BACKGROUND:Hyperprolactinemia (HPRL) can lead to various health complications. Among patients with schizophrenia, it may be linked to antipsychotic medications and other contributing factors. Sex-based differences in HPRL have been observed, and its association with breast cancer in this population remains unclear. OBJECTIVE:To investigate overall and sex-specific risk factors for HPRL in patients with schizophrenia and to examine the incidence of breast cancer in this population. METHODS:A retrospective cohort study was conducted among inpatients with schizophrenia who underwent prolactin monitoring in a Chinese hospital. Participants were categorized into HPRL and non-HPRL groups, and binary logistic regression was performed to identify factors associated with HPRL. RESULTS:Among 1,425 patients analyzed, the overall incidence of HPRL was 63.37%, with higher rates in females (67.99%) compared to males (57.31%). HPRL was positively associated with thyroid- stimulating hormone levels, repetitive transcranial magnetic stimulation frequency, female sex, and the use of first-generation antipsychotics, amisulpride, olanzapine, risperidone, paliperidone, perospirone, and trihexyphenidyl. Negative associations were found with aspartate aminotransferase, fasting plasma glucose, total bilirubin levels, and aripiprazole use. Sex-specific factors included thyroid- stimulating hormone and sulpiride use in men; olanzapine use in women; and differing associations of aspartate aminotransferase, direct bilirubin, age, and urea nitrogen depending on sex. Four female patients developed breast cancer. CONCLUSION:Multiple pharmacological and non-pharmacological factors contribute to HPRL in patients with schizophrenia, with notable sex-specific differences. The potential role of HPRL in breast cancer development among female patients requires further investigation.

As a prevalent comorbidity in schizophrenia, metabolic syndrome (MetS) exerts complex influences on residual symptoms and therapeutic outcomes of antipsychotic treatment. This study investigates the underlying neuroimaging, physiological and genetic mechanisms. At baseline, 142 participants were categorized into four groups according to diagnoses of schizophrenia and MetS. During follow-up, schizophrenia patients with and without MetS (SCZ-MetS and SCZ-nMetS) underwent 4-week antipsychotic treatment. Functional and structural magnetic resonance images, metabolic indicators and clinical scales were collected to investigate effects of MetS on gray matter volume (GMV), functional connectivity (FC) of schizophrenia patients, and related clinical implications. Using cytochrome P450 2D6 (CYP2D6) polymorphisms and brain-wide gene expression profiles, we explored genetic mechanisms of the therapeutic link between MetS and schizophrenia. SCZ-MetS showed greater insular GMV atrophy and functional dysconnectivity. Indirect effects of fasting blood glucose (FBG) on negative symptoms via insular GMV atrophy were observed. However, during follow-up, we observed group × time interactions on GMV and FC in insula. Increased GMV of the right insula in SCZ-MetS was correlated with the remission rate of positive symptoms. A moderation effect of FBG on this correlation was revealed. Finally, CYP2D6 polymorphisms and gene expression related to antipsychotic-response explained group × time interaction of GMV. Collectively, glucose metabolism, insular volume and FC underlie two distinct effects of MetS on: residual negative symptoms and therapeutic outcomes of positive symptoms in schizophrenia. The genetic mechanisms linking MetS to therapeutic outcomes involve CYP2D6 polymorphisms and the expression of genes related to antipsychotic-response.

