Blood Oxygen Level-dependent Fluctuations Research Articles

On the interplay between state-dependent reconfigurations of global signal correlation and BOLD fluctuations: An fMRI study

BackgroundThe dynamics of global, state-dependent reconfigurations in brain connectivity are yet unclear. We aimed at assessing reconfigurations of the global signal correlation coefficient (GSCORR), a measure of the connectivity between each voxel timeseries and the global signal, from resting-state to a stop-signal task. The secondary aim was to assess the relationship between GSCORR and blood-oxygen-level-dependent (BOLD) activations or deactivation across three different trial-conditions (GO, STOP-correct, and STOP-incorrect). MethodsAs primary analysis we computed whole-brain, voxel-wise GSCORR during resting-state (GSCORR-rest) and stop-signal task (GSCORR-task) in 107 healthy subjects aged 21–50, deriving GSCORR-shift as GSCORR-task minus GSCORR-rest. GSCORR-tr and trGSCORR-shift were also computed on the task residual time series to quantify the impact of the task-related activity during the trials. To test the secondary aim, brain regions were firstly divided in one cluster showing significant task-related activation and one showing significant deactivation across the three trial conditions. Then, correlations between GSCORR-rest/task/shift and activation/deactivation in the two clusters were computed. As sensitivity analysis, GSCORR-shift was computed on the same sample after performing a global signal regression and GSCORR-rest/task/shift were correlated with the task performance. ResultsSensory and temporo-parietal regions exhibited a negative GSCORR-shift. Conversely, associative regions (ie. left lingual gyrus, bilateral dorsal posterior cingulate gyrus, cerebellum areas, thalamus, posterolateral parietal cortex) displayed a positive GSCORR-shift (FDR-corrected p < 0.05). GSCORR-shift showed similar patterns to trGSCORR-shift (magnitude increased) and after global signal regression (magnitude decreased). Concerning BOLD changes, Brodmann area 6 and inferior parietal lobule showed activation, while posterior parietal lobule, cuneus, precuneus, middle frontal gyrus showed deactivation (FDR-corrected p < 0.05). No correlations were found between GSCORR-rest/task/shift and beta-coefficients in the activation cluster, although negative correlations were observed between GSCORR-task and GO/STOP-correct deactivation (Pearson rho=-0.299/-0.273; Bonferroni-p < 0.05). Weak associations between GSCORR and task performance were observed (uncorrected p < 0.05). ConclusionGSCORR state-dependent reconfiguration indicates a reallocation of functional resources to associative areas during stop-signal task. GSCORR, activation and deactivation may represent distinct proxies of brain states with specific neurofunctional relevance.

Quantification of mediation effects of white matter functional characteristics on cognitive decline in aging.

Cognitive decline with aging involves multifactorial processes, including changes in brain structure and function. This study focuses on the role of white matter functional characteristics, as reflected in blood oxygenation level-dependent signals, in age-related cognitive deterioration. Building on previous research confirming the reproducibility and age-dependence of blood oxygenation level-dependent signals acquired via functional magnetic resonance imaging, we here employ mediation analysis to test if aging affects cognition through white matter blood oxygenation level-dependent signal changes, impacting various cognitive domains and specific white matter regions. We used independent component analysis of resting-state blood oxygenation level-dependent signals to segment white matter into coherent hubs, offering a data-driven view of white matter's functional architecture. Through correlation analysis, we constructed a graph network and derived metrics to quantitatively assess regional functional properties based on resting-state blood oxygenation level-dependent fluctuations. Our analysis identified significant mediators in the age-cognition relationship, indicating that aging differentially influences cognitive functions by altering the functional characteristics of distinct white matter regions. These findings enhance our understanding of the neurobiological basis of cognitive aging, highlighting the critical role of white matter in maintaining cognitive integrity and proposing new approaches to assess interventions targeting cognitive decline in older populations.

