Brain and Behavior最新文献

Introduction: Although it is well established that people with diabetes are at an increased risk of developing neuropsychiatric disorders, including depression and anxiety, the mechanisms that mediate this relationship are not fully understood. The use of preclinical models can be helpful in the investigation of mechanisms. For example, studies have shown that chronic hyperglycemia (HG), induced by administration of streptozotocin (STZ) to mice, induces neuroinflammation and depressive-like behaviors in classic tests of antidepressant efficacy (e.g., forced swim test, splash test). However, there is a need to establish more specific assessments of affective dysfunction, including assessment of changes within the negative valeence systems. It has been previously reported that HG rodents show increased susceptibility to fear conditioning, potentially through increased salience of negative stimuli. Based on this, we sought to determine whether this enhanced fear memory is sensitive to fluoxetine (FLX), a commonly used antidepressant.

Methods: Male C57BL/6J mice were administered 50 mg/kg STZ per day for five consecutive days or an equal volume of citrate buffer to induce HG. Four weeks after HG induction, a time at which behavioral changes are well established, mice started daily treatment with 10 mg/kg FLX or saline vehicle. After approximately 2 weeks of treatment, mice were evaluated for activity (i.e., marble burying and open field) and memory within the fear conditioning paradigm.

Results: As previously reported, mice with HG showed reduced marble burying, reduced open field activity, and increased freezing in the conditioning context. Although FLX treatment did not reverse HG-induced burying or activity effects, it did reverse HG-facilitated freezing. This effect was independent of changes in HG-induced hippocampal Tnf expression.

Conclusions: This provides support for the utilization of the fear conditioning task to understand HG-associated changes in the negative valence systems. It also provides additional confirmatory data indicating that the basal lateral amygdala is sensitive to HG-induced dysfunction.

Introduction: The infant-parent relationship is theorized to be related to the origins of psychotic experiences, given the key role of infant-parent attachment and early-life caregiving in children's neurodevelopmental trajectories. Yet, the magnitude of this association is not well understood, and research is often based on self-reports. We examined the relationship of disconnected and extremely insensitive parenting and disorganized infant attachment with the occurrence of psychotic experiences in childhood and adolescence. We additionally examined the role of maternal experiences of loss, a hypothesized antecedent of disconnected parenting, disorganized attachment, and psychotic experiences.

Methods: This prospective study (N = 627) is embedded in the Generation R Study. Maternal experiences of loss within 2 years of the child's birth were self-reported. Parenting behaviors (based on continuous scores) and the infant-parent attachment were observed when infants were 14 months old. Psychotic experiences were self-reported via questionnaires at ages 10 and 14 years. We used a structural equation model adjusted for covariates to assess the association between maternal loss experiences, parenting behaviors, infant disorganized attachment, and psychotic experiences.

Results: Extreme insensitive parenting was associated with more hallucinations and delusions at age 14 years (hallucinations OR = 1.34, 95% CI = 1.07-1.66; delusions OR = 1.31, 95% CI = 1.02-1.68). Disorganized infant attachment and disconnected parenting were not related to psychotic experiences. Maternal experiences of loss were not associated with psychotic experiences, and we found no evidence for a pathway between maternal experiences of loss, parenting behaviors, or disorganized attachment, and subsequent psychotic experiences.

Conclusion: This study suggests that the role of disorganized infant-parent attachment in the risk of psychotic experiences of children from the general population might be smaller than expected. Instead, our results suggest that adverse caregiving behaviors related to harsh and maltreating parenting very early in development may predict psychotic experiences in adolescence.

Background: Cardio-cerebrovascular events continue to pose major life-threatening risks worldwide. Though approved for treatment of angina pectoris and ischemic stroke, the effects of tongxinluo, as a traditional Chinese medicine, on stroke and major adverse cardiovascular events (MACE) after atherosclerotic cardiovascular disease (ASCVD) remain controversial.

Objective: This study aims to assess the efficacy of tongxinluo in the secondary prevention of ASCVD.

Methods: The present systematic review was conducted following PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. In this study-level meta-analysis, we conducted a comprehensive search of medical libraries and clinical trial registries, spanning from their inception until November 20, 2024, and randomized controlled trials (RCTs) comparing tongxinluo versus no tongxinluo in a secondary prevention. The ASCVD population was included. The primary outcome was stroke and MACE. The secondary outcome was MACE and myocardial infarction.

Results and conclusion: Four RCTs, including 7087 patients with known coronary artery disease, ischemic stroke, or carotid artery plaque, were included in the analysis. Compared to placebo, tongxinluo numerically decreased the risk of stroke with a RR of 0.84 (95% CI: 0.61-1.17, p = 0.31). For the outcome of MACE, tongxinluo reduced the risk by 28% (RR: 0.72, 95% CI: 0.59-0.88, p = 0.001). Patients randomized to tongxinluo had a RR of 0.70 (95% CI: 0.54-0.92, p = 0.01) for cardiovascular mortality and 0.74 (95% CI: 0.56-0.92, p = 0.01) for all-cause mortality. In summary, in patients with ASCVD, tongxinluo tended to decrease the incidence of stroke, and reduced the composite of stroke, myocardial infarction, and cardiovascular mortality by 28%.

