Impaired visual-motor functional connectivity in first-episode medication-naïve patients with major depressive disorder.

The perceptual dysfunctions have been fundamental causes of cognitive and emotional problems in patients with major depressive disorder. However, visual system impairment in depression has been underexplored. Here, we explored functional connectivity in a large cohort of first-episode medication-naïve patients with major depressive disorder (n = 190) and compared it with age- and sex-matched healthy controls (n = 190). A recently developed individual-oriented approach was applied to parcellate the cerebral cortex into 92 regions of interest using resting-state functional magnetic resonance imaging data. Significant reductions in functional connectivities were observed between the right lateral occipitotemporal junction within the visual network and 2 regions of interest within the sensorimotor network in patients. The volume of right lateral occipitotemporal junction was also significantly reduced in major depressive disorder patients, indicating that this visual region is anatomically and functionally impaired. Behavioral correlation analysis showed that the reduced functional connectivities were significantly associated with inhibition control in visual-motor processing in patients. Taken together, our data suggest that functional connectivity between visual network and sensorimotor network already shows a significant reduction in the first episode of major depressive disorder, which may interfere with the inhibition control in visual-motor processing. The lateral occipitotemporal junction may be a hub of disconnection and may play a role in the pathophysiology of major depressive disorder.

Impact of the day/night cycle on functional connectome in ageing male and female mice.

To elucidate how time of day, sex, and age affect functional connectivity (FC) in mice, we aimed to examine whether the mouse functional connectome varied with the day/night cycle and whether it depended on sex and age. We explored C57Bl6/J mice (6♀ and 6♂) at mature age (5 ± 1 months) and middle-age (14 ± 1 months). Each mouse underwent Blood Oxygen-Level-Dependent (BOLD) resting-state functional MRI (rs-fMRI) on a 7T scanner at four different times of the day, two under the light condition and two under the dark condition. Data processing consisted of group independent component analysis (ICA) and region-level analysis using resting-state networks (RSNs) derived from literature. Linear mixed-effect models (LMEM) were used to assess the effects of sex, lighting condition and their interactions for each RSN obtained with group-ICA (RSNs-GICA) and six bilateral RSNs adapted from literature (RSNs-LIT). Our study highlighted new RSNs in mice related to day/night alternation in addition to other networks already reported in the literature. In mature mice, we found sex-related differences in brain activation only in one RSNs-GICA comprising the cortical, hippocampal, midbrain and cerebellar regions of the right hemisphere. In males, brain activity was significantly higher in the left hippocampus, the retrosplenial cortex, the superior colliculus, and the cerebellum regardless of lighting condition; consistent with the role of these structures in memory formation and integration, sleep, and sex-differences in memory processing. Experimental constraints limited the analysis to the impact of light/dark cycle on the RSNs for middle-aged females. We detected significant activation in the pineal gland during the dark condition, a finding in line with the nocturnal activity of this gland. For the analysis of RSNs-LIT, new variables "sexage" (sex and age combined) and "edges" (pairs of RSNs) were introduced. FC was calculated as the Pearson correlation between two RSNs. LMEM revealed no effect of sexage or lighting condition. The FC depended on the edges, but there were no interaction effects between sexage, lighting condition and edges. Interaction effects were detected between i) sex and lighting condition, with higher FC in males under the dark condition, ii) sexage and edges with higher FC in male brain regions related to vision, memory, and motor action. We conclude that time of day and sex should be taken into account when designing, analyzing, and interpreting functional imaging studies in rodents.

Small vessel disease and cognitive reserve oppositely modulate global network redundancy and cognitive function: A study in middle-to-old aged community participants.

