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The human brain is organized as a complex, hierarchical network. However, the structural covariance patterns among brain regions and the underlying biological substrates of such covariance networks remain to be clarified. The present study proposed a novel individualized structural covariance network termed voxel-based texture similarity networks (vTSNs) based on 76 refined voxel-based textural features derived from structural magnetic resonance images. Validated in three independent longitudinal healthy cohorts (40, 23, and 60 healthy participants, respectively) with two common brain atlases, we found that the vTSN could robustly resolve inter-subject variability with high test-retest reliability. In contrast to the regional-based texture similarity networks (rTSNs) that calculate radiomic features based on region-of-interest information, vTSNs had higher inter- and intra-subject variability ratios and test-retest reliability in connectivity strength and network topological properties. Moreover, the Spearman correlation indicated a stronger association of the gene expression similarity network (GESN) with vTSNs than with rTSNs (vTSN: r = 0.600, rTSN: r = 0.433, z = 39.784, P < 0.001). Hierarchical clustering identified 3 vTSN subnets with differential association patterns with 13 coexpression modules, 16 neurotransmitters, 7 electrophysiology, 4 metabolism, and 2 large-scale structural and 4 functional organization maps. Moreover, these subnets had unique biological hierarchical organization from the subcortex-limbic system to the ventral neocortex and then to the dorsal neocortex. Based on 424 unrelated, qualified healthy subjects from the Human Connectome Project, we found that vTSNs could sensitively represent sex differences, especially for connections in the subcortex-limbic system and between the subcortex-limbic system and the ventral neocortex. Moreover, a multivariate variance component model revealed that vTSNs could explain a significant proportion of inter-subject behavioral variance in cognition (80.0 %) and motor functions (63.4 %). Finally, using 494 healthy adults (aged 19-80 years old) from the Southwest University Adult Lifespan Dataset, the Spearman correlation identified a significant association between aging and vTSN strength, especially within the subcortex-limbic system and between the subcortex-limbic system and the dorsal neocortex. In summary, our proposed vTSN is robust in uncovering individual variability and neurobiological brain processes, which can serve as biologically plausible measures for linking biological processes and human behavior., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Injury to the spinal cord of children may cause potential brain reorganizations, affecting their rehabilitation. However, the specific functional alterations of children after complete spinal cord injury (CSCI) remain unclear., Purpose: To explore the specific functional changes in local brain and the relationship with clinical characteristics in pediatric CSCI patients, clarifying the impact of CSCI on brain function in developing children., Study Type: Prospective., Subjects: Thirty pediatric CSCI patients (7.83 ± 1.206 years) and 30 age-, gender-matched healthy children as controls (HCs) (8.77 ± 2.079 years)., Field Strength/sequence: 3.0 T/Resting-state functional MRI (rs-fMRI) using echo-planar-imaging (EPI) sequence., Assessment: Amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) were used to characterize regional neural function., Statistical Tests: Two-sample t-tests were used to compare the ALFF, fALFF, ReHo values of the brain between pediatric CSCI and HCs (voxel-level FWE correction, P < 0.05). Spearman correlation analyses were performed to analyze the associations between the ALFF, fALFF, ReHo values in altered regions and the injury duration, sensory motor scores of pediatric CSCI patients (P < 0.05). Then receiver operating characteristic (ROC) analysis was conducted to identify possible sensitive imaging indicators for clinical therapy., Results: Compared with HCs, pediatric CSCI showed significantly decreased ALFF in the right postcentral gyrus (S1), orbitofrontal cortex, and left superior temporal gyrus (STG), increased ALFF in bilateral caudate nucleus, thalamus, middle cingulate gyrus, and cerebellar lobules IV-VI, and increased ReHo in left cerebellum Crus II and Brodmann area 21. The ALFF value in the right S1 negatively correlated with the pinprick and light touch sensory scores of pediatric CSCI. When the left STG was used as an imaging biomarker for pediatric CSCI, it achieved the highest area under the curve of 0.989., Conclusions: These findings may provide potential neural mechanisms for sensory motor and cognitive-emotional deficits in children after CSCI., Evidence Level: 2 TECHNICAL EFFICACY: Stage 5., (© 2023 International Society for Magnetic Resonance in Medicine.)

Genome-wide association studies of brain imaging phenotypes are mainly performed in European populations, but other populations are severely under-represented. Here, we conducted Chinese-alone and cross-ancestry genome-wide association studies of 3,414 brain imaging phenotypes in 7,058 Chinese Han and 33,224 white British participants. We identified 38 new associations in Chinese-alone analyses and 486 additional new associations in cross-ancestry meta-analyses at P < 1.46 × 10 -11 for discovery and P < 0.05 for replication. We pooled significant autosomal associations identified by single- or cross-ancestry analyses into 6,443 independent associations, which showed uneven distribution in the genome and the phenotype subgroups. We further divided them into 44 associations with different effect sizes and 3,557 associations with similar effect sizes between ancestries. Loci of these associations were shared with 15 brain-related non-imaging traits including cognition and neuropsychiatric disorders. Our results provide a valuable catalog of genetic associations for brain imaging phenotypes in more diverse populations., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Exposure to preadult environmental exposures may have long-lasting effects on mental health by affecting the maturation of the brain and personality, two traits that interact throughout the developmental process. However, environment-brain-personality covariation patterns and their mediation relationships remain unclear. In 4297 healthy participants (aged 18-30 years), we combined sparse multiple canonical correlation analysis with independent component analysis to identify the three-way covariation patterns of 59 preadult environmental exposures, 760 adult brain imaging phenotypes, and five personality traits, and found two robust environment-brain-personality covariation models with sex specificity. One model linked greater stress and less support to weaker functional connectivity and activity in the default mode network, stronger activity in subcortical nuclei, greater thickness and volume in the occipital, parietal and temporal cortices, and lower agreeableness, consciousness and extraversion as well as higher neuroticism. The other model linked higher urbanicity and better socioeconomic status to stronger functional connectivity and activity in the sensorimotor network, smaller volume and surface area and weaker functional connectivity and activity in the medial prefrontal cortex, lower white matter integrity, and higher openness to experience. We also conducted mediation analyses to explore the potential bidirectional mediation relationships between adult brain imaging phenotypes and personality traits with the influence of preadult environmental exposures and found both environment-brain-personality and environment-personality-brain pathways. We finally performed moderated mediation analyses to test the potential interactions between macro- and microenvironmental exposures and found that one category of exposure moderated the mediation pathways of another category of exposure. These results improve our understanding of the effects of preadult environmental exposures on the adult brain and personality traits and may facilitate the design of targeted interventions to improve mental health by reducing the impact of adverse environmental exposures., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Urbanicity is a growing environmental challenge for mental health. Here, we investigate correlations of urbanicity with brain structure and function, neuropsychology and mental illness symptoms in young people from China and Europe (total n = 3,867). We developed a remote-sensing satellite measure (UrbanSat) to quantify population density at any point on Earth. UrbanSat estimates of urbanicity were correlated with brain volume, cortical surface area and brain network connectivity in the medial prefrontal cortex and cerebellum. UrbanSat was also associated with perspective-taking and depression symptoms, and this was mediated by neural variables. Urbanicity effects were greatest when urban exposure occurred in childhood for the cerebellum, and from childhood to adolescence for the prefrontal cortex. As UrbanSat can be generalized to different geographies, it may enable assessments of correlations of urbanicity with mental illness and resilience globally., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Genes involved in pain and touch sensations have been studied extensively, but very few studies have tried to link them with neural activities in the brain. Here, we aimed to identify genes preferentially correlated to painful activation patterns by linking the spatial patterns of gene expression of Allen Human Brain Atlas with the pain-elicited neural responses in the human brain, with a parallel, control analysis for identification of genes preferentially correlated to tactile activation patterns. We identified 1828 genes whose expression patterns preferentially correlated to painful activation patterns and 411 genes whose expression patterns preferentially correlated to tactile activation pattern at the cortical level. In contrast to the enrichment for astrocyte and inhibitory synaptic transmission of genes preferentially correlated to tactile activation, the genes preferentially correlated to painful activation were mainly enriched for neuron and opioid- and addiction-related pathways and showed significant overlap with pain-related genes identified in previous studies. These findings not only provide important evidence for the differential genetic architectures of specific brain activation patterns elicited by painful and tactile stimuli but also validate a new approach to studying pain- and touch-related genes more directly from the perspective of neural responses in the human brain., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Canonical correlation analysis (CCA), a multivariate approach to identifying correlations between two sets of variables, is becoming increasingly popular in neuroimaging studies on brain-behavior relationships. However, the CCA stability in neuroimaging applications has not been systematically investigated. Although it is known that the number of subjects should be greater than the number of variables due to the curse of dimensionality, it is unclear at what subject-to-variable ratios (SVR) and at what correlation strengths the CCA stability can be maintained. Here, we systematically assessed the CCA stability, in the context of investigating the relationship between the brain structural/functional imaging measures and the behavioral measures, by measuring the similarity of the first-mode canonical variables across randomly sampled subgroups of subjects from a large set of 936 healthy subjects. Specifically, we tested how the CCA stability changes with SVR under two different brain-behavior correlation strengths. The same tests were repeated using an independent data set (n = 700) for validation. The results confirmed that both SVR and correlation strength affect greatly the CCA stability-the CCA stability cannot be guaranteed if the SVR is not sufficiently high or the brain-behavior relationship is not sufficiently strong. Based on our quantitative characterization of CCA stability, we provided a practical guideline to help correct interpretation of CCA results and proper applications of CCA in neuroimaging studies on brain-behavior relationships., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Studies have indicated that the dorsal attention network (DAN) and the ventral attention network (VAN) functionally interact via several fronto-parietal connector hubs. However, the anatomical connectivity profiles of these connector hubs, and the coupling between the anatomical and functional connectivities of them, are still unknown. In the present study, we found that functional connector hubs anatomically bridged the DAN and VAN based on multimodal magnetic resonance imaging data from the Human Connectome Project (HCP) Consortium and an independent Chinese cohort. The three hubs had unique anatomical connectivity patterns with the attention sub-networks. For each connector hub, the pattern of anatomical connectivity resembled the functional one. Finally, the strength of the anatomical connectivity of these connector hubs was positively associated with the functional connectivity at the group- and individual-levels. Our findings help to better understand the anatomical mechanisms underlying the functional interactions between the DAN and the VAN., (Copyright © 2021. Published by Elsevier Inc.)

