Explore the vast range of titles available.

Both cortical and cerebellar developmental differences have been implicated in attention‐deficit/hyperactivity disorder (ADHD). Recently accumulating neuroimaging studies have highlighted hierarchies as a fundamental principle of brain organization, suggesting the importance of assessing hierarchy abnormalities in ADHD. A novel gradient‐based resting‐state functional connectivity analysis was applied to investigate the cerebro‐cerebellar disturbed hierarchy in children and adolescents with ADHD. We found that the interaction of functional gradient between diagnosis and age was concentrated in default mode network (DMN) and visual network (VN). At the same time, we also found that the opposite gradient changes of DMN and VN caused the compression of the cortical main gradient in ADHD patients, implicating the co‐occurrence of both low‐ (visual processing) and high‐order (self‐related thought) cognitive dysfunction manifesting in abnormal cerebro‐cerebellar organizational hierarchy in ADHD. Our study provides a neurobiological framework to better understand the co‐occurrence and interaction of both low‐level and high‐level functional abnormalities in the cortex and cerebellum in ADHD. We found the abnormal interaction of diagnosis and age in DMN (default mode network) and VN (visual network) in attention‐deficit/hyperactivity disorder (ADHD). The opposite gradient change of VN portion and DMN portion leads to the compression of cortex in ADHD.

We study the homogenization of an elastic material made of an elastic matrix in contact with highly contrasted three-dimensional elastic rigid fibres with circular cross section. The interaction between the matrix and the fibres is described by a local interface adhesion law. Assuming that the Lamé constants in the fibres and the stiffness coefficient of the adhesive have appropriate orders of magnitude, we derive a class of deformation energies involving second gradient functionals, third gradient functionals, and a functional energy associated with inner torsion.

Our understanding of cerebellar involvement in brain disorders has evolved from motor processing to high-level cognitive and affective processing. Recent neuroscience progress has highlighted hierarchy as a fundamental principle for the brain organization. Despite substantial research on cerebellar dysfunction in schizophrenia, there is a need to establish a neurobiological framework to better understand the co-occurrence and interaction of low- and high-level functional abnormalities of cerebellum in schizophrenia. To help to establish such a framework, we investigated the abnormalities in the distribution of sensorimotor-supramodal hierarchical processing topography in the cerebellum and cerebellar-cerebral circuits in schizophrenia using a novel gradient-based resting-state functional connectivity (FC) analysis (96 patients with schizophrenia vs 120 healthy controls). We found schizophrenia patients showed a compression of the principal motor-to-supramodal gradient. Specifically, there were increased gradient values in sensorimotor regions and decreased gradient values in supramodal regions, resulting in a shorter distance (compression) between the sensorimotor and supramodal poles of this gradient. This pattern was observed in intra-cerebellar, cerebellar-cerebral, and cerebral-cerebellar FC. Further investigation revealed hyper-connectivity between sensorimotor and cognition areas within cerebellum, between cerebellar sensorimotor and cerebral cognition areas, and between cerebellar cognition and cerebral sensorimotor areas, possibly contributing to the observed compressed pattern. These findings present a novel mechanism that may underlie the co-occurrence and interaction of low- and high-level functional abnormalities of cerebellar and cerebro-cerebellar circuits in schizophrenia. Within this framework of abnormal motor-to-supramodal organization, a cascade of impairments stemming from disrupted low-level sensorimotor system may in part account for high-level cognitive cerebellar dysfunction in schizophrenia.

The angular gyrus (AG), given its rich connectivity and its location where multisensory information converges, is a functionally and anatomically heterogeneous structure. Using the state‐of‐the‐art functional gradient approach and transcription‐neuroimaging association analysis, we sought to determine whether there is an overarching hierarchical organization of the AG and if so, how it is modulated by the underlying genetic architecture. Resting‐state functional MRI data of 793 healthy subjects were obtained from discovery and validation datasets. Functional gradients of the AG were calculated based on the voxel‐wise AG‐to‐cerebrum functional connectivity patterns. Combined with the Allen Human Brain Atlas, we examined the spatial correlations between the AG functional gradient and gene expression. The dominant gradient topography showed a dorsoanterior–ventroposterior hierarchical organization of the AG, which was related to its intrinsic geometry. Concurrently, AG functional subdivisions corresponding to canonical functional networks (behavioral domains) were distributed along the dominant gradient in a hierarchical manner, that is, from the default mode network ( cognition) at one extreme to the visual and sensorimotor networks (perception and action) at the other extreme. Remarkably, we established a link between the AG dominant gradient and gene expression, with two gene sets strongly contributing to this link but diverging on their functional annotation and specific expression. Our findings represent a significant conceptual advance in AG functional organization, and may introduce novel approaches and testable questions to the investigation of AG function and anatomy in health and disease. We comprehensively characterized the overarching hierarchical organization of the angular gyrus and its underlying genetic architecture by applying a combined approach of the functional gradient and transcription‐neuroimaging association to large‐scale discovery and validation rs‐fMRI datasets.

