Structural Brain Networks Research Articles

Impaired structural and reserved functional topological organizations of brain networks in Parkinson’s disease with freezing of gait

Freezing of gait (FOG) is a common disabling motor disturbance in Parkinson's disease (PD). Our study aimed to probe the topological organizations of structural and functional brain networks and their coupling in FOG. In this cross-sectional retrospective study, a total of 30 PD patients with FOG (PD-FOG), 40 patients without FOG, and 25 healthy controls (HCs) underwent clinical assessments and magnetic resonance imaging (MRI) scanning. Large-scale structural and functional brain networks were constructed. Subsequently, global and nodal graph theoretical properties and functional-structural coupling were investigated. Finally, correlations between the altered brain topological properties and freezing severity were analyzed in PD-FOG. For structural networks, at the global level, PD-FOG exhibited increased normalized characteristic path length (P=0.040, Bonferroni-corrected) and decreased global efficiency (P=0.005, Bonferroni-corrected) compared with controls, and showed reduced global (P=0.001, Bonferroni-corrected) and local (P=0.032, Bonferroni-corrected) efficiency relative to patients without FOG. At the nodal level, nodal efficiency of structural networks was reduced in PD-FOG compared with PD patients without FOG, located in the left supplementary motor area (SMA), gyrus rectus, and middle cingulate cortex (MCC) (all P<0.05, Bonferroni-corrected). Notably, altered global and nodal properties of structural networks were significantly correlated with Freezing of Gait Questionnaire scores [all P<0.05, false discovery rate (FDR)-corrected]. However, only an increase in local efficiency (P=0.003, Bonferroni-corrected) of functional networks was identified in PD-FOG compared with those without FOG. No significant structural-functional coupling was detected among the 3 groups. This study demonstrates the extensively impaired structural and relatively reserved functional network topological organizations in PD-FOG. Our results also provide evidence that the pathogenesis of PD-FOG is primarily attributable to network vulnerability established by crucial structural damage, especially in the left SMA, gyrus rectus, and MCC.

Network structure-function coupling and neurocognition in cerebral small vessel disease

BackgroundCerebral small vessel disease is a leading cause of cognitive decline and vascular dementia. Small vessel disease pathology changes structural brain networks, but its impact on functional networks remains poorly understood. Structural and functional networks are closely coupled in healthy individuals, and decoupling is associated with clinical symptoms in other neurological conditions. We tested the hypothesis that structural–functional network coupling is related to neurocognitive outcomes in 262 small vessel disease patients. MethodsParticipants underwent multimodal magnetic resonance imaging and cognitive assessment in 2011 and 2015. Structural connectivity networks were reconstructed using probabilistic diffusion tractography, while functional connectivity networks were estimated from resting-state functional magnetic resonance imaging. Structural and functional networks were then correlated to calculate a measure of structural–functional network coupling for each participant. ResultsLower whole-brain coupling was associated with reduced processing speed and greater apathy both cross-sectionally and longitudinally. In addition, coupling within the cognitive control network was associated with all cognitive outcomes, suggesting that neurocognitive outcomes in small vessel disease may be related to the functioning of this intrinsic connectivity network. ConclusionsOur work demonstrates the influence of structural–functional connectivity network decoupling in small vessel disease symptomatology. Cognitive control network function may be investigated in future studies.

Increased structural connectivity in high schizotypy.

The link between brain structural connectivity and schizotypy was explored in two healthy participant cohorts, collected at two different neuroimaging centres, comprising 140 and 115 participants, respectively. The participants completed the Schizotypal Personality Questionnaire (SPQ), through which their schizotypy scores were calculated. Diffusion-MRI data were used to perform tractography and to generate the structural brain networks of the participants. The edges of the networks were weighted with the inverse radial diffusivity. Graph theoretical metrics of the default mode, sensorimotor, visual, and auditory subnetworks were derived and their correlation coefficients with the schizotypy scores were calculated. To the best of our knowledge, this is the first time that graph theoretical measures of structural brain networks are investigated in relation to schizotypy. A positive correlation was found between the schizotypy score and the mean node degree and mean clustering coefficient of the sensorimotor and the default mode subnetworks. The nodes driving these correlations were the right postcentral gyrus, the left paracentral lobule, the right superior frontal gyrus, the left parahippocampal gyrus, and the bilateral precuneus, that is, nodes that exhibit compromised functional connectivity in schizophrenia. Implications for schizophrenia and schizotypy are discussed.