It was reported that acupuncture could treat Alzheimer's disease (AD) with the potential mechanisms remaining unclear. The aim of the study is to explore the effect of the combination stimulus of Hegu (LI4) and Taichong (LR3) on the resting-state brain networks in AD, beyond the default network (DMN). Twenty-eight subjects including 14 AD patients and 14 healthy controls (HCs) matched by age, gender, and educational level were recruited in this study. After the baseline resting-state MRI scans, the manual acupuncture stimulation was performed for 3 minutes, and then, another 10 minutes of resting-state fMRI scans was acquired. In addition to the DMN, five other resting-state networks were identified by independent component analysis (ICA), including left frontal parietal network (lFPN), right frontal parietal network (rFPN), visual network (VN), sensorimotor network (SMN), and auditory network (AN). And the impaired connectivity in the lFPN, rFPN, SMN, and VN was found in AD patients compared with those in HCs. After acupuncture, significantly decreased connectivity in the right middle frontal gyrus (MFG) of rFPN ( P = 0.007) was identified in AD patients. However, reduced connectivity in the right inferior frontal gyrus (IFG) ( P = 0.047) and left superior frontal gyrus (SFG) ( P = 0.041) of lFPN and some regions of the SMN (the left inferior parietal lobula ( P = 0.004), left postcentral gyrus (PoCG) ( P = 0.001), right PoCG ( P = 0.032), and right MFG ( P = 0.010)) and the right MOG of VN ( P = 0.003) was indicated in HCs. In addition, after controlling for the effect of acupuncture on HCs, the functional connectivity of the right cerebellum crus I, left IFG, and left angular gyrus (AG) of lFPN showed to be decreased, while the left MFG of IFPN and the right lingual gyrus of VN increased in AD patients. These findings might have some reference values for the interpretation of the combination stimulus of Hegu (LI4) and Taichong (LR3) in AD patients, which could deepen our understanding of the potential mechanisms of acupuncture on AD., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Shaozhen Ji et al.)

Dementia affects millions of elderly worldwide causing remarkable costs to society, but effective treatment is still lacking. Acupuncture is one of the complementary therapies that has been applied to cognitive deficits such as Alzheimer's disease (AD) and vascular cognitive impairment (VCI), while the underlying mechanisms of its therapeutic efficiency remain elusive. Neuroplasticity is defined as the ability of the nervous system to adapt to internal and external environmental changes, which may support some data to clarify mechanisms how acupuncture improves cognitive impairments. This review summarizes the up-to-date and comprehensive information on the effectiveness of acupuncture treatment on neurogenesis and gliogenesis, synaptic plasticity, related regulatory factors, and signaling pathways, as well as brain network connectivity, to lay ground for fully elucidating the potential mechanism of acupuncture on the regulation of neuroplasticity and promoting its clinical application as a complementary therapy for AD and VCI., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Shaozhen Ji et al.)

Neuroticism is a heritable personality trait associated with negative emotionality; however, we know little regarding the association between the microscale and macroscale neurobiological substrates of human neuroticism. Cross-scale correlation analysis may provide such information. In this study, voxel-wise neuroimaging-neuroticism correlation analyses consistently showed a positive correlation between neuroticism and functional connectivity density (FCD) in the ventral striatum in 274 young Chinese adults. Partial least squares regression analysis showed that the FCD-neuroticism correlation map was significantly spatially correlated with gene expression profiles in each of six donated human brains. Neuroticism-related genes derived from the six donors consistently showed significant enrichment in the chemical synaptic transmission, circadian entrainment, long-term potentiation, inflammatory mediator regulation of transient receptor potential channels, and amphetamine addiction pathways. The protein-protein interaction analysis revealed four hub genes involved in the above pathways, including G protein subunit gamma 10, 5-hydroxytryptamine receptor 2C, prodynorphin, and calcium/calmodulin-dependent protein kinase II alpha. By combining multiscale correlation analyses and functional annotations, this study advances our understanding of the genetic and neural substrates of human neuroticism and emphasizes the importance of striatal functional properties in human neuroticism., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

A systematic characterization of the similarities and differences among different methods for detecting structural brain abnormalities in schizophrenia, such as voxel-based morphometry (VBM), tensor-based morphometry (TBM), and projection-based thickness (PBT), is important for understanding the brain pathology in schizophrenia and for developing effective biomarkers for a diagnosis of schizophrenia. However, such studies are still lacking. Here, we performed VBM, TBM, and PBT analyses on T1-weighted brain MR images acquired from 116 patients with schizophrenia and 116 healthy controls. We found that, although all methods detected wide-spread structural changes, different methods captured different information - only 10.35% of the grey matter changes in cortex were detected by all three methods, and VBM only detected 11.36% of the white matter changes detected by TBM. Further, pattern classification between patients and controls revealed that combining different measures improved the classification accuracy (81.9%), indicating that fusion of different structural measures serves as a better neuroimaging marker for the objective diagnosis of schizophrenia.