Altered Resting‐state fMRI BOLD Signal Fluctuations in the Spectrum of Alzheimer’s Dementia and in Patients with White Matter Hyperintensities

AbstractBackgroundAltered fluctuations in blood oxygen level dependent (BOLD) signal during resting‐state functional magnetic resonance imaging (rs‐fMRI) have been considered indicative of decreased cerebrovascular health. Previous studies reported changes in BOLD fluctuations associated with Alzheimer’s dementia (AD) and white matter hyperintensities (WMH). However, to date, there has been no large‐scale study involving patients with AD, mild cognitive impairment (MCI), subjective cognitive decline (SCD), and control subjects (CON) that has explored local AD‐ and WMH‐related effects in BOLD fluctuations.MethodWe calculated the voxel‐based coefficient of variation (CV: standard deviation divided by the mean) and the relative CV (rCV: CV divided by the mean CV of the whole‐brain) of the rs‐fMRI BOLD signal in the large multicentric DZNE DELCODE cohort. After spatial preprocessing, regression of movement parameters, movement spikes, and scanner drift, low‐pass filtering and exclusion of subjects with high motion, CV and rCV maps were obtained and compared with respect to (A) clinical diagnosis (AD: n = 79; MCI: n = 113; SCD: n = 314; CON: n = 192) and cerebrospinal fluid Aß42/40 (AD: n = 41; MCI: n = 64; SCD: n = 139; CON: n = 77); and (B) effects of vascular‐related lesions, here WMH.ResultThe CV and rCV of the precuneus and middle cingulum indicated increasingly reduced BOLD fluctuation across the clinical groups towards AD. Interestingly, we observed increases in rCV in the basal ganglia and frontal white matter in AD compared with CON. Of note, lower CSF Aß42/40 (more pathological) was associated to reduced CV and rCV in the precuneus and with lower rCV in the right angular gyrus. Subjects with higher WMH volume showed widespread reductions of CV in white matter near the left angular gyrus and reduced rCV in large portions of white matter and subcortical gray matter.ConclusionThe AD spectrum exhibits altered BOLD fluctuations that are at least partially tied to actual amyloid differences. Larger WMH are associated with reduced BOLD signal fluctuations consistent with widespread white matter pathology ‐ beyond the effects of diagnosis. We argue that rCV is a useful complement to CV to detect these changes that might reflect cerebrovascular impairment.

Altered Resting‐state fMRI BOLD Signal Fluctuations in the Spectrum of Alzheimer’s Dementia and in Patients with White Matter Hyperintensities

AbstractBackgroundAltered fluctuations in blood oxygen level dependent (BOLD) signal during resting‐state functional magnetic resonance imaging (rs‐fMRI) have been considered indicative of decreased cerebrovascular health. Previous studies reported changes in BOLD fluctuations associated with Alzheimer’s dementia (AD) and white matter hyperintensities (WMH). However, to date, there has been no large‐scale study involving patients with AD, mild cognitive impairment (MCI), subjective cognitive decline (SCD), and control subjects (CON) that has explored local AD‐ and WMH‐related effects in BOLD fluctuations.MethodWe calculated the voxel‐based coefficient of variation (CV: standard deviation divided by the mean) and the relative CV (rCV: CV divided by the mean CV of the whole‐brain) of the rs‐fMRI BOLD signal in the large multicentric DZNE DELCODE cohort. After spatial preprocessing, regression of movement parameters, movement spikes, and scanner drift, low‐pass filtering and exclusion of subjects with high motion, CV and rCV maps were obtained and compared with respect to (A) clinical diagnosis (AD: n = 79; MCI: n = 113; SCD: n = 314; CON: n = 192) and cerebrospinal fluid Aβ42/40 (AD: n = 41; MCI: n = 64; SCD: n = 139; CON: n = 77); and (B) effects of vascular‐related lesions, here WMH.ResultThe CV and rCV of the precuneus and middle cingulum indicated increasingly reduced BOLD fluctuation across the clinical groups towards AD. Interestingly, we observed increases in rCV in the basal ganglia and frontal white matter in AD compared with CON. Of note, lower CSF Aβ42/40 (more pathological) was associated to reduced CV and rCV in the precuneus and with lower rCV in the right angular gyrus. Subjects with higher WMH volume showed widespread reductions of CV in white matter near the left angular gyrus and reduced rCV in large portions of white matter and subcortical gray matter.ConclusionThe AD spectrum exhibits altered BOLD fluctuations that are at least partially tied to actual amyloid differences. Larger WMH are associated with reduced BOLD signal fluctuations consistent with widespread white matter pathology ‐ beyond the effects of diagnosis. We argue that rCV is a useful complement to CV to detect these changes that might reflect cerebrovascular impairment.