Cerebral small vessel disease (SVD) can disrupt the global brain network and lead to cognitive impairment. Conversely, cognitive reserve (CR) can improve one's cognitive ability to handle damaging effects like SVD, partly by optimizing the brain network's organization. Understanding how SVD and CR collectively influence brain networks could be instrumental in preventing cognitive impairment. Recently, brain redundancy has emerged as a critical network protective metric, providing a nuanced perspective of changes in network organization. However, it remains unclear how SVD and CR affect global redundancy and subsequently cognitive function. Here, we included 121 community-dwelling participants who underwent neuropsychological assessments and a multimodal MRI examination. We visually examined common SVD imaging markers and assessed lifespan CR using the Cognitive Reserve Index Questionnaire. We quantified the global redundancy index (RI) based on the dynamic functional connectome. We then conducted multiple linear regressions to explore the specific cognitive domains related to RI and the associations of RI with SVD and CR. We also conducted mediation analyses to explore whether RI mediated the relationships between SVD, CR, and cognition. We found negative correlations of RI with the presence of microbleeds (MBs) and the SVD total score, and a positive correlation of RI with leisure activity-related CR (CRI-leisure). RI was positively correlated with memory and fully mediated the relationships between the MBs, CRI-leisure, and memory. Our study highlights the potential benefits of promoting leisure activities and keeping brain redundancy for memory preservation in older adults, especially those with SVD.

Adaptive-to-maladaptive gradient of emotion regulation tendencies are embedded in the functional-structural hybrid connectome.

BACKGROUND: Emotion regulation tendencies are well-known transdiagnostic markers of psychopathology, but their neurobiological foundations have mostly been examined within the theoretical framework of cortical-subcortical interactions. METHODS: We explored the connectome-wide neural correlates of emotion regulation tendencies using functional and diffusion magnetic resonance images of healthy young adults (N = 99; age 20-30; 28 females). We first tested the importance of considering both the functional and structural connectome through intersubject representational similarity analyses. Then, we employed a canonical correlation analysis between the functional-structural hybrid connectome and 23 emotion regulation strategies. Lastly, we sought to externally validate the results on a transdiagnostic adolescent sample (N = 93; age 11-19; 34 females). RESULTS: First, interindividual similarity of emotion regulation profiles was significantly correlated with interindividual similarity of the functional-structural hybrid connectome, more so than either the functional or structural connectome. Canonical correlation analysis revealed that an adaptive-to-maladaptive gradient of emotion regulation tendencies mapped onto a specific configuration of covariance within the functional-structural hybrid connectome, which primarily involved functional connections in the motor network and the visual networks as well as structural connections in the default mode network and the subcortical-cerebellar network. In the transdiagnostic adolescent dataset, stronger functional signatures of the found network were associated with higher general positive affect through more frequent use of adaptive coping strategies. CONCLUSIONS: Taken together, our study illustrates a gradient of emotion regulation tendencies that is best captured when simultaneously considering the functional and structural connections across the whole brain.

Aberrant brain network topology in youth with a familial risk for bipolar disorder: a task-based fMRI connectome study.

BACKGROUND: Youth with a family history of bipolar disorder (BD) may be at increased risk for mood disorders and for developing side effects after antidepressant exposure. The neurobiological basis of these risks remains poorly understood. We aimed to identify biomarkers underlying risk by characterizing abnormalities in the brain connectome of symptomatic youth at familial risk for BD. METHODS: Depressed and/or anxious youth (n = 119, age = 14.9 ± 1.6 years) with a family history of BD but no prior antidepressant exposure and typically developing controls (n = 57, age = 14.8 ± 1.7 years) received functional magnetic resonance imaging (fMRI) during an emotional continuous performance task. A generalized psychophysiological interaction (gPPI) analysis was performed to compare their brain connectome patterns, followed by machine learning of topological metrics. RESULTS: High-risk youth showed weaker connectivity patterns that were mainly located in the default mode network (DMN) (network weight = 50.1%) relative to controls, and connectivity patterns derived from the visual network (VN) constituted the largest proportion of aberrant stronger pairs (network weight = 54.9%). Global local efficiency (Elocal, p = .022) and clustering coefficient (Cp, p = .029) and nodal metrics of the right superior frontal gyrus (SFG) (Elocal: p < .001; Cp: p = .001) in the high-risk group were significantly higher than those in healthy subjects, and similar patterns were also found in the left insula (degree: p = .004; betweenness: p = .005; age-by-group interaction, p = .038) and right hippocampus (degree: p = .003; betweenness: p = .003). The case-control classifier achieved a cross-validation accuracy of 78.4%. CONCLUSIONS: Our findings of abnormal connectome organization in the DMN and VN may advance mechanistic understanding of risk for BD. Neuroimaging biomarkers of increased network segregation in the SFG and altered topological centrality in the insula and hippocampus in broader limbic systems may be used to target interventions tailored to mitigate the underlying risk of brain abnormalities in these at-risk youth.

