Age-atypical brain functional networks in autism spectrum disorder: a normative modeling approach.

BACKGROUND: Despite extensive research into the neural basis of autism spectrum disorder (ASD), the presence of substantial biological and clinical heterogeneity among diagnosed individuals remains a major barrier. Commonly used case‒control designs assume homogeneity among subjects, which limits their ability to identify biological heterogeneity, while normative modeling pinpoints deviations from typical functional network development at individual level. METHODS: Using a world-wide multi-site database known as Autism Brain Imaging Data Exchange, we analyzed individuals with ASD and typically developed (TD) controls (total n = 1218) aged 5-40 years, generating individualized whole-brain network functional connectivity (FC) maps of age-related atypicality in ASD. We then used local polynomial regression to estimate a networkwise normative model of development and explored correlations between ASD symptoms and brain networks. RESULTS: We identified a subset exhibiting highly atypical individual-level FC, exceeding 2 standard deviation from the normative value. We also identified clinically relevant networks (mainly default mode network) at cohort level, since the outlier rates decreased with age in TD participants, but increased in those with autism. Moreover, deviations were linked to severity of repetitive behaviors and social communication symptoms. CONCLUSIONS: Individuals with ASD exhibit distinct, highly individualized trajectories of brain functional network development. In addition, distinct developmental trajectories were observed among ASD and TD individuals, suggesting that it may be challenging to identify true differences in network characteristics by comparing young children with ASD to their TD peers. This study enhances understanding of the biological heterogeneity of the disorder and can inform precision medicine.

Histochemical studies on the distribution and accumulation of trans-polyisoprene in the rubber-producing plant Eucommia ulmoides.

Eucommia ulmoides rubber (EUR) is a high-quality natural rubber resource, which can be extracted from different organs of the Eucommia ulmoides tree. In this study, EUR was isolated from the leaves, barks, and pericarps, and the structural characteristics and physicochemical properties of EUR were systematically determined. The accumulation and distribution of EUR in different tissues were assessed through in situ observations combined with cellular and subcellular scales. The preliminary analyses indicated that the variations in the physicochemical properties of EUR across different tissues were associated with its accumulation microstructure. Further analyses by SEM and TEM showed that the initial cell differentiation and fusion resulted in the formation of tubular structures without any nucleus. A limited number of rubber particles were generated within the cytoplasm, concurrent with aggregation and fusion. Eventually, rubber particles filled the entire cytoplasm, and organelles disappeared to form highly aggregated filamentous structures. In addition, the number and area of EUR-containing cells were closely related to the organization sizes of barks and leaves. This study provided valuable insights into Eucommia ulmoides histology and the rubber industry.

Mindfulness Meditation Training Reduces Gaming Cravings by Reshaping the Functional Connectivity Between the Default Mode Network and Executive Control-Related Brain Regions.

BACKGROUND: Internet gaming disorder (IGD) can lead to psychological problems and cause behavioral problems in individuals. Traditional interventions have been ineffective in treating IGD. Meanwhile, mindfulness meditation (MM) is an emerging method that has proven to be effective for treating psychiatric disorders. In this study, MM was used to intervene in IGD and to explore its neural mechanism. METHODS: Eighty participants were recruited through advertisements. Eventually, 61 completed the 1-month training (MM group, n = 31; progressive muscle relaxation [PMR] group, n = 30), including a pretest, 8 training sessions, and a posttest. Regional homogeneity and degree centrality were calculated, and the tests (pre- and post-) and group (MM and PMR) analysis of variance was performed. The overlapping results were obtained as region of interest for functional connectivity (FC) analyses. Behavioral data and neurotransmitter availability maps were correlated with FC. RESULTS: Compared with PMR, MM decreased the severity of addiction and game craving in IGD. Brain imaging results showed that the FC between and within the executive control and default mode networks/reward-related regions were enhanced. Significant negative correlations were observed between FC and dopamine receptor D2, dopamine transporter, and vesicular acetylcholine transporter. Significant positive correlations were observed between FCs and serotonin and aminobutyric acid receptors. CONCLUSIONS: This study confirmed the effectiveness of MM in treating IGD. MM altered the default mode and enhanced top-down control over game cravings. These findings were revealed by the correlations between brain regions and behavioral and biochemical effects. The results show the neural mechanism of MM in reducing IGD and lay the foundation for future research.