Neuromodulation of striatal D1 cells shapes BOLD fluctuations in anatomically connected thalamic and cortical regions.

Understanding how the brain's macroscale dynamics are shaped by underlying microscale mechanisms is a key problem in neuroscience. In animal models, we can now investigate this relationship in unprecedented detail by directly manipulating cellular-level properties while measuring the whole-brain response using resting-state fMRI. Here, we focused on understanding how blood-oxygen-level-dependent (BOLD) dynamics, measured within a structurally well-defined striato-thalamo-cortical circuit in mice, are shaped by chemogenetically exciting or inhibiting D1 medium spiny neurons (MSNs) of the right dorsomedial caudate putamen (CPdm). We characterize changes in both the BOLD dynamics of individual cortical and subcortical brain areas, and patterns of inter-regional coupling (functional connectivity) between pairs of areas. Using a classification approach based on a large and diverse set of time-series properties, we found that CPdm neuromodulation alters BOLD dynamics within thalamic subregions that project back to dorsomedial striatum. In the cortex, changes in local dynamics were strongest in unimodal regions (which process information from a single sensory modality) and weakened along a hierarchical gradient towards transmodal regions. In contrast, a decrease in functional connectivity was observed only for cortico-striatal connections after D1 excitation. Our results show that targeted cellular-level manipulations affect local BOLD dynamics at the macroscale, such as by making BOLD dynamics more predictable over time by increasing its self-correlation structure. This contributes to ongoing attempts to understand the influence of structure-function relationships in shaping inter-regional communication at subcortical and cortical levels.

Non-invasive estimation of arterial blood pressure fluctuations using a peripheral photoplethysmograph inside the MRI scanner.

The blood-oxygen-level-dependent (BOLD) signal measured by functional magnetic resonance imaging (fMRI) is modulated by neural activity through the neurovascular coupling effect, as well as non-neural factors of physiological origin such as heart rate, respiration, and arterial blood pressure (ABP). While the former two effects have been previously characterized, the modulation of the BOLD signal by ABP fluctuations is still poorly understood. This is largely due to the difficulty of obtaining reliable ABP measurements in the MRI environment. Here, we propose a combined experimental and mathematical modeling framework to estimate ABP fluctuations inside the MRI scanner using photoplethysmography (PPG). Specifically, we used concurrent PPG and ABP measurements obtained outside the scanner to train the mathematical model and applied it to PPG measurements obtained inside the MRI scanner. Our results suggest good agreement between the model-predicted and experimentally measured ABP fluctuations and region specific correlations with the BOLD fluctuations.

Reliability of resting-state functional connectivity in the human spinal cord: Assessing the impact of distinct noise sources

