Meta-analysis of structural and functional abnormalities in behavioral addictions.

BACKGROUND: The incidence of behavioral addictions (BAs) associated with scientific and technological advances has been increasing steadily. Unfortunately, a large number of studies on the structural and functional abnormalities have shown poor reproducibility, and it remains unclear whether different addictive behaviors share common underlying abnormalities. Therefore, our objective was to conduct a quantitative meta-analysis of different behavioral addictions to provide evidence-based evidence of common structural and functional changes. METHODS: We conducted systematic searches in PubMed, Web of Science and Scopus from January 2010 to December 2023, supplementing reference lists of high-quality relevant meta-analyses and reviews, to identify eligible voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies. Using anisotropic seed-based D-Mapping (AES-SDM) meta-analysis methods, we compared brain abnormalities between BAs and healthy controls (HCs). RESULTS: There were 11 GMV studies (287 BAs and 292 HCs) and 26 fMRI studies (577 BAs and 545 HCs) that met inclusion criteria. Compared with HCs, BAs demonstrated significant reductions in gray matter volume (GMV) in (1) right anterior cingulate gyri extending into the adjacent superior frontal gyrus, as well as in the left inferior frontal gyrus and right striatum. (2) the bilateral precuneus, right supramarginal gyrus, and right fusiform gyrus were hyperfunction; (3) the left medial cingulate gyrus extended to the superior frontal gyrus, the left inferior frontal gyrus, and right middle temporal gyrus had hypofunction. CONCLUSIONS: Our study identified structural and functional impairments in brain regions involved in executive control, cognitive function, visual memory, and reward-driven behavior in BAs. Notably, fronto-cingulate regions may serve as common biomarkers of BAs.

Altered intrinsic neural timescales and neurotransmitter activity in males with tobacco use disorder.

Previous researches of tobacco use disorder (TUD) has overlooked the hierarchy of cortical functions and single modality design separated the relationship between macroscopic neuroimaging aberrance and microscopic molecular basis. At present, intrinsic timescale gradient of TUD and its molecular features are not fully understood. Our study recruited 146 male subjects, including 44 heavy smokers, 50 light smokers and 52 non-smokers, then obtained their rs-fMRI data and clinical scales related to smoking. Intrinsic neural timescale (INT) method was performed to describe how long neural information was stored in a brain region by calculating the autocorrelation function (ACF) of each voxel to examine the difference in the ability of information integration among the three groups. Then, correlation analyses were conducted to explore the relationship between INT abnormalities and clinical scales of smokers. Finally, cross-modal JuSpace toolbox was used to investigate the association between INT aberrance and the expression of specific receptor/transporters. Compared to healthy controls, TUD subjects displayed decreased INT in control network (CN), default mode network (DMN), sensorimotor areas and visual cortex, and such trend of decreasing INT was more pronounced in heavy smokers. Moreover, various neurotransmitters (including dopaminergic, acetylcholine and µ-opioid receptors) were involved in the molecular mechanism of timescale decreasing and differed in heavy and light smokers. These findings supplied novel insights into the brain functional aberrance in TUD from an intrinsic neural dynamic perspective and confirm INT was a potential neurobiological marker. And also established the connection between macroscopic imaging aberrance and microscopic molecular changes in TUD.

Changes in aspartate metabolism in the medial-prefrontal cortex of nicotine addicts based on J-edited magnetic resonance spectroscopy.

