rs-fMRI Studies Research Articles

A longitudinal study of functional brain complexity in progressive Alzheimer's disease

AbstractINTRODUCTIONCross‐sectional resting‐state functional magnetic resonance imaging (rsfMRI) studies have revealed altered complexity with advanced Alzheimer's disease (AD) stages. The current study conducted longitudinal rsfMRI complexity analyses in AD.METHODSLinear mixed‐effects (LME) models were implemented to evaluate altered rates of disease progression in complexity across disease groups.RESULTSThe LME models revealed complexity of the higher frequency in the CNtoMCI group (those converted from cognitively normal [CN] to mild cognitive impairment [MCI]) decayed faster over time versus CN in the prefrontal and lateral occipital cortex; complexity of the lower frequency decayed faster in AD versus CN in various frontal and temporal regions (p < 0.05 & Benjamini–Hochberg corrected with q < 0.05).DISCUSSIONLocal functional brain activities decayed in the early stage of the disease, and long‐range communications were impacted in the later stage. Our study demonstrated longitudinal changes in AD‐related rsfMRI complexity, indicating its potential as an imaging biomarker of AD.Highlights We conducted longitudinal resting state functional magnetic resonance imaging (rsfMRI) complexity analyses using the Alzheimer's Disease Neuroimaging Initiative dataset. Higher‐frequency complexity in the CNtoMCI group (those transitioning from cognitively normal [CN] to mild cognitive impairment [MCI]) was found to decay faster over time compared to CN, specifically in the prefrontal and lateral occipital cortex. Lower‐frequency complexity was found to decay faster in AD versus CN in various frontal and temporal regions. This study demonstrated that longitudinal changes in rsfMRI complexity could serve as a potential imaging biomarker for Alzheimer's disease.

Functional MRI-Specific Alternations in default mode network in obsessive-compulsive disorder: A voxel-based meta-analysis.

Obsessive-compulsive disorder (OCD) is a common and debilitating mental disorder. Neuroimaging studies have highlighted that the dysfunctional default mode network (DMN) plays a key role in the pathophysiology mechanisms of OCD. However, the findings of impaired DMN regions have been inconsistent. We employed meta-analysis to identify the fMRI-specific abnormalities of the DMN in OCD. PubMed, Web of science and Embase were searched to screen resting-state functional magnetic resonance imaging (rs-fMRI) studies on the amplitude of low-frequency fluctuation/fractional amplitude of low-frequency fluctuation (ALFF/fALFF) and regional homogeneity (ReHo) of the DMN in OCD patients. Based on the activation likelihood estimation (ALE) algorithm, we compared all patients with OCD and control group in a primary meta-analysis, and analyzed the unmedicated OCD without comorbidities in secondary meta-analyses. A total of 26 eligible studies with 1219 OCD patients (707men) and 1238 healthy controls (684 men) were included in the primary meta-analysis. We concluded specific changes in brain regions of DMN, mainly in the left medial frontal gurus (MFG), bilateral superior temporal gyrus (STG), bilateral inferior parietal lobule (IPL), bilateral precuneus (PCUN), bilateral posterior cingulate cortex (PCC), and right parahippocampal gyrus (PHG). OCD patients showed dysfunction in the DMN, including impaired local important nodal brain regions. The PCC/PCUN appear to be the most affected regions within the DMN, providing valuable insights into understanding the potential pathophysiology of OCD and targets for clinical interventions.

Born Connected: Do Infants Already Have Adult-Like Multi-Scale Connectivity Networks?

