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Sleep disturbance is a core feature of affective and neurodegenerative disorders. This study tracks long-term sleep disturbance trajectories and their links to incident Alzheimer's disease (AD) and longitudinal clinical and pathological changes. A total of 774 non-demented participants from the ADNI cohort were included. Sleep disturbance (NPI sleep item) trajectories over 8 years were identified via group-based trajectory modeling. Cox proportional hazards regression was used to estimate the risk of incident AD. Linear mixed-effects models were used to assess longitudinal changes in cognition, structural magnetic resonance imaging, amyloid-&#x3b2; positron emission tomography (A&#x3b2;-PET), fluorodeoxyglucose (FDG)-PET, and cerebrospinal fluid (CSF) biomarkers. Three trajectories emerged: "Low-stable" (37.2%), "High-peaked" (21.0%), and "Moderate-increasing" (41.8%). Compared to those without sleep disturbance, a significantly elevated risk of incident AD was associated with "High-peaked" (hazard ratio [HR]&#x202f;=&#x202f;3.28; 95% confidence interval [CI] = 1.89-5.70; p&#x202f;<&#x202f;0.001) and "Moderate-increasing" trajectories (HR&#x202f;=&#x202f;2.13; 95% CI = 1.28-3.53; p&#x202f;=&#x202f;0.003) but not with the "Low-stable" trajectory (p&#x202f;=&#x202f;0.888). Participants with "High-peaked" trajectory exhibited faster declines in cognition (MMSE, memory, executive function) (p&#x202f;<&#x202f;0.050) and a steeper reduction in CSF A&#x3b2;1-42 levels (p&#x202f;=&#x202f;0.038) than those with non-sleep disturbance. However, there were no significant differences between groups in the rates of hippocampal, entorhinal, or middle temporal atrophy, global A&#x3b2;-PET burden, or FDG-PET changes (p&#x202f;>&#x202f;0.050). "High-peaked" and "Moderate-increasing" sleep trajectories predict higher AD risk, faster cognitive decline, and faster A&#x3b2;1-42 reduction. Long-term monitoring of sleep behaviors is essential for identifying and stratifying individuals at high risk for AD.

Paroxysmal kinesigenic dyskinesia is a rare neurological disorder characterized by brief, recurrent motor attacks that significantly impair quality of life. Prior studies have largely relied on unimodal data, which offer partial insights into neural regulation but are constrained by trade-offs between temporal and spatial resolution. To address this limitation, we developed a multimodal recognition and tracing framework integrating electroencephalography and functional magnetic resonance imaging. We propose GTBL-AF, a deep multimodal neural architecture that captures spatial connectivity and temporal dynamics of brain function through graph attention, Transformers, and bidirectional long short-term memory networks, with cross-attention enabling modality-level fusion. GTBL-AF achieved 94.2% classification accuracy in paroxysmal kinesigenic dyskinesia recognition, significantly outperforming unimodal methods. Incorporating dipole-based electroencephalography source localization and phase-locking value connectivity, we observed increased temporal complexity and reorganized functional connections in key cortical regions, including the prefrontal cortex, temporal pole, and parietal association areas. Whole-brain analyses using sample entropy and small-world metrics revealed greater dynamic uncertainty and enhanced small-world properties in paroxysmal kinesigenic dyskinesia patients, indicative of compensatory neural regulation. Furthermore, network-based statistics identified aberrant synchronous connectivity within circuits mediating cognitive control and motor initiation. This study presents a deep EEG-fMRI multimodal fusion framework for PKD and provides evidence of widespread network reorganization. These findings may contribute to a better understanding of PKD pathophysiology and provide a methodological reference for future multimodal-assisted diagnosis and individualized clinical assessment. The online version contains supplementary material available at 10.1007/s11571-026-10504-5.