The investigation of spontaneous fluctuations of the blood-oxygen-level-dependent (BOLD) signal has recently been extended from the brain to the spinal cord, where it has stimulated interest from a clinical perspective. A number of resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated robust functional connectivity between the time series of BOLD fluctuations in bilateral dorsal horns and between those in bilateral ventral horns, in line with the functional neuroanatomy of the spinal cord. A necessary step prior to extension to clinical studies is assessing the reliability of such resting-state signals, which we aimed to do here in a group of 45 healthy young adults at the clinically prevalent field strength of 3T. When investigating connectivity in the entire cervical spinal cord, we observed fair to good reliability for dorsal-dorsal and ventral-ventral connectivity, whereas reliability was poor for within- and between-hemicord dorsal-ventral connectivity. Considering how prone spinal cord fMRI is to noise, we extensively investigated the impact of distinct noise sources and made two crucial observations: removal of physiological noise led to a reduction in functional connectivity strength and reliability – due to the removal of stable and participant-specific noise patterns – whereas removal of thermal noise considerably increased the detectability of functional connectivity without a clear influence on reliability. Finally, we also assessed connectivity within spinal cord segments and observed that while the pattern of connectivity was similar to that of whole cervical cord, reliability at the level of single segments was consistently poor. Taken together, our results demonstrate the presence of reliable resting-state functional connectivity in the human spinal cord even after thoroughly accounting for physiological and thermal noise, but at the same time urge caution if focal changes in connectivity (e.g. due to segmental lesions) are to be studied, especially in a longitudinal manner.

Abnormal Spontaneous Blood Oxygenation Level Dependent Fluctuations in Children with Focal Cortical Dysplasias: Initial Findings in Surgically Confirmed Cases.

Focal cortical dysplasias (FCD) are a frequent cause of drug-resistant epilepsy in children but are often undetected on structural magnetic resonance imaging (MRI). We aimed to measure and validate the variation of resting state functional MRI (rs-fMRI) blood oxygenation level dependent (BOLD) metrics in surgically proven FCDs in children, to assess the potential yield for detecting and understanding these lesions. We prospectively included pediatric patients with surgically proven FCD with inconclusive structural MRI and healthy controls, who underwent a ten-minute rs-fMRI acquired at 3T. Rs-fMRI data was pre-processed and maps of values of regional homogeneity (ReHo), degree centrality (DC), amplitude of low frequency fluctuations (ALFF) and fractional ALFF (fALFF) were calculated. The variations of BOLD metrics within the to-be-resected areas were analyzed visually, and quantitatively using lateralization indices. BOLD metrics variations were also analyzed in fluorodeoxyglucose-positron emission tomography (FDG-PET) hypometabolic areas. We included 7 patients (range: 3-15 years) and 6 aged-matched controls (range: 6-17 years). ReHo lateralization indices were positive in the to-be-resected areas in 4/7 patients, and in 6/7 patients in the additional PET hypometabolic areas. These indices were significantly higher compared to controls in 3/7 and 4/7 patients, respectively. Visual analysis revealed a good spatial correlation between high ReHo areas and MRI structural abnormalities (when present) or PET hypometabolic areas. No consistent variation was seen using DC, ALFF, or fALFF. Resting-state fMRI metrics, noticeably increase in ReHo, may have potential to help detect MRI-negative FCDs in combination with other morphological and functional techniques, used in clinical practice and epilepsy-surgery screening.

Genome-wide association study of the human brain functional connectome reveals strong vascular component underlying global network efficiency

Complex brain networks play a central role in integrating activity across the human brain, and such networks can be identified in the absence of any external stimulus. We performed 10 genome-wide association studies of resting state network measures of intrinsic brain activity in up to 36,150 participants of European ancestry in the UK Biobank. We found that the heritability of global network efficiency was largely explained by blood oxygen level-dependent (BOLD) resting state fluctuation amplitudes (RSFA), which are thought to reflect the vascular component of the BOLD signal. RSFA itself had a significant genetic component and we identified 24 genomic loci associated with RSFA, 157 genes whose predicted expression correlated with it, and 3 proteins in the dorsolateral prefrontal cortex and 4 in plasma. We observed correlations with cardiovascular traits, and single-cell RNA specificity analyses revealed enrichment of vascular related cells. Our analyses also revealed a potential role of lipid transport, store-operated calcium channel activity, and inositol 1,4,5-trisphosphate binding in resting-state BOLD fluctuations. We conclude that that the heritability of global network efficiency is largely explained by the vascular component of the BOLD response as ascertained by RSFA, which itself has a significant genetic component.