Aberrant dynamic Functional-Structural connectivity coupling of Large-scale brain networks in poststroke motor dysfunction

Background and purposeStroke may lead to widespread functional and structural reorganization in the brain. Several studies have reported a potential correlation between functional network changes and structural network changes after stroke. However, it is unclear how functional-structural relationships change dynamically over the course of one resting-state fMRI scan in patients following a stroke; furthermore, we know little about their relationships with the severity of motor dysfunction. Therefore, this study aimed to investigate dynamic functional and structural connectivity (FC-SC) coupling and its relationship with motor function in subcortical stroke from the perspective of network dynamics. MethodsResting-state functional magnetic resonance imaging and diffusion tensor imaging were obtained from 39 S patients (19 severe and 20 moderate) and 22 healthy controls (HCs). Brain structural networks were constructed by tracking fiber tracts in diffusion tensor imaging, and structural network topology metrics were calculated using a graph-theoretic approach. Independent component analysis, the sliding window method, and k-means clustering were used to calculate dynamic functional connectivity and to estimate different dynamic connectivity states. The temporal patterns and intergroup differences of FC-SC coupling were analyzed within each state. We also calculated dynamic FC-SC coupling and its relationship with functional network efficiency. In addition, the correlation between FC-SC coupling and the Fugl-Meyer assessment scale was analyzed. ResultsFor SC, stroke patients showed lower global efficiency than HCs (all P < 0.05), and severely affected patients had a higher characteristic path length (P = 0.003). For FC and FC-SC coupling, stroke patients predominantly showed lower local efficiency and reduced FC-SC coupling than HCs in state 2 (all P < 0.05). Furthermore, severely affected patients also showed lower local efficiency (P = 0.031) and reduced FC-SC coupling (P = 0.043) in state 3, which was markedly linked to the severity of motor dysfunction after stroke. In addition, FC-SC coupling was correlated with functional network efficiency in state 2 in moderately affected patients (r = 0.631, P = 0.004) but not significantly in severely affected patients. ConclusionsStroke patients show abnormal dynamic FC-SC coupling characteristics, especially in individuals with severe injuries. These findings may contribute to a better understanding of the anatomical functional interactions underlying motor deficits in stroke patients and provide useful information for personalized rehabilitation strategies.

Recovery of Brain Network Integration and Segregation During the Loss and Recovery of Consciousness Induced by Sevoflurane.

Anesthetic-induced loss of consciousness (LOC) has been studied using functional connectivity (FC) and functional network analysis (FNA), manifested as fragmentation of the whole-brain functional network. However, how the fragmented brain networks reversibly recover during the recovery of consciousness (ROC) remains vague. This study aims to investigate the changes in brain network structure during ROC, to better understand the network fragmentation during anesthesia, thus providing insights into consciousness monitoring. We analyzed EEG data recorded from 15 individuals anesthetized by sevoflurane. By investigating the properties of functional networks generated using different brain atlases and performing community detection for functional networks, we explored the changes in brain network structure to understand how fragmented brain networks recover during the ROC. We observed an overall larger FC magnitude during LOC than in the conscious state. The ROC was accompanied by the increasing binary network efficiency, decreasing FC magnitude, and decreasing community similarity with the functional atlas. Furthermore, we observed a negative correlation between modularity and community number ( [Formula: see text] and , linear regression test), in which modularity increased and community number decreased during ROC. Our results show that a larger FC magnitude reveals excessive synchronization of neuronal activities during LOC. The increasing binary network efficiency, decreasing community number, and decreasing community similarity indicate the recovery of functional network integration. The increasing modularity implies the recovery of functional network segregation during ROC. The results suggest the limitation of FC magnitude and modularity in monitoring anesthetized states and the potential of integrated information theory to evaluate consciousness.