Numerous studies report abnormal cerebral cortex volume (CCV) in autism spectrum disorder (ASD); however, genes related to CCV abnormalities in ASD remain largely unknown. Here, we identify genes associated with CCV alterations in ASD by performing spatial correlations between the gene expression of 6 donated brains and neuroimaging data from 1,404 ASD patients and 1,499 controls. Based on spatial correlations between gene expression and CCV differences from two independent meta-analyses and between gene expression and individual CCV distributions of 404 patients and 496 controls, we identify 417 genes associated with both CCV differences and individual CCV distributions. These genes are enriched for genetic association signals and genes downregulated in the ASD post-mortem brain. The expression patterns of these genes are correlated with brain activation patterns of language-related neural processes frequently impaired in ASD. These findings highlight a model whereby genetic risk impacts gene expression (downregulated), which leads to CCV alterations in ASD., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

A common variant (rs53576, G/A) in the oxytocin receptor (OXTR) gene is associated with individual differences in social behavior and may increase the risk for neuropsychiatric disorders characterized by social impairment, especially autism. Although recent functional magnetic resonance imaging (fMRI) studies have identified functional connectivity alteration in some brain regions in risk A allele carriers, it is currently unknown whether this dysfunctional connectivity causes disruption of the topological properties of brain functional networks. We applied a graph-theoretical analysis to investigate the topological properties of brain networks derived from resting-state fMRI in relation to AA homozygotes versus G allele carriers in 290 cognitive normal young adults. We found both AA homozygotes and G allele carriers demonstrated small-world properties; however, male AA homozygotes showed lower normalized clustering coefficient, small-worldness, and local efficiency compared with male G allele carriers, no differences survived after Bonferroni correction; and the inter-group differences of all three metrics exhibited an allele-load-dependent trend (AA < AG < GG), indicating a randomization shift of their brain functional networks. No significant results were observed in any global measures in female AA homozygotes as compared to female G allele carriers. Our results suggested that the topological patterns of brain functional networks were altered in OXTR rs53576 male homozygotes for the risk A allele compared with male G allele carriers, providing evidence for the disruption of integrity in large-scale intrinsic brain networks in a sex-dimorphic manner.

Visualization of the brain in its native environment is important for understanding common brain diseases. Herein, bright luminogens with remarkable aggregation-induced emission (AIE) characteristics and high quantum yields of up to 42.6% in the solid state are synthesized through facile reaction routes. The synthesized molecule, namely BTF, shows ultrabright far-red/near-infrared emission and can be fabricated into AIE dots by a simple nanoprecipitation procedure. Due to their high brightness, large Stokes shift, good biocompatibility, satisfactory photostability, and large three-photon absorption cross section, the AIE dots can be utilized as efficient fluorescent nanoprobes for in vivo brain vascular imaging through the intact skull by a three-photon fluorescence microscopy imaging technique. This is the first example of using AIE dots for the visualization of the cerebral stroke process through the intact skull of a mouse with high penetration depth and good image contrast. Such good results are anticipated to open up a new venue in the development of efficient emitters with strong nonlinear optical effects for noninvasive bioimaging of living brain., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The Chinese Imaging Genetics (CHIMGEN) study establishes the largest Chinese neuroimaging genetics cohort and aims to identify genetic and environmental factors and their interactions that are associated with neuroimaging and behavioral phenotypes. This study prospectively collected genomic, neuroimaging, environmental, and behavioral data from more than 7000 healthy Chinese Han participants aged 18-30 years. As a pioneer of large-sample neuroimaging genetics cohorts of non-Caucasian populations, this cohort can provide new insights into ethnic differences in genetic-neuroimaging associations by being compared with Caucasian cohorts. In addition to micro-environmental measurements, this study also collects hundreds of quantitative macro-environmental measurements from remote sensing and national survey databases based on the locations of each participant from birth to present, which will facilitate discoveries of new environmental factors associated with neuroimaging phenotypes. With lifespan environmental measurements, this study can also provide insights on the macro-environmental exposures that affect the human brain as well as their timing and mechanisms of action.

Fluorescence probes in the NIR-IIa region show drastically improved imaging owing to the reduced photon scattering and autofluorescence in biological tissues. Now, NIR-IIa polymer dots (Pdots) are developed with a dual fluorescence enhancement mechanism. First, the aggregation induced emission of phenothiazine was used to reduce the nonradiative decay pathways of the polymers in condensed states. Second, fluorescence quenching was minimized by different levels of steric hindrance to further boost the fluorescence. The resulting Pdots displayed a fluorescence QY of ca. 1.7 % in aqueous solution, suggesting an enhancement of ca. 21 times in comparison with the original polymer in tetrahydrofuran (THF) solution. Small-animal imaging by using the NIR-IIa Pdots exhibited a remarkable improvement in penetration depth and signal to background ratio, as confirmed by through-skull and through-scalp fluorescent imaging of the cerebral vasculature of live mice., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Apart from amyloid β deposition and tau neurofibrillary tangles, Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuronal loss and astrocytosis in the cerebral cortex. The goal of this study is to investigate genetic factors associated with the neuronal proportion in health and disease. To identify cell-autonomous genetic variants associated with neuronal proportion in cortical tissues, we inferred cellular population structure from bulk RNA-Seq derived from 1536 individuals. We identified the variant rs1990621 located in the TMEM106B gene region as significantly associated with neuronal proportion (p value = 6.40 × 10 -07 ) and replicated this finding in an independent dataset (p value = 7.41 × 10 -04 ) surpassing the genome-wide threshold in the meta-analysis (p value = 9.42 × 10 -09 ). This variant is in high LD with the TMEM106B non-synonymous variant p.T185S (rs3173615; r 2  = 0.98) which was previously identified as a protective variant for frontotemporal lobar degeneration (FTLD). We stratified the samples by disease status, and discovered that this variant modulates neuronal proportion not only in AD cases, but also several neurodegenerative diseases and in elderly cognitively healthy controls. Furthermore, we did not find a significant association in younger controls or schizophrenia patients, suggesting that this variant might increase neuronal survival or confer resilience to the neurodegenerative process. The single variant and gene-based analyses also identified an overall genetic association between neuronal proportion, AD and FTLD risk. These results suggest that common pathways are implicated in these neurodegenerative diseases, that implicate neuronal survival. In summary, we identified a protective variant in the TMEM106B gene that may have a neuronal protection effect against general aging, independent of disease status, which could help elucidate the relationship between aging and neuronal survival in the presence or absence of neurodegenerative disorders. Our findings suggest that TMEM106B could be a potential target for neuronal protection therapies to ameliorate cognitive and functional deficits.

The salience network (SN) is mainly involved in detecting and filtering multimodal salient stimuli, and mediating the switch between the default mode network and central executive network. Early studies have indicated a right-sided dominance in the functional organization of the SN; however, the anatomical basis of the functional lateralization remains unclear. Here, we hypothesized that the structural connectivity profile between the frontoinsular cortex (FIC) and dorsal anterior cingulate cortex (dACC), which are two core hubs of the SN, is also dominant in the right hemisphere. Based on diffusion and resting-state functional magnetic resonance imaging (rfMRI) of adult healthy volunteers in independent datasets, we found a stable right-sided laterality of both the FIC-dACC structural and functional connectivity in both the human connectome project cohort and a local Chinese cohort. Furthermore, a significant effect of aging on the integrity of the right FIC-dACC structural connectivity was also identified. The right-sided laterality of the structural organization of the SN may help us to better understand the functional roles of the SN in the normal human brain., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Catechol-O-methyltransferase (COMT) affects brain connectivity via modulating the dopamine system, with an expected greater effect of haplotypes than single-nucleotide polymorphism (SNP). The action pathway from COMT to dopamine to connectivity is theoretically dependent on the gene expression of dopamine receptors. Here, we aimed to investigate the impact of COMT haplotypes on brain functional connectivity density (FCD) in hundreds of healthy young subjects, and to disclose the association between the COMT-FCD statistical map and the spatial expression of the dopamine receptor genes. We found an inverted U-shaped modulation of COMT haplotypes on FCD in the left inferior parietal lobule that is mainly connected to the frontal and parietal cortices, with APS homozygotes exhibiting greater FCD than the other five groups. However, we failed to identify any significant effect of any SNP on FCD. Utilizing gene expression data collected from Allen human brain atlas, we found the COMT-FCD statistical map was significantly associated with the expression patterns of the dopamine receptor genes. Our results suggest that COMT haplotypes have greater impact on functional connectivity than a single genetic variation and that the association between COMT and functional connectivity may be dependent on the gene expression of dopamine receptors.

