Targeted ablation of the left middle cervical ganglion prevents ventricular arrhythmias and cardiac injury induced by AMI.

Cardiac sympathetic overactivation is a critical driver in the progression of acute myocardial infarction (AMI). The left middle cervical ganglion (LMCG) is an important extracardiac sympathetic ganglion. However, the regulatory effects of LMCG on AMI have not yet been fully documented. In the present study, we detected that the LMCG was innervated by abundant sympathetic components and exerted an excitatory effect on the cardiac sympathetic nervous system in response to stimulation. In canine models of AMI, targeted ablation of LMCG reduced the sympathetic indexes of heart rate variability and serum norepinephrine, resulting in suppressed cardiac sympathetic activity. Moreover, LMCG ablation could improve ventricular electrophysiological stability, evidenced by the prolonged ventricular effective refractory period, elevated action potential duration, increased ventricular fibrillation threshold, and enhanced connexin43 expression, consequently showing antiarrhythmic effects. Additionally, compared with the control group, myocardial infarction size, circulating cardiac troponin I, and myocardial apoptosis were significantly reduced, accompanied by preserved cardiac function in canines subjected to LMCG ablation. Finally, we performed the left stellate ganglion (LSG) ablation and compared its effects with LMCG destruction. The results indicated that LMCG ablation prevented ventricular electrophysiological instability, cardiac sympathetic activation, and AMI-induced ventricular arrhythmias with similar efficiency as LSG denervation. In conclusion, this study demonstrated that LMCG ablation suppressed cardiac sympathetic activity, stabilized ventricular electrophysiological properties and mitigated cardiomyocyte death, resultantly preventing ischemia-induced ventricular arrhythmias, myocardial injury, and cardiac dysfunction. Neuromodulation therapy targeting LMCG represented a promising strategy for the treatment of AMI.

The protective effect of vitamin D supplementation as adjunctive therapy to antidepressants on brain structural and functional connectivity of patients with major depressive disorder: a randomized controlled trial.

BACKGROUND: Growing evidence points to the pivotal role of vitamin D in the pathophysiology and treatment of major depressive disorder (MDD). However, there is a paucity of longitudinal research investigating the effects of vitamin D supplementation on the brain of MDD patients. METHODS: We conducted a double-blind randomized controlled trial in 46 MDD patients, who were randomly allocated into either VD (antidepressant medication + vitamin D supplementation) or NVD (antidepressant medication + placebos) groups. Data from diffusion tensor imaging, resting-state functional MRI, serum vitamin D concentration, and clinical symptoms were obtained at baseline and after an average of 7 months of intervention. RESULTS: Both VD and NVD groups showed significant improvement in depression and anxiety symptoms but with no significant differences between the two groups. However, a greater increase in serum vitamin D concentration was found to be associated with greater improvement in depression and anxiety symptoms in VD group. More importantly, neuroimaging data demonstrated disrupted white matter integrity of right inferior fronto-occipital fasciculus along with decreased functional connectivity between right frontoparietal and medial visual networks after intervention in NVD group, but no changes in VD group. CONCLUSIONS: These findings suggest that vitamin D supplementation as adjunctive therapy to antidepressants may not only contribute to improvement in clinical symptoms but also help preserve brain structural and functional connectivity in MDD patients.

Tumor necrosis factor receptor-associated factor 5 protects against intimal hyperplasia by regulation of macrophage polarization via directly targeting PPARγ.

