The majority of functional neuroscience studies have focused on the brain's response to a task or stimulus. However, the brain is very active even in the absence of explicit input or output. In this Article we review recent studies examining spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal of functional magnetic resonance imaging as a potentially important and revealing manifestation of spontaneous neuronal activity. Although several challenges remain, these studies have provided insight into the intrinsic functional architecture of the brain, variability in behaviour and potential physiological correlates of neurological and psychiatric disease.

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Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging.

BACKGROUND AND PURPOSE: In subjects who are performing no prescribed cognitive task, functional connectivity mapped with MR imaging (fcMRI) shows regions with synchronous fluctuations of cerebral blood flow. When specific tasks are performed, functional MR imaging (fMRI) can map locations in which regional cerebral blood flow increases synchronously with the performance of the task. We tested the hypothesis that fcMRI maps, based on the synchrony of low-frequency blood flow fluctuations, identify brain regions that show activation on fMRI maps of sensorimotor, visual, language, and auditory tasks. METHODS: In four volunteers, task-activation fMRI and functional connectivity (restingstate) fcMRI data were acquired. A small region of interest (in an area that showed maximal task activation) was chosen, and the correlation coefficient of the corresponding resting-state signal with the signal of all other voxels in the resting data set was calculated. The correlation coefficient was decomposed into frequency components and its distribution determined for each fcMRI map. The fcMRI maps were compared with the fMRI maps. RESULTS: For each task, fcMRI maps based on one to four seed voxel(s) produced clusters of voxels in regions of eloquent cortex. For each fMRI map a closely corresponding fcMRI map was obtained. The frequencies that predominated in the cross-correlation coefficients for the functionally related regions were below 0.1 Hz. CONCLUSION: Functionally related brain regions can be identified by means of their synchronous slow fluctuations in signal intensity. Such blood flow synchrony can be detected in sensorimotor areas, expressive and receptive language regions, and the visual cortex by fcMRI. Regions identified by the slow synchronous fluctuations are similar to those activated by motor, language, or visual tasks.

http://www.ajnr.org/content/ajnr/21/9/1636.full.pdf

Mapping Functionally Related Regions of Brain with Functional Connectivity MR Imaging

https://sites.oxy.edu/clint/physio/article/Twoviewsofbrainfunction_raichle.pdf

Two views of brain function

Optical approaches to investigate cerebral function and metabolism have long been applied in invasive studies. From the neuron cultured in vitro to the exposed cortex in the human during neurosurgical procedures, high spatial resolution can be reached and several processes such as membrane potential, cell swelling, metabolism of mitochondrial chromophores, and vascular response can be monitored, depending on the respective preparation. The authors focus on an extension of optical methods to the noninvasive application in the human. Starting with the pioneering work of Jobsis 25 years ago, near-infrared spectroscopy (NIRS) has been used to investigate functional activation of the human cerebral cortex. Recently, several groups have started to use imaging systems that allow the generation of images of a larger area of the subject's head and, thereby, the production of maps of cortical oxygenation changes. Such images have a much lower spatial resolution compared with the invasively obtained optical images. The noninvasive NIRS images, however, can be obtained in undemanding set-ups that can be easily combined with other functional methods, in particular EEG. Moreover, NIRS is applicable to bedside use. The authors briefly review some of the abundant literature on intrinsic optical signals and the NIRS imaging studies of the past few years. The weaknesses and strengths of the approach are critically discussed. The authors conclude that NIRS imaging has two major advantages: it can address issues concerning neurovascular coupling in the human adult and can extend functional imaging approaches to the investigation of the diseased brain.