Total sleep deprivation (TSD) is common in modern society leading to deterioration of multiple aspects of cognition. Dynamic interaction effect of circadian rhythmicity and homeostatic sleep pressure on sustained attention have been intensively investigated, while how this effect was represented on performance and cerebral responses to working memory, another important element of many neurobehavioral tasks, was not well elucidated. Thirty-six healthy subjects with intermediate chronotype performed the Sternberg working-memory task (SWMT) while undergoing functional magnetic resonance imaging every 2 hr from 10:00 p.m. on the first day to 6:00 a.m. on the second day. Using data from three imaging sessions (10:00 p.m., 04:00 a.m., and 06:00 a.m.), we found that the slowest SWMT reaction time and weakest cerebral responses were not at the end of TSD (06:00 a.m.) but during the early morning (04:00 a.m.) hours of the TSD. In addition, during this worst period of TSD, reaction time for the SWMT were found to be negatively correlated with task-related activation in the angular gyrus and positively correlated with the degree of negative correlation between the control and default networks. Our results revealed a rebound of SWMT reaction time and cerebral responses after the mid-time point of regular biological sleep night and provided more evidence that different cognitive tasks are differentially affected by sleep loss and circadian rhythmicity., (© 2019 Wiley Periodicals, Inc.)

How pain emerges from cortical activities remains an unresolved question in pain neuroscience. A first step toward addressing this question consists in identifying brain activities that occur preferentially in response to painful stimuli in comparison to non-painful stimuli. A key confound that has affected this important comparison in many previous studies is the intensity of the stimuli generating painful and non-painful sensations. Here, we compared the brain activity during iso-intense painful and tactile sensations sampled by functional MRI in 51 healthy participants. Specifically, the perceived intensity was recorded for every stimulus and only the stimuli with rigorously matched perceived intensity were selected and compared between painful and tactile conditions. We found that all brain areas activated by painful stimuli were also activated by tactile stimuli, and vice versa. Neural responses in these areas were correlated with the perceived stimulus intensity, regardless of stimulus modality. More importantly, among these activated areas, we further identified a number of brain regions showing stronger responses to painful stimuli than to tactile stimuli when perceived intensity was carefully matched, including the bilateral opercular cortex, the left supplementary motor area and the right frontal middle and inferior areas. Among these areas, the right frontal middle area still responded more strongly to painful stimuli even when painful stimuli were perceived less intense than tactile stimuli, whereas in this condition other regions showed stronger responses to tactile stimuli. In contrast, the left postcentral gyrus, the visual cortex, the right parietal inferior gyrus, the left parietal superior gyrus and the right cerebellum had stronger responses to tactile stimuli than to painful stimuli when perceived intensity was matched. When tactile stimuli were perceived less intense than painful stimuli, the left postcentral gyrus and the right parietal inferior gyrus still responded more strongly to tactile stimuli while other regions now showed similar responses to painful and tactile stimuli. These results suggest that different brain areas may be engaged differentially when processing painful and tactile information, although their neural activities are not exclusively dedicated to encoding information of only one modality but are strongly determined by perceived stimulus intensity regardless of stimulus modality., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction, and white matter (WM) microstructural impairments play a critical role in T2DM-related cognitive decline. Disruptions to the WM have been detected in T2DM patients before clinical diagnosis of cognitive dysfunction. Herein, we investigated changes in brain structural topological properties and their correlation with behavior in T2DM patients without complications., Methods: Diffusion tensor imaging (DTI) structural network topological analysis was performed on T2DM patients and healthy controls. Intergroup differences in global and nodal parameters were analyzed, and correlations between the network parameters and behavioral performance were tested., Results: Type 2 diabetes mellitus patients exhibited preserved small-world properties, but altered nodal properties, including decreased efficiency in the right hippocampus, right amygdala, left pallidum, left postcentral gyrus, and right pole of the superior temporal gyrus, and increased degree in the right inferior frontal gyrus. Correlations were also found between the altered global and nodal parameters and behavioral performance., Conclusions: The results verified the existence of WM structural network changes and the association between structural properties and cognitive state in T2DM patients before the occurrence of complications. Research of structural properties may contribute to our understanding of the intrinsic links between T2DM and cognition., (© 2018 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Crohn's disease (CD) has been reported to relate with the functional and structural alterations in several local brain regions. However, it remains unknown whether the possible abnormalities of information transmission and integration between brain regions are associated with CD. The purpose of this study was to investigate the topological alterations of brain functional networks and the potential relationships between the neuroimaging findings and CD clinical characteristics. 43 remissive CD patients and 37 matched healthy controls (HCs) were recruited to obtain their resting-state functional magnetic resonance imaging (fMRI) data. Independent component analysis was applied to decompose fMRI data for building brain functional networks. The local and global topological properties of networks and connectivity of brain regions were computed within each group. We then examined the relationships between the topological patterns and CD clinical characteristics. Compared to HCs, CD patients exhibited disrupted local and global topological patterns of brain functional networks including the decreased nodal graph metrics in the subcortical, sensorimotor, cognitive control and default-mode networks and dysfunctional interactions within and among these four networks. The connectivity strength of putamen negatively correlated with CD duration in patients. Moreover, CD patients with high level of anxiety and/or depression had altered local topological patterns associated with anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) compared to other patients. By revealing CD-related changes in topological patterns of brain functional networks, our findings provide further neuroimaging evidence on the pathophysiology of CD involved in pain, sensory, emotional and/or cognitive processing.

Specific biomarker reflecting neurobiological substrates of schizophrenia (SZ) is required for its diagnosis and treatment selection of SZ. Evidence from neuroimaging has implicated disrupted functional connectivity in the pathophysiology. We aimed to develop and validate a method of disease definition for SZ by resting-state functional connectivity using radiomics strategy. This study included 2 data sets collected with different scanners. A total of 108 first-episode SZ patients and 121 healthy controls (HCs) participated in the current study, among which 80% patients and HCs (n = 183) and 20% (n = 46) were selected for training and testing in intra-data set validation and 1 of the 2 data sets was selected for training and the other for testing in inter-data set validation, respectively. Functional connectivity was calculated for both groups, features were selected by Least Absolute Shrinkage and Selection Operator (LASSO) method, and the clinical utility of its features and the generalizability of effects across samples were assessed using machine learning by training and validating multivariate classifiers in the independent samples. We found that the accuracy of intra-data set training was 87.09% for diagnosing SZ patients by applying functional connectivity features, with a validation in the independent replication data set (accuracy = 82.61%). The inter-data set validation further confirmed the disease definition by functional connectivity features (accuracy = 83.15% for training and 80.07% for testing). Our findings demonstrate a valid radiomics approach by functional connectivity to diagnose SZ, which is helpful to facilitate objective SZ individualized diagnosis using quantitative and specific functional connectivity biomarker.