Connectome-based prediction modeling of cognitive control using functional and structural connectivity.

BACKGROUND: Cognitive control involves flexibly configuring mental resources and adjusting behavior to achieve goal-directed actions. It is associated with the coordinated activity of brain networks, although it remains unclear how both structural and functional brain networks can predict cognitive control. Connectome-based predictive modeling (CPM) is a powerful tool for predicting cognitive control based on brain networks. METHODS: The study used CPM to predict cognitive control in 102 healthy adults from the UCLA Consortium for Neuropsychiatric Phenomics dataset and further compared structural and functional connectome characteristics that support cognitive control. RESULTS: Our results showed that both structural (r values 0.263-0.375) and functional (r values 0.336-0.503) connectomes can significantly predict individuals' cognitive control subcomponents. There is overlap between the functional and structural networks of all three cognitive control subcomponents, particularly in the frontoparietal (FP) and motor (Mot) networks, while each subcomponent also has its own unique weight prediction network. Overall, the functional and structural connectivity that supports different cognitive control subcomponents manifests overlapping and distinct spatial patterns. CONCLUSIONS: The structural and functional connectomes provide complementary information for predicting cognitive control ability. Integrating information from both connectomes offers a more comprehensive understanding of the neural underpinnings of cognitive control.

Multivariate resting-state functional connectomes predict and characterize obesity phenotypes.

The univariate obesity-brain associations have been extensively explored, while little is known about the multivariate associations between obesity and resting-state functional connectivity. We therefore utilized machine learning and resting-state functional connectivity to develop and validate predictive models of 4 obesity phenotypes (i.e. body fat percentage, body mass index, waist circumference, and waist-height ratio) in 3 large neuroimaging datasets (n = 2,992). Preliminary evidence suggested that the resting-state functional connectomes effectively predicted obesity/weight status defined by each obesity phenotype with good generalizability to longitudinal and independent datasets. However, the differences between resting-state functional connectivity patterns characterizing different obesity phenotypes indicated that the obesity-brain associations varied according to the type of measure of obesity. The shared structure among resting-state functional connectivity patterns revealed reproducible neuroimaging biomarkers of obesity, primarily comprising the connectomes within the visual cortex and between the visual cortex and inferior parietal lobule, visual cortex and orbital gyrus, and amygdala and orbital gyrus, which further suggested that the dysfunctions in the perception, attention and value encoding of visual information (e.g. visual food cues) and abnormalities in the reward circuit may act as crucial neurobiological bases of obesity. The recruitment of multiple obesity phenotypes is indispensable in future studies seeking reproducible obesity-brain associations.

Heritability of individualized cortical network topography.

