The ability to discriminate signal from noise plays a key role in the analysis and interpretation of functional magnetic resonance imaging (fMRI) measures of brain activity. Over the past two ...decades, a number of major sources of noise have been identified, including system-related instabilities, subject motion, and physiological fluctuations. This article reviews the characteristics of the various noise sources as well as the mechanisms through which they affect the fMRI signal. Approaches for distinguishing signal from noise and the associated challenges are also reviewed. These challenges reflect the fact that some noise sources, such as respiratory activity, are generated by the same underlying brain networks that give rise to functional signals that are of interest.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The global signal is widely used as a regressor or normalization factor for removing the effects of global variations in the analysis of functional magnetic resonance imaging (fMRI) studies. However, ...there is considerable controversy over its use because of the potential bias that can be introduced when it is applied to the analysis of both task-related and resting-state fMRI studies. In this paper we take a closer look at the global signal, examining in detail the various sources that can contribute to the signal. For the most part, the global signal has been treated as a nuisance term, but there is growing evidence that it may also contain valuable information. We also examine the various ways that the global signal has been used in the analysis of fMRI data, including global signal regression, global signal subtraction, and global signal normalization. Furthermore, we describe new ways for understanding the effects of global signal regression and its relation to the other approaches.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
There has been growing interest in the use of resting-state functional magnetic resonance imaging (rsfMRI) for the assessment of disease and treatment, and a number of studies have reported ...significant disease-related changes in resting-state blood oxygenation level dependent (BOLD) signal amplitude and functional connectivity. rsfMRI is particularly suitable for clinical applications because the approach does not require the patient to perform a task and scans can be obtained in a relatively short amount of time. However, the mechanisms underlying resting-state BOLD activity are not well understood and thus the interpretation of changes in resting state activity is not always straightforward. The BOLD signal represents the hemodynamic response to neural activity, and changes in resting-state activity can reflect a complex combination of neural, vascular, and metabolic factors. This paper examines the role of neurovascular factors in rsfMRI and reviews approaches for the interpretation and analysis of resting state measures in the presence of confounding factors.
•Application of BOLD signal model in rsfMRI•Normalization and calibration methods in rsfMRI•Interpretation of rsfMRI studies in the presence of neurovascular confounds
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In resting-state functional magnetic resonance imaging (fMRI), functional connectivity measures can be influenced by the presence of a strong global component. A widely used pre-processing method for ...reducing the contribution of this component is global signal regression, in which a global mean time series signal is projected out of the fMRI time series data prior to the computation of connectivity measures. However, the use of global signal regression is controversial because the method can bias the correlation values to have an approximately zero mean and may in some instances create artifactual negative correlations. In addition, while many studies treat the global signal as a non-neural confound that needs to be removed, evidence from electrophysiological and fMRI measures in primates suggests that the global signal may contain significant neural correlates. In this study, we used simultaneously acquired fMRI and electroencephalographic (EEG) measures of resting-state activity to assess the relation between the fMRI global signal and EEG measures of vigilance in humans. We found that the amplitude of the global signal (defined as the standard deviation of the global signal) exhibited a significant negative correlation with EEG vigilance across subjects studied in the eyes-closed condition. In addition, increases in EEG vigilance due to the ingestion of caffeine were significantly associated with both a decrease in global signal amplitude and an increase in the average level of anti-correlation between the default mode network and the task-positive network.
•Global signal amplitude (GSamp) is negatively correlated with EEG vigilance.•Caffeine-induced decreases in GSamp are related to increases in EEG vigilance.•Increases in EEG vigilance are related to increases in DMN-TPN anti-correlation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A component based method (CompCor) for the reduction of noise in both blood oxygenation level-dependent (BOLD) and perfusion-based functional magnetic resonance imaging (fMRI) data is presented. In ...the proposed method, significant principal components are derived from noise regions-of-interest (ROI) in which the time series data are unlikely to be modulated by neural activity. These components are then included as nuisance parameters within general linear models for BOLD and perfusion-based fMRI time series data. Two approaches for the determination of the noise ROI are considered. The first method uses high-resolution anatomical data to define a region of interest composed primarily of white matter and cerebrospinal fluid, while the second method defines a region based upon the temporal standard deviation of the time series data. With the application of CompCor, the temporal standard deviation of resting-state perfusion and BOLD data in gray matter regions was significantly reduced as compared to either no correction or the application of a previously described retrospective image based correction scheme (RETROICOR). For both functional perfusion and BOLD data, the application of CompCor significantly increased the number of activated voxels as compared to no correction. In addition, for functional BOLD data, there were significantly more activated voxels detected with CompCor as compared to RETROICOR. In comparison to RETROICOR, CompCor has the advantage of not requiring external monitoring of physiological fluctuations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Changes in vigilance or alertness during a typical resting state fMRI scan are inevitable and have been found to affect measures of functional brain connectivity. Since it is not often feasible to ...monitor vigilance with EEG during fMRI scans, it would be of great value to have methods for estimating vigilance levels from fMRI data alone. A recent study, conducted in macaque monkeys, proposed a template-based approach for fMRI-based estimation of vigilance fluctuations. Here, we use simultaneously acquired EEG/fMRI data to investigate whether the same template-based approach can be employed to estimate vigilance fluctuations of awake humans across different resting-state conditions. We first demonstrate that the spatial pattern of correlations between EEG-defined vigilance and fMRI in our data is consistent with the previous literature. Notably, however, we observed a significant difference between the eyes-closed (EC) and eyes-open (EO) conditions, finding stronger negative correlations with vigilance in regions forming the default mode network and higher positive correlations in thalamus and insula in the EC condition when compared to the EO condition. Taking these correlation maps as “templates” for vigilance estimation, we found that the template-based approach produced fMRI-based vigilance estimates that were significantly correlated with EEG-based vigilance measures, indicating its generalizability from macaques to humans. We also demonstrate that the performance of this method was related to the overall amount of variability in a subject's vigilance state, and that the template-based approach outperformed the use of the global signal as a vigilance estimator. In addition, we show that the template-based approach can be used to estimate the variability across scans in the amplitude of the vigilance fluctuations. We discuss the benefits and tradeoffs of using the template-based approach in future fMRI studies.
