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...

MRI was extended to the measurement of changes in oxidative metabolism in the normal human during functionally induced changes in cellular activity. A noninvasive MRI method that is model-independent calibrates the blood oxygen level dependent (BOLD) signal of functional MRI (fMRI) against perfusion-sensitive MRI, using carbon dioxide breathing as a physiological reference standard. This calibration procedure provides a regional measurement of the expected sensitivity of the fMRI BOLD signal to changes in the cellular activity of the brain. Maps of the BOLD signal calibration factor showed regional heterogeneity, indicating that the magnitude of functionally induced changes in the BOLD signal will be dependent on both the local change in blood f low and the local baseline physiology of the cerebral cortex. BOLD signal magnitude is shown to be reduced by 32% from its expected level by the action of oxygen metabolism. The calibrated fMRI technique was applied to stimulation of the human visual cortex with an alternating radial checkerboard pattern. With this stimulus oxygen consumption increased 16% whereas blood f low increased 45%. Although this result is consistent with previous findings of a significant difference between the increase in blood f low and oxygen consumption, it does indicate clearly that oxidative metabolism is a significant component of the metabolic response of the brain to functionally induced changes in cellular activity.Functionally related changes in neuronal activity in the normal brain are reliably accompanied by changes in local cerebral blood flow (CBF) (1). The degree to which the cerebral metabolic rate for oxygen (CMR O2 ) also changes with activityrelated increases and decreases in neuronal activity remains controversial. Although some reports show little or no taskinduced increase in CMR O2 (2-4), others have shown varying degrees of coupling of oxidative metabolism to glucose consumption and blood flow (5-7), both of which increase dramatically with task activation (3,4,8). Some have suggested that the reason CBF changes more than CMR O2 during functionally related increases in neuronal activity (decreases have not been addressed) is to enhance the diffusion-limited delivery of oxygen to the tissue (9-11).Current functional MRI (fMRI) methods rely on the fact that CBF changes more than CMR O2 , producing localized changes in tissue oxygen content. These localized changes in tissue oxygen content change magnetic fields in a manner that can be detected with MRI. This signal has been termed the blood oxygen level dependent (BOLD) signal of fMRI (12, 13). The fMRI BOLD signal has been viewed as a reasonable marker of functionally related changes in neuronal activity. The magnitude of the BOLD signal, of course, is dependent on the relationship between changes, if any, in CMR O2 and the changes in CBF. The greater the increase in CMR O2 for any increase in CBF, the smaller the BOLD signal becomes and vice versa.In this paper we examine the degree to which the relationship betw...