Thaploo D, Joshi A, Yilmaz E
… +3 more, Yildirim D, Altundag A, Hummel T
Behav Brain Funct
· 2023 Dec · PMID 38115149
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OBJECTIVE: Parosmia is a qualitative olfactory dysfunction presenting as "distorted odor perception" in presence of an odor source. Aim of this study was to use resting state functional connectivity to gain more informat...OBJECTIVE: Parosmia is a qualitative olfactory dysfunction presenting as "distorted odor perception" in presence of an odor source. Aim of this study was to use resting state functional connectivity to gain more information on the alteration of olfactory processing at the level of the central nervous system level. METHODS: A cross sectional study was performed in 145 patients with parosmia (age range 20-76 years; 90 women). Presence and degree of parosmia was diagnosed on the basis of standardized questionnaires. Participants also received olfactory testing using the "Sniffin' Sticks". Then they underwent resting state scans using a 3 T magnetic resonance imaging scanner while fixating on a cross. RESULTS: Whole brain analyses revealed reduced functional connectivity in salience as well as executive control networks. Region of interest-based analyses also supported reduced functional connectivity measures between primary and secondary olfactory eloquent areas (temporal pole, supramarginal gyrus and right orbitofrontal cortex; dorso-lateral pre-frontal cortex and the right piriform cortex). CONCLUSIONS: Participants with parosmia exhibited a reduced information flow between memory, decision making centers, and primary and secondary olfactory areas.
Zhang W, Yin J, Gao BY
… +5 more, Lu X, Duan YJ, Liu XY, Li MZ, Jiang S
Behav Brain Funct
· 2023 Dec · PMID 38110991
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As a kind of environmental noise, infrasonic noise has negative effects on various human organs. To date, research has shown that infrasound impairs cognitive function, especially the ability for learning and memory. Pre...As a kind of environmental noise, infrasonic noise has negative effects on various human organs. To date, research has shown that infrasound impairs cognitive function, especially the ability for learning and memory. Previously, we demonstrated that impaired learning and memory induced by infrasound was closely related with glia activation; however, the underlying mechanisms remain unclear. Connexin 43 hemichannels (Cx43 HCs), which are mainly expressed in hippocampal astrocytes, are activated under pathological conditions, lending support to the hypothesis that Cx43 HCs might function in the impaired learning and memory induced by infrasound. This study revealed that that blocking hippocampal Cx43 HCs or downregulating hippocampal Cx43 expression significantly alleviated impaired learning and memory induced by infrasound. We also observed that infrasound exposure led to the abundant release of glutamate and ATP through Cx43 HCs. In addition, the abundant release of glutamate and ATP depended on proinflammatory cytokines. Our finds suggested that the enhanced release of ATP and glutamate by astroglial Cx43 HCs may be involved in the learning and memory deficits caused by infrasound exposure.
Behav Brain Funct
· 2023 Dec · PMID 38093326
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BACKGROUND: Childhood trauma is one of the most extensively studied and well-supported environmental risk factors for the development of mental health problems. The human tryptophan hydroxylase 2 (TPH2) gene is one of th...BACKGROUND: Childhood trauma is one of the most extensively studied and well-supported environmental risk factors for the development of mental health problems. The human tryptophan hydroxylase 2 (TPH2) gene is one of the most promising candidate genes in numerous psychiatric disorders. However, it is now widely acknowledged that neither genetic variation nor environmental exposure alone can fully explain all the phenotypic variance observed in psychiatric disorders. Therefore, it is necessary to consider the interaction between the two factors in psychiatric research. METHODS: We enrolled a sizable nonclinical cohort of 786 young, healthy adults who underwent structural MRI scans and completed genotyping, the Childhood Trauma Questionnaire (CTQ) and behavioural scores. We identified the interaction between childhood trauma and the TPH2 rs7305115 gene polymorphism in the gray matter volume (GMV) of specific brain subregions and the behaviour in our sample using a multiple linear regression framework. We utilized mediation effect analysis to identify environment /gene-brain-behaviour relationships. RESULTS: We found that childhood trauma and TPH2 rs7305115 interacted in both behaviour and the GMV of brain subregions. Our findings indicated that the GMV of the right posterior parietal thalamus served as a significant mediator supporting relationship between childhood trauma (measured by CTQ score) and anxiety scores in our study population, and the process was partly modulated by the TPH2 rs7305115 gene polymorphism. Moreover, we found only a main effect of childhood trauma in the GMV of the right parahippocampal gyrus area, supporting the relationship between childhood trauma and anxiety scores as a significant mediator. CONCLUSIONS: Our findings suggest that early-life trauma may have a specific and long-term structural effect on brain GMV, potentially leading to altered cognitive and emotional processes involving the parahippocampal gyrus and thalamus that may also be modulated by the TPH2 gene polymorphism. This finding highlights the importance of considering genetic factors when examining the impact of early-life experiences on brain structure and function. Gene‒environment studies can be regarded as a powerful objective supplement for targeted therapy, early diagnosis and treatment evaluation in the future.