Human cortex is patterned by a complex and interdigitated web of large-scale functional networks. Recent methodological breakthroughs reveal variation in the size, shape, and spatial topography of cortical networks across individuals. While spatial network organization emerges across development, is stable over time, and is predictive of behavior, it is not yet clear to what extent genetic factors underlie interindividual differences in network topography. Here, leveraging a nonlinear multidimensional estimation of heritability, we provide evidence that individual variability in the size and topographic organization of cortical networks are under genetic control. Using twin and family data from the Human Connectome Project (n = 1,023), we find increased variability and reduced heritability in the size of heteromodal association networks (h2 : M = 0.34, SD = 0.070), relative to unimodal sensory/motor cortex (h2 : M = 0.40, SD = 0.097). We then demonstrate that the spatial layout of cortical networks is influenced by genetics, using our multidimensional estimation of heritability (h2-multi; M = 0.14, SD = 0.015). However, topographic heritability did not differ between heteromodal and unimodal networks. Genetic factors had a regionally variable influence on brain organization, such that the heritability of network topography was greatest in prefrontal, precuneus, and posterior parietal cortex. Taken together, these data are consistent with relaxed genetic control of association cortices relative to primary sensory/motor regions and have implications for understanding population-level variability in brain functioning, guiding both individualized prediction and the interpretation of analyses that integrate genetics and neuroimaging.

The Effect of Sleep Deprivation on Brain Fingerprint Stability: A Magnetoencephalography Validation Study.

This study examined the stability of the functional connectome (FC) over time using fingerprint analysis in healthy subjects. Additionally, it investigated how a specific stressor, namely sleep deprivation, affects individuals' differentiation. To this aim, 23 healthy young adults underwent magnetoencephalography (MEG) recording at three equally spaced time points within 24 h: 9 a.m., 9 p.m., and 9 a.m. of the following day after a night of sleep deprivation. The findings indicate that the differentiation was stable from morning to evening in all frequency bands, except in the delta band. However, after a night of sleep deprivation, the stability of the FCs was reduced. Consistent with this observation, the reduced differentiation following sleep deprivation was found to be negatively correlated with the effort perceived by participants in completing the cognitive task during sleep deprivation. This correlation suggests that individuals with less stable connectomes following sleep deprivation experienced greater difficulty in performing cognitive tasks, reflecting increased effort.

Existence of Functional Connectome Fingerprint during Infancy and Its Stability over Months.

The functional connectome fingerprint is a cluster of individualized brain functional connectivity patterns that are capable of distinguishing one individual from others. Although its existence has been demonstrated in adolescents and adults, whether such individualized patterns exist during infancy is barely investigated despite its importance in identifying the origin of the intrinsic connectome patterns that potentially mirror distinct behavioral phenotypes. To fill this knowledge gap, capitalizing on a longitudinal high-resolution structural and resting-state functional MRI dataset with 104 human infants (53 females) with 806 longitudinal scans (age, 16-876 d) and infant-specific functional parcellation maps, we observe that the brain functional connectome fingerprint may exist since infancy and keeps stable over months during early brain development. Specifically, we achieve an ∼78% individual identification rate by using ∼5% selected functional connections, compared with the best identification rate of 60% without connection selection. The frontoparietal networks recognized as the most contributive networks in adult functional connectome fingerprinting retain their superiority in infants despite being widely acknowledged as rapidly developing systems during childhood. The existence and stability of the functional connectome fingerprint are further validated on adjacent age groups. Moreover, we show that the infant frontoparietal networks can reach similar accuracy in predicting individual early learning composite scores as the whole-brain connectome, again resembling the observations in adults and highlighting the relevance of functional connectome fingerprint to cognitive performance. For the first time, these results suggest that each individual may retain a unique and stable marker of functional connectome during early brain development.SIGNIFICANCE STATEMENT Functional connectome fingerprinting during infancy featuring rapid brain development remains almost uninvestigated even though it is essential for understanding the early individual-level intrinsic pattern of functional organization and its relationship with distinct behavioral phenotypes. With an infant-tailored functional connection selection and validation strategy, we strive to provide the delineation of the infant functional connectome fingerprint by examining its existence, stability, and relationship with early cognitive performance. We observe that the brain functional connectome fingerprint may exist since early infancy and remains stable over months during the first 2 years. The identified key contributive functional connections and networks for fingerprinting are also verified to be highly predictive for cognitive score prediction, which reveals the association between infant connectome fingerprint and cognitive performance.

Effects of phase encoding direction on test-retest reliability of human functional connectome.

