rs-fMRI Signals Research Articles

Functional, but minimal microstructural brain changes present in aging Canadian football league players years after retirement

This brain imaging study examined subjects with a history of repetitive concussive and sub-concussive impacts sustained over the course of their careers in the Canadian Football League (CFL). We hypothesized that microstructural and functional abnormalities, assessed using diffusion tensor imaging (DTI) and resting state functional magnetic resonance imaging (rsfMRI) respectively, would be present in these retired athletes, that are not present in matched controls. Seventeen aging, retired CFL players (aged 58.5±6.2y, ranged 45–66) completed three neuropsychological tests, and had anatomical, diffusion and functional MRI scans performed. Healthy age- and sex-matched control data (n = 2117) were used to develop a subject-specific and region-wise Z-scoring approach. Regional DTI fractional anisotropy (FA) and rsfMRI signal complexity (fractal dimension; FD) Z-score data was further analyzed as a subject-specific total, left, and right injury burden (IB) value for each MRI metric. Microstructural abnormality was detected in 6 of 17 subjects based on DTI FA. The rsfMRI data showed 4 subjects with higher total FDIB, and several regions had Z-score outliers detected in multiple subjects. The right pre-motor cortex, right hippocampus dentate gyrus, and right visual cortex were the most abnormally functioning grey matter brain regions. Total FAIB was negatively correlated with career length, social functioning, and significantly with emotional well-being, and positively correlated with physical health. Total FDIB was negatively correlated with energy and fatigue and general health, and positively correlated with age, career length, and education. This study provides evidence of brain changes years after professional athletes have retired.

Wavelet-Based Fractal Analysis of rs-fMRI for Classification of Alzheimer's Disease.

The resting-state functional magnetic resonance imaging (rs-fMRI) modality has gained widespread acceptance as a promising method for analyzing a variety of neurological and psychiatric diseases. It is established that resting-state neuroimaging data exhibit fractal behavior, manifested in the form of slow-decaying auto-correlation and power-law scaling of the power spectrum across low-frequency components. With this property, the rs-fMRI signal can be broken down into fractal and nonfractal components. The fractal nature originates from several sources, such as cardiac fluctuations, respiration and system noise, and carries no information on the brain’s neuronal activities. As a result, the conventional correlation of rs-fMRI signals may not accurately reflect the functional dynamic of spontaneous neuronal activities. This problem can be solved by using a better representation of neuronal activities provided by the connectivity of nonfractal components. In this work, the nonfractal connectivity of rs-fMRI is used to distinguish Alzheimer’s patients from healthy controls. The automated anatomical labeling (AAL) atlas is used to extract the blood-oxygenation-level-dependent time series signals from 116 brain regions, yielding a 116 × 116 nonfractal connectivity matrix. From this matrix, significant connections evaluated using the p-value are selected as an input to a classifier for the classification of Alzheimer’s vs. normal controls. The nonfractal-based approach provides a good representation of the brain’s neuronal activity. It outperformed the fractal and Pearson-based connectivity approaches by 16.4% and 17.2%, respectively. The classification algorithm developed based on the nonfractal connectivity feature and support vector machine classifier has shown an excellent performance, with an accuracy of 90.3% and 83.3% for the XHSLF dataset and ADNI dataset, respectively. For further validation of our proposed work, we combined the two datasets (XHSLF+ADNI) and still received an accuracy of 90.2%. The proposed work outperformed the recently published work by a margin of 8.18% and 11.2%, respectively.

Resting-state functional magnetic resonance imaging signal variations in aging: The role of neural activity.

Resting‐state functional magnetic resonance imaging (rs‐fMRI) has been extensively used to study brain aging, but the age effect on the frequency content of the rs‐fMRI signal has scarcely been examined. Moreover, the neuronal implications of such age effects and age–sex interaction remain unclear. In this study, we examined the effects of age and sex on the rs‐fMRI signal frequency using the Leipzig mind–brain–body data set. Over a frequency band of up to 0.3 Hz, we found that the rs‐fMRI fluctuation frequency is higher in the older adults, although the fluctuation amplitude is lower. The rs‐fMRI signal frequency is also higher in men than in women. Both age and sex effects on fMRI frequency vary with the frequency band examined but are not found in the frequency of physiological‐noise components. This higher rs‐fMRI frequency in older adults is not mediated by the electroencephalograph (EEG)‐frequency increase but a likely link between fMRI signal frequency and EEG entropy, which vary with age and sex. Additionally, in different rs‐fMRI frequency bands, the fMRI‐EEG amplitude ratio is higher in young adults. This is the first study to investigate the neuronal contribution to age and sex effects in the frequency dimension of the rs‐fMRI signal and may lead to the development of new, frequency‐based rs‐fMRI metrics. Our study demonstrates that Fourier analysis of the fMRI signal can reveal novel information about aging. Furthermore, fMRI and EEG signals reflect different aspects of age‐ and sex‐related brain differences, but the signal frequency and complexity, instead of amplitude, may hold their link.