The human brain undergoes remarkable development with the first six postnatal months witnessing the most dramatic structural and functional changes, making this period critical for in-depth research. rsfMRI studies have identified intrinsic connectivity networks (ICNs), including the default mode network, in infants. Although early formation of these networks has been suggested, the specific identification and number of ICNs reported in infants vary widely, leading to inconclusive findings. In adults, ICNs have provided valuable insights into brain function, spanning various mental states and disorders. A recent study analyzed data from over 100,000 subjects and generated a template of 105 multi-scale ICNs enhancing replicability and generalizability across studies. Yet, the presence of these ICNs in infants has not been investigated. This study addresses this significant gap by evaluating the presence of these multi-scale ICNs in infants, offering critical insight into the early stages of brain development and establishing a baseline for longitudinal studies. To accomplish this goal, we employ two sets of analyses. First, we employ a fully data-driven approach to investigate the presence of these ICNs from infant data itself. Towards this aim, we also introduce burst independent component analysis (bICA), which provides reliable and unbiased network identification. The results reveal the presence of these multi-scale ICNs in infants, showing a high correlation with the template (rho > 0.5), highlighting the potential for longitudinal continuity in such studies. We next demonstrate that reference-informed ICA-based techniques can reliably estimate these ICNs in infants, highlighting the feasibility of leveraging the NeuroMark framework for robust brain network extraction. This approach not only enhances cross-study comparisons across lifespans but also facilitates the study of brain changes across different age ranges. In summary, our study highlights the novel discovery that the infant brain already possesses ICNs that are widely observed in older cohorts.

Aberrant intrinsic brain activities in functional gastrointestinal disorders revealed by seed-based d mapping with permutation of subject images.

Functional gastrointestinal disorders (FGIDs) are characterized by complex interactions between the gut and brain, leading to altered brain function and symptom manifestation. We used neuroimaging meta-analytic techniques in order to analyze the correlation between FGIDs and aberrant brain activity. A systematic review was performed to ascertain resting-state functional magnetic resonance imaging (rs-fMRI) studies examining brain function in FGIDs. Pooled meta-analyses by seed-based d mapping with permutation of subject images (SDM-PSI) were performed to assess variations in regional brain activity, and sensitivity analyses were applied to evaluate the robustness of findings. Meta-regression analyses were then carried out to examine possible links between demographic factors and neuroimaging changes. Our meta-analysis revealed significant changes in regional brain activities among FGIDs patients compared to healthy controls (HC). Increased brain activation was observed in several regions including the postcentral gyrus, calcarine fissure/surrounding cortex, superior frontal gyrus, and insula, while decreased activity was noted in the left posterior cingulate gyrus, right median cingulate/paracingulate gyri, and the left caudate nucleus. Furthermore, meta-regression analyses indicated negative associations between disease duration and alterations in specific brain regions. These findings underscored the intricate interplay between gut dysfunction and aberrant brain activity in FGIDs. Early intervention and multidisciplinary approaches addressing both gastrointestinal symptoms and associated emotional distress are crucial for improving the quality of life of the patients.

Strategies for motion- and respiration-robust estimation of fMRI intrinsic neural timescales

Abstract Intrinsic neural timescales (INT) reflect the time window of neural integration within a brain region and can be measured via resting-state functional magnetic resonance imaging (rs-fMRI). Despite the potential relevance of INT to cognition, brain organization, and neuropsychiatric illness, the influences of physiological artifacts on rs-fMRI INT have not been systematically considered. Two artifacts, head motion and respiration, pose serious issues in rs-fMRI studies. Here, we described their impact on INT estimation and tested the ability of two denoising strategies for mitigating these artifacts, high-motion frame censoring and global signal regression (GSR). We used a subset of the Human Connectome Project Young Adult (HCP-YA) dataset with runs annotated for breathing patterns (Lynch et al., 2020) and at least one “clean” (reference) run that had minimal head motion and no respiration artifacts; other runs from the same participants (n = 46) were labeled as “non-clean.” We found that non-clean runs exhibited brain-wide increases in INT compared with their respective clean runs and that the magnitude of error in INT between non-clean and clean runs correlated with the amount of head motion. Importantly, effect sizes were comparable with INT effects reported in the clinical literature. GSR and high-motion frame censoring improved the similarity between INT maps from non-clean runs and their respective clean run. Using a pseudo-random frame-censoring approach, we uncovered a relationship between the number of censored frames and both the mean INT and mean error, suggesting that frame censoring itself biases INT estimation. A group-level correction procedure reduced this bias and improved similarity between non-clean runs and their respective clean run. Based on our findings, we offer recommendations for rs-fMRI INT studies, which include implementing GSR and high-motion frame censoring with Lomb–Scargle interpolation of censored frames, and performing group-level correction of the bias introduced by frame censoring.