Continuing medical education (CME) is crucial for maintaining the competency of general practitioners (GPs). Understanding factors associated with GPs' perceived necessity of CME is essential for optimizing training programs, especially in resource-constrained regions. This study aimed to identify factors associated with GPs' perceived necessity of CME in Southeast Henan, China. A cross-sectional survey was conducted among GPs in Zhoukou City, Southeast Henan, from August to September 2024. Data were collected via an online questionnaire. The primary outcome was the perceived necessity of CME (binary: yes/no). Univariable and multivariable logistic regression analyses were employed to identify factors associated with this outcome. Structural equation modeling (SEM) was used to explore pathways linking CME policy cognition, self-efficacy, attitude towards CME, and perceived necessity. Among 5537 eligible registered GPs, 2,480 valid responses were obtained (response rate, 44.8%). Overall, 35.6% perceived CME as necessary, whereas 89.6% had participated in CME during the previous three years. In the multivariable model, understanding the linkage between CME credits and career advancement showed the strongest positive association with perceived CME necessity (adjusted odds ratio [aOR]=3.74, 95% CI: 2.97-4.72). Organizational support (aOR=1.76), high self-directed learning ability (aOR=1.60), absence of anxiety (aOR=1.37), and more than 30 years of practice experience (aOR=1.58) were also positively associated with perceived CME necessity. The perceived necessity of CME among GPs was associated with policy awareness, organizational support, psychological factors, and professional experience. These findings may inform policy transparency, organizational support, and tiered CME curricula that address the needs of GPs with different competency levels.

Global increases in occupational heat exposure are raising concerns about worker safety and cognitive performance during prolonged and repeated shifts. At present, the cumulative effects of repeated heat exposure on cognitive performance remain unclear. This exploratory study examined cognitive performance and perceived workload across three consecutive days of simulated occupational heat stress. Twenty physically active adults (age: 27&#x2009;&#xb1;&#x2009;6 years [5 female]) completed two randomized crossover trials comprising three consecutive 8-h workdays under hot (35&#xb0;C; 63% RH; WBGT 31&#xb0;C) and control (18&#xb0;C; 53% RH; WBGT 14&#xb0;C) conditions wearing minimal clothing (<&#x2009;1 Clo). Participants performed moderate-intensity physical work (~4.3 METs) using a 30-min work:30-min rest schedule. Cognitive performance was assessed at start-of-day, midday, and end-of-day using the Joggle Research battery, evaluating sensorimotor speed, processing speed, and attention, visuospatial perception, sustained attention, and visual memory. Perceived workload was assessed at start-of-day and end-of-day using the NASA Task Load Index. Cognitive performance was largely preserved across domains within and across repeated workdays, with no evidence of cumulative impairment (p&#x2009;&#x2265;&#x2009;0.170). Unexpectedly, sustained attention improved in the heat. Perceived physical workload was higher in the heat, while perceived mental workload was unchanged. Under prescribed work-rest conditions, cognitive performance appears to be maintained across consecutive days of occupational heat exposure in young, physically active adults. Future work should explore the relationship between heat and cognition in larger, more diverse work populations and in more challenging conditions.

Postural instability is a hallmark of advanced Parkinson's disease (PD) and substantially increases fall risk, injury incidence, and loss of functional independence. However, the mechanisms underlying impaired postural control, particularly sensory reweighting and adaptive regulation, remain incompletely understood. To characterize postural control in PD using rambling-trembling decomposition and stabilogram diffusion analysis (SDA), and to examine the effects of visual and cognitive demands as well as their clinical relevance. Sixty-four participants (42 PD; 62.81&#x202f;&#xb1;&#x202f;10.98 years; 22 age-matched healthy controls, 61.27&#x202f;&#xb1;&#x202f;12.29 years) performed quiet standing under four conditions combining vision (eyes open/closed) and cognitive load (single/dual task). Center of pressure signals were analyzed using linear metrics, rambling-trembling decomposition, and SDA parameters. Functional mobility and cognitive status were assessed. PD participants exhibited greater sway, increased rambling displacement, elevated trembling velocity, and prolonged critical time, indicating impairments across central, peripheral, and stochastic domains. Visual reweighting was disrupted, as patients failed to adapt postural dynamics under visual and cognitive constraints, while controls showed context-dependent modulation. Postural parameters were significantly associated with functional mobility in PD but not in controls, whereas associations with global cognition were limited. Postural instability in PD reflects a loss of adaptive control across multiple mechanisms linked to impaired visual reweighting. Multiscale postural analysis may provide clinically relevant markers and support the use of sensory and cognitive challenges in assessment and rehabilitation.