Laminar-specific functional connectivity mapping with multi-slice line-scanning fMRI.

Despite extensive studies detecting laminar functional magnetic resonance imaging (fMRI) signals to illustrate the canonical microcircuit, the spatiotemporal characteristics of laminar-specific information flow across cortical regions remain to be fully investigated in both evoked and resting conditions at different brain states. Here, we developed a multislice line-scanning fMRI (MS-LS) method to detect laminar fMRI signals in adjacent cortical regions with high spatial (50 μm) and temporal resolution (100 ms) in anesthetized rats. Across different trials, we detected either laminar-specific positive or negative blood-oxygen-level-dependent (BOLD) responses in the surrounding cortical region adjacent to the most activated cortex under the evoked condition. Specifically, in contrast to typical Layer (L) 4 correlation across different regions due to the thalamocortical projections for trials with positive BOLD, a strong correlation pattern specific in L2/3 was detected for trials with negative BOLD in adjacent regions, which indicated brain state-dependent laminar-fMRI responses based on corticocortical interaction. Also, in resting-state (rs-) fMRI study, robust lag time differences in L2/3, 4, and 5 across multiple cortices represented the low-frequency rs-fMRI signal propagation from caudal to rostral slices. In summary, our study provided a unique laminar fMRI mapping scheme to better characterize trial-specific intra- and inter-laminar functional connectivity in evoked and resting-state MS-LS.

Gaining insight into the neural basis of resting-state fMRI signal

The blood oxygenation level-dependent (BOLD)-based resting-state functional magnetic resonance imaging (rsfMRI) has been widely used as a non-invasive tool to map brain-wide connectivity architecture. However, the neural basis underpinning the resting-state BOLD signal remains elusive. In this study, we combined simultaneous calcium-based fiber photometry with rsfMRI in awake animals to examine the relationship of the BOLD signal and spiking activity at the resting state. We observed robust couplings between calcium and BOLD signals in the dorsal hippocampus as well as other distributed areas in the default mode network (DMN), suggesting that the calcium measurement can reliably predict the rsfMRI signal. In addition, using the calcium signal recorded as the ground truth, we assessed the impacts of different rsfMRI data preprocessing pipelines on functional connectivity mapping. Overall, our results provide important evidence suggesting that spiking activity measured by the calcium signal plays a key role in the neural mechanism of resting-state BOLD signal.

Non-Oscillatory Connectivity Approach for Classification of Autism Spectrum Disorder Subtypes Using Resting-State fMRI

Resting-state functional magnetic resonance imaging (rs-fMRI) is an efficient tool to measure brain connectivity and it can reveal patterns that distinguish autism spectrum disorder (ASD) from normal controls (NC). It is established that the fractal nature of neuroimaging signals will affect the estimation of brain&#x2019;s functional connectivity. Therefore, the ordinary correlation of rs-fMRI may not provide the original neuronal activity of the brain. In this work, the non-oscillatory brain connectivity method is proposed to distinguish subtypes of ASD from NC. The three subtypes of ASD namely autistic disorder (ATD), Asperger&#x2019;s disorder (APD), and Pervasive developmental disorder-not other specified (PDD) are classified from NC by extracting the non-oscillatory connectivity from the BOLD rs-fMRI signal. A number of significant connections are extracted by utilizing the <inline-formula> <tex-math notation="LaTeX">$p$ </tex-math></inline-formula>-value analysis and these significant connections are fed to machine learning (ML) classifiers for classification of ASD subtypes against normal control. The performance for binary classification is recorded at accuracy of 98.6&#x0025;, 97.2&#x0025;, 97.2&#x0025;, respectively, for ATD vs. NC, APD vs. NC and PDD vs. NC. Whereas, for multiclass (ATD, APD, PDD and NC), the best accuracy is 88.9&#x0025;. Both binary and multiclass classification outperformed the conventional Pearson correlation-based connectivity and benchmark approaches in terms of accuracy, sensitivity, specificity. This work demonstrates the great potential of non-oscillatory connectivity approaches, not only for autism diagnosis but also for other neurological disorders.

