Estimation of static and dynamic functional connectivity in resting-state fMRI using zero-frequency resonator.

Resting-state functional magnetic resonance imaging (rs-fMRI) is increasingly being used to infer the functional organization of the brain. Blood oxygen level-dependent (BOLD) features related to spontaneous neuronal activity, are yet to be clearly understood. Prior studies have hypothesized that rs-fMRI is spontaneous event-related and these events convey crucial information about the neuronal activity in estimating resting state functional connectivity (FC). Attempts have been made to extract these temporal events using a predetermined threshold. However, the thresholding methods in addition to being very sensitive to noise, may consider redundant events or exclude the low-valued inflection points. Here, we extract the event-related temporal onsets from the rs-fMRI time courses using a zero-frequency resonator (ZFR). The ZFR reflects the transient behavior of the BOLD events at its output. The conditional rate (CR) of the BOLD events occurring in a time course with respect to a seed time course is used to derive static FC. The temporal activity around the estimated events called high signal-to-noise ratio (SNR) segments are also obtained in the rs-fMRI time course and are then used to compute static and dynamic FCs during rest. Coactivation pattern (CAP) is the dynamic FC obtained using the high SNR segments driven by the ZFR. The static FC demonstrates that the ZFR-based CR distinguishes the coactivation and non-coactivation scores well in the distribution. CAP analysis demonstrated the stable and longer dwell time dominant resting state functional networks with high SNR segments driven by the ZFR. Static and dynamic FC analysis underpins that the ZFR-driven temporal onsets of BOLD events derive reliable and consistent FCs in the resting brain using a subset of the time points.

Delayed cerebrovascular reactivity in individuals with spinal cord injury in the right inferior parietal lobe: a breath-hold functional near-infrared spectroscopy study.

Cerebrovascular reactivity (CVR) reflects the ability of blood vessels to dilate or constrict in response to a vasoactive stimulus, and allows researchers to assess the brain's vascular health. Individuals with spinal cord injury (SCI) are at an increased risk for autonomic dysfunction in addition to cognitive impairments, which have been linked to a decline in CVR; however, there is currently a lack of brain-imaging studies that investigate how CVR is altered after SCI. In this study, we used a breath-holding hypercapnic stimulus and functional near-infrared spectroscopy (fNIRS) to investigate CVR alterations in individuals with SCI (n = 20, 14M, 6F, mean age = 46.3 ± 10.2 years) as compared to age- and sex-matched able-bodied (AB) controls (n = 25, 19M, 6F, mean age = 43.2 ± 12.28 years). CVR was evaluated by its amplitude and delay components separately by using principal component analysis and cross-correlation analysis, respectively. We observed significantly delayed CVR in the right inferior parietal lobe in individuals with SCI compared to AB controls (linear mixed-effects model, fixed-effects estimate = 6.565, Satterthwaite's t-test, t = 2.663, p = 0.008), while the amplitude of CVR was not significantly different. The average CVR delay in the SCI group in the right inferior parietal lobe was 14.21 s (sd: 6.60 s), and for the AB group, the average delay in the right inferior parietal lobe was 7.08 s (sd: 7.39 s). CVR delays were also associated with the duration since injury in individuals with SCI, in which a longer duration since injury was associated with a shortened delay in CVR in the right inferior parietal region (Pearson's r-correlation, r = -0.59, p = 0.04). This study shows that fNIRS can be used to quantify changes in CVR in individuals with SCI, and may be further used in rehabilitative settings to monitor the cerebrovascular health of individuals with SCI.

Effects of Tasks on Functional Brain Connectivity Derived from Inter-Individual Correlations: Insights from Regional Homogeneity of Functional MRI Data.