A comparative study of interhemispheric functional connectivity in patients with basal ganglia ischemic stroke.

Voxel-mirrored homotopic connectivity (VMHC) is utilized to assess the functional connectivity of neural networks by quantifying the similarity between corresponding regions in the bilateral hemispheres of the brain. The exploration of VMHC abnormalities in basal ganglia ischemic stroke (BGIS) patients across different cerebral hemispheres has been limited. This study seeks to establish a foundation for understanding the functional connectivity status of both brain hemispheres in BGIS patients through the utilization of VMHC analysis utilizing resting-state functional magnetic resonance imaging (rs-fMRI). This study examined a total of 38 patients with left basal ganglia ischemic stroke (LBGIS), 44 patients with right basal ganglia ischemic stroke (RBGIS), and 41 individuals in a healthy control (HC) group. Rs-fMRI studies were performed on these patients, and the pre-processed rs-fMRI data were analyzed using VMHC method. Subsequently, the VMHC values were compared between three groups using a one-way ANOVA and post hoc analysis. Correlation analysis with clinical scales was also conducted. The results indicated that compared to the HC group, significant differences were detected in postcentral gyrus, extending to precentral gyrus in both BGIS groups. Post hoc analysis showed that in the pairwise ROI-based comparison, individuals with LBGIS and RBGIS exhibited reduced VMHC values compared to HC groups. There was no significant difference between the LBGIS and RBGIS groups. In the LBGIS group, the VMHC value showed a negative correlation with NIHSS and a positive correlation with BI. The analysis of VMHC in rs-fMRI revealed a pattern of brain functional remodeling in patients with unilateral BGIS, marked by reduced synchronization and coordination between hemispheres. This may contribute to the understanding of the neurological mechanisms underlying motor dysfunction in these patients.

Meta-analysis of resting-state fMRI in cervical spondylosis patients using AES-SDM.

Resting-state functional magnetic resonance imaging (rs-fMRI) reveals diverse neural activity patterns in cervical spondylosis (CS) patients. However, the reported results are inconsistent. Therefore, our objective was to conduct a meta-analysis to synthesize the findings from existing rs-fMRI studies and identify consistent patterns of neural brain activity alterations in patients with CS. A systematic search was conducted across PubMed, Web of Knowledge, Embase, Google Scholar, and CNKI for rs-fMRI studies that compared CS patients with healthy controls (HCs), up to January 28, 2024. Significant cluster coordinates were extracted for comprehensive analysis. We included 16 studies involving 554 CS patients and 488 HCs. CS patients demonstrated decreased brain function in the right superior temporal gyrus and left postcentral gyrus, and increased function in the left superior frontal gyrus. Jackknife sensitivity analysis validated the robustness of these findings, and Egger's test confirmed the absence of significant publication bias (p > 0.05). Meta-regression showed no significant impact of age or disease duration differences on the results. This meta-analysis confirms consistent alterations in specific brain regions in CS patients, highlighting the potential of rs-fMRI to refine diagnostic and therapeutic strategies. https://www.crd.york.ac.uk/prospero/, identifier CRD42024496263.

Evaluation of Intra- and Inter-Network Connectivity within Major Brain Networks in Drug-Resistant Depression Using rs-fMRI.

Background: Major Depressive Disorder (MDD) is a significant challenge in modern medicine due to its unclear underlying causes. Brain network dysfunction is believed to play a key role in its pathophysiology. Resting-state functional MRI (rs-fMRI), a neuroimaging technique, enables the in vivo assessment of functional connectivity (FC) between brain regions, offering insights into these network dysfunctions. The aim of this study was to evaluate abnormalities in FC within major brain networks in patients with drug-resistant MDD. Methods: The study group consisted of 26 patients with drug-resistant MDD and an age-matched control group (CG) of 26 healthy subjects. The rs-fMRI studies were performed on a 3T MR scanner (Philips, Ingenia) using a 32-channel head and neck coil. Imaging data were statistically analyzed, focusing on the intra- and inter-network FC of the following networks: default mode (DMN), sensorimotor (SMN), visual (VN), salience (SN), cerebellar (CN), dorsal attention (DAN), language (LN), and frontoparietal (FPN). Results: In patients with MDD, the intra-network analysis showed significantly decreased FC between nodes within VN compared to CG. In contrast, the inter-network analysis showed significantly increased FC between nodes from VN and SN or VN and DAN compared to CG. Decreased FC was found between SN and CN or SN and FPN as well as VN and DAN nodes compared to CG. Conclusions: Patients with MDD showed significant abnormalities in resting-state cortical activity, mainly regarding inter-network functional connectivity. These results contribute to the knowledge on the pathomechanism of MDD and may also be useful for developing new treatments.