Deng K, Jin W, Jiang K
… +13 more, Li Z, Im H, Chen S, Du H, Guan S, Ge W, Wei C, Zhang B, Wang P, Zhao G, Chen C, Liu L, Wang Q
Behav Brain Funct
· 2023 Dec · PMID 38041182
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This study explored whether amygdala reactivity predicted the greed personality trait (GPT) using both task-based and resting-state functional connectivity analyses (n = 452). In Cohort 1 (n = 83), task-based functional...This study explored whether amygdala reactivity predicted the greed personality trait (GPT) using both task-based and resting-state functional connectivity analyses (n = 452). In Cohort 1 (n = 83), task-based functional magnetic resonance imaging (t-fMRI) results from a region-of-interest (ROI) analysis revealed no direct correlation between amygdala reactivity to fearful and angry faces and GPT. Instead, whole-brain analyses revealed GPT to robustly negatively vary with activations in the right ventromedial prefrontal cortex (vmPFC), supramarginal gyrus, and angular gyrus in the contrast of fearful + angry faces > shapes. Moreover, task-based psychophysiological interaction (PPI) analyses showed that the high GPT group showed weaker functional connectivity of the vmPFC seed with a top-down control network and visual pathways when processing fearful or angry faces compared to their lower GPT counterparts. In Cohort 2, resting-state functional connectivity (rs-FC) analyses indicated stronger connectivity between the vmPFC seed and the top-down control network and visual pathways in individuals with higher GPT. Comparing the two cohorts, bilateral amygdala seeds showed weaker associations with the top-down control network in the high group via PPI analyses in Cohort 1. Yet, they exhibited distinct rs-FC patterns in Cohort 2 (e.g., positive associations of GPT with the left amygdala-top-down network FC but negative associations with the right amygdala-visual pathway FC). The study underscores the role of the vmPFC and its functional connectivity in understanding GPT, rather than amygdala reactivity.
Liu J, Liu QR, Wu ZM
… +13 more, Chen QR, Chen J, Wang Y, Cao XL, Dai MX, Dong C, Liu Q, Zhu J, Zhang LL, Li Y, Wang YF, Liu L, Yang BR
Behav Brain Funct
· 2023 Nov · PMID 37986005
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BACKGROUND: Autistic traits (ATs) are frequently reported in children with Attention-Deficit/Hyperactivity Disorder (ADHD). This study aimed to examine ATs in children with ADHD from both behavioral and neuroimaging pers...BACKGROUND: Autistic traits (ATs) are frequently reported in children with Attention-Deficit/Hyperactivity Disorder (ADHD). This study aimed to examine ATs in children with ADHD from both behavioral and neuroimaging perspectives. METHODS: We used the Autism Spectrum Screening Questionnaire (ASSQ) to assess and define subjects with and without ATs. For behavioral analyses, 67 children with ADHD and ATs (ADHD + ATs), 105 children with ADHD but without ATs (ADHD - ATs), and 44 typically developing healthy controls without ATs (HC - ATs) were recruited. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data and analyzed the mean amplitude of low-frequency fluctuation (mALFF) values (an approach used to depict different spontaneous brain activities) in a sub-sample. The imaging features that were shared between ATs and ADHD symptoms or that were unique to one or the other set of symptoms were illustrated as a way to explore the "brain-behavior" relationship. RESULTS: Compared to ADHD-ATs, the ADHD + ATs group showed more global impairment in all aspects of autistic symptoms and higher hyperactivity/impulsivity (HI). Partial-correlation analysis indicated that HI was significantly positively correlated with all aspects of ATs in ADHD. Imaging analyses indicated that mALFF values in the left middle occipital gyrus (MOG), left parietal lobe (PL)/precuneus, and left middle temporal gyrus (MTG) might be specifically related to ADHD, while those in the right MTG might be more closely associated with ATs. Furthermore, altered mALFF in the right PL/precuneus correlated with both ADHD and ATs, albeit in diverse directions. CONCLUSIONS: The co-occurrence of ATs in children with ADHD manifested as different behavioral characteristics and specific brain functional alterations. Assessing ATs in children with ADHD could help us understand the heterogeneity of ADHD, further explore its pathogenesis, and promote clinical interventions.