Research on brain functional connectivity often relies on intra-individual moment-to-moment correlations of functional brain activity, typically using techniques like functional MRI (fMRI). Inter-individual correlations are also employed on data from fMRI and positron emission tomography (PET). Many past studies have not specified tasks for participants, keeping them in an implicit "resting" condition. This lack of task specificity raises questions about how different tasks impact inter-individual correlation estimates. In our analysis of fMRI data from 100 unrelated participants, scanned during seven task conditions and in a resting state, we calculated Regional Homogeneity (ReHo) for each task as a regional measure of brain functions. We found that changes in ReHo due to different tasks were relatively small compared with the variations across brain regions. Cross-region variations of ReHo were highly correlated between different tasks. Similarly, whole-brain inter-individual correlation patterns were remarkably consistent across the tasks, showing correlations greater than 0.78. Changes in inter-individual correlations between tasks were primarily driven by connectivity in the visual, somatomotor, default mode network, and the interactions between them. The subtle yet statistically significant differences in functional connectivity may be linked to specific brain regions associated with the studied tasks. Future studies should consider task design when exploring inter-individual connectivity in specific brain systems.

The neurostructural consequences of glaucoma and their overlap with disorders exhibiting emotional dysregulations: A voxel-based meta-analysis and tripartite system model.

BACKGROUND: Glaucoma, a progressive neurodegenerative disorder leading to irreversible blindness, is associated with heightened rates of generalized anxiety and depression. This study aims to comprehensively investigate brain morphological changes in glaucoma patients, extending beyond visual processing areas, and explores overlaps with morphological alterations observed in anxiety and depression. METHODS: A comparative meta-analysis was conducted, using case-control studies of brain structural integrity in glaucoma patients. We aimed to identify regions with gray matter volume (GMV) changes, examine their role within distinct large-scale networks, and assess overlap with alterations in generalized anxiety disorder (GAD) and major depressive disorder (MDD). RESULTS: Glaucoma patients exhibited significant GMV reductions in visual processing regions (lingual gyrus, thalamus). Notably, volumetric reductions extended beyond visual systems, encompassing the left putamen and insula. Behavioral and functional network decoding revealed distinct large-scale networks, implicating visual, motivational, and affective domains. The insular region, linked to pain and affective processes, displayed reductions overlapping with alterations observed in GAD. LIMITATIONS: While the study identified significant morphological alterations, the number of studies from both the glaucoma and GAD cohorts remains limited due to the lack of independent studies meeting our inclusion criteria. CONCLUSION: The study proposes a tripartite brain model for glaucoma, with visual processing changes related to the lingual gyrus and additional alterations in the putamen and insular regions tied to emotional or motivational functions. These neuroanatomical changes extend beyond the visual system, implying broader implications for brain structure and potential pathological developments, providing insights into the overall neurological consequences of glaucoma.

Tracts in the limbic system show microstructural alterations post COVID-19 recovery.

Delirium, memory loss, attention deficit and fatigue are frequently reported by COVID survivors, yet the neurological pathways underlying these symptoms are not well understood. To study the possible mechanisms for these long-term sequelae after COVID-19 recovery, we investigated the microstructural properties of white matter in Indian cohorts of COVID-recovered patients and healthy controls. For the cross-sectional study presented here, we recruited 44 COVID-recovered patients and 29 healthy controls in New Delhi, India. Using deterministic whole-brain tractography on the acquired diffusion MRI scans, we traced 20 white matter tracts and compared fractional anisotropy, axial, mean and radial diffusivity between the cohorts. Our results revealed statistically significant differences (PFWE < 0.01) in the uncinate fasciculus, cingulum cingulate, cingulum hippocampus and arcuate fasciculus in COVID survivors, suggesting the presence of microstructural abnormalities. Additionally, in a subsequent subgroup analysis based on infection severity (healthy control, non-hospitalized patients and hospitalized patients), we observed a correlation between tract diffusion measures and COVID-19 infection severity. Although there were significant differences between healthy controls and infected groups, we found no significant differences between hospitalized and non-hospitalized COVID patients. Notably, the identified tracts are part of the limbic system and orbitofrontal cortex, indicating microstructural differences in neural circuits associated with memory and emotion. The observed white matter alterations in the limbic system resonate strongly with the functional deficits reported in Long COVID. Overall, our study provides additional evidence that damage to the limbic system could be a neuroimaging signature of Long COVID. The findings identify targets for follow-up studies investigating the long-term physiological and psychological impact of COVID-19.