Frequency-specific static and dynamic neural activity indices in children with different attention deficit hyperactivity disorder subtypes: a resting-state fMRI study.

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood. Numerous resting-state functional magnetic resonance imaging (rs-fMRI) studies in ADHD have been performed using traditional low-frequency bands (0.01-0.08 Hz). However, the neural activity patterns of frequency subbands in ADHD still require further investigation. The purpose of this study is to explore the frequency-dependent characteristics and neural activity patterns of ADHD subtypes. We selected the ADHD combined type (ADHD-C, N = 25), ADHD inattentive type (ADHD-I, N = 26) and typically developing (TD, N = 28) children from the ADHD-200 Consortium. Based on the slow-5 band (0.01-0.027 Hz) and slow-4 band (0.027-0.073 Hz), we generated static and dynamic fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) maps for each participant. A flexible-factorial analysis of variance model was performed on static and temporal dynamic rs-fMRI measurements within two subbands. Results revealed that the orbital-frontal gyrus, precuneus, superior temporal gyrus and angular gyrus were found to have obvious frequency band and group interaction effects. The intrinsic neural activity differences among three groups were more prominent in the slow-5 frequency band compared to the slow-4 band. In addition, the indices of significant interaction regions showed correlations with the progression of the disease and the features in slow-5 showed an advantageous diagnostic performance compared with those in slow-4. The results suggested the intrinsic neural activities of ADHD subtypes were frequency-dependent. The frequency-specific analysis of static and dynamic brain activity may provide a deeper understanding of neurophysiological dysfunction patterns in ADHD subtypes and provide supplementary information for assessing ADHD subtypes.

Convergent functional change of frontoparietal network in obsessive-compulsive disorder: a voxel-based meta-analysis.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric illness with complex clinical manifestations. Cognitive dysfunction may underlie OC symptoms. The frontoparietal network (FPN) is a key region involved in cognitive control. However, the findings of impaired FPN regions have been inconsistent. We employed meta-analysis to identify the fMRI-specific abnormalities of the FPN in OCD. PubMed, Web of Science, Scopus, and EBSCOhost were searched to screen resting-state functional magnetic resonance imaging (rs-fMRI) studies exploring dysfunction in the FPN of OCD patients using three indicators: the amplitude of low-frequency fluctuation/fractional amplitude of low-frequency fluctuation (ALFF/fALFF), regional homogeneity (ReHo) and functional connectivity (FC). We compared all patients with OCD and control group in a primary analysis, and divided the studies by medication in secondary meta-analyses with the activation likelihood estimation (ALE) algorithm. A total of 31 eligible studies with 1359 OCD patients (756 men) and 1360 healthy controls (733 men) were included in the primary meta-analysis. We concluded specific changes in brain regions of FPN, mainly in the left dorsolateral prefrontal cortex (DLPFC, BA9), left inferior frontal gyrus (IFG, BA47), left superior temporal gyrus (STG, BA38), right posterior cingulate cortex (PCC, BA29), right inferior parietal lobule (IPL, BA40) and bilateral caudate. Additionally, altered connectivity within- and between-FPN were observed in the bilateral DLPFC, right cingulate gyrus and right thalamus. The secondary analyses showed improved convergence relative to the primary analysis. OCD patients showed dysfunction FPN, including impaired local important nodal brain regions and hypoconnectivity within the FPN (mainly in the bilateral DLPFC), during the resting state. Moreover, FPN appears to interact with the salience network (SN) and default mode network (DMN) through pivotal brain regions. Consistent with the hypothesis of fronto-striatal circuit dysfunction, especially in the dorsal cognitive circuit, these findings provide strong evidence for integrating two pathophysiological models of OCD.

