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.

Nicotine addiction and overweight affect intrinsic neural activity and neurotransmitter activity: A fMRI study of interaction effects.

BACKGROUND: Nicotine addiction and overweight often co-exist, but the neurobiological mechanism of their co-morbidity remains to be clarified. In this study, we explore how nicotine addiction and overweight affect intrinsic neural activity and neurotransmitter activity. METHODS: This study included 54 overweight people and 54 age-, sex-, and handedness-matched normal-weight individuals, who were further divided into four groups based on nicotine addiction. We used a two-way factorial design to compare intrinsic neural activity (calculated by the fALFF method) in four groups based on resting-state functional magnetic resonance images (rs-fMRI). Furthermore, the correlation between fALFF values and PET- and SPECT-derived maps to examine specific neurotransmitter system changes underlying nicotine addiction and overweight. RESULTS: Nicotine addiction and overweight affect intrinsic neural activity by themselves. In combination, they showed antagonistic effects in the interactive brain regions (left insula and right precuneus). Cross-modal correlations displayed that intrinsic neural activity changes in the interactive brain regions were related to the noradrenaline system (NAT). CONCLUSION: Due to the existence of interaction, nicotine partially restored the changes of spontaneous activity in the interactive brain regions of overweight people. Therefore, when studying one factor alone, the other should be used as a control variable. Besides, this work links the noradrenaline system with intrinsic neural activity in overweight nicotine addicts. By examining the interactions between nicotine addiction and overweight from neuroimaging and molecular perspectives, this study provides some ideas for the treatment of both co-morbidities.

Integrative brain structural and molecular analyses of interaction between tobacco use disorder and overweight among male adults.

Tobacco smoking and overweight lead to adverse health effects, which remain an important public health problem worldwide. Researches indicate overlapping pathophysiology may contribute to tobacco use disorder (TUD) and overweight, but the neurobiological interaction mechanism between the two factors is still unclear. This study used a mixed sample design, including the following four groups: (i) overweight long-term smokers (n = 24, age = 31.80 ± 5.70, cigarettes/day = 20.50 ± 7.89); (ii) normal weight smokers (n = 28, age = 31.29 ± 5.56, cigarettes/day = 16.11 ± 8.35); (iii) overweight nonsmokers (n = 19, age = 33.05 ± 5.60), and (iv) normal weight nonsmokers (n = 28, age = 31.68 ± 6.57), a total of 99 male subjects. All subjects underwent T1-weighted high-resolution MRI. We used voxel-based morphometry to compare gray matter volume (GMV) among the four groups. Then, JuSpace toolbox was used for cross-modal correlations of MRI-based modalities with nuclear imaging derived estimates, to examine specific neurotransmitter system changes underlying the two factors. Our results illustrate a significant antagonistic interaction between TUD and weight status in left dorsolateral prefrontal cortex (DLPFC), and a quadratic effect of BMI on DLPFC GMV. For main effect of TUD, long-term smokers were associated with greater GMV in bilateral OFC compared with nonsmokers irrespective of weight status, and such alteration is negatively associated with pack-year and FTND scores. Furthermore, we also found GMV changes related to TUD and overweight are associated with µ-opioid receptor system and TUD-related GMV alterations are associated with noradrenaline transporter maps. This study sheds light on novel multimodal neuromechanistic about the relationship between TUD and overweight, which possibly provides hints into future treatment for the special population of comorbid TUD and overweight.

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.

Explore the effects of overweight and smoking on spontaneous brain activity: Independent and reverse.

