Functional brain network controllability dysfunction in Alzheimer's disease and its relationship with cognition and gene expression profiling.

Objective. In recent studies, network control theory has been applied to clarify transitions between brain states, emphasizing the significance of assessing the controllability of brain networks in facilitating transitions from one state to another. Despite these advancements, the potential alterations in functional network controllability associated with Alzheimer's disease (AD), along with the underlying genetic mechanisms responsible for these alterations, remain unclear.Approach. We conducted a comparative analysis of functional network controllability measures between patients with AD (n= 64) and matched normal controls (NCs,n= 64). We investigated the association between altered controllability measures and cognitive function in AD. Additionally, we conducted correlation analyses in conjunction with the Allen Human Brain Atlas to identify genes whose expression was correlated with changes in functional network controllability in AD, followed by a set of analyses on the functional features of the identified genes.Main results. In comparison to NCs, patients with AD exhibited a reduction in average controllability, predominantly within the default mode network (DMN) (63% of parcellations), and an increase in average controllability within the limbic (LIM) network (33% of parcellations). Conversely, AD patients displayed a decrease in modal controllability within the LIM network (27% of parcellations) and an increase in modal controllability within the DMN (80% of parcellations). In AD patients, a significant positive correlation was found between the average controllability of the salience network and the mini-mental state examination scores. The changes in controllability measures exhibited spatial correlation with transcriptome profiles. The significant genes identified exhibited enrichment in neurobiologically relevant pathways and demonstrated preferential expression in various tissues, cell types, and developmental periods.Significance. Our findings have the potential to offer new insights into the genetic mechanisms underlying alterations in the controllability of functional networks in AD. Additionally, these results offered perspectives for a deeper understanding of the pathogenesis and the development of therapeutic strategies for AD.

STW-MD: a novel spatio-temporal weighting and multi-step decision tree method for considering spatial heterogeneity in brain gene expression data.

Gene expression during brain development or abnormal development is a biological process that is highly dynamic in spatio and temporal. Previous studies have mainly focused on individual brain regions or a certain developmental stage. Our motivation is to address this gap by incorporating spatio-temporal information to gain a more complete understanding of brain development or abnormal brain development, such as Alzheimer's disease (AD), and to identify potential determinants of response. In this study, we propose a novel two-step framework based on spatial-temporal information weighting and multi-step decision trees. This framework can effectively exploit the spatial similarity and temporal dependence between different stages and different brain regions, and facilitate differential gene analysis in brain regions with high heterogeneity. We focus on two datasets: the AD dataset, which includes gene expression data from early, middle and late stages, and the brain development dataset, spanning fetal development to adulthood. Our findings highlight the advantages of the proposed framework in discovering gene classes and elucidating their impact on brain development and AD progression across diverse brain regions and stages. These findings align with existing studies and provide insights into the processes of normal and abnormal brain development.

Atypical dynamic network reconfiguration and genetic mechanisms in patients with major depressive disorder.

BACKGROUND: Brain dynamics underlie complex forms of flexible cognition or the ability to shift between different mental modes. However, the precise dynamic reconfiguration based on multi-layer network analysis and the genetic mechanisms of major depressive disorder (MDD) remains unclear. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data were acquired from the REST-meta-MDD consortium, including 555 patients with MDD and 536 healthy controls (HC). A time-varying multi-layer network was constructed, and dynamic modular characteristics were used to investigate the network reconfiguration. Additionally, partial least squares regression analysis was performed using transcriptional data provided by the Allen Human Brain Atlas (AHBA) to identify genes associated with atypical dynamic network reconfiguration in MDD. RESULTS: In comparison to HC, patients with MDD exhibited lower global and local recruitment coefficients. The local reduction was particularly evident in the salience and subcortical networks. Spatial transcriptome correlation analysis revealed an association between gene expression profiles and atypical dynamic network reconfiguration observed in MDD. Further functional enrichment analyses indicated that positively weighted reconfiguration-related genes were primarily associated with metabolic and biosynthetic pathways. Additionally, negatively enriched genes were predominantly related to programmed cell death-related terms. CONCLUSIONS: Our findings offer robust evidence of the atypical dynamic reconfiguration in patients with MDD from a novel perspective. These results offer valuable insights for further exploration into the mechanisms underlying MDD.