Detecting Alzheimer's Disease Stages and Frontotemporal Dementia in Time Courses of Resting-State fMRI Data Using a Machine Learning Approach.

Early, accurate diagnosis of neurodegenerative dementia subtypes such as Alzheimer's disease (AD) and frontotemporal dementia (FTD) is crucial for the effectiveness of their treatments. However, distinguishing these conditions becomes challenging when symptoms overlap or the conditions present atypically. Resting-state fMRI (rs-fMRI) studies have demonstrated condition-specific alterations in AD, FTD, and mild cognitive impairment (MCI) compared to healthy controls (HC). Here, we used machine learning to build a diagnostic classification model based on these alterations. We curated all rs-fMRIs and their corresponding clinical information from the ADNI and FTLDNI databases. Imaging data underwent preprocessing, time course extraction, and feature extraction in preparation for the analyses. The imaging features data and clinical variables were fed into gradient-boosted decision trees with fivefold nested cross-validation to build models that classified four groups: AD, FTD, HC, and MCI. The mean and 95% confidence intervals for model performance metrics were calculated using the unseen test sets in the cross-validation rounds. The model built using only imaging features achieved 74.4% mean balanced accuracy, 0.94 mean macro-averaged AUC, and 0.73 mean macro-averaged F1 score. It accurately classified FTD (F1 = 0.99), HC (F1 = 0.99), and MCI (F1 = 0.86) fMRIs but mostly misclassified AD scans as MCI (F1 = 0.08). Adding clinical variables to model inputs raised balanced accuracy to 91.1%, macro-averaged AUC to 0.99, macro-averaged F1 score to 0.92, and improved AD classification accuracy (F1 = 0.74). In conclusion, a multimodal model based on rs-fMRI and clinical data accurately differentiates AD-MCI vs. FTD vs. HC.

A confounder controlled machine learning approach: Group analysis and classification of schizophrenia and Alzheimer's disease using resting-state functional network connectivity.

Resting-state functional magnetic resonance imaging (rs-fMRI) has increasingly been used to study both Alzheimer's disease (AD) and schizophrenia (SZ). While most rs-fMRI studies being conducted in AD and SZ compare patients to healthy controls, it is also of interest to directly compare AD and SZ patients with each other to identify potential biomarkers shared between the disorders. However, comparing patient groups collected in different studies can be challenging due to potential confounds, such as differences in the patient's age, scan protocols, etc. In this study, we compared and contrasted resting-state functional network connectivity (rs-FNC) of 162 patients with AD and late mild cognitive impairment (LMCI), 181 schizophrenia patients, and 315 cognitively normal (CN) subjects. We used confounder-controlled rs-FNC and applied machine learning algorithms (including support vector machine, logistic regression, random forest, and k-nearest neighbor) and deep learning models (i.e., fully-connected neural networks) to classify subjects in binary and three-class categories according to their diagnosis labels (e.g., AD, SZ, and CN). Our statistical analysis revealed that FNC between the following network pairs is stronger in AD compared to SZ: subcortical-cerebellum, subcortical-cognitive control, cognitive control-cerebellum, and visual-sensory motor networks. On the other hand, FNC is stronger in SZ than AD for the following network pairs: subcortical-visual, subcortical-auditory, subcortical-sensory motor, cerebellum-visual, sensory motor-cognitive control, and within the cerebellum networks. Furthermore, we observed that while AD and SZ disorders each have unique FNC abnormalities, they also share some common functional abnormalities that can be due to similar neurobiological mechanisms or genetic factors contributing to these disorders' development. Moreover, we achieved an accuracy of 85% in classifying subjects into AD and SZ where default mode, visual, and subcortical networks contributed the most to the classification and accuracy of 68% in classifying subjects into AD, SZ, and CN with the subcortical domain appearing as the most contributing features to the three-way classification. Finally, our findings indicated that for all classification tasks, except AD vs. SZ, males are more predictable than females.