This study aims to explore the changes of the aspartate (Asp) level in the medial-prefrontal cortex (mPFC) of subjects with nicotine addiction (nicotine addicts [NAs]) using the J-edited 1 H MR spectroscopy (MRS), which may provide a positive imaging evidence for intervention of NA. From March to August 2022, 45 males aged 40-60 years old were recruited from Henan Province, including 21 in NA and 24 in nonsmoker groups. All subjects underwent routine magnetic resonance imaging (MRI) and J-edited MRS scans on a 3.0 T MRI scanner. The Asp level in mPFC was quantified with reference to the total creatine (Asp/Cr) and water (Aspwater-corr , with correction of the brain tissue composition) signals, respectively. Two-tailed independent samples t-test was used to analyze the differences in levels of Asp and other coquantified metabolites (including total N-acetylaspartate [tNAA], total cholinine [tCho], total creatine [tCr], and myo-Inositol [mI]) between the two groups. Finally, the correlations of the Asp level with clinical characteristic assessment scales were performed using the Spearman criteria. Compared with the control group (n = 22), NAs (n = 18) had higher levels of Asp (Asp/Cr: p = .005; Aspwater-corr : p = .004) in the mPFC, and the level of Asp was positively correlated with the daily smoking amount (Asp/Cr: p < .001; Aspwater-corr : p = .004). No significant correlation was found between the level of Asp and the years of nicotine use, Fagerstrom Nicotine Dependence (FTND), Russell Reason for Smoking Questionnaire (RRSQ), or Barratt Impulsivity Scale (BIS-11) score. The elevated Asp level was observed in mPFC of NAs in contrast to nonsmokers, and the Asp level was positively correlated with the amount of daily smoking, which suggests that nicotine addiction may result in elevated Asp metabolism in the human brain.

Static and dynamic changes of intrinsic brain local connectivity in internet gaming disorder.

BACKGROUND: Studies have revealed that intrinsic neural activity varies over time. However, the temporal variability of brain local connectivity in internet gaming disorder (IGD) remains unknown. The purpose of this study was to explore the alterations of static and dynamic intrinsic brain local connectivity in IGD and whether the changes were associated with clinical characteristics of IGD. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed on 36 individuals with IGD (IGDs) and 44 healthy controls (HCs) matched for age, gender and years of education. The static regional homogeneity (sReHo) and dynamic ReHo (dReHo) were calculated and compared between two groups to detect the alterations of intrinsic brain local connectivity in IGD. The Internet Addiction Test (IAT) and the Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the severity of online gaming addiction and sleep quality, respectively. Pearson correlation analysis was used to evaluate the relationship between brain regions with altered sReHo and dReHo and IAT and PSQI scores. Receiver operating characteristic (ROC) curve analysis was used to reveal the potential capacity of the sReHo and dReHo metrics to distinguish IGDs from HCs. RESULTS: Compared with HCs, IGDs showed both increased static and dynamic intrinsic local connectivity in bilateral medial superior frontal gyrus (mSFG), superior frontal gyrus (SFG), and supplementary motor area (SMA). Increased dReHo in the left putamen, pallidum, caudate nucleus and bilateral thalamus were also observed. ROC curve analysis showed that the brain regions with altered sReHo and dReHo could distinguish individuals with IGD from HCs. Moreover, the sReHo values in the left mSFG and SMA as well as dReHo values in the left SMA were positively correlated with IAT scores. The dReHo values in the left caudate nucleus were negatively correlated with PSQI scores. CONCLUSIONS: These results showed impaired intrinsic local connectivity in frontostriatothalamic circuitry in individuals with IGD, which may provide new insights into the underlying neuropathological mechanisms of IGD. Besides, dynamic changes of intrinsic local connectivity in caudate nucleus may be a potential neurobiological marker linking IGD and sleep quality.

Increased spontaneous activity of the superior frontal gyrus with reduced functional connectivity to visual attention areas and cerebellum in male smokers.