Martín-González E, Prados-Pardo Á, Sawiak SJ
… +5 more, Dalley JW, Padro D, Ramos-Cabrer P, Mora S, Moreno-Montoya M
Behav Brain Funct
· 2023 Nov · PMID 37932782
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Compulsivity is considered a transdiagnostic dimension in obsessive-compulsive and related disorders, characterized by heterogeneous cognitive and behavioral phenotypes associated with abnormalities in cortico-striatal-t...Compulsivity is considered a transdiagnostic dimension in obsessive-compulsive and related disorders, characterized by heterogeneous cognitive and behavioral phenotypes associated with abnormalities in cortico-striatal-thalamic-cortical circuitry. The present study investigated the structural morphology of white and gray matter in rats selected for low- (LD) and high- (HD) compulsive drinking behavior on a schedule-induced polydipsia (SIP) task. Regional brain morphology was assessed using ex-vivo high-resolution magnetic resonance imaging (MRI). Voxel-based morphometry of segmented MRI images revealed larger white matter volumes in anterior commissure and corpus callosum of HD rats compared with LD rats. HD rats also showed significantly larger regional volumes of dorsolateral orbitofrontal cortex, striatum, amygdala, hippocampus, midbrain, sub-thalamic nucleus, and cerebellum. By contrast, the medial prefrontal cortex was significantly smaller in HD rats compared with LD rats with no significant group differences in whole brain, ventricular, or cerebrospinal fluid volumes. These findings show that limbic cortico-basal ganglia structures implicated in impulse control disorders are distinct in rats that are vulnerable to develop compulsive behavior. Such abnormalities may be relevant to the etiology of compulsive disorders in humans.
Behav Brain Funct
· 2023 Oct · PMID 37798774
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BACKGROUND: The study aimed to determine how the resting-state EEG (rsEEG) complexity changes both over time and space (channels). The complexity of rsEEG and its sex/gender differences were examined using the multivaria...BACKGROUND: The study aimed to determine how the resting-state EEG (rsEEG) complexity changes both over time and space (channels). The complexity of rsEEG and its sex/gender differences were examined using the multivariate Multiscale Entropy (mMSE) in 95 healthy adults. Following the probability maps (Giacometti et al. in J Neurosci Methods 229:84-96, 2014), channel sets have been identified that correspond to the functional networks. For each channel set the area under curve (AUC), which represents the total complexity, MaxSlope-the maximum complexity change of the EEG signal at thefine scales (1:4 timescales), and AvgEnt-to the average entropy level at coarse-grained scales (9:12 timescales), respectively, were extracted. To check dynamic changes between the entropy level at the fine and coarse-grained scales, the difference in mMSE between the #9 and #4 timescale (DiffEnt) was also calculated. RESULTS: We found the highest AUC for the channel sets corresponding to the somatomotor (SMN), dorsolateral network (DAN) and default mode (DMN) whereas the visual network (VN), limbic (LN), and frontoparietal (FPN) network showed the lowest AUC. The largest MaxSlope were in the SMN, DMN, ventral attention network (VAN), LN and FPN, and the smallest in the VN. The SMN and DAN were characterized by the highest and the LN, FPN, and VN by the lowest AvgEnt. The most stable entropy were for the DAN and VN while the LN showed the greatest drop of entropy at the coarse scales. Women, compared to men, showed higher MaxSlope and DiffEnt but lower AvgEnt in all channel sets. CONCLUSIONS: Novel results of the present study are: (1) an identification of the mMSE features that capture entropy at the fine and coarse timescales in the channel sets corresponding to the main resting-state networks; (2) the sex/gender differences in these features.
Wang Q, Hu S, Qi L
… +5 more, Wang X, Jin G, Wu D, Wang Y, Ren L
Behav Brain Funct
· 2023 Oct · PMID 37784181
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BACKGROUND: Emerging evidence suggests bidirectional causal relationships between sleep disturbance and psychiatric disorders, but the underlying mechanisms remain unclear. Understanding the bidirectional causality betwe...BACKGROUND: Emerging evidence suggests bidirectional causal relationships between sleep disturbance and psychiatric disorders, but the underlying mechanisms remain unclear. Understanding the bidirectional causality between sleep traits and brain imaging-derived phenotypes (IDPs) will help elucidate the mechanisms. Although previous studies have identified a range of structural differences in the brains of individuals with sleep disorders, it is still uncertain whether grey matter (GM) volume alterations precede or rather follow from the development of sleep disorders. RESULTS: After Bonferroni correction, the forward MR analysis showed that insomnia complaint remained positively associated with the surface area (SA) of medial orbitofrontal cortex (β, 0.26; 95% CI, 0.15-0.37; P = 5.27 × 10). In the inverse MR analysis, higher global cortical SA predisposed individuals less prone to suffering insomnia complaint (OR, 0.89; 95%CI, 0.85-0.94; P = 1.51 × 10) and short sleep (≤ 6 h; OR, 0.98; 95%CI, 0.97-0.99; P = 1.51 × 10), while higher SA in posterior cingulate cortex resulted in a vulnerability to shorter sleep durations (β, - 0.09; 95%CI, - 0.13 to - 0.05; P = 1.21 × 10). CONCLUSIONS: Sleep habits not only result from but also contribute to alterations in brain structure, which may shed light on the possible mechanisms linking sleep behaviours with neuropsychiatric disorders, and offer new strategies for prevention and intervention in psychiatric disorders and sleep disturbance.