Beyond the Visible—Imaging the Human Brain with Light:

We have recently demonstrated using functional magnetic resonance imaging the presence of synchronous low-frequency fluctuations of signal intensities from the resting human brain that have a high degree of temporal correlation (p < 00001) both within and across the sensorimotor cortex A statistically significant overlap between the resting-state functional connectivity map and the task-activation map due to bilateral finger tapping was obtained Similar results have been obtained in the auditory and visual cortex Because the pulse sequence used for collecting data was sensitive to blood flow and blood oxygenation, these low-frequency fluctuations of signal intensity may have arisen from variations of both The objective of this study was simultaneously to determine the contribution of the blood oxygenation level signal and the flow signal to physiological fluctuations in the resting brain using the flow-sensitive alternating inversion recovery pulse sequence In all subjects, the functional connectivity maps obtained from BOLD had a greater coincidence with task-activation maps than the corresponding functional connectivity maps obtained from blood-flow signals at the same level of statistical significance Results of this study suggest that while variations in blood flow might contribute to functional connectivity maps, BOLD signals play a dominant role in the mechanism that gives rise to functional connectivity in the resting human brain

Simultaneous assessment of flow and BOLD signals in resting-state functional connectivity maps

To study the changes in cortical oxidative metabolism and blood volume during behavioral state transitions, we employed reflectance spectrophotometry of the cortical cytochrome c oxidase (cyt aa3) redox state and blood volume in unanesthetized cats implanted with bilateral cortical windows and EEG electrodes. Continuous oscillations in the redox state and blood volume (∼9/min) were observed during waking and sleep. These primarily metabolic oscillations of relatively high amplitude were usually synchronous in homotopic cortical areas, and persisted during barbiturate-induced electrocortical silence. Their mean amplitude and frequency did not vary across different behavioral/EEG states, although the mean levels of cyt aa3 oxidation and blood volume during rapid eye movement (REM) sleep significantly exceeded those during waking and slow-wave sleep. These data suggest the existence of a spontaneously oscillating metabolic phenomenon in cortex that is not directly related to neuroelectric activity. A superim...

Low-Frequency Oscillations of Cortical Oxidative Metabolism in Waking and Sleep

Interhemispheric synchrony of slow oscillations of cortical blood volume and cytochrome aa3 redox state in unanesthetized rabbits.

The purpose of this study was to determine the frequency characteristics and the degree of interhemispheric synchrony of slow (<0.5 Hz), spontaneous oscillations of the regional cortical cytochrome oxidase redox state (CYT) and blood volume (CBV) in unanesthetized animals. We implanted bilateral cortical windows and electrodes for polysomnography in 7 cats and 3 rabbits. The animals were atraumatically restrained during multiple 3–6 hour sessions for up to 8 weeks, and relative changes in the cortical CYT and CBV were monitored by dual wavelength reflectance spectrophotometry at 603 nm and 590 nm. Continuous oscillations of CYT and CBV, unrelated to pulse or respiration, were always observed in each animal. Frequency (FFT) analysis over time revealed a nonstationary distribution of frequencies below 0.4 Hz, with most of the spectral power being contained in the 0–0.25 Hz band during both waking and sleep. Although the time-frequency plots of the CYT and CBV signals were similar, an occasional dissociation between the CYT and CBV oscillations was found. Analysis of simultaneous bilateral cortical optical recordings revealed a significant and sustained interhemispheric cross-correlation over time between the CYT as well as the CBV oscillations during stable recordings as long as 60 min. We conclude that: 1) CYT and CBV levels normally oscillate at <0.4 Hz in the unanesthetized cat and rabbit cortex; 2) these complex oscillations, whose frequencies are non-stationary over time, nevertheless show sustained interhemispheric synchrony between 50 mm2 homotopic cortical regions; and 3) these oscillations may in part represent fluctuations of the metabolic rate.

Boris J. Leheta

Papers

Low-Frequency Oscillations of Cortical Oxidative Metabolism in Waking and Sleep

Interhemispheric synchrony of slow oscillations of cortical blood volume and cytochrome aa3 redox state in unanesthetized rabbits.

Slow Oscillations of Cytochrome Oxidase Redox State and Blood Volume in Unanesthetized Cat and Rabbit Cortex