Influenza a Neuraminidase-Based Bivalent mRNA Vaccine Induces Th1-Type Immune Response and Provides Protective Effects in Mice.

Vaccines are one of the most effective means of preventing influenza A, typically containing the hemagglutinin (HA) of the influenza A virus. However, antigenic drift and shift of the influenza A virus can lead to instability in vaccine efficacy. Compared to HA, the antigenic variation rate of neuraminidase (NA) is slower. In traditional inactivated influenza vaccines, although they contain a certain amount of NA, there are significant differences between different batches, which cannot consistently induce NA-based immune responses. Therefore, NA is often overlooked in vaccine development. In this study, we report an mRNA vaccine encoding the NA of two strains of influenza A virus. The experimental results demonstrated that when matched with the viral strain, this mRNA vaccine induced high levels of neutralizing antibodies, providing a protective effect to mice in viral challenge experiments, and this immune response was shown to be biased towards the Th1 type. In summary, this study demonstrates that NA is a promising potential antigen, providing new insights for the development of influenza A virus vaccines.

RNA-binding protein QKI promotes the progression of HCC by interacting with long non-coding RNA EGOT.

BACKGROUND: RNA-binding proteins are revealed to play important roles during the progression of hepatocellular carcinoma (HCC). However, the regulatory mechanisms of RNA-binding protein Quaking (QKI) in the expression and role of long non-coding RNAs (lncRNAs) in HCC cells remain not well understood. METHODS: Cell Counting Kit-8, wound-healing, Transwell and colony-forming assays were performed to evaluate the effects of QKI and lncRNA EGOT on proliferation and migration of HCC cells. Tumor growth of HCC was analyzed using a mouse xenograft model. Immunoprecipitation (RIP) assay was used to investigate the interaction between QKI and EGOT. RESULTS: The expression of QKI was significantly upregulated in HCC tissues and the higher QKI level was significantly associated with a poorer prognosis. Overexpression of QKI promoted the proliferation, migration, and colony-forming ability of HCC cells in vitro and tumor growth of HCC in vivo. Mechanistically, QKI protein could bind to EGOT RNA and increase its expression. Inhibition of EGOT attenuated the effects of QKI on the malignant phenotypes of HCC cells. In addition, both QKI and EGOT could activate the SAPK/JNK signaling pathway in HCC cells. CONCLUSIONS: Our findings indicated that QKI exerted promotive effects on the malignant phenotypes of HCC through its interaction with EGOT.

Wanting-liking dissociation and altered dopaminergic functioning: Similarities between internet gaming disorder and tobacco use disorder.

Background: Although internet gaming disorder (IGD) has been included in the DSM-5 for approximately 10 years, debate remains regarding its existence and classification. Methods: The current research incorporated three approaches. First, implicit association tests were used to examine for potential dissociation between wanting and liking in IGD. Second, brain features in wanting and liking circuits were tested and compared with tobacco use disorder (TUD) when performing a cue-craving task to explore the neural features of wanting and liking. Third, dopaminergic systems were investigated in IGD and TUD using neuromelanin-sensitive MRI. Results: The implicit association test results supported a wanting-liking dissociation in IGD participants. Functional MRI data suggested neural correlates underlying wanting-liking dissociation in IGD and TUD participants, with positive correlations suggesting greater dissociation with increasing addiction severity. Neuromelanin results suggest dopaminergic differences in IGD and TUD relative to healthy control participants. Conclusions: A wanting-liking dissociation in IGD participants suggests gaming motivations in IGD relating to incentive sensitization rather than hedonic responses. The neuromelanin-sensitive MRI results suggest dopaminergic involvement in IGD and TUD. The findings suggest similar brain-behaviour mechanisms for IGD and TUD based on an incentive-sensitization model for addiction, having implications for potential therapeutic strategies and policy-based interventions.

Efficacy and Neural Mechanisms of Mindfulness Meditation Among Adults With Internet Gaming Disorder: A Randomized Clinical Trial.