The majority of human connectome studies in the literature based on functional magnetic resonance imaging (fMRI) data use either an anterior-to-posterior (AP) or a posterior-to-anterior (PA) phase encoding direction (PED). However, whether and how PED would affect test-retest reliability of functional connectome is unclear. Here, in a sample of healthy subjects with two sessions of fMRI scans separated by 12 weeks (two runs per session, one with AP, the other with PA), we tested the influence of PED on global, nodal, and edge connectivity in the constructed brain networks. All data underwent the state-of-the-art Human Connectome Project (HCP) pipeline to correct for phase-encoding-related distortions before entering analysis. We found that at the global level, the PA scans showed significantly higher intraclass correlation coefficients (ICCs) for global connectivity compared with AP scans, which was particularly prominent when using the Seitzman-300 atlas (versus the CAB-NP-718 atlas). At the nodal level, regions most strongly affected by PED were consistently mapped to the cingulate cortex, temporal lobe, sensorimotor areas, and visual areas, with significantly higher ICCs during PA scans compared with AP scans, regardless of atlas. Better ICCs were also observed during PA scans at the edge level, in particular when global signal regression (GSR) was not performed. Further, we demonstrated that the observed reliability differences between PEDs may relate to a similar effect on the reliability of temporal signal-to-noise ratio (tSNR) in the same regions (that PA scans were associated with higher reliability of tSNR than AP scans). Averaging the connectivity outcome from the AP and PA scans could increase median ICCs, especially at the nodal and edge levels. Similar results at the global and nodal levels were replicated in an independent, public dataset from the HCP-Early Psychosis (HCP-EP) study with a similar design but a much shorter scan session interval. Our findings suggest that PED has significant effects on the reliability of connectomic estimates in fMRI studies. We urge that these effects need to be carefully considered in future neuroimaging designs, especially in longitudinal studies such as those related to neurodevelopment or clinical intervention.

A joint subspace mapping between structural and functional brain connectomes.

Understanding the connection between the brain's structural connectivity and its functional connectivity is of immense interest in computational neuroscience. Although some studies have suggested that whole brain functional connectivity is shaped by the underlying structure, the rule by which anatomy constraints brain dynamics remains an open question. In this work, we introduce a computational framework that identifies a joint subspace of eigenmodes for both functional and structural connectomes. We found that a small number of those eigenmodes are sufficient to reconstruct functional connectivity from the structural connectome, thus serving as low-dimensional basis function set. We then develop an algorithm that can estimate the functional eigen spectrum in this joint space from the structural eigen spectrum. By concurrently estimating the joint eigenmodes and the functional eigen spectrum, we can reconstruct a given subject's functional connectivity from their structural connectome. We perform elaborate experiments and demonstrate that the proposed algorithm for estimating functional connectivity from the structural connectome using joint space eigenmodes gives competitive performance as compared to the existing benchmark methods with better interpretability.

Modules in connectomes of phase-synchronization comprise anatomically contiguous, functionally related regions.

Modules in brain functional connectomes are essential to balancing segregation and integration of neuronal activity. Connectomes are the complete set of pairwise connections between brain regions. Non-invasive Electroencephalography (EEG) and Magnetoencephalography (MEG) have been used to identify modules in connectomes of phase-synchronization. However, their resolution is suboptimal because of spurious phase-synchronization due to EEG volume conduction or MEG field spread. Here, we used invasive, intracerebral recordings from stereo-electroencephalography (SEEG, N = 67), to identify modules in connectomes of phase-synchronization. To generate SEEG-based group-level connectomes affected only minimally by volume conduction, we used submillimeter accurate localization of SEEG contacts and referenced electrode contacts in cortical gray matter to their closest contacts in white matter. Combining community detection methods with consensus clustering, we found that the connectomes of phase-synchronization were characterized by distinct and stable modules at multiple spatial scales, across frequencies from 3 to 320 Hz. These modules were highly similar within canonical frequency bands. Unlike the distributed brain systems identified with functional Magnetic Resonance Imaging (fMRI), modules up to the high-gamma frequency band comprised only anatomically contiguous regions. Notably, the identified modules comprised cortical regions involved in shared repertoires of sensorimotor and cognitive functions including memory, language and attention. These results suggest that the identified modules represent functionally specialised brain systems, which only partially overlap with the brain systems reported with fMRI. Hence, these modules might regulate the balance between functional segregation and functional integration through phase-synchronization.