OBJECTIVES: Intimal hyperplasia is a serious clinical problem associated with the failure of therapeutic methods in multiple atherosclerosis-related coronary heart diseases, which are initiated and aggravated by the polarization of infiltrating macrophages. The present study aimed to determine the effect and underlying mechanism by which tumor necrosis factor receptor-associated factor 5 (TRAF5) regulates macrophage polarization during intimal hyperplasia. METHODS: TRAF5 expression was detected in mouse carotid arteries subjected to wire injury. Bone marrow-derived macrophages, mouse peritoneal macrophages and human myeloid leukemia mononuclear cells were also used to test the expression of TRAF5 in vitro. Bone marrow-derived macrophages upon to LPS or IL-4 stimulation were performed to examine the effect of TRAF5 on macrophage polarization. TRAF5-knockout mice were used to evaluate the effect of TRAF5 on intimal hyperplasia. RESULTS: TRAF5 expression gradually decreased during neointima formation in carotid arteries in a time-dependent manner. In addition, the results showed that TRAF5 expression was reduced in classically polarized macrophages (M1) subjected to LPS stimulation but was increased in alternatively polarized macrophages (M2) in response to IL-4 administration, and these changes were demonstrated in three different types of macrophages. An in vitro loss-of-function study with TRAF5 knockdown plasmids or TRAF5-knockout mice revealed high expression of markers associated with M1 macrophages and reduced expression of genes related to M2 macrophages. Subsequently, we incubated vascular smooth muscle cells with conditioned medium of polarized macrophages in which TRAF5 expression had been downregulated or ablated, which promoted the proliferation, migration and dedifferentiation of VSMCs. Mechanistically, TRAF5 knockdown inhibited the activation of anti-inflammatory M2 macrophages by directly inhibiting PPARγ expression. More importantly, TRAF5-deficient mice showed significantly aggressive intimal hyperplasia. CONCLUSIONS: Collectively, this evidence reveals an important role of TRAF5 in the development of intimal hyperplasia through the regulation of macrophage polarization, which provides a promising target for arterial restenosis-related disease management.

Genetic mechanisms underlying brain functional homotopy: a combined transcriptome and resting-state functional MRI study.

Functional homotopy, the high degree of spontaneous activity synchrony and functional coactivation between geometrically corresponding interhemispheric regions, is a fundamental characteristic of the intrinsic functional architecture of the brain. However, little is known about the genetic mechanisms underlying functional homotopy. Resting-state functional magnetic resonance imaging data from a discovery dataset (656 healthy subjects) and 2 independent cross-race, cross-scanner validation datasets (103 and 329 healthy subjects) were used to calculate voxel-mirrored homotopic connectivity (VMHC) indexing brain functional homotopy. In combination with the Allen Human Brain Atlas, transcriptome-neuroimaging spatial correlation analysis was conducted to identify genes linked to VMHC. We found 1,001 genes whose expression measures were spatially associated with VMHC. Functional enrichment analyses demonstrated that these VMHC-related genes were enriched for biological functions including protein kinase activity, ion channel regulation, and synaptic function as well as many neuropsychiatric disorders. Concurrently, specific expression analyses showed that these genes were specifically expressed in the brain tissue, in neurons and immune cells, and during nearly all developmental periods. In addition, the VMHC-associated genes were linked to multiple behavioral domains, including vision, execution, and attention. Our findings suggest that interhemispheric communication and coordination involve a complex interaction of polygenes with a rich range of functional features.

Genetic mechanisms underlying gray matter volume changes in patients with drug-naive first-episode schizophrenia.

Brain structural damage is a typical feature of schizophrenia. Investigating such disease phenotype in patients with drug-naive first-episode schizophrenia (DFSZ) may exclude the confounds of antipsychotics and illness chronicity. However, small sample sizes and marked clinical heterogeneity have precluded definitive identification of gray matter volume (GMV) changes in DFSZ as well as their underlying genetic mechanisms. Here, GMV changes in DFSZ were assessed using a neuroimaging meta-analysis of 19 original studies, including 605 patients and 637 controls. Gene expression data were derived from the Allen Human Brain Atlas and processed with a newly proposed standardized pipeline. Then, we used transcriptome-neuroimaging spatial correlations to identify genes associated with GMV changes in DFSZ, followed by a set of gene functional feature analyses. Meta-analysis revealed consistent GMV reduction in the right superior temporal gyrus, right insula and left inferior temporal gyrus in DFSZ. Moreover, we found that these GMV changes were spatially correlated with expression levels of 1,201 genes, which exhibited a wide range of functional features. Our findings may provide important insights into the genetic mechanisms underlying brain morphological abnormality in schizophrenia.

