ABSTRACT
Mental illnesses extract a high personal and societal cost, and thus explorations of the links between mental illness and functional connectivity in the brain are critical. Investigating major mental illnesses, believed to arise from disruptions in sophisticated neural connections, allows us to comprehend how these neural network disruptions may be linked to altered cognition, emotional regulation, and social interactions. Although neuroimaging has opened new avenues to explore neural alterations linked to mental illnesses, the field still requires precise and sensitive methodologies to inspect these neural substrates of various psychological disorders. In this study, we employ a hierarchical methodology to derive double functionally independent primitives (dFIPs) from resting state functional magnetic resonance neuroimaging data (rs-fMRI). These dFIPs encapsulate canonical overlapping patterns of functional network connectivity (FNC) within the brain. Our investigation focuses on the examination of how combinations of these dFIPs relate to different mental disorder diagnoses. The central aim is to unravel the complex patterns of FNC that correspond to the diverse manifestations of mental illnesses. To achieve this objective, we used a large brain imaging dataset from multiple sites, comprising 5805 total individuals diagnosed with schizophrenia (SCZ), autism spectrum disorder (ASD), bipolar disorder (BPD), major depressive disorder (MDD), and controls. The key revelations of our study unveil distinct patterns associated with each mental disorder through the combination of dFIPs. Notably, certain individual dFIPs exhibit disorder-specific characteristics, while others demonstrate commonalities across disorders. This approach offers a novel, data-driven synthesis of intricate neuroimaging data, thereby illuminating the functional changes intertwined with various mental illnesses. Our results show distinct signatures associated with psychiatric disorders, revealing unique connectivity patterns such as heightened cerebellar connectivity in SCZ and sensory domain hyperconnectivity in ASD, both contrasted with reduced cerebellar-subcortical connectivity. Utilizing the dFIP concept, we pinpoint specific functional connections that differentiate healthy controls from individuals with mental illness, underscoring its utility in identifying neurobiological markers. In summary, our findings delineate how dFIPs serve as unique fingerprints for different mental disorders.
ABSTRACT
Despite increasing interest in the dynamics of functional brain networks, most studies focus on the changing relationships over time between spatially static networks or regions. Here we propose an approach to study dynamic spatial brain networks in human resting state functional magnetic resonance imaging (rsfMRI) data and evaluate the temporal changes in the volumes of these 4D networks. Our results show significant volumetric coupling (i.e., synchronized shrinkage and growth) between networks during the scan, that we refer to as dynamic spatial network connectivity (dSNC). We find that several features of such dynamic spatial brain networks are associated with cognition, with higher dynamic variability in these networks and higher volumetric coupling between network pairs positively associated with cognitive performance. We show that these networks are modulated differently in individuals with schizophrenia versus typical controls, resulting in network growth or shrinkage, as well as altered focus of activity within a network. Schizophrenia also shows lower spatial dynamical variability in several networks, and lower volumetric coupling between pairs of networks, thus upholding the role of dynamic spatial brain networks in cognitive impairment seen in schizophrenia. Our data show evidence for the importance of studying the typically overlooked voxel-wise changes within and between brain networks.
Subject(s)
Connectome , Magnetic Resonance Imaging , Nerve Net , Schizophrenia , Humans , Schizophrenia/diagnostic imaging , Schizophrenia/physiopathology , Adult , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Male , Female , Young Adult , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/etiology , Brain/diagnostic imaging , Brain/physiopathologyABSTRACT
Children's brains dynamically adapt to the stimuli from the internal state and the external environment, allowing for changes in cognitive and mental behavior. In this work, we performed a large-scale analysis of dynamic functional connectivity (DFC) in children aged 9~11 years, investigating how brain dynamics relate to cognitive performance and mental health at an early age. A hybrid independent component analysis framework was applied to the Adolescent Brain Cognitive Development (ABCD) data containing 10,988 children. We combined a sliding-window approach with k-means clustering to identify five brain states with distinct DFC patterns. Interestingly, the occurrence of a strongly connected state with the most within-network synchrony and the anticorrelations between networks, especially between the sensory networks and between the cerebellum and other networks, was negatively correlated with cognitive performance and positively correlated with dimensional psychopathology in children. Meanwhile, opposite relationships were observed for a DFC state showing integration of sensory networks and antagonism between default-mode and sensorimotor networks but weak segregation of the cerebellum. The mediation analysis further showed that attention problems mediated the effect of DFC states on cognitive performance. This investigation unveils the neurological underpinnings of DFC states, which suggests that tracking the transient dynamic connectivity may help to characterize cognitive and mental problems in children and guide people to provide early intervention to buffer adverse influences.