Automatically targeting the dorsolateral subthalamic nucleus for functional connectivity-guided rTMS therapy

Aim: Many resting-state functional magnetic resonance imaging (rs-fMRI) studies have provided evidence that repetitive transcranial magnetic stimulation (rTMS) exerts treatment effects via functional connectivity (FC) from a superficial stimulation target to a deep effective region. The dorsolateral subthalamic nucleus (DL-STN) is an effective target in deep brain stimulation surgery for Parkinson’s disease (PD), but its targeting highly depends on well-trained neurosurgeons and is not easily used for FC-guided rTMS. We aimed to devise a method for automatically localizing the DL-STN, and further develop a one-stop plug-in of rs-fMRI FC analysis to assist future individualized FC-guided rTMS. Methods: Based on structural and iron-sensitive MRI of 78 participants, two raters defined the DL-STN coordinates with very high reliability. The averaged coordinates in the standard Montreal Neurological Institute (MNI) space were: left DL-STN, x: -11.89 ± 0.82, y: -14.51 ± 1.00, and z: -6.40 ± 1.01 and the right DL-STN, x: 12.53 ± 0.77, y: -13.97 ± 0.86, and z: -6.57 ± 0.99. As the individual distances from the averaged coordinates were less than 3 mm (within one voxel for most rs-fMRI studies) for all 78 participants, we defined the average coordinates as AutoSTN. We then developed a one-stop plug-in named Connectivity and Coordinates Converting Assistant Toolbox (CC-CAT) and performed AutoSTN FC analysis. Results: The AutoSTN seed showed significant FC with the motor cortices in all participants. Conclusion: The AutoSTN-based rs-fMRI FC could guide future rTMS on PD. The one-stop plug-in CC-CAT can be used for any FC-guided rTMS treatment.

Brain functional network changes in patients with juvenile myoclonic epilepsy: a study based on graph theory and Granger causality analysis.

Many resting-state functional magnetic resonance imaging (rs-fMRI) studies have shown that the brain networks are disrupted in adolescent patients with juvenile myoclonic epilepsy (JME). However, previous studies have mainly focused on investigating brain connectivity disruptions from the perspective of static functional connections, overlooking the dynamic causal characteristics between brain network connections. In our study involving 37 JME patients and 35 Healthy Controls (HC), we utilized rs-fMRI to construct whole-brain functional connectivity network. By applying graph theory, we delved into the altered topological structures of the brain functional connectivity network in JME patients and identified abnormal regions as key regions of interest (ROIs). A novel aspect of our research was the application of a combined approach using the sliding window technique and Granger causality analysis (GCA). This method allowed us to delve into the dynamic causal relationships between these ROIs and uncover the intricate patterns of dynamic effective connectivity (DEC) that pervade various brain functional networks. Graph theory analysis revealed significant deviations in JME patients, characterized by abnormal increases or decreases in metrics such as nodal betweenness centrality, degree centrality, and efficiency. These findings underscore the presence of widespread disruptions in the topological features of the brain. Further, clustering analysis of the time series data from abnormal brain regions distinguished two distinct states indicative of DEC patterns: a state of strong connectivity at a lower frequency (State 1) and a state of weak connectivity at a higher frequency (State 2). Notably, both states were associated with connectivity abnormalities across different ROIs, suggesting the disruption of local properties within the brain functional connectivity network and the existence of widespread multi-functional brain functional networks damage in JME patients. Our findings elucidate significant disruptions in the local properties of whole-brain functional connectivity network in patients with JME, revealing causal impairments across multiple functional networks. These findings collectively suggest that JME is a generalized epilepsy with localized abnormalities. Such insights highlight the intricate network dysfunctions characteristic of JME, thereby enriching our understanding of its pathophysiological features.