Altered white matter functional pathways in Alzheimer's disease.

Alzheimer's disease (AD) is associated with functional disruption in gray matter (GM) and structural damage to white matter (WM), but the relationship to functional signal in WM is unknown. We performed the functional connectivity (FC) and graph theory analysis to investigate abnormalities of WM and GM functional networks and corpus callosum among different stages of AD from a publicly available dataset. Compared to the controls, AD group showed significantly decreased FC between the deep WM functional network (WM-FN) and the splenium of corpus callosum, between the sensorimotor/occipital WM-FN and GM visual network, but increased FC between the deep WM-FN and the GM sensorimotor network. In the clinical groups, the global assortativity, modular interaction between occipital WM-FN and visual network, nodal betweenness centrality, degree centrality, and nodal clustering coefficient in WM- and GM-FNs were reduced. However, modular interaction between deep WM-FN and sensorimotor network, and participation coefficients of deep WM-FN and splenium of corpus callosum were increased. These findings revealed the abnormal integration of functional networks in different stages of AD from a novel WM-FNs perspective. The abnormalities of WM functional pathways connect downward to the corpus callosum and upward to the GM are correlated with AD.

Corticostriatal causality analysis in children and adolescents with attention-deficit/hyperactivity disorder.

AIM: The effective connectivity between the striatum and cerebral cortex has not been fully investigated in attention-deficit/hyperactivity disorder (ADHD). Our objective was to explore the interaction effects between diagnosis and age on disrupted corticostriatal effective connectivity and to represent the modulation function of altered connectivity pathways in children and adolescents with ADHD. METHODS: We performed Granger causality analysis on 300 participants from a publicly available Attention-Deficit/Hyperactivity Disorder-200 dataset. By computing the correlation coefficients between causal connections between striatal subregions and other cortical regions, we estimated the striatal inflow and outflow connection to represent intermodulation mechanisms in corticostriatal pathways. RESULTS: Interactions between diagnosis and age were detected in the superior occipital gyrus within the visual network, medial prefrontal cortex, posterior cingulate gyrus, and inferior parietal lobule within the default mode network, which is positively correlated with hyperactivity/impulsivity severity in ADHD. Main effect of diagnosis exhibited a general higher cortico-striatal causal connectivity involving default mode network, frontoparietal network and somatomotor network in ADHD compared with comparisons. Results from high-order effective connectivity exhibited a disrupted information pathway involving the default mode-striatum-somatomotor-striatum-frontoparietal networks in ADHD. CONCLUSION: The interactions detected in the visual-striatum-default mode networks pathway appears to be related to the potential distraction caused by long-term abnormal information input from the retina in ADHD. Higher causal connectivity and weakened intermodulation may indicate the pathophysiological process that distractions lead to the impairment of motion planning function and the inhibition/control of this unplanned motion signals in ADHD.

Brain activation during the N-back working memory task in individuals with spinal cord injury: a functional near-infrared spectroscopy study.

