Advances in functional magnetic resonance imaging (fMRI) acquisition have improved signal to noise to the point where the physiology of the subject is the dominant noise source in resting state fMRI data (rsfMRI). Among these systemic, non-neuronal physiological signals, respiration and to some degree cardiac fluctuations can be removed through modeling, or in the case of newer, faster acquisitions such as simultaneous multislice acquisition, simple spectral filtering. However, significant low frequency physiological oscillation (∼0.01-0.15 Hz) remains in the signal. This is problematic, as it is the precise frequency band occupied by the neuronally modulated hemodynamic responses used to study brain connectivity, precluding its removal by spectral filtering. The source of this signal, and its method of production and propagation in the body, have not been conclusively determined. Here, we summarize the defining characteristics of the systemic low frequency noise signal, and review some current theories about the signal source and the evidence supporting them. The strength and distribution of the systemic LFO signal make characterizing and removing it essential for accurate quantification, especially for resting state connectivity, when no stimulation can be compared with the signal. Widespread correlated non-neuronal signals obscure and distort the more localized patterns of neuronal correlations between interacting brain regions; they may even cause apparent connectivity between regions with no neuronal interaction. Here, we discuss a simple method we have developed to parse the global, moving, blood-borne signal from the stationary, neuronal connectivity signals, substantially reducing the negative correlations that result from global signal regression. Finally, we will discuss some of the uses to which the moving systemic low frequency oscillation can be put if we consider it a "signal" carrying information, rather than simply "noise" complicating the interpretation of resting state connectivity. Properly utilizing this signal may offer insights into subtle hemodynamic alterations that can be used as early indicators of circulatory dysfunction in a number of neuropsychiatric conditions, such as prodromal stroke, moyamoya, and Alzheimer's disease.

With the rapid increase in new fNIRS users employing commercial software, there is a concern that many studies are biased by suboptimal processing methods. The purpose of this study is to provide a visual reference showing the effects of different processing methods, to help inform researchers in setting up and evaluating a processing pipeline. We show the significant impact of pre- and post-processing choices and stress again how important it is to combine data from both hemoglobin species in order to make accurate inferences about the activation site.

Low-frequency oscillations (LFOs) in the range of 0.01–0.15 Hz are commonly observed in functional imaging studies, such as blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) and functional near-infrared spectroscopy (fNIRS). Some of these LFOs are nonneuronal and are closely related to autonomic physiological processes. In the current study, we conducted a concurrent resting-state fMRI and NIRS experiment with healthy volunteers. LFO data was collected simultaneously at peripheral sites (middle fingertip and big toes) by NIRS, and centrally in the brain by BOLD fMRI. The cross-correlations of the LFOs collected from the finger, toes, and brain were calculated. Our data show that the LFOs measured in the periphery (NIRS signals) and in the brain (BOLD fMRI) were strongly correlated with varying time delays. This demonstrates that some portion of the LFOs actually reflect systemic physiological circulatory effects. Furthermore, we demonstrated that NIRS is effective for measuring the peripheral LFOs, and that these LFOs and the temporal shifts between them are consistent in healthy participants and may serve as useful biomarkers for detecting and monitoring circulatory dysfunction.

Blood oxygenation level-dependent fMRI contrast depends on the volume and oxygenation of blood flowing through the circulatory system. The effects on image intensity depend temporally on the arrival of blood within a voxel, and signal can be monitored during the time course of such blood flow. It has been previously shown that the passage of global endogenous variations in blood volume and oxygenation can be tracked as blood passes through the brain by determining the strength and peak time lag of their cross-correlation with blood oxygenation level-dependent data. By manipulating blood composition using transient hypercarbia and hyperoxia, we can induce much larger oxygenation and volume changes in the blood oxygenation level-dependent signal than result from natural endogenous fluctuations. This technique was used to examine cerebrovascular parameters in healthy subjects (n = 8) and subjects with intracranial stenosis (n = 22), with a subgroup of intracranial stenosis subjects scanned before and after surgical revascularization (n = 6). The halfwidth of cross-correlation lag times in the brain was larger in IC stenosis subjects (21.21 ± 14.22 s) than in healthy control subjects (8.03 ± 3.67), p < 0.001, and was subsequently reduced in regions that co-localized with surgical revascularization. These data show that blood circulatory timing can be measured robustly and longitudinally throughout the brain using simple respiratory challenges.