Frontiers in Behavioral Neuroscience最新文献

Background: Early intervention services (EIS) for first-episode psychosis (FEP) play a key role in shaping a better disease trajectory for both affective and non-affective psychosis. Psychotic disorders tend to present sex differences both from an epidemiological and clinical perspective.

Aims: The primary aim of this study is to investigate sex-based differences in outcome of patients admitted to EIS for FEP, analysing clinical differences and recovery rates during a 24 months long follow-up.

Methods: A longitudinal cohort study was conducted. Patients were those admitted to the EIS in Ferrara between 2012 and February 27th, 2025 who met the following enrolment criteria: (a) diagnosed with affective or non-affective FEP; (b) not being treated for more than 24 months; (c) absence of intellectual disability; (d) aged between 18 and 35 years; (e) absence of organic psychosis. Socio-demographic and clinical characteristics were collected at program admission. The HoNOS (Health of the Nation Outcome Scale) was administered at baseline and every 6 months for the 24 months follow-up to compare sex differences in terms of symptoms severity and clinical recovery (HoNOS total score <8). Outcomes over time were compared between groups using mixed effects models repeated measures analysis of variance (MMRM).

Results: A total of 174 patients were included in the study, most were males (74.1%), and most men vs. women were born in Italy (81.4% vs. 66.7%, p = 0.04). At admission, men had significantly higher rates of cannabis use (56.6% vs. 22.2%), tobacco use (62% vs. 28.9%), and alcohol misuse (51.2% vs. 15.5%) (p < 0.001). Men, compared to women, at 6 and 12 months showed significantly lower clinical severity than women (11.9 vs. 14.5, p = 0.03; 9.4 vs. 11.9, p = 0.05 respectively), and higher probability of being in recovery at 12 months (p = 0.04), indicating a faster clinical improvement. At 24-month, more men than women were NEET (Not in Education, Employment or Training) (26.3% vs. 8%, p = 0.04).

Conclusion: Overall, our study highlighted significant sex differences both at admission as well as in outcomes. Men tend to improve more rapidly than women, then reaching a plateau with no substantial differences between sexes at 24 months. Further studies should identify sex-specific outcome predictors that could help in early patients' identification, thus leading to improve clinical trajectories and long-term prognosis.

Background: Preclinical studies have shown that exposure to a multisensory, stimulating environment (environmental enrichment, EE) can prevent the development of addictive behaviors and reduce the risk of relapse in animal models. However, the extent to which these preclinical findings apply to human addiction remains largely unknown. In this research, we investigated the role of EE in human substance use disorders (SUDs).

Methods: A new self-report measure of perceived EE was developed to test, in human participants, whether EE is associated with lower levels of SUD. This scale was administered to two distinct groups: regular smokers (N = 286) and patients diagnosed with severe alcohol use disorder (N = 52). Smokers also provided demographic information and data on nicotine use, while patients with alcohol use disorder reported pre-hospitalization drug intake, detoxification history, and levels of depression and anxiety.

Results: The EE scale demonstrated adequate psychometric properties, including a stable factorial structure and high test-retest reliability over 1 month. Among smokers, higher scores were significantly associated with lower nicotine consumption, dependence and craving. In patients with alcohol use disorder, lower scores were linked to a history of more frequent relapse. These effects were independent from depression and anxiety.

Conclusion: Environmental enrichment, as perceived and self-reported by individuals, appears to be a promising construct for understanding vulnerability and resilience in human addiction. The scale may serve as a valuable translational tool between preclinical and clinical models, with potential implications for the development of new intervention strategies for SUD.

The development of metacognition and executive functions supports adaptive and goal-oriented behavior in adulthood. Therefore, effective screening of these skills is essential for implementing early interventions in educational and clinical settings. While neuropsychological tests usually focus on a single skill and require clinicians to use lengthy batteries, the Metacognitive Wisconsin Card Sorting Test (Meta-WCST) assesses metacognition, executive functions, and their interaction. However, this test has not yet been scientifically validated for children with either typical or atypical development. This gap highlights both a methodological shortcoming and a missed opportunity for developmental neuropsychology. In this review, we provide a comprehensive analysis of studies involving the Meta-WCST, aiming to evaluate its translational potential for developmental applications. Despite several methodological limitations in the current literature, our evaluation indicates that the Meta-WCST can be adapted to developmental contexts through targeted improvements to theoretical and computational frameworks, data analysis methods, and protocol procedures. These considerations have meaningful implications for multiple areas of developmental neuropsychology, including scientific research, educational practices, and clinical assessments.

Introduction: Parkinson's disease (PD) is characterized by non-motor impairments including symptoms anxiety. These disturbances manifest in up to 40% of patients, most often early in the course of disease. While disruptive to all patients' lives, signs of anxiety are also more prevalent and/or more severe in female PD patients. Unfortunately, anxiolytic drugs are rarely used to manage these signs, as these medications can increase PD patients' risks for worsening of cognitive deficits and falls. The treatments commonly used in PD to improve patients' motor function or lessen signs of depression are often without positive effect on measures of anxiety. Thus, clinical needs for successful treatment of anxiety symptoms in PD are frequently unmet.