Hypergraph representation of multimodal brain networks for patients with end-stage renal disease associated with mild cognitive impairment

The structure and function of brain networks (BN) may be altered in patients with end-stage renal disease (ESRD). However, there are relatively few attentions on ESRD associated with mild cognitive impairment (ESRDaMCI). Most studies focus on the pairwise relationships between brain regions, without taking into account the complementary information of functional connectivity (FC) and structural connectivity (SC). To address the problem, a hypergraph representation method is proposed to construct a multimodal BN for ESRDaMCI. First, the activity of nodes is determined by connection features extracted from functional magnetic resonance imaging (fMRI) (i.e., FC), and the presence of edges is determined by physical connections of nerve fibers extracted from diffusion kurtosis imaging (DKI) (i.e., SC). Then, the connection features are generated through bilinear pooling and transformed into an optimization model. Next, a hypergraph is constructed according to the generated node representation and connection features, and the node degree and edge degree of the hypergraph are calculated to obtain the hypergraph manifold regularization (HMR) term. The HMR and L1 norm regularization terms are introduced into the optimization model to achieve the final hypergraph representation of multimodal BN (HRMBN). Experimental results show that the classification performance of HRMBN is significantly better than that of several state-of-the-art multimodal BN construction methods. Its best classification accuracy is 91.0891%, at least 4.3452% higher than that of other methods, verifying the effectiveness of our method. The HRMBN not only achieves better results in ESRDaMCI classification, but also identifies the discriminative brain regions of ESRDaMCI, which provides a reference for the auxiliary diagnosis of ESRD.

Brain Functional Networks with Dynamic Hypergraph Manifold Regularization for Classification of End-Stage Renal Disease Associated with Mild Cognitive Impairment

The structure and function of brain networks have been altered in patients with end-stage renal disease (ESRD). Manifold regularization (MR) only considers the pairing relationship between two brain regions and cannot represent functional interactions or higher-order relationships between multiple brain regions. To solve this issue, we developed a method to construct a dynamic brain functional network (DBFN) based on dynamic hypergraph MR (DHMR) and applied it to the classification of ESRD associated with mild cognitive impairment (ESRDaMCI). The construction of DBFN with Pearson’s correlation (PC) was transformed into an optimization model. Node convolution and hyperedge convolution superposition were adopted to dynamically modify the hypergraph structure, and then got the dynamic hypergraph to form the manifold regular terms of the dynamic hypergraph. The DHMR and L1 norm regularization were introduced into the PC-based optimization model to obtain the final DHMR-based DBFN (DDBFN). Experiment results demonstrated the validity of the DDBFN method by comparing the classification results with several related brain functional network construction methods. Our work not only improves better classification performance but also reveals the discriminative regions of ESRDaMCI, providing a reference for clinical research and auxiliary diagnosis of concomitant cognitive impairments.

Signed graph representation learning for functional-to-structural brain network mapping.

MRI-derived brain networks have been widely used to understand functional and structural interactions among brain regions, and factors that affect them, such as brain development and diseases. Graph mining on brain networks can facilitate the discovery of novel biomarkers for clinical phenotypes and neurodegenerative diseases. Since brain functional and structural networks describe the brain topology from different perspectives, exploring a representation that combines these cross-modality brain networks has significant clinical implications. Most current studies aim to extract a fused representation by projecting the structural network to the functional counterpart. Since the functional network is dynamic and the structural network is static, mapping a static object to a dynamic object may not be optimal. However, mapping in the opposite direction (i.e., from functional to structural networks) are suffered from the challenges introduced by negative links within signed graphs. Here, we propose a novel graph learning framework, named as Deep Signed Brain Graph Mining or DSBGM, with a signed graph encoder that, from an opposite perspective, learns the cross-modality representations by projecting the functional network to the structural counterpart. We validate our framework on clinical phenotype and neurodegenerative disease prediction tasks using two independent, publicly available datasets (HCP and OASIS). Our experimental results clearly demonstrate the advantages of our model compared to several state-of-the-art methods.

MSTGC: Multi-Channel Spatio-Temporal Graph Convolution Network for Multi-Modal Brain Networks Fusion.

