Sex differences in alterations of brain functional network in tobacco use disorder.

INTRODUCTION: Many studies have found sex differences in alterations of brain function in cigarette smoking adults from the perspective of functional activity or connectivity. However, no studies have systematically found different alteration patterns in brain functional topology of cigarette smoking men and women from three perspectives: nodal and network efficiency, and modular connections. METHODS: Fifty-six tobacco use disorder (TUD) participants (25 women) and 66 non-TUD participants (28 women) underwent a resting-state functional magnetic resonance imaging scan. The whole-brain functional networks were constructed and a two-way analysis of covariance with false discovery rate correction (q < 0.05) were performed to investigate whether men and women TUD participants had different alterations in the topological features at global, modular and nodal levels. RESULTS: Compared to non-TUD participants, men but not women TUD participants showed significantly lower global efficiency (lower inter-modular connections between the visual and executive control, between the visual and subcortical modules did not pass the correction) and significantly lower nodal global efficiency in the right superior occipital gyrus, bilateral fusiform gyrus, the right pallidum, right putamen, the bilateral paracentral lobule, the postcentral gyrus, and lower nodal local efficiency in the left paracentral lobule. CONCLUSIONS: Men and women TUD participants have different topological properties of brain functional network, which may contribute to our understanding of neural mechanisms underlying sex differences in TUD. IMPLICATIONS: Compared to non-TUD participants, we found men but not women TUD participants with significantly lower network metrics at global, modular and nodal level, which could improve our understanding of neural mechanisms underlying sex differences in TUD and lay a solid foundation for future sex-based TUD prevention and treatment.

Highly active antiretroviral therapy-related effects on morphological connectivity in HIV.

OBJECTIVE: Suboptimal concentration of the antiretroviral drug is insufficient to inhibit HIV destruction on brain structure and function due to the resistance of blood brain barrier. We aimed to investigate highly active antiretroviral therapy (HAART)-related effects on the morphological connectivity in people with HIV (PWH). DESIGN: Case-control study. METHODS: Fifty-five HAART-treated for more than 3 months and 54 untreated PWH, as well as 66 demographically matched healthy controls underwent a high-resolution 3D T1-weighted MRI. Individual-level morphological brain network based on gray matter volume of 90 brain regions was constructed and network topological properties were analyzed. Network-based statistics (NBS) was performed to identify sub-networks showing significant differences in morphological connectivity. Correlation and mediation analyses were employed to evaluate associations between the morphological properties and clinical variables of PWH. RESULTS: Although PWH exhibited small-world architecture in their morphological brain networks, untreated PWH demonstrated altered network properties while HAART-treated PWH showed relatively similar network properties compared to healthy controls. Furthermore, HAART-related effects were mainly involved the bilateral putamen and left thalamus. The findings of NBS further indicated the cortico-striatum-thalamic-cortical loop was involved in the therapeutic-associated morphological network. The positive correlations between the HAART treatment and nodal degree and efficiency of the putamen were mediated by the number of CD4 + T lymphocytes. CONCLUSIONS: The topological properties are recovered to normal in PWH after HAART and the effects induced by HAART are mostly within the cortical-subcortical circuit.

Interaction effects between smoking and internet gaming disorder on resting-state functional connectivity of the ventral tegmental area and hippocampus.

Background: Many reports have focused on cigarette smoking and internet gaming disorder (IGD), with widespread alterations of resting-state functional connectivity (rsFC) in the reward and memory circuits, respectively. Epidemiological studies have also shown high comorbidity of cigarette smoking and IGD. However, the underlying mechanisms are still unknown. Therefore, this study investigates the comorbidity and interaction effects between smoking and IGD from the rsFC perspective. Methods: Resting-state functional magnetic imaging data were collected from 60 healthy controls (HC), 46 smokers, 38 IGD individuals, and 34 IGD comorbid with smoking (IGDsm) participants. Voxel-wise rsFC maps were calculated for all subjects with the ventral tegmental area, rostral hippocampus, and caudal hippocampus as regions of interest, respectively. Results: Significant interaction effects between smoking and IGD were mainly involved in the reward and memory circuits; that is, the rsFC between the ventral tegmental area and right nucleus accumbens, between the rostral hippocampus and bilateral nucleus accumbens, sensorimotor areas, and left middle temporal gyrus. Specifically, in these circuits, smokers showed decreased rsFC compared to the HC group, while IGDsm showed increased rsFC compared to smokers and IGD individuals. The IGDsm and HC groups showed no significant difference. The altered rsFC also correlated with clinical measures. Conclusion: These findings indicate that lower rsFC in smokers or IGD individuals increases under the effect of another type of addiction, such as smoking and IGD, but only increases to the normal state, which might explain the comorbidity and interaction between smoking and IGD from the perspective of functional circuits.