Frontal cortical functional connectivity is impacted by anaesthesia in macaques.

A critical aspect of neuroscience is to establish whether and how brain networks evolved across primates. To date, most comparative studies have used resting-state functional magnetic resonance imaging (rs-fMRI) in anaesthetized nonhuman primates and in awake humans. However, anaesthesia strongly affects rs-fMRI signals. The present study investigated the impact of the awareness state (anaesthesia vs. awake) within the same group of macaque monkeys on the rs-fMRI functional connectivity organization of a well-characterized network in the human brain, the cingulo-frontal lateral network. Results in awake macaques show that rostral seeds in the cingulate sulcus exhibited stronger correlation strength with rostral compared to caudal lateral frontal cortical areas, while more caudal seeds displayed stronger correlation strength with caudal compared to anterior lateral frontal cortical areas. Critically, this inverse rostro-caudal functional gradient was abolished under anaesthesia. This study demonstrated a similar functional connectivity (FC) organization of the cingulo-frontal cortical network in awake macaque to that previously uncovered in the human brain pointing toward a preserved FC organization from macaque to human. However, it can only be observed in awake state suggesting that this network is sensitive to anaesthesia and warranting significant caution when comparing FC patterns across species under different states.

PIRACY: An Optimized Pipeline for Functional Connectivity Analysis in the Rat Brain.

Resting state functional MRI (rs-fMRI) is a widespread and powerful tool for investigating functional connectivity (FC) and brain disorders. However, FC analysis can be seriously affected by random and structured noise from non-neural sources, such as physiology. Thus, it is essential to first reduce thermal noise and then correctly identify and remove non-neural artifacts from rs-fMRI signals through optimized data processing methods. However, existing tools that correct for these effects have been developed for human brain and are not readily transposable to rat data. Therefore, the aim of the present study was to establish a data processing pipeline that can robustly remove random and structured noise from rat rs-fMRI data. It includes a novel denoising approach based on the Marchenko-Pastur Principal Component Analysis (MP-PCA) method, FMRIB’s ICA-based Xnoiseifier (FIX) for automatic artifact classification and cleaning, and global signal regression (GSR). Our results show that: (I) MP-PCA denoising substantially improves the temporal signal-to-noise ratio, (II) the pre-trained FIX classifier achieves a high accuracy in artifact classification, and (III) both independent component analysis (ICA) cleaning and GSR are essential steps in correcting for possible artifacts and minimizing the within-group variability in control animals while maintaining typical connectivity patterns. Reduced within-group variability also facilitates the exploration of potential between-group FC changes, as illustrated here in a rat model of sporadic Alzheimer’s disease.

Correlation of abnormalities in resting state fMRI with executive functioning in chronic schizophrenia

BackgroundAlthough previous studies have consistently demonstrated that neurocognitive and social cognitive impairments are commonly observed in schizophrenia, the neural substrates of deficits of cognitive function remain unclear, especially for the chronic schizophrenia. There has been little resting-state functional magnetic resonance imaging (rs-fMRI) study of cognitive function in chronic schizophrenia. In this study we aimed to investigate the changes of rs-fMRI signals with regional homogeneity (ReHo), and explore the correlations between abnormal regional activity and cognitive function in chronic schizophrenia. MethodsAltogether 76 subjects, 37 patients with chronic schizophrenia and 39 normal controls matched approximately for age, gender and education level were enrolled. All subjects were evaluated psychotic symptoms by Positive and Negative Syndrome Scale (PANSS) and cognitive function by Wisconsin Card Sorting Test (WCST). Conventional MRI and rs-fMRI were performed in all subjects. ReHo was calculated to measure the temporal synchronization of a given voxel and its neighboring voxels based on Kendall coefficient of concordance (KCC) in the rs-fMRI. ResultsFor the numbers of achieved categories, percentage of conceptual level response in the scores of WCST, the patient group was significantly lower than the control group (p<0.05). For the total errors, perseverative errors, non-perseverative errors, the patient group was significantly higher than the control group (p<0.05). Significant differences in ReHo were found in 11 regions (included five activated and five with decreased activity in the cerebrum and one with decreased activity in the cerebellum) in the chronic schizophrenia patients when compared with the normal controls. The ReHo map clusters that were significantly different between the two groups showed no significant correlation with clinical symptoms. Correlation of the whole brain with subscores of PANSS-T, PANSS-P, PANSS-N and WCST were significantly found in some regions. ConclusionsThe study identified five increased and six decreased spontaneous synchrony in the cerebrum and cerebellum in chronic schizophrenia patients compared to the normal matched controls, which were associated with positive, negative symptoms, and deficits of executive functioning.