Accumulating evidence suggested that overweight and smoking often co-exist. However, current neuroimaging researches have almost always studied smoking or overweight status separately. Here we sought to investigate the neurobiological mechanisms of this comorbid association, by detecting spontaneous brain activity changes associated with smoking and weight status separately and collectively. We used 2 × 2 factorial design and included the following four groups: overweight/normal-weight smokers (n = 34/n = 30) and overweight/normal-weight non-smokers (n = 22/n = 24). The spontaneous brain activity among the four groups was comparable using an amplitude of low-frequency fluctuation (ALFF) method based on resting-state fMRI (rs-fMRI). Furthermore, correlation analyses between brain activity changes, smoking severity and BMI values were performed. A main effect of smoking was discovered in the default mode network (DMN) and visual network related brain regions. Moreover, overweight people had high ALFF value in the brain regions associated with reward and executive control. More importantly, smoking and overweight both affected brain activity of the middle temporal gyrus (MTG), but the effect was opposite. And the brain activity of MTG was negatively correlated with smoking years, pack year and BMI value. These results suggest that smoking and overweight not only affect spontaneous brain activity alone, but also paradoxically affect spontaneous brain activity in the MTG. This suggests that we need to control for weight as a variable when studying spontaneous brain activity in smokers. Besides, this interaction may provide a neurological explanation for the comorbidity of overweight and smoking and a target for the treatment of comorbid populations.

Abnormal resting-state effective connectivity in reward network among long-term male smokers.

BACKGROUND: Tobacco addiction is a chronic, relapsing mental disorder characterized by compulsive tobacco seeking and smoking. Current evidence shows that tobacco addiction exerts their initial reinforcing effects by activating reward circuits in the brain, but the causal connectivity among reward circuits is still unclear. Therefore, it is vital to understand how the reward network works to lead to the compulsive smoking behaviour. METHOD: We applied dynamic causal modelling (DCM) to resting-state functional magnetic resonance (rs-fMRI) to characterize changes in effective connectivity (EC) among eight major hubs from reward network between 76 long-term male smokers and 55 nonsmoking volunteers (matched with age, gender and education). RESULTS: Relative to the healthy controls, long-term smokers had stronger ECs from the right anterior insula to left ventral striatum, posterior cingulate cortex (PCC) to ventral tegmental area (VTA), PCC to left anterior insula, left anterior insula to VTA, and ventromedial prefrontal cortex (vmPFC) to PCC and weaker ECs from the VTA to left ventral striatum, right anterior insula to right ventral striatum, and anterior cingulate cortex (ACC) to right anterior insula. CONCLUSIONS: Overall, our findings revealed disrupted neural causal interactions among parts of the reward network associated with tobacco addiction, expanding the growing evidence for the potential neurobiological mechanisms of tobacco addiction. We found abnormalities within the mesocorticolimbic system and a top-down regulation disorder in the dopamine-dependent process of response inhibition and salience attribution among long-term smokers, which may facilitate the development of effective therapies in tobacco addiction.

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.

Weight Status Modulated Brain Regional Homogeneity in Long-Term Male Smokers.

Background: Tobacco smoking and being overweight could lead to adverse health effects, which remain an important public health problem worldwide. Research indicates that overlapping pathophysiology may contribute to tobacco addiction and being overweight, but the neurobiological interaction mechanism between the two factors is still unclear. Methods: The current study used a mixed sample design, including the following four groups: (i) overweight long-term smokers (n = 24); (ii) normal-weight smokers (n = 28); (iii) overweight non-smokers (n = 19), and (iv) normal-weight non-smokers (n = 28), for a total of 89 male subjects. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI). Regional homogeneity (ReHo) was used to compare internal cerebral activity among the four groups. Interaction effects between tobacco addiction and weight status on ReHo were detected using a two-way analysis of variance, correcting for age, years of education, and head motion. Results: A significant interaction effect between tobacco addiction and weight status is shown in right superior frontal gyrus. Correlation analyses show that the strengthened ReHo value in the right superior frontal gyrus is positively associated with pack-year. Besides, the main effect of tobacco addiction is specially observed in the occipital lobe and cerebellum posterior lobe. As for the main effect of weight status, the right lentiform nucleus, left postcentral gyrus, and brain regions involved in default mode network (DMN) survived. Conclusions: These results shed light on an antagonistic interaction on brain ReHo between tobacco addiction and weight status in the right superior frontal gyrus, which may be a clinical neuro-marker of comorbid tobacco addiction and overweight. Our findings may provide a potential target to develop effective treatments for the unique population of comorbid tobacco addiction and overweight people.

Alternations in Dynamic and Static Functional Connectivity Density in Chronic Smokers.