Background: Chronic smokers have abnormal spontaneous regional activity and disrupted functional connectivity as revealed by previous neuroimaging studies. Combining different dimensions of resting-state functional indicators may help us learn more about the neuropathological mechanisms of smoking. Methods: The amplitude of low frequency fluctuations (ALFF) of 86 male smokers and 56 male non-smokers were first calculated. Brain regions that displayed significant differences in ALFF between two groups were selected as seeds for further functional connectivity analysis. Besides, we examined correlations between brain areas with abnormal activity and smoking measurements. Results: Increased ALFF in left superior frontal gyrus (SFG), left medial superior frontal gyrus (mSFG) and middle frontal gyrus (MFG) as well as decreased ALFF in right calcarine sulcus were observed in smokers compared with non-smokers. In the seed-based functional connectivity analysis, smokers showed attenuated functional connectivity with left SFG in left precuneus, left fusiform gyrus, left lingual gyrus, left cerebellum 4 5 and cerebellum 6 as well as lower functional connectivity with left mSGF in left fusiform gyrus, left lingual gyrus, left parahippocampal gyrus (PHG), left calcarine sulcus, left cerebellum 4 5, cerebellum 6 and cerebellum 8 (GRF corrected, Pvoxel < 0.005, Pcluster<0.05). Furthermore, attenuated functional connectivity with left mSGF in left lingual gyrus and PHG displayed a negative correlation with FTND scores (r = -0.308, p = 0.004; r = -0.326, p = 0.002 Bonferroni corrected). Conclusion: Our findings of increased ALFF in SFG with reduced functional connectivity to visual attention areas and cerebellum subregions may shed new light on the pathophysiology of smoking.

White matter microstructural abnormalities and gray matter volume alterations in obsessive-compulsive disorder: A coordinate-based meta-analysis.

OBJECTIVE: A comprehensive meta-analysis using correlated coordinate data to explore abnormalities in white matter (WM) microarchitecture and changes in gray matter volume (GMV) in patients with obsessive-compulsive disorder (OCD). METHODS: We reviewed 23 reported studies of diffusion tensor imaging (DTI) in OCD patients. The differences in WM fractional anisotropy (FA) between OCD patients and healthy controls (HCs) were investigated using tract-based spatial statistics (TBSS) and voxel-based analysis (VBA), respectively, and the results of the two methods were compared. In addition, we will explore changes in OCD GMV by analyzing studies (n = 21) using the voxel-based morphometry (VBM) approach and comparing the difference between adults and adolescents. RESULTS: In the pooled meta-analysis, WM study results presented that compared with HCs, OCD patients had higher FA in right lenticular nucleus (putamen), and lower FA in corpus callosum (CC), left insula, right cerebellum (hemispheric lobule), right gyrus rectal and left inferior parietal gyri. However, in subgroup analysis, there was a significant difference in FA changes between TBSS and VBA in OCD patients compared with HCs. In addition, we found that the GMV of OCD patients was significantly increased in left striatum and left precentral gyrus, and significantly decreased in right inferior frontal gyrus triangular part, right superior temporal gyrus and right hippocampus. Compared with adolescents, adult patients have increased GMV in left lenticular nucleus putamen. CONCLUSION: The meta-analysis showed that OCD patients had abnormal WM microarchitecture and altered GMV. These changes may be closely related to the pathophysiological mechanism of the disease.

Meta-Analysis of Structural and Functional Brain Abnormalities in Cocaine Addiction.

Background: Previous voxel-based morphometric (VBM) and functional magnetic resonance imaging (fMRI) studies have shown changes in brain structure and function in cocaine addiction (CD) patients compared to healthy controls (HC). However, the results of these studies are poorly reproducible, and it is unclear whether there are common and specific neuroimaging changes. This meta-analysis study aimed to identify structural, functional, and multimodal abnormalities in CD patients. Methods: The PubMed database was searched for VBM and task-state fMRI studies performed in CD patients between January 1, 2010, and December 31, 2021, using the SEED-BASE d MAP software package to perform two independent meta-groups of functional neural activation and gray matter volume, respectively. Analysis, followed by multimodal analysis to uncover structural, functional, and multimodal abnormalities between CD and HC. Results: The meta-analysis included 14 CD fMRI studies (400 CD patients and 387 HCs) and 11 CD VBM studies (368 CD patients and 387 controls). Structurally, VBM analysis revealed significantly lower gray matter volumes in the right superior temporal gyrus, right insula, and right retrocentral gyrus than in the HC. On the other hand, the right inferior parietal gyrus increased in gray matter (GM) volume in CD patients. Functionally, fMRI analysis revealed activation in the right temporal pole, right insula, and right parahippocampal gyrus. In the right inferior parietal gyrus, the left inferior parietal gyrus, the left middle occipital gyrus, and the right middle frontal gyrus, the degree of activation was lower. Conclusion: This meta-analysis showed that CD patients had significant brain GM and neural changes compared with normal controls. Furthermore, multi-domain assessments capture different aspects of neuronal alterations in CD, which may help develop effective interventions for specific functions.