Objective: Patients with Cushing's disease (CD) exhibit white matter (WM) microstructural injury, yet the underlying mechanisms remain incompletely understood. This study aims to investigate the role of glymphatic function in WM damage among patients with CD.

Methods: A total of 69 patients with CD and 64 healthy controls(HC) were enrolled. Glymphatic system function was evaluated using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. WM microstructural injury across 42 tracts was assessed via fractional anisotropy (FA) and mean diffusivity (MD). Serum cortisol levels were quantified using chemiluminescence immunoassay.

Results: Compared with HC, patients with CD exhibited significantly reduced DTI-ALPS indices (p = 0.026). Widespread WM microstructural injury was observed, characterized by decreased FA in 25 tracts and increased MD in 40 tracts. Correlation analyses revealed that in patients with CD, the DTI-ALPS index showed a significant positive correlation with FA values of the right superior longitudinal fasciculus III (SLF III_R; r = 0.42, p = 0.033) and a significant negative correlation with 00:00 cortisol levels (r = -0.354, p = 0.004). Furthermore, mediation analysis confirmed that the DTI-ALPS index fully mediated the effect of 00:00 cortisol level on the reduction of FA in the SLF III_R (ACME = -0.138, 95% CI: [-0.319, -0.013], p = 0.021).

Conclusion: This study provides the first evidence of glymphatic functional impairment in patients with CD. Our findings suggest that aberrantly elevated midnight cortisol levels serve as a primary driver of this glymphatic functional impairment. Furthermore, this impaired glymphatic function fully mediates the impact of 00:00 cortisol levels on microstructural injury to the SLF III_R.

Objective: Myasthenia gravis (MG) is an autoimmune disease involving several immune mechanisms. Recently, semaphorins have emerged as potential diagnostic and prognostic biomarkers in autoimmune neurological and non-neurological diseases. This study investigated the role of immune semaphorins, namely semaphorins 3A, 3F, 4A, 4D, and 7A, in the diagnosis and prognosis of MG and their potential as biomarkers.

Methods: Serum levels of semaphorin 3A, 3F, 4A, 4D, and 7A were compared between 41 patients with MG and 39 healthy controls. Patients were grouped according to the Myasthenia Gravis Activities of Daily Living scale, and differences in semaphorin levels between groups were analyzed.

Result: Semaphorin 4A levels were significantly lower, whereas semaphorin 7A levels were higher in patients with MG than in controls. However, no significant correlation was found between the disease stage and semaphorin levels.

Conclusion: Our findings suggest that the levels of semaphorin 4A and 7A may not only support the diagnosis of MG and aid in differential diagnosis but also shed light on the development of future therapeutic protocols targeting semaphorin proteins and receptors in other autoimmune and inflammatory diseases.

Objective: To examine the association between alterations in specific fiber tracts and 6-m gait speed and cognitive function in patients with clinically diagnosed Alzheimer's disease (AD) using fixel-based analysis (FBA).

Methods: Participants included 26 probable AD patients with slow gait speed (AD-SGS), 28 without slow gait speed (AD-nSGS), and 28 normal controls (NC).  All subjects underwent neuropsychological assessment, 6-m gait speed testing, and cranial magnetic resonance imaging (MRI) scans. FBA was employed to derive white matter (WM) fiber metrics, including fiber density (FD), fiber cross-sectional area (FC), and fiber density and cross-sectional area (FDC). After adjustment for age and sex, the mean index values of the fiber tracts showing significant between-group differences were extracted for the correlation between fiber properties, neuropsychological test scores, and parameters related to physical function.

Results: AD-SGS group exhibited significantly reduced FD and FDC in the left inferior fronto-occipital fasciculus (IFOF_L) compared to AD-nSGS group. In probable AD patients, FDC values of IFOF_L were positively correlated with global cognitive function, attention and calculation abilities, executive and visuospatial functions, and information processing speed. Furthermore, FD value of IFOF_L was positively correlated with 6-m gait speed.

Conclusions: In this clinically diagnosed AD patient with slow gait speed, the microstructural integrity of IFOF_L is closely linked to both cognitive decline and motor deficits. The structural deterioration of this tract is associated with the interplay between gait disturbance and impairments in executive and visuospatial functions, and information processing speed in this clinical context.

Background: Edaravone dexborneol is a neuroprotective agent combining the free-radical scavenging properties of edaravone and the anti-inflammatory, blood-brain barrier-modulating effects of dexborneol. While international trials have demonstrated favorable safety and potential clinical benefit, data in Filipino patients remain lacking. This study evaluated the real-world safety and tolerability of edaravone dexborneol among Filipino patients with acute ischemic stroke.