Previous studies have implicated abnormal functional coordination in brain regions of smokers. Neuroimaging studies demonstrated alternations in brain connectivity by using the resting-state functional connectivity (rsFC) method which arbitrarily chooses specific networks or seed regions as priori selections and cannot provide a full picture of the FC changes in chronic smokers. The aim of this study was to investigate the whole-brain functional coordination measured by functional connectivity density (FCD). As the variance of brain activity, dynamic FCD (dFCD) was performed to investigate dynamic changes of whole-brain integration in chronic smokers. In total, 120 chronic smokers and 56 nonsmokers were recruited, and static FCD and dFCD were performed to investigate aberrance of whole-brain functional coordination. Shared aberrance in visual areas has been found in both static and dFCD study in chronic smokers. Furthermore, the results exhibited that both heavy and light smokers demonstrated decreased dFCD in the visual cortex and left precuneus, and also increased dFCD in the right orbitofrontal cortex, left caudate, right putamen, and left thalamus compared with nonsmokers. In addition, alternations of dFCD have been found between heavy and light smokers. Furthermore, the dFCD variations showed significant positive correlation with smoking-related behaviors. The results demonstrated that chronic smokers not only have some initial areas, but also have some regions associated with severity of cigarette smoking. Lastly, dFCD could provide more subtle variations in chronic smokers, and the combination of static and dFCD may deepen our understanding of the brain alternations in chronic smokers.

Meta-analysis of structural and functional brain alterations in internet gaming disorder.

Background: Many neuroimaging studies have reported abnormalities in brain structure and function in internet gaming disorder (IGD). However, the findings were divergent. We aimed to provide evidence-based evidence of structural and functional changes in IGD by conducting a meta-analysis integrating these studies quantitatively. Method: A systematic search was conducted in PubMed, ScienceDirect, Web of Science, and Scopus from January 1, 2010 to October 31, 2021, to identify eligible voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies. Brain alternations between IGD subjects and healthy controls (HCs) were compared using the anisotropic seed-based d mapping (AES-SDM) meta-analytic method. Meta-regression analysis was used to investigate the relationship between gray matter volume (GMV) alterations and addiction-related clinical features. Results: The meta-analysis contained 15 VBM studies (422 IGD patients and 354 HCs) and 30 task-state fMRI studies (617 IGD patients and 550 HCs). Compared with HCs, IGD subjects showed: (1) reduced GMV in the bilateral anterior/median cingulate cortex, superior/inferior frontal gyrus and supplementary motor area; (2) hyperactivation in the bilateral inferior frontal gyrus, precentral gyrus, left precuneus, right inferior temporal gyrus and right fusiform; (3) hypoactivation in the bilateral lingual and the left middle frontal gyrus; and (4) both decreased GMV and increased activation in the left anterior cingulate. Furthermore, Meta-regression revealed that GMV reduction in left anterior cingulate were positively correlated with BIS-11 score [r = 0.725, p = 0.012(uncorrected)] and IAT score [r = 0.761, p = 0.017(uncorrected)]. Conclusion: This meta-analysis showed structural and functional impairments in brain regions related to executive control, cognitive function and reward-based decision making in IGD. Furthermore, multi-domain assessments captured different aspects of neuronal changes in IGD, which may help develop effective interventions as potential therapeutic targets.

Meta-analysis of structural and functional alterations of brain in patients with attention-deficit/hyperactivity disorder.

Background: A large and growing body of neuroimaging research has concentrated on patients with attention-deficit/hyperactivity disorder (ADHD), but with inconsistent conclusions. This article was intended to investigate the common and certain neural alterations in the structure and function of the brain in patients with ADHD and further explore the differences in brain alterations between adults and children with ADHD. Methods: We conducted an extensive literature search of whole-brain voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies associated with ADHD. Two separate meta-analyses with the seed-based d mapping software package for functional neural activation and gray matter volume (GMV) were carried out, followed by a joint analysis and a subgroup analysis. Results: This analysis included 29 VBM studies and 36 fMRI studies. Structurally, VBM analysis showed that the largest GMV diminutions in patients with ADHD were in several frontal-parietal brain regions, the limbic system, and the corpus callosum. Functionally, fMRI analysis discovered significant hypoactivation in several frontal-temporal brain regions, the right postcentral gyrus, the left insula, and the corpus callosum. Conclusion: This study showed that abnormal alterations in the structure and function of the left superior frontal gyrus and the corpus callosum may be the key brain regions involved in the pathogenesis of ADHD in patients and may be employed as an imaging metric for patients with ADHD pending future research. In addition, this meta-analysis discovered neuroanatomical or functional abnormalities in other brain regions in patients with ADHD as well as findings that can be utilized to guide future research.