Importance: The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), recently identified internet gaming disorder (IGD) as a condition warranting more research, and few empirically validated treatments exist. Mindfulness meditation (MM) has multiple health benefits; however, its efficacy in treating IGD and potential neural mechanisms underlying MM treatment of the disorder remain largely unknown. Objective: To explore the efficacy of MM used to treat adults with IGD and to identify neural mechanisms underlying MM. Design, Setting, and Participants: This randomized clinical trial was performed from October 1 to November 30, 2023, at Hangzhou Normal University in Hangzhou, China. Adults (aged ≥18 years) who met at least 6 of the 9 DSM-5-TR proposed criteria for IGD were recruited to receive either MM or progressive muscle relaxation (PMR). Data analysis was performed on December 1, 2023. Intervention: Participants underwent MM training (an 8-session meditation program that focuses on attention and acceptance) and PMR training (an 8-time program for body relaxation) delivered in groups that met 2 times each week for 4 weeks. Main Outcomes and Measures: This per-protocol analysis included only participants who finished the pretest assessment, 8 training sessions, and posttest assessment. The main outcomes were addiction severity (measured with the DSM-5-TR proposed criteria for IGD and with Internet Addiction Test scores), gaming craving (measured with Questionnaire for Gaming Urges scores), and blood oxygen level-dependent signals assessed with cue-craving tasks on fMRI. Behavioral and brain measurements were compared using analysis of variance. Functional connectivity (FC) among identified brain regions was measured to test connectivity changes associated with MM. Results: This study included 64 adults with IGD. A total of 32 participants received MM (mean [SD] age, 20.3 [1.9] years; 17 women [53%]) and 32 received PMR (mean [SD] age, 20.2 [1.5] years; 16 women [50%]). The severity of IGD decreased in the MM group (pretest vs posttest: mean [SD], 7.0 [1.1] vs 3.6 [0.8]; P < .001) and in the PMR group (mean [SD], 7.1 [0.9] vs 6.0 [0.9]; P = .04). The MM group had a greater decrease in IGD severity than the PMR group (mean [SD] score change for the MM group vs the PMR group, -3.6 [0.3] vs -1.1 [0.2]; P < .001). Mindfulness meditation was associated with decreased brain activation in the bilateral lentiform nuclei (r = 0.40; 95% CI, 0.19 to 0.60; P = .02), insula (r = 0.35; 95% CI, 0.09 to 0.60; P = .047), and medial frontal gyrus (MFG; r = 0.43; 95% CI, 0.16 to 0.70; P = .01). Increased MFG-lentiform FC and decreased craving (pretest vs posttest: mean [SD], 58.8 [15.7] vs 33.6 [12.0]; t = -8.66; ƞ2 = 0.30; P < .001) was observed after MM, and changes in MFG-lentiform FC mediated the relationship between increased mindfulness and decreased craving (mediate effect, -0.17; 95% CI, -0.32 to -0.08; P = .03). Conclusions and Relevance: In this study, MM was more effective in decreasing addiction severity and gaming cravings compared with PMR. These findings indicate that MM may be an effective treatment for IGD and may exert its effects by altering frontopallidal pathways. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2300075869.

rTMS effects on urges and severity of tobacco use disorder operate independently of a retrieval-extinction component and involve frontal-striatal pathways.

BACKGROUND: Although smoking remains a leading cause of preventable disease, the treatment options for smoking are limited. The present study evaluated the neural features underlying effects of repetitive transcranial magnetic stimulation (rTMS) for reducing smoking cravings. In addition, the efficacy of a simulated retrieval-extinction procedure to augment rTMS efficacy was examined. METHODS: Sixty-one individuals with tobacco use disorder (TUD) were randomized into three groups: classic rTMS, retrieval rTMS (viewed smoking videos before rTMS), and sham rTMS. rTMS was performed on the left dorsolateral prefrontal cortex (DLPFC) over 5 days using a standard figure-8 coil. Smoking cravings and brain responses to smoking cues were measured before and after rTMS treatment. Changes in functional connectivity (FC) among different brain regions were calculated. RESULTS: rTMS reduced smoking urges in TUD. Both active-rTMS groups demonstrated greater activations of the DLPFC, caudate, and bilateral insula relative to the sham group. Increased FC was observed between executive and reward network brain regions, and decreased FC was observed within reward network regions. Compared with standard rTMS, retrieval-extinction rTMS demonstrated similar outcomes and was associated with less activation of the medial frontal gyrus. CONCLUSIONS: rTMS increased activations in brain regions implicated in executive control and reward processing. Strengthened prefrontal-striatal pathway suggests that rTMS enhanced top-down control over smoking cravings. The retrieval-extinction process, although associated with some different and multiple similar neural correlates as the standard rTMS, did not enhance cessation outcomes.

