Resting-state Functional Connectivity Networks Research Articles

Associations among environmental unpredictability, changes in resting-state functional connectivity, and adolescent psychopathology in the ABCD study

Abstract Background Unpredictability is a core but understudied dimension of adversities and has been receiving increasing attention recently. The effects of unpredictability on psychopathology and the underlying neural mechanisms, however, remain unclear. It is also unknown how unpredictability interacts with other dimensions of adversities in predicting brain development and psychopathology of youth. Methods We applied cluster robust standard errors to examine how unpredictability was associated with the developmental changes in resting-state functional connectivity (rsFC) of large-scale brain networks implicated in psychopathology, as well as the moderating role of deprivation, using data from the Adolescent Brain Cognitive Development (ABCD) study, which included four measurements from baseline (mean ± s.d. age, 119.13 ± 7.51 months; 2815 females) to 3-year follow-up (N = 5885). Results After controlling for threat, unpredictability was associated with a smaller increase in rsFC within default mode network (DMN) and a smaller decrease in rsFC between cingulo-opercular network (CON) and DMN. Neighborhood educational deprivation moderated the associations between unpredictability and changes in rsFC within DMN and fronto-parietal network (FPN), as well as between CON and DMN. A smaller decrease in rsFC between CON and DMN mediated the association between unpredictability and externalizing problems. Neighborhood educational deprivation moderated the indirect pathway from unpredictability to externalizing problems via a smaller decrease in CON-DMN rsFC. Conclusions Our findings shed light on the neural mechanisms underlying the associations between unpredictability and adolescents' psychopathology and the moderating role of deprivation, highlighting the significance of providing stable environment and abundant educational opportunities to facilitate optimal development.

Changes in resting-state functional connectivity of large-scale brain networks in bulimia nervosa: evidence from causal analysis.

Bulimia nervosa (BN) has been observationally linked to the functional connectivity (FC) of large-scale brain networks, but the biological mechanisms remain unclear. This study used two-sample Mendelian randomization (MR) with genetic variations as instrumental variables (IVs) to explore potential causal relationships between FC and BN. Summary data from genome-wide association studies (GWAS) involving 2,564 individuals were analyzed to identify genetically predicted BN. Functional magnetic resonance imaging parameters and materials were sourced from the UK Biobank. The variables underwent independent component analysis processing by the database to generate the final GWAS dataset. Various methods, including MR Pleiotropy RESidual Sum and Outlier, MR Egger, and weighted median, were employed to detect heterogeneity and pleiotropy, with inverse variance weighting serving as the principal estimation method (P < 0.05). The FC imaging-derived phenotypes revealed that BN exerted a causal influence on the FC between large-scale networks, including the visual network, default mode network (DMN), frontoparietal network, somatosensory network (SSN), and ventral attention network. Additionally, BN had a causal impact on the within-network FC of both the DMN and SSN. The study provides evidence that BN leads to further changes in FC patterns within and between large-scale brain networks.

Functional connectivity in resting-state networks relates to short-term global cognitive functioning in cardiac arrest survivors.

Long-term cognitive impairment is common in cardiac arrest survivors. Screening to identify patients at risk is recommended. Functional magnetic resonance brain imaging (fMRI) holds potential to contribute to prediction of cognitive outcomes. In this study, we investigated the possible value of early changes in resting-state networks for predicting short and long-term cognitive functioning of cardiac arrest survivors. We performed a prospective multicenter cohort study in cardiac arrest survivors in three Dutch hospitals. Resting-state fMRI scans were acquired within a month after cardiac arrest. We primarily focused on functional connectivity within the default-mode network (DMN) and salience network (SN), and additionally explored functional connectivity in seven other networks. Cognitive outcome was measured using the Montreal Cognitive Assessment (MoCA) during hospital admission and at 3 and 12 months, and by neuropsychological examination (NPE) at 12 months. We tested mixed effects models to evaluate the value of connectivity within the networks for predicting global cognitive outcomes at the three time points, and long-term cognitive outcomes in the memory, attention, and executive functioning domains. We included 80 patients (age 60 ± 11 years, 72 (90%) male). MoCA scores increased significantly between hospital admission and 3 months (ΔMoCAhospital-3M = 2.89, p < 0.01), but not between 3 and 12 months (ΔMoCA3M-12M = 0.38, p = 0.52). Connectivity within the DMN, SN, and dorsal attention network (DAN) was positively related to global cognitive functioning during hospital admission (βDMN = 0.85, p = 0.03; βSN = 1.48, p < 0.01; βDAN = 0.96, p = 0.01), but not at 3 and 12 months. Network connectivity was also unrelated to long-term memory, attention, or executive functioning. Resting-state functional connectivity in the DMN, SN, and DAN measured in the first month after cardiac arrest is related to short-term global, but not long-term global or domain-specific cognitive performance of survivors. These results do not support the value of functional connectivity within these RSNs for prediction of long-term cognitive performance after cardiac arrest.