Brain microstructural alterations in the left precuneus mediate the association between KIBRA polymorphism and working memory in healthy adults: a diffusion kurtosis imaging study

Kidney and brain expressed protein (KIBRA) rs17070145 is associated with working memory function and cognitive processes. However, the neural mechanisms underlying these associations are not fully understood. This study aimed to explore the effect of KIBRA polymorphism on brain microstructure and blood oxygenation level dependent (BOLD) fluctuations using diffusion kurtosis imaging (DKI) and resting-state functional magnetic resonance imaging (fMRI) in 163 young adults. We also investigated that whether the imaging alterations mediated the association between KIBRA gene and working memory performance. Voxel-based analysis of DKI data showed that KIBRA C-allele carriers exhibited increased axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) as well as decreased fractional anisotropy (FA), mean kurtosis (MK) and radial kurtosis (RK) compared with KIBRA TT homozygotes, primarily involving the prefrontal lobe, left precuneus and the left superior parietal white matter. Meanwhile, KIBRA C-allele carriers exhibited decreased amplitude of low-frequency fluctuation (ALFF) in the left precuneus compared to KIBRA TT homozygotes. Mediation analysis revealed that the DKI metrics (MK and RK) of the left precuneus mediated the effect of the KIBRA polymorphism on working memory performance. Moreover, the MK and RK in the left precuneus were positively correlated with ALFF in the same brain region. These findings suggest that abnormal DKI parameters may provide a gene-brain-behavior pathway in which KIBRA rs17070145 affects working memory by modulating brain microstructure in the left precuneus. This illustrates that DKI may provide additional biological information and reveal new insights into the neural mechanisms of the KIBRA polymorphism.

Typical resting-state activity of the brain requires visual input during an early sensitive period.

Sensory deprivation, following a total loss of one sensory modality e.g. vision, has been demonstrated to result in compensatory plasticity. It is yet not known to which extent neural changes, e.g. higher resting-state activity in visual areas (cross-modal plasticity) as a consequence of blindness, reverse, when sight is restored. Here, we used functional MRI to acquire blood oxygen level-dependent resting-state activity during an eyes open and an eyes closed state in congenital cataract-reversal individuals, developmental cataract-reversal individuals, congenitally permanently blind individuals and sighted controls. The amplitude of low frequency fluctuation of the blood oxygen level-dependent signal—a neural marker of spontaneous brain activity during rest—was analyzed. In accordance with previous reports, in normally sighted controls we observed an increase in amplitude of low-frequency fluctuation during rest with the eyes open compared with rest with eyes closed in visual association areas and in parietal cortex but a decrease in auditory and sensorimotor regions. In congenital cataract-reversal individuals, we found an increase of the amplitude of slow blood oxygen level-dependent fluctuations in visual cortex during rest with eyes open compared with rest with eyes closed too but this increase was larger in amplitude than in normally sighted controls. In contrast, congenital cataract-reversal individuals lagged a similar increase in parietal regions and did not show the typical decrease of amplitude of low-frequency fluctuation in auditory cortex. Congenitally blind individuals displayed an overall higher amplitude in slow blood oxygen level-dependent fluctuations in visual cortex compared with sighted individuals and compared with congenital cataract-reversal individuals in the eyes closed condition. Higher amplitude of low-frequency fluctuation in visual cortex of congenital cataract-reversal individuals than in normally sighted controls during eyes open might indicate an altered excitatory–inhibitory balance of visual neural circuits. By contrast, the lower parietal increase and the missing downregulation in auditory regions suggest a reduced influence of the visual system on multisensory and the other sensory systems after restoring sight in congenitally blind individuals. These results demonstrate a crucial dependence of visual and multisensory neural system functioning on visual experience during a sensitive phase in human brain development.