Evaluation of Pericardial Thickening and Adhesion Using High-Frequency Ultrasound.

BACKGROUND: Routine echocardiography using a standard-frequency ultrasound probe has insufficient spatial resolution to clearly visualize the parietal pericardium (PP). High-frequency ultrasound (HFU) has enhanced axial resolution. The aim of this study was to use a commercially available high-frequency linear probe to evaluate apical PP thickness (PPT) and pericardial adhesion in both normal pericardium and pericardial diseases. METHODS: From April 2002 to March 2022, 227 healthy individuals, 205 patients with apical aneurysm (AA) and 80 patients with chronic constrictive pericarditis (CP) were recruited to participate in this study. All subjects underwent both standard-frequency ultrasound and HFU to image the apical PP (APP) and pericardial adhesion. Some subjects underwent computed tomography (CT). RESULTS: Apical PPT was measured using HFU and found to be 0.60 ± 0.01 mm (0.37-0.87 mm) in normal control subjects, 1.22 ± 0.04 mm (0.48-4.53 mm) in patients with AA, and 2.91 ± 0.17 mm (1.13-9.01 mm) in patients with CP. Tiny physiologic effusions were observed in 39.2% of normal individuals. Pericardial adhesion was detected in 69.8% of patients with local pericarditis due to AA and 97.5% of patients with CP. Visibly thickened visceral pericardium was observed in six patients with CP. Apical PPT measurements obtained by HFU correlated well with those obtained by CT in those patients with CP. However, CT could clearly visualize the APP in only 45% of normal individuals and 37% of patients with AA. In 10 patients with CP, both HFU and CT demonstrated equal ability to visualize the very thickened APP. CONCLUSIONS: Apical PPT measured using HFU in normal control subjects ranged from 0.37 to 0.87 mm, consistent with previous reports from necropsy studies. HFU had higher resolution in distinguishing local pericarditis of the AA from normal individuals. HFU was superior to CT in imaging APP lesions, as CT failed to visualize the APP in more than half of both normal individuals and patients with AA. The fact that all 80 patients with CP in our study had significantly thickened APP raises doubt regarding the previously reported finding that 18% of patients with CP had normal PPT.

Multicentre registration of wake-up stroke in China (MCRWUSC): a protocol for a prospective, multicentre, registry-based cohort study.

INTRODUCTION: Wake-up stroke (WUS) is a type of acute ischaemic stroke (AIS) that occurs during sleep with unknown time of symptom onset. The best treatment is usually not suitable for WUS, as thrombolysis is usually provided to patients who had a symptomatic AIS within a definite 4.5 hours, and WUS remains a therapeutic quandary. Efforts to explore the onset time characteristics of patients who had a WUS and the risk factors affecting poor prognosis support a role for providing new insights by performing multicentre cohort study. METHODS AND ANALYSIS: This multicentre, nationwide prospective registry will include 21 comprehensive stroke centres, with a goal of recruiting 550 patients who had a WUS in China. In this study, clinical data including patient's clinical characteristics, stroke onset time, imaging findings, therapeutic interventions and prognosis (the National Institutes of Health Stroke Scale Score and the modified Rankin Scale Score at different time points) will be used to develop prediction models for stroke onset time and prognostic evaluation using the fast-processing of ischemic stroke software. The purpose of this study is to identify risk factors influencing prognosis, to investigate the relationship between the time when the symptoms are found and the actual onset time and to establish an artificial intelligence-based model to predict the prognosis of patients who had a WUS. ETHICS AND DISSEMINATION: This study is approved by the ethics committee of Shanghai Pudong Hospital (Shanghai, China) and rest of all participating centres. The findings will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: ChiCTR2100049133.