•Template-based approach can be used to estimate vigilance fluctuations of awake humans at rest.•The approach can be used when external vigilance monitoring (such as with EEG) is not feasible.•Performance of this method is related to the amount of variability in a subject's vigilance state.•It can be used to estimate the variability across runs in the amplitude of the vigilance fluctuations.•Template-based approach outperforms the use of the global signal as a vigilance estimator.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Improving cerebrovascular function may be a key mechanism whereby a healthy lifestyle, of which a healthy diet combined with increased physical activity levels is a cornerstone, protects against ...cognitive impairments. In this respect, effects on cerebral blood flow (CBF)-a sensitive physiological marker of cerebrovascular function-are of major interest. This review summarizes the impact of specific dietary determinants and physical exercise on CBF in adults and discusses the relation between these effects with potential changes in cognitive function. A limited number of randomized controlled trials have already demonstrated the beneficial effects of an acute intake of nitrate and polyphenols on CBF, but evidence for a relationship between these effects as well as improvements in cognitive functioning is limited. Moreover, long-term trans-resveratrol supplementation has been shown to increase CBF in populations at increased risk of accelerated cognitive decline. Long-term supplementation of
long-chain polyunsaturated fatty acids may also increase CBF, but related effects on cognitive performance have not yet been found. Significant decreases in cerebral perfusion were observed by commonly consumed amounts of caffeine, while alcohol intake was shown to increase CBF in a dose-dependent way. However, the long-term effects are not clear. Finally, long-term exercise training may be a promising approach to improve CBF, as increases in perfusion may contribute to the beneficial effects on cognitive functioning observed following increased physical activity levels.
In resting-state functional connectivity magnetic resonance imaging (fcMRI) studies, measures of functional connectivity are often calculated after the removal of a global mean signal component. ...While the application of the global signal regression approach has been shown to reduce the influence of physiological artifacts and enhance the detection of functional networks, there is considerable controversy regarding its use as the method can lead to significant bias in the resultant connectivity measures. In addition, evidence from recent studies suggests that the global signal is linked to neural activity and may carry clinically relevant information. For instance, in a prior study we found that the amplitude of the global signal was negatively correlated with EEG measures of vigilance across subjects and experimental runs. Furthermore, caffeine-related decreases in global signal amplitude were associated with increases in EEG vigilance. In this study, we extend the prior work by examining measures of global signal amplitude and EEG vigilance under eyes-closed (EC) and eyes-open (EO) resting-state conditions. We show that changes (EO minus EC) in the global signal amplitude are negatively correlated with the associated changes in EEG vigilance. The slope of this EO–EC relation is comparable with the slope of the previously reported relation between caffeine-related changes in the global signal amplitude and EEG vigilance. Our findings provide further support for a basic relationship between global signal amplitude and EEG vigilance.
•Abbreviations: global signal amplitude (GSamp); eyes open (EO); eyes closed (EC)•Changes (EO–EC) in GSamp are inversely correlated with changes in EEG vigilance.•EO–EC relation between GSamp and vigilance is comparable to caffeine-related relation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The ability to discriminate signal from noise plays a key role in the analysis and interpretation of functional magnetic resonance imaging (fMRI) measures of brain activity. Over the past two ...decades, a number of major sources of noise have been identified, including system-related instabilities, subject motion, and physiological fluctuations. This article reviews the characteristics of the various noise sources as well as the mechanisms through which they affect the fMRI signal. Approaches for distinguishing signal from noise and the associated challenges are also reviewed. These challenges reflect the fact that some noise sources, such as respiratory activity, are generated by the same underlying brain networks that give rise to functional signals that are of interest.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Measures of resting-state functional magnetic resonance imaging (rsfMRI) activity have been shown to be sensitive to cognitive function and disease state. However, there is growing evidence that ...variations in vigilance can lead to pronounced and spatially widespread differences in resting-state brain activity. Unless properly accounted for, differences in vigilance can give rise to changes in resting-state activity that can be misinterpreted as primary cognitive or disease-related effects. In this paper, we examine in detail the link between vigilance and rsfMRI measures, such as signal variance and functional connectivity. We consider how state changes due to factors such as caffeine and sleep deprivation affect both vigilance and rsfMRI measures and review emerging approaches and methodological challenges for the estimation and interpretation of vigilance effects.
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