Dynamic Altered Amplitude of Low-Frequency Fluctuations in Patients With Major Depressive Disorder.

Background: Major depressive disorder (MDD) has demonstrated abnormalities of static intrinsic brain activity measured by amplitude of low-frequency fluctuation (ALFF). Recent studies regarding the resting-state functional magnetic resonance imaging (rs-fMRI) have found the brain activity is inherently dynamic over time. Little is known, however, regarding the temporal dynamics of local neural activity in MDD. Here, we investigated whether temporal dynamic changes in spontaneous neural activity are influenced by MDD. Methods: We recruited 81 first-episode, drug-naive MDD patients and 64 age-, gender-, and education-matched healthy controls who underwent rs-fMRI. A sliding-window approach was then adopted for the estimation of dynamic ALFF (dALFF), which was used to measure time-varying brain activity and then compared between the two groups. The relationship between altered dALFF variability and clinical variables in MDD patients was also analyzed. Results: MDD patients showed increased temporal variability (dALFF) mainly focused on the bilateral thalamus, the bilateral superior frontal gyrus, the right middle frontal gyrus, the bilateral cerebellum posterior lobe, and the vermis. Furthermore, increased dALFF variability values in the right thalamus and right cerebellum posterior lobe were positively correlated with MDD symptom severity. Conclusions: The overall results suggest that altered temporal variability in corticocerebellar-thalamic-cortical circuit (CCTCC), involved in emotional, executive, and cognitive, is associated with drug-naive, first-episode MDD patients. Moreover, our study highlights the vital role of abnormal dynamic brain activity in the cerebellar hemisphere associated with CCTCC in MDD patients. These findings may provide novel insights into the pathophysiological mechanisms of MDD.

Shared gray matter alterations in subtypes of addiction: a voxel-wise meta-analysis.

BACKGROUND: Numerous studies based on voxel-based morphometry (VBM) have revealed gray matter (GM) alterations in multiple brain regions for addiction. However, findings are poorly replicated, and it remains elusive whether distinct diagnoses of addiction are underpinned by shared abnormalities. Our aim was to conduct a quantitative meta-analysis of structural neuroimaging studies investigating GM abnormalities in two main categories of addiction: substance use disorders (SUD) and behavioral addictions (BA). METHOD: A systematic database search was conducted in several databases from Jan 1, 2010, to Oct 23, 2020, to identify eligible VBM studies. Meta-analysis was performed with the seed-based d mapping software package to compare alternations between individuals with addiction-related disorders and healthy controls (HC). RESULTS: A total of 59 VBM studies including 2096 individuals with addiction-related disorders and 2637 HC met the inclusion criteria. Individuals with addiction-related disorders showed shared GM volume decrease in bilateral prefrontal cortex, bilateral insula, bilateral rolandic operculum, left superior temporal gyrus, and right Heschl gyrus and GM increase in right lingual gyrus and right fusiform gyrus comparing with HC (p < 0.005). Subgroup analysis found heterogeneity between SUD and BA mainly in left inferior occipital gyrus and right striatum (p < 0.005). Meta-regression revealed that GM atrophy in right anterior cingulate (r = 0.541, p = 0.03 (uncorrected)) and left inferior frontal gyrus (r = 0.595, p = 0.015) were positively correlated with higher impulsivity. CONCLUSIONS: This meta-analysis identified a concordance across subtypes of addiction in terms of the brain structural changes in prefrontal and insula areas, which may relate to higher impulsivity observed across addiction diagnoses. This concordance provides an organizing model that emphasizes the importance of shared neural substrates in addiction.