Static and dynamic BOLD fMRI components along white matter fibre tracts and their dependence on the orientation of the local diffusion tensor axis relative to the B0-field

Recent studies have reported functional MRI (fMRI) activation within cerebral white matter (WM) using blood-oxygenation-level-dependent (BOLD) contrast. Many blood vessels in WM run parallel to the fibre bundles, and other studies observed dependence of susceptibility contrast-based measures of blood volume on the local orientation of the fibre bundles relative to the magnetic field or B0 axis. Motivated by this, we characterized the dependence of gradient-echo BOLD fMRI on fibre orientation (estimated by the local diffusion tensor) relative to the B0 axis to test whether the alignment between bundles and vessels imparts an orientation dependence on resting-state BOLD fluctuations in the WM. We found that the baseline signal level of the T2*-weighted data is 11% higher in voxels containing fibres parallel to B0 than those containing perpendicular fibres, consistent with a static influence of either fibre or vessel orientation on local T2* values. We also found that BOLD fluctuations in most bundles exhibit orientation effects expected from oxygenation changes, with larger amplitudes from voxels containing perpendicular fibres. Different magnitudes of this orientation effect were observed across the major WM bundles, with inferior fasciculus, corpus callosum and optic radiation exhibiting 14–19% higher fluctuations in voxels containing perpendicular compared to parallel fibres.

Altered Brain Activity in Depression of Parkinson's Disease: A Meta-Analysis and Validation Study.

BackgroundThe pathophysiology of depression in Parkinson’s disease (PD) is not fully understood. Studies based upon functional MRI (fMRI) showed the alterations in the blood-oxygen-level-dependent (BOLD) fluctuations in multiple brain regions pertaining to depression in PD. However, large variance was observed across previous studies. Therefore, we conducted a meta-analysis to quantitatively evaluate the results in previous publications and completed an independent regions-of-interests (ROIs)-based analysis using our own data to validate the results of the meta-analysis.MethodsWe searched PubMed, Embase, and Web of Science to identify fMRI studies in PD patients with depression. Using signed differential mapping (SDM) method, we performed a voxel-based meta-analysis. Then, a validation study by using multiscale entropy (MSE) in 28 PD patients with depression and 25 PD patients without depression was conducted. The fMRI scan was completed in anti-depression-medication-off state. The ROIs of the MSE analysis were the regions identified by the meta-analysis.ResultsA total of 126 PD patients with depression and 153 PD patients without depression were included in meta-analysis. It was observed that the resting-state activities within the posterior cingulate gyrus, supplementary motor area (SMA), and cerebellum were altered in depressed patients. Then, in the validation study, these regions were used as ROIs. PD patients with depression had significantly lower MSE of the BOLD fluctuations in these regions (posterior cingulate gyrus: F = 0.856, p = 0.049; SMA: F = 0.914, p = 0.039; cerebellum: F = 0.227, p = 0.043).ConclusionOur study revealed that the altered BOLD activity in cingulate, SMA, and cerebellum of the brain were pertaining to depression in PD.

Functional Connectivity of the Brain Across Rodents and Humans.

Resting-state functional magnetic resonance imaging (rs-fMRI), which measures the spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signal, is increasingly utilized for the investigation of the brain’s physiological and pathological functional activity. Rodents, as a typical animal model in neuroscience, play an important role in the studies that examine the neuronal processes that underpin the spontaneous fluctuations in the BOLD signal and the functional connectivity that results. Translating this knowledge from rodents to humans requires a basic knowledge of the similarities and differences across species in terms of both the BOLD signal fluctuations and the resulting functional connectivity. This review begins by examining similarities and differences in anatomical features, acquisition parameters, and preprocessing techniques, as factors that contribute to functional connectivity. Homologous functional networks are compared across species, and aspects of the BOLD fluctuations such as the topography of the global signal and the relationship between structural and functional connectivity are examined. Time-varying features of functional connectivity, obtained by sliding windowed approaches, quasi-periodic patterns, and coactivation patterns, are compared across species. Applications demonstrating the use of rs-fMRI as a translational tool for cross-species analysis are discussed, with an emphasis on neurological and psychiatric disorders. Finally, open questions are presented to encapsulate the future direction of the field.