Analysis of functional MRI signal complexity based on permutation fuzzy entropy in bipolar disorder.

Bipolar disorder is a manifestation of an emotional disease and is associated with emotional and cognitive dysfunction. The entropy-based method has been widely used to study the complexity of resting-state functional MRI (rs-fMRI) signals in mental diseases; however, alterations in the brain rs-fMRI signal complexities in bipolar disorder patients remain unclear, and previously used entropy methods are sensitive to noise. Here, we performed a work using permutation fuzzy entropy (PFEN), which has better performance than previously used methods, to analyze the brain complexity of bipolar disorder patients. Based on PFEN research, we obtained brain entropy maps of 49 bipolar disorder patients and 49 normal control, extracted the regions of interest to analyze the complexity of abnormal brain regions and further analyzed the correlation between the PFEN values of abnormal brain regions and the clinical measurement scores. Compared with the values in the normal control group, we found that significantly increased PFEN values mainly appeared in the middle temporal gyrus, angular gyrus, superior occipital gyrus and medial superior frontal gyrus, and the decreased PFEN values were found in the inferior temporal gyrus in bipolar disorder patients. In addition, the PFEN values of the angular gyrus was significantly negatively correlated with clinical scores. These findings improve our understanding of the pathophysiology of bipolar disorder patients.

Altered Regional Brain Homogeneity of BOLD Signal in CADASIL: A Resting State fMRI Study.

The cognitive decline in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is assumed to be due to a cortical-subcortical disconnection secondary to damage to the cerebral white matter (WM). Using resting state functional MRI (rsfMRI) and analysis of the regional homogeneity (ReHo), we examined a group of CADASIL patients and a group of healthy subjects in order to: (1) explore possible differences between the two groups; and (2) to assess, in CADASIL patients, whether any ReHo abnormalities correlate with individual burdens of WM T2 -weighted hyperintensity and diffusion tensor imaging (DTI)-derived index of mean diffusivity (MD) of the cerebral WM, an index reflecting microstructural damage in CADASIL. Twenty-three paucisymptomatic CADASIL patients (13 females; age mean ± standard deviation = 43.6 ± 11.1 years; three symptomatic and 20 with no or few symptoms) and 16 healthy controls (nine females; age 46.6 ± 11.0 years) were examined with T1 -weighted, T2 -weighted fluid attenuated inversion recovery images, DTI, and rsfMRI. When compared to controls, CADASIL patients showed four clusters of significantly lower ReHo values in cortical areas belonging to networks involved in inhibition and attention, including the right insula, the left superior frontal gyrus, and the bilateral anterior cingulated cortex. ReHo changes did not correlate with an individual patient's lesion burden or MD. This study reveals decreased ReHo of rsfMRI signals in cortical areas involved in inhibition and attention processes, suggesting a potential role for these functional cortical changes in CADASIL.

Multiview Feature Learning With Multiatlas-Based Functional Connectivity Networks for MCI Diagnosis.