Reduced Brain Gray Matter Volume in Patients With First-Episode Major Depressive Disorder: A Quantitative Meta-Analysis.

Background: The findings of many neuroimaging studies in patients with first-episode major depressive disorder (MDD), and even those of previous meta-analysis, are divergent. To quantitatively integrate these studies, we performed a meta-analysis of gray matter volumes using voxel-based morphometry (VBM). Methods: We performed a comprehensive literature search for relevant studies and traced the references up to May 1, 2021 to select the VBM studies between first-episode MDD and healthy controls (HC). A quantitative meta-analysis of VBM studies on first-episode MDD was performed using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) method, which allows a familywise error rate (FWE) correction for multiple comparisons of the results. Meta-regression was used to explore the effects of demographics and clinical characteristics. Results: Nineteen studies, with 22 datasets comprising 619 first-episode MDD and 707 HC, were included. The pooled and subgroup meta-analysis showed robust gray matter reductions in the left insula, the bilateral parahippocampal gyrus extending into the bilateral hippocampus, the right gyrus rectus extending into the right striatum, the right superior frontal gyrus (dorsolateral part), the left superior frontal gyrus (medial part) and the left superior parietal gyrus. Meta-regression analyses showed that higher HDRS scores were significantly more likely to present reduced gray matter volumes in the right amygdala, and the mean age of MDD patients in each study was negatively correlated with reduced gray matter in the left insula. Conclusions: The present meta-analysis revealed that structural abnormalities in the fronto-striatal-limbic and fronto-parietal networks are essential characteristics in first-episode MDD patients, which may become a potential target for clinical intervention.

Structural and Functional Brain Abnormalities in Internet Gaming Disorder and Attention-Deficit/Hyperactivity Disorder: A Comparative Meta-Analysis.

Background: Patients with Internet gaming disorder (IGD) and attention-deficit/hyperactivity disorder (ADHD) have high comorbidity but it is still unknown whether these disorders have shared and distinctive neuroimage alterations. Objective: The aim of this meta-analysis was to identify shared and disorder-specific structural, functional, and multimodal abnormalities between IGD and ADHD. Methods: A systematic literature search was conducted for whole-brain voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies comparing people with IGD or ADHD with healthy controls. Regional gray matter volume (GMV) and fMRI differences were compared over the patient groups and then a quantitative comparison was performed to find abnormalities (relative to controls) between IGD and ADHD using seed-based d mapping meta-analytic methods. Result: The meta-analysis contained 14 IGD VBM studies (contrasts covering 333 IGDs and 335 HCs), 26 ADHD VBM studies (1,051 patients with ADHD and 887 controls), 30 IGD fMRI studies (603 patients with IGD and 564 controls), and 29 ADHD fMRI studies (878 patients with ADHD and 803 controls). Structurally, VBM analysis showed disorder-specific GMV abnormality in the putamen among IGD subjects and orbitofrontal cortex in ADHD and shared GMV in the prefrontal cortex. Functionally, fMRI analysis discovered that IGD-differentiating increased activation in the precuneus and shared abnormal activation in anterior cingulate cortex, insular, and striatum. Conclusion: IGD and ADHD have shared and special structural and functional alterations. IGD has disorder-differentiating structural alterations in the putamen and ADHD has alterations in the orbitofrontal cortex. Disorder-differentiating fMRI activations were predominantly observed in the precuneus among IGD subjects and shared impairing function connection was in the rewards circuit (including ACC, OFC, and striatum).

More than just statics: Temporal dynamic changes of intrinsic brain activity in cigarette smoking.