Purpose To investigate neural substrates underlying attention deficit in patients with chronic subcortical stroke by combining voxel-based lesion-symptom mapping (VLSM) and diffusion-tensor (DT) tractography. Materials and Methods Institutional review board approval and written informed consent were obtained. Diffusion magnetic resonance imaging data were prospectively acquired from August 1, 2014, to March 30, 2015, in 49 patients (32 men, 17 women; mean age, 55.7 years ± 8.0; age range, 40-71 years) with subcortical infarctions in the basal ganglia and neighboring regions and 52 control subjects (30 men, 22 women; mean age, 54.4 years ± 7.5; age range, 40-68 years). A modified version of the attention network test was used to assess visual attention function. On the basis of the lesion map at the acute stage, VLSM was used to identify lesion locations related to attention deficit in patients with stroke. DT tractography then was used to determine the responsible impaired connections by using diffusion data at the chronic stage (>6 months after stroke). Results When compared with control subjects, patients with chronic stroke exhibited prolonged reaction time (RT) of correct responses (P = .009). VLSM revealed that acute stroke lesion in the right caudate nucleus and nearby white matter (found in seven patients) was correlated with the prolonged RT (P < .05). DTT showed that the responsible lesion was located in the right thalamic- and caudate-prefrontal pathways in control subjects. The subgroup with right-sided brain damage had significantly decreased fractional anisotropy in these pathways (P < .001), which were correlated with the prolonged RT (P = .009 for the thalamic-prefrontal pathway, P < .001 for the caudate-prefrontal pathway). Conclusion Thalamic-prefrontal and caudate-prefrontal pathways impaired by stroke lesions appear to underlie attention deficit in patients with subcortical stroke in the right hemisphere., (© RSNA, 2018 Online supplemental material is available for this article.)

The effects of acupuncture can be characterized by clear individual differences. Several revealing studies suggest an underlying role of inherited genetic factor in interindividual variability in response to acupuncture treatment. It remains unclear, however, if the modulation of acupuncture on resting brain function is influenced by genetic factors. Catechol-o-methyltransferase (COMT) Val158Met polymorphism has been shown to regulate the resting brain network, especially in the default mode network (DMN), which is a target area that responds to acupuncture stimulation. Therefore, the present study investigated the effect of COMT Val158Met polymorphism on the modulation of acupuncture in DMN connectivity in healthy Chinese young adults. Using mixed-design ANOVA analysis, we found a significant interactive effect between acupuncture and the COMT gene. For subjects carrying the Val/Met genotype, acupuncture induced decreased DMN connectivity with the left middle frontal gyrus during the post-acupuncture stage compared with the pre-acupuncture stage, which was not observed in Val/Val homozygous subjects. These results demonstrated that during sustained periods after acupuncture stimulation, the brain network is likely under genetic control, and COMT might be a candidate gene that regulates the resting DMN response to acupuncture stimulation.

Total sleep deprivation (TSD) is increasingly common in modern society bringing various neurobehavioural effects. Dynamic changes of behaviour performances during TSD have been reported extensively, while the cerebral activation underlying such changes have not been elucidated clearly. This study aimed to investigate dynamic changes in cerebral responses to the fastest and slowest psychomotor vigilance task (PVT) trials during TSD. Thirty-six healthy subjects with intermediate chronotype performed the PVT while undergoing functional magnetic resonance imaging every 2 h from 22:00 hours on the first day to 06:00 hours on the second day (i.e. 22:00, 12:00, 02:00, 04:00 and 06:00 hours; a total of five imaging sessions). Behaviourally, significant time effects were found for the PVT performance. For imaging results, significant activation alterations were found in the cognitive control network and the default mode network (DMN) for the fastest and slowest PVT trials, respectively. Time-course analysis indicated that the largest differences for behavioural results and imaging results happened in session 4 and became more prominent in session 5. Our findings provide more detailed information about the process of sustained attention activation during one night of TSD and add information regarding the effect of circadian rhythmicity and homeostatic sleep pressure on regional brain responses., (© 2017 European Sleep Research Society.)

Recent studies suggest dysfunctional brain-gut interactions are involved in the pathophysiology of functional dyspepsia (FD). However, limited studies have investigated brain structural abnormalities in FD patients. This study aimed to identify potential differences in both cortical thickness and subcortical volume in FD patients compared to healthy controls (HCs) and to explore relationships of structural abnormalities with clinical symptoms. Sixty-nine patients and forty-nine HCs underwent 3T structural magnetic resonance imaging scans. Cortical thickness and subcortical volume were compared between the groups across the cortical and subcortical regions, respectively. Regression analysis was then performed to examine relationships between the structure alternations and clinical symptoms in FD patients. Our results showed that FD patients had decreased cortical thickness compared to HCs in the distributed brain regions including the dorsolateral prefrontal cortex (dlPFC), ventrolateral prefrontal cortex (vlPFC), medial prefrontal cortex (mPFC), anterior/posterior cingulate cortex (ACC/PCC), insula, superior parietal cortex (SPC), supramarginal gyrus and lingual gyrus. Significantly negative correlations were observed between the Nepean Dyspepsia Index (NDI) and cortical thickness in the mPFC, second somatosensory cortex (SII), ACC and parahippocampus (paraHIPP). And significantly negative correlations were found between disease duration and the cortical thickness in the vlPFC, first somatosensory cortex (SI) and insula in FD patients. These findings suggest that FD patients have structural abnormalities in brain regions involved in sensory perception, sensorimotor integration, pain modulation, affective and cognitive controls. The relationships between the brain structural changes and clinical symptoms indicate that the alternations may be a consequence of living with FD.

Purpose: Premature ejaculation (PE) is one of the most common sexual dysfunctions in men. However, there has been little research evaluating alterations in brain structure related to PE. We aimed to investigate the characteristics of nonmedicated PE patients in terms of brain morphometry., Materials and Methods: The sample consisted with 32 medication-naïve adult men with clinical diagnosed PE and matched 31 healthy controls. All participants received diagnostic interviews and 3.0 Tesla MRI scans. Automatic segmentation processing of MRI structure images was performed using FreeSurfer software and cerebral cortical thickness between groups was compared., Results: The PE group had thicker cortex in widespread regions, including the frontal, parietal and occipital lobe, and limbic system, compared with the healthy control group (P < 0.05). Moreover, the duration is negatively correlated with the mean cortical thickness of the right medial orbitofrontal cortex, right precentral gyrus and left superior frontal cortex (R 2 = 0.29, P < 0.003; R 2 = 0.163, P < 0.04; R 2 = 0.2, P < 0.02), while the Premature Ejaculation Diagnostic Tool score is negatively correlated with the mean cortical thickness of the left caudal middle frontal cortex (R 2 = 0.33, P < 0.005)., Conclusion: The result highlights the structural features of PE and suggests the relationship with the severity of impairment is related to the severity of anatomic abnormality with the relevant brain region. These results support the value of imaging measures as markers for understanding the physiopathology of PE., Level of Evidence: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:656-662., (© 2017 International Society for Magnetic Resonance in Medicine.)

With the help of advanced neuroimaging approaches, previous studies revealed structural and functional brain changes in smokers compared with healthy non-smokers. Homotopic resting-state functional connectivity between the corresponding regions in cerebral hemispheres may help us to deduce the changes of functional coordination in the whole brain of young male smokers. Functional homotopy reflects an essential aspect of brain function and communication between the left and right cerebral hemispheres, which is important for the integrity of brain function. However, few studies used voxel mirrored homotopic connectivity (VMHC) method to investigate the changes of homotopic connectivity in young male smokers. Twenty-seven young male smokers and 27 matched healthy male non-smokers were recruited in our study. Compared with healthy male non-smokers, young male smokers showed decreased VMHC values in the insula and putamen, and increased VMHC values in the prefrontal cortex. Correlation analysis demonstrated that there were significant positive correlations between the average VMHC values of the prefrontal cortex and pack-years in young male smokers. In addition, significant negative correlation was found between the average VMHC values in the insula and pack-years. Our results revealed the disrupted homotopic resting-state functional connectivity in young male smokers. The novel findings may extend our understanding of smoking., (© 2017 Society for the Study of Addiction.)