Multi-modal brain networks characterize the complex connectivities among different brain regions from structure and function aspects, which have been widely used in the analysis of brain diseases. Although many multi-modal brain network fusion methods have been proposed, most of them are unable to effectively extract the spatio-temporal topological characteristics of brain network while fusing different modalities. In this paper, we develop an adaptive multi-channel graph convolution network (GCN) fusion framework with graph contrast learning, which not only can effectively mine both the complementary and discriminative features of multi-modal brain networks, but also capture the dynamic characteristics and the topological structure of brain networks. Specifically, we first divide ROI-based series signals into multiple overlapping time windows, and construct the dynamic brain network representation based on these windows. Second, we adopt adaptive multi-channel GCN to extract the spatial features of the multi-modal brain networks with contrastive constraints, including multi-modal fusion InfoMax and inter-channel InfoMin. These two constraints are designed to extract the complementary information among modalities and specific information within a single modality. Moreover, two stacked long short-term memory units are utilized to capture the temporal information transferring across time windows. Finally, the extracted spatio-temporal features are fused, and multilayer perceptron (MLP) is used to realize multi-modal brain network prediction. The experiment on the epilepsy dataset shows that the proposed method outperforms several state-of-the-art methods in the diagnosis of brain diseases.

Editorial: Functional and structural brain network construction, representation and application

Editorial: Functional and structural brain network construction, representation and application

Structural brain network deviations predict recovery after traumatic brain injury

ObjectiveTraumatic brain injury results in diffuse axonal injury and the ensuing maladaptive alterations in network function are associated with incomplete recovery and persistent disability. Despite the importance of axonal injury as an endophenotype in TBI, there is no biomarker that can measure the aggregate and region-specific burden of axonal injury. Normative modeling is an emerging quantitative case-control technique that can capture region-specific and aggregate deviations in brain networks at the individual patient level. Our objective was to apply normative modeling in TBI to study deviations in brain networks after primarily complicated mild TBI and study its relationship with other validated measures of injury severity, burden of post-TBI symptoms, and functional impairment. MethodWe analyzed 70 T1-weighted and diffusion-weighted MRIs longitudinally collected from 35 individuals with primarily complicated mild TBI during the subacute and chronic post-injury periods. Each individual underwent longitudinal blood sampling to characterize blood protein biomarkers of axonal and glial injury and assessment of post-injury recovery in the subacute and chronic periods. By comparing the MRI data of individual TBI participants with 35 uninjured controls, we estimated the longitudinal change in structural brain network deviations. We compared network deviation with independent measures of acute intracranial injury estimated from head CT and blood protein biomarkers. Using elastic net regression models, we identified brain regions in which deviations present in the subacute period predict chronic post-TBI symptoms and functional status. ResultsPost-injury structural network deviation was significantly higher than controls in both subacute and chronic periods, associated with an acute CT lesion and subacute blood levels of glial fibrillary acid protein (r = 0.5, p = 0.008) and neurofilament light (r = 0.41, p = 0.02). Longitudinal change in network deviation associated with change in functional outcome status (r = -0.51, p = 0.003) and post-concussive symptoms (BSI: r = 0.46, p = 0.03; RPQ: r = 0.46, p = 0.02). The brain regions where the node deviation index measured in the subacute period predicted chronic TBI symptoms and functional status corresponded to areas known to be susceptible to neurotrauma. ConclusionNormative modeling can capture structural network deviations, which may be useful in estimating the aggregate and region-specific burden of network changes induced by TAI. If validated in larger studies, structural network deviation scores could be useful for enrichment of clinical trials of targeted TAI-directed therapies.

Structural brain network connectivity mediates the association between polygenic score for tumor necrosis factor-α and processing speed in acute depression

Structural brain network connectivity mediates the association between polygenic score for tumor necrosis factor-α and processing speed in acute depression

Hemisphere-Separated Cross-Connectome Aggregating Learning via VAE-GAN for Brain Structural Connectivity Synthesis

The brain network is an effective tool and has been widely used in the field of brain neurodegenerative disease analysis. Due to the high cost of accessing medical image data, efforts have been devoted to investigating data augmentation. However, the brain network containing topological characteristics of non-European space is different from the traditional image data, which makes it challenging to synthesize brain structural connectivity and limits the application of brain network analysis. In this paper, a Hemisphere-separated Cross-connectome Aggregating Learning (HCAL) model is proposed to synthesize realistic and diverse brain structural connectivities. Specifically, the latent representation is transformed from structural connectivity by the graph variational autoencoder (GVAE). To generate more diverse and high-quality structural connectivities, the hemisphere-separated generator with a cross-connectome aggregating mechanism is developed to first learn local topological patterns by splitting the whole brain into inter- and intra-hemispheres, then capture global topological characteristics among all the neighbors for each brain region. Also, the connectivity-aware discriminator is devised to make the adversarial training stable and enhance the disease diagnosis. Evaluations of the public Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset show that the proposed model generates brain structural networks with higher quality and more diversity than related methods. In addition, the classification performance using the augmented data achieved by our approach achieves an accuracy improvement of over 3% compared with the competing method. The proposed model provides an alternative way to synthesize brain networks for connectivity-based disease analysis.