Compressed primary-to-transmodal gradient is accompanied with subcortical alterations and linked to neurotransmitters and cellular signatures in major depressive disorder.

Major depressive disorder (MDD) has been shown to involve widespread changes in low-level sensorimotor and higher-level cognitive functions. Recent research found that a primary-to-transmodal gradient could capture a cortical hierarchical organization ranging from perception and action to cognition in healthy subjects, but a prominent gradient dysfunction in MDD patients. However, whether and how this cortical gradient is linked to subcortical impairments and whether it is reflected in the microscale neurotransmitter systems and cell type-specific transcriptional signatures remain largely unknown. Data were acquired from 323 MDD patients and 328 sex- and age-matched healthy controls derived from the REST-meta-MDD project, and the human brain neurotransmitter systems density maps and gene expression data were drawn from two publicly available datasets. We investigated alterations of the primary-to-transmodal gradient in MDD patients and their correlations with clinical symptoms of depression and anxiety, as well as  their paralleled subcortical impairments. The correlations between MDD-related gradient alterations and densities of the neurotransmitter systems and gene expression information were assessed, respectively. The results demonstrated that MDD patients had a compressed primary-to-transmodal gradient accompanied by paralleled alterations in subcortical regions including the caudate, amygdala, and thalamus. The case-control gradient differences were spatially correlated with the densities of the neurotransmitter systems including the serotonin and dopamine receptors, and meanwhile with gene expression enriched in astrocytes, excitatory and inhibitory neuronal cells. These findings mapped the paralleled subcortical impairments in cortical hierarchical organization and also helped us understand the possible molecular and cellular substrates of the co-occurrence of high-level cognitive impairments with low-level sensorimotor abnormalities in MDD.

A metabolism-functional connectome sparse coupling method to reveal imaging markers for Alzheimer's disease based on simultaneous PET/MRI scans.

Abnormal glucose metabolism and hemodynamic changes in the brain are closely related to cognitive function, providing complementary information from distinct biochemical and physiological processes. However, it remains unclear how to effectively integrate these two modalities across distinct brain regions. In this study, we developed a connectome-based sparse coupling method for hybrid PET/MRI imaging, which could effectively extract imaging markers of Alzheimer's disease (AD) in the early stage. The FDG-PET and resting-state fMRI data of 56 healthy controls (HC), 54 subjective cognitive decline (SCD), and 27 cognitive impairment (CI) participants due to AD were obtained from SILCODE project (NCT03370744). For each participant, the metabolic connectome (MC) was constructed by Kullback-Leibler divergence similarity estimation, and the functional connectome (FC) was constructed by Pearson correlation. Subsequently, we measured the coupling strength between MC and FC at various sparse levels, assessed its stability, and explored the abnormal coupling strength along the AD continuum. Results showed that the sparse MC-FC coupling index was stable in each brain network and consistent across subjects. It was more normally distributed than other traditional indexes and captured more SCD-related brain areas, especially in the limbic and default mode networks. Compared to other traditional indices, this index demonstrated best classification performance. The AUC values reached 0.748 (SCD/HC) and 0.992 (CI/HC). Notably, we found a significant correlation between abnormal coupling strength and neuropsychological scales (p < .05). This study provides a clinically relevant tool for hybrid PET/MRI imaging, allowing for exploring imaging markers in early stage of AD and better understanding the pathophysiology along the AD continuum.

Graph-matching distance between individuals' functional connectomes varies with relatedness, age, and cognitive score.