Objective: To use a promising analytical method, namely intersubject synchronisation (ISS), to evaluate the brain activity associated with the instant effects of acupuncture and compare the findings with traditional general linear model (GLM) methods., Methods: 30 healthy volunteers were recruited for this study. Block-designed manual acupuncture stimuli were delivered at SP6, and de qi sensations were measured after acupuncture stimulation. All subjects underwent functional MRI (fMRI) scanning during the acupuncture stimuli. The fMRI data were separately analysed by ISS and traditional GLM methods., Results: All subjects experienced de qi sensations. ISS analysis showed that the regions activated during acupuncture stimulation at SP6 were mainly divided into five clusters based on the time courses. The time courses of clusters 1 and 2 were in line with the acupuncture stimulation pattern, and the active regions were mainly involved in the sensorimotor system and salience network. Clusters 3, 4 and 5 displayed an almost contrary time course relative to the stimulation pattern. The brain regions activated included the default mode network, descending pain modulation pathway and visual cortices. GLM analysis indicated that the brain responses associated with the instant effects of acupuncture were largely implicated in sensory and motor processing and sensory integration., Conclusion: The ISS analysis considered the sustained effect of acupuncture and uncovered additional information not shown by GLM analysis. We suggest that ISS may be a suitable approach to investigate the brain responses associated with the instant effects of acupuncture., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Frontotemporal dementia with parkinsonism-linked to chromosome 17 (FTDP-17) is a rare autosomal dominant neurodegenerative disorder. Most patients with FTDP-17 carry the mutation in the microtubule-associated protein tau (MAPT) gene. Striatum is predominantly and early affected in FTDP-17. Five family members (two symptomatic patients and three presymptomatic mutation carriers) from a Chinese pedigree of FTDP-17 with N279K mutation in MAPT were enrolled. Parkinsonism was the initial symptom for symptomatic patients. 2b-carbomethoxy-3b-(4-trimethylstannylphenyl) tropane (11C-CFT) uptake was obviously affected in the putamen of two presymptomatic mutation carriers. Presymptomatic case 3, whose 11C-CFT uptake in the right putamen was normal at baseline, was still free of parkinsonism during follow-up. In conclusion, 11C-CFT-positron emission tomography could be a potential biomarker for the presymptomatic stage of FTDP-17 to predict the disease onset.

Aerobic exercise produces changes in cerebral oxyhaemoglobin (O 2 Hb) concentration; however, the effects of exercise on O 2 Hb during the post-exercise period remain to be established. The aim of the present study was to evaluate O 2 Hb levels during and after a 20-min bout of moderate-intensity cycling exercise. After a 3-min rest period, 12 healthy volunteers (9 women, 3 men) cycled for 20 min at an intensity corresponding to 50% of their VO 2 max, after which they were monitored during a 15-min post-exercise rest period. O 2 Hb levels in the right (R-PFC) and left prefrontal cortices (L-PFC), right (R-PMA) and left premotor areas (L-PMA), supplementary motor area (SMA), and primary motor cortex (M1) were measured using near-infrared spectroscopy. A one-way repeated-measures analysis of variance (ANOVA) was performed to compare mean pre-exercise O 2 Hb levels with O 2 Hb levels during the last 5 min of exercise and the last 5 min of the post-exercise rest period. O 2 Hb levels increased significantly (p < 0.01) between the pre-exercise rest period and the last 5 min of the exercise session for each region of interest (range: 0.040-0.085 mM·cm). O 2 Hb levels did not return to pre-exercise values during the 15-min post-exercise rest period. O 2 Hb levels during the last 5 min of the post-exercise rest period were significantly higher than pre-exercise values in the L-PFC, L-PMA, SMA, and M1 (p < 0.01). Our results indicate that cortical oxygenation persists for at least 15 min following a 20-min bout of moderate-intensity cycling, and that aerobic exercise may facilitate neuroplasticity.

We aimed to detect alterations in diffusion characteristics of brain white matter in hepatic myelopathy (HM) patients. Liver cirrhosis patients with (n=25) and without (n=18) HM after transjugular intrahepatic portosystemic shunt and 26 healthy controls were enrolled in this study. All participants were scanned with diffusion tensor imaging on a 3T Siemens scanner. Tract-based spatial statistics analysis was used to detect abnormalities of intracranial white matter tracts. Correlations between clinical characteristics and diffusion metrics were also calculated. HM patients showed widespread decreased fractional anisotropy values in association fibers, callosal fibers, thalamic fibers, and limbic system fibers (P<0.01, family-wise error-corrected) compared with healthy controls. In addition, HM patients showed lower fractional anisotropy values in the corpus callosum, corona radiata, external capsule, and superior longitudinal fasciculus compared with cirrhosis patients without myelopathy (P<0.01, family-wise error-corrected). Furthermore, limb muscle strength grading was correlated with the diffusion characteristics of the corpus callosum and superior longitudinal fasciculus in HM patients (P<0.05). HM patients suffer from more distinct changes of white matter fiber tracts than cirrhosis patients without myelopathy. In addition, alterations of the corpus callosum and superior longitudinal fasciculus may be associated with the major motor disturbance in HM. Our finding may shed light on the underlying neuropathological mechanism of HM.

Alterations in grey matter structure and functional connectivity (FC) are pathological features of major depressive disorder (MDD). However, the relationship between brain structural and functional impairments in MDD remains uncertain. Thus, the aim of this study was to investigate the relationship between alterations in grey matter volume (GMV) and resting-state global functional connectivity density (rs-gFCD) in MDD. Forty-five patients with MDD and 48 healthy controls underwent structural and resting-state functional magnetic resonance imaging (fMRI). GMV and rs-gFCD maps of each subject were created, and the intergroup differences in these neuroimaging metrics were evaluated. Compared to healthy controls, patients with MDD displayed reduced GMV in the left insula, putamen, amygdala and hippocampus (mainly in the limbic system). In contrast, decreased rs-gFCD was observed in the left postcentral and precentral gyri, right fusiform gyrus and lingual gyrus (mainly in the sensory system). Furthermore, we found no significant correlations between GMV and rs-gFCD in these brain regions. Finally, overlap ratio analysis demonstrated that the spatial distribution patterns of intergroup differences on the GMV and rs-gFCD maps were distinct. Our findings suggest that the presence of distinct spatial distribution patterns of brain atrophy and global FC impairments might be pathological features of MDD.

Response conflict can be induced by priming multiple responses competing for control of action in trials. The N2 is one functionally-related cognitive control index for response conflict. And yet the underlying whiter matter neural substrates of inter-individual difference in conflict N2 remain unclear. So the aim of present study was to address the white matter microstructure of the N2 responsible for conflict by directly relating the amplitude cost of the event-related potential (ERP) N2 component to diffusion tensor imaging (DTI) indices in healthy subjects. Thirty healthy subjects underwent DTI scanning and electrophysiology recording during a modified Flanker task. N2 was a stimulus-locked negative ERP component. Fractional anisotropy (FA) was calculated based on DTI measures and was assumed to reflect the integrity of myelinate fiber bundles. Therefore, we tested the relationship between N2 amplitude and FA in brain white matter. Results showed that FA, an index for white matter characteristics, in the right superior longitudinal fasciculus (SLF) was significantly positively associated with N2 amplitude cost. The N2 amplitude cost also predicted response time (RT) cost in the Flanker task. Higher FA was associated with larger N2 amplitude cost, suggesting that changes in white matter integrity in the SLF may account for changes in efficient transmission of fronto-parietal modulatory conflict signals., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Imaging the brain with high integrity is of great importance to neuroscience and related applications. X-ray computed tomography (CT) and magnetic resonance imaging (MRI) are two clinically used modalities for deep-penetration brain imaging. However, their spatial resolution is quite limited. Two-photon fluorescence microscopic (2PFM) imaging with its femtosecond (fs) excitation wavelength in the traditional near-infrared (NIR) region (700-1000 nm) is able to realize deep-tissue and high-resolution brain imaging. However, it requires craniotomy and cranial window or skull-thinning techniques due to photon scattering of the excitation light. Herein, based on a type of aggregation-induced emission luminogen (AIEgen) DCDPP-2TPA with a large three-photon absorption (3PA) cross section at 1550 nm and deep-red emission, we realized through-skull three-photon fluorescence microscopic (3PFM) imaging of mouse cerebral vasculature without craniotomy and skull-thinning. Reduced photon scattering of a 1550 nm fs excitation laser allowed it to effectively penetrate the skull and tightly focus onto DCDPP-2TPA nanoparticles (NPs) in the cerebral vasculature, generating bright three-photon fluorescence (3PF) signals. In vivo 3PF images of the cerebral vasculature at various vertical depths were obtained, and a vivid 3D reconstruction of the vascular architecture beneath the skull was built. As deep as 300 μm beneath the skull, small blood vessels of 2.4 μm could still be recognized.