Functional connectome hierarchy dysfunction in Alzheimer's disease and its relationship with cognition and gene expression profiling.

Numerous researches have shown that the human brain organizes as a continuum axis crossing from sensory motor to transmodal cortex. Functional network alterations were commonly found in Alzheimer's disease (AD). Whether the hierarchy of AD brain networks has changed and how these changes related to gene expression profiling and cognition is unclear. Using resting-state functional magnetic resonance imaging data from 233 subjects (185 AD patients and 48 healthy controls), we studied the changes in the functional network gradients in AD. Moreover, we investigated the relationships between gradient alterations and cognition, and gene expression profiling, respectively. We found that the second gradient organizes as a continuum axis crossing from the sensory motor to the transmodal cortex. Compared to the healthy controls, the secondary gradient scores of the visual and somatomotor network (SOM) increased significantly in AD, and the secondary gradient scores of default mode and frontoparietal network decreased significantly in AD. The secondary gradient scores of SOM and salience network (SAL) significantly positively correlated with memory function in AD. The secondary gradient in SAL also significantly positively correlated with language function. The AD-related second gradient alterations were spatially associated with the gene expression and the relevant genes enriched in neurobiology-related pathways, specially expressed in various tissues, cell types, and developmental stages. These findings suggested the changes in the functional network gradients in AD and deepened our understanding of the correlation between macroscopic gradient structure and microscopic gene expression profiling in AD.

Resolving heterogeneity in Alzheimer's disease based on individualized structural covariance network.

The heterogeneity of Alzheimer's disease (AD) poses a challenge to precision medicine. We aimed to identify distinct subtypes of AD based on the individualized structural covariance network (IDSCN) analysis and to research the underlying neurobiology mechanisms. In this study, 187 patients with AD (age = 73.57 ± 6.00, 50% female) and 143 matched normal controls (age = 74.30 ± 7.80, 44% female) were recruited from the Alzheimer's Disease Neuroimaging Initiative (ADNI) project database, and T1 images were acquired. We utilized the IDSCN analysis to generate individual-level altered structural covariance network and performed k-means clustering to subtype AD based on structural covariance network. Cognition, disease progression, morphological features, and gene expression profiles were further compared between subtypes, to characterize the heterogeneity in AD. Two distinct AD subtypes were identified in a reproducible manner, and we named the two subtypes as slow progression type (subtype 1, n = 104, age = 76.15 ± 6.44, 42% female) and rapid progression type (subtype 2, n = 83, age = 71.98 ± 8.72, 47% female), separately. Subtype 1 had better baseline visuospatial function than subtype 2 (p < 0.05), whereas subtype 2 had better baseline memory function than subtype 1 (p < 0.05). Subtype 2 showed worse progression in memory (p = 0.003), language (p = 0.003), visuospatial function (p = 0.020), and mental state (p = 0.038) than subtype 1. Subtype 1 often shared increased structural covariance network, mainly in the frontal lobe and temporal lobe regions, whereas subtype 2 often shared increased structural covariance network, mainly in occipital lobe regions and temporal lobe regions. Functional annotation further revealed that all differential structural covariance network between the two AD subtypes were mainly implicated in memory, learning, emotion, and cognition. Additionally, differences in gray matter volume (GMV) between AD subtypes were identified, and genes associated with GMV differences were found to be enriched in the terms potassium ion transport, synapse organization, and histone modification and the pathways viral infection, neurodegeneration-multiple diseases, and long-term depression. The two distinct AD subtypes were identified and characterized with neuroanatomy, cognitive trajectories, and gene expression profiles. These comprehensive results have implications for neurobiology mechanisms and precision medicine.