BackgroundSchizophrenia is characterized by substantial clinical heterogeneity, with average differences between males and females in symptom presentation, cognitive function, and treatment response. The cortico-thalamo-cerebellar circuit (CTCC) has been implicated in schizophrenia; however, whether schizophrenia-related alterations in CTCC functional connectivity vary by sex remains unclear. This study examined diagnosis-by-sex interaction effects on CTCC-related functional connectivity using resting-state functional magnetic resonance imaging.MethodsResting-state fMRI data were obtained from 108 patients with schizophrenia (53 females) and 93 healthy controls (54 females). Seed-based functional connectivity (FC) analysis and independent component analysis (ICA) were used to examine group-by-sex interaction effects on CTCC-related functional organization.ResultsSignificant diagnosis-by-sex interaction effects were identified in several connections involving CTCC-related basal ganglia, thalamic, cerebellar, and cortical regions. Post hoc analyses indicated that male patients exhibited increased FC between basal ganglia, thalamic, or cerebellar seed regions and temporal or calcarine cortical areas. Female patients showed a different pattern, including reduced FC between primary sensory cortical regions and basal ganglia or thalamic seed regions. These findings indicate that schizophrenia-related CTCC connectivity alterations differed between male and female participants. Chlorpromazine-equivalent dose was not significantly associated with the interaction-related functional connectivity values in either female or male patients.ConclusionsSex moderated selected patterns of CTCC-related functional connectivity in schizophrenia. The findings represent group-level differences with substantial potential overlap between males and females and should not be interpreted as evidence of categorical brain sexual dimorphism or directional circuit mechanisms. Larger, prospectively sex-balanced studies incorporating longitudinal, dynamic, and effective-connectivity analyses are needed to confirm these findings and clarify their functional significance.

BACKGROUND:Depression is a common mental disorder affecting hundreds of millions worldwide. Targeting microglial peroxisome proliferator-activated receptor gamma (PPARγ) is regarded as one of the strategies to improve depression. However, a PPARγ activator capable of targeting brain microglia is currently lacking. OBJECTIVES:To screen novel natural PPARγ agonists targeting brain microglia from phytomedicine and analyze their antidepressant mechanisms. METHOD:Natural PPARγ agonists targeting brain microglia were identified from phytomedicine through molecular docking, kinetic simulations, surface plasmon resonance, and in vitro and in vivo approaches. The depression animal model was established using chronic unpredictable mild stress (CUMS). Depressive-like behaviors were evaluated using systematic behavioral analysis. Immunohistochemistry and Golgi staining were employed to evaluate the microglial phenotype and synaptic plasticity. The role of microglial PPARγ in improvement of neuroinflammation, synaptic impairment and depression was investigated in transgenic mice with conditional Pparg deletion in microglia. RESULTS:A total of 18 potential compounds capable of activating microglial PPARγ were identified. Among them, asperosaponin VI (ASA-VI) showed stable binding affinity for multiple PPARγ subtypes and promoted PPARγ nuclear translocation in microglia. ASA-VI driven the phenotypic transformation of microglia toward a neuroprotective phenotype and inhibited neuroinflammation in vitro and in vivo. ASA-VI also improved hippocampal synaptic impairment and depressive-like behaviors in CUMS-exposed mice. Critically, conditional knockout of Pparg in microglia abolished the therapeutic effects of ASA-VI on neuroinflammation, synaptic impairment and depression. CONCLUSION:Our findings identify ASA-VI as a microglial PPARγ activator that remodels microglial phenotype, suppresses neuroinflammation and alleviates stress-induced depression and synaptic impairment.

Background Emerging evidence has highlighted the cerebellum's role in emotion and cognition through cerebello-cerebral interactions. However, the manner in which the cerebellum integrates with the cerebral triple core networks, the default mode network (DMN), central executive network (CEN), and salience network (SN), in Major Depressive Disorder (MDD) remains unclear. Methods Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 119 patients with MDD and 106 healthy control (HC) subjects. Voxel-wise functional connectivity (FC) between the cerebral cortex and cerebellum was subsequently constructed. To evaluate cerebello-cerebral functional integration based on voxel-wise FC, functional gradient analysis and independent component analysis (ICA) were performed. Results The cerebral triple core network components were found to map onto cerebellar motor and cognitive functional modules. In patients with MDD, reduced mapping of the cerebral DMN and SN components to the cerebellum was observed. Additionally, patients exhibited compression of the cerebello-cerebral functional gradient within both motor and cognitive modules. The triple core networks showed increased contributions to cerebellar cognitive modules, whereas the DMN demonstrated decreased contributions to cerebellar motor modules in MDD. These cerebello-cerebral interaction patterns were significantly correlated with clinical assessment measures, including scores on the Trail Making Test (TMT) and the Emotion Regulation Questionnaire (ERQ). Conclusions These findings indicate disrupted functional integration between the cerebral triple core networks and the cerebellum in MDD. The results further support the cerebellum's involvement in disease pathogenesis and suggest potential neurobiological markers for diagnosis and intervention.