Functional connectivity (FC) networks built from resting-state functional magnetic resonance imaging (rs-fMRI) has shown promising results for the diagnosis of Alzheimer's disease and its prodromal stage, that is, mild cognitive impairment (MCI). FC is usually estimated as a temporal correlation of regional mean rs-fMRI signals between any pair of brain regions, and these regions are traditionally parcellated with a particular brain atlas. Most existing studies have adopted a predefined brain atlas for all subjects. However, the constructed FC networks inevitably ignore the potentially important subject-specific information, particularly, the subject-specific brain parcellation. Similar to the drawback of the "single view" (versus the "multiview" learning) in medical image-based classification, FC networks constructed based on a single atlas may not be sufficient to reveal the underlying complicated differences between normal controls and disease-affected patients due to the potential bias from that particular atlas. In this study, we propose a multiview feature learning method with multiatlas-based FC networks to improve MCI diagnosis. Specifically, a three-step transformation is implemented to generate multiple individually specified atlases from the standard automated anatomical labeling template, from which a set of atlas exemplars is selected. Multiple FC networks are constructed based on these preselected atlas exemplars, providing multiple views of the FC network-based feature representations for each subject. We then devise a multitask learning algorithm for joint feature selection from the constructed multiple FC networks. The selected features are jointly fed into a support vector machine classifier for multiatlas-based MCI diagnosis. Extensive experimental comparisons are carried out between the proposed method and other competing approaches, including the traditional single-atlas-based method. The results indicate that our method significantly improves the MCI classification, demonstrating its promise in the brain connectome-based individualized diagnosis of brain diseases.

Origin of the Time Lag Phenomenon and the Global Signal in Resting-State fMRI.

The global mean signal of resting-state fMRI (rs-fMRI) shows a characteristic spatiotemporal pattern that is closely related to the pattern of vascular perfusion. Although being increasingly adopted in the mapping of the flow of neural activity, the mechanism that gives rise to the BOLD signal time lag remains controversial. In the present study, we compared the time lag of the global mean signal with those of the local network components obtained by applying temporal independent component analysis to the resting-state fMRI data, as well as by using simultaneous wide-field visual stimulation, and demonstrated that the time lag patterns are highly similar across all types of data. These results suggest that the time lag of the rs-fMRI signal reflects the local variance of the hemodynamic responses rather than the arrival or transit time of the stimulus, whether the trigger is neuronal or non-neuronal in origin as long as it is mediated by local hemodynamic responses. Examinations of the internal carotid artery signal further confirmed that the arterial signal is tightly inversely coupled with the global mean signal in accordance with previous studies, presumably reflecting the blood flow or blood pressure changes that are occurring almost simultaneously in the internal carotid artery and the cerebral pial/capillary arteries, within the low-frequency component in human rs-fMRI.

Predicting the fMRI Signal Fluctuation with Recurrent Neural Networks Trained on Vascular Network Dynamics.

Resting-state functional MRI (rs-fMRI) studies have revealed specific low-frequency hemodynamic signal fluctuations (<0.1 Hz) in the brain, which could be related to neuronal oscillations through the neurovascular coupling mechanism. Given the vascular origin of the fMRI signal, it remains challenging to separate the neural correlates of global rs-fMRI signal fluctuations from other confounding sources. However, the slow-oscillation detected from individual vessels by single-vessel fMRI presents strong correlation to neural oscillations. Here, we use recurrent neural networks (RNNs) to predict the future temporal evolution of the rs-fMRI slow oscillation from both rodent and human brains. The RNNs trained with vessel-specific rs-fMRI signals encode the unique brain oscillatory dynamic feature, presenting more effective prediction than the conventional autoregressive model. This RNN-based predictive modeling of rs-fMRI datasets from the Human Connectome Project (HCP) reveals brain state-specific characteristics, demonstrating an inverse relationship between the global rs-fMRI signal fluctuation with the internal default-mode network (DMN) correlation. The RNN prediction method presents a unique data-driven encoding scheme to specify potential brain state differences based on the global fMRI signal fluctuation, but not solely dependent on the global variance.

Relationship Between Basic Properties of BOLD Fluctuations and Calculated Metrics of Complexity in the Human Connectome Project.

Resting state functional MRI (rs-fMRI) creates a rich four-dimensional data set that can be analyzed in a variety of ways. As more researchers come to view the brain as a complex dynamical system, tools are increasingly being drawn from other fields to characterize the complexity of the brain’s activity. However, given that the signal measured with rs-fMRI arises from the hemodynamic response to neural activity, the extent to which complexity metrics reflect neural complexity as compared to signal properties related to image quality remains unknown. To provide some insight into this question, correlation dimension, approximate entropy and Lyapunov exponent were calculated for different rs-fMRI scans from the same subject to examine their reliability. The metrics of complexity were then compared to several properties of the rs-fMRI signal from each brain area to determine if basic signal features could explain differences in the complexity metrics. Differences in complexity across brain areas were highly reliable and were closely linked to differences in the frequency profiles of the rs-fMRI signal. The spatial distributions of the complexity and frequency metrics suggest that they are both influenced by location-dependent signal properties that can obscure changes related to neural activity.