Functional connectomes (FCs), represented by networks or graphs that summarize coactivation patterns between pairs of brain regions, have been related at a population level to age, sex, cognitive/behavioral scores, life experience, genetics, and disease/disorders. However, quantifying FC differences between individuals also provides a rich source of information with which to map to differences in those individuals' biology, experience, genetics or behavior. In this study, graph matching is used to create a novel inter-individual FC metric, called swap distance, that quantifies the distance between pairs of individuals' partial FCs, with a smaller swap distance indicating the individuals have more similar FC. We apply graph matching to align FCs between individuals from the the Human Connectome Project N = 997 and find that swap distance (i) increases with increasing familial distance, (ii) increases with subjects' ages, (iii) is smaller for pairs of females compared to pairs of males, and (iv) is larger for females with lower cognitive scores compared to females with larger cognitive scores. Regions that contributed most to individuals' swap distances were in higher-order networks, that is, default-mode and fronto-parietal, that underlie executive function and memory. These higher-order networks' regions also had swap frequencies that varied monotonically with familial relatedness of the individuals in question. We posit that the proposed graph matching technique provides a novel way to study inter-subject differences in FC and enables quantification of how FC may vary with age, relatedness, sex, and behavior.

Stability of specific personality network features corresponding to openness trait across different adult age periods: A machine learning analysis.

The functional connectivity patterns of the brain during resting state are closely related to an individual's cognition, emotion, behavior, and social interactions, making it an important research method to measure personality traits in an unbiased way, replacing traditional paper-and-pencil tests. However, due to the dynamic nature of the brain, whether the changes in functional connectivity caused by age can stably map onto personality traits has not been previously investigated. This study focuses on whether network features that are significantly related to personality traits can effectively distinguish subjects with different personality traits, and whether these network features vary across different periods of adulthood. The study included 343 healthy adult participants, divided into early adulthood and middle adulthood groups according to the age threshold of 35. Resting-state functional magnetic resonance imaging (fMRI) and the Big Five personality questionnaire were collected. we investigated the relationship between personality traits and intrinsic whole-brain functional connectome. We then used support vector machine (SVM) to evaluate the performance of personality network features in distinguishing subjects with high and low scores in the early-adulthood sample, and cross-validated in the mid-adulthood sample. Additionally, edge-based analysis (NBS) was used to explore the stability of personality networks across the two age samples. Our results show that the network features corresponding to openness personality trait are stable and can effectively differentiate subjects with different scores in both age samples. Furthermore, this study found that these network features vary to some extent across different periods of adulthood. These findings provide new evidence and insights into the application of resting-state functional connectivity patterns in measuring personality traits and help us better understand the dynamic characteristics of the human brain.

Functional Connectome Hierarchy Distortions in Female Nurses With Occupational Burnout and Its Gene Expression Signatures.

BACKGROUND: Burnout has become a serious public health issue worldwide, particularly during the COVID-19 pandemic. Functional connectome impairments associated with occupational burnout were widely distributed, involving both low-level sensorimotor cortices and high-level association cortices. PURPOSE: To investigate whether there are hierarchical perturbations in the functional connectomes and if these perturbations are potentially influenced by genetic factors in nurses who feel "burned out." STUDY TYPE: Prospective, case control. POPULATION: Thirty-three female nurses with occupational burnout (aged 27-40, 32.42 ± 3.37) and 32 matched nurses who were not feeling burned out (aged 27-42, 32.50 ± 4.21). FIELD STRENGTH/SEQUENCE: 3.0 T, gradient-echo echo-planar imaging sequence (GE-EPI). ASSESSMENT: Gradient-based techniques were used to depict the perturbations in the multi-dimensional hierarchical structure of the macroscale connectome. Gene expression data were acquired from the Allen Human Brain Atlas. STATISTICAL TESTS: Cortex-wide multivariate analyses were used for between-group differences in gradients as well as association analyses between the hierarchy distortions and the MBI score (FDR corrected). Partial least squares, spin test and bootstrapping were utilized together to select the gene sets (FDR corrected). Gene enrichment analyses (GO, KEGG and cell-type) were further performed. Significance level: P < 0.05. RESULTS: There were significant gradient distortions, with strong between-group effects in the somatosensory network and moderate effects in the higher-order default-mode network, which were significantly correlated with the gene expression profiles (r = 0.3171). The most related genes were broadly involved in the cellular response to minerals, neuronal plasticity, and the circadian rhythm pathway (q value < 0.01). Significant enrichments were found in excitatory (r = 0.2588), inhibitory neurons (r = 0.2610), and astrocytes cells (r = 0.2633). Regions affected by burnout severity were mainly distributed in the association and visual cortices. DATA CONCLUSION: By connecting in vivo imaging to genes, cell classes, and clinical data, this study provides a framework to understand functional impairments in occupational burnout and how the microscopic genetic architecture drive macroscopic distortions. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Predicting superagers by machine learning classification based on the functional brain connectome using resting-state functional magnetic resonance imaging.