Reciprocal modulation between cigarette smoking and internet gaming disorder on participation coefficient within functional brain networks.

Many reports indicated that cigarette smoking was associated with internet gaming disorder (IGD). However, the underlying mechanism of comorbidity between smoking and IGD and whether they had interaction effects on topological organization of brain functional network are still unknown. Therefore, we investigated the interaction between smoking and IGD in resting-state brain functional networks for 60 healthy controls, 46 smokers, 38 IGD individuals and 34 IGD comorbid with smoking participants. The modular structures of functional networks were explored and participation coefficient (Pc) was used to characterize the importance of each brain region in the communication between modules. Significant main effect of IGD was found in the left superior frontal gyrus, bilateral medial part of superior frontal gyrus and bilateral posterior cingulate gyrus with lower Pc in IGD group than in non-IGD group. Significant interaction effects between smoking and IGD were found in the left posterior orbital gyrus, right lateral orbital gyrus, left supramarginal gyrus, left middle temporal gyrus and left inferior temporal gyrus. The interaction in these brain regions was characterized by no significant difference or significantly decreased Pc in smokers or IGD individuals while significantly increased Pc in IGD comorbid with smoking group under the influence of IGD or smoking. Our findings provide valuable information underlying the neurophysiological mechanisms of smoking and IGD, and also offer a potential target for future clinical treatment of smoking and IGD comorbidity.

Sex-Dependent Alterations of Regional Homogeneity in Cigarette Smokers.

Biological sex may play a large role in cigarette use and cessation outcomes and neuroimaging studies have demonstrated that cigarette smoking is associated with sex-related differences in brain structure and function. However, less is known about sex-specific alterations in spontaneous brain activity in cigarette smokers. In this study, we investigated the sex-related effects of cigarette smoking on local spontaneous brain activity using regional homogeneity (ReHo) based on resting-state fMRI. Fifty-six smokers (24 females) and sixty-three (25 females) healthy non-smoking controls were recruited. Whole-brain voxelwise 2-way analysis of covariance of ReHo was performed to detect brain regions with sex-dependent alterations on the spontaneous brain activity. Compared to non-smokers, smokers exhibited significant ReHo differences in several brain regions, including the right medial orbitofrontal cortex extended to the ventral striatum/amygdala/parahippocampus, left precuneus, and bilateral cerebellum crus. Smoking and sex interaction analysis revealed that male smokers showed significantly lower ReHo in the right ventral striatum, left cerebellum crus1, and left fusiform gyrus compared to male non-smokers, whereas there are no significant differences between female smokers and non-smokers. Furthermore, the ReHo within the left cerebellum crus1 was negatively correlated with craving scores in male smokers but not in female smokers. Such sex-dependent differences in spontaneous brain activity lays a foundation for further understanding the neural pathophysiology of sex-specific effects of nicotine addiction and promoting more effective health management of quitting smoking.

Functional Connectivity Features of Resting-State Functional Magnetic Resonance Imaging May Distinguish Migraine From Tension-Type Headache.