Background: The cerebellum is a critical node implicated in the pathology of schizophrenia. Previous studies have demonstrated that dance interventions can enhance cerebellar functional connectivity in healthy individuals. These findings suggest that dance intervention might represent a promising treatment for patients with schizophrenia.Methods: A total of 32 patients with schizophrenia were randomly assigned to two groups: a dance group (n = 18) and an aerobic exercise group (n = 14). Clinical symptoms and cognitive function, along with resting-state functional magnetic resonance imaging (fMRI) data, were collected from all participants at baseline and post-intervention. The cerebellar motor (CBCm) and cerebellar cognitive (CBCc) regions were defined for the calculation of dynamic functional connectivity (dFC). Repeated-measures analyses of covariance (ANCOVAs) were conducted for statistical analysis.Result: Significant interaction effects were observed for cognitive function and dFC. Dance intervention specifically enhanced cognitive function, as assessed by the Continuous Performance Test-Identical Pairs (CPT-IP) and the Hopkins Verbal Learning Test-Revised (HVLT-R). Moreover, increased dFC was observed between the CBCm and the left medial superior frontal gyrus, left superior occipital gyrus, and right cuneus, as well as between the CBCc and the right median cingulate cortex and the left inferior temporal gyrus in the dance intervention group. Additionally, dFC between the CBCc and the median cingulate gyrus showed a positive correlation with CPT-IP (r = 0.412, p = 0.026) and HVLT-R (r = 0.414, p = 0.021) scores.Conclusions: These findings suggest that dance intervention specifically enhances cerebellar connectivity patterns, potentially improving attention and verbal memory in patients with schizophrenia.Clinical Trial Registration: No: ChiCTR2100049273, https://www.chictr.org.cn/showproj.html?proj=65597.

BACKGROUND:Enhancing stress resilience through hippocampal neural stem cell (NSC) activation is a promising way to reduce depression risk. Earlier studies show that asperosaponin Ⅵ (ASA-VI) can efficiently cross the blood-brain barrier and provide neuroprotective benefits, but its role in activating NSC and improving stress resilience has not been explored. PURPOSE:This study aims to explore the therapeutic potential and molecular mechanisms of ASA-VI in enhancing stress resilience through hippocampal NSC activation. METHODS:We compared the hippocampal neurogenesis between high-stress resilience (HSR) mice and low-stress resilience (LSR) mice using immunohistochemistry, and explored the role of neurogenesis in maintaining stress resilience by inhibiting NSC activation with temozolomide. We evaluated the effect of ASA-VI on NSC proliferation and differentiation using both in vitro and in vivo investigations. Comprehensive methodologies, including hippocampal transcriptome analysis, western blotting, immunolocalization and pharmacological blocker treatment, were utilized to identify the involvement of the PI3K/Akt pathway in ASA-VI activating NSC. RESULTS:HSR mice had more Ki67+-GFAP+ cells, BrdU+-DCX+ cells, and BrdU+-NeuN+ cells in hippocampus than LSR mice. Inhibiting NSC activation with temozolomide reduced stress resilience and worsened depressive symptoms in CMS-exposed mice. We also found that ASA-VI strongly promoted NSC proliferation and neuronal differentiation in vitro. In CMS mice, ASA-VI prevented stress-induced impairments in neurogenesis at all stages, from NSC activation to neuron maturation. Consequently, ASA-VI significantly increased the proportion of stress-resilient mice and alleviated depressive-like behaviors. Transcriptomic and biochemical analyses revealed that ASA-VI activates the PI3K/Akt signaling pathway in NSC. Notably, the pro-neurogenic and resilience-enhancing effects of ASA-VI were eliminated by the PI3K inhibitor LY294002. CONCLUSION:Our findings identify ASA-VI as a novel agent that enhances stress resilience and prevents depression by activating the PI3K/Akt pathway in NSC.