Cognitive impairments have frequently been reported in individuals with spinal cord injury (SCI) across different domains such as working memory, attention, and executive function. The mechanism of cognitive impairment after SCI is not well understood due to the heterogeneity of SCI sample populations, and may possibly be due to factors such as cardiovascular dysfunction, concomitant traumatic brain injury (TBI), hypoxia, sleep disorders, and body temperature dysregulation. In this study, we implement the Neuropsychiatric Unit Cognitive Assessment Tool (NUCOG) to assess cognitive differences between individuals with SCI and age-matched able-bodied (AB) controls. We then use an N-back working memory task and functional near-infrared spectroscopy (fNIRS) to elucidate the neurovascular correlates of cognitive function in individuals with SCI. We observed significant differences between the SCI and AB groups on measures of executive function on the NUCOG test. On the N-back task, across the three levels of difficulty: 0-back, 2-back, and 3-back, no significant differences were observed between the SCI and AB group; however, both groups performed worse as the level of difficulty increased. Although there were no significant differences in N-back performance scores between the two groups, functional brain hemodynamic activity differences were observed between the SCI and AB groups, with the SCI group exhibiting higher maximum oxygenated hemoglobin concentration in the right inferior parietal lobe. These findings support the use of fNIRS to study cognitive function in individuals with SCI and may provide a useful tool during rehabilitation to obtain quantitative functional brain activity metrics.

Explorations of using a convolutional neural network to understand brain activations during movie watching.

Neuroimaging studies increasingly use naturalistic stimuli like video clips to trigger complex brain activations, but the complexity of such stimuli makes it difficult to assign specific functions to the resulting brain activations, particularly for higher-level content like social interactions. To address this challenge, researchers have turned to deep neural networks, e.g., convolutional neural networks (CNNs). CNNs have shown success in image recognition due to their different levels of features enabling high performance. In this study, we used pre-trained VGG-16, a popular CNN model, to analyze video data and extract hierarchical features from low-level shallow layers to high-level deeper layers, linking these activations to different levels of activation of the human brain. We hypothesized that activations in different layers of VGG-16 would be associated with different levels of brain activation and visual processing hierarchy in the brain. We were also curious about which brain regions would be associated with deeper convolutional layers in VGG-16. The study analyzed a functional MRI (fMRI) dataset where participants watched the cartoon movie Partly Cloudy. Frames of the videos were fed into VGG-16, and activation maps from different kernels and layers were extracted. Time series of the average activation patterns for each kernel were created and fed into a voxel-wise model to study brain activations. Results showed that lower convolutional layers (1st convolutional layer) were mostly associated with lower visual regions, but some kernels (6, 19, 24, 42, 55, and 58) surprisingly showed associations with activations in the posterior cingulate cortex, part of the default mode network. Deeper convolutional layers were associated with more anterior and lateral portions of the visual cortex (e.g., the lateral occipital complex) and the supramarginal gyrus. Analyzing activation features associated with different brain regions showed the promise and limitations of using CNNs to link video content to brain functions.

Aberrant interhemispheric structural and functional connectivity within whole brain in schizophrenia.

OBJECTIVE: Schizophrenia is a serious mental disorder whose etiology remains unclear. Although numerous studies have analyzed the abnormal gray matter functional activity and whole-brain anatomical changes in schizophrenia, fMRI signal fluctuations from white matter have usually been ignored and rarely reported in the literature. METHODS: We employed 45 schizophrenia subjects and 75 healthy controls (HCs) from a publicly available fMRI dataset. By combining the voxel-mirrored homotopic connectivity (VMHC) measure and fiber tracking method, we investigated the interhemispheric functional and structural connectivity within whole brain in schizophrenia. RESULTS: Compared to HCs, patients with schizophrenia exhibited significantly reduced VMHC in the bilateral middle occipital gyrus, precentral gyrus, postcentral gyrus and corpus callosum. Fiber tracking results showed the changes in structural connectivity for the bilateral precentral gyrus, and the bilateral corpus callosum, and the fiber bundles connecting bilateral precentral gyrus and connecting the bilateral corpus callosum passed through the posterior midbody, isthmus and splenium of mid-sagittal corpus callosum, which closely related to the interhemispheric integration of visual and auditory information. More importantly, we observed a negative correlation between averaged VMHC values in the postcentral gyrus and SAPS scores, and a positive correlation between the fractional anisotropy of fiber bundle connecting the bilateral precentral gyrus and Matrix Reasoning scores in schizophrenia. CONCLUSION: Our findings provide a novel perspective of white matter functional images on understanding abnormal interhemispheric visual and auditory information transfer in schizophrenia.