Cognition and Ventral Attention Network Connectivity: Associations With Treatment Response in Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a highly heterogeneous disorder, which makes it difficult to link clinical phenotypes with biomarkers to improve treatment outcomes. Findings from previous studies suggest that cognitive measures such as verbal memory or attention paired with within-ventral attention network (VAN) or salience network resting-state functional connectivity may predict treatment response among individuals with PTSD. In a sample comprising 20 individuals with PTSD and 10 healthy control group individuals, the investigators subtyped individuals by using both discriminant function analysis and standardized norms for a single measure of memory and neuropsychological batteries of memory, attention, and executive functioning; attempted to replicate previous findings of lower within-VAN connectivity among individuals with cognitive impairment; and explored whether within-VAN connectivity paired with cognitive impairment predicted treatment outcomes. PTSD patients with cognitive impairment (defined by using a discriminant function analysis with verbal memory performance) had greater within-VAN resting-state functional connectivity compared with control group individuals and cognitively intact PTSD patients at a level that fell short of statistical significance (F=3.41; df=2, 21; ηp2=0.237). The interaction between verbal memory performance and within-VAN connectivity also predicted treatment-related change in PTSD symptoms at a level that also fell short of statistical significance (β=-0.442). These findings somewhat support the clinical utility of identifying cognitive phenotypes within PTSD (by using discriminant function analysis and verbal memory performance) to predict treatment outcomes.

Network-level enrichment provides a framework for biological interpretation of machine learning results.

Machine learning algorithms are increasingly being utilized to identify brain connectivity biomarkers linked to behavioral and clinical outcomes. However, research often prioritizes prediction accuracy at the expense of biological interpretability, and inconsistent implementation of ML methods may hinder model accuracy. To address this, our paper introduces a network-level enrichment approach, which integrates brain system organization in the context of connectome-wide statistical analysis to reveal network-level links between brain connectivity and behavior. To demonstrate the efficacy of this approach, we used linear support vector regression (LSVR) models to examine the relationship between resting-state functional connectivity networks and chronological age. We compared network-level associations based on raw LSVR weights to those produced from the forward and inverse models. Results indicated that not accounting for shared family variance inflated prediction performance, the k-best feature selection via Pearson correlation reduced accuracy and reliability, and raw LSVR model weights produced network-level associations that deviated from the significant brain systems identified by forward and inverse models. Our findings offer crucial insights for applying machine learning to neuroimaging data, emphasizing the value of network enrichment for biological interpretation.

Altered functional connectivity of resting-state networks and the correlation with clinical characteristics in intermittent exotropia adult patients: a resting-state magnetic resonance imaging study

