (TLA), measured from MRI, was equivalent across groups. We subdivided 43 definite MS patients into three groups based on MRI findings: seven in the MS-F group (mean TLA = 41.4 cm2) and seven in the MS-NF group (mean TLA = 50.0 cm2); 29 MS patients served as a low lesion burden control group (MS-C; mean TLA = 6.4 cm2). The groups did not differ with regard to demographic and illness characteristics. Although the three subgroups obtained comparable scores on a measure of global cognitive functioning (verbal intelligence), the MS-F group achieved significantly fewer categories and made more total errors on the WCST than did the MS-NF and MS-C groups. The MS-F group made significantly more perseverative responses than the MS-C group and nonsignificantly more than the MS-NF group. These results suggest that the pattern of cognitive decline in MS is a function of the location of demyelinating lesions within the cerebral hemispheric white matter. Finally, we supplement the group study results with a case report of an MS patient who was studied serially with MRI and cognitive testing.

The goals of this study were to evaluate brain activation in patients with probable Alzheimer's disease (AD), mild cognitive impairment (MCI), and controls while performing a working memory (WM) task. Eleven AD patients, ten MCI subjects, and nine controls underwent functional magnetic resonance imaging (fMRI) while performing a visual WM task. Statistical parametric maps of brain activation were obtained in each group, and group activation difference maps were generated. Ability to perform the task did not differ among the groups. Activation was observed in the parahippocampal region, superior-middle-inferior frontal gyri, parietal region, anterior-posterior cingulate, fusiform gyrus, and basal ganglia. MCI and AD groups showed more activation than the controls in the right superior frontal gyrus, bilateral middle temporal, middle frontal, anterior cingulate, and fusiform gyri. Activation in the right parahippocampal gyrus, left inferior frontal gyrus, bilateral cingulate and lingual gyri, right lentiform nucleus, right fusiform gyrus, and left supramarginal gyrus in the AD group was less than in the MCI group. The WM task evoked activation in widely distributed regions, consistent with previous fMRI studies. AD and MCI patients showed an increased extent of activation and recruitment of additional areas.

Summary: Using magnetic resonance (MR) echo-planar imaging (EPI), we recently demonstrated the prescnce of low-frequency fluctuations «0,1 Hz) in MR signal inten sity from thc resting human brain that have a high degree of temporal correlation (p < 103) within and across associ ated regions of the sensorimotor cortex, These fluctuations in MR signal intensity are belicved to arise from fluctua tions in capillary blood flow and oxygenation, A substantial overlap between the activation map generated by bilateral finger tapping and temporally-correlated voxels from the sensorimotor oortex obtained during rest was observed, In the work reported here, we investigated whether respira tory hypercapnia, which is known to suspend spontane ous oscillations in regional cerebral blood flow, influences these low-frequency fluctuations, The magnitude of low- 301frequency fluctuations was reversibly diminished during hypercapnia, reSUlting in a substantial decrease of the tem poral correlation both within and across contralateral hemi spheres of the sensorimotor cortex, After the breathing mixture was returned to ambient air, the magnitude and spatial extent of the temporal correlation of low-frequency fluctuations returned to normaL Results of this study sup port the hypothesis that low-frequency

FMRI of tactile, motor, and language tasks is feasible in patients with cerebral tumors. FMRI shows promise as a means of determining the risk of a postoperative motor deficit from surgical resection of frontal or parietal tumors.

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