Superagers are defined as older adults who have youthful memory performance comparable to that of middle-aged adults. Classifying superagers based on the brain connectome using machine learning modeling can provide important insights on the physiology underlying successful aging. We aimed to investigate the unique patterns of functional brain connectome of superagers and develop predictive models to differentiate superagers from typical agers based on machine learning methods. We obtained resting-state functional magnetic resonance imaging (rsfMRI) data and cognitive measures from 32 superagers and 58 typical agers. The accuracies of three machine learning methods including the linear support vector machine classifier (SV), the random forest classifier (RF), and the logistic regression classifier (LR) in predicting superagers were comparable (SV = 0.944, RF = 0.944, LR = 0.944); however, RF achieved the highest area under the curve (AUC; 0.979). An ensemble learning method combining the three classifiers achieved the highest AUC (0.986). The most discriminative nodes for predicting superagers encompassed areas in the precuneus; posterior cingulate gyrus; insular cortex; and superior, middle, and inferior frontal gyrus, which were located in default, salient, and multiple-demand networks. Thus, rsfMRI data can provide high accuracy for predicting superagers, thereby capturing and describing the unique characteristics of their functional brain connectome.

Static and dynamic topological organization of brain functional connectome in acute mild traumatic brain injury.

BACKGROUND: Prior studies have detected topological changes of brain functional networks in patients with acute mild traumatic brain injury (mTBI). However, the alterations of dynamic topological characteristics in mTBI have been scarcely elucidated. PURPOSE: To evaluate static and dynamic functional connectivity topological networks in patients with acute mTBI using resting-state functional magnetic resonance imaging (fMRI). MATERIAL AND METHODS: A total of 55 patients with acute mTBI and 55 age-, sex-, and education-matched healthy controls (HCs) were enrolled in this study. All participants underwent resting-state fMRI scans, and data were analyzed using graph-theory methods and a sliding window approach. Post-traumatic cognitive performance and resting-state fMRI data were collected within one week after injury. Static and dynamic functional connectivity patterns were determined by independent component analysis. Spearman's correlation analysis was further performed between fMRI changes and Montreal cognitive assessment (MoCA) scores. RESULTS: Global efficiency was lower (P = 0.02), and local efficiency (P < 0.001) and mean Cp (P < 0.001) were higher in patients with acute mTBI than in HCs. Local efficiency was correlated with visuospatial/executive performance (r = -0.421; P = 0.002) in patients with acute mTBI. Significant differences in nodal efficiency and node degree centrality (P < 0.01) were found between the mTBI and HC groups. For dynamic properties, patients with mTBI showed higher variance (P = 0.016) in global efficiency than HCs. CONCLUSIONS: The present study shows that patients with mTBI have abnormal brain functional connectome topology, especially the dynamic graph theory characteristics, which provide new insights into the role of topological network properties in patients with acute mTBI.