Behav Brain Funct
· 2023 Sep · PMID 37749598
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BACKGROUND: Living a happy and meaningful life is an eternal topic in positive psychology, which is crucial for individuals' physical and mental health as well as social functioning. Well-being can be subdivided into ple...BACKGROUND: Living a happy and meaningful life is an eternal topic in positive psychology, which is crucial for individuals' physical and mental health as well as social functioning. Well-being can be subdivided into pleasure attainment related hedonic well-being or emotional well-being, and self-actualization related eudaimonic well-being or psychological well-being plus social well-being. Previous studies have mostly focused on human brain morphological and functional mechanisms underlying different dimensions of well-being, but no study explored brain network mechanisms of well-being, especially in terms of topological properties of human brain morphological similarity network. METHODS: Therefore, in the study, we collected 65 datasets including magnetic resonance imaging (MRI) and well-being data, and constructed human brain morphological network based on morphological distribution similarity of cortical thickness to explore the correlations between topological properties including network efficiency and centrality and different dimensions of well-being. RESULTS: We found emotional well-being was negatively correlated with betweenness centrality in the visual network but positively correlated with eigenvector centrality in the precentral sulcus, while the total score of well-being was positively correlated with local efficiency in the posterior cingulate cortex of cortical thickness network. CONCLUSIONS: Our findings demonstrated that different dimensions of well-being corresponded to different cortical hierarchies: hedonic well-being was involved in more preliminary cognitive processing stages including perceptual and attentional information processing, while hedonic and eudaimonic well-being might share common morphological similarity network mechanisms in the subsequent advanced cognitive processing stages.
Behav Brain Funct
· 2023 Sep · PMID 37726856
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Emotion regulation (ER) refers to the process through which people influence the occurrence, experience, and expression of emotions. It can be established in an explicit (voluntary) or implicit (automatic) way, both of w...Emotion regulation (ER) refers to the process through which people influence the occurrence, experience, and expression of emotions. It can be established in an explicit (voluntary) or implicit (automatic) way, both of which are essential for mental and physical well-being. Recent evidence has highlighted the potential of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) targeting the prefrontal cortex (PFC) to modulate ER. However, previous studies have only evaluated the effects of TMS and tDCS on explicit ER, leaving implicit ER relatively unexplored. In this review and meta-analysis, we systematically evaluated the effects of TMS and tDCS over the PFC on the two forms of ER, using both subjective and physiological response as outcome indicators. Twenty-seven studies were included in our study. Both subjective (Hedges' g = - 0.20) and physiological (Hedges' g = - 0.65) results indicated a significant effect of TMS and tDCS targeting PFC on down-regulation of explicit ER, but not implicit ER (Hedges' g = - 0.04). Moreover, moderation analysis indicated that the effect of TMS and tDCS on the down-regulating of subjective experience was moderated by several factors, including stimulation method, target area, target hemisphere, and stimulation timing. Specifically, our results showed that applying TMS or targeting the right PFC, particularly the right ventrolateral prefrontal cortex, or using offline TMS and tDCS produced a larger stimulation effect on ER. In summary, these findings suggest that TMS and tDCS has a positive effect on explicit, but not implicit ER. The distinct TMS and tDCS effect on the two forms of ER help deepen our understanding of TMS and tDCS use and provide valuable insights for the development of tailored TMS and tDCS protocols for explicit and implicit regulation.