•Left and right hemispheric functional gradients are largely mirrored.•Hemispheric functional gradients show brain asymmetries.•Sex influences the degree of hemispheric functional gradient asymmetry.•Hemispheric functional gradients per se are modulated by sex.•The observed hemisphere- and sex-related effects are reproducible. The left and right hemispheres of the human brain are two connected but relatively independent functional modules; they show multidimensional asymmetries ranging from particular local brain unit properties to entire hemispheric connectome topology. To date, however, it remains largely unknown whether and how hemispheric functional hierarchical structures differ between hemispheres. In the present study, we adopted a newly developed resting-state (rs) functional connectivity (FC)-based gradient approach to evaluate hemispheric functional hierarchical structures and their asymmetries in right-handed healthy young adults. Our results showed an overall mirrored principal functional gradient between hemispheres, with the sensory cortex and the default-mode network (DMN) anchored at the two opposite ends of the gradient. Interestingly, the left hemisphere showed a significantly larger full range of the principal gradient in both males and females, with males exhibiting greater leftward asymmetry. Similarly, the principal gradient component scores of two regions around the middle temporal gyrus and posterior orbitofrontal cortex exhibited similar hemisphere × sex interaction effects: a greater degree of leftward asymmetry in males than in females. Moreover, we observed significant main hemisphere and sex effects in distributed regions across the entire hemisphere. All these results are reproducible and robust between test-retest rs-fMRI sessions. Our findings provide evidence of functional gradients that enhance the present understanding of human brain asymmetries in functional organization and highlight the impact of sex on hemispheric functional gradients and their asymmetries.

•GGE-GTCS possessed an extended principal gradient, suggesting an excessive functional segregation.•GGE-GTCS showed an altered principal gradient score in both transmodal and unimodal systems.•Both principal and secondary connectome gradients were associated with clinical features.•The main results were reproduced using multiple processing configurations and were validated using an independent sample. Genetic generalized epilepsy is a network disorder typically involving distributed areas identified by classical neuroanatomy. However, the finer topological relationships in terms of continuous spatial arrangement between these systems are still ambiguous. Connectome gradients provide the topological representations of human macroscale hierarchy in an abstract low-dimensional space by embedding the functional connectome into a set of axes. Leveraging connectome gradients, we systematically scrutinized abnormalities of functional connectome gradient in patients with genetic generalized epilepsy with tonic-clonic seizure (GGE-GTCS, n = 78) compared to healthy controls (HC, n = 85), and further examined the reproducibility across multiple processing configurations and in an independent validation sample (patients with GGE-GTCS, n = 28; HC, n = 31). Our findings demonstrated an extended principal gradient at different spatial scales, network-level and vertex-level, in patients with GGE-GTCS. We found consistent results across processing parameters and in validation sample. The extended principal gradient revealed the excessive functional segregation between unimodal and transmodal systems associated with duration of epilepsy and age at seizure onset in patients. Furthermore, the connectivity profile of regions with abnormal principal gradients verified the disrupted functional hierarchy revealed by gradients. Together, our findings provided a novel view of functional system hierarchy alterations, which facilitated a continuous spatial arrangement of macroscale networks, to increase our understanding of the functional connectome hierarchy in generalized epilepsy.