Methods: This was a single-center, open-label, single-arm, prospective study conducted under a compassionate-use program. Patients aged 18-80 years with clinically confirmed acute ischemic stroke within 48 h of onset received edaravone dexborneol (30 mg edaravone + 7.5 mg dexborneol) twice daily for 14 days. Safety monitoring continued until Day 20. Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) were classified using the International Council for Harmonisation (ICH E2A) criteria, and causality was assessed using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) categories.

Results: Twenty-seven of 29 enrolled patients completed the 14-day regimen. Mean age was 55.7 ± 12.8 years; 66.7% were male. Overall, 15 patients (55.6%) experienced at least one TEAE, most commonly headache (29.6%), which occurred on Day 0 and resolved within 0.7 ± 1.2 days. Elevated liver enzymes were observed in 25.9% for aspartate transaminase (AST) as well as for alanine aminotransferase (ALT), generally mild and self-limited. One patient developed both moderate transaminitis and acute kidney injury, attributed to concurrent antituberculosis therapy rather than the study drug. No treatment discontinuations, life-threatening reactions, or deaths occurred.

Conclusion: Edaravone dexborneol demonstrated a favorable safety profile in Filipino patients with acute ischemic stroke, with adverse events (AE) predominantly mild, transient, and reversible. These real-world findings align with international data and support their potential incorporation into acute stroke management pathways in the Philippines.

Introduction: Creative ability is an important outcome of developmental support programs, as it helps to lay the foundation for better long-term participation and well-being. Children with learning differences risk underdeveloping this potential, especially those in rural, low-resource African settings.

Aim and methods: This study aimed to determine the potential outcomes of Create2Grow, a new community-based occupational therapy visual arts group intervention for children aged 8 to 12 years with mild to moderate neurodevelopmental disorders, using a case series research design with eight children recruited via convenience sampling.

Results: The intervention had a large clinical effect on participants' caregiver-rated Canadian Occupational Performance Measure scores (d = 1.5) and clinician-rated Creative Participation Assessment scores (d = 1.76) from pre- to post-intervention. Create2Grow was also rated as highly in demand, acceptable, and practical for the target group. Low study attrition rates showed that the intervention could be effectively implemented at a local school within the community.

Conclusion: Create2Grow is a promising solution to promoting the creative ability of children with learning differences in rural, low-resource settings in Africa.

Objective: Opioid use disorder is associated with persistent molecular and cellular changes in the brain, leading to compulsive drug-seeking behaviors. This study aimed to evaluate the effects of olanzapine (OLZ), a D2-like dopamine receptor (D2R) antagonist, on morphine dependence using the conditioned place preference (CPP) model.

Methods: Morphine-induced CPP was established by subcutaneous (sc) administration of morphine (5 mg/kg) for three consecutive days. OLZ at doses of 1.5, 3, and 4.5 mg/kg was administered intraperitoneally (ip) during different phases of CPP: acquisition, expression, and extinction. Behavioral assessments included measurement of conditioning scores and locomotor activity. D2R protein expression in the hippocampus (HIP) was evaluated using western blotting.

Results: OLZ reduced both acquisition and expression of morphine-induced CPP in a dose-dependent manner. Additionally, OLZ facilitated extinction by shortening the duration of the extinction phase. Western blot analysis showed a significant reduction in D2R protein expression in the expression and extinction phases in the OLZ-treated groups compared to the morphine-only group. Importantly, effective doses of OLZ did not impair locomotor activity.

Conclusion: OLZ attenuates morphine-induced CPP and downregulates D2R expression in the HIP without affecting general locomotor function. These findings suggest a potential therapeutic role for OLZ in the management of opioid-related behaviors. Further research is needed to determine its clinical relevance.

Purpose: Glioma progression is often accompanied by language dysfunction, and postoperative recurrence is nearly inevitable, especially in high-grade cases. This study aimed to identify valuable language-based prognostic markers and improve risk management strategies.

Methods: A retrospective longitudinal cohort of 191 glioma patients (2010-2018) was analyzed. Language status was assessed using the Aphasia Battery of Chinese (ABC), adapted from the Western Aphasia Battery. Principal component analysis (PCA) addressed collinearity in language scores, and Cox regression identified predictors for a survival model. Bootstrap validation and SHapley Additive exPlanations (SHAP) were used to confirm model stability and interpretability. Logistic regression was used to test associations between predictors and pathological molecular parameters.

Results: Auditory verbal comprehension & writing and repetition emerged as key language predictors in the Cox model, achieving an AUC of 0.834. SHAP analysis confirmed their dominant contribution, defining the model as the Language Tests Combinations (LTC) model. Two-sample t-tests revealed significant differences in language scores between IDH1/2-mutant and wild-type groups. Logistic regression showed strong correlations between language predictors and molecular parameters (MGMT codeletion: AUC = 0.922; 1p/19q: AUC = 0.813; IDH1/2: AUC = 0.748), with tumor locations included as dummy variables.

Conclusion: Language components were identified as robust predictors of glioma recurrence and were significantly associated with key molecular features. The LTC model represents an internally validated and interpretable exploratory prognostic framework that may complement existing risk-stratification approaches and inform future studies on postoperative glioma management.