ABSTRACT
The most discriminative and revealing patterns in the neuroimaging population are often confined to smaller subdivisions of the samples and features. Especially in neuropsychiatric conditions, symptoms are expressed within micro subgroups of individuals and may only underly a subset of neurological mechanisms. As such, running a whole-population analysis yields suboptimal outcomes leading to reduced specificity and interpretability. Biclustering is a potential solution since subject heterogeneity makes one-dimensional clustering less effective in this realm. Yet, high dimensional sparse input space and semantically incoherent grouping of attributes make post hoc analysis challenging. Therefore, we propose a deep neural network called semantic locality preserving auto decoder (SpaDE), for unsupervised feature learning and biclustering. SpaDE produces coherent subgroups of subjects and neural features preserving semantic locality and enhancing neurobiological interpretability. Also, it regularizes for sparsity to improve representation learning. We employ SpaDE on human brain connectome collected from schizophrenia (SZ) and healthy control (HC) subjects. The model outperforms several state-of-the-art biclustering methods. Our method extracts modular neural communities showing significant (HC/SZ) group differences in distinct brain networks including visual, sensorimotor, and subcortical. Moreover, these bi-clustered connectivity substructures exhibit substantial relations with various cognitive measures such as attention, working memory, and visual learning.
ABSTRACT
There are a growing number of neuroimaging studies motivating joint structural and functional brain connectivity. Brain connectivity of different modalities provides insight into brain functional organization by leveraging complementary information, especially for brain disorders such as schizophrenia. In this paper, we propose a multi-modal independent component analysis (ICA) model that utilizes information from both structural and functional brain connectivity guided by spatial maps to estimate intrinsic connectivity networks (ICNs). Structural connectivity is estimated through whole-brain tractography on diffusion-weighted MRI (dMRI), while functional connectivity is derived from resting-state functional MRI (rs-fMRI). The proposed structural-functional connectivity and spatially constrained ICA (sfCICA) model estimates ICNs at the subject level using a multi-objective optimization framework. We evaluated our model using synthetic and real datasets (including dMRI and rs-fMRI from 149 schizophrenia patients and 162 controls). Multi-modal ICNs revealed enhanced functional coupling between ICNs with higher structural connectivity, improved modularity, and network distinction, particularly in schizophrenia. Statistical analysis of group differences showed more significant differences in the proposed model compared to the unimodal model. In summary, the sfCICA model showed benefits from being jointly informed by structural and functional connectivity. These findings suggest advantages in simultaneously learning effectively and enhancing connectivity estimates using structural connectivity.
ABSTRACT
Objective: Understanding the neurobiology of cognitive dysfunction in psychotic disorders remains elusive, as does developing effective interventions. Limited knowledge about the biological heterogeneity of cognitive dysfunction hinders progress. This study aimed to identify subgroups of patients with psychosis with distinct patterns of functional brain alterations related to cognition (cognitive biotypes). Methods: B-SNIP consortium data (2,270 participants including participants with psychotic disorders, relatives, and controls) was analyzed. Researchers used reference-informed independent component analysis and the NeuroMark 100k multi-scale intrinsic connectivity networks (ICN) template to obtain subject-specific ICNs and whole-brain functional network connectivity (FNC). FNC features associated with cognitive performance were identified through multivariate joint analysis. K-means clustering identified subgroups of patients based on these features in a discovery set. Subgroups were further evaluated in a replication set and in relatives. Results: Two biotypes with different functional brain alteration patterns were identified. Biotype 1 exhibited brain-wide alterations, involving hypoconnectivity in cerebellar-subcortical and somatomotor-visual networks and worse cognitive performance. Biotype 2 exhibited hyperconnectivity in somatomotor-subcortical networks and hypoconnectivity in somatomotor-high cognitive processing networks, and better preserved cognitive performance. Demographic, clinical, cognitive, and FNC characteristics of biotypes were consistent in discovery and replication sets, and in relatives. 70.12% of relatives belonged to the same biotype as their affected family members. Conclusions: These findings suggest two distinctive psychosis-related cognitive biotypes with differing functional brain patterns shared with their relatives. Patient stratification based on these biotypes instead of traditional diagnosis may help to optimize future research and clinical trials addressing cognitive dysfunction in psychotic disorders.