Zhao Y, Zhong Y, Chen W
… +4 more, Chang S, Cao Q, Wang Y, Yang L
Behav Brain Funct
· 2023 Sep · PMID 37658396
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OBJECTIVE: Working memory (WM) deficits have frequently been linked to attention deficit hyperactivity disorder (ADHD). Despite previous studies suggested its high heritability, its genetic basis, especially in ADHD, rem...OBJECTIVE: Working memory (WM) deficits have frequently been linked to attention deficit hyperactivity disorder (ADHD). Despite previous studies suggested its high heritability, its genetic basis, especially in ADHD, remains unclear. The current study aimed to comprehensively explore the genetic basis of visual-spatial working memory (VSWM) in ADHD using wide-ranging genetic analyses. METHODS: The current study recruited a cohort consisted of 802 ADHD individuals, all met DSM-IV ADHD diagnostic criteria. VSWM was assessed by Rey-Osterrieth complex figure test (RCFT), which is a widely used psychological test include four memory indexes: detail delayed (DD), structure delayed (SD), structure immediate (SI), detail immediate (DI). Genetic analyses were conducted at the single nucleotide polymorphism (SNP), gene, pathway, polygenic and protein network levels. Polygenic Risk Scores (PRS) were based on summary statistics of various psychiatric disorders, including ADHD, autism spectrum disorder (ASD), major depressive disorder (MDD), schizophrenia (SCZ), obsessive compulsive disorders (OCD), and substance use disorder (SUD). RESULTS: Analyses at the single-marker level did not yield significant results (5E-08). However, the potential signals with P values less than E-05 and their mapped genes suggested the regulation of VSWM involved both ocular and neural system related genes, moreover, ADHD-related genes were also involved. The gene-based analysis found RAB11FIP1, whose encoded protein modulates several neurodevelopment processes and visual system, as significantly associated with DD scores (P = 1.96E-06, P = 0.036). Candidate pathway enrichment analyses (N = 53) found that forebrain neuron fate commitment significantly enriched in DD (P = 4.78E-04, Padj = 0.025), and dopamine transport enriched in SD (P = 5.90E-04, Padj = 0.031). We also observed a significant negative relationship between DD scores and ADHD PRS scores (P = 0.0025, Empirical P = 0.048). CONCLUSIONS: Our results emphasized the joint contribution of ocular and neural genes in regulating VSWM. The study reveals a shared genetic basis between ADHD and VSWM, with GWAS indicating the involvement of ADHD-related genes in VSWM. Additionally, the PRS analysis identifies a significant relationship between ADHD-PRS and DD scores. Overall, our findings shed light on the genetic basis of VSWM deficits in ADHD, and may have important implications for future research and clinical practice.
Behav Brain Funct
· 2023 Aug · PMID 37620941
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BACKGROUND: Cross-frequency phase-amplitude coupling (PAC) of cortical oscillations is observed within and across cortical regions during higher-order cognitive processes. Particularly, the PAC of alpha and gamma waves i...BACKGROUND: Cross-frequency phase-amplitude coupling (PAC) of cortical oscillations is observed within and across cortical regions during higher-order cognitive processes. Particularly, the PAC of alpha and gamma waves in the occipital cortex is closely associated with visual perception. In theory, gamma oscillation is a neuronal representation of visual stimuli, which drives the duty cycle of visual perception together with alpha oscillation. Therefore, it is believed that the timing of entrainment in alpha-gamma PAC may play a critical role in the performance of visual perception. We hypothesized that transcranial alternating current stimulation (tACS) with gamma waves entrained at the troughs of alpha waves would enhance the dynamic visual acuity (DVA). METHOD: We attempted to modulate the performance of DVA by using tACS. The waveforms of the tACS were tailored to target PAC over the occipital cortex. The waveforms contained gamma (80 Hz) waves oscillating at either the peaks or troughs of alpha (10 Hz) waves. Participants performed computerized DVA task before, immediately after, and 10 min after each stimulation sessions. EEG and EOG were recorded during the DVA task to assess inter-trial phase coherence (ITPC), the alpha-gamma PAC at occipital site and the eye movements. RESULTS: tACS with gamma waves entrained at alpha troughs effectively enhanced DVA, while the tACS with gamma waves entrained at alpha peaks did not affect DVA performance. Importantly, analyses of EEG and EOG showed that the enhancement of DVA performance originated solely from the neuromodulatory effects, and was not related to the modulation of saccadic eye movements. Consequently, DVA, one of the higher-order cognitive abilities, was successfully modulated using tACS with a tailored waveform. CONCLUSIONS: Our experimental results demonstrated that DVA performances were enhanced when tACS with gamma bursts entrained on alpha wave troughs were applied over the occipital cortex. Our findings suggest that using tACS with tailored waveforms, modulation of complex neuronal features could effectively enhance higher-order cognitive abilities such as DVA, which has never been modulated with conventional noninvasive brain stimulation methods.