LINC00514 promotes lipogenesis and tumor progression in esophageal squamous cell carcinoma by sponging miR­378a­5p to enhance SPHK1 expression.

Increasing evidence has demonstrated that long non­coding RNAs serve pivotal roles in tumor development, progression, metastasis and metabolism. However, to the best of our knowledge, the roles and molecular mechanisms of long intergenic nonprotein­coding RNA 00514 (LINC00514) in esophageal squamous cell carcinoma (ESCC) remain unknown. The present study found that LINC00514 and sphingosine kinase 1 (SPHK1) were both upregulated in ESCC tissues and cells, and their high expression levels were closely associated with Tumor­Node­Metastasis stage, lymph node metastasis and poor prognosis of patients with ESCC. Functionally, knockdown of LINC00514 inhibited cell proliferation and invasion, and led to the downregulation of lipogenesis­related proteins, including SPHK1, fatty acid synthase, acetyl­coenzyme (Co)A carboxylase α and stearoyl­CoA desaturase 1, whereas LINC00514 overexpression promoted cell proliferation and invasion in ESCC KYSE150 and KYSE30 cells, and upregulated expression of lipogenesis­related proteins. Mechanistically, LINC00514 functioned as a competing endogenous RNA by sponging microRNA (miR)­378a­5p, resulting in the upregulation of SPHK1, which was accompanied by the activation of lipogenesis­related pathways, to promote ESCC cell proliferation and invasion. Taken together, these findings suggest that LINC00514 may participate in ESCC lipogenesis, and targeting the LINC00514/miR­378a­5p/SPHK1 signaling axis may be a novel and promising therapeutic strategy for management of patients with ESCC.

Long non-coding RNA SLC2A1-AS1 induced by GLI3 promotes aerobic glycolysis and progression in esophageal squamous cell carcinoma by sponging miR-378a-3p to enhance Glut1 expression.

BACKGROUND: Emerging evidence demonstrates that lncRNAs play pivotal roles in tumor energy metabolism; however, the detailed mechanisms of lncRNAs in the regulation of tumor glycolysis remain largely unknown. METHODS: The expression of SLC2A1-AS1 was investigated by TCGA, GEO dataset and qRT-PCR. The binding of GLI3 to SLC2A1-AS1 promoter was detected by Luciferase Reporter Assay System and Ago2-RIP assay. FISH was performed to determine the localization of SLC2A1-AS1 in ESCC cells. Double Luciferase Report assay was used to investigate the interaction of miR-378a-3p with SLC2A1-AS1 and Glut1. Gain-of-function and Loss-of-function assay were performed to dissect the function of SLC2A1-AS1/miR-378a-3p/Glut1 axis in ESCC progression in vitro and in vivo. RESULTS: We identified a novel lncRNA SLC2A1-AS1 in ESCC. SLC2A1-AS1 was frequently overexpressed in ESCC tissues and cells, and its overexpression was associated with TNM stage, lymph node metastasis and poor prognosis of ESCC patients. Importantly, GLI3 and SLC2A1-AS1 formed a regulatory feedback loop in ESCC cells. SLC2A1-AS1 promoted cell growth in vitro and in vivo, migration and invasion, and suppressed apoptosis, leading to EMT progression and increased glycolysis in ESCC cells. SLC2A1-AS1 functioned as ceRNA for sponging miR-378a-3p, resulting in Glut1 overexpression in ESCC cells. MiR-378a-3p inhibited cell proliferation and invasion as well as induced apoptosis, resulting in reduced glycolysis, which was partly reversed by SLC2A1-AS1 or Glut1 overexpression in ESCC cells. CONCLUSION: SLC2A1-AS1 plays important roles in ESCC development and progression by regulating glycolysis, and SLC2A1-AS1/miR-378a-3p/Glut1 regulatory axis may be a novel therapeutic target in terms of metabolic remodeling of ESCC patients.