ABSTRACT
Dynamic functional network connectivity (dFNC) analysis is a widely used approach for studying brain function and offering insight into how brain networks evolve over time. Typically, dFNC studies utilized fixed spatial maps and evaluate transient changes in coupling among time courses estimated from independent component analysis (ICA). This manuscript presents a complementary approach that relaxes this assumption by spatially reordering the components dynamically at each timepoint to optimize for a smooth gradient in the FNC (i.e., a smooth gradient among ICA connectivity values). Several methods are presented to summarize dynamic FNC gradients (dFNGs) over time, starting with static FNC gradients (sFNGs), then exploring the reordering properties as well as the dynamics of the gradients themselves. We then apply this approach to a dataset of schizophrenia (SZ) patients and healthy controls (HC). Functional dysconnectivity between different brain regions has been reported in schizophrenia, yet the neural mechanisms behind it remain elusive. Using resting state fMRI and ICA on a dataset consisting of 151 schizophrenia patients and 160 age and gender-matched healthy controls, we extracted 53 intrinsic connectivity networks (ICNs) for each subject using a fully automated spatially constrained ICA approach. We develop several summaries of our functional network connectivity gradient analysis, both in a static sense, computed as the Pearson correlation coefficient between full time series, and a dynamic sense, computed using a sliding window approach followed by reordering based on the computed gradient, and evaluate group differences. Static connectivity analysis revealed significantly stronger connectivity between subcortical (SC), auditory (AUD) and visual (VIS) networks in patients, as well as hypoconnectivity in sensorimotor (SM) network relative to controls. sFNG analysis highlighted distinctive clustering patterns in patients and HCs along cognitive control (CC)/ default mode network (DMN), as well as SC/ AUD/ SM/ cerebellar (CB), and VIS gradients. Furthermore, we observed significant differences in the sFNGs between groups in SC and CB domains. dFNG analysis suggested that SZ patients spend significantly more time in a SC/ CB state based on the first gradient, while HCs favor the SM/DMN state. For the second gradient, however, patients exhibited significantly higher activity in CB domains, contrasting with HCs' DMN engagement. The gradient synchrony analysis conveyed more shifts between SM/ SC networks and transmodal CC/ DMN networks in patients. In addition, the dFNG coupling revealed distinct connectivity patterns between SC, SM and CB domains in SZ patients compared to HCs. To recap, our results advance our understanding of brain network modulation by examining smooth connectivity trajectories. This provides a more complete spatiotemporal summary of the data, contributing to the growing body of current literature regarding the functional dysconnectivity in schizophrenia patients. By employing dFNG, we highlight a new perspective to capture large scale fluctuations across the brain while maintaining the convenience of brain networks and low dimensional summary measures.
ABSTRACT
A primary challenge to the data-driven analysis is the balance between poor generalizability of population-based research and characterizing more subject-, study- and population-specific variability. We previously introduced a fully automated spatially constrained independent component analysis (ICA) framework called NeuroMark and its functional MRI (fMRI) template. NeuroMark has been successfully applied in numerous studies, identifying brain markers reproducible across datasets and disorders. The first NeuroMark template was constructed based on young adult cohorts. We recently expanded on this initiative by creating a standardized normative multi-spatial-scale functional template using over 100,000 subjects, aiming to improve generalizability and comparability across studies involving diverse cohorts. While a unified template across the lifespan is desirable, a comprehensive investigation of the similarities and differences between components from different age populations might help systematically transform our understanding of the human brain by revealing the most well-replicated and variable network features throughout the lifespan. In this work, we introduced two significant expansions of NeuroMark templates first by generating replicable fMRI templates for infants, adolescents, and aging cohorts, and second by incorporating structural MRI (sMRI) and diffusion MRI (dMRI) modalities. Specifically, we built spatiotemporal fMRI templates based on 6,000 resting-state scans from four datasets. This is the first attempt to create robust ICA templates covering dynamic brain development across the lifespan. For the sMRI and dMRI data, we used two large publicly available datasets including more than 30,000 scans to build reliable templates. We employed a spatial similarity analysis to identify replicable templates and investigate the degree to which unique and similar patterns are reflective in different age populations. Our results suggest remarkably high similarity of the resulting adapted components, even across extreme age differences. With the new templates, the NeuroMark framework allows us to perform age-specific adaptations and to capture features adaptable to each modality, therefore facilitating biomarker identification across brain disorders. In sum, the present work demonstrates the generalizability of NeuroMark templates and suggests the potential of new templates to boost accuracy in mental health research and advance our understanding of lifespan and cross-modal alterations.