Behav Brain Funct
· 2023 Jul · PMID 37454095
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BACKGROUND: Stressful events and meaning-making toward them play an important role in adolescents' life and growth. However, ignoring positive stressful events leads to negativity bias; further, the neural mechanisms of...BACKGROUND: Stressful events and meaning-making toward them play an important role in adolescents' life and growth. However, ignoring positive stressful events leads to negativity bias; further, the neural mechanisms of meaning-making are unclear. We aimed to verify the mediating role of meaning-making in stressful events and stress-related growth and the function of the default mode network (DMN) during meaning-making in this functional magnetic resonance imaging (fMRI) study. METHODS: Participants comprised 59 university students. Stressful life events, meaning-making, and stress-related growth were assessed at baseline, followed by fMRI scanning during a meaning-making task aroused by mental simulation. General linear modeling and psychophysiological interaction (PPI) analyses were used to explore the activation and functional connectivity of DMN during meaning-making. RESULTS: Mental simulation triggered meaning-making, and DMN activity decreased during meaning-making. Activation of the DMN was negatively correlated with coping flexibility, an indicator of stress-related growth. PPI analysis showed that meaning-making was accompanied by diminished connectivity in the DMN. DMN activation during meaning-making can mediate the relationship between positive stressful events and coping flexibility. CONCLUSIONS: Decreased DMN activity and diminished functional connectivity in the DMN occurred during meaning-making. Activation of the DMN during meaning-making could mediate the relationship between positive stressful events and stress-related growth, which provides a cognitive neural basis for the mediating role of meaning-making in the relationship between stressful events and indicators of stress-related growth. IMPLICATIONS: This study supports the idea that prosperity makes heroes, expands the meaning-making model, and suggests the inclusion of enhancing personal resources and meaning-making in education. This study was the first to validate the activation pattern and functional connectivity of the DMN during meaning-making aroused by mental simulation using an fMRI task-state examination, which can enhance our sense of meaning and provide knowledge that can be used in clinical psychology interventions. TRIAL REGISTRATION: The study protocol was pre-registered in Open Science Framework (see osf.io/ahm6e for details).
Yun Y, Wang X, Xu J
… +4 more, Chen J, Wang X, Yang P, Qin L
Behav Brain Funct
· 2023 Jun · PMID 37322485
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BACKGROUND: Neuroinflammation has been identified as one of the primary pathogenic factors of neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no dedicated treatments available in clinics to alle...BACKGROUND: Neuroinflammation has been identified as one of the primary pathogenic factors of neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no dedicated treatments available in clinics to alleviate neuroinflammation in NPSLE. It has been proposed that stimulating basal forebrain (BF) cholinergic neurons may provide potent anti-inflammatory effects in several inflammatory diseases, but its potential role in NPSLE remains unexplored. This study aims to investigate whether and how stimulating BF cholinergic neurons has a protective effect on NPSLE. RESULTS: Optogenetic stimulation of BF cholinergic neurons significantly ameliorated olfactory dysfunction and anxiety- and depression-like phenotype in pristane induced lupus (PIL) mice. The increased expression of adhesion molecules (P-selectin and vascular cell adhesion molecule-1 (VCAM-1)), leukocyte recruitment, blood-brain barrier (BBB) leakage were significantly decreased. Notably, the brain histopathological changes, including the elevated levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), IgG deposition in the choroid plexus and lateral ventricle wall and lipofuscin accumulation in the cortical and hippocampal neurons, were also significantly attenuated. Furthermore, we confirmed the colocalization between the BF cholinergic projections and the cerebral vessels, and the expression of α7-nicotinic acetylcholine receptor (α7nAChR) on the cerebral vessels. CONCLUSION: Our data indicate that stimulation of BF cholinergic neurons could play a neuroprotective role in the brain through its cholinergic anti-inflammatory effects on cerebral vessels. Therefore, this may be a promising preventive target for NPSLE.
Behav Brain Funct
· 2023 Jun · PMID 37259151
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KIAA0319, a well-studied candidate gene, has been shown to be associated with reading ability and developmental dyslexia. In the present study, we investigated whether KIAA0319 affects reading ability by interacting with...KIAA0319, a well-studied candidate gene, has been shown to be associated with reading ability and developmental dyslexia. In the present study, we investigated whether KIAA0319 affects reading ability by interacting with the parental education level and whether rapid automatized naming (RAN), phonological awareness and morphological awareness mediate the relationship between KIAA0319 and reading ability. A total of 2284 Chinese children from primary school grades 3 and 6 participated in this study. Chinese character reading accuracy and word reading fluency were used as measures of reading abilities. The cumulative genetic risk score (CGS) of 13 SNPs in KIAA0319 was calculated. Results revealed interaction effect between CGS of KIAA0319 and parental education level on reading fluency. The interaction effect suggested that individuals with a low CGS of KIAA0319 were better at reading fluency in a positive environment (higher parental educational level) than individuals with a high CGS. Moreover, the interaction effect coincided with the differential susceptibility model. The results of the multiple mediator model revealed that RAN mediates the impact of the genetic cumulative effect of KIAA0319 on reading abilities. These findings provide evidence that KIAA0319 is a risk vulnerability gene that interacts with environmental factor to impact reading abilities and demonstrate the reliability of RAN as an endophenotype between genes and reading associations.