BackgroundThe pathogenesis of intermittent exotropia (IXT) remains unclear. The study aims to investigate alterations of resting-state networks (RSNs) in IXT adult patients using resting-state functional magnetic resonance imaging (rs-fMRI) data to explore the potential neural mechanisms.MethodsTwenty-six IXT adult patients and 22 age-, sex-, handedness-, and education-matched healthy controls (HCs) underwent fMRI scanning and ophthalmological examinations. Brain areas with significant functional connectivity (FC) differences between the IXT and HC groups were selected as regions of interest (ROI) and mean z-scores were calculated to control for individual differences.ResultsCompared with HCs, IXT patients exhibited altered FC in various brain regions within RSNs involved in binocular fusion, stereopsis, ocular movement, emotional processes and social cognition, including the default mode network (DMN), the dorsal attention network (DAN), the visual network (VN), the sensorimotor network (SMN), the executive control network (ECN), the frontoparietal network (FPN) and the auditory network (AN). The degree of exodeviation was positively correlated with FC value of left middle occipital gyrus (MOG) within the VN. Correspondingly, we found a negative correlation between the degree of exodeviation and the FC value of left angular gyrus (AG) within FPN (P < 0.05). The FNC analysis between different RSNs also provides evidence on visual-motor cortical plasticity.ConclusionsIXT patients showed widespread changes of brain activity within RSNs related to binocular fusion, stereopsis, oculomotor control, emotional processes, and social cognition. These findings extend our current understanding of the neuropathological mechanisms of IXT.Trial registrationBeginning date of the trial: 2021-09-01. Date of registration:2021-07-18. Trial registration number: ChiCTR 2,100,048,852. Trial registration site: http://www.chictr.org.cn/index.aspx.

Associations Between Changes in Psychological Resilience and Resting-State Functional Connectivity Throughout Pediatric Concussion Recovery.

Purpose: This study investigated the association between psychological resilience and resting-state network functional connectivity of three major brain networks in pediatric concussion. Methods: This was a substudy of a randomized controlled trial, recruiting children with concussion and orthopedic injury. Participants completed the Connor-Davidson Resilience 10 Scale and underwent magnetic resonance imaging at 72 h and 4-weeks postinjury. We explored associations between resilience and connectivity with the default mode network (DMN), central executive network (CEN), and salience network (SN) at both timepoints and also any change that occurred over time. We also explored associations between resilience and connectivity within each network. Results: A total of 67 children with a concussion (median age = 12.87 [IQR: 11.79-14.36]; 46% female) and 30 with orthopedic injury (median age = 12.27 [IQR: 11.19-13.94]; 40% female) were included. Seed-to-voxel analyses detected a positive correlation between 72-h resilience and CEN connectivity in the concussion group. Group moderated associations between resilience and SN connectivity at 72 h, as well as resilience and DMN connectivity over time. Regions-of-interest analyses identified group as a moderator of longitudinal resilience and within-DMN connectivity. Conclusions: These results suggest that neural recovery from concussion could be reliant on resilience. Resilience was related to functional connectivity with three of the main networks in the brain that are often impacted by concussion. Improving resilience might be investigated as a modifiable variable in children as both a protective and restorative in the context of concussion. Clinical Trial Registration Identifier: NCT05105802. PedCARE+MRI team (see Supplementary Appendix S1).

The "limbic network," comprising orbitofrontal and anterior temporal cortex, is part of an extended default network: Evidence from multi-echo fMRI.

Resting-state functional magnetic resonance imaging (fMRI) investigations have provided a view of the default network (DN) as composed of a specific set of frontal, parietal, and temporal cortical regions. This spatial topography is typically defined with reference to an influential network parcellation scheme that designated the DN as one of seven large-scale networks (Yeo et al., 2011). However, the precise functional organization of the DN is still under debate, with studies arguing for varying subnetwork configurations and the inclusion of subcortical regions. In this vein, the so-called limbic network-defined as a distinct large-scale network comprising the bilateral temporal poles, ventral anterior temporal lobes, and orbitofrontal cortex-is of particular interest. A large multi-modal and multi-species literature on the anatomical, functional, and cognitive properties of these regions suggests a close relationship to the DN. Notably, these regions have poor signal quality with conventional fMRI acquisition, likely obscuring their network affiliation in most studies. Here, we leverage a multi-echo fMRI dataset with high temporal signal-to-noise and whole-brain coverage, including orbitofrontal and anterior temporal regions, to examine the large-scale network resting-state functional connectivity of these regions and assess their associations with the DN. Consistent with our hypotheses, our results support the inclusion of the majority of the orbitofrontal and anterior temporal cortex as part of the DN and reveal significant heterogeneity in their functional connectivity. We observed that left-lateralized regions within the temporal poles and ventral anterior temporal lobes, as well as medial orbitofrontal regions, exhibited the greatest resting-state functional connectivity with the DN, with heterogeneity across DN subnetworks. Overall, our findings suggest that, rather than being a functionally distinct network, the orbitofrontal and anterior temporal regions comprise part of a larger, extended default network.

