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The precuneus shows considerable heterogeneity in multiple dimensions including anatomy, function, and involvement in brain disorders. Leveraging the state-of-the-art functional gradient approach, we aimed to investigate the hierarchical organization of the precuneus, which may hold promise for a unified understanding of precuneus heterogeneity. Resting-state functional MRI data from 793 healthy individuals were used to discover and validate functional gradients of the precuneus, which were calculated based on the voxel-wise precuneus-to-cerebrum functional connectivity patterns. Then, we further explored the potential relationships of the precuneus functional gradients with cortical morphology, intrinsic geometry, canonical functional networks, and behavioral domains. We found that the precuneus principal and secondary gradients showed dorsoanterior-ventral and ventroposterior-dorsal organizations, respectively. Concurrently, the principal gradient was associated with cortical morphology, and both the principal and secondary gradients showed geometric distance dependence. Importantly, precuneus functional subdivisions corresponding to canonical functional networks (behavioral domains) were distributed along both gradients in a hierarchical manner, i.e., from the sensorimotor network (somatic movement and sensation) at one extreme to the default mode network (abstract cognitive functions) at the other extreme for the principal gradient and from the visual network (vision) at one end to the dorsal attention network (top-down control of attention) at the other end for the secondary gradient. These findings suggest that the precuneus functional gradients may provide mechanistic insights into the multifaceted nature of precuneus heterogeneity. [ABSTRACT FROM AUTHOR]

Heterogeneity of the cingulate cortex is evident in multiple dimensions including anatomy, function, connectivity, and involvement in networks and diseases. Using the recently developed functional connectivity gradient approach and resting-state functional MRI data, we found three functional connectivity gradients that captured distinct dimensions of cingulate hierarchical organization. The principal gradient exhibited a radiating organization with transitions from the middle toward both anterior and posterior parts of the cingulate cortex and was related to canonical functional networks and corresponding behavioral domains. The second gradient showed an anterior–posterior axis across the cingulate cortex and had prominent geometric distance dependence. The third gradient displayed a marked differentiation of subgenual and caudal middle with other parts of the cingulate cortex and was associated with cortical morphology. Aside from providing an updated framework for understanding the multifaceted nature of cingulate heterogeneity, the observed hierarchical organization of the cingulate cortex may constitute a novel research agenda with potential applications in basic and clinical neuroscience. Analysis of resting-state fMRI data reveals the presence of functional connectivity gradients of the human cingulate cortex, which updates our understanding of cingulate heterogeneity. [ABSTRACT FROM AUTHOR]

The diverse functional roles of the insula may emerge from its heavy connectivity to an extensive network of cortical and subcortical areas. Despite several previous attempts to investigate the hierarchical organization of the insula by applying the recently developed gradient approach to insula‐to‐whole brain connectivity data, little is known about whether and how there is variability across connectivity gradients of the insula to different cerebral systems. Resting‐state functional MRI data from 793 healthy subjects were used to discover and validate functional connectivity gradients of the insula, which were computed based on its voxel‐wise functional connectivity profiles to distinct cerebral systems. We identified three primary patterns of functional connectivity gradients of the insula to distinct cerebral systems. The connectivity gradients to the higher‐order transmodal associative systems, including the prefrontal, posterior parietal, temporal cortices, and limbic lobule, showed a ventroanterior‐dorsal axis across the insula; those to the lower‐order unimodal primary systems, including the motor, somatosensory, and occipital cortices, displayed radiating transitions from dorsoanterior toward both ventroanterior and dorsoposterior parts of the insula; the connectivity gradient to the subcortical nuclei exhibited an organization along the anterior–posterior axis of the insula. Apart from complementing and extending previous literature on the heterogeneous connectivity patterns of insula subregions, the presented framework may offer ample opportunities to refine our understanding of the role of the insula in many brain disorders. [ABSTRACT FROM AUTHOR]