Background: Migraineurs often exhibited abnormalities in cognition, emotion, and resting-state functional connectivity (rsFC), whereas patients with tension-type headache (TTH) rarely exhibited these abnormalities. The aim of this study is to explore whether rsFC alterations in brain regions related to cognition and emotion could be used to distinguish patients with migraine from patients with TTH. Methods: In this study, Montreal Cognitive Assessment (MoCA), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and rsFC analyses were used to assess the cognition, anxiety, and depression of 24 healthy controls (HCs), 24 migraineurs, and 24 patients with TTH. Due to their important roles in neuropsychological functions, the bilateral amygdala and hippocampus were chosen as seed regions for rsFC analyses. We further assessed the accuracy of the potential rsFC alterations for distinguishing migraineurs from non-migraineurs (including HCs and patients with TTH) by the receiver operating characteristic (ROC) analysis. Associations between headache characteristics and rsFC features were calculated using a multi-linear regression model. This clinical trial protocol has been registered in the Chinese Clinical Trial Registry (registry number: ChiCTR1900024307, Registered: 5 July 2019-Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=40817). Results: Migraineurs showed lower MoCA scores (p = 0.010) and higher SAS scores (p = 0.017) than HCs. Migraineurs also showed decreased rsFC in the bilateral calcarine/cuneus, lingual gyrus (seed: left amygdala), and bilateral calcarine/cuneus (seed: left hippocampus) in comparison to HCs and patients with TTH. These rsFC features demonstrated significant distinguishing capabilities and got a sensitivity of 82.6% and specificity of 81.8% with an area under the curve (AUC) of 0.868. rsFC alterations showed a significant correlation with headache frequency in migraineurs (p = 0.001, Pc = 0.020). Conclusion: The rsFC of amygdala and hippocampus with occipital lobe can be used to distinguish patients with migraine from patients with TTH. Clinical Trial Registration: [http://www.chictr.org.cn/showproj.aspx?proj=40817], identifier [ChiCTR1900024307].

Potential dynamic regional brain biomarkers for early discrimination of autism and language development delay in toddlers.

Background: The early diagnosis of autism in children is particularly important. However, there is no obvious objective indices for the diagnosis of autism spectrum disorder (ASD), especially in toddlers aged 1-3 years with language development delay (LDD). The early differential diagnosis of ASD is challenging. Objective: To examine differences in the dynamic characteristics of regional neural activity in toddlers with ASD and LDD, and whether the differences can be used as an imaging biomarker for the early differential diagnosis of ASD and LDD. Methods: Dynamic regional homogeneity (dReHo) and dynamic amplitude of low-frequency fluctuations (dALFF) in 55 children with ASD and 31 with LDD, aged 1-3 years, were compared. The correlations between ASD symptoms and the values of dReHo/dALFF within regions showing significant between-group differences were analyzed in ASD group. We further assessed the accuracy of dynamic regional neural activity alterations to distinguish ASD from LDD using receiver operating characteristic (ROC) analysis. Results: Compared with the LDD group, the ASD group showed increased dReHo in the left cerebellum_8/Crust2 and right cerebellum_Crust2, and decreased dReHo in the right middle frontal gyrus (MFG) and post-central gyrus. Patients with ASD also exhibited decreased dALFF in the right middle temporal gyrus (MFG) and right precuneus. Moreover, the Childhood Autism Rating Scale score was negatively correlated with the dReHo of the left cerebellum_8/crust2 and right cerebellum_crust2. The dReHo value of the right MFG was negatively correlated with social self-help of the Autism Behavior Checklist score. Conclusion: The pattern of resting-state regional neural activity variability was different between toddlers with ASD and those with LDD. Dynamic regional indices might be novel neuroimaging biomarkers that allow differentiation of ASD from LDD in toddlers.

Repeated fluoxetine treatment induces transient and long-term astrocytic plasticity in the medial prefrontal cortex of normal adult rats.

Fluoxetine (Flx)-induced neuronal plasticity plays an important role in the effective treatment of depression and mood disorders. It is less understood whether repeated Flx treatment induces astrocytic plasticity that outlasts the presence of the drug in the body. We showed previously that Flx-induced neuronal plasticity in the medial prefrontal cortex (mPFC) persisted up to 20 days after the treatment. In this study, adult rats were subjected to a 15-day repeated Flx treatment at a daily dose of 20 mg/kg body weight. Astrocytic metabolites and markers were assessed in the mPFC at day 1 (d1) and day 20 (d20) after the treatment. Significant transient reductions in the concentrations of astrocytic metabolites taurine and myo-inositol and the expressions of glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4) were observed in the mPFC of Flx-treated rats at d1, which recovered to the control levels at d20. Further, Flx treatment resulted in long-lasting changes in Kir4.1 expression in the mPFC, which remained downregulated at d20. The expression of 5-HT1A receptor in the mPFC of Flx-treated rats was downregulated at d1 but became upregulated at d20. In summary, repeated Flx treatment induces both transient and long-term astrocytic plasticity in the mPFC of adult rats. The changes observed at d1 are consistent with disturbed water homeostasis and astrocytic de-maturation in the mPFC. The persistent changes in the expressions of Kir4.1 and 5-HT1A at d20, presumably of the astrocytic origin, might have contributed to the long-term neurotrophic effects of repeated Flx treatment in the mPFC.

