Functional MRI (fMRI) has uncovered widespread hemodynamic fluctuations in the brain during rest. Recent electroencephalographic work in humans and microelectrode recordings in anesthetized monkeys have shown this activity to be correlated with slow changes in neural activity. Here we report that the spontaneous fluctuations in the local field potential (LFP) measured from a single cortical site in monkeys at rest exhibit widespread, positive correlations with fMRI signals over nearly the entire cerebral cortex. This correlation was especially consistent in a band of upper gamma-range frequencies (40-80 Hz), for which the hemodynamic signal lagged the neural signal by 6-8 s. A strong, positive correlation was also observed in a band of lower frequencies (2-15 Hz), albeit with a lag closer to zero. The global pattern of correlation with spontaneous fMRI fluctuations was similar whether the LFP signal was measured in occipital, parietal, or frontal electrodes. This coupling was, however, dependent on the monkey's behavioral state, being stronger and anticipatory when the animals' eyes were closed. These results indicate that the often discarded global component of fMRI fluctuations measured during the resting state is tightly coupled with underlying neural activity.cortex | electrophysiology | local field potential | functional connectivity | monkey T he mammalian cerebral cortex is subdivided into specialized regions for various cognitive functions, such as the processing of sensory stimuli, memory, and the execution of movements. This functional specialization notwithstanding, the brain does not cease to show pronounced dynamic activity in the absence of cognitive or sensory stimulation. Significant ongoing spontaneous activity has been demonstrated using optical (1, 2), electrophysiological (3-5), and functional imaging (6, 7) techniques in several species under a variety of behavioral states. FMRI allows for visualization of large-scale, spatial patterns of such intrinsic activity, which is achieved by mapping patterns of activity covariation between brain regions. The temporal correlation between fluctuations in different regions is then often taken as a measure of "functional connectivity" between the corresponding brain areas (8-11). These fluctuations typically exhibit their highest intervoxel coherence at low temporal frequencies (<0.1 Hz) and can be observed during alertness (12, 13), sleep (14, 15), light sedation (16), and general anesthesia (17,18). Experiments are beginning to address the spatiotemporal characteristics of these spontaneous fluctuations in animal models (19)(20)(21), with initial studies in macaques suggesting a human-like pattern of functional connectivity (7,22).In humans, spontaneous activity is typically investigated in the so-called resting state, a term that is only loosely defined and which typically amounts to a subject lying in the scanner without an explicit stimulus or task. Under these conditions, analysis of spatiotemporal coherence of fMRI activity reveals several distin...

Tractography based on diffusion-weighted MRI (DWI) is widely used for mapping the structural connections of the human brain. Its accuracy is known to be limited by technical factors affecting in vivo data acquisition, such as noise, artifacts, and data undersampling resulting from scan time constraints. It generally is assumed that improvements in data quality and implementation of sophisticated tractography methods will lead to increasingly accurate maps of human anatomical connections. However, assessing the anatomical accuracy of DWI tractography is difficult because of the lack of independent knowledge of the true anatomical connections in humans. Here we investigate the future prospects of DWI-based connectional imaging by applying advanced tractography methods to an ex vivo DWI dataset of the macaque brain. The results of different tractography methods were compared with maps of known axonal projections from previous tracer studies in the macaque. Despite the exceptional quality of the DWI data, none of the methods demonstrated high anatomical accuracy. The methods that showed the highest sensitivity showed the lowest specificity, and vice versa. Additionally, anatomical accuracy was highly dependent upon parameters of the tractography algorithm, with different optimal values for mapping different pathways. These results suggest that there is an inherent limitation in determining long-range anatomical projections based on voxelaveraged estimates of local fiber orientation obtained from DWI data that is unlikely to be overcome by improvements in data acquisition and analysis alone.T he creation of a comprehensive map of the connectional neuroanatomy of the human brain would be a fundamental achievement in neuroscience. However, despite the numerous efforts to date (for a historical review, see ref. 1), creating this map remains a challenge. A major limitation is that the current goldstandard technique for mapping structural connections, which requires the injection of axonal tracers, cannot be used in humans. The introduction of diffusion-weighted MRI (DWI) (2-4) and the subsequent advent of diffusion tensor MRI (DTI) (5) opened the possibility of exploring the structural properties of white matter in the living human brain (6). Local DWI measures are used clinically for the early detection of stroke and for the characterization of neurological disorders such as multiple sclerosis, epilepsy, and brain gliomas, among others (7). In addition, tractography approaches (8-12) that can infer structural brain connectivity based on brain-wide local DWI measurement have been developed (for reviews, see refs. 13 and 14). The success of DWI tractography as a method for studying fiber trajectories has led to a systematic characterization of large white-matter pathways of the living human brain (e.g., ref. 15), and now it is used routinely to provide a structural explanation for aspects of human brain function (16).A major limitation of DWI tractography is that its characterization of axonal pathways is based on indirec...