Parkinson's disease (PD) patients exhibit deficits in primary sensorimotor and higher‐order executive functions. The gradient reflects the functional spectrum in sensorimotor‐associated areas of the brain. We aimed to determine whether the gradient is disrupted in PD patients and how this disruption is associated with treatment outcome. Seventy‐six patients (mean age, 59.2 ± 12.4 years [standard deviation], 44 women) and 34 controls participants (mean age, 58.1 ± 10.0 years [standard deviation], 19 women) were evaluated. We explored functional and structural gradients in PD patients and control participants. Patients were followed during 2 weeks of multidisciplinary intensive rehabilitation therapy (MIRT). The Unified Parkinson's Disease Rating Scale Part III (UPDRS‐III) was administered to patients before and after treatment. We investigated PD‐related alterations in the principal functional and structural gradients. We further used a support vector machine (SVM) and correlation analysis to assess the classification ability and treatment outcomes related to PD gradient alterations, respectively. The gradients showed significant differences between patients and control participants, mainly in somatosensory and visual networks involved in primary function, and higher‐level association networks (dorsal attentional network (DAN) and default mode network (DMN)) related to motor control and execution. On the basis of the combined functional and structural gradient features of these networks, the SVM achieved an accuracy of 91.2% in discriminating patients from control participants. Treatment reduced the gradient difference. The altered gradient exhibited a significant correlation with motor improvement and was mainly distributed across the visual network, DAN and DMN. This study revealed damage to gradients in the brain characterized by sensorimotor and executive control deficits in PD patients. The application of gradient features to neurological disorders could lead to the development of potential diagnostic and treatment markers for PD. We are the first study to investigate somatomotor‐association impairment and MIRT‐induced brain functional and structural alterations in PD by assessing functional and structural gradients. Abnormal functional and structural gradients were distributed over networks including the primary sensorimotor network and the higher association network related to motor control and executive.

A common coordinate space enabling comparison across individuals is vital to understanding human brain organization and individual differences. By leveraging dimensionality reduction algorithms, high-dimensional fMRI data can be represented in a low-dimensional space to characterize individual features. Such a representative space encodes the functional architecture of individuals and enables the observation of functional changes across time. However, determining comparable functional features across individuals in resting-state fMRI in a way that simultaneously preserves individual-specific connectivity structure can be challenging. In this work we propose scalable joint embedding to simultaneously embed multiple individual brain connectomes within a common space that allows individual representations across datasets to be aligned. Using Human Connectome Project data, we evaluated the joint embedding approach by comparing it to the previously established orthonormal alignment model. Alignment using joint embedding substantially increased the similarity of functional representations across individuals while simultaneously capturing their distinct profiles, allowing individuals to be more discriminable from each other. Additionally, we demonstrated that the common space established using resting-state fMRI provides a better overlap of task-activation across participants. Finally, in a more challenging scenario - alignment across a lifespan cohort aged from 6 to 85 - joint embedding provided a better prediction of age (r2 = 0.65) than the prior alignment model. It facilitated the characterization of functional trajectories across lifespan. Overall, these analyses establish that joint embedding can simultaneously capture individual neural representations in a common connectivity space aligning functional data across participants and populations and preserve individual specificity.

Understanding how function and structure are organized and their coupling with clinical traits in individuals with autism spectrum disorder (ASD) is a primary goal in network neuroscience research for ASD. Atypical brain functional networks and structures in individuals with ASD have been reported, but whether these associations show heterogeneous hierarchy modeling in adolescents and adults with ASD remains to be clarified. In this study, 176 adolescent and 74 adult participants with ASD without medication or comorbidities and sex, age matched healthy controls (HCs) from 19 research groups from the openly shared Autism Brain Imaging Data Exchange II database were included. To investigate the relationship between the functional gradient, structural changes, and clinical symptoms of brain networks in adolescents and adults with ASD, functional gradient and voxel‐based morphometry (VBM) analyses based on 1000 parcels defined by Schaefer mapped to Yeo's seven‐network atlas were performed. Pearson's correlation was calculated between the gradient scores, gray volume and density, and clinical traits. The subsystem‐level analysis showed that the second gradient scores of the default mode networks and frontoparietal network in patients with ASD were relatively compressed compared to adolescent HCs. Adult patients with ASD showed an overall compression gradient of 1 in the ventral attention networks. In addition, the gray density and volumes of the subnetworks showed no significant differences between the ASD and HC groups at the adolescent stage. However, adults with ASD showed decreased gray density in the limbic network. Moreover, numerous functional gradient parameters, but not VBM parameters, in adolescents with ASD were considerably correlated with clinical traits in contrast to those in adults with ASD. Our findings proved that the atypical changes in adolescent ASD mainly involve the brain functional network, while in adult ASD, the changes are more related to brain structure, including gray density and volume. These changes in functional gradients or structures are markedly correlated with clinical traits in patients with ASD. Our study provides a novel understanding of the pathophysiology of the structure–function hierarchy in ASD. The brain atypical changes in adolescent participants with autism mainly involve the brain functional network. In adult participants with autism, the brain changes are more related to brain structure including grey density and volume. These changes in functional gradients or structures were correlated with parts of clinical traits in autism spectrum disorder.

[This corrects the article DOI: 10.3389/fnins.2023.1084270.].