Connectome-based prediction of the severity of autism spectrum disorder.

Background: Autism spectrum disorder (ASD) is characterized by social and behavioural deficits. Current diagnosis relies on behavioural criteria, but machine learning, particularly connectome-based predictive modelling (CPM), offers the potential to uncover neural biomarkers for ASD. Objective: This study aims to predict the severity of ASD traits using CPM and explores differences among ASD subtypes, seeking to enhance diagnosis and understanding of ASD. Methods: Resting-state functional magnetic resonance imaging data from 151 ASD patients were used in the model. CPM with leave-one-out cross-validation was conducted to identify intrinsic neural networks that predict Autism Diagnostic Observation Schedule (ADOS) scores. After the model was constructed, it was applied to independent samples to test its replicability (172 ASD patients) and specificity (36 healthy control participants). Furthermore, we examined the predictive model across different aspects of ASD and in subtypes of ASD to understand the potential mechanisms underlying the results. Results: The CPM successfully identified negative networks that significantly predicted ADOS total scores [r (df = 150) = 0.19, P = 0.008 in all patients; r (df = 104) = 0.20, P = 0.040 in classic autism] and communication scores [r (df = 150) = 0.22, P = 0.010 in all patients; r (df = 104) = 0.21, P = 0.020 in classic autism]. These results were reproducible across independent databases. The networks were characterized by enhanced inter- and intranetwork connectivity associated with the occipital network (OCC), and the sensorimotor network (SMN) also played important roles. Conclusions: A CPM based on whole-brain resting-state functional connectivity can predicted the severity of ASD. Large-scale networks, including the OCC and SMN, played important roles in the predictive model. These findings may provide new directions for the diagnosis and intervention of ASD, and maybe could be the targets in novel interventions.

Gender difference in network relationship between inter-temporal decisions and prefrontal activation levels in internet gaming disorder.

Background: Impulsivity and decision-making are key factors in addiction. However, little is known about how gender and time sensitivity affect impulsivity in internet gaming disorder (IGD). Objective: To investigate the gender difference of impulsive decision-making and relevant brain responses in IGD. Methods: We conducted a functional magnetic resonance imaging (fMRI) study with 123 participants, including 59 IGD individuals (26 females) and 64 matched recreational game users (RGUs, 23 females). Participants performed a delay-discounting task during fMRI scanning. We examined gender-by-group effects on behavioral and neural measures to explore the preference for immediate over delayed rewards and the associated brain activity. We also investigated the network correlations between addiction severity and behavioral and neural measures, and analyzed the mediating role of brain activity in the link between delay discounting parameters and IGD severity. Results: We found significant gender-by-group interactions. The imaging results revealed gender-by-group interactions in the dorsolateral prefrontal cortex, medial frontal gyrus, and inferior frontal gyrus (IFG). Post hoc analysis indicated that, for females, RGUs showed higher activity than IGD individuals in these brain regions, while for males IGD individuals exhibited higher activity than RGUs. The activation in the left IFG mediated the relation between Internet Addiction Test score and discount rate in females. In males, the activation in the right dlPFC mediated the relation between IAT score and time sensitivity. Discussion: Our findings imply that male IGD participants demonstrate impaired intertemporal decisions associated with neural dysfunction. Influencing factors for impulsive decision-making in IGD diverge between males (time sensitivity) and females (discount rate). These findings augment our comprehension of the neural underpinnings of gender differences in IGD and bear significant implications for devising effective intervention strategies for treating people with IGD.