Primary dysmenorrhea (PDM), characterized by cramping pain in the lower abdomen, is a common gynecological disorder in women of child-bearing age. An increasing number of neuroimaging studies have emphasized that PDM is associated with functional and structural abnormalities in the regions related to the default mode network (DMN). Based on resting-state functional magnetic resonance imaging (fMRI), the aim of this study was to use amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) to investigate changes of the intrinsic brain activity in the DMN in PDM. Pearson correlation analysis was conducted to assess relationships between the neuroimaging findings and clinical symptoms. Forty-eight PDM patients and thirty-eight matched healthy controls participated in this study. Compared to healthy controls, PDM patients had increased ALFF in the precuneus, dorsomedial prefrontal cortex (dmPFC) and anterior cingulate cortex (ACC) and decreased ALFF in the thalamus. PDM patients also had decreased connectivity between the precuneus and left dmPFC and right ACC, while increased connectivity between the precuneus and left thalamus. In addition, the ALFF in the left dmPFC in PDM patients positively correlated with disease duration. Our findings provide further evidence of the DMN-related abnormalities in PDM patients which might contribute to a better understanding of the pathophysiology of this disease.

Genetic variations of APOE and KIBRA have been associated with human memory and Alzheimer's disease. APOE and KIBRA can jointly modulate glutamate receptor to influence long-term potentiation; however, their interactions on brain functional connectivity remain unknown. Here, we investigated additive and epistatic interactions between APOE and KIBRA (rs17070145) on brain functional connectivity density (FCD) in 267 healthy young adults. A voxel-based FCD analysis was performed to identify brain regions with significant APOE-KIBRA interaction. Additive effects showed decreased FCD in the left parahippocampal gyrus and the right middle temporal gyrus and increased FCD in the bilateral middle occipital gyri, with the increase of the number of the risk-alleles of APOE and KIBRA. Epistatic effects showed APOE × KIBRA interaction in the FCD of the dorsolateral prefrontal cortex (DLPFC). The FCD of the DLPFC showed APOE risk-allele-dependent reduction (ε2 > ε3 > ε4) in KIBRA TT homozygotes, but APOE risk-allele-dependent increase (ε2 < ε3 < ε4) in KIBRA C-carriers. FCD differences were only significant between the 2 extreme subgroups in both additive and epistatic analyses. These findings suggest that APOE and KIBRA have region-dependent additive and epistatic interactions on brain connectivity in healthy young adults., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The purpose of this study was to explore the neural mechanism in Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) using resting-state functional magnetic resonance imaging. The functional magnetic resonance imaging was performed on 31 male CP/CPPS-patients and 31 age and education matched male healthy controls on a 3-T magnetic resonance imaging unit. A two-sample t-test was adopted to reveal the regional homogeneity between the patients and healthy controls. The mean regional homogeneity values in the alerted brain regions of patients were correlated with the clinical measurements by using Pearson's correlation analyses. The CP/CPPS-patients had significantly decreased regional homogeneity in the bilateral anterior cingulate cortices, insular cortices and right medial prefrontal cortex, while significantly increased regional homogeneity in the brainstem and right thalamus compared with the healthy controls. In the CP/CPPS-patients, the mean regional homogeneity value in the left anterior cingulate cortex, bilateral insular cortices and brainstem were respectively correlated with the National Institutes of Health Chronic Prostatitis Symptom Index total score and pain subscale. These brain regions are important in the pain modulation process. Therefore, an impaired pain modulatory system, either by decreased descending pain inhibition or enhanced pain facilitation, may explain the pain symptoms in CP/CPPS.

Objectives: According to aquaporin-4 antibody (AQP4-Ab), neuromyelitis optica (NMO) can be divided into seropositive and seronegative subgroups. The purpose of this study was to a) compare the distribution of spinal cord and brain magnetic resonance imaging (MRI) lesions between seropositive and seronegative NMO patients; b) explore occult brain damage in seropositive and seronegative NMO patients; and c) explore the contribution of visible lesions to occult grey and white matter damage in seropositive and seronegative NMO patients., Materials and Methods: Twenty-two AQP4-Ab seropositive and 14 seronegative NMO patients and 30 healthy controls were included in the study. Two neuroradiologists independently measured the brain lesion volume (BLV) and the length of spinal cord lesion (LSCL) and recorded the region of brain lesions. The normal-appearing grey matter volume (NAGM-GMV) and white matter fractional anisotropy (NAWM-FA) were calculated for each subject to evaluate occult brain damage., Results: The seropositive patients displayed more extensive damage in the spinal cord than the seronegative patients, and the seronegative group had a higher proportion of patients with brainstem lesions (28.57%) than the seropositive group (4.55%, P=0.064). Both NMO subgroups exhibited reduced NAGM-GMV and NAWM-FA compared with the healthy controls. NAGM-GMV was negatively correlated with LSCL in the seropositive group (r s =-0.444, P=0.044) and with BLV in the seronegative group (r s =-0.768, P=0.002). NAWM-FA was also negatively correlated with BLV in the seropositive group (r s =-0.682, P<0.001)., Conclusion: Our findings suggest that the occult brain damage in these two NMO subgroups may be due to different mechanisms, which need to be further clarified., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Studying the neural correlates of smoking behaviors in young adulthood is of great importance to improve treatment outcomes. In previous addiction studies, the important roles of the salience network (SN) in drug cue processing and cognitive control have been revealed. Unfortunately, few studies focused on the resting-state functional connectivity and structural integrity abnormalities of SN in young adult smokers, and less is known about its association with smoking behaviors and cognitive control deficits. Thirty-one young male adult smokers and 30 age-, education- and gender-matched nonsmokers participated in this study. The structural and functional connectivity differences of SN were investigated between young adult smokers and nonsmokers by using diffusion tensor imaging (DTI) and resting-state functional connectivity (RSFC), which were then correlated with the smoking behavioral assessments (pack-years and Fagerström Test for Nicotine Dependence (FTND)) as well as impaired cognitive control measured by the Stroop task. Within SN, reduced RSFC and increased fractional anisotropy (FA) were found between the anterior cingulate cortex (ACC) and the right insula in young adult smokers relative to nonsmokers. The RSFC between the ACC and right insula was negatively correlated with the number of errors during the incongruent condition of the Stroop task in young adult smokers. Additionally, the right insula-ACC RSFC was negatively correlated with pack-years in young adult smokers. Our results revealed abnormal RSFC and structural integrity within the SN in young adult smokers, which shed new insights into the neural mechanism of nicotine dependence.