Age-related changes in the association of resting-state fMRI signal variability and global functional connectivity in non-demented healthy people

Research suggests that the aging relates to variability of resting-state fMRI (rs-fMRI) signal and the functional connectivity. However, the association between the spatial and temporal activity of resting-state fMRI signal was less documented. We recruited 477 healthy Han Chinese participants, who were separated into young, middle and old groups to investigate the relationship between the variability and global functional connectivity (gFC) in different age ranges using standard deviation (SD) of time series and gFC, respectively. Our analysis revealed the changing patterns during healthy aging: 1) 17 brain regions(Olfactory_L, Orbital_L etc.) were identified to have significant association of age with both SD and gFC respectively by linear regression analysis; 2) Two typical associations could be observed between SD and gFC: positive and negative correlations; 3) The variation ratio of SD to gFC was changing with age at the voxel level by using unsupervised clustering method. It is the first time to combine voxel-wise variability and gFC together for the study of age-related changes with rs-fMRI signal. This study may provide a new clue for understanding the synchronization of human brain based on SD and gFC due to the effect of aging.

Alterations of functional and structural connectivity in patients with brain metastases.

Metastases are the most prevalent tumors in the brain and are commonly associated with high morbidity and mortality. Previous studies have suggested that brain tumors can induce a loss of functional connectivity and alter the brain network architecture. Little is known about the effect of brain metastases on whole-brain functional and structural connectivity networks. In this study, 14 patients with brain metastases and 16 healthy controls underwent resting state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). We constructed functional connectivity network using rs-fMRI signal correlations and structural connectivity network using DTI tractography. Graph theoretical analysis was employed to calculate network properties. We further evaluated the performance of brain networks after metastases resection by a simulated method. Compared to healthy controls, patients with brain metastases showed an altered “small-world” architecture in both functional and structural connectivity networks, shifting to a more randomness organization. Besides, the coupling strength of functional-structural connectivity was decreased in patients. After removing nodes infiltrated by metastases, aggravated disruptions were found in both functional and structural connectivity networks, and the alterations of network properties correlated with the removed hubs number. Our findings suggest that brain metastases interfere with the optimal network organization and relationship of functional and structural connectivity networks, and tumor resection involving hubs could cause a worse performance of brain networks. This study provides neuroimaging guidance for neurosurgical planning and postoperative assessment of brain metastases from the aspect of brain networks.

Stage detection of mild cognitive impairment via fMRI using Hilbert Huang transform based classification framework.

This work aims to establish a classification framework for the diagnosis of mild cognitive impairment (MCI) at different stages (early MCI and late MCI) through direct analysis of resting-state functional magnetic resonance imaging (rs-fMRI) signals and using the accuracy (total correct rate), specificity (correct rate of late MCI) and sensitivity (correct rate of early MCI) to validate its classification performance. All fMR images of subjects were parcellated into 116 regions of interest (ROIs) by applying the Anatomical Automatic Labeling (AAL) template, and the average rs-fMRI signals of each ROI were extracted. The Hilbert-Huang transform (HHT) was introduced into the framework to decompose each rs-fMRI signal into a series of intrinsic mode functions (IMFs) and to analyze these nonstationary and nonlinear time-series from the perspective of multiresolution. After obtaining the instantaneous frequencies and amplitudes of all IMFs of a signal, the Hilbert weighted frequencies (HWFs) were calculated and combined into a vector as the feature of the corresponding ROI. Support Vector Machine (SVM) was implemented to classify MCI at different stages. We used the independent two-sample t-test as the feature selection method and measured the classification performance through the leave-one-out cross-validation (LOOCV) method. Results on 77 early MCI (eMCI) and 64 late MCI (lMCI) with baseline rs-fMRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) yielded 87.94% classification accuracy. Some of the brain regions with significant differences found by previous studies have been confirmed in this work. We found that HWF characteristics exhibited a significant downward trend in all cerebellar regions. The rs-fMRI signals in differential brain regions have not changed completely, but only altered in some narrow frequency bands. The analysis results showed that during the progress of MCI, the main changes of rs-fMRI were concentrated in IMF3, while IMFs with other indexes also contained HWF features with high SVM weights, such as Orbitofrontal superior frontal gyrus in IMF2, Insula in IMF4, and Lobule Ⅲ of vermis in IMF5, indicating that other IMFs provide important information for the diagnosis of MCI as well. This work confirmed the classification ability of HHT-based classification framework in classification of at different stages of MCI. Through the analysis, we found that during the progress of MCI the main changes of rs-fMRI were concentrated in IMF3, and HWF characteristics showed a significant downward trend in all cerebellar regions.

