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.

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.

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.

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.

Brain T1ρ mapping for grading and IDH1 gene mutation detection of gliomas: a preliminary study.

INTRODUCTION: The longitudinal relaxation time in the rotating frame (T1ρ) has proved to be sensitive to metabolism and useful in application to neurodegenerative diseases. However, few literature exists on its utility in gliomas. Thus, this study was conducted to explore the performance of T1ρ mapping in tumor grading and characterization of isocitrate dehydrogenase 1 (IDH1) gene mutation status of gliomas. METHODS: Fifty-seven patients with gliomas underwent brain MRI and quantitative measurements of T1ρ and apparent diffusion coefficient (ADC) were recorded. Parameters were compared between high-grade gliomas (HGG) and low-grade gliomas (LGG) and between IDH1 mutant and wildtype groups. RESULTS: HGG showed significantly higher T1ρ values in both the solid and peritumoral edema areas compared with LGG (P < 0.001 and P = 0.005, respectively), whereas no significant differences in the two areas were found for ADC (both P > 0.05). Receiver operating characteristic (ROC) curve analysis showed that T1ρ value in the solid area achieved the highest area under the ROC curve (AUC, 0.841) in grading with a sensitivity of 80.6% and a specificity of 81.0%. In the grade II/III glioma group, multivariate logistic regression showed that both tumor frontal lobe location (odds ratio [OR] 526.608; P = 0.045) and T1ρ value of the peritumoral edema area (OR 0.863; P = 0.037) were significant predictors of IDH1 mutation. Using the combination, the diagnostic sensitivity and specificity for IDH1 mutated gliomas were 93.3% and 88.9%, respectively. CONCLUSIONS: Our study shows the feasibility of applying T1ρ mapping in assessing the histologic grade and IDH1 mutation status of gliomas.

Difference in the functional connectivity of the dorsolateral prefrontal cortex between smokers with nicotine dependence and individuals with internet gaming disorder.

BACKGROUND: It has been reported that internet gaming disorder (IGD) and smokers with nicotine dependence (SND) share clinical characteristics, such as over-engagement despite negative consequences and cravings. This study is to investigate the alterations in the resting-state functional connectivity (rsFC) of the dorsolateral prefrontal cortex (DLPFC) observed in SND and IGD. In this study, 27 IGD, 29 SND, and 33 healthy controls (HC) underwent a resting-state functional magnetic resonance imaging (rs-fMRI) scan. DLPFC connectivity was determined in all participates by investigating the synchronized low-frequency fMRI signal fluctuations using a temporal seed-based correlation method. RESULTS: Compared with the HC group, the IGD and SND groups showed decreased rsFC with DLPFC in the right insula and left inferior frontal gyrus with DLPFC. Compared with SND group, the IGD subjects exhibited increased rsFC in the left inferior temporal gyrus and right inferior orbital frontal gyrus and decreased rsFC in the right middle occipital gyrus, supramarginal gyrus, and cuneus with DLPFC. CONCLUSION: Our results confirmed that SND and IGD share similar neural mechanisms related to craving and impulsive inhibitions. The significant difference in rsFC with DLPFC between the IGD and SND subjects may be attributed to the visual and auditory stimulation generated by long-term internet gaming.

Synthesis of 6-hydroxyaurone analogues and evaluation of their α-glucosidase inhibitory and glucose consumption-promoting activity: Development of highly active 5,6-disubstituted derivatives.

A series of 6-hydroxyaurones and their analogues have been synthesized and evaluated for their in vitro α-glucosidase inhibitory and glucose consumption-promoting activity. These compounds exhibited varying degrees of α-glucosidase inhibitory activity, 11 of them showing higher potency than that of the control standard acarbose (IC50=50.30µM). Surprisingly, analogues devoid of a substituent at C-2 but having an aryl group at C-5 were found to be highly active (e.g., 7f, IC50=9.88µM). Docking analysis substantiated these findings. The kinetic analysis of compound 7f, the most potent α-glucosidase inhibitor of this study, revealed that it inhibited α-glucosidase in an irreversible and mixed competitive mode. In addition, compounds 7f and 10c exhibited significant glucose consumption promoting activity at 1µM.

Characterizing Brain Iron Deposition in Patients with Subcortical Vascular Mild Cognitive Impairment Using Quantitative Susceptibility Mapping: A Potential Biomarker.