The significance and limited influence of cerebrovascular reactivity on age and sex effects in task- and resting-state brain activity.

Functional MRI measures the blood-oxygen-level dependent signals, which provide an indirect measure of neural activity mediated by neurovascular responses. Cerebrovascular reactivity affects both task-induced and resting-state blood-oxygen-level dependent activity and may confound inter-individual effects, such as those related to aging and biological sex. We examined a large dataset containing breath-holding, checkerboard, and resting-state tasks. We used the breath-holding task to measure cerebrovascular reactivity, used the checkerboard task to obtain task-based activations, and quantified resting-state activity with amplitude of low-frequency fluctuations and regional homogeneity. We hypothesized that cerebrovascular reactivity would be correlated with blood-oxygen-level dependent measures and that accounting for these correlations would result in better estimates of age and sex effects. We found that cerebrovascular reactivity was correlated with checkerboard task activations in the visual cortex and with amplitude of low-frequency fluctuations and regional homogeneity in widespread fronto-parietal regions, as well as regions with large vessels. We also found significant age and sex effects in cerebrovascular reactivity, some of which overlapped with those observed in amplitude of low-frequency fluctuations and regional homogeneity. However, correcting for the effects of cerebrovascular reactivity had very limited influence on the estimates of age and sex. Our results highlight the limitations of accounting for cerebrovascular reactivity with the current breath-holding task.

Boosting interpersonal emotion regulation through facial imitation: functional neuroimaging foundations.

Empathic function, which is primarily manifested by facial imitation, is believed to play a pivotal role in interpersonal emotion regulation for mood reinstatement. To explore this association and its neural substrates, we performed a questionnaire survey (study l) to identify the relationship between empathy and interpersonal emotion regulation; and a task-mode fMRI study (study 2) to explore how facial imitation, as a fundamental component of empathic processes, promotes the interpersonal emotion regulation effect. Study 1 showed that affective empathy was positively correlated with interpersonal emotion regulation. Study 2 showed smaller negative emotions in facial imitation interpersonal emotion regulation (subjects imitated experimenter's smile while followed the interpersonal emotion regulation guidance) than in normal interpersonal emotion regulation (subjects followed the interpersonal emotion regulation guidance) and Watch conditions. Mirror neural system (e.g. inferior frontal gyrus and inferior parietal lobe) and empathy network exhibited greater activations in facial imitation interpersonal emotion regulation compared with normal interpersonal emotion regulation condition. Moreover, facial imitation interpersonal emotion regulation compared with normal interpersonal emotion regulation exhibited increased functional coupling from mirror neural system to empathic and affective networks during interpersonal emotion regulation. Furthermore, the connectivity of the right orbital inferior frontal gyrus-rolandic operculum lobe mediated the association between the accuracy of facial imitation and the interpersonal emotion regulation effect. These results show that the interpersonal emotion regulation effect can be enhanced by the target's facial imitation through increased functional coupling from mirror neural system to empathic and affective neural networks.

Structural Connectomes of COVID-Survivors Show Disruption in Global Integration and Small-Worldness.

Even after recovery from the COVID-19 infection, there have been a multitude of cases reporting post-COVID neurological symptoms including memory loss, brain fog, and attention deficit. Many studies have observed localized microstructural damages in the white matter regions of COVID survivors, indicating potential damage to the axonal pathways in the brain. Therefore, in this study, we have investigated the global impact of localized damage to white matter tracts using graph theoretical analysis of the structural connectome of 45 COVID-recovered subjects and 30 Healthy Controls (HCs). We have implemented Diffusion Tensor Imaging based reconstruction followed by deterministic tractography to extract structural connections among different regions of the brain. Interpreting this structural connectivity as weighted undirected graphs, we have used graph theoretical measures like global efficiency, characteristic path length (CPL), clustering coefficient (CC), modularity, Fiedler value, and assortativity coefficient to quantify the global integration, segregation, and robustness of the brain networks. We statistically compare the cohorts based on these graph measures by employing permutation testing for 100,000 permutations. Post multiple comparisons error correction, we find that the COVID-recovered cohort shows a reduction in global efficiency and CC while they exhibit higher modularity and CPL. This disruption of the balance between global integration and segregation indicates the loss of small-world property in COVID survivors' connectomes which has been linked with other disorders such as cognitive impairment and Alzheimer's. Overall, our study sheds light on the alterations in structural connectivity and its role in post-COVID symptoms.