Hypoactive Visual Cortex, Prefrontal Cortex and Insula during Self-Face Recognition in Adults with First-Episode Major Depressive Disorder.

Self-face recognition is a vital aspect of self-referential processing, which is closely related to affective states. However, neuroimaging research on self-face recognition in adults with major depressive disorder is lacking. This study aims to investigate the alteration of brain activation during self-face recognition in adults with first-episode major depressive disorder (FEMDD) via functional magnetic resonance imaging (fMRI); FEMDD (n = 59) and healthy controls (HC, n = 36) who performed a self-face-recognition task during the fMRI scan. The differences in brain activation signal values between the two groups were analyzed, and Pearson correlation analysis was used to evaluate the relationship between the brain activation of significant group differences and the severity of depressive symptoms and negative self-evaluation; FEMDD showed significantly decreased brain activation in the bilateral occipital cortex, bilateral fusiform gyrus, right inferior frontal gyrus, and right insula during the task compared with HC. No significant correlation was detected between brain activation with significant group differences and the severity of depression and negative self-evaluation in FEMDD or HC. The results suggest the involvement of the malfunctioning visual cortex, prefrontal cortex, and insula in the pathophysiology of self-face recognition in FEMDD, which may provide a novel therapeutic target for adults with FEMDD.

Associations between polygenic risk scores and accelerated brain ageing in smokers.

BACKGROUND: Smoking contributes to a variety of neurodegenerative diseases and neurobiological abnormalities, suggesting that smoking is associated with accelerated brain aging. However, the neurobiological mechanisms affected by smoking, and whether they are genetically influenced, remain to be investigated. METHODS: Using structural magnetic resonance imaging data from the UK Biobank (n = 33 293), a brain age predictor was trained on non-smoking healthy groups and tested on smokers to obtain the BrainAge Gap (BAG). The cumulative effect of multiple common genetic variants associated with smoking was then calculated to acquire a polygenic risk score (PRS). The relationship between PRS, BAG, total gray matter volume (tGMV), and smoking parameters was explored and further genes included in the PRS were annotated to identify potential molecular mechanisms affected by smoking. RESULTS: The BrainAge in smokers was predicted with very high accuracy (r = 0.725, MAE = 4.16). Smokers had a greater BAG (Cohen's d = 0.074, p < 0.0001) and higher PRS (Cohen's d = 0.63, p < 0.0001) than non-smokers. A higher PRS was associated with increased amount of smoking, mediated by BAG and tGMV. Several neurotransmitters and ion channel pathways were enriched in the group of smoking-related genes involved in addiction, brain synaptic plasticity, and some neurological disorders. CONCLUSION: By using a simplified single indicator of the entire brain (BAG) in combination with the PRS, this study highlights the greater BAG in smokers and its linkage with genes and smoking behavior, providing insight into the neurobiological underpinnings and potential features of smoking-related aging.

Atypical hemispheric lateralization of brain function and structure in autism: a comprehensive meta-analysis study.

BACKGROUND: Characteristic changes in the asymmetric nature of the human brain are associated with neurodevelopmental differences related to autism. In people with autism, these differences are thought to affect brain structure and function, although the structural and functional bases of these defects are yet to be fully characterized. METHODS: We applied a comprehensive meta-analysis to resting-state functional and structural magnetic resonance imaging datasets from 370 people with autism and 498 non-autistic controls using seven datasets of the Autism Brain Imaging Data Exchange Project. We studied the meta-effect sizes based on standardized mean differences and standard deviations (s.d.) for lateralization of gray matter volume (GMV), fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo). We examined the functional correlates of atypical laterality through an indirect annotation approach followed by a direct correlation analysis with symptom scores. RESULTS: In people with autism, 85, 51, and 51% of brain regions showed a significant diagnostic effect for lateralization in GMV, fALFF, and ReHo, respectively. Among these regions, 35.7% showed overlapping differences in lateralization in GMV, fALFF, and ReHo, particularly in regions with functional annotations for language, motor, and perceptual functions. These differences were associated with clinical measures of reciprocal social interaction, communication, and repetitive behaviors. A meta-analysis based on s.d. showed that people with autism had lower variability in structural lateralization but higher variability in functional lateralization. CONCLUSION: These findings highlight that atypical hemispheric lateralization is a consistent feature in autism across different sites and may be used as a neurobiological marker for autism.