Methods: The work presented here used longitudinal Elevated Plus Maze (EPM) testing in male and female wild type rats and in male and female rats with knockout of the PTEN-induced putative kinase 1 gene (Pink1^-/- ) to determine whether these are suitable models for translational studies examining the neural substrates that underpin the sex-specific expression of anxiety symptoms in PD.

Results: Behavioral testing in male and female wild type and Pink1^-/- rats showed that Pink1^-/- rats of both biological sex initially displayed hyperlocomotion and broad, possibly impulsive exploration of all portions of the elevated plus maze, including its open, unprotected spaces. While these behaviors persisted in Pink1^-/- males, by 7 months of age, EPM performance in female Pink1^-/- rats changed dramatically and included convergent behavioral measures indicative of significantly heightened anxiety, e.g., reduced open arm entries, slower speeds of ambulation in open arms, avoidance of distal ends of open arms. These and other signs of an anxiety remained through final testing of the female Pink1^-/- cohort at 12 months of age.

Discussion: Unlike a surprising number of other rodent models of PD that fail to emulate clinically observed anxiety and/or male/female differences in these signs, the data presented here identify Pink1^-/- rats as strongly suited to lead translational efforts to better understand the neurobiological and neuroendocrine bases for anxiety symptoms in PD, their sex differences and their sex-specific sensitivities to therapeutic interventions.

Early life adversity (ELA) increases risk for multiple psychiatric disorders that are characterized by reward-related dysfunction. Disrupted reward-related processes are commonly observed in humans and rodents following ELA. Rodent studies have shown sex differences in response to natural and drug rewards at baseline, following ELA, and in rodent models of psychiatric diseases that are potentiated by ELA. Yet, less is known regarding the development of ELA-induced alterations in reward-related responses, including how these may differ by sex. To this end, we tested behavioral responses to consummatory and social rewards in control and scarcity-adversity male and female rats using sucrose preference, palatable food consumption, and social play tests during peripuberty and adolescence. Our results suggest no impact of early life scarcity-adversity during peripuberty, but sex- and reward-dependent adolescent effects in which females display reduced sucrose preference whereas males display lower levels of social play solicitations (i.e., dorsal contacts). These findings suggest age-, sex-, and reward-specific effects of early life scarcity-adversity in response to consummatory and social rewards, which appear to emerge during adolescence.

Introduction: The case of the Texas shooter is an event that marked human history, as an 18-year-old young man cold-bloodedly murdered 21 victims.

Objective: To analyze the psychological factors that could explain the antisocial behavior of the case under study.

Methodology: Through clinical behavioral analysis and data collection from the case, a psychological profile was constructed to identify specific factors that provide greater clarity regarding the risk factors associated with the violent act, which enabled the development of this perspective article.

Results: The study delves into several factors that could be considered determining and causal to the antisocial behavior in this case, including child abuse, family violence, bullying, animal cruelty, the impact of maltreatment on brain development, and the relationship between antisocial behavior and the use of violent video games.

Discussion: The analysis concludes by emphasizing the need to identify the causal factors of antisocial behavior in the early stages of human development. Additionally, it highlights the importance of implementing early interventions that can positively influence the factors described in this article.

Recent breakthroughs in marker-less pose-estimation have driven a significant transformation in computer-vision approaches. Despite the emergence of state-of-the-art keypoint-detection algorithms, the extent to which these tools are employed and the nature of their application in scientific research has yet to be systematically documented. We systematically reviewed the literature to assess how pose-estimation techniques are currently applied in rodent (rat and mouse) models. Our analysis categorized each study by its primary focus: tool-development, method-focused, and study-focused studies. We mapped emerging trends alongside persistent gaps. We conducted a comprehensive search of Crossref, OpenAlex PubMed, and Scopus for articles published on rodent pose-estimation from 2016 through 2025, retrieving 16,412 entries. Utilizing an AI-assisted screening tool, we subsequently reviewed the top ∼1,000 titles and abstracts. 67 papers met our criteria: 30 tool-focused reports, 28 method-focused studies, and nine study-focused papers. Publication frequency trend has accelerated in recent years, with more than half of these studies published after 2021. Through a detailed review of the selected studies, we charted emerging trends and key patterns, from the emergence of new keypoint-detection methods to their integration into behavioral experiments and adoption in various disease contexts. Despite significant progress in marker-less pose-estimation technologies, their widespread application remains limited. Many laboratories still rely on traditional behavioral assays, under-using advanced tools. Establishing standardized protocols is the key step to bridge this gap, which will ultimately realize the full potential of marker-less pose-estimation and even greater insight into preclinical behavioral science.