Subject(s)
Brain , Magnetic Resonance Imaging , Humans , Adult , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/standards , Brain/diagnostic imaging , Adolescent , Young Adult , Male , Aged , Female , Middle Aged , Infant , Child , Aging/physiology , Child, Preschool , Reproducibility of Results , Image Processing, Computer-Assisted/methods , Image Processing, Computer-Assisted/standards , Aged, 80 and over , Neuroimaging/methods , Neuroimaging/standards , Diffusion Magnetic Resonance Imaging/methods , Diffusion Magnetic Resonance Imaging/standardsABSTRACT
Much of the complexity and diversity found in nature are driven by nonlinear phenomena, and this holds true for the brain. Nonlinear dynamics theory has been successfully utilized in explaining brain functions from a biophysics standpoint, and the field of statistical physics continues to make substantial progress in understanding brain connectivity and function. This study delves into complex brain functional connectivity using biophysical nonlinear dynamics approaches. We aim to uncover hidden information in high-dimensional and nonlinear neural signals, with the hope of providing a useful tool for analyzing information transitions in functionally complex networks. By utilizing phase portraits and fuzzy recurrence plots, we investigated the latent information in the functional connectivity of complex brain networks. Our numerical experiments, which include synthetic linear dynamics neural time series and a biophysically realistic neural mass model, showed that phase portraits and fuzzy recurrence plots are highly sensitive to changes in neural dynamics, and they can also be used to predict functional connectivity based on structural connectivity. Furthermore, the results showed that phase trajectories of neuronal activity encode low-dimensional dynamics, and the geometric properties of the limit-cycle attractor formed by the phase portraits can be used to explain the neurodynamics. Additionally, our results showed that the phase portrait and fuzzy recurrence plots can be used as functional connectivity descriptors, and both metrics were able to capture and explain nonlinear dynamics behavior during specific cognitive tasks. In conclusion, our findings suggest that phase portraits and fuzzy recurrence plots could be highly effective as functional connectivity descriptors, providing valuable insights into nonlinear dynamics in the brain.
ABSTRACT
Psychosis (including symptoms of delusions, hallucinations, and disorganized conduct/speech) is a main feature of schizophrenia and is frequently present in other major psychiatric illnesses. Studies in individuals with first-episode (FEP) and early psychosis (EP) have the potential to interpret aberrant connectivity associated with psychosis during a period with minimal influence from medication and other confounds. The current study uses a data-driven whole-brain approach to examine patterns of aberrant functional network connectivity (FNC) in a multi-site dataset comprising resting-state functional magnetic resonance images (rs-fMRI) from 117 individuals with FEP or EP and 130 individuals without a psychiatric disorder, as controls. Accounting for age, sex, race, head motion, and multiple imaging sites, differences in FNC were identified between psychosis and control participants in cortical (namely the inferior frontal gyrus, superior medial frontal gyrus, postcentral gyrus, supplementary motor area, posterior cingulate cortex, and superior and middle temporal gyri), subcortical (the caudate, thalamus, subthalamus, and hippocampus), and cerebellar regions. The prominent pattern of reduced cerebellar connectivity in psychosis is especially noteworthy, as most studies focus on cortical and subcortical regions, neglecting the cerebellum. The dysconnectivity reported here may indicate disruptions in cortical-subcortical-cerebellar circuitry involved in rudimentary cognitive functions which may serve as reliable correlates of psychosis.
Subject(s)
Psychotic Disorders , Schizophrenia , Humans , Magnetic Resonance Imaging/methods , Psychotic Disorders/pathology , Brain , Schizophrenia/diagnosis , Cerebellum , Brain Mapping/methodsABSTRACT
Children's brains dynamically adapt to the stimuli from the internal state and the external environment, allowing for changes in cognitive and mental behavior. In this work, we performed a large-scale analysis of dynamic functional connectivity (DFC) in children aged 9 ~ 11 years, investigating how brain dynamics relate to cognitive performance and mental health at an early age. A hybrid independent component analysis framework was applied to the Adolescent Brain Cognitive Development (ABCD) data containing 10,988 children. We combined a sliding-window approach with k-means clustering to identify five brain states with distinct DFC patterns. Interestingly, the occurrence of a strongly connected state was negatively correlated with cognitive performance and positively correlated with dimensional psychopathology in children. Meanwhile, opposite relationships were observed for a sparsely connected state. The composite cognitive score and the ADHD score were the most significantly correlated with the DFC states. The mediation analysis further showed that attention problems mediated the effect of DFC states on cognitive performance. This investigation unveils the neurological underpinnings of DFC states, which suggests that tracking the transient dynamic connectivity may help to characterize cognitive and mental problems in children and guide people to provide early intervention to buffer adverse influences.