Default mode network (DMN) disruption and systemic inflammation are hallmarks of major depressive disorder (MDD), but their relationship with behavioral impairments is unclear. This study aimed to characterize DMN spatiotemporal dynamics in MDD and link them to inflammation and behavioral deficits. Resting-state functional magnetic resonance imaging data were obtained from 87 MDD and 104 healthy controls (HC). Periodic spatiotemporal patterns (PSTPs) were defined by the switching of anti-correlation between the DMN and task-positive network. Functional couplings between DMN and cerebral networks within these patterns were then calculated. Subsequently, associations between DMN subsystem couplings and behaviors were assessed, and lasso regression was used to evaluate their predictive effects on behavior. Moderation analyses and cytokine-based subgroup comparisons were further conducted to examine the effect of inflammation on brain–behavior relationships. In MDD, couplings within the DMN increased, whereas couplings between DMN and attention and salience networks decreased. Additionally, the association was observed between DMN B coupling and Trail Making Test Part B (TMT-B) performance in MDD. These alterations also predicted the digital span test (DST). Moderation analyses showed that interleukin (IL)-17 A strengthened DMN–behavior associations, whereas IL-8 attenuated them. Consistently, higher IL-17 A levels were associated with more pronounced DMN coupling abnormalities, while lower IL-8 levels were linked to DST and TMT-B deficits. This study demonstrates internal enhancement and external decoupling of the DMN in MDD, along with the differential modulation of inflammation on brain–behavior relationships. These findings provide new insights into the pathophysiology of MDD. Not applicable.

BackgroundNonsuicidal self-injury (NSSI) is a complex behavior prevalent among adolescents, particularly females and those with depression. The DSM-5 introduced recommended diagnostic criteria for NSSI, yet many adolescents engaging in NSSI do not meet these standards. The neurobiological distinctions between adolescents with NSSI who fulfill the DSM-5 criteria (NSSI+) and those who do not (NSSI-) remain unclear.MethodsSixty-three female depressive adolescents (40 NSSI+, 23 NSSI-) and 35 healthy controls (HCs) were included and underwent resting-state functional magnetic resonance imaging, diffusion tensor imaging and high-resolution T1-weighted imaging. We explored differences in brain structure-function interactions by applying structural-functional connectivity (SC-FC) coupling analysis using multimodal neuroimaging data. Partial Spearman’s correlation analyses were used to identify association between SC-FC coupling and clinical features.ResultsThe NSSI+ group had notably distinct SC-FC coupling in task-positive network regions including decreased SC-FC coupling (greater decoupling) in the left dorsolateral superior frontal gyrus and increased coupling in the bilateral medial precuneus and right opercular inferior frontal gyrus, as compared to the NSSI- group. Moreover, the NSSI+ group displayed widespread coupling abnormalities across multiple networks compared to the HC group, while the NSSI- group only differed in the left dorsolateral superior frontal gyrus. Correlational analyses linked decoupling indices to several clinical features, particularly in the right subgenual anterior cingulate among the NSSI- participants.ConclusionsThese findings indicate that SC-FC coupling patterns distinguish NSSI subtypes in depressed female adolescents, with more severe NSSI associated with altered coupling in prefrontal, precuneus, and inferior frontal regions involved in executive control and attentional processing. The right subgenual anterior cingulate cortex—showing multiple clinical correlations—emerges as a potential target for early intervention of NSSI behavior. These findings highlight the utility of SC-FC coupling as a neural marker for NSSI subtyping and intervention planning.