The human sensorimotor cortex has multiple subregions showing functional commonalities and differences, likely attributable to their connectivity profiles. However, the molecular substrates underlying such connectivity profiles are unclear. Here, transcriptome‐neuroimaging spatial correlation analyses were performed between transcriptomic data from the Allen human brain atlas and resting‐state functional connectivity (rsFC) of 24 fine‐grained sensorimotor subregions from 793 healthy subjects. Results showed that rsFC of six sensorimotor subregions were associated with expression measures of six gene sets that were specifically expressed in brain tissue. These sensorimotor subregions could be classified into the polygenic‐ and oligogenic‐modulated subregions, whose rsFC were related to gene sets diverging on their numbers (hundreds vs. dozens) and functional characteristics. First, the former were specifically expressed in multiple types of neurons and immune cells, yet the latter were not specifically expressed in any cortical cell types. Second, the former were preferentially expressed during the middle and late stages of cortical development, while the latter showed no preferential expression during any stages. Third, the former were prone to be enriched for general biological functions and pathways, but the latter for specialized biological functions and pathways. Fourth, the former were enriched for neuropsychiatric disorders, whereas this enrichment was absent for the latter. Finally, although the identified genes were commonly associated with sensorimotor behavioral processes, the polygenic‐modulated subregions associated genes were additionally related to vision and dementia. These findings may advance our understanding of the functional homogeneity and heterogeneity of the human sensorimotor cortex from the perspective of underlying genetic architecture. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates that gut microbiota can influence cognition via the gut–brain axis, and brain networks play a critical role during the process. However, little is known about how brain network topology and structural–functional connectivity (SC–FC) coupling contribute to gut microbiota-related cognition. Fecal samples were collected from 157 healthy young adults, and 16S amplicon sequencing was used to assess gut diversity and enterotypes. Topological properties of brain structural and functional networks were acquired by diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI data), and SC–FC coupling was further calculated. 3-Back, digit span, and Go/No-Go tasks were employed to assess cognition. Then, we tested for potential associations between gut microbiota, complex brain networks, and cognition. The results showed that gut microbiota could affect the global and regional topological properties of structural networks as well as node properties of functional networks. It is worthy of note that causal mediation analysis further validated that gut microbial diversity and enterotypes indirectly influence cognitive performance by mediating the small-worldness (Gamma and Sigma) of structural networks and some nodal metrics of functional networks (mainly distributed in the cingulate gyri and temporal lobe). Moreover, gut microbes could affect the degree of SC–FC coupling in the inferior occipital gyrus, fusiform gyrus, and medial superior frontal gyrus, which in turn influence cognition. Our findings revealed novel insights, which are essential to provide the foundation for previously unexplored network mechanisms in understanding cognitive impairment, particularly with respect to how brain connectivity participates in the complex crosstalk between gut microbiota and cognition. [ABSTRACT FROM AUTHOR]

Evidence suggests the pivotal role of vitamin D in the pathophysiology of major depressive disorder (MDD) via its effects on the brain. Gender differences exist in both depression and vitamin D level. Our objective was to investigate the association between gender, vitamin D, clinical manifestations, and functional network connectivity in a large sample of MDD patients and healthy controls. Resting-state functional MRI data were collected from 122 patients and 119 controls, with independent component analysis adopted to examine large-scale inter- and intranetwork functional connectivity. Serum concentration of vitamin D (SCVD) and clinical manifestations were also assessed. MDD patients exhibited lower SCVD than controls in females but not males. Moreover, we identified a female-specific association between lower SCVD and poorer cognitive performance. Concurrently, MDD-related functional network connectivity changes were correlated with SCVD in females as well as depression and anxiety symptoms in female patients. Remarkably, MDD- and SCVD-related functional network connectivity alterations mediated the associations between SCVD and cognition in females. Aside from providing evidence for a female-specific neurobiological mechanism whereby low vitamin D might contribute to MDD and its associated clinical characteristics, our findings inform a novel conceptualization that adjuvant vitamin D supplementation therapy may yield clinical benefits in improving treatment outcomes in female patients with MDD. [ABSTRACT FROM AUTHOR]