ABSTRACT
Many psychiatric and neurological disorders show significant heritability, indicating strong genetic influence. In parallel, dynamic functional network connectivity (dFNC) measures functional temporal coupling between brain networks in a time-varying manner and has proven to identify disease-related changes in the brain. However, it remains largely unclear how genetic risk contributes to brain dysconnectivity that further manifests into clinical symptoms. The current work aimed to address this gap by proposing a novel joint ICA (jICA)-based "dynamic fusion" framework to identify dynamically tuned SNP manifolds by linking static SNPs to dynamic functional information of the brain. The sliding window approach was utilized to estimate four dFNC states and compute subject-level state-specific dFNC features. Each state of dFNC features were then combined with 12946 SZ risk SNPs for jICA decomposition, resulting in four parallel fusions in 32861 European ancestry individuals within the UK Biobank cohort. The identified joint SNP-dFNC components were further validated for SZ relevance in an aggregated SZ cohort, and compared for across-state similarity to indicate level of dynamism. The results supported that dynamic fusion yielded "static" and "dynamic" components (i.e., high and low across-state similarity, respectively) for SNP and dFNC modalities. As expected, the SNP components presented a mixture of static and dynamic manifolds, with the latter largely driven by fusion with dFNC. We also showed that some of the dynamic SNP manifolds uniquely elicited by fusion with state-specific dFNC features complemented each other in terms of biological interpretation. This dynamic fusion framework thus allows expanding the SNP modality to manifolds in the time dimension, which provides a unique lens to elicit unique SNP correlates of dFNC otherwise unseen, promising additional insights on how genetic risk links to disease-related dysconnectivity.
ABSTRACT
Functional correspondences are known to exist within the brains of both human and non-human primates however, our understanding of this phenomenon remains largely incomplete. The examination of the topological characteristics inherent in whole-brain functional connectivity bears immense promise in elucidating shared as well as distinctive patterns across different species. In this investigation, we applied topological graph analysis to brain networks and scrutinized the congruencies and disparities within the connectomes of human and marmoset monkey brains. The findings brought to light noteworthy similarities in functional connectivity patterns distributed across the entire brain, with a particular emphasis on the dorsal attention network, default mode network and visual network. Moreover, we discerned unique neural connections between humans and marmosets during both resting and task-oriented states. In essence, our study reveals a combination of shared and divergent functional brain connections underlying spontaneous and specific cognitive functions across these two species.
Subject(s)
Callithrix , Connectome , Animals , Humans , Brain Mapping , Neural Pathways , Magnetic Resonance Imaging , BrainABSTRACT
BACKGROUND: Accurate psychiatric risk assessment requires biomarkers that are both stable and adaptable to development. Functional network connectivity (FNC), which steadily reconfigures over time, potentially contains abundant information to assess psychiatric risks. However, the absence of suitable analytical methodologies has constrained this area of investigation. METHODS: We investigated the brainwide risk score (BRS), a novel FNC-based metric that contrasts the relative distances of an individual's FNC to that of psychiatric disorders versus healthy control references. To generate group-level disorder and healthy control references, we utilized a large brain imaging dataset containing 5231 total individuals diagnosed with schizophrenia, autism spectrum disorder, major depressive disorder, and bipolar disorder and their corresponding healthy control individuals. The BRS metric was employed to assess the psychiatric risk in 2 new datasets: Adolescent Brain Cognitive Development (ABCD) Study (n = 8191) and Human Connectome Project Early Psychosis (n = 170). RESULTS: The BRS revealed a clear, reproducible gradient of FNC patterns from low to high risk for each psychiatric disorder in unaffected adolescents. We found that low-risk ABCD Study adolescent FNC patterns for each disorder were strongly present in over 25% of the ABCD Study participants and homogeneous, whereas high-risk patterns of each psychiatric disorder were strongly present in about 1% of ABCD Study participants and heterogeneous. The BRS also showed its effectiveness in predicting psychosis scores and distinguishing individuals with early psychosis from healthy control individuals. CONCLUSIONS: The BRS could be a new image-based tool for assessing psychiatric vulnerability over time and in unaffected individuals, and it could also serve as a potential biomarker, facilitating early screening and monitoring interventions.