Neuroimmune hypothesis posits that inflammation plays a key role in shared neurobiological substrate responsible for the comorbidity between schizophrenia and metabolic syndrome (MS). However, the specific neural mechanisms by which inflammation contributes to this comorbidity remain elusive. This study investigated whether inflammation-related brain microstructural alterations were associated with this comorbidity and its concomitant cognitive deficits. We utilized multi-site data from independent centers. Applying the two-factor experimental design, a total of 398 participants were included and categorized into four groups based on diagnoses of schizophrenia and MS: schizophrenia patients with/without metabolic syndrome (SZ-wMS and SZ-nMS), and healthy controls with/without metabolic syndrome (HC-wMS and HC-nMS). By leveraging diffusion and structural magnetic resonance imaging, free water (FW) was estimated to quantify the microstructure in cerebral gray matter. Clinical assessments included peripheral inflammatory cytokines and cognitive function tests. Interaction effects of schizophrenia and MS on brain microstructural FW were revealed, with SZ-wMS exhibiting exacerbated microstructural alterations in frontotemporal lobes compared with SZ-nMS, HC-wMS and HC-nMS groups. More pronounced cognitive deficits in multiple cognitive domains were also observed in SZ-wMS group. In SZ-wMS group, correlations between elevated FW within frontotemporal lobes and both peripheral level of interleukin-8 and scores of multiple cognitive functions were revealed. In addition, an indirect effect of interleukin-8 on delayed recall via FW of right middle frontal gyrus was revealed. Several findings were validated within each independent dataset. These results suggest that inflammation-related microstructural FW alterations within frontotemporal lobes may be associated with the comorbidity of schizophrenia and MS and the associated long-term memory decline.

Background: NLRP3-mediated microglial pyroptosis drives neuroinflammation in depression, and targeting this pathway represents a promising strategy to alleviate neuroinflammation. Akebia saponin D (ASD) is a pentacyclic triterpenoid saponin that crosses the blood–brain barrier and exhibits potent anti-inflammatory and neuroprotective properties. However, whether ASD ameliorates NLRP3-mediated microglial pyroptosis and the underlying molecular mechanisms remain unclear.Purpose: This study aimed to investigate whether ASD alleviates NLRP3-mediated microglial pyroptosis and remodels microglial phenotype, and to determine whether these effects are mediated by the PPAR-γ signaling pathway.Methods: The effects of ASD on NLRP3-mediated pyroptosis and microglial phenotype were evaluated in LPS+ATP-stimulated BV-2 microglia and in the hippocampus of mice chronically challenged with LPS. PPAR-γ activation was assessed by quantifying its phosphorylation and nuclear translocation. The involvement of PPAR-γ was pharmacologically tested using the selective antagonist GW9662 and genetically validated using microglia-specific Pparg conditional knockout (Pparg-CKO) mice.Results: ASD dose-dependently reduced the expression of pyroptosis-related markers (NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-18, and IL-1β) both in LPS+ATP-stimulated BV-2 microglia and in the hippocampus of LPS-challenged mice. In the hippocampus, ASD decreased the proportion of NLRP3⁺-Caspase-1+ microglia, CD68⁺ microglia, and amoeboid microglia, as well as the levels of pro-inflammatory makers (iNOS, IL-6 and TNF-α). Conversely, ASD increased the proportion of CD206⁺ microglia and the levels of neuroprotective markers (Arg-1, IL-4 and IL-10). ASD activates the microglial PPAR-γ and reprograms the hippocampal transcriptome in LPS-challenged mice. Blocking the PPAR-γ using GW9662 nullified the inhibitory effects of ASD on NLRP3-mediated microglial pyroptosis and phenotypic remodeling in hippocampus of LPS-challenged mice. Moreover, conditional knockout of microglial Pparg significantly attenuated the ameliorative effects of ASD on LPS-induced neuroinflammation and depressive-like behaviors.Conclusion: ASD activates microglial PPAR-γ to inhibit NLRP3-mediated pyroptosis and remodel microglial phenotype toward a neuroprotective state, thereby ameliorating neuroinflammation and depressive-like behaviors.