Acupuncture modulates emotional network resting-state functional connectivity in patients with insomnia disorder: a randomized controlled trial and fMRI study

BackgroundInsomnia disorder (ID) is one of the most common sleep problems, usually accompanied by anxiety and depression symptoms. Functional magnetic resonance imaging (fMRI) study suggests that both poor sleep quality and negative emotion are linked to the dysregulation of brain network related to emotion processing in ID patients. Acupuncture therapy has been proven effective in improving sleep quality and mood of ID patients, but the involved neurobiological mechanism remains unclear. We aimed to investigate the modulation effect of acupuncture on resting-state functional connectivity (rsFC) of the emotional network (EN) in patients experiencing insomnia.MethodsA total of 30 healthy controls (HCs) and 60 ID patients were enrolled in this study. Sixty ID patients were randomly assigned to real and sham acupuncture groups and attended resting-state fMRI scans before and after 4 weeks of acupuncture treatment. HCs completed an MRI/fMRI scan at baseline. The rsFC values within EN were calculated, and Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), Hyperarousal Scale (HAS), and actigraphy data were collected for clinical efficacy evaluation.ResultsResting-state FC analysis showed abnormalities in rsFC centered on the thalamus and dorsolateral prefrontal cortex within EN of ID patients compared to HCs. After real acupuncture treatment, rsFC of the anterior cingulate cortex, hippocampus, and amygdala were increased compared with the sham acupuncture group (p < 0.05, FDR corrected). In real acupuncture group, the rsFC value was decreased between left amygdala and left thalamus after 4 weeks of treatment compared with baseline. A trend of correlation was found that the increased rsFC value between the right amygdala and left hippocampus was positively correlated with the decreased HAMA scores across all ID patients, and the decreased left amygdala rsFC value with the left thalamus was negatively correlated with the increased sleep efficiency in the real acupuncture group.ConclusionOur findings showed that real acupuncture could produce a positive effect on modulating rsFC within network related to emotion processing in ID patients, which may illustrate the central mechanism underlying acupuncture for insomnia in improving sleep quality and emotion regulation.Trial registrationhttp://www.chictr.org.cn., ChiCTR1800015282, 20/03/2018.

Salience network resting state functional connectivity during airway inflammation in asthma: A feature of mental health resilience?

BackgroundInflammation is an established contributor to the pathophysiology of depression and the prevalence of depression in those with chronic inflammatory disease is two- to four-fold higher than the general population. Yet little is known about the neurobiological changes that confer depression or resilience to depression, that occur when episodes of heightened inflammation are frequent or span many years. MethodsWe used an innovative combination of longitudinal resting state functional magnetic resonance imaging coupled to segmental bronchial provocation with allergen (SBP-Ag) to assess changes in resting state functional connectivity (rsFC) of the salience network (SN) caused by an acute inflammatory exacerbation in twenty-six adults (15 female) with asthma and varying levels of depressive symptoms. Eosinophils measured in bronchoalveolar lavage fluid and blood provided an index of allergic inflammation and the Beck Depression Inventory provided an index of depressive symptoms. ResultsWe found that in those with the highest symptoms of depression at baseline, SN rsFC declined most from pre- to post-SBP-Ag in the context of a robust eosinophilic response to challenge, but in those with low depressive symptoms SN rsFC was maintained or increased, even in those with the most pronounced SBP-Ag response. ConclusionsThus, the maintenance of SN rsFC during inflammation may be a biomarker of resilience to depression, perhaps via more effective orchestration of large-scale brain network dynamics by the SN. These findings advance our understanding of the functional role of the SN during inflammation and inform treatment recommendations for those with comorbid inflammatory disease and depression.

