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Sleep disturbance is one of the most frequent somatic symptoms in major depressive disorder (MDD), but the neural mechanisms behind it are not well understood. Sleep efficiency (SE) is a good indicator of early awakening and difficulty falling asleep in MDD patients. Our study aimed to investigate the relationship between sleep efficiency and brain function in MDD patients. We recruited 131 MDD patients from the Fourth People's Hospital in Hefei, and 71 well-matched healthy controls who were enrolled from the community. All subjects underwent resting-state functional MRI. Brain function was measured using the fractional amplitude of low-frequency fluctuation (fALFF), sleep efficiency was objectively measured by polysomnography (PSG), and clinical scales were used to evaluate depressive symptoms and sleep status. Multivariate regression analysis was performed to assess the relationship between the amplitude of the low frequency fluctuation fraction and sleep efficiency. Three brain regions with relevance to sleep efficiency in MDD patients were found: inferior occipital gyrus (Number of voxels = 25, peak MNI coordinate x/y/z = −42/-81/-6, Peak intensity = 4.3148), middle occipital gyrus (Number of voxels = 55, peak MNI coordinate x/y/z = −30/-78/18, Peak intensity = 5.111), and postcentral gyrus (Number of voxels = 26, peak MNI coordinate x/y/z = −27/-33/60, Peak intensity = 4.1263). But there was no significant relationship between fALFF and SE in the healthy controls. The reduced sleep efficiency in MDD may be related to their lower neural activity in the inferior occipital gyrus, middle occipital gyrus, and postcentral gyrus. The findings may provide a potential neuroimaging basis for the clinical intervention in patients with major depressive disorder with sleep disturbances. [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]

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]

Highlights • This study aimed to identify changes in the topological organization of the motor execution network in alcohol dependence (AD). • At the global level, AD patients exhibited increased local specialization, indicative of a shift toward regular networks. • At the node level, nodal degree was higher in AD patients in the cerebellum. • At the edge level, we observed a cerebello–thalamo–striato–cortical circuit with altered functional connectivity strength in AD. • These findings may provide important insights into the neurobiology of the AD-related motor impairments. Abstract Motor function damage is one of the most common symptoms in patients with alcohol dependence (AD). However, relatively little is known about the neuropathology of the motor impairments in AD. The aim of this study was to identify changes in the topological organization of the motor execution network in AD. Here, a total of 39 male individuals, including 19 AD patients and 20 age-matched healthy controls, underwent resting-state functional magnetic resonance imaging (fMRI). The motor execution network was constructed and analyzed using graph theoretical approaches. Topological properties (including global, nodal and edge measures) were compared between the two groups. At the global level, AD patients exhibited increased local specialization (indexed by increased clustering coefficient and local efficiency) relative to healthy controls, indicating that the motor execution network of AD patients shifts toward regularization. At the node level, nodal degree was higher in AD patients in the cerebellum. At the edge level, we observed a cerebello–thalamo–striato–cortical circuit with altered functional connectivity strength in AD patients. These findings suggest that topological architecture of the motor execution network is disrupted in AD patients, which may provide important insights into the neurobiology of the AD-related motor impairments. [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]

Background: Sleep disturbance is a common and key symptom that affects most of patients with major depressive disorder (MDD). However, neural substrates underlying sleep disturbance and their clinical relevance in depression remain unclear.Methods: Ninety-six MDD patients underwent resting-state functional MRI. Fractional amplitude of low-frequency fluctuation (fALFF) and resting-state functional connectivity (rsFC) were used to measure brain function. Overnight polysomnography was performed to objectively measure sleep efficiency (SE), which was used to classify patients into normal sleep efficiency (NSE) and low sleep efficiency (LSE) groups. Between-group differences in fALFF and rsFC were examined using two-sample t-tests. Moreover, correlation and mediation analyses were conducted to test for potential associations between SE, brain functional changes, and clinical variables.Results: LSE group showed decreased fALFF in right cuneus, thalamus, and middle temporal gyrus compared to NSE group. MDD patients with low SE also exhibited lower rsFC of right cuneus to right lateral temporal cortex, which was associated with more severe depression and anxiety symptoms. More importantly, mediation analyses revealed that the relationships between SE and severity of depression and anxiety symptoms were significantly mediated by the altered rsFC. In addition, these low SE-related brain functional alterations were not affected by antidepressant medication and were independent of structural changes.Limitations: The lack of healthy controls because of "first-night effect".Conclusion: These findings not only may expand existing knowledge about neuropathology of sleep disturbance in depression, but also may inform real-world clinical practice by improving depression and anxiety symptoms through sleep regulation. [ABSTRACT FROM AUTHOR]