Sex-specific effects of cigarette smoking on caudate and amygdala volume and resting-state functional connectivity.

Recent studies have demonstrated sex-specific differences in etiology, course and brain dysfunction that are associated with cigarette smoking. However, little is known about sex-specific differences in subcortical structure and function. In this study, structural and resting-state functional magnetic resonance imaging (fMRI) data were collected from 60 cigarette smokers (25 females) and 67 nonsmokers (28 females). The structural MRI was applied to identify deficits in sex-specific subcortical volume. Using resting-state fMRI, sex-related alterations in resting-state functional connectivity (rsFC) were investigated in subcortical nuclei with volume deficits as seed regions. Compared to nonsmokers, male but not female smokers demonstrated a significantly smaller volume in the left caudate, while female but not male smokers showed a smaller volume in the right amygdala. Resting-state FC analysis revealed that male but not female smokers had increased rsFC between the left caudate and the left prefrontal cortex but decreased rsFC within the bilateral caudate and between the right amygdala and right orbitofrontal cortex (OFC). Furthermore, the right amygdala volume was negatively correlated with the impulsivity score in female but not male smokers. The rsFC of the right amygdala-OFC circuit was negatively associated with the craving score in male but not female smokers. These findings indicate that cigarette smoking may have differential effects on the caudate and amygdala volumes as well as rsFC between men and women, contributing to our knowledge of sex-specific effects of nicotine addiction. Such sex-specific differences in subcortical structure and function may provide a methodological framework for the development of sex-specific relapse prevention therapies.

Interaction Between Smoking and Internet Gaming Disorder on Spontaneous Brain Activity.

Converging lines of evidence indicates that smoking and internet gaming disorder (IGD) affect spontaneous brain activity, respectively. However, little is known about whether these two factors work together on the human brain. In this study, we investigated the interaction between smoking and IGD on local spontaneous brain activity using amplitude of low-frequency fluctuation (ALFF) based on resting-state fMRI (rs-fMRI). Forty-six cigarette smokers, 38 IGD individuals, 34 participants with both IGD and cigarette smoking (IGD-Smoking), and 60 healthy individuals involved in the study. Voxel-wise analysis of covariance of ALFF revealed that there were significant interactions between IGD by smoking in the right medial pre-frontal cortex (MPFC)/ventral striatum, bilateral cerebellar, and visual-related regions as well as the left temporal gyrus. In the right MPFC/ventral striatum and left temporal gyrus, ALFF in smoking group was significantly higher than healthy group while there were no significant ALFF differences between IGD-Smoking group and IGD group. While in the bilateral cerebellar and visual-related regions, ALFF in the smoking group was significantly lower than healthy group while ALFF in IGD-Smoking group did not show significant difference with IGD group. In addition, in the smoking group, ALFF of the right MPFC/ventral striatum was associated positively with anxiety and depression scores while the ALFF value in the smoking group had a trend toward negative correlation with SDS scores in the bilateral cerebellar and visual-related regions. The ALFF value in the smoking group was associated positively with anxiety score in the left temporal gyrus. These findings indicate that smoking and IGD interacted with each other in the human brain. Our results, in terms of spontaneous brain activity, may imply the fact that IGD people are more tended to get smoking. Moreover, it is possible to predict that smokers may be more easily to get internet addiction than healthy people.

Mapping accumulative whole-brain activities during environmental enrichment with manganese-enhanced magnetic resonance imaging.