The presence and pattern of iron accumulation in subcortical vascular mild cognitive impairment (svMCI) and their effects on cognition have rarely been investigated. We aimed to examine brain iron deposition in svMCI subjects using quantitative susceptibility mapping (QSM). Moreover, we aimed to investigate the correlation between brain iron deposition and the severity of cognitive impairment as indicated by z-scores. We recruited 20 subcortical ischemic vascular disease (SIVD) patients who fulfilled the criteria for svMCI. The control group comprised 19 SIVD patients without cognitive impairment. The SIVD and control groups were matched based on age, gender, and years of education. Both groups underwent QSM using a 3.0T MRI system. Susceptibility maps were reconstructed from in vivo data, which were acquired with a three-dimensional spoiled gradient recalled sequence. Then, regions of interest were drawn manually on the map of each subject. The inter-group differences of susceptibility values were explored in deep gray matter nuclei, including the bilateral pulvinar nucleus of the thalamus, head of caudate nucleus, globus pallidus, putamen, hippocampus, substantia nigra, and red nucleus. The correlations between regional iron deposition and composite z-score, memory z-score, language z-score, attention-executive z-score and visuospatial z-score were assessed using partial correlation analysis, with patient age and gender as covariates. Compared with the control, the svMCI group had elevated susceptibility values within the bilateral hippocampus and right putamen. Furthermore, the susceptibility value in the right hippocampus was negatively correlated with memory z-score and positively correlated with language z-score. The susceptibility value in the right putamen was negatively correlated with attention-executive z-score in the svMCI group. However, composite z-score were unrelated to susceptibility values. Our results suggest that brain iron deposition has clinical relevance as a biomarker for cognition. In addition, our results highlight the importance of iron deposition in understanding svMCI-associated cognitive deficits in addition to conventional MRI markers.

Application of a Simplified Method for Estimating Perfusion Derived from Diffusion-Weighted MR Imaging in Glioma Grading.

Purpose: To evaluate the feasibility of a simplified method based on diffusion-weighted imaging (DWI) acquired with three b-values to measure tissue perfusion linked to microcirculation, to validate it against from perfusion-related parameters derived from intravoxel incoherent motion (IVIM) and dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging, and to investigate its utility to differentiate low- from high-grade gliomas. Materials and Methods: The prospective study was approved by the local institutional review board and written informed consent was obtained from all patients. From May 2016 and May 2017, 50 patients confirmed with glioma were assessed with multi-b-value DWI and DCE MR imaging at 3.0 T. Besides conventional apparent diffusion coefficient (ADC0,1000) map, perfusion-related parametric maps for IVIM-derived perfusion fraction (f) and pseudodiffusion coefficient (D*), DCE MR imaging-derived pharmacokinetic metrics, including Ktrans, ve and vp, as well as a metric named simplified perfusion fraction (SPF), were generated. Correlation between perfusion-related parameters was analyzed by using the Spearman rank correlation. All imaging parameters were compared between the low-grade (n = 19) and high-grade (n = 31) groups by using the Mann-Whitney U test. The diagnostic performance for tumor grading was evaluated with receiver operating characteristic (ROC) analysis. Results: SPF showed strong correlation with IVIM-derived f and D* (ρ = 0.732 and 0.716, respectively; both P < 0.001). Compared with f, SPF was more correlated with DCE MR imaging-derived Ktrans (ρ = 0.607; P < 0.001) and vp (ρ = 0.397; P = 0.004). Among all parameters, SPF achieved the highest accuracy for differentiating low- from high-grade gliomas, with an area under the ROC curve value of 0.942, which was significantly higher than that of ADC0,1000 (P = 0.004). By using SPF as a discriminative index, the diagnostic sensitivity and specificity were 87.1% and 94.7%, respectively, at the optimal cut-off value of 19.26%. Conclusion: The simplified method to measure tissue perfusion based on DWI by using three b-values may be helpful to differentiate low- from high-grade gliomas. SPF may serve as a valuable alternative to measure tumor perfusion in gliomas in a noninvasive, convenient and efficient way.

Different resting-state functional connectivity alterations in smokers and nonsmokers with Internet gaming addiction.

This study investigated changes in resting-state functional connectivity (rsFC) of posterior cingulate cortex (PCC) in smokers and nonsmokers with Internet gaming addiction (IGA). Twenty-nine smokers with IGA, 22 nonsmokers with IGA, and 30 healthy controls (HC group) underwent a resting-state fMRI scan. PCC connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. Compared with the nonsmokers with IGA, the smokers with IGA exhibited decreased rsFC with PCC in the right rectus gyrus. Left middle frontal gyrus exhibited increased rsFC. The PCC connectivity with the right rectus gyrus was found to be negatively correlated with the CIAS scores in the smokers with IGA before correction. Our results suggested that smokers with IGA had functional changes in brain areas related to motivation and executive function compared with the nonsmokers with IGA.