Aberrant global and local dynamic properties in schizophrenia with instantaneous phase method based on Hilbert transform.

BACKGROUND: Emerging functional imaging studies suggest that schizophrenia is associated with aberrant spatiotemporal interaction which may result in aberrant global and local dynamic properties. METHODS: We investigated the dynamic functional connectivity (FC) by using instantaneous phase method based on Hilbert transform to detect abnormal spatiotemporal interaction in schizophrenia. Based on resting-state functional magnetic resonance imaging, two independent datasets were included, with 114 subjects from COBRE [51 schizophrenia patients (SZ) and 63 healthy controls (HCs)] and 96 from OpenfMRI (36 SZ and 60 HCs). Phase differences and instantaneous coupling matrices were firstly calculated at all time points by extracting instantaneous parameters. Global [global synchrony and intertemporal closeness (ITC)] and local dynamic features [strength of FC (sFC) and variability of FC (vFC)] were compared between two groups. Support vector machine (SVM) was used to estimate the ability to discriminate two groups by using all aberrant features. RESULTS: We found SZ had lower global synchrony and ITC than HCs on both datasets. Furthermore, SZ had a significant decrease in sFC but an increase in vFC, which were mainly located at prefrontal cortex, anterior cingulate cortex, temporal cortex and visual cortex or temporal cortex and hippocampus, forming significant dynamic subnetworks. SVM analysis revealed a high degree of balanced accuracy (85.75%) on the basis of all aberrant dynamic features. CONCLUSIONS: SZ has worse overall spatiotemporal stability and extensive FC subnetwork lesions compared to HCs, which to some extent elucidates the pathophysiological mechanism of schizophrenia, providing insight into time-variation properties of patients with other mental illnesses.

Smoking is associated with lower brain volume and cognitive differences: A large population analysis based on the UK Biobank.

The evidence about the association of smoking with both brain structure and cognitive functions remains inconsistent. Using structural magnetic resonance imaging from the UK Biobank (n = 33,293), we examined the relationships between smoking status, dosage, and abstinence with total and 166 regional brain gray matter volumes (GMV). The relationships between the smoking parameters with cognitive function, and whether this relationship was mediated by brain structure, were then investigated. Smoking was associated with lower total and regional GMV, with the extent depending on the frequency of smoking and on whether smoking had ceased: active regular smokers had the lowest GMV (Cohen's d = -0.362), and former light smokers had a slightly smaller GMV (Cohen's d = -0.060). The smaller GMV in smokers was most evident in the thalamus. Higher lifetime exposure (i.e., pack-years) was associated with lower total GMV (ß = -311.84, p = 8.35 × 10-36). In those who ceased smoking, the duration of abstinence was associated with a larger total GMV (ß = 139.57, p = 2.36 × 10-08). It was further found that reduced cognitive function was associated with smoker parameters and that the associations were partially mediated by brain structure. This is the largest scale investigation we know of smoking and brain structure, and these results are likely to be robust. The findings are of associations between brain structure and smoking, and in the future, it will be important to assess whether brain structure influences smoking status, or whether smoking influences brain structure, or both.

Abnormal hemispheric asymmetry of both brain function and structure in attention deficit/hyperactivity disorder: a meta-analysis of individual participant data.