Molecular mechanisms underlying resting-state brain functional correlates of behavioral inhibition.

Previous literature has established the presence of sex differences in behavioral inhibition as well as its neural substrates and related disease risk. However, there is limited evidence that speaks directly to the question of whether or not there are sex-dependent associations between behavioral inhibition and resting-state brain function and, if so, how they are modulated by the underlying molecular mechanisms. We computed functional connectivity density (FCD) using resting-state functional MRI data to examine their associations with behavioral inhibition ability measured using a Go/No-Go task across a large cohort of 510 healthy young adults. Then, we examined the spatial relationships of the FCD correlates of behavioral inhibition with gene expression and neurotransmitter atlases to explore their potential genetic architecture and neurochemical basis. A significant negative correlation between behavioral inhibition and FCD in the left superior parietal lobule was found in females but not males. Further spatial correlation analyses demonstrated that the identified neural correlates of behavioral inhibition were associated with expression of gene categories predominantly implicating essential components of the cerebral cortex (glial cell, neuron, axon, dendrite, and synapse) and ion channel activity, as well as were linked to the serotonergic system. Our findings may not only yield important insights into the molecular mechanisms underlying the female-specific neural substrates of behavioral inhibition, but also provide a critical context for understanding how biological sex might contribute to variation in behavioral inhibition and its related disease risk.

Functional connectivity gradients of the insula to different cerebral systems.

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.

Functional hierarchy of the angular gyrus and its underlying genetic architecture.

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 (abstract 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.

Nek6 knockdown polarized macrophages into a pro-inflammatory phenotype via inhibiting STAT3 expression.

Recently macrophage polarization has emerged as playing an essential role in the oathogenesis of atherosclerosis, which is the most important underlying process in many types of cardiovascular diseases. Although Nek6 has been reported to be involved in various cellular processes, the effect of Nek6 on macrophage polarization remains unknown. Macrophages exposed to lipopolysaccharide (LPS) or IL-4 were used to establish an in vitro model for the study of regulation of classically (M1) or alternatively (M2) activated macrophage. Bone marrow-derived macrophages (BMDMs) transfected with short hairpin RNA-targeting Nek6 were then in functional studies. We observed that Nek6 expression was decreased in both peritoneal macrophages (PMs) and BMDMs stimulated by LPS. This effect was seen at both mRNA and protein level. The opposite results were obtained after administration of IL-4. Macrophage-specific Nek6 knockdown significantly exacerbated pro-inflammatory M1 polarized macrophage gene expression in response to LPS challenge, but the anti-inflammatory response gene expression that is related to M2 macrophages was attenuated by Nek6 silencing followed by treatment with IL-4. Mechanistic studies exhibited that Nek6 knockdown inhibited the phosphorylated STAT3 expression that mediated the effect on macrophage polarization regulated by AdshNek6. Moreover, decreased Nek6 expression was also observed in atherosclerotic plaques. Collectively, these evidences suggested that Nek6 acts as a crucial site in macrophage polarization, and that this operates in a STAT3-dependent manner.

Neural mechanism underlying the beneficial effect of Theory of Mind psychotherapy on early-onset schizophrenia: a randomized controlled trial.