Characterizing the spatiotemporal features of functional connectivity across the white matter and gray matter during the naturalistic condition.

Introduction: The naturalistic stimuli due to its ease of operability has attracted many researchers in recent years. However, the influence of the naturalistic stimuli for whole-brain functions compared with the resting state is still unclear. Methods: In this study, we clustered gray matter (GM) and white matter (WM) masks both at the ROI- and network-levels. Functional connectivity (FC) and inter-subject functional connectivity (ISFC) were calculated in GM, WM, and between GM and WM under the movie-watching and the resting-state conditions. Furthermore, intra-class correlation coefficients (ICC) of FC and ISFC were estimated on different runs of fMRI data to denote the reliability of them during the two conditions. In addition, static and dynamic connectivity indices were calculated with Pearson correlation coefficient to demonstrate the associations between the movie-watching and the resting-state. Results: As the results, we found that the movie-watching significantly affected FC in whole-brain compared with the resting-state, but ISFC did not show significant connectivity induced by the naturalistic condition. ICC of FC and ISFC was generally higher during movie-watching compared with the resting-state, demonstrating that naturalistic stimuli could promote the reliability of connectivity. The associations between static and dynamic ISFC were weakly negative correlations in the naturalistic stimuli while there is no correlation between them under resting-state condition. Discussion: Our findings confirmed that compared to resting-state condition, the connectivity indices under the naturalistic stimuli were more reliable and stable to investigate the normal functional activities of the human brain, and might promote the applications of FC in the cerebral dysfunction in various mental disorders.

Comparative analysis of group information-guided independent component analysis and independent vector analysis for assessing brain functional network characteristics in autism spectrum disorder.

Introduction: Group information-guided independent component analysis (GIG-ICA) and independent vector analysis (IVA) are two methods that improve estimation of subject-specific independent components in neuroimaging studies. These methods have shown better performance than traditional group independent component analysis (GICA) with respect to intersubject variability (ISV). Methods: In this study, we compared the patterns of community structure, spatial variance, and prediction performance of GIG-ICA and IVA-GL, respectively. The dataset was obtained from the publicly available Autism Brain Imaging Data Exchange (ABIDE) database, comprising 75 healthy controls (HC) and 102 Autism Spectrum Disorder (ASD) participants. The greedy rule was used to match components from IVA-GL and GIG-ICA in order to compare the similarities between the two methods. Results: Robust correspondence was observed between the two methods the following networks: cerebellum network (CRN; |r| = 0.7813), default mode network (DMN; |r| = 0.7263), self-reference network (SRN; |r| = 0.7818), ventral attention network (VAN; |r| = 0.7574), and visual network (VSN; |r| = 0.7503). Additionally, the Sensorimotor Network demonstrated the highest similarity between IVA-GL and GIG-ICA (SOM: |r| = 0.8125). Our findings revealed a significant difference in the number of modules identified by the two methods (HC: p < 0.001; ASD: p < 0.001). GIG-ICA identified significant differences in FNC between HC and ASD compared to IVA-GL. However, in correlation analysis, IVA-GL identified a statistically negative correlation between FNC of ASD and the social total subscore of the classic Autism Diagnostic Observation Schedule (ADOS: pi = -0.26, p = 0.0489). Moreover, both methods demonstrated similar prediction performances on age within specific networks, as indicated by GIG-ICA-CRN (R2 = 0.91, RMSE = 3.05) and IVA-VAN (R2 = 0.87, RMSE = 3.21). Conclusion: In summary, IVA-GL demonstrated lower modularity, suggesting greater sensitivity in estimating networks with higher intersubject variability. The improved age prediction of cerebellar-attention networks underscores their importance in the developmental progression of ASD. Overall, IVA-GL may be appropriate for investigating disorders with greater variability, while GIG-ICA identifies functional networks with distinct modularity patterns.

