We report that visual stimulation produces an easily detectable (5-20%) transient increase in the intensity of water proton magnetic resonance signals in human primary visual cortex in gradient echo images at 4-T magnetic-field strength. The observed changes predominantly occur in areas containing gray matter and can be used to produce highspatial-resolution functional brain maps in humans. Reducing the image-acquisition echo time from 40 msec to 8 msec reduces the amplitude of the fractional signal change, suggesting that it is produced by a change in apparent transverse relaxation time T2. The amplitude, sign, and echo-time dependence of these intrinsic signal changes are consistent with the idea that neural activation increases regional cerebral blood flow and concomitantly increases venous-blood oxygenation.Magnetic-resonance imaging (MRI) of rodent brains at high (7-T) magnetic-field strength shows proton signal-intensity alterations related to blood oxygenation in regions close to local blood vessels (1-3). We have termed this phenomenon blood oxygenation-level-dependent (BOLD) contrast and have demonstrated that the underlying mechanism is a magnetic-susceptibility variation caused by deoxyhemoglobin, an endogenous paramagnetic contrast agent. It was further demonstrated that this magnetic-susceptibility effect could be used to measure in vivo changes in hemodynamics. For example, pharmacologically induced changes in cerebral blood flow and oxygen utilization produce measurable changes in BOLD contrast in the rat cerebral cortex. Similar results have recently been demonstrated in cat brain (4).There is increased evidence that a local elevation in human-brain venous-blood oxygenation accompanies an increase in neuronal activity (5-8). For example, positron emission tomography imaging experiments demonstrate stimulation-produced increases in regional cerebral blood flow without significantly changing local oxygen use, thus predicting an elevation in venous-blood oxygenation (6, 7). This result suggested that BOLD contrast imaging could be used to map human mental operations. To examine whether detectable intrinsic magnetic-susceptibility changes are produced in the human brain in response to neuronal activation, we studied the effect of visual stimulation on gradient echo images of human visual cortex acquired at high-magneticfield strength. In general, high-field strength increases the magnitude of susceptibility contrast effects, accentuating BOLD contrast. MATERIALS AND METHODSMRI experiments were done with a 4-T whole-body imaging system with actively shielded gradient coils [Sisco (Sunnyvale, CA)/Siemens (Erlangen, F.R.G.)]. Approval for these human experiments was obtained from the institutional review board of the University of Minnesota Medical School. Radiofrequency power deposition was kept two orders of magnitude below Food and Drug Administration specificabsorption rate guidelines. A snugly fitted head holder with a curved-surface radiofrequency coil (14 cm in diameter) was used to limit...

It recently has been demonstrated that magnetic resonance imaging can be used to map changes in brain hemodynamics produced by human mental operations. One method under development relies on blood oxygenation level-dependent (BOLD) contrast: a change in the signal strength of brain water protons produced by the paramagnetic effects of venous blood deoxyhemoglobin. Here we discuss the basic quantitative features of the observed BOLD-based signal changes, including the signal amplitude and its magnetic field dependence and dynamic effects such as a pronounced oscillatory pattern that is induced in the signal from primary visual cortex during photic stimulation experiments. The observed features are compared with the results of Monte Carlo simulations of water proton intravoxel phase dispersion produced by local field gradients generated by paramagnetic deoxyhemoglobin in nearby venous blood vessels. The simulations suggest that the effect of water molecule diffusion is strong for the case of blood capillaries, but, for larger venous blood vessels, water diffusion is not an important determinant of deoxyhemoglobin-induced signal dephasing. We provide an expression for the apparent in-plane relaxation rate constant (R2*) in terms of the main magnetic field strength, the degree of the oxygenation of the venous blood, the venous blood volume fraction in the tissue, and the size of the blood vessel.

Characterization of large-scale brain networks using blood-oxygenation-level-dependent functional magnetic resonance imaging is typically based on the assumption of network stationarity across the duration of scan. Recent studies in humans have questioned this assumption by showing that within-network functional connectivity fluctuates on the order of seconds to minutes. Time-varying profiles of resting-state networks (RSNs) may relate to spontaneously shifting, electrophysiological network states and are thus mechanistically of particular importance. However, because these studies acquired data from awake subjects, the fluctuating connectivity could reflect various forms of conscious brain processing such as passive mind wandering, active monitoring, memory formation, or changes in attention and arousal during image acquisition. Here, we characterize RSN dynamics of anesthetized macaques that control for these accounts, and compare them to awake human subjects. We find that functional connectivity among nodes comprising the "oculomotor (OCM) network" strongly fluctuated over time during awake as well as anaesthetized states. For time dependent analysis with short windows (<60 s), periods of positive functional correlations alternated with prominent anticorrelations that were missed when assessed with longer time windows. Similarly, the analysis identified network nodes that transiently link to the OCM network and did not emerge in average RSN analysis. Furthermore, time-dependent analysis reliably revealed transient states of large-scale synchronization that spanned all seeds. The results illustrate that resting-state functional connectivity is not static and that RSNs can exhibit nonstationary, spontaneous relationships irrespective of conscious, cognitive processing. The findings imply that mechanistically important network information can be missed when using average functional connectivity as the single network measure.

The experience of pain is subjectively different from the fear and anxiety caused by threats of pain. Functional magnetic resonance imaging in healthy humans was applied to dissociate neural activation patterns associated with acute pain and its anticipation. Expectation of pain activated sites within the medial frontal lobe, insular cortex, and cerebellum distinct from, but close to, locations mediating pain experience itself. Anticipation of pain can in its own right cause mood changes and behavioral adaptations that exacerbate the suffering experienced by chronic pain patients. Selective manipulations of activity at these sites may offer therapeutic possibilities for treating chronic pain.

High resolution functional MRI (fMRI) experiments were performed in human visual cortex at 0.5, 1.5, and 4 T to determine the blood oxygenation level dependent (BOLD) field strength response within regions of obvious venous vessels and cortical gray matter ("tissue"). T2*-weighted FLASH images were collected in single- and multi-echo mode and used to determine the intrinsic BOLD parameters, namely, signal-to-noise ratio (psi), the apparent transverse relaxation rate (R2*) and the change in R2* (deltaR2*) between the activated and baseline states. The authors find the average percentage signal change (deltaS/S, measured at TE = T2*) to be large in vessels (13.3 +/- 2.3%, 18.4 +/- 4.0%, and 15.1 +/- 1.2%) compared with that in tissue (1.4 +/- 0.7%, 1.9 +/- 0.7%, and 3.3 +/- 0.2%) at 0.5, 1.5, and 4 T, respectively. The signal-to-noise ratio in optimized, fully relaxed proton density weighted gradient echo images was found to increase linearly with respect to the static magnetic field strength (B0). The predicted upper bound on BOLD contrast-to-noise ratio (deltaS/R)max as a function of field strength was calculated and found to behave less than linearly in voxels containing vessels larger than the voxel itself and greater than linearly in voxels containing a mixture of capillaries and veins/venules with a diameter less than that of the voxel.