Leveraging Distributed Brain Signal at Rest to Predict Internalizing Symptoms in Youth: Deriving a Polyneuro Risk Score From the ABCD Study Cohort

BackgroundThe prevalence of internalizing psychopathology rises precipitously from early to mid-adolescence, yet the underlying neural phenotypes that give rise to depression and anxiety during this developmental period remain unclear. MethodsYouths from the Adolescent Brain Cognitive Development (ABCD) Study (ages 9–10 years at baseline) with a resting-state functional magnetic resonance imaging scan and mental health data were eligible for inclusion. Internalizing subscale scores from the Brief Problem Monitor-Youth Form were combined across 2 years of follow-up to generate a cumulative measure of internalizing symptoms. The total sample (N = 6521) was split into a large discovery dataset and a smaller validation dataset. Brain-behavior associations of resting-state functional connectivity with internalizing symptoms were estimated in the discovery dataset. The weighted contributions of each functional connection were aggregated using multivariate statistics to generate a polyneuro risk score (PNRS). The predictive power of the PNRS was evaluated in the validation dataset. ResultsThe PNRS explained 10.73% of the observed variance in internalizing symptom scores in the validation dataset. Model performance peaked when the top 2% functional connections identified in the discovery dataset (ranked by absolute β weight) were retained. The resting-state functional connectivity networks that were implicated most prominently were the default mode, dorsal attention, and cingulo-parietal networks. These findings were significant (p < 1 × 10−6) as accounted for by permutation testing (n = 7000). ConclusionsThese results suggest that the neural phenotype associated with internalizing symptoms during adolescence is functionally distributed. The PNRS approach is a novel method for capturing relationships between resting-state functional connectivity and behavior.

Triple network resting-state functional connectivity patterns of alcohol heavy drinking.

Previous neuroimaging research in alcohol use disorder (AUD) has found altered functional connectivity in the brain's salience, default mode, and central executive (CEN) networks (i.e. the triple network model), though their specific associations with AUD severity and heavy drinking remains unclear. This study utilized resting-state fMRI to examine functional connectivity in these networks and measures of alcohol misuse. Seventy-six adult heavy drinkers completed a 7-min resting-state functional MRI scan during visual fixation. Linear regression models tested if connectivity in the three target networks was associated with past 12-month AUD symptoms and number of heavy drinking days in the past 30days. Exploratory analyses examined correlations between connectivity clusters and impulsivity and psychopathology measures. Functional connectivity within the CEN network (right and left lateral prefrontal cortex [LPFC] seeds co-activating with 13 and 15 clusters, respectively) was significantly associated with AUD symptoms (right LPFC: β = .337, p-FDR = .016; left LPFC: β = .291, p-FDR = .028) but not heavy drinking (p-FDR > .749). Post-hoc tests revealed six clusters co-activating with the CEN network were associated with AUD symptoms-right middle frontal gyrus, right inferior parietal gyrus, left middle temporal gyrus, and left and right cerebellum. Neither the default mode nor the salience network was significantly associated with alcohol variables. Connectivity in the left LPFC was correlated with monetary delay discounting (r =.25, p = .03). These findings support previous associations between connectivity within the CEN network and AUD severity, providing additional specificity to the relevance of the triple network model to AUD.

Resting-State Functional Connectivity Predicts Cochlear-Implant Speech Outcomes.

Cochlear implants (CIs) have revolutionized hearing restoration for individuals with severe or profound hearing loss. However, a substantial and unexplained variability persists in CI outcomes, even when considering subject-specific factors such as age and the duration of deafness. In a pioneering study, we use resting-state functional near-infrared spectroscopy to predict speech-understanding outcomes before and after CI implantation. Our hypothesis centers on resting-state functional connectivity (FC) reflecting brain plasticity post-hearing loss and implantation, specifically targeting the average clustering coefficient in resting FC networks to capture variation among CI users. Twenty-three CI candidates participated in this study. Resting-state functional near-infrared spectroscopy data were collected preimplantation and at 1 month, 3 months, and 1 year postimplantation. Speech understanding performance was assessed using consonant-nucleus-consonant words in quiet and Bamford-Kowal-Bench sentences in noise 1-year postimplantation. Resting-state FC networks were constructed using regularized partial correlation, and the average clustering coefficient was measured in the signed weighted networks as a predictive measure for implantation outcomes. Our findings demonstrate a significant correlation between the average clustering coefficient in resting-state functional networks and speech understanding outcomes, both pre- and postimplantation. This approach uses an easily deployable resting-state functional brain imaging metric to predict speech-understanding outcomes in implant recipients. The results indicate that the average clustering coefficient, both pre- and postimplantation, correlates with speech understanding outcomes.