An enriched environment (EE) provides multi-dimensional stimuli to the brain. EE exposure for days to months induces functional and structural neuroplasticity. In this study, manganese-enhanced magnetic resonance imaging (MEMRI) was used to map the accumulative whole-brain activities associated with a 7-day EE exposure in freely-moving adult male mice, followed by c-Fos immunochemical assessments. Relative to the mice residing in a standard environment (SE), the mice subjected to EE treatment had significantly enhanced regional MEMRI signal intensities in the prefrontal cortex, somatosensory cortices, basal ganglia, amygdala, motor thalamus, lateral hypothalamus, ventral hippocampus and midbrain dopaminergic areas at the end of the 7-day exposure, likely attributing to enhanced Mn2+ uptake/transport associated with brain activities at both the regional and macroscale network levels. Some of, but not all, the brain regions in the EE-treated mice showing enhanced MEMRI signal intensity had accompanying increases in c-Fos expression. The EE-treated mice were also found to have significantly increased overall amount of food consumption, decreased body weight gain and upregulated tyrosine hydroxylase (TH) expression in the midbrain dopaminergic areas. Taken together, these results demonstrated that the 7-day EE exposure was associated with elevated cumulative activities in the nigrostriatal, mesolimbic and corticostriatal circuits underpinning reward, motivation, cognition, motor control and appetite regulation. Such accumulative activities might have served as the substrate of EE-related neuroplasticity and the beneficial effects of EE treatment on neurological/psychiatric conditions including drug addiction, Parkinson's disease and eating disorder.

Region-Specific Changes of Insular Cortical Thickness in Heavy Smokers.

Insula plays an essential role in maintaining the addiction to cigarette smoking and smoking-related alterations on the insular volume and density have been reported in smokers. However, less is known about the effects of chronic cigarette smoking on the insular cortical thickness. In this study, we explored the region-specific changes of insular cortical thickness in heavy smokers and their relations with smoking-related variables. 37 heavy smokers (29 males, mean age 47.19 ± 7.22 years) and 37 non-smoking healthy controls (29 males, mean age 46.95 ± 8.45 years) participated in the study. Subregional insular cortical thickness was evaluated and compared between the two groups. Correlation analysis was performed to investigate relationships between the insular cortical thickness and clinical characteristics in heavy smokers. There was no statistical difference on the cortical thickness in the left insula (p = 0.536) between the two groups while heavy smokers had a slightly thinner cortical thickness in the right insula (p = 0.048). In addition, heavy smokers showed a greater cortical thinning in the anterior (p = 0.0084) and superior (p = 0.0054) segment of the circular sulcus of the right insula as well as the inferior (p = 0.012) segment of the circular sulcus of the left insula. Moreover, the cortical thickness of the superior segment of the circular sulcus of the left insula was correlated negatively with nicotine severity (r = -0.423; p = 0.009) and the longer cigarette exposure was associated with the cortical thinning in the long insular gyrus and central sulcus of the right insula (r = -0.475; p = 0.003). Our findings indicate that chronic cigarette use is associated with region-specific insular thinning, which has the potential to improve our understanding of the specific roles of insular subregions in nicotine addiction.

Altered nuclei-specific thalamic functional connectivity patterns in multiple sclerosis and their associations with fatigue and cognition.

BACKGROUND: The thalamus, affected early in multiple sclerosis (MS), is a heterogeneous composition of functionally distinct nuclei and is associated with fatigue, cognition, and other outcomes. However, most previous functional imaging studies considered the thalamus only as a whole. OBJECTIVE: To investigate MS-related abnormalities in nuclei-specific thalamic functional connectivity (FC) and their associations with fatigue and cognitive outcomes. METHODS: Resting-state functional magnetic resonance imaging (fMRI) was analyzed in 64 MS patients and 26 healthy controls (HC). Whole-brain FC maps for four thalamic subregions seeds were computed for each subject. FC maps were compared between groups, and group by FC interaction effects were assessed for fatigue and cognitive measures. RESULTS: MS patients had decreased FC between the left medial thalamic nuclei and left angular gyrus and reduced FC between the left posterior thalamic nuclei and left supramarginal gyrus, as well as decreased right medial thalamic nuclei connectivity with bilateral caudate/thalamus and left cerebellar areas (p < 0.05 corrected). MS patients had increased FC between the left anterior thalamic nuclei and anterior cingulate cortex bilaterally. There were significant relationships between connectivity alterations and fatigue and cognitive measures between groups (p < 0.05 corrected). CONCLUSION: FC alteration is nuclei-specific and is differentially associated with fatigue and cognition.