Fatemeh B, Koorosh S, Amir S
… +2 more, Yaghoub F, Javad MZ
Behav Brain Funct
· 2023 May · PMID 37231523
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BACKGROUND: Alzheimer's disease is accompanied by an abnormal high accumulation of cis-P tau. However, the long-term changes in behavior following tau accumulation remains under debate. The present study investigated the...BACKGROUND: Alzheimer's disease is accompanied by an abnormal high accumulation of cis-P tau. However, the long-term changes in behavior following tau accumulation remains under debate. The present study investigated the long-term effects of tauopathy on learning and memory, synaptic plasticity, and hippocampal cell numbers. RESULTS: Cis-P tau was microinjected into the dorsal hippocampus to generate Alzheimer's like-disease model in C57BL/6 mice. Cis-P tau injected animals showed a significant impairment in learning and memory in Y-maze and Barnes maze tests. In another group of animals, the generation of long-term potentiation (LTP) was evaluated in hippocampal slices 7 months after cis-P tau injection. LTP induction was disrupted only in the dorsal but not ventral hippocampal slices. The basal synaptic transmission was also reduced in dorsal hippocampal slices. In addition, hippocampal sampling was done, and the number of cells was assessed by Nissl staining. Obtained results indicated that the number of survived cells was significantly reduced in the dorsal and ventral hippocampus of cis P-tau injected animals compared to the animals in control group. However, the decrement of cell number was higher in the dorsal compared to the ventral hippocampus. CONCLUSIONS: In conclusion, intra-hippocampal cis-P tau injection produced learning and memory impairment at 7 months after its injection. This impairment might result from LTP disruption and a significant decrease in the number of neurons in the dorsal hippocampus.
González-Portilla M, Mellado S, Montagud-Romero S
… +3 more, Rodríguez de Fonseca F, Pascual M, Rodríguez-Arias M
Behav Brain Funct
· 2023 May · PMID 37226219
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The lipid oleoylethanolamide (OEA) has been shown to affect reward-related behavior. However, there is limited experimental evidence about the specific neurotransmission systems OEA may be affecting to exert this modulat...The lipid oleoylethanolamide (OEA) has been shown to affect reward-related behavior. However, there is limited experimental evidence about the specific neurotransmission systems OEA may be affecting to exert this modulatory effect. The aim of this study was to evaluate the effects of OEA on the rewarding properties of cocaine and relapse-related gene expression in the striatum and hippocampus. For this purpose, we evaluated male OF1 mice on a cocaine-induced CPP procedure (10 mg/kg) and after the corresponding extinction sessions, we tested drug-induced reinstatement. The effects of OEA (10 mg/kg, i.p.) were evaluated at three different timepoints: (1) Before each cocaine conditioning session (OEA-C), (2) Before extinction sessions (OEA-EXT) and (3) Before the reinstatement test (OEA-REINST). Furthermore, gene expression changes in dopamine receptor D1 gene, dopamine receptor D2 gene, opioid receptor µ, cannabinoid receptor 1, in the striatum and hippocampus were analyzed by qRT-PCR. The results obtained in the study showed that OEA administration did not affect cocaine CPP acquisition. However, mice receiving different OEA treatment schedules (OEA-C, OEA-EXT and OEA-REINST) failed to display drug-induced reinstatement. Interestingly, the administration of OEA blocked the increase of dopamine receptor gene D1 in the striatum and hippocampus caused by cocaine exposure. In addition, OEA-treated mice exhibited reduced striatal dopamine receptor gene D2 and cannabinoid receptor 1. Together, these findings suggest that OEA may be a promising pharmacological agent in the treatment of cocaine use disorder.
Li X, Zhang H, Yang L
… +5 more, Dong X, Han Y, Su Y, Li W, Li W
Behav Brain Funct
· 2023 Apr · PMID 37055801
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Increasing evidence has shown that the NOD-like receptor protein 1 (NLRP1) inflammasome is associated with Aβ generation and deposition, which contributes to neuronal damage and neuronal-inflammation in Alzheimer's disea...Increasing evidence has shown that the NOD-like receptor protein 1 (NLRP1) inflammasome is associated with Aβ generation and deposition, which contributes to neuronal damage and neuronal-inflammation in Alzheimer's disease (AD). However, the specific mechanism of NLRP1 inflammasome in the pathogenesis of AD is still unclear. It has been reported that autophagy dysfunction can aggravate the pathological symptoms of AD and plays an important role in regulating Aβ generation and clearance. We hypothesized that NLRP1 inflammasome activation may induce autophagy dysfunction contributing to the progression of AD. In the present study, we observed the relationship between Aβ generation and NLRP1 inflammasome activation, as well as AMPK/mTOR mediated-autophagy dysfunction in WT 9-month-old (M) mice, APP/PS1 6 M and APP/PS1 9 M mice. Additionally, we further studied the effect of NLRP1 knockdown on cognitive function, Aβ generation, neuroinflammation and AMPK/mTOR mediated autophagy in APP/PS1 9 M mice. Our results indicated that NLRP1 inflammasome activation and AMPK/mTOR mediated-autophagy dysfunction are closely implicated in Aβ generation and deposition in APP/PS1 9 M mice, but not in APP/PS1 6 M mice. Meanwhile, we found that knockdown of NLRP1 significantly improved learning and memory impairments, decreased the expressions of NLRP1, ASC, caspase-1, p-NF-κB, IL-1β, APP, CTF-β, BACE1 and Aβ, and decreased the level of p-AMPK, Beclin 1 and LC3 II, and increased the level of p-mTOR and P62 in APP/PS1 9 M mice. Our study suggested that inhibition of NLRP1 inflammasome activation improves AMPK/mTOR mediated-autophagy dysfunction, resulting in the decrease of Aβ generation, and NLRP1 and autophagy might be important targets to delay the progression of AD.