There is a proof-of-concept that microbial metabolites provide a molecular connection between the gut and the brain. Extensive research has established a link between gut Bacteroides and human cognition, yet the metabolic and neural mechanisms underlying this association remain largely unknown. Here, we collected fecal samples, resting-state functional MRI, and cognitive data from a large and homogeneous sample of 157 healthy young adults. 16S rRNA gene sequencing was conducted with abundances of Bacteroides and metabolic pathways quantified by species annotation and functional prediction analyses, respectively. Large-scale intra- and internetwork functional connectivity was measured using independent component analysis. Results showed that gut Bacteroides were related to multiple metabolic pathways, which in turn were associated with widespread functional network connectivity. Furthermore, functional network connectivity mediated the associations between some Bacteroides- related metabolic pathways and cognition. Remarkably, arginine and proline metabolism, phenylalanine metabolism, and biosynthesis of unsaturated fatty acids act as the key metabolic pathways that are most contributive, and the executive control and sensorimotor systems contribute most strongly at the neural level. Our findings suggest complex poly-pathway and poly-network processes linking Bacteroides to cognition, more generally yielding a novel conceptualization of targeting gut Bacteroides as an intervention strategy for individuals with cognitive impairment. [ABSTRACT FROM AUTHOR]

Network neuroscience has broadly conceptualized the functions of the brain as complex communication within and between large‐scale neural networks. Nevertheless, whether and how the gut microbiota influence functional network connectivity that in turn impact human behaviors has yet to be determined. We collected fecal samples from 157 healthy young adults and used 16S sequencing to assess gut microbial diversity and enterotypes. Large‐scale inter‐ and intranetwork functional connectivity was measured using a combination of resting‐state functional MRI data and independent component analysis. Sleep quality and core executive functions were also evaluated. Then, we tested for potential associations between gut microbiota, functional network connectivity and behaviors. We found significant associations of gut microbial diversity with internetwork functional connectivity between the executive control, default mode and sensorimotor systems, and intranetwork connectivity of the executive control system. Moreover, some internetwork functional connectivity mediated the relations of microbial diversity with sleep quality, working memory, and attention. In addition, there was a significant effect of enterotypes on intranetwork connectivity of the executive control system, which could mediate the link between enterotypes and executive function. Our findings not only may expand existing biological knowledge of the gut microbiota‐brain‐behavior relationships from the perspective of large‐scale functional network organization, but also may ultimately inform a translational conceptualization of how to improve sleep quality and executive functions through the regulation of gut microbiota. [ABSTRACT FROM AUTHOR]

Neuroimaging research has revealed significant changes in brain structure and function in patients with cervical spondylotic myelopathy(CSM). The thalamus plays a crucial role in this process, although its mechanisms of action remain incompletely understood. This study aimed to investigate whether spinal cord compression leads to alterations in the functional connectivity between the thalamus and the cerebral cortex, and to determine if such changes are associated with structural and functional remodeling of the brain in patients with CSM, and to identify potential neuroimaging biomarkers for classification. The study included 40 patients with CSM and 34 healthy controls(HCs) who underwent resting-state functional magnetic resonance imaging(fMRI) and structural MRI scans. Brain structural and functional metrics were quantified using functional connectivity(FC), fractional amplitude of low-frequency fluctuations(fALFF), surface-based morphometry(SBM), and independent component analysis(ICA) based on functional and structural MRI. Patients with CSM exhibited significantly reduced fALFF in the bilateral lateral lingual gyrus, bilateral calcarine fissure, left precentral gyrus and postcentral gyrus, left middle and superior occipital gyrus, left superior marginal gyrus, left inferior parietal gyrus, and right Rolandic operculum. ICA results revealed weakened functional connectivity between the sensorimotor network (SMN) and the left and right frontoparietal network(FPN), and lateral visual network (lVN), along with decreased connectivity between lVN and rFPN, and increased connectivity between lFPN and rFPN. Patients with CSM also had decreased sulcus depth in the bilateral insula, left precentral and postcentral gyrus, and right lingual gyrus and calcarine fissure. Furthermore, cervical spondylotic myelopathy patients showed decreased functional connectivity between the left ventral posterolateral nucleus (VPL) of the thalamus and the right middle occipital gyrus (MOG). Finally,multimodal neuroimaging with support vector machine(SVM) classified patients with CSM and healthy controls with 86.00% accuracy. Our study revealed that the decrease in functional connectivity between the thalamus and cortex mediated by spinal cord compression leads to structural and functional reorganization of the cortex. Features based on neuroimaging markers have the potential to become neuroimaging biomarkers for CSM. • CSM patients exhibit significant alterations in both brain structure and function. • Reduced thalamo-cortical synchronization in CSM patients mediates brain remodeling. • Neuroimaging metrics with SVM can accurately classify CSM patients and healthy controls. [ABSTRACT FROM AUTHOR]