Structural-functional connectivity deficits of callosal-white matter-cortical circuits in schizophrenia.

Schizophrenia is increasingly recognized as a disorder with altered integration between large-scale functional networks and cortical-subcortical pathways. This spatial long-distance information communication must be associated with white matter (WM) fiber bundles. With accumulating evidence that WM functional signals reflect the intrinsic neural activities, how the deep callosal organization modulates cortical functional activities through WM remains unclear in schizophrenia. Using a data-driven method, we identified nine WM and gray matter (GM) functional networks, and then parcellated corpus callosum into distinct sub-regions. Combining functional connectivity and fiber tracking analysis, we estimated the structural and functional connectivity changes of callosal-WM-cortical circuits in schizophrenia. We observed higher structural and functional connectivity between corpus callosum, WM and GM functional networks involving visual network (visual processing), executive control network (executive controls), ventral attention network (processing of salience), and limbic network (emotion processing) in schizophrenia compared to healthy controls. We also found nine abnormal pathways of callosal-WM-cortical circuits involving the above networks and default mode network (self-related thought). These results highlight the role of connectivity deficits in callosal-WM-cortical circuits may play in understanding the delusions, hallucinations and cognitive impairment of schizophrenia.

The Significance and Limited Influence of Cerebrovascular Reactivity on Age and Sex Effects in Task- and Resting-State Brain Activity.

Functional MRI (fMRI) measures the blood-oxygen-level dependent (BOLD) signals, which provide an indirect measure of neural activity mediated by neurovascular responses. Cerebrovascular reactivity affects both task-induced and resting-state BOLD activity and may confound inter-individual effects observed in BOLD-based measures, such as those related to aging and biological sex. To investigate this, we examined a large open-access fMRI dataset containing a breath-holding task, checkerboard task, and resting-state scans. We used the breath-holding task to measure cerebrovascular reactivity, used the checkerboard task to obtain task-based activations, and from the resting-state data, we quantified the resting-state amplitude of low-frequency fluctuations (ALFF), and resting-state regional homogeneity (ReHo). We hypothesized that cerebrovascular reactivity would be correlated with BOLD measures and that accounting for these correlations would result in better estimates of age and sex effects. Our analysis showed that cerebrovascular reactivity was correlated with checkerboard task activations in the visual cortex and with ALFF and ReHo in widespread fronto-parietal regions, as well as regions with large vessels. We also found significant age and sex effects in cerebrovascular reactivity, some of which overlapped with those observed in ALFF and ReHo scores. Finally, we demonstrated that correcting for the effects of cerebrovascular reactivity had very limited influence on the estimates of age and sex. Our results highlight the limitations of accounting for cerebrovascular reactivity with the current breath-holding task.

Whole-brain structure-function coupling abnormalities in mild cognitive impairment: a study combining amplitude of low-frequency fluctuations and voxel-based morphometry.