Subject(s)
Autism Spectrum Disorder , Depressive Disorder, Major , Mental Disorders , Humans , Adolescent , Autism Spectrum Disorder/diagnostic imaging , Magnetic Resonance Imaging/methods , Risk Factors , Biomarkers , Brain/diagnostic imagingABSTRACT
BACKGROUND: Schizophrenia research reveals sex differences in incidence, symptoms, genetic risk factors, and brain function. However, a knowledge gap remains regarding sex-specific schizophrenia alterations in brain function. Schizophrenia is considered a dysconnectivity syndrome, but the dynamic integration and segregation of brain networks are poorly understood. Recent advances in resting-state functional magnetic resonance imaging allow us to study spatial dynamics, the phenomenon of brain networks spatially evolving over time. Nevertheless, estimating time-resolved networks remains challenging due to low signal-to-noise ratio, limited short-time information, and uncertain network identification. METHODS: We adapted a reference-informed network estimation technique to capture time-resolved networks and their dynamic spatial integration and segregation for 193 individuals with schizophrenia and 315 control participants. We focused on time-resolved spatial functional network connectivity, an estimate of network spatial coupling, to study sex-specific alterations in schizophrenia and their links to genomic data. RESULTS: Our findings are consistent with the dysconnectivity and neurodevelopment hypotheses and with the cerebello-thalamo-cortical, triple-network, and frontoparietal dysconnectivity models, helping to unify them. The potential unification offers a new understanding of the underlying mechanisms. Notably, the posterior default mode/salience spatial functional network connectivity exhibits sex-specific schizophrenia alteration during the state with the highest global network integration and is correlated with genetic risk for schizophrenia. This dysfunction is reflected in regions with weak functional connectivity to corresponding networks. CONCLUSIONS: Our method can effectively capture spatially dynamic networks, detect nuanced schizophrenia effects including sex-specific ones, and reveal the intricate relationship of dynamic information to genomic data. The results also underscore the clinical potential of dynamic spatial dependence and weak connectivity.
ABSTRACT
PURPOSE OF REVIEW: Over the last decade, evidence suggests that a combination of behavioral and neuroimaging findings can help illuminate changes in functional dysconnectivity in schizophrenia. We review the recent connectivity literature considering several vital models, considering connectivity findings, and relationships with clinical symptoms. We reviewed resting state fMRI studies from 2017 to 2023. We summarized the role of two sets of brain networks (cerebello-thalamo-cortical (CTCC) and the triple network set) across three hypothesized models of schizophrenia etiology (neurodevelopmental, vulnerability-stress, and neurotransmitter hypotheses). RECENT FINDINGS: The neurotransmitter and neurodevelopmental models best explained CTCC-subcortical dysfunction, which was consistently connected to symptom severity and motor symptoms. Triple network dysconnectivity was linked to deficits in executive functioning, and the salience network (SN)-default mode network dysconnectivity was tied to disordered thought and attentional deficits. This paper links behavioral symptoms of schizophrenia (symptom severity, motor, executive functioning, and attentional deficits) to various hypothesized mechanisms.