Aberration in the asymmetric nature of the human brain is associated with several mental disorders, including attention deficit/hyperactivity disorder (ADHD). In ADHD, these aberrations are thought to reflect key hemispheric differences in the functioning of attention, although the structural and functional bases of these defects are yet to be fully characterized. In this study, we applied a comprehensive meta-analysis to multimodal imaging datasets from 627 subjects (303 typically developing control [TDCs] and 324 patients with ADHD) with both resting-state functional and structural magnetic resonance imaging (MRI), from seven independent publicly available datasets of the ADHD-200 sample. We performed lateralization analysis and calculated the combined effects of ADHD on each of three cortical regional measures (grey matter volume - GMV, fractional amplitude of low frequency fluctuations at rest -fALFF, and regional homogeneity -ReHo). We found that compared with TDC, 68%,73% and 66% of regions showed statistically significant ADHD disorder effects on the asymmetry of GMV, fALFF, and ReHo, respectively, (false discovery rate corrected, q = 0.05). Forty-one percent (41%) of regions had both structural and functional abnormalities in asymmetry, located in the prefrontal, frontal, and subcortical cortices, and the cerebellum. Furthermore, brain asymmetry indices in these regions were higher in children with more severe ADHD symptoms, indicating a crucial pathoplastic role for asymmetry. Our findings highlight the functional asymmetry in ADHD which has (1) a strong structural basis, and thus is likely to be developmental in nature; and (2) is strongly linked to symptom burden and IQ and may carry a possible prognostic value for grading the severity of ADHD.

Associations between smoking and accelerated brain ageing.

Smoking accelerates the ageing of multiple organs. However, few studies have quantified the association between smoking, especially smoking cessation, and brain ageing. Using structural magnetic resonance imaging data from the UK Biobank (n = 33,293), a brain age predictor was trained using a machine learning technique in the non-smoker group (n = 14,667) and then tested in the smoker group (n = 18,626) to determine the relationships between BrainAge Gap (predicted age - true age) and smoking parameters. Further, we examined whether smoking was associated with poorer cognition and whether this relationship was mediated by brain age. The predictor achieved an appreciable performance in training data (r = 0.712, mean-absolute-error [MAE] = 4.220) and test data (r = 0.725, MAE = 4.160). On average, smokers showed a larger BrainAge Gap (+0.304 years, Cohens'd = 0.083) than controls, more explicitly, the extents vary depending on their smoking characteristic that active regular smokers had the largest BrainAge Gap (+1.190 years, Cohens'd = 0.321), and light smokers had a moderate BrainAge Gap (+0.478, Cohens'd = 0.129). The increased smoking amount was associated with a larger BrainAge Gap (ß = 0.035, p = 1.72 × 10-20) while a longer duration of quitting smoking in ex-smokers was associated with a smaller BrainAge Gap (ß = -0.015, p = 2.14 × 10-05). Furthermore, smoking was associated with poorer cognition, and this relationship was partially mediated by BrainAge Gap. The study provides insight into the association between smoking, brain ageing, and cognition, which provide more publicly acceptable propaganda against smoking.

Risk factors for mortality in critically ill patients with COVID-19 in Huanggang, China: A single-center multivariate pattern analysis.

To date, the coronavirus disease 2019 (COVID-19) has a worldwide distribution. Risk factors for mortality in critically ill patients, especially detailed self-evaluation indicators and laboratory-examination indicators, have not been well described. In this paper, a total of 192 critically ill patients (142 were discharged and 50 died in the hospital) with COVID-19 were included. Self-evaluation indicators including demographics, baseline characteristics, and symptoms and detailed lab-examination indicators were extracted. Data were first compared between survivors and nonsurvivors. Multivariate pattern analysis (MVPA) was performed to identify possible risk factors for mortality of COVID-19 patients. MVPA achieved a relatively high classification accuracy of 93% when using both self-evaluation indicators and laboratory-examination indicators. Several self-evaluation factors related to COVID-19 were highly associated with mortality, including age, duration (time from illness onset to admission), and the Barthel index (BI) score. When the duration, age increased by 1 day, 1 year, BI decreased by 1 point, the mortality increased by 3.6%, 2.4%, and 0.9% respectively. Laboratory-examination indicators including C-reactive protein, white blood cell count, platelet count, fibrin degradation products, oxygenation index, lymphocyte count, and d-dimer were also risk factors. Among them, duration was the strongest predictor of all-cause mortality. Several self-evaluation indicators that can simply be obtained by questionnaires and without clinical examination were the risk factors of all-cause mortality in critically ill COVID-19 patients. The prediction model can be used by individuals to improve health awareness, and by clinicians to identify high-risk individuals.