Cognitive processes involve input from multiple sensory modalities and obvious differences in the level of cognitive function can be observed between individuals. Evidence to date understanding the biological basis of tactile cognitive variability, however, is limited compared with other forms of sensory cognition. Data from auditory and visual cognition research suggest that variations in both genetics and intrinsic brain function might contribute to individual differences in tactile cognitive performance. In the present study, by using the tactual performance test (TPT), a widely used neuropsychological assessment tool, we investigated the effects of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and resting-state brain functional connectivity (FC) on interindividual variability in TPT performance in healthy, young Chinese adults. Our results showed that the BDNF genotypes and resting-state FC had significant effects on the variability in TPT performance, together accounting for 32.5% and 19.1% of the variance on TPT total score and Memory subitem score respectively. Having fewer Met alleles, stronger anticorrelations between left posterior superior temporal gyrus and somatosensory areas (right postcentral gyrus and right parietal operculum cortex), and greater positive correlation between left parietal operculum cortex and left central opercular cortex, all correspond with better performance of TPT task. And FC between left parietal operculum cortex and left central opercular cortex might be a mediator of the relationship between BDNF genotypes and Memory subitem score. These data demonstrate a novel contribution of intrinsic brain function to tactile cognitive capacity, and further confirm the genetic basis of tactile cognition. Our findings might also explain the interindividual differences in cognitive ability observed in those who are blind and/or deaf from a new perspective., (Copyright © 2017. Published by Elsevier Ltd.)

Purpose To investigate auditory verbal hallucination (AVH)-specific patterns of brain activity within the resting-state networks (RSNs) that have been proposed to underpin the neural mechanisms of schizophrenia (SZ). Materials and Methods This cross-sectional study was approved by the local ethics committee, and written informed consent was obtained from all participants prospectively recruited. Independent component analysis was used to investigate RSNs in 17 patients with first-episode untreated SZ with AVHs, 15 patients with SZ without AVHs, and 19 healthy control subjects who underwent resting-state functional magnetic resonance imaging. Dual regression was implemented to perform between-group analysis. Regional brain function was then explored within RSNs by using the amplitude of low-frequency fluctuation. Two-sample t tests were used to compare regional brain function between the two patient groups, and Pearson correlation analysis was used to characterize the relationship between imaging findings and severity of AVHs. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of these brain function measures. Results Independent component analysis demonstrated symptom-specific abnormal disrupted coactivation within the auditory, default mode, executive, motor, and frontoparietal networks and was pronounced in the auditory cortex, supramarginal gyrus, insula, putamen, dorsolateral prefrontal cortex, angular gyrus, precuneus, and thalamus (P < .05 with false discovery rate correction). Amplitude of low-frequency fluctuation analysis demonstrated similar patterns within these RSNs (P < .05 with false discovery rate correction). Furthermore, a positive correlation between the degree of coactivation within the motor network and the severity of AVHs was observed in patients with SZ with AVHs (r = 0.67, P = .003). The area under the receiver operating characteristic curve was 0.76-0.90 for all RSNs. Conclusion These findings indicate that dysfunctional brain regions are involved in auditory processing, language production and monitoring, and sensory information filtering in patients with SZ with AVHs, which may be helpful in furthering the understanding of pathophysiological correlates of AVHs in SZ. Online supplemental material is available for this article.

Acyltransferases catalyze essential reactions in the buildup and remodeling of glycerophospholipids and contribute to the maintenance and diversity of cellular membranes. Transmembrane protein 68 (TMEM68) is an evolutionarily conserved protein of unknown function, that forms a distinct subgroup within the glycerophospholipid acyltransferase family. In the current study we expressed murine TMEM68 for the first time in mammalian cells to characterize its subcellular localization, topology, and possible biological function(s). We show that TMEM68 is an integral membrane protein and orients both, the N- and C-terminus towards the cytosol. Live cell imaging demonstrated that TMEM68 is localized mainly at the endoplasmic reticulum (ER), but not at cellular lipid droplets (LDs). The positioning of TMEM68 at the ER was dependent on its first transmembrane domain (TMD), which by itself was sufficient to target cytosolic green fluorescence protein (GFP) to the ER. In contrast, a second TMD was dispensable for ER localization of TMEM68. Finally, we found that among multiple murine tissues the expression level of TMEM68 transcripts was highest in brain. We conclude that TMEM68 is an integral ER membrane protein and a putative acyltransferase involved in brain glycerolipid metabolism.

The goal of the study was to investigate cerebral blood flow (CBF) and its connectivity (an across-subject covariance measure) patterns of schizophrenia (SZ) patients with auditory verbal hallucinations (AVHs). A total of demographically matched 25 SZ patients with AVHs, 25 without AVHs, and 25 healthy controls (HCs) underwent resting state perfusion imaging using a pulsed arterial spin labeling sequence. CBF and its connectivity were analyzed and then CBF topological properties were calculated. AVHs patients exhibited decreased CBF in the bilateral superior and middle frontal gyri and postcentral gyri, and right supplementary motor area compared with SZ patients without AVHs. SZ patients without AVHs showed reduced CBF in the left middle frontal gyrus relative to HCs. Moreover, AVHs groups showed distinct connectivity pattern, an intermediate level between HCs and patients without AVHs in the global efficiency. Our study demonstrates aberrant CBF in the brain regions associated with inner speech monitoring and language processing in SZ patients with AVHs. The complex network measures showed by CBF-derived functional connectivity indicate dysconnectivity between different functional units within the network of AVHs in SZ. Our findings might shed light on the neural underpinnings behind AVHs in this devastating disease at the level of CBF and its connectivity., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Although previous studies found that aberrations in gray matter volume (GMV) and global functional connectivity density (gFCD) are important characteristics of schizophrenia, to the best of our knowledge no study to date has investigated the associations between the spatial distribution patterns of GMV and gFCD alterations. We investigated pattern changes in gFCD and GMV among patients with schizophrenia and their associated spatial distributions., Methods: Ninety-five patients with schizophrenia and 93 matched healthy controls underwent structural and resting-state functional MRI scanning to assess gFCD and GMV., Results: We found that gFCD increased in the subcortical regions (caudate, pallidum, putamen, and thalami) and limbic system (left hippocampus and parahippocampus), and decreased in the posterior parieto-occipito-temporal cortices (postcentral gyri, occipital cortex, temporo-occipital conjunction, and inferior parietal lobule), in patients with schizophrenia. By contrast, we found decreased GMV in brain regions including the frontal, parietal, temporal, occipital, cingulate cortices, and the insular, striatum, thalamus in these patients. Increased gFCD primarily occurred in subcortical regions including the basal ganglia and some regions of the limbic system. Decreased gFCD appeared primarily in the cortical regions. There were no statistically significant correlations between changes in gFCD and GMV, and their spatial distribution patterns, in different regions., Conclusions: Our findings indicate that gFCD and GMV are both perturbed in multiple brain regions in schizophrenia. gFCD and GMV consistently decreased in the cortical regions, with the exception of the Supplementary Motor Area (SMA). However, in the sub-cortical regions, the alterations of gFCD and GMV showed the opposite pattern, with increased gFCD and decreased GMV simultaneously observed in these regions. Overall, our findings suggest that structural and functional alterations appear to contribute independently to the neurobiology of schizophrenia.

It remains unknown whether spinal cord injury (SCI) could indirectly impair or reshape the white matter (WM) of human brain and whether these changes are correlated with injury severity, duration, or clinical performance. We choose tract-based spatial statistics (TBSS) to investigate the possible changes in whole-brain white matter integrity and their associations with clinical variables in fifteen patients with SCI. Compared with the healthy controls, the patients exhibited significant decreases in WM fractional anisotropy (FA) in the left angular gyrus (AG), right cerebellum (CB), left precentral gyrus (PreCG), left lateral occipital region (LOC), left superior longitudinal fasciculus (SLF), left supramarginal gyrus (SMG), and left postcentral gyrus (PostCG) ( p < 0.01, TFCE corrected). No significant differences were found in all diffusion indices between the complete and incomplete SCI. However, significantly negative correlation was shown between the increased radial diffusivity (RD) of left AG and total motor scores (uncorrected p < 0.05). Our findings provide evidence that SCI can cause not only direct degeneration but also transneuronal degeneration of brain WM, and these changes may be irrespective of the injury severity. The affection of left AG on rehabilitation therapies need to be further researched in the future., Competing Interests: The authors declare no competing financial interests.