Dance integrates bodily movement, rhythmic perception, and emotional expression, engaging complex sensorimotor and affective systems. However, its impact on the structural organization of empathy-related brain networks remains insufficiently understood. In this study, we adopted a data-driven approach to construct a structural empathy network based on neuroimaging data from 80 healthy university students and applied Granger causality analysis (GCA) to identify the directional impact of empathy on regional gray matter changes. Empathy ability was assessed using the interpersonal reactivity index (IRI) scale. To further examine training-induced neuroplasticity, we employed an independent sample consisting of 25 dancers and 25 musicians, alongside 40 matched controls without formal artistic experience. Inter-regional structural similarity, based on gray matter probability distributions, was calculated to capture modality-specific plasticity due to dance/music training. Compared to musicians and controls, dancers exhibited significantly higher gray matter probability distributions, which indicates enhanced structural similarity between the left superior temporal gyrus and the left precuneus, left postcentral gyrus, and right paracentral lobule. Notably, this increased structural similarity was also associated with the empathy score (r = -0.87, p < 0.05, family-wise error [FWE] corrected). These findings suggest strengthened cross-modal integration between perceptual and sensorimotor systems, potentially underpinning affective resonance. Our findings highlight the domain-specific neuroplasticity of the structural empathy network induced by dance training and provide novel insights into how embodied practices shape socio-emotional brain circuits. Chinese Clinical Trials Register: ChiCTR2200059526.

Background Schizophrenia is a severe psychiatric disorder characterized by cognitive deficits as well as positive and negative symptoms. It is considered a disorder of widespread network dysconnectivity, including aberrant connectivity between the thalamus and the visual pathway. However, the relationships between the thalamus and various regions of the dorsal and ventral visual pathways in schizophrenia, and how the thalamus affects interactions among these visual regions, remain unclear.Methods Resting-state functional magnetic resonance imaging, task-state functional magnetic resonance imaging, and diffusion tensor imaging data were acquired to examine the neural activity within the thalamus and the visual pathway, along with the relationships between them (i.e. functional connectivity, structural connectivity, and structure-function coupling). We also correlated the altered imaging parameters with clinical characteristics. Furthermore, based on previous molecular imaging in healthy controls, we explored the spatial associations between altered imaging parameters and receptor/transporter distributions.Results We found significantly decreased neural activity and widespread altered thalamo-visual pathway connectivity in both dorsal and ventral pathways in schizophrenia patients. Moreover, schizophrenia patients exhibited altered mediation effects within the thalamo-dorsal visual pathway, involving MT, V1, V2, and V3. Abnormal neural activity and connectivity were related to disease duration and positive symptom severity. Altered neural activity of MT was correlated with the density of multiple neurotransmitters.Conclusions Our findings further expand our understanding of thalamo-visual pathway dysconnectivity and primary information-processing deficits in schizophrenia, which may be related to clinical symptoms. Our findings may provide more potential insights for non-invasive intervention treatments.

Background Schizophrenia is a severe mental disorder that imposes significant social burdens. Traditional treatmens, however, have limited effectiveness in addressing negative symptoms and cognitive deficits. Recent studies have indicated interventions promoting sensorimotor integration may offer potential benefits for schizophrenia treatment. The current study aimes to investigate the effects of dance training as an intervention for patients with chronic schizophrenia. Methods This study recruited 34 individuals with schizophrenia, who were randomly allocated to either a dance intervention group (n = 18) or an aerobic exercise group (n = 14) for a 3-month program including fifty-minute sessions three times per week. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Nurses’ Observation Scale for Inpatient Evaluation (NOISE). Cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Meanwhile, physiological indicators were also collected to explore the underlying physiological effects of the dance intervention. All measurements were taken before and after the interventions. Results The PANSS total scores (P < 0.01**), PANSS negative scores (p < 0.001**), NOISE score (p < 0.001**), MCCB cognitive scores, and physiological indicators were significantly changed after the intervention in both groups compared with baseline. Post-hoc analysis revealed notable improvements in the specific cognitive subscales, including the Continuous Operation Test-identical pairs (CPT-IP, p = 0.026*), Hopkins Verbal Learning Test-Revised (HVLT-R, p = 0.019*) and the physiological indicators Cystatin C (CYS-C, p = 0.037*) in the dance intervention group. Additionally, significant correlation were found between PANSS positive score and Total Bilirubin (TBIL) (r = 0.449, p = 0.028*), as well as between CPT-IP and Cystatin C (CYS-C) (r = 0.501, p = 0.008**) were found in both groups. Conclusion While both interventions resulted in improvements in clinical symptoms and cognitive function, the dance intervention specifically enhanced attention and verbal memory. Dance and aerobic exercise induced different changes in physiological indicators, which might be the physiological basis for improvements in clinical symptoms and cognitive function.