Controlling for the effect of arterial-CO2 fluctuations in resting-state fMRI: Comparing end-tidal CO2 clamping and retroactive CO2 correction

The BOLD signal, as the basis of functional MRI, arises from both neuronal and vascular factors, with their respective contributions to resting state-fMRI still unknown. Among the factors contributing to “physiological noise”, dynamic arterial CO2 fluctuations constitutes the strongest and the most widespread modulator of the grey-matter rs-fMRI signal. Some important questions are: (1) if we were able to clamp arterial CO2 such that fluctuations are removed, what would happen to rs-fMRI measures? (2) falling short of that, is it possible to retroactively correct for CO2 effects with equivalent outcome? In this study 13 healthy subjects underwent two rs-fMRI acquisitions. During the “clamped” run, end-tidal CO2 (PETCO2) is clamped to the average PETCO2 level of each participant, while during the “free-breathing” run, the PETCO2 level is passively monitored but not controlled. PETCO2 correction was applied to the free-breathing data by convolving PETCO2 with its BOLD response function, and then regressing out the result. We computed the BOLD resting-state fluctuation amplitude (RSFA), as well as seed-independent mean functional connectivity (FC) as the weighted global brain connectivity (wGBC). Furthermore, connectivity between conditions were compared using coupled intrinsic-connectivity distribution (ICD) method. We ensured that PETCO2 clamping did not significantly alter heart-beat and respiratory variation. We found that neither PETCO2 clamping nor correction produced significant change in RSFA and wGBC. In terms of the ICD, PETCO2 clamping and correction both reduced FC strength in the majority of grey matter regions, although the effect of PETCO2 correction is considerably smaller than the effect of PETCO2 clamping. Interestingly, we found the effect of the commonly employed white-mater/cerebrospinal-fluid regression to be similar to that of PETCO2 clamping than global-signal regression. Nonetheless, both methods reduce functional connectivity significantly more than does PETCO2 clamping.Furthermore, while PETCO2 clamping reduced inter-subject variability in FC, PETCO2 correction increased the variability. Overall PETCO2 correction is not the equivalent of PETCO2 clamping, although it shifts FC values towards the same direction as clamping does.

The association between resting-state functional magnetic resonance imaging and aortic pulse-wave velocity in healthy adults.

Resting‐state functional magnetic resonance imaging (rs‐fMRI) is frequently used to study brain function; but, it is unclear whether BOLD‐signal fluctuation amplitude and functional connectivity are associated with vascular factors, and how vascular‐health factors are reflected in rs‐fMRI metrics in the healthy population. As arterial stiffening is a known age‐related cardiovascular risk factor, we investigated the associations between aortic stiffening (as measured using pulse‐wave velocity [PWV]) and rs‐fMRI metrics. We used cardiac MRI to measure aortic PWV (an established indicator of whole‐body vascular stiffness), as well as dual‐echo pseudo‐continuous arterial‐spin labeling to measure BOLD and CBF dynamics simultaneously in a group of generally healthy adults. We found that: (1) higher aortic PWV is associated with lower variance in the resting‐state BOLD signal; (2) higher PWV is also associated with lower BOLD‐based resting‐state functional connectivity; (3) regions showing lower connectivity do not fully overlap with those showing lower BOLD variance with higher PWV; (4) CBF signal variance is a significant mediator of the above findings, only when averaged across regions‐of‐interest. Furthermore, we found no significant association between BOLD signal variance and systolic blood pressure, which is also a known predictor of vascular stiffness. Age‐related vascular stiffness, as measured by PWV, provides a unique scenario to demonstrate the extent of vascular bias in rs‐fMRI signal fluctuations and functional connectivity. These findings suggest that a substantial portion of age‐related rs‐fMRI differences may be driven by vascular effects rather than directly by brain function.