Disrupted White Matter Functional Connectivity With the Cerebral Cortex in Migraine Patients.

Background: In attempts to understand the migraine patients’ overall brain functional architecture, blood oxygenation level-dependent (BOLD) signals in the white matter (WM) and gray matter (GM) were considered in the current study. Migraine, a severe and multiphasic brain condition, is characterized by recurrent attacks of headaches. BOLD fluctuations in a resting state exhibit similar temporal and spectral profiles in both WM and GM. It is feasible to explore the functional interactions between WM tracts and GM regions in migraine.Methods: Forty-eight migraineurs without aura (MWoA) and 48 healthy controls underwent resting-state functional magnetic resonance imaging. Pearson’s correlations between the mean time courses of 48 white matter (WM) bundles and 82 gray matter (GM) regions were computed for each subject. Two-sample t-tests were performed on the Pearson’s correlation coefficients (CC) to compare the differences between the MWoA and healthy controls in the GM-averaged CC of each bundle and the WM-averaged CC of each GM region.Results: The MWoAs exhibited an overall decreased average temporal CC between BOLD signals in 82 GM regions and 48 WM bundles compared with healthy controls, while little was increased. In particular, WM bundles such as left anterior corona radiata, left external capsule and bilateral superior longitudinal fasciculus had significantly decreased mean CCs with GM in MWoA. On the other hand, 16 GM regions had significantly decreased mean CCs with WM in MWoA, including some areas that are parts of the somatosensory regions, auditory cortex, temporal areas, frontal areas, cingulate cortex, and parietal cortex.Conclusion: Decreased functional connections between WM bundles and GM regions might contribute to disrupted functional connectivity between the parts of the pain processing pathway in MWoAs, which indicated that functional and connectivity abnormalities in cortical regions may not be limited to GM regions but are instead associated with functional abnormalities in WM tracts.

Relationships between correlated spikes, oxygen and LFP in the resting-state primate

Resting-state functional MRI (rsfMRI) provides a view of human brain organization based on correlation patterns of blood oxygen level dependent (BOLD) signals recorded across the whole brain. The neural basis of resting-state BOLD fluctuations and their correlation remains poorly understood. We simultaneously recorded oxygen level, spikes, and local field potential (LFP) at multiple sites in awake, resting monkeys. Following a spike, the average local oxygen and LFP voltage responses each resemble a task-driven BOLD response, with LFP preceding oxygen by 0.5 s. Between sites, features of the long-range correlation patterns of oxygen, LFP, and spikes are similar to features seen in rsfMRI. Most of the variance shared between sites lies in the infraslow frequency band (0.01–0.1 Hz) and in the infraslow envelope of higher-frequency bands (e.g. gamma LFP). While gamma LFP and infraslow LFP are both strong correlates of local oxygen, infraslow LFP explains significantly more of the variance shared between correlated oxygen signals than any other electrophysiological signal. Together these findings are consistent with a causal relationship between infraslow LFP and long-range oxygen correlations in the resting state.

Resting-state functional MRI signal fluctuation amplitudes are correlated with brain amyloid-β deposition in patients with mild cognitive impairment

Mounting evidence suggests that amyloid-β (Aβ) and vascular etiologies are intertwined in the pathogenesis of Alzheimer’s disease (AD). Blood-oxygen-level-dependent (BOLD) signals, measured by resting-state functional MRI (rs-fMRI), are associated with neuronal activity and cerebrovascular hemodynamics. Nevertheless, it is unclear if BOLD fluctuations are associated with Aβ deposition in individuals at high risk of AD. Thirty-three patients with amnestic mild cognitive impairment underwent rs-fMRI and AV45 PET. The AV45 standardized uptake value ratio (AV45-SUVR) was calculated using cerebral white matter as reference, to assess Aβ deposition. The whole-brain normalized amplitudes of low-frequency fluctuations (sALFF) of local BOLD signals were calculated in the frequency band of 0.01–0.08 Hz. Stepwise increasing physiological/vascular signal regressions on the rs-fMRI data examined whether sALFF-AV45 correlations were driven by vascular hemodynamics, neuronal activities, or both. We found that sALFF and AV45-SUVR were negatively correlated in regions of default-mode and visual networks (precuneus, angular, lingual and fusiform gyri). Regions with higher sALFF had less Aβ accumulation. Correlated cluster sizes in MNI space (r ≈ −0.47) were reduced from 3018 mm3 to 1072 mm3 with stronger cardiovascular regression. These preliminary findings imply that local brain blood fluctuations due to vascular hemodynamics or neuronal activity can affect Aβ homeostasis.