Background Enhancing stress resilience constitutes a pivotal strategy in mitigating the risk of depression, making it a critical component of both prevention and treatment. In the current work, we identified a compound, gastrodin (GAS), as capable of enhancing stress resilience, as demonstrated by its ability to protect against depression following chronic stress exposure. Objectives To elucidate the potential of GAS to promote neurogenesis under chronic stress, along with the associated cellular and molecular processes involved. Method We evaluated the effect of GAS on NSPC proliferation and differentiation using both in vitro and in vivo investigations. Neurogenesis was inhibited using temozolomide to verify GAS’s impact on stress resilience. Comprehensive methodologies, including hippocampal transcriptome analysis and western blotting, were utilized to identify the involvement of the Wnt/β-catenin pathway. Immunolocalization was conducted to confirm β-catenin’s nuclear translocation in SOX2+ cells within the hippocampal dentate gyrus subgranular zone. Results GAS demonstrated robust stimulation of NSPC proliferation and neuronal differentiation, enhancing adult hippocampal neurogenesis under conditions of chronic stress. Inhibition of neurogenesis negated GAS’s protective effects on stress resilience. Integrated analysis pointed to the Wnt/β-catenin signaling pathway within NSPCs as a crucial mechanism facilitating GAS-promoted neurogenesis. Inhibiting Wnt expression or blocking β-catenin’s nuclear translocation abolished GAS’s neurogenic and stress-resilience enhancing effects. Conclusion These results suggested that GAS directly activates the Wnt/β-catenin signaling pathway, which promotes the proliferation and neuronal differentiation of NSPCs, thereby enhancing adult hippocampal neurogenesis and promoting stress resilience to mitigate the risk of depression.

Neuroimaging research has demonstrated that long-term dance and music training can induce structural changes in the brain. However, most previous studies have focused on isolated structural metrics, neglecting the interregional similarities across cortical areas. In this study, we applied a novel morphometric measure, Morphometric Inverse Divergence (MIND), to assess cortical structural similarity in individuals with professional dance or music training. A total of 89 participants were incorporated in the study, including 25 dancers, 24 musicians, and 40 healthy controls (HC). Our findings showed that both dancers and musicians exhibited higher MIND values compared to HC, with musicians displaying significant differences particularly in the default mode network and somatomotor network. Furthermore, MIND values between the insula and superior parietal lobule, as well as between the superior frontal gyrus and cingulate gyrus, were positively correlated with the total IRI score and the Fantasy subscale. Both shared and distinct MIND patterns were identified between dancers and musicians. Musicians exhibited greater structural similarity in auditory cortical regions, whereas dancers showed increased similarity in visual and kinesthetic areas. Importantly, only the dancer group demonstrated a significant association between MIND values and empathic imagination. These findings provide new insights into how long-term artistic training influences cortical structure and social cognitive abilities.

Background:Mild cognitive impairment (MCI) is characterized by abnormal changes in spatiotemporal neuronal specificity responses. Simultaneous electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) offers a novel approach to measure these changes. Emerging evidence suggests that acupuncture may enhance cognitive function by modulating spatial or temporal central activity in individuals with MCI. However, no studies have investigated the detailed mechanisms underlying this effect. Methods:This randomized controlled neuroimaging trial will enroll 60 patients with MCI, who will be randomly assigned to one of two groups: a real acupuncture (RA) group or a sham acupuncture (SA) group. The trial period will last 12 weeks, during which participants will receive 24 sessions of acupuncture twice weekly. The primary outcome measure will be the improvement in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score from baseline to post-treatment. Secondary outcomes will include improvements in specific cognitive domains such as memory, executive function, language, and attention. Simultaneous EEG-fMRI combined with correlation analysis, regression analysis, and joint independent component analysis (jICA) will elucidate the spatiotemporal central modulatory mechanisms of acupuncture in MCI patients. Discussion:This study may reveal that real acupuncture can treat cognitive impairment by modulating the brain's spatiotemporal neuronal specificity activity. Our findings will provide scientific evidence for the efficacy of acupuncture in the treatment of MCI and further add to the understanding of the neural mechanisms. Clinical Trial Registration:ClinicalTrials.gov, identifier [ChiCTR2400084666].