Sound influences motor functions and sound perception is conversely modulated by locomotion. Accumulating evidence supports an interconnection between the auditory system and the basal ganglia (BG), which has functional implications on the interaction between the two systems. Substantial evidence now supports auditory cortex and auditory thalamus inputs to the tri-laminar region of the tail of the striatum (tTS) in rodents. Thalamic input modulates the response gain of striatal neurons, whereas cortical input shapes their frequency tuning. Only recently has our understanding of BG projections to the auditory system advanced. GABAergic neurons in the tTS, which receive input from the auditory cortex, project to the posterior globus pallidus external segment (GPe). Posterior GPe, in turn, sends strong GABAergic projections to the non-lemniscal auditory thalamus (NLAT) and moderate projections to the cuneiform nucleus (CnF). The BG and auditory system are thus interconnected at multiple levels, forming a loop circuit in which the auditory system projects to the striatum and receives BG output via the NLAT. This circuit may mediate BG influence on auditory processing; however, the absence of motor cortex input to the tTS raises questions about its role in movement-related modulation of auditory responses. Given that the NLAT serves as a neural substrate for sound-cued aversive associative learning, BG output to the NLAT may influence learning processes. The pathway connecting the auditory system and CnF via the BG may underlie rhythmic entrainment in healthy individuals and therapeutic effects of rhythmic cues on gait in Parkinson's disease.

Introduction: Traumatic brain injury is the leading cause of death and disability in individuals under 40 years old. It induces various neuropathological outcomes, including cognitive, emotional, and physiological deficits, likely linked to early neuroinflammatory processes. In an animal model, mild traumatic brain injury (mTBI) has been shown to elevate oxidative stress biomarkers, such as advanced oxidation protein products (AOPP) and malondialdehyde (MDA), which persist for over a week. Despite extensive research on anti-inflammatory and neuroprotective therapies, most preclinical and clinical studies report limited efficacy. Synthetic glucocorticoids offer potential for early treatment of TBI-induced neuroinflammation, but clinical use is hindered by adverse effects and poor central nervous system biodistribution. Triamcinolone possesses anti-inflammatory, anti-angiogenic, and microglial inhibitory properties, although it has poor solubility and limited blood-brain barrier (BBB) penetration. Lipid nanocapsules (LNCs) may enhance TR solubility, bioavailability, BBB permeation, and intracellular delivery. This study aimed to evaluate the efficacy of triamcinolone-loaded LNCs (NT) on oxidative stress and cognitive-emotional outcomes following mTBI.

Methods: Adult male Wistar rats were subjected to closed-head mTBI via a 45 g weight-drop method, under anesthesia. Animals received NT, conventional triamcinolone, or empty LNCs, 15 minutes and 24 hours post-injury. They were sacrificed 24 hours, 1 or 7 days later for biochemical analysis of AOPP, MDA, and antioxidant enzymes (catalase and superoxide dismutase) activity in the hippocampus, prefrontal, and motor cortices. Separate cohorts underwent behavioral tests assessing memory (novel object recognition, Y-maze, and fear conditioning), 7 days after mTBI.

Results: mTBI induced significant impairments in recognition memory and fear retention, as well as increased AOPP, MDA, and CAT activity. SOD levels peaked at 24 h and normalized by day 7. NT, but not conventional TR, effectively prevented behavioral deficits and normalized OS markers. Importantly, early NT treatment reduced CAT overactivation at 7 days.

Discussion: This study provides the first evidence of the efficacy of NT in mitigating cognitive and emotional sequelae following mTBI, likely through enhanced brain delivery and early modulation of oxidative stress pathways.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction and restricted, repetitive behaviors (RRBs). These symptoms may stem from cognitive flexibility deficits, with dysfunction in the prefrontal cortex (PFC) and related neural circuits proposed as underlying mechanisms.

Objectives: This study examined whether transcranial direct current stimulation (tDCS) could enhance PFC activity and functional connectivity, thereby improving cognitive flexibility in a valproic acid (VPA)-induced ASD rat model.

Methods: Pregnant Sprague-Dawley rats were administered VPA (600 mg/kg, E12.5) or saline. VPA-exposed offspring exhibiting curved tails received tDCS and underwent behavioral tests, including the three-chamber social interaction test and cross-maze rule-shifting task, while local field potentials (LFPs) were recorded. Immunohistochemistry was performed to evaluate microglial activation (Iba1 +) and synaptic density (PSD95).

Results: Valproic acid -exposed offspring displayed significant social interaction deficits and impaired cognitive flexibility, alongside disrupted functional connectivity in frontal-striato-hippocampal circuits. Neuroinflammatory analysis revealed elevated Iba1+ microglial density (p < 0.05) and increased PSD95 expression (p < 0.05). After tDCS intervention, VPA rats exhibited restored sociability and cognitive performance, normalized functional connectivity, and significantly reduced microglial activation (p < 0.05), though PSD95 levels were unaffected.

Conclusion: Our results indicate that tDCS ameliorates ASD-like phenotypes in VPA rats, potentially through microglial suppression and PFC network synchronization. These findings support neuromodulation as a promising therapeutic approach for ASD-related cognitive dysfunction.