Alzheimer's disease (AD), one of the leading diseases of the nervous system, is accompanied by symptoms such as loss of memory, thinking and language skills. Both mild cognitive impairment (MCI) and very mild cognitive impairment (VMCI) are the transitional pathological stages between normal aging and AD. While the changes in whole-brain structural and functional information have been extensively investigated in AD, The impaired structure-function coupling remains unknown. The current study employed the OASIS-3 dataset, which includes 53 MCI, 90 VMCI, and 100 Age-, gender-, and education-matched normal controls (NC). Several structural and functional parameters, such as the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and The ALFF/VBM ratio, were used To estimate The whole-brain neuroimaging changes In MCI, VMCI, and NC. As disease symptoms became more severe, these regions, distributed in the frontal-inf-orb, putamen, and paracentral lobule in the white matter (WM), exhibited progressively increasing ALFF (ALFFNC < ALFFVMCI < ALFFMCI), which was similar to the tendency for The cerebellum and putamen in the gray matter (GM). Additionally, as symptoms worsened in AD, the cuneus/frontal lobe in the WM and the parahippocampal gyrus/hippocampus in the GM showed progressively decreasing structure-function coupling. As the typical focal areas in AD, The parahippocampal gyrus and hippocampus showed significant positive correlations with the severity of cognitive impairment, suggesting the important applications of the ALFF/VBM ratio in brain disorders. On the other hand, these findings from WM functional signals provided a novel perspective for understanding the pathophysiological mechanisms involved In cognitive decline in AD.

Individual differences in time-varying and stationary brain connectivity during movie watching from childhood to early adulthood: Age, sex, and behavioral associations.

Spatially remote brain regions exhibit dynamic functional interactions across various task conditions. While time-varying functional connectivity during movie watching shows sensitivity to movie content, stationary functional connectivity remains relatively stable across videos. These findings suggest that dynamic and stationary functional interactions may represent different aspects of brain function. However, the relationship between individual differences in time-varying and stationary connectivity and behavioral phenotypes remains elusive. To address this gap, we analyzed an open-access functional MRI dataset comprising participants aged 5-22 years, who watched two cartoon movie clips. We calculated regional brain activity, time-varying connectivity, and stationary connectivity, examining associations with age, sex, and behavioral assessments. Model comparison revealed that time-varying connectivity was more sensitive to age and sex effects compared with stationary connectivity. The preferred age models exhibited quadratic log age or quadratic age effects, indicative of inverted-U shaped developmental patterns. In addition, females showed higher consistency in regional brain activity and time-varying connectivity than males. However, in terms of behavioral predictions, only stationary connectivity demonstrated the ability to predict full-scale intelligence quotient. These findings suggest that individual differences in time-varying and stationary connectivity may capture distinct aspects of behavioral phenotypes.

Transcriptomic and Macroscopic Architectures of Multimodal Covariance Network Reveal Molecular-Structural-Functional Co-alterations.

Human cognition is usually underpinned by intrinsic structure and functional neural co-activation in spatially distributed brain regions. Owing to lacking an effective approach to quantifying the covarying of structure and functional responses, how the structural-functional circuits interact and how genes encode the relationships, to deepen our knowledge of human cognition and disease, are still unclear. Here, we propose a multimodal covariance network (MCN) construction approach to capture interregional covarying of the structural skeleton and transient functional activities for a single individual. We further explored the potential association between brain-wide gene expression patterns and structural-functional covarying in individuals involved in a gambling task and individuals with major depression disorder (MDD), adopting multimodal data from a publicly available human brain transcriptomic atlas and 2 independent cohorts. MCN analysis showed a replicable cortical structural-functional fine map in healthy individuals, and the expression of cognition- and disease phenotype-related genes was found to be spatially correlated with the corresponding MCN differences. Further analysis of cell type-specific signature genes suggests that the excitatory and inhibitory neuron transcriptomic changes could account for most of the observed correlation with task-evoked MCN differences. In contrast, changes in MCN of MDD patients were enriched for biological processes related to synapse function and neuroinflammation in astrocytes, microglia, and neurons, suggesting its promising application in developing targeted therapies for MDD patients. Collectively, these findings confirmed the correlations of MCN-related differences with brain-wide gene expression patterns, which captured genetically validated structural-functional differences at the cellular level in specific cognitive processes and psychiatric patients.