DJing and its potential Neurophysiological Implications

The “Art of DJing” is based on general features of the human brain processing that have deep neurobiological roots. Professional DJs who exhibits movement-timing performance does real life mixing using a variety of techniques, including complex beatmatching, blending, rhythm matching, cuing, and others. Mixing involves the activation of the brain´s auditory and memory centers, the frontal lobe for planning, and the motor and sensory cortex for coordination of manual control and sensory contact, and influence and potentially re-shape functional and structural brain networks. Dichotic brain experience the tracks separately to each ear and artificial enhancement the lateralization of each track, helping the DJ to mix with greater musical clarity. It is a repetitive process, triggering a significant change in an evoked brain potential vital for the cognitive functions, and which can modulate or balance auditory spatial attention. In addition, track selection focuses on the experience of pleasant feelings with evidence suggesting that music influences the dopaminergic mesolimbic pathway in the brain, the same pathway that is activated by drugs of abuse and natural rewards, such as food and sex. This paper not only aims to explain how the practice of DJing leads to an ordered activation of specific brain functions and areas, but also discusses why DJing is such a great neuropsychological skill eminently based on brain foundations. Keywords: DJing, Mixing, Neuroscience, Brain, Neuropsychological Skills.

Application of the concept of neural networks surgery in cerebrovascular disease treatment

Based on advanced techniques, both the brain structural network and functional network can be reflected, giving rise to a new field: neural networks. Entering the 21st century, along with the extensive research on neural networks and the digital brain imaging field of neuromodulation, the neurosurgical field has entered into a novel stage: neural networks surgery. Neural networks surgery was developed to devote to protecting the cognitive function of patients with central nervous system diseases. By lucubrate, multiple new views of cerebrovascular disease have emerged. In this paper, we review the applications of this novel concept in treating cerebrovascular diseases, primarily through three aspects: disease mechanism, progression, and treatment strategy. Based on recent research, the development of a novel treatment system for cerebrovascular diseases might help clarify the course of these diseases, provide optimal treatment strategies, and protect the cognitive function of patients to the greatest extent.

Dynamic analysis of epileptic causal brain networks based on directional transfer function

Epilepsy is a neurological disease with disordered brain network connectivity. It is important to analyze the brain network mechanism of epileptic seizure from the perspective of directed functional connectivity. In this paper, causal brain networks were constructed for different sub-bands of epileptic electroencephalogram (EEG) signals in interictal, preictal and ictal phases by directional transfer function method, and the information transmission pathway and dynamic change process of brain network under different conditions were analyzed. Finally, the dynamic changes of characteristic attributes of brain networks with different rhythms were analyzed. The results show that the topology of brain network changes from stochastic network to rule network during the three stage and the node connections of the whole brain network show a trend of gradual decline. The number of pathway connections between internal nodes of frontal, temporal and occipital regions increase. There are a lot of hub nodes with information outflow in the lesion region. The global efficiency in ictal stage of α, β and γ waves are significantly higher than in the interictal and the preictal stage. The clustering coefficients in preictal stage are higher than in the ictal stage and the clustering coefficients in ictal stage are higher than in the interictal stage. The clustering coefficients of frontal, temporal and parietal lobes are significantly increased. The results of this study indicate that the topological structure and characteristic properties of epileptic causal brain network can reflect the dynamic process of epileptic seizures. In the future, this study has important research value in the localization of epileptic focus and prediction of epileptic seizure.

Altered single-subject gray matter structural networks in social anxiety disorder.

Previous fMRI studies have reported more random brain functional graph configurations in social anxiety disorder (SAD). However, it is still unclear whether the same configurations would occur in gray matter (GM) graphs. Structural MRI was performed on 49 patients with SAD and on 51 age- and gender-matched healthy controls (HC). Single-subject GM networks were obtained based on the areal similarities of GM, and network topological properties were analyzed using graph theory. Group differences in each topological metric were compared, and the structure-function coupling was examined. These network measures were further correlated with the clinical characteristics in the SAD group. Compared with controls, the SAD patients demonstrated globally decreased clustering coefficient and characteristic path length. Altered topological properties were found in the fronto-limbic and sensory processing systems. Altered metrics were associated with the illness duration of SAD. Compared with the HC group, the SAD group exhibited significantly decreased structural-functional decoupling. Furthermore, structural-functional decoupling was negatively correlated with the symptom severity in SAD. These findings highlight less-optimized topological configuration of the brain structural networks in SAD, which may provide insights into the neural mechanisms underlying the excessive fear and avoidance of social interactions in SAD.