Complexity Analysis of Resting-State and Task fMRI Using Multiscale Sample Entropy.

Functional magnetic resonance imaging (fMRI) is a powerful tool that allows for analysis of neural activity via the measurement of blood-oxygenation-level-dependent (BOLD) signal. The BOLD fluctuations can exhibit different levels of complexity, depending upon the conditions under which they are measured. We examined the complexity of both resting-state and task-based fMRI using sample entropy (SampEn) as a surrogate for signal predictability. We found that within most tasks, regions of the brain that were deemed task-relevant displayed significantly low levels of SampEn, and there was a strong negative correlation between parcel entropy and amplitude.

Resting-State Functional Connectivity in Mathematical Expertise.

To what extent are different levels of expertise reflected in the functional connectivity of the brain? We addressed this question by using resting-state functional magnetic resonance imaging (fMRI) in mathematicians versus non-mathematicians. To this end, we investigated how the two groups of participants differ in the correlation of their spontaneous blood oxygen level-dependent fluctuations across the whole brain regions during resting state. Moreover, by using the classification algorithm in machine learning, we investigated whether the resting-state fMRI networks between mathematicians and non-mathematicians were distinguished depending on features of functional connectivity. We showed diverging involvement of the frontal–thalamic–temporal connections for mathematicians and the medial–frontal areas to precuneus and the lateral orbital gyrus to thalamus connections for non-mathematicians. Moreover, mathematicians who had higher scores in mathematical knowledge showed a weaker connection strength between the left and right caudate nucleus, demonstrating the connections’ characteristics related to mathematical expertise. Separate functional networks between the two groups were validated with a maximum classification accuracy of 91.19% using the distinct resting-state fMRI-based functional connectivity features. We suggest the advantageous role of preconfigured resting-state functional connectivity, as well as the neural efficiency for experts’ successful performance.

Verification of a Central Pacemaker in Brain Stem by Phase-Coupling Analysis Between HR Interval- and BOLD-Oscillations in the 0.10-0.15 Hz Frequency Band.

The origin of slow intrinsic oscillations in resting states of functional magnetic resonance imaging (fMRI) signals is still a matter of debate. The present study aims to test the hypothesis that slow blood oxygenation level-dependent (BOLD) oscillations with frequency components greater than 0.10 Hz result from a central neural pacemaker located in the brain stem. We predict that a central oscillator modulates cardiac beat-to-beat interval (RRI) fluctuations rapidly, with only a short neural lag around 0.3 s. Spontaneous BOLD fluctuations in the brain stem, however, are considerably delayed due to the hemodynamic response time of about ∼2–3 s. In order to test these predictions, we analyzed the time delay between slow RRI oscillations from thorax and BOLD oscillations in the brain stem by calculating the phase locking value (PLV). Our findings show a significant time delay of 2.2 ± 0.2 s between RRI and BOLD signals in 12 out of 23 (50%) participants in axial slices of the pons/brain stem. Adding the neural lag of 0.3 s to the observed lag of 2.2 s we obtain 2.5 s, which is the time between neural activity increase and BOLD increase, termed neuro-BOLD coupling. Note, this time window for neuro-BOLD coupling in awake humans is surprisingly of similar size as in awake head-fixed adult mice (Mateo et al., 2017).