BACKGROUND: Psychosocial interventions have emerged as an important component of a comprehensive therapeutic approach in early-onset schizophrenia, typically representing a more severe form of the disorder. Despite the feasibility and efficacy of Theory of Mind (ToM) psychotherapy for schizophrenia, relatively little is known regarding the neural mechanism underlying its effect on early-onset schizophrenia. METHODS: We performed a randomized, active controlled trial in patients with early-onset schizophrenia, who were randomly allocated into either an intervention (ToM psychotherapy) or an active control (health education) group. Diffusion tensor imaging data were collected to construct brain structural networks, with both global and regional topological properties measured using graph theory. RESULTS: We enrolled 28 patients with early-onset schizophrenia in our study. After 5 weeks of treatment, both the intervention and active control groups showed significant improvement in psychotic symptoms, yet the improvement was greater in the intervention group. Importantly, in contrast with no brain structural network change after treatment in the active control group, the intervention group showed increased nodal centrality of the left insula that was associated with psychotic symptom improvement. LIMITATIONS: We did not collect important information concerning the participants' cognitive abilities, particularly ToM performance. CONCLUSION: These findings suggest a potential neural mechanism by which ToM psychotherapy exerts a beneficial effect on early-onset schizophrenia via strengthening the coordination capacity of the insula in brain structural networks, which may provide a clinically translatable biomarker for monitoring or predicting responses to ToM psychotherapy.Clinical trial registration: NCT05577338; ClinicalTrials.gov.

Sex-dependent gut microbiota-brain-cognition associations: a multimodal MRI study.

BACKGROUND: There is bidirectional communication between the gut microbiota and the brain. Empirical evidence has demonstrated sex differences in both the gut microbiome and the brain. However, the effects of sex on the gut microbiota-brain associations have yet to be determined. We aim to elucidate the sex-specific effects of gut microbiota on brain and cognition. METHODS: One hundred fifty-seven healthy young adults underwent brain structural, perfusion, functional and diffusion MRIs to measure gray matter volume (GMV), cerebral blood flow (CBF), functional connectivity strength (FCS) and white matter integrity, respectively. Fecal samples were collected and 16S amplicon sequencing was utilized to assess gut microbial diversity. Correlation analyses were conducted to test for sex-dependent associations between microbial diversity and brain imaging parameters, and mediation analysis was performed to further characterize the gut microbiota-brain-cognition relationship. RESULTS: We found that higher gut microbial diversity was associated with higher GMV in the right cerebellum VI, higher CBF in the bilateral calcarine sulcus yet lower CBF in the left superior frontal gyrus, higher FCS in the bilateral paracentral lobule, and lower diffusivity in widespread white matter regions in males. However, these associations were absent in females. Of more importance, these neuroimaging biomarkers significantly mediated the association between gut microbial diversity and behavioral inhibition in males. CONCLUSIONS: These findings highlight sex as a potential influential factor underlying the gut microbiota-brain-cognition relationship, and expose the gut microbiota as a biomarker-driven and sex-sensitive intervention target for mental disorders with abnormal behavioral inhibition.

Frequency-dependent genetic modulation of neuronal oscillations: a combined transcriptome and resting-state functional MRI study.

Neuronal oscillations within certain frequency bands are assumed to associate with specific neural processes and cognitive functions. To examine this hypothesis, transcriptome-neuroimaging spatial correlation analysis was applied to resting-state functional magnetic resonance imaging data from 793 healthy individuals and gene expression data from the Allen Human Brain Atlas. We found that expression measures of 336 genes were correlated with fractional amplitude of low-frequency fluctuations (fALFF) in the slow-4 band (0.027-0.073 Hz), whereas there were no expression-fALFF correlations for the other frequency bands. Furthermore, functional enrichment analyses showed that these slow-4 fALFF-related genes were mainly enriched for ion channel, synaptic function, and neuronal system as well as many neuropsychiatric disorders. Specific expression analyses demonstrated that these genes were specifically expressed in brain tissue, in neurons, and during the late stage of cortical development. Concurrently, the fALFF-related genes were linked to multiple behavioral domains, including dementia, attention, and emotion. In addition, these genes could construct a protein-protein interaction network supported by 30 hub genes. Our findings of a frequency-dependent genetic modulation of spontaneous neuronal activity may support the concept that neuronal oscillations within different frequency bands capture distinct neurobiological processes from the perspective of underlying molecular mechanisms.

Genetic Architecture Underlying Differential Resting-state Functional Connectivity of Subregions Within the Human Visual Cortex.