Identifying and quantifying robust risk factors for mortality in critically ill patients with COVID-19 using quantile regression.

OBJECTIVE: Many laboratory indicators form a skewed distribution with outliers in critically ill patients with COVID-19, for which robust methods are needed to precisely determine and quantify fatality risk factors. METHOD: A total of 192 critically ill patients (142 were discharged and 50 died in the hospital) with COVID-19 were included in the sample. Quantile regression was used to determine discrepant laboratory indexes between survivors and non-survivors and quantile shift (QS) was used to quantify the difference. Logistic regression was then used to calculate the odds ratio (OR) and the predictive power of death for each risk indicator. RESULTS: After adjusting for multiple comparisons and controlling numerous confounders, quantile regression revealed that the laboratory indexes of non-survivors were significantly higher in C-reactive protein (CRP; QS = 0.835, p < .001), white blood cell counts (WBC; QS = 0.743, p < .001), glutamic oxaloacetic transaminase (AST; QS = 0.735, p < .001), blood glucose (BG; QS = 0.608, p = .059), fibrin degradation product (FDP; QS = 0.730, p = .080), and partial pressure of carbon dioxide (PCO2), and lower in oxygen saturation (SO2; QS = 0.312, p < .001), calcium (Ca2+; QS = 0.306, p = .073), and pH. Most of these indexes were associated with an increased fatality risk, and predictive for the probability of death. Especially, CRP is the most prominent index with and odds ratio of 205.97 and predictive accuracy of 93.2%. CONCLUSION: Laboratory indexes provided reliable information on mortality in critically ill patients with COVID-19, which might help improve clinical prediction and treatment at an early stage.

A multivariate pattern analysis of resting-state functional MRI data in Naïve and chronic betel quid chewers.

Betel quid (BQ) is the fourth most commonly consumed psychoactive substance in the world. However, comprehensive functional magnetic resonance imaging (fMRI) studies exploring the neurophysiological mechanism of BQ addiction are lacking. Betel-quid-dependent (BQD) individuals (n = 24) and age-matched healthy controls (HC) (n = 26) underwent fMRI before and after chewing BQ. Multivariate pattern analysis (MVPA) was used to explore the acute effects of BQ-chewing in both groups. A cross-sectional comparison was conducted to explore the chronic effects of BQ-chewing. Regression analysis was used to investigate the relationship between altered circuits of BQD individuals and the severity of BQ addiction. MVPA achieved classification accuracies of up to 90% in both groups for acute BQ-chewing. Suppression of the default-mode network was the most prominent feature. BQD showed more extensive and intensive within- and between-network dysconnectivity of the default, frontal-parietal, and occipital regions associated with high-order brain functions such as self-awareness, inhibitory control, and decision-making. In contrast, the chronic effects of BQ on the brain function were mild, but impaired circuits were predominately located in the default and frontal-parietal networks which might be associated with compulsive drug use. Simultaneously quantifying the effects of both chronic and acute BQ exposure provides a possible neuroimaging-based BQ addiction foci. Results from this study may help us understand the neural mechanisms involved in BQ-chewing and BQ dependence.

Bipolar Mood State Reflected in Functional Connectivity of the Hate Circuit: A Resting-State Functional Magnetic Resonance Imaging Study.