BACKGROUNDS/OBJECTIVE:Deep brain stimulation (DBS) has proved the viability of alleviating depression symptoms by stimulating deep reward-related nuclei. This study aims to investigate the abnormal connectivity profiles among superficial, intermediate, and deep brain regions within the reward circuit in major depressive disorder (MDD) and therefore provides references for identifying potential superficial cortical targets for non-invasive neuromodulation. METHODS:Resting-state functional magnetic resonance imaging data were collected from a cohort of depression patients (N = 52) and demographically matched healthy controls (N = 60). Utilizing existing DBS targets as seeds, we conducted step-wise functional connectivity (sFC) analyses to delineate hierarchical pathways linking to cerebral cortices. Subsequently, the mediation effects of cortical regions on the interaction within reward-related circuits were further explored by constructing mediation models. RESULTS:In both cohorts, sFC analysis revealed two reward-related pathways from the deepest DBS targets to intermediate regions including the thalamus, insula, and anterior cingulate cortex (ACC), then to the superficial cortical cortex including medial frontal cortex, posterior default mode network (pDMN), and right dorsolateral prefrontal cortex (DLPFC). Patients exhibited reduced sFC in bilateral thalamus and medial frontal cortex in short and long steps respectively compared to healthy controls. We also discovered the disappearance of the mediation effects of superficial cortical regions on the interaction between DBS targets and intermediate regions in reward-related pathways in patients with MDD. CONCLUSION:Our findings support abnormal hierarchical connectivity and mediation effects in reward-related brain regions at different depth levels in MDD, which might elucidate the underlying pathophysiological mechanisms and inspire novel targets for non-invasive interventions.

BACKGROUND:Chronic stress is widely recognized as a critical factor that impairs synaptic plasticity dependent brain function and behavior, contributing to the onset of depression and anxiety disorders, which subsequently undermine learning and memory processes. Gastrodin (GAS), a prominent bioactive constituent of Gastrodiae Rhizoma exhibiting notable neuroprotective properties, holds significant potential for the prevention and treatment of stress-induced neurological dysfunction. However, the protective effects of GAS on stress-induced synaptic plasticity impairment and the underlying mechanisms have yet to be fully elucidated. OBJECTIVES:To investigate the potential of GAS in protecting synaptic plasticity from chronic stress and its underlying cellular and molecular mechanisms. METHOD:A chronic stress model was constructed in C57BL/6J mice, and the effects of GAS on synaptic plasticity were examined using Golgi staining and immunohistochemistry. Systematic behavioral analysis was employed to assess the impact of GAS on depressive- and anxiety-like behaviors and cognitive function of mice. Metabolomics, transcriptomics, Western blotting, immunolocalization, enzyme-linked immunosorbent assay, and the administration of signal blockers were utilized to investigate the cellular and molecular pathways via which GAS safeguards synaptic plasticity. RESULTS:The results showed that chronic stress exposure reduces the dendritic arbor complexity, density of dendritic spines, proportion of mushroom spines of hippocampal neurons, as well as disrupts synaptic function, impairs cognitive function and induces depressive-like behaviors. Importantly, impairment of hippocampal synaptic plasticity, anxiety- and depressive-like behaviors, and cognitive decline induced by chronic stress were significantly ameliorated following GAS treatment. Moreover, we identified the cAMP/PKA/CREB signaling in hippocampal neurons as a potential mechanism through which GAS prevents synaptic plasticity impairment from chronic stress exposure. Blockade of cAMP/PKA/CREB signaling abolished the protective effects of GAS on synaptic plasticity of hippocampal neurons and behaviors in stress-exposed mice. CONCLUSION:This study is the first to identify GAS as a potential natural compound for alleviating stress-induced synaptic plasticity impairment and behavioral dysfunction by activating the cAMP/PKA/CREB signaling pathway in hippocampal neurons, offering a promising strategy for stress-induced neurological disorders.