Low vitamin D is linked to major depressive disorder (MDD) through affecting the brain. Gender difference is apparent in MDD and vitamin D level. We aimed to examine the association between gender, vitamin D, clinical presentations, and brain functional connectivity in a large cohort of MDD patients and comparison subjects. Resting-state functional MRI data from 122 patients and 119 controls were collected to perform a combined analysis of functional connectivity density (FCD) and seed-based functional connectivity (FC). Peripheral venous blood samples were obtained to measure serum concentration of vitamin D (SCVD). Clinical presentations (symptoms profiles and cognition) were also assessed. We found an interaction of group and gender on SCVD in which MDD patients demonstrated lower SCVD than controls in females rather than males. Concurrently, lower SCVD was associated with worse cognitive performance (prospective memory and sustained attention). Compared with controls, female MDD patients showed reduced FCD and FC of the left middle frontal gyrus, which were related to lower SCVD. Importantly, these FCD and FC changes mediated the relationship between lower SCVD and cognitive dysfunction. Our findings suggest that functional connectivity abnormalities may serve as neural substrates underlying the associations between low vitamin D and cognitive impairments in female MDD patients, providing unique insight into treatment and prevention of MDD and its related cognitive dysfunction from the perspective of regulating circulating vitamin D. • Depressive patients exhibited lower vitamin D than controls in females but not males. • There is a female-specific relation between lower vitamin D and poorer cognition. • Depression-related functional connectivity changes related with vitamin D in females. • Connectivity changes mediated relations between vitamin D and cognition in females. [ABSTRACT FROM AUTHOR]

Functional stability is a newly developed dynamic functional connectivity approach. The objective of this study was to adopt functional stability to investigate diagnosis-associated abnormalities (patients vs. controls) and status-related changes (acute vs. remitted status) in brain function in major depressive disorder (MDD). 132 MDD patients and 102 healthy controls underwent resting-state functional MRI as well as clinical and cognitive assessment at baseline, with 48 patients completing follow-up examinations at an average of 7 months. Results showed no group differences in baseline functional stability and no longitudinal functional stability changes from acute to remitted status in patients. However, we found that baseline functional stability in the dorsal and ventral anterior cingulate cortex, calcarine sulcus, and middle occipital gyrus could predict improvement in depressive symptoms from acute to remitted status in MDD patients, with longitudinal functional stability changes in these regions related to the degree of symptom improvement. In addition, lower baseline functional stability in the inferior temporal gyrus could predict a greater improvement in sustained attention, which was associated with a greater functional stability increase in this region. Our findings highlight functional stability as a potential prognostic biomarker to predict and track disease progression or stratify MDD patients for optimizing disease management and treatment strategies. • Baseline functional stability could predict clinical improvement in MDD patients. • Longitudinal functional stability changes related to clinical improvement degree. • Baseline functional stability could predict cognitive improvement in MDD patients. • Longitudinal functional stability changes related to cognitive improvement degree. [ABSTRACT FROM AUTHOR]