BACKGROUND: Previous studies suggested bipolar disorder caused an aberrant alteration in the insular, putamen, and left superior frontal gyrus, which are the main components of the hate circuit. However, the relationship between the hate circuit and the pathophysiologic substrate underlying different phases of bipolar disorder remain unclear. In this study, we aimed to identify group differences of resting-state functional connectivity within the hate circuit in healthy controls (HCs) and bipolar patients in different mood states. METHODS: Resting-state functional magnetic resonance imaging of the brain were acquired from 54 HCs and 81 patients with bipolar disorder including 20 with bipolar mania (BM), 35 with bipolar depression (BD), and 26 with bipolar euthymia (BE). We selected bilateral insula (L.INS and R.INS), bilateral putamen (L.PUT and R.PUT), and left superior frontal gyrus (L.SFGd) as seed regions, and conducted the seed-based functional connectivity analysis to identify group differences of connectivity strength within the hate circuit. Spearman correlations were performed to evaluate the relationship between the hate circuit and manic/depressive symptoms. RESULTS: Significant group differences of connectivity strength within the hate circuit were found in links of the R.INS-L.SFGd, R.PUT-L.SFGd, and L.INS- R.PUT after false discovery rate was corrected. The BM group showed an opposite hate circuit pattern to BD, BE, and HCs. The BD group showed decreased hate circuit connectivity in the L.INS-R.PUT compared with the BE group. No significant difference was detected among BD, BE, and HCs. Furthermore, functional connectivity of the R.INS-L.SFGd and R.PUT-L.SFGd were positively correlated with manic symptoms, while the L.INS- R.PUT was negatively correlated with depressive symptoms. CONCLUSIONS: Our preliminary findings suggest that altered functional connectivity of the hate circuit in different mood phases may be related to state markers and underpin the neuropathological basis of bipolar disorder.

Acute and Chronic Effects of Betel Quid Chewing on Brain Functional Connectivity.

BACKGROUND: The active alkaloid in Betel quid is arecoline. Consumption of betel quid is associated with both acute effects and longer-term addictive effects. Despite growing evidence that betel quid use is linked with altered brain function and connectivity, the neurobiology of this psychoactive substance in initial acute chewing, and long-term dependence, is not clear. METHODS: In this observational study, functional magnetic resonance imaging in a resting-state was performed in 24 male betel quid-dependent chewers and 28 male controls prior to and promptly after betel quid chewing. Network-based statistics were employed to determine significant differences in functional connectivity between brain networks for both acute effects and in long-term betel users versus controls. A support vector machine was employed for pattern classification analysis. RESULTS: Before chewing betel quid, higher functional connectivity in betel quid-dependent chewers than in controls was found between the temporal, parietal and frontal brain regions (right medial orbitofrontal cortex, right lateral orbital frontal cortex, right angular gyrus, bilateral inferior temporal gyrus, superior parietal gyrus, and right medial superior frontal gyrus). In controls, the effect of betel quid chewing was significantly increased functional connectivity between the subcortical regions (caudate, putamen, pallidum, and thalamus), and the visual cortex (superior occipital gyrus and right middle occipital gyrus). CONCLUSION: These findings show that individuals who chronically use betel quid have higher functional connectivity than controls of the orbitofrontal cortex, and inferior temporal and angular gyri. Acute effects of betel quid are to increase the functional connectivity of some visual cortical areas (which may relate to the acute symptoms) and the basal ganglia and thalamus.

Predicting human inhibitory control from brain structural MRI.