Sex differences in resting-state cerebral activity alterations in internet gaming disorder.

Although evidence has shown that the prevalence rates of Internet gaming disorder (IGD) differ between males and females, few studies have examined whether such sex differences extend to brain function. This study aimed to explore the sex differences in resting-state cerebral activity alterations in IGD. Thirty male participants with IGD (IGDm), 23 female participants with IGD (IGDf), and 30 male and 22 female age-matched healthy controls (HC) underwent resting-state functional MRI. Maps of the amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) were constructed. A two-factor ANCOVA model was performed, with sex and diagnosis as the between-subject factors. Then, post hoc pair-wise comparisons were performed using two-sample t-tests within the interaction masks. The Barratt Impulsiveness Scale-11 (BIS-11) was used to assess the behavioral inhibition function. We found that the ALFF values in the orbital part of the left superior frontal gyrus (SFG) were lower in IGDm than in HCm, which were negatively correlated with BIS-11 scores. IGDm also demonstrated lower connectivity between the orbital part of the left SFG and the posterior cingulate cortex (PCC), the right angular gyrus, and the right dorsolateral prefrontal cortex than HCm. Furthermore, IGDm had lower seed connectivity between the orbital part of the left SFG and the PCC than ICDf. Our findings suggest that (1) the altered ALFF values in the orbital part of the left SFG represent a clinically relevant biomarker for the behavioral inhibition function of IGDm; (2) IGD may interact with sex-specific patterns of FC in male and female subjects.

Brain Iron at Quantitative MRI Is Associated with Disability in Multiple Sclerosis.

Purpose To study deep gray matter susceptibility in multiple sclerosis (MS) by using quantitative susceptibility mapping (QSM) and to assess the relationship between susceptibility and clinical disability. Materials and Methods For this prospective study between March 2009 and November 2013, 600 participants with MS (452 with relapsing-remitting MS and 148 with secondary progressive MS) and 250 age- and sex-matched healthy control participants were imaged with 3.0-T MRI to measure magnetic susceptibility. Deep gray matter susceptibility (in parts per billion) was analyzed by using region of interest and voxelwise methods. QSM and MRI volumetric differences between study groups and associations with clinical outcomes were assessed. Analysis of covariance, multivariable linear regression, and voxelwise analyses, controlling for age and sex, were used to compare study groups and to explore associations between MRI and clinical outcomes. Results Compared with control participants, participants with MS presented with lower thalamic susceptibility (-7.5 ppb vs -1.1 ppb; P < .001) and higher susceptibility of basal ganglia (62 ppb vs 54.8 ppb; P < .001). Lower thalamic susceptibility was associated with longer disease duration (ß = -0.42; P = .002), higher degree of disability (ß = -0.64; P = .03), and secondary-progressive course (ß = -4.3; P = .009). Higher susceptibility of the globus pallidus was associated with higher disability (ß = 2; P = .03). After correcting for each individual structural volume in voxelwise analysis, lower thalamic susceptibility and higher susceptibility of the globus pallidus remained associated with clinical disability (P < .05). Conclusion Quantitative susceptibility mapping (QSM) suggests that altered deep gray matter iron is associated with the evolution of multiple sclerosis (MS) and on disability accrual, independent of tissue atrophy. © RSNA, 2018 Online supplemental material is available for this article.

Alterations of Resting-State Static and Dynamic Functional Connectivity of the Dorsolateral Prefrontal Cortex in Subjects with Internet Gaming Disorder.