Resting state global brain activity induces bias in fMRI motion estimates

Abstract Head motion is a significant source of artifacts in resting-state fMRI (rsfMRI) studies and has been shown to affect resting-state functional connectivity (rsFC) measurements. In many rsfMRI studies, motion parameters estimated from volume registration are used to characterize head motion and to mitigate motion artifacts in rsfMRI data. While prior task-based fMRI studies have shown that task-evoked brain activations may induce temporally correlated bias in the motion estimates, resulting in artificial activations after registration, relatively little is known about neural-related bias in rsfMRI motion parameters. In this study, we demonstrate that neural-related bias exists in rsfMRI motion estimates and characterize the potential effects of the bias on rsFC estimates. Using a public multi-echo rsfMRI dataset, we use the differences between motion estimates from the first echo and second echo data as a measure of neural-induced bias. We show that the resting-state global activity of the brain, as characterized with the global signal (GS), induces bias in the motion estimates in the y- and z-translational axes. Furthermore, we demonstrate that the GS-related bias reflects superior-inferior and anterior-posterior asymmetries in the GS beta coefficient map. Finally, we demonstrate that regression with biased motion estimates can negatively bias rsFC estimates and also reduce rsFC differences between young and old subjects.

The brain entropy dynamics in resting state.

As a novel measure for irregularity and complexity of the spontaneous fluctuations of brain activities, brain entropy (BEN) has attracted much attention in resting-state functional magnetic resonance imaging (rs-fMRI) studies during the last decade. Previous studies have shown its associations with cognitive and mental functions. While most previous research assumes BEN is approximately stationary during scan sessions, the brain, even at its resting state, is a highly dynamic system. Such dynamics could be characterized by a series of reoccurring whole-brain patterns related to cognitive and mental processes. The present study aims to explore the time-varying feature of BEN and its potential links with general cognitive ability. We adopted a sliding window approach to derive the dynamical brain entropy (dBEN) of the whole-brain functional networks from the HCP (Human Connectome Project) rs-fMRI dataset that includes 812 young healthy adults. The dBEN was further clustered into 4 reoccurring BEN states by the k-means clustering method. The fraction window (FW) and mean dwell time (MDT) of one BEN state, characterized by the extremely low overall BEN, were found to be negatively correlated with general cognitive abilities (i.e., cognitive flexibility, inhibitory control, and processing speed). Another BEN state, characterized by intermediate overall BEN and low within-state BEN located in DMN, ECN, and part of SAN, its FW, and MDT were positively correlated with the above cognitive abilities. The results of our study advance our understanding of the underlying mechanism of BEN dynamics and provide a potential framework for future investigations in clinical populations.

Sleep deprivation changes frequency-specific functional organization of the resting human brain

Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies have widely explored the temporal connection changes in the human brain following long-term sleep deprivation (SD). However, the frequency-specific topological properties of sleep-deprived functional networks remain virtually unclear. In this study, thirty-seven healthy male subjects underwent resting-state fMRI during rested wakefulness (RW) and after 36 hours of SD, and we examined frequency-specific spectral connection changes (0.01–0.08 Hz, interval = 0.01 Hz) caused by SD. First, we conducted a multivariate pattern analysis combining linear SVM classifiers with a robust feature selection algorithm, and the results revealed that accuracies of 74.29%-84.29% could be achieved in the classification between RW and SD states in leave-one-out cross-validation at different frequency bands, moreover, the spectral connection at the lowest and highest frequency bands exhibited higher discriminative power. Connection involving the cingulo-opercular network increased most, while connection involving the default-mode network decreased most following SD. Then we performed a graph-theoretic analysis and observed reduced low-frequency modularity and high-frequency global efficiency in the SD state. Moreover, hub regions, which were primarily situated in the cerebellum and the cingulo-opercular network after SD, exhibited high discriminative power in the aforementioned classification consistently. The findings may indicate the frequency-dependent effects of SD on the functional network topology and its efficiency of information exchange, providing new insights into the impact of SD on the human brain.