Estimating effective connectivity in Alzheimer's disease progression: A dynamic causal modeling study.

Alzheimer's disease (AD) affects the whole brain from the cellular level to the entire brain network structure. The causal relationship among brain regions concerning the different AD stages is not yet investigated. This study used Dynamic Causal Modeling (DCM) method to assess effective connectivity (EC) and investigate the changes that accompany AD progression. We included the resting-state fMRI data of 34 AD patients, 31 late mild cognitive impairment (LMCI) patients, 34 early MCI (EMCI) patients, and 31 cognitive normal (CN) subjects selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The parametric Empirical Bayes (PEB) method was used to infer the effective connectivities and the corresponding probabilities. A linear regression analysis was carried out to test if the connection strengths could predict subjects' cognitive scores. The results showed that the connections reduced from full connection in the CN group to no connection in the AD group. Statistical analysis showed the connectivity strengths were lower for later-stage patients. Linear regression analysis showed that the connection strengths were partially predictive of the cognitive scores. Our results demonstrated the dwindling connectivity accompanying AD progression on causal relationships among brain regions and indicated the potential of EC as a loyal biomarker in AD progression.

Integration of structural brain networks is related to openness to experience: A diffusion MRI study with CSD-based tractography.

Openness to experience is one of the big five traits of personality which recently has been the subject of several studies in neuroscience due to its importance in understanding various cognitive functions. However, the neural basis of openness to experience is still unclear. Previous studies have found largely heterogeneous results, suggesting that various brain regions may be involved in openness to experience. Here we suggested that performing structural connectome analysis may shed light on the neural underpinnings of openness to experience as it provides a more comprehensive look at the brain regions that are involved in this trait. Hence, we investigated the involvement of brain network structural features in openness to experience which has not yet been explored to date. The magnetic resonance imaging (MRI) data along with the openness to experience trait score from the self-reported NEO Five-Factor Inventory of 100 healthy subjects were evaluated from Human Connectome Project (HCP). CSD-based whole-brain probabilistic tractography was performed using diffusion-weighted images as well as segmented T1-weighted images to create an adjacency matrix for each subject. Using graph theoretical analysis, we computed global efficiency (GE) and clustering coefficient (CC) which are measures of two important aspects of network organization in the brain: functional integration and functional segregation respectively. Results revealed a significant negative correlation between GE and openness to experience which means that the higher capacity of the brain in combining information from different regions may be related to lower openness to experience.

Structural brain network lateralization across childhood and adolescence.

Developmental lateralization of brain function is imperative for behavioral specialization, yet few studies have investigated differences between hemispheres in structural connectivity patterns, especially over the course of development. The present study compares the lateralization of structural connectivity patterns, or topology, across children, adolescents, and young adults. We applied a graph theory approach to quantify key topological metrics in each hemisphere including efficiency of information transfer between regions (global efficiency), clustering of connections between regions (clustering coefficient [CC]), presence of hub-nodes (betweenness centrality [BC]), and connectivity between nodes of high and low complexity (hierarchical complexity [HC]) and investigated changes in these metrics during development. Further, we investigated BC and CC in seven functionally defined networks. Our cross-sectional study consisted of 211 participants between the ages of 6 and 21 years with 93% being right-handed and 51% female. Global efficiency, HC, and CC demonstrated a leftward lateralization, compared to a rightward lateralization of BC. The sensorimotor, default mode, salience, and language networks showed a leftward asymmetry of CC. BC was only lateralized in the salience (right lateralized) and dorsal attention (left lateralized) networks. Only a small number of metrics were associated with age, suggesting that topological organization may stay relatively constant throughout school-age development, despite known underlying changes in white matter properties. Unlike many other imaging biomarkers of brain development, our study suggests topological lateralization is consistent across age, highlighting potential nonlinear mechanisms underlying developmental specialization.