Intrinsic functional connectivity mediates the effect of personality traits on depressive symptoms.

Personality traits have been proposed as risk factors for depressive symptoms. However, the neural mechanism behind these relationships is unclear. This study examined the possible mediating effect of resting-state functional connectivity networks on these relationships. Data from 153 healthy Germans were obtained from the MPI-Leipzig Mind-Brain-Body: Neuroanatomy & Connectivity Protocol database. Network-based statistics were used to identify significant functional connectivity networks that were positively and negatively associated with the personality traits of neuroticism, conscientiousness, and extraversion, with and without demographical covariates. Mediation analyses were performed for each personality trait and depressive symptoms with the significant positive and negative network strengths of the respective personality traits as mediators. Neuroticism, conscientiousness, and extraversion were significantly correlated with depressive symptoms. Network-based statistics identified patterns of functional connectivity that were significantly associated with neuroticism and conscientiousness. After controlling for demographical covariates, significant conscientiousness-associated and extraversion-associated networks emerged. Mediation analysis concluded that only the neuroticism-positive network mediated the effect of neuroticism on depressive symptoms. When age and sex were controlled, the extraversion-positive network completely mediated the effect of extraversion on depressive symptoms. These findings revealed that patterns of intrinsic functional networks predict personality traits and suggest that the relationship between personality traits and depressive symptoms may in part be due to their common patterns of intrinsic functional networks.

Changes in functional connectivity and structural covariance between the fronto-parietal network and medial orbitofrontal cortex are associated with disinhibition in restrained eaters.

Disinhibition, characterized by a loss of dietary control, is a significant risk factor for diet failure and the onset of eating disorders in restrained eaters. This study employs resting-state functional connectivity and structural covariance network analyses to explore the neural associations underlying this behavior. By analyzing functional MRI data from 63 female college students, we found that increased disinhibition correlates with enhanced functional connectivity between the medial orbitofrontal cortex and key components of the inhibition system, particularly within the fronto-parietal network. Moreover, we observed a relationship between the structural covariance of the medial orbitofrontal cortex and the inferior parietal lobule and the severity of disinhibition. Importantly, the functional connectivity between the medial orbitofrontal cortex and the inferior parietal lobule predicts the severity of binge eating symptoms in these individuals. These findings indicate that imbalances in the interaction between the brain's reward and inhibition systems can lead to dietary failures and eating disorders, emphasizing the need for targeted interventions.

Parkinson's Disease Risk Variant rs9638616 is Non-Specifically Associated with Altered Brain Structure and Function.

A genome-wide association study (GWAS) variant associated with Parkinson's disease (PD) risk in Asians, rs9638616, was recently reported, and maps to WBSCR17/GALNT17, which is involved in synaptic transmission and neurite development. To test the association of the rs9638616 T allele with imaging-derived measures of brain microstructure and function. We analyzed 3-Tesla MRI and genotyping data from 116 early PD patients (aged 66.8±9.0 years; 39% female; disease duration 1.25±0.71 years) and 57 controls (aged 68.7±7.4 years; 54% female), of Chinese ethnicity. We performed voxelwise analyses for imaging-genetic association of rs9638616 T allele with white matter tract fractional anisotropy (FA), grey matter volume and resting-state network functional connectivity. The rs9638616 T allele was associated with widespread lower white matter FA (t = -1.75, p = 0.042) and lower functional connectivity of the supplementary motor area (SMA) (t = -5.05, p = 0.001), in both PD and control groups. Interaction analysis comparing the association of rs9638616 and FA between PD and controls was non-significant. These imaging-derived phenotypes mediated the association of rs9638616 to digit span (indirect effect: β= -0.21 [-0.42,-0.05], p = 0.031) and motor severity (indirect effect: β= 0.15 [0.04,0.26], p = 0.045). We have shown that a novel GWAS variant which is biologically linked to synaptic transmission is associated with white matter tract and functional connectivity dysfunction in the SMA, supported by changes in clinical motor scores. This provides pathophysiologic clues linking rs9638616 to PD risk and might contribute to future risk stratification models.