Smoking is companied with altered intrinsic activity of the brain measured by amplitude of low-frequency fluctuation. Evidence has revealed that human brain activity is a highly dynamic and rapidly changing system. How exactly cigarette smoking affect temporal dynamic intrinsic brain activity is not fully understood nor is it clear how smoking severity influences spontaneous brain activity. Dynamic amplitude of low-frequency fluctuation (dALFF) was used to examine the dynamic temporal variability in 93 participants (63 smokers, 30 nonsmokers). We further divided smokers into light and heavy smokers. The temporal variability in intrinsic brain activity among these groups was compared. Correlation analyses were performed between dALFF in areas showing group differences and smoking behaviour (e.g., the Fagerström Test for Nicotine Dependence [FTND] scores and pack-years). Smokers showed significantly increased dALFF in the left inferior/middle frontal gyrus, right orbitofrontal gyrus, right insula, left superior/medial frontal gyrus and right middle frontal gyrus than nonsmokers. Light smokers showed increased dALFF variability in the left prefrontal cortex. Heavy smokers showed increased dynamics in specific brain regions, including the right postcentral gyrus, right insula and left precentral gyrus. Furthermore, the temporal variability in dALFF in the left superior/medial frontal gyrus, left superior/middle frontal gyrus, right middle frontal gyrus and right insula was positively correlated with pack-years or FTND. Combined, these results suggest that smokers increase stable and persistent spontaneous brain activity in prefrontal cortex, involved impaired gold-directed action and value-based decision-making. In addition, individuals with heavier smoking severity show increased perturbance on spontaneous brain activity of perception and sensorimotor, related to increased reliance.

The stage-specifically accelerated brain aging in never-treated first-episode patients with depression.

Depression associated with structural brain abnormalities is hypothesized to be related with accelerated brain aging. However, there is far from a unified conclusion because of clinical variations such as medication status, cumulative illness burden. To explore whether brain age is accelerated in never-treated first-episode patients with depression and its association with clinical characteristics, we constructed a prediction model where gray matter volumes measured by voxel-based morphometry derived from T1-weighted MRI scans were treated as features. The prediction model was first validated using healthy controls (HCs) in two Chinese Han datasets (Dataset 1, N = 130 for HCs and N = 195 for patients with depression; Dataset 2, N = 270 for HCs) separately or jointly, then the trained prediction model using HCs (N = 400) was applied to never-treated first-episode patients with depression (N = 195). The brain-predicted age difference (brain-PAD) scores defined as the difference between predicted brain age and chronological age, were calculated for all participants and compared between patients with age-, gender-, educational level-matched HCs in Dataset 1. Overall, patients presented higher brain-PAD scores suggesting patients with depression having an "older" brain than expected. More specially, this difference occurred at illness onset (illness duration <3 months) and following 2 years then disappeared as the illness further advanced (>2 years) in patients. This phenomenon was verified by another data-driven method and significant correlation between brain-PAD scores and illness duration in patients. Our results reveal that accelerated brain aging occurs at illness onset and suggest it is a stage-dependent phenomenon in depression.

Meta-analysis of brain gray matter changes in chronic smokers.

BACKGROUND: Previous studies based on voxel-based morphometry (VBM) had revealed brain gray matter (GM) changes in chronic smokers relative to nonsmokers. However, not all studies reported entirely consistent findings, or even opposite. The aim of this study was to conduct a quantitative meta-analysis of VBM studies of chronic smokers. METHOD: A systematic database search was conducted in PubMed and Web of Knowledge from January 1, 2000 to January 31, 2020 to identify eligible VBM studies. Meta-analysis was performed with the Seed-based d Mapping software package to compare alternations between chronic cigarette smokers and nonsmokers. In addition, meta-regression analysis were performed to examine the influences of cigarette per day, smoking history and FTND. RESULTS: A total of 17 VBM studies including 905 smokers and 1344 nonsmokers met the inclusion criteria. The results of this meta-analysis showed that the chronic smokers showed a robust GM volume decrease in bilateral prefrontal cortex and left insular and a GM increase in the right lingual cortex and left occipital cortex. Moreover, meta-regression analysis showed that cigarette per day, smoking history and FTND were partly associated with GM changes in chronic smokers. CONCLUSIONS: This meta-analysis indicated that chronic cigarette smokers had significant and robust brain GM alternations compared with nonsmokers. Longitudinal studies should be performed in the future to explore whether these brain regions could be used as potential therapeutic neuro-target for nicotine dependence.