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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]

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]

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]

• A Bayesian model is used to parse depression heterogeneity from both dimensional and categorical prospect. • Three latent factors with distinct but partially overlapping whole-brain hypo- and hyper-resting-state functional connectivity patterns were identified in depression. • The Bayesian model allows an individual to express one or more factors to varying degrees, highlighting the presence of interindividual variability. • The latent factor subgroups captured heterogeneous depression-related RSFC abnormalities more effectively compared to the traditional case-control analysis. Major depressive disorder (MDD) is a heterogeneous syndrome, and understanding its neural mechanisms is crucial for the advancement of personalized medicine. However, conventional subtyping studies often categorize MDD patients into a single subgroup, neglecting the continuous interindividual variations. This implies a pressing need for a dimensional approach. 230 first-episode drug-naïve MDD patients and 395 healthy controls were obtained from 5 sites via the Rest-meta-MDD project. A Bayesian model was used to decompose the resting-state functional connectivity (RSFC) into multiple distinct RSFC patterns (refer to as "factors"), and each individual was allowed to express multiple factors to varying degrees (dimensional subtyping). The associations between demographic and clinical variables with the identified factors were calculated. We identified three latent factors with distinct but partially overlapping hypo- and hyper-RSFC patterns. Most participants co-expressed multiple latent factors. All factors shared abnormal RSFC involving the default mode network and frontoparietal network, but the directionality partially differed across factors. All factors were not significantly associated with demographic and clinical variables. These findings shed light on the interindividual variability in MDD and could form the basis for developing novel therapeutic approaches that capitalize on the heterogeneity of MDD. [ABSTRACT FROM AUTHOR]

There is evidence that major depressive disorder (MDD) is related to serum lipid level alterations. However, the neural correlates underlying this association remain poorly understood. Forty-nine patients with MDD and fifty healthy controls (HCs) underwent structural, resting-state functional and diffusion magnetic resonance imaging scans. Voxel-based morphometry, functional connectivity (FC) and tract-based spatial statistics analyses were performed to assess brain structure and function, respectively. Blood samples were collected to measure serum levels of lipid variables including total cholesterol, triglyceride and high density lipoprotein cholesterol (HDL-C). Correlation and mediation analyses were conducted to investigate the associations of serum lipid levels with brain imaging measures in MDD patients and HCs, respectively. We found that the serum HDL-C level in MDD patients was lower than that in HCs. The lower serum HDL-C level was associated with lower gray matter volume (GMV) in ventromedial prefrontal cortex (VMPFC), higher within-network FC of the default mode network, and lower micro-structural integrity in multiple white matter regions in MDD patients. Moreover, the within-default mode network FC mediated the relationship between GMV in VMPFC and serum HDL-C level; white matter integrity in genu of corpus callosum mediated the relationship between serum HDL-C level and depressive symptom severity. However, we did not observe any correlations between serum lipids and brain imaging parameters in HCs. These findings help to identify neural correlates underlying the association between depression and serum HDL-C change, which may provide new insight into intervention, treatment and prevention of depression from the perspective of regulating serum lipids. • Depression patients had lower serum high density lipoprotein cholesterol level. • It was associated with lower gray matter volume in ventromedial prefrontal cortex. • It was associated with higher functional connectivity in default mode network. • It was associated with lower micro-structural integrity in multiple white matter regions. • Mediation relationships were observed between serum lipid, brain, depressive symptom. [ABSTRACT FROM AUTHOR]

Background: The cerebellum plays an important role in the neural mechanism of depression and its static functional connectivity (FC) with the cerebrum is disrupted in patients with major depressive disorder (MDD). However, cerebellar-cerebral dynamic FC alterations in MDD remain largely unknown.Methods: 50 patients with MDD and 36 well-matched healthy controls underwent resting-state functional magnetic resonance imaging. Cerebellar-cerebral dynamic FC analyses were performed using the cerebellar seeds previously identified as being involved in the executive, default-mode, affective-limbic, and motor networks. Inter-group differences in the cerebellar dynamic FC and their associations with clinical and cognitive variables were examined.Results: Compared to healthy controls, patients with MDD had decreased cerebellar-cerebral dynamic FC of the cerebellar subregions connecting with the executive, default-mode and affective-limbic networks. The dynamic FC of the cerebellar subregion connecting with the affective-limbic network was related to severity of depression and anxiety symptoms in MDD patients. The dynamic FC of the cerebellar subregions connecting with the default-mode and affective-limbic networks were related to sustained attention and prospective memory in controls, while the correlations were inverse or non-significant in patients.Limitations: The fairly modest sample size and potential medication effect may increase the instability of the results.Conclusions: Our findings provide further evidence for the pivotal role of the cerebellum in the neuropathology of depression, pointing to potential targets of cerebellar-cerebral pathways for alternative intervention or monitoring therapeutic responses. [ABSTRACT FROM AUTHOR]

Lifelong premature ejaculation (LPE) has been linked to altered brain function and structure. Although the middle temporal gyrus (MTG) is consistently more affected in LPE, its functional and structural changes have yet to be determined at the subregional level. To explore the functional and structural changes of MTG in LPE at the subregional level based on a combined analysis of multimodal magnetic resonance imaging data. 25 patients with LPE and 21 healthy controls underwent resting-state functional and structural magnetic resonance imaging scans. The MTG was parcellated into the anterior part of the MTG (aMTG), middle part of the MTG, posterior part of the MTG, and sulcus part of the MTG. Resting-state functional connectivity (rsFC) and gray matter volume (GMV) of each MTG subregion were calculated and compared between the 2 groups. The functional and structural changes of MTG at the subregional level were assessed in patients with LPE and controls, as well as the correlation of them with premature ejaculation diagnostic tool and Beck Depression Inventory. Despite similar rsFC patterns of each MTG subregion in both groups, quantitative comparison analyses revealed that patients with LPE showed increased rsFC between the left aMTG and the right cuneus (0.34 ± 0.12 vs 0.17 ± 0.17), between the right aMTG and the right parahippocampal gyrus (0.36 ± 0.16 vs 0.15 ± 0.10), and between the right middle MTG and the left MTG (0.40 ± 0.14 vs 0.18 ± 0.15) relative to controls (P <.05, cluster-level family-wise error corrected). Moreover, validation analyses revealed that these results remained significant after adjusting for depression. However, there were no significant group differences in GMV in all the MTG subregions (P >.05, Bonferroni corrected). In addition, no significant correlations between rsFC and GMV of the MTG subregions and the clinical variables were found in patients with LPE (P >.05, Bonferroni corrected). Functional hyperconnectivity in the MTG subregions may facilitate a more sophisticated understanding of the neuropathological mechanism underlying LPE. There are no previous studies examining functional and structural changes in LPE at the MTG subregional level. The main limitation is the small sample size. We present evidence that individuals with LPE have a selective functional hyperconnectivity yet preserved structural integrity in the MTG subregions, which may facilitate a more sophisticated understanding of the neuropathological mechanism underlying LPE by highlighting the critical role of the MTG in this disorder. Zhang T, Tang D, Cai H, et al. Selective Functional Hyperconnectivity in the Middle Temporal Gyrus Subregions in Lifelong Premature Ejaculation. J Sex Med 2020;17:1457–1466. [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]