The human visual cortex is a heterogeneous entity that has multiple subregions showing substantial variability in their functions and connections. We aimed to identify genes associated with resting-state functional connectivity (rsFC) of visual subregions using transcriptome-neuroimaging spatial correlations in discovery and validation datasets. Results showed that rsFC of eight visual subregions were associated with expression measures of eight gene sets, which were specifically expressed in brain tissue and showed the strongest correlations with visual behavioral processes. Moreover, there was a significant divergence in these gene sets and their functional features between medial and lateral visual subregions. Relative to those associated with lateral subregions, more genes associated with medial subregions were found to be enriched for neuropsychiatric diseases and more diverse biological functions and pathways, and to be specifically expressed in multiple types of neurons and immune cells and during the middle and late stages of cortical development. In addition to shared behavioral processes, lateral subregion associated genes were uniquely correlated with high-order cognition. These findings of commonalities and differences in the identified rsFC-related genes and their functional features across visual subregions may improve our understanding of the functional heterogeneity of the visual cortex from the perspective of underlying genetic architecture.

Transcriptional substrates underlying functional connectivity profiles of subregions within the human sensorimotor cortex.

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.

Functional connectivity of the central autonomic and default mode networks represent neural correlates and predictors of individual personality.

There is solid evidence for the prominent involvement of the central autonomic and default mode systems in shaping personality. However, whether functional connectivity of these systems can represent neural correlates and predictors of individual variation in personality traits is largely unknown. Resting-state functional magnetic resonance imaging data of 215 healthy young adults were used to construct the sympathetic (SN), parasympathetic (PN), and default mode (DMN) networks, with intra- and internetwork functional connectivity measured. Personality factors were assessed using the five-factor model. We examined the associations between personality factors and functional network connectivity, followed by performance of personality prediction based on functional connectivity using connectome-based predictive modeling (CPM), a recently developed machine learning approach. All personality factors (neuroticism, extraversion, conscientiousness, and agreeableness) other than openness were significantly correlated with intra- and internetwork functional connectivity of the SN, PN, and DMN. Moreover, the CPM models successfully predicted conscientiousness and agreeableness at the individual level using functional network connectivity. Our findings may expand existing knowledge regarding the neural substrates underlying personality.

Large-scale functional network connectivity mediate the associations of gut microbiota with sleep quality and executive functions.

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.

Establishing a new human hypertrophic cardiomyopathy-specific model using human embryonic stem cells.

Symptom of ventricular hypertrophy caused by cardiac troponin T (TNNT2) mutations is mild, while patients often showed high incidence of sudden cardiac death. The 92nd arginine to glutamine mutation (R92Q) of cTnT was one of the mutant hotspots in hypertrophic cardiomyopathy (HCM). However, there are no such human disease models yet. To solve this problem, we generated TNNT2 R92Q mutant hESC cell lines (heterozygote or homozygote) using TALEN mediated homologous recombination in this study. After directed cardiac differentiation, we found a relative larger cell size in both heterozygous and homozygous TNNT2 R92Q hESC-cardiomyocytes. Expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and sarcoplasmic reticulum Ca2+-ATPase2a (SERCA2a) were downregulated, while myocyte specific enhancer factor 2c (MEF2c) and the ratio of beta myosin to alpha myosin heavy chain (MYH7/MYH6) were increased in heterozygous TNNT2 R92Q hESC-cardiomyocytes. TNNT2 R92Q mutant cardiomyocytes exhibited efficient responses to heart-related pharmaceutical agents. We also found TNNT2 R92Q heterozygous mutant cardiomyocytes showed increased calcium sensitivity and contractility. Further, engineered heart tissues (EHTs) prepared by combining rat decellularized heart extracellular matrices with heterozygous R92Q mutant cardiomyocytes showed similar drug responses as to HCM patients and increased sensitivity to caspofungin-induced cardiotoxicity. Using RNA-sequencing of TNNT2 R92Q heterozygous mutant cardiomyocytes, we found dysregulation of calcium might participated in the early development of hypertrophy. Our hESC-derived TNNT2 R92Q mutant cardiomyocytes and EHTs are good in vitro human disease models for future disease studies and drug screening.