The anatomical structure of the human brain varies widely, as does individual cognitive behavior. It is important and interesting to study the relationship between brain structure and cognitive behavior. There has however been little previous work on the relationship between inhibitory control and brain structure. The goal of this study was to elucidate possible cortical markers related to inhibitory control using structural magnetic resonance imaging (sMRI) data. In this study, we analyzed sMRI data and inhibitory control behavior measurement values from 361 healthy adults from the Human Connectome Project (HCP). The data of all participants were divided into two datasets. In the first dataset, we first constructed individual brain morphometric similarity networks by calculating the inter-regional statistical similarity relationship of nine cortical characteristic measures (such as volume) for each brain area obtained from sMRI data. Areas that covary in their morphology are termed 'connected'. After that, we used a brain connectome-based predictive model (CPM) to search for 'connected' brain areas that were significantly related to inhibitory control. This is a purely data-driven method with built-in cross-validation. Two different 'connected' patterns were observed for high and low inhibitory control networks. The high inhibitory control network comprised 25 'connections' (edges between nodes), mostly involving nodes in the prefrontal and especially orbitofrontal cortex and inferior frontal gyrus. In the low inhibitory control network, nodes were scattered between parietal, occipital and limbic areas. Furthermore, these 'connections' were verified as reliable and generalizable in a cross-validation dataset. Two regions of interest, the right ventromedial prefrontal cortex including a part of medial area 10 (R.OFCmed) and left middle temporal gyrus (L.MTG) were crucial nodes in the two networks, respectively, which suggests that these two regions may be fundamentally involved in inhibitory control. Our findings potentially help to understand the relationship between areas with a correlated cortical structure and inhibitory control, and further help to reveal the brain systems related to inhibition and its disorders.

Functional, Anatomical, and Morphological Networks Highlight the Role of Basal Ganglia-Thalamus-Cortex Circuits in Schizophrenia.

Evidence from electrophysiological, functional, and structural research suggests that abnormal brain connectivity plays an important role in the pathophysiology of schizophrenia. However, most previous studies have focused on single modalities only, each of which is associated with its own limitations. Multimodal combinations can more effectively utilize various information, but previous multimodal research mostly focuses on extracting local features, rather than carrying out research based on network perspective. This study included 135 patients with schizophrenia and 148 sex- and age-matched healthy controls. Functional magnetic resonance imaging, diffusion tensor imaging, and structural magnetic resonance imaging data were used to construct the functional, anatomical, and morphological networks of each participant, respectively. These networks were used in combination with machine learning to identify more consistent biomarkers of brain connectivity and explore the relationships between different modalities. We found that although each modality had divergent connectivity biomarkers, the convergent pattern was that all were mostly located within the basal ganglia-thalamus-cortex circuit. Furthermore, using the biomarkers of these 3 modalities as a feature yielded the highest classification accuracy (91.75%, relative to a single modality), suggesting that the combination of multiple modalities could be effectively utilized to obtain complementary information regarding different mode networks; furthermore, this information could help distinguish patients. These findings provide direct evidence for the disconnection hypothesis of schizophrenia, suggesting that abnormalities in the basal ganglia-thalamus-cortex circuit can be used as a biomarker of schizophrenia.

Brain-Wide Functional Dysconnectivity in Schizophrenia: Parsing Diathesis, Resilience, and the Effects of Clinical Expression.

BACKGROUND: The functional dysconnectivity observed from functional magnetic resonance imaging (fMRI) studies in schizophrenia is also seen in unaffected siblings indicating its association with the genetic diathesis. We intended to apportion resting-state dysconnectivity into components that represent genetic diathesis, clinical expression or treatment effect, and resilience. METHODS: fMRI data were acquired from 28 schizophrenia patients, 28 unaffected siblings, and 60 healthy controls. Based on Dosenbach's atlas, we extracted time series of 160 regions of interest. After constructing functional network, we investigated between-group differences in strength and diversity of functional connectivity and topological properties of undirected graphs. RESULTS: Using analysis of variance, we found 88 dysconnectivities. Post hoc t tests revealed that 62.5% were associated with genetic diathesis and 21.6% were associated with clinical expression. Topologically, we observed increased degree, clustering coefficient, and global efficiency in the sibling group compared to both patients and controls. CONCLUSION: A large portion of the resting-state functional dysconnectivity seen in patients represents a genetic diathesis effect. The most prominent network-level disruption is the dysconnectivity among nodes of the default mode and salience networks. Despite their predisposition, unaffected siblings show a pattern of resilience in the emergent connectomic topology. Our findings could potentially help refine imaging genetics approaches currently used in the pursuit of the pathophysiology of schizophrenia.