Background: A variety of functional metrics derived from resting-state functional magnetic resonance imaging (rs-fMRI) have been employed to explore spontaneous brain activity changes in major depressive disorder (MDD) and have enjoyed significant success in unraveling the neurobiological mechanisms underlying this disorder. However, it is unclear whether spatial and temporal coupling relationships among these rs-fMRI metrics are altered in MDD.Methods: 50 patients with MDD and 36 well-matched healthy controls underwent rs-fMRI scans. A dynamic analysis was applied to compute multiple frequently used metrics including fractional amplitude of low frequency fluctuations, regional homogeneity, voxel-mirrored homotopic connectivity, degree centrality and global signal connectivity. Kendall's W was used to calculate volume-wise (across voxels) and voxel-wise (across time windows) concordance among these metrics. Inter-group differences in the concordance and their associations with clinical and cognitive variables were tested.Results: Compared to healthy controls, patients with MDD showed decreased whole gray matter volume-wise concordance. Despite similar spatial distributions, quantitative comparison analysis revealed that MDD patients exhibited reduced voxel-wise concordance in multiple cortical and subcortical regions. Moreover, the lower concordance was associated with worse performances in prospective memory and sustained attention in the MDD group.Limitations: The study design of fairly modest sample size did not allow us to perform a full analysis of the potential effects of medication and illness duration.Conclusions: Our findings suggest that spatial and temporal decoupling of multiple resting-state brain activity metrics may help elucidate the neural mechanisms of cognitive deficits in depression. [ABSTRACT FROM AUTHOR]

Background The field of microbiota-gut-brain research in animals has progressed, while the exact nature of gut microbiota-brain-cognition relationship in humans is not completely elucidated, likely due to small sample sizes and single neuroimaging modality utilized to delineate limited aspects of the brain. We aimed to comprehensively investigate such association in a large sample using multimodal MRI. Methods Fecal samples were collected from 157 healthy young adults and 16S sequencing was used to assess gut microbial diversity and enterotypes. Five brain imaging measures, including regional homogeneity (ReHo) and functional connectivity density (FCD) from resting-state functional MRI, cerebral blood flow (CBF) from arterial spin labeling, gray matter volume (GMV) from structural MRI, and fractional anisotropy (FA) from diffusion tensor imaging, were jointly analyzed with a data-driven multivariate fusion method. Cognition was evaluated by 3-back and digit span tasks. Results We found significant associations of gut microbial diversity with ReHo, FCD, CBF, and GMV within the frontoparietal, default mode and visual networks, as well as with FA in a distributed set of juxtacortical white matter regions. In addition, there were FCD, CBF, GMV, and FA differences between Prevotella- versus Bacteroides-enterotypes in females and between Prevotella- versus Ruminococcaceae-enterotypes in males. Moreover, the identified neuroimaging fusion biomarkers could mediate the associations between microbial diversity and cognition. Conclusions Our findings not only expand existing knowledge of the microbiota-gut-brain axis, but also have potential clinical and translational implications by exposing the gut microbiota as a promising treatment and prevention target for cognitive impairment and related brain disorders. • Gut microbiota-brain-cognition association was assessed using multimodal MRI. • Multimodal MRI measures were jointly analyzed with a multivariate fusion method. • Gut microbial diversity was correlated with multiple neuroimaging fusion measures. • There were differences in multiple neuroimaging fusion measures between enterotypes. • Fusion biomarkers mediated the relations between microbial diversity and cognition. [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]