Oroszi T, Geerts E, Rajadhyaksha R
… +3 more, Nyakas C, van Heuvelen MJG, van der Zee EA
Behav Brain Funct
· 2023 Mar · PMID 36941713
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BACKGROUND: Alzheimer's disease (AD) is the core cause of dementia in elderly populations. One of the main hallmarks of AD is extracellular amyloid beta (Aβ) accumulation (APP-pathology) associated with glial-mediated ne...BACKGROUND: Alzheimer's disease (AD) is the core cause of dementia in elderly populations. One of the main hallmarks of AD is extracellular amyloid beta (Aβ) accumulation (APP-pathology) associated with glial-mediated neuroinflammation. Whole-Body Vibration (WBV) is a passive form of exercise, but its effects on AD pathology are still unknown. METHODS: Five months old male J20 mice (n = 26) and their wild type (WT) littermates (n = 24) were used to investigate the effect of WBV on amyloid pathology and the healthy brain. Both J20 and WT mice underwent WBV on a vibration platform or pseudo vibration treatment. The vibration intervention consisted of 2 WBV sessions of 10 min per day, five days per week for five consecutive weeks. After five weeks of WBV, the balance beam test was used to assess motor performance. Brain tissue was collected to quantify Aβ deposition and immunomarkers of astrocytes and microglia. RESULTS: J20 mice have a limited number of plaques at this relatively young age. Amyloid plaque load was not affected by WBV. Microglia activation based on IBA1-immunostaining was significantly increased in the J20 animals compared to the WT littermates, whereas CD68 expression was not significantly altered. WBV treatment was effective to ameliorate microglia activation based on morphology in both J20 and WT animals in the Dentate Gyrus, but not so in the other subregions. Furthermore, GFAP expression based on coverage was reduced in J20 pseudo-treated mice compared to the WT littermates and it was significantly reserved in the J20 WBV vs. pseudo-treated animals. Further, only for the WT animals a tendency of improved motor performance was observed in the WBV group compared to the pseudo vibration group. CONCLUSION: In accordance with the literature, we detected an early plaque load, reduced GFAP expression and increased microglia activity in J20 mice at the age of ~ 6 months. Our findings indicate that WBV has beneficial effects on the early progression of brain pathology. WBV restored, above all, the morphology of GFAP positive astrocytes to the WT level that could be considered the non-pathological and hence "healthy" level. Next experiments need to be performed to determine whether WBV is also affective in J20 mice of older age or other AD mouse models.
Behav Brain Funct
· 2023 Mar · PMID 36941632
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BACKGROUND: Theoretical models posit abnormalities in cortico-striatal pathways in two of the most common neurodevelopmental disorders (Developmental dyslexia, DD, and Attention deficit hyperactive disorder, ADHD), but i...BACKGROUND: Theoretical models posit abnormalities in cortico-striatal pathways in two of the most common neurodevelopmental disorders (Developmental dyslexia, DD, and Attention deficit hyperactive disorder, ADHD), but it is still unclear what distinct cortico-striatal dysfunction might distinguish language disorders from others that exhibit very different symptomatology. Although impairments in tasks that depend on the cortico-striatal network, including reinforcement learning (RL), have been implicated in both disorders, there has been little attempt to dissociate between different types of RL or to compare learning processes in these two types of disorders. The present study builds upon prior research indicating the existence of two learning manifestations of RL and evaluates whether these processes can be differentiated in language and attention deficit disorders. We used a two-step RL task shown to dissociate model-based from model-free learning in human learners. RESULTS: Our results show that, relative to neurotypicals, DD individuals showed an impairment in model-free but not in model-based learning, whereas in ADHD the ability to use both model-free and model-based learning strategies was significantly compromised. CONCLUSIONS: Thus, learning impairments in DD may be linked to a selective deficit in the ability to form action-outcome associations based on previous history, whereas in ADHD some learning deficits may be related to an incapacity to pursue rewards based on the tasks' structure. Our results indicate how different patterns of learning deficits may underlie different disorders, and how computation-minded experimental approaches can differentiate between them.