Prenatal and childhood air pollution exposure, cellular immune biomarkers, and brain connectivity in early adolescents

IntroductionAmbient air pollution is a neurotoxicant with hypothesized immune-related mechanisms. Adolescent brain structural and functional connectivity may be especially vulnerable to ambient pollution due to the refinement of large-scale brain networks during this period, which vary by sex and have important implications for cognitive, behavioral, and emotional functioning. In the current study we explored associations between air pollutants, immune markers, and structural and functional connectivity in early adolescence by leveraging cross-sectional sex-stratified data from the Adolescent Brain Cognitive Development℠ Study®. MethodsPollutant concentrations of fine particulate matter, nitrogen dioxide, and ozone were assigned to each child's primary residential address during the prenatal period and childhood (9-10 years-old) using an ensemble-based modeling approach. Data collected at 11-13 years-old included resting-state functional connectivity of the default mode, frontoparietal, and salience networks and limbic regions of interest, intracellular directional and isotropic diffusion of available white matter tracts, and markers of cellular immune activation. Using partial least squares correlation, a multivariate data-driven method that identifies important variables within latent dimensions, we investigated associations between 1) pollutants and structural and functional connectivity, 2) pollutants and immune markers, and 3) immune markers and structural and functional connectivity, in each sex separately. ResultsAir pollution exposure was related to white matter intracellular directional and isotropic diffusion at ages 11–13 years, but the direction of associations varied by sex. There were no associations between pollutants and resting-state functional connectivity at ages 11–13 years. Childhood exposure to nitrogen dioxide was negatively correlated with white blood cell count in males. Immune biomarkers were positively correlated with white matter intracellular directional diffusion in females and both white matter intracellular directional and isotropic diffusion in males. Lastly, there was a reliable negative correlation between lymphocyte-to-monocyte ratio and default mode network resting-state functional connectivity in females, as well as a compromised immune marker profile associated with lower resting-state functional connectivity between the salience network and the left hippocampus in males. In post-hoc exploratory analyses, we found that the PLSC-identified white matter tracts and resting-state networks related to processing speed and cognitive control performance from the NIH Toolbox. ConclusionsWe identified novel links between childhood nitrogen dioxide and cellular immune activation in males, and brain network connectivity and immune markers in both sexes. Future research should explore the potentially mediating role of immune activity in how pollutants affect neurological outcomes as well as the potential consequences of immune-related patterns of brain connectivity in service of improved brain health for all.

Resting-State Network Functional Connectivity Analysis: A Multimodal Imaging and Computational Modeling Approach

Functional connectivity is referred to as the temporal interaction between different brain regions that are spatially distant from each other. It is commonly examined during resting states by classifying resting-state functional connectivity (rs-FC) patterns and their associated synchronized activity to understand the underlying neural mechanisms that support cognitive processes. With the advancement of cutting-edge neuronal systems, multimodal imaging, and computational advances have served as promising tools for rs-FC studies. Despite having reviewed resting-state networks and their influence on a range of health anomalies in the existing literature, there nevertheless remains a lack of reviews that delve into diverse imaging modalities and computational modeling approaches for rs-FC analysis. Therefore, this systematic review aims to provide an understanding of these technologies that analyze the resting-state network functional connectivity and their correlation to cognitive functions. Through a systematic approach to analyzing studies, the most frequently employed modality was functional magnetic resonance imaging (fMRI) due to its high spatial resolution. Key findings demonstrated that higher functional connectivity levels are often linked to greater Exin ratios, which subsequently affect large-scale functional brain synchronization. Across various computational models, a non-parametric classifier has shown promise for rs-FC analysis in various contexts due to its ability to handle multiple EEG features. Moreover, the multivariate model is identified to have superior performance with a predictive area under the curve (AUC) of ~0.77. Overall, the present study underscores the vitality of using imaging and computational tools in elucidating the intricacies of rs-FC and its effects on individual cognition.

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.

114. Association of Polygenic Risk for Bipolar Disorder With Resting-State Network Functional Connectivity in Youth

114. Association of Polygenic Risk for Bipolar Disorder With Resting-State Network Functional Connectivity in Youth