Selective Functional Hyperconnectivity in the Middle Temporal Gyrus Subregions in Lifelong Premature Ejaculation.

BACKGROUND: 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. AIM: 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. METHODS: 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. OUTCOMES: 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. RESULTS: 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). CLINICAL IMPLICATIONS: Functional hyperconnectivity in the MTG subregions may facilitate a more sophisticated understanding of the neuropathological mechanism underlying LPE. STRENGTHS AND LIMITATIONS: 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. CONCLUSIONS: 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.

Large-Scale Internetwork Functional Connectivity Mediates the Relationship between Serum Triglyceride and Working Memory in Young Adulthood.

Previous research has demonstrated that serum lipid profile is associated with cognitive function as well as brain structure and function in middle-aged, elderly, and clinical populations. However, the nature and extent of lipids-brain-cognition relationships in young adulthood are largely unknown. In this study, 157 healthy young adults underwent resting-state functional MRI scans. Functional connectivity between and within 14 functional networks were calculated using independent component analysis. Peripheral venous blood samples were collected to measure serum lipids. Working memory was assessed using a 3-back task. Linear regression, correlation, and mediation analyses were conducted to test for potential associations between serum lipids, inter- and intranetwork functional connectivity, and working memory performance. We found that higher serum triglyceride (TG) level was correlated with stronger connectivity between left frontoparietal and ventral attention networks, between right frontoparietal and dorsal attention networks, between right frontoparietal and dorsal sensorimotor networks, between right frontoparietal and lateral visual networks, and between salience (SN) and ventral sensorimotor (vSMN) networks, as well as lower connectivity between posterior default mode and left frontoparietal networks, between left frontoparietal and medial visual networks, and between ventral attention and dorsal sensorimotor networks. In addition, higher SN-vSMN connectivity was related to lower 3-back accuracy. More importantly, the relationship between serum TG and 3-back accuracy was mediated by SN-vSMN connectivity. Our findings not only may expand existing knowledge regarding serum lipids-brain-cognition relations from the perspective of large-scale functional network organization but also may inform a translational conceptualization of how to improve cognitive function through regulating serum lipids.

Altered neurovascular coupling in neuromyelitis optica.

Neurovascular coupling reflects the close relationship between neuronal activity and cerebral blood flow (CBF), providing a new mechanistic insight into health and disease. Neuromyelitis optica (NMO) is an autoimmune inflammatory demyelinating disease of the central nervous system and shows cognitive decline-related brain gray matter abnormalities besides the damage of optic nerve and spinal cord. We aimed to investigate neurovascular coupling alteration and its clinical significance in NMO by using regional homogeneity (ReHo) to measure neuronal activity and CBF to measure vascular response. ReHo was calculated from functional MRI and CBF was computed from arterial spin labeling (ASL) in 56 patients with NMO and 63 healthy controls. Global neurovascular coupling was assessed by across-voxel CBF-ReHo correlations and regional neurovascular coupling was evaluated by CBF/ReHo ratio. Correlations between CBF/ReHo ratio and clinical variables were explored in patients with NMO. Global CBF-ReHo coupling was decreased in patients with NMO relative to healthy controls (p = .009). Patients with NMO showed decreased CBF/ReHo ratio (10.9%-17.3% reduction) in the parietal and occipital regions and increased CBF/ReHo ratio (8.0%-13.3% increase) in the insular, sensorimotor, temporal and prefrontal regions. Some of these abnormalities cannot be identified by a single CBF or ReHo analysis. Both abnormally decreased and increased CBF/ReHo ratios were correlated with more severe clinical impairments and cognitive decline in patients with NMO. These findings suggested that patients with NMO show abnormal neurovascular coupling, which is associated with disease severity and cognitive impairments.