Internet gaming disorder (IGD), a major behavior disorder, has gained increasing attention. Recent studies indicate altered resting-state static functional connectivity (FC) of the dorsolateral prefrontal cortex (DLPFC) in subjects with IGD. Whereas static FC often provides information on functional changes in subjects with IGD, investigations of temporal changes in FC between the DLPFC and the other brain regions may shed light on the dynamic characteristics of brain function associated with IGD. Thirty subjects with IGD and 30 healthy controls (HCs) matched for age, gender and education status were recruited. Using the bilateral DLPFC as seeds, static FC and dynamic FC maps were calculated and compared between groups. Correlations between alterations in static FC and dynamic FC and clinical variables were also investigated within the IGD group. The IGD group showed significantly lower static FC between the right DLPFC and the left rolandic operculum while higher static FC between the right DLPFC and the left pars triangularis when compared to HCs. The IGD group also had significantly decreased dynamic FC between the right DLPFC and the left insula, right putamen and left precentral gyrus, and increased dynamic FC in the left precuneus. Moreover, the dynamic FC between the right DLPFC and the left insula was negatively correlated with the severity of IGD. Dynamic FC can be used as a powerful supplement to static FC, helping us obtain a more comprehensive understanding of large-scale brain network activity in IGD and put forward new ideas for behavioral intervention therapy for it.

Structural Covariance of Gray Matter Volume in HIV Vertically Infected Adolescents.

Human immunodeficiency virus (HIV) infection significantly affect neurodevelopmental and behavioral outcomes. We investigated whether alterations of gray matter organization and structural covariance networks with vertical HIV infection adolescents exist, by using the GAT toolbox. MRI data were analysed from 25 HIV vertically infected adolescents and 33 HIV-exposed-uninfected control participants. The gray matter volume (GMV) was calculated, and structural brain networks were reconstructed from gray matter co-variance. Gray matter losses were pronounced in anterior cingulate cortex (ACC), right pallidum, right occipital lobe, inferior parietal lobe, and bilateral cerebellum crus. The global brain network measures were not significantly different between the groups; however, the nodal alterations were most pronounced in frontal, temporal, basal ganglia, cerebellum, and temporal lobes. Brain hubs in the HIV-infected subjects increased in number and tended to shift to sensorimotor and temporal areas. In the HIV-infected subjects, decreased GMVs in ACC and bilateral cerebellum were related to lower Mini-Mental State Examination scores; the CD4 counts were positively related to the GMVs in ACC and sensorimotor areas. These findings suggest that focally reduced gray matter, disrupted nodal profiles of structural wirings, and a shift in hub distribution may represent neuroanatomical biomarkers of HIV infection on the developing brain.

Iron-related gene variants and brain iron in multiple sclerosis and healthy individuals.

Brain iron homeostasis is known to be disturbed in multiple sclerosis (MS), yet little is known about the association of common gene variants linked to iron regulation and pathological tissue changes in the brain. In this study, we investigated the association of genetic determinants linked to iron regulation with deep gray matter (GM) magnetic susceptibility in both healthy controls (HC) and MS patients. Four hundred (400) patients with MS and 150 age- and sex-matched HCs were enrolled and obtained 3 T MRI examination. Three (3) single nucleotide polymorphisms (SNPs) associated with iron regulation were genotyped: two SNPs in the human hereditary hemochromatosis protein gene HFE: rs1800562 (C282Y mutation) and rs1799945 (H63D mutation), as well as the rs1049296 SNP in the transferrin gene (C2 mutation). The effects of disease and genetic status were studied using quantitative susceptibility mapping (QSM) voxel-based analysis (VBA) and region-of-interest (ROI) analysis of the deep GM. The general linear model framework was used to compare groups. Analyses were corrected for age and sex, and adjusted for false discovery rate. We found moderate increases in susceptibility in the right putamen of participants with the C282Y (+ 6.1 ppb) and H63D (+ 6.9 ppb) gene variants vs. non-carriers, as well as a decrease in thalamic susceptibility of progressive MS patients with the C282Y mutation (left: - 5.3 ppb, right: - 6.7 ppb, p < 0.05). Female MS patients had lower susceptibility in the caudate (- 6.0 ppb) and putamen (left: - 3.9 ppb, right: - 4.6 ppb) than men, but only when they had a wild-type allele (p < 0.05). Iron-gene linked increases in putamen susceptibility (in HC and relapsing remitting MS) and decreases in thalamus susceptibility (in progressive MS), coupled with apparent sex interactions, indicate that brain iron in healthy and disease states may be influenced by genetic factors.