Subject(s)
Schizophrenia , Humans , Schizophrenia/diagnostic imaging , Brain/diagnostic imaging , Brain Mapping/methods , Magnetic Resonance Imaging/methods , Neurotransmitter Agents , Neural Pathways/diagnostic imagingABSTRACT
Functional magnetic resonance imaging (fMRI) studies often estimate brain intrinsic connectivity networks (ICNs) from temporal relationships between hemodynamic signals using approaches such as independent component analysis (ICA). While ICNs are thought to represent functional sources that play important roles in various psychological phenomena, current approaches have been tailored to identify ICNs that mainly reflect linear statistical relationships. However, the elements comprising neural systems often exhibit remarkably complex nonlinear interactions that may be involved in cognitive operations and altered in psychiatric conditions such as schizophrenia. Consequently, there is a need to develop methods capable of effectively capturing ICNs from measures that are sensitive to nonlinear relationships. Here, we advance a novel approach to estimate ICNs from explicitly nonlinear whole-brain functional connectivity (ENL-wFC) by transforming resting-state fMRI (rsfMRI) data into the connectivity domain, allowing us to capture unique information from distance correlation patterns that would be missed by linear whole-brain functional connectivity (LIN-wFC) analysis. Our findings provide evidence that ICNs commonly extracted from linear (LIN) relationships are also reflected in explicitly nonlinear (ENL) connectivity patterns. ENL ICN estimates exhibit higher reliability and stability, highlighting our approach's ability to effectively quantify ICNs from rsfMRI data. Additionally, we observed a consistent spatial gradient pattern between LIN and ENL ICNs with higher ENL weight in core ICN regions, suggesting that ICN function may be subserved by nonlinear processes concentrated within network centers. We also found that a uniquely identified ENL ICN distinguished individuals with schizophrenia from healthy controls while a uniquely identified LIN ICN did not, emphasizing the valuable complementary information that can be gained by incorporating measures that are sensitive to nonlinearity in future analyses. Moreover, the ENL estimates of ICNs associated with auditory, linguistic, sensorimotor, and self-referential processes exhibit heightened sensitivity towards differentiating between individuals with schizophrenia and controls compared to LIN counterparts, demonstrating the translational value of our approach and of the ENL estimates of ICNs that are frequently reported as disrupted in schizophrenia. In summary, our findings underscore the tremendous potential of connectivity domain ICA and nonlinear information in resolving complex brain phenomena and revolutionizing the landscape of clinical FC analysis.
ABSTRACT
When viewing the brain as a sophisticated, nonlinear dynamic system, employing complexity measures offers a valuable way to measure the intricate and dynamic aspects of spontaneous psychotic brain activity. These measures can help us identify irregularities and patterns in complex systems. In our study, we utilized fuzzy recurrence plots and sample entropy to evaluate the dynamic characteristics of psychiatric disorders. This assessment focused on understanding the temporal and spatial neural activity patterns, and more specifically, we applied complexity measures to investigate the functional connectivity within the psychotic brain. This involves understanding how different brain regions synchronize their activity, and complexity measures can reveal the patterns of these connections. It provides a means to understand how different brain regions interact and communicate under resting-state abnormal conditions. This study offers evidence demonstrating that fuzzy recurrence plots can serve as descriptors for functional connectivity and discusses their relevance to sample entropy in the context of the psychotic brain. In summary, complexity measures offer valuable insights that enrich our comprehension of atypical brain activity and the complexities present in the psychotic brain.
ABSTRACT
Despite increasing interest in the dynamics of functional brain networks, most studies focus on the changing relationships over time between spatially static networks or regions. Here we propose an approach to study dynamic spatial brain net-works in human resting state functional magnetic resonance imaging (rsfMRI) data and evaluate the temporal changes in the volumes of these 4D networks. Our results show significant volumetric coupling (i.e., synchronized shrinkage and growth) between networks during the scan. We find that several features of such dynamic spatial brain networks are associated with cognition, with higher dynamic variability in these networks and higher volumetric coupling between network pairs positively associated with cognitive performance. We show that these networks are modulated differently in individuals with schizophrenia versus typical controls, resulting in network growth or shrinkage, as well as altered focus of activity within a network. Schizophrenia also shows lower spatial dynamical variability in several networks, and lower volumetric coupling between pairs of networks, thus upholding the role of dynamic spatial brain networks in cognitive impairment seen in schizophrenia. Our data show evidence for the importance of studying the typically overlooked voxelwise changes within and between brain networks.
ABSTRACT
Functional correspondences are known to exist within the brains of both human and non-human primates; however, our understanding of this phenomenon remains largely incomplete. The examination of the topological characteristics inherent in whole-brain functional connectivity bears immense promise in elucidating shared as well as distinctive patterns across different species. In this investigation, we applied topological graph analysis to brain networks and scrutinized the congruencies and disparities within the connectomes of human and marmoset monkey brains. The findings brought to light noteworthy similarities in functional connectivity patterns distributed across the entire brain, with a particular emphasis on the dorsal attention network, default mode network and visual network. Moreover, we discerned unique neural connections between humans and marmosets during both resting and task-oriented states. In essence, our study reveals a combination of shared and divergent functional brain connections underlying spontaneous and specific cognitive functions across these two species.