Label-based meta-analysis of functional brain dysconnectivity across mood and psychotic disorders

BackgroundResting-state functional magnetic resonance imaging (rsfMRI) studies have revealed patterns of functional brain dysconnectivity in psychiatric disorders such as major depression disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ). Although these disorders have been mostly studied in isolation, there is mounting evidence of shared neurobiological alterations across them. MethodsTo uncover the nature of the relatedness between these psychiatric disorders, we conducted an innovative meta-analysis of dysconnectivity findings reported separately in MDD, BD and SZ. Rather than relying on a classical voxel level coordinate-based approach, our procedure extracted relevant neuroanatomical labels from text data and examined findings at the whole brain network level. Data were drawn from 428 rsfMRI studies investigating MDD (158 studies, 7429 patients/7414 controls), BD (81 studies, 3330 patients/4096 patients) and/or SZ (223 studies, 11,168 patients/11,754 controls). Permutation testing revealed commonalities and differences in hypoconnectivity and hyperconnectivity patterns across disorders. ResultsHypoconnectivity and hyperconnectivity patterns of higher-order cognitive (default-mode, fronto-parietal, cingulo-opercular) networks were similarly observed across the three disorders. By contrast, dysconnectivity of lower-order (somatomotor, visual, auditory) networks in some cases differed between disorders, notably dissociating SZ from BD and MDD. ConclusionsFindings suggest that functional brain dysconnectivity of higher-order cognitive networks is largely transdiagnostic in nature while that of lower-order networks may best discriminate between mood and psychotic disorders, thus emphasizing the relevance of motor and sensory networks to psychiatric neuroscience.

The expert's knowledge combined with AI outperforms AI alone in seizure onset zone localization using resting state fMRI.

We evaluated whether integration of expert guidance on seizure onset zone (SOZ) identification from resting state functional MRI (rs-fMRI) connectomics combined with deep learning (DL) techniques enhances the SOZ delineation in patients with refractory epilepsy (RE), compared to utilizing DL alone. Rs-fMRI was collected from 52 children with RE who had subsequently undergone ic-EEG and then, if indicated, surgery for seizure control (n = 25). The resting state functional connectomics data were previously independently classified by two expert epileptologists, as indicative of measurement noise, typical resting state network connectivity, or SOZ. An expert knowledge integrated deep network was trained on functional connectomics data to identify SOZ. Expert knowledge integrated with DL showed a SOZ localization accuracy of 84.8 ± 4.5% and F1 score, harmonic mean of positive predictive value and sensitivity, of 91.7 ± 2.6%. Conversely, a DL only model yielded an accuracy of <50% (F1 score 63%). Activations that initiate in gray matter, extend through white matter, and end in vascular regions are seen as the most discriminative expert-identified SOZ characteristics. Integration of expert knowledge of functional connectomics can not only enhance the performance of DL in localizing SOZ in RE but also lead toward potentially useful explanations of prevalent co-activation patterns in SOZ. RE with surgical outcomes and preoperative rs-fMRI studies can yield expert knowledge most salient for SOZ identification.

Differential Effect of Global Signal Regression Between Awake and Anesthetized Conditions in Mice.

Introduction: In resting-state functional magnetic resonance imaging (rs-fMRI) studies, global signal regression (GSR) is a controversial preprocessing strategy. It effectively eliminates global noise driven by motion and respiration but also can introduce artifacts and remove functionally relevant metabolic information. Most preclinical rs-fMRI studies are performed in anesthetized animals, and anesthesia will alter both metabolic and neuronal activity. Methods: In this study, we explored the effect of GSR on rs-fMRI data collected under anesthetized and awake state in mice (n = 12). We measured global signal amplitude, and also functional connectivity (FC), functional connectivity density (FCD) maps, and brain modularity, all commonly used data-driven analysis methods to quantify connectivity patterns. Results: We found that global signal amplitude was similar between the awake and anesthetized states. However, GSR had a different impact on connectivity networks and brain modularity changes between states. We demonstrated that GSR had a more prominent impact on the anesthetized state, with a greater decrease in functional connectivity and increased brain modularity. We classified mice using the change in amplitude of brain modularity coefficient (ΔQ) before and after GSR processing. The results revealed that, when compared with the largest ΔQ group, the smallest ΔQ group had increased FCD in the cortex region in both the awake and anesthetized states. This suggests differences in individual mice may affect how GSR differentially affects awake versus anesthetized functional connectivity. Discussion: This study suggests that, for rs-fMRI studies which compare different physiological states, researchers should use GSR processing with caution.