BackgroundPhysical exercise is widely recognized for its cognitive benefits; however, the effect of menopausal status in modulating the cognitive effects of exercise is not definitively established.ObjectiveTo examine the cognitive benefits of two 6-month physical exercise programs in cognitively healthy older women across adulthood, and whether menopause status moderates these benefits.MethodsIn a post hoc analysis of a randomized controlled trial, 93 cognitively healthy women (aged 20-67; 43% at post-menopause) were assigned to either aerobic exercise (AE) or stretching/toning (ST) 4 days a week for six months. Neuropsychological assessment, cardiorespiratory exercise test, and blood draw were performed at baseline, 3-months, and 6-months. Linear mixed-effects regression models assessed whether menopausal status moderated the impact of exercise on executive functions and processing speed.ResultsSeventy-six participants (81.7%) completed the intervention. A time-by-group-by-menopause interaction emerged after 3 months (&#x3b2;&#x2009;=&#x2009;-0.89; p&#x2009;=&#x2009;0.001) and 6 months (&#x3b2;&#x2009;=&#x2009;-0.67, p&#x2009;=&#x2009;0.016). Post-menopausal women in the AE group showed greater improvement in executive functions compared to the ST group and pre-menopausal women. Models controlled for age, education, and baseline cognitive performance.ConclusionsOur results provide novel evidence that AE improves cognition with pronounced executive functions benefits in post-menopausal women, a population at higher risk for dementia. Since women are at a higher risk of developing Alzheimer's disease compared to men, these findings support AE as a relevant strategy to promote women's brain health. Although this is a secondary analysis, it may inform future exercise trials targeting women.

Hepatic encephalopathy (HE) is a complex neurocognitive disorder stemming from liver dysfunction, ranging from subtle cognitive impairments to profound coma. It develops when the liver's detoxification capacity is compromised, leading to an accumulation of neurotoxins like ammonia that disrupt brain function. From an intensivist's perspective, HE is more than mere confusion; it's a critical brain-liver syndrome demanding careful airway management, hemodynamic stability, and vigilance against cerebral edema and intracranial hypertension. HE is categorized into three types: Type A, associated with acute liver failure (ALF), poses the highest risk for rapid neurological decline and cerebral herniation, making it particularly relevant in critical care. Type C, prevalent in cirrhotic patients, is more common and often coexists with other organ failures. Type B HE, though less recognized, occurs with portosystemic shunting. For intensivists and anesthesiologists, prompt recognition and a structured management approach are paramount. This involves identifying and treating precipitating factors, stabilizing cardiorespiratory function, reducing ammonia levels, and preventing cerebral edema. Ongoing assessment of liver function and consideration for urgent liver transplantation, especially in Type A HE, are crucial. A deep understanding of HE's pathophysiology guides aggressive interventions such as continuous renal replacement therapy, plasma exchange, and intracranial pressure monitoring in select cases.

"What's in a name?" is more than a literary question for advanced Parkinson's disease (APD). Although APD is widely used in clinical practice, what constitutes "advanced" remains poorly defined and inconsistently applied. Existing definitions have often anchored APD to motor complications, treatment complexity, or eligibility for device-aided therapies (DATs). These approaches are useful for referral and treatment planning, but they risk mistaking a treatment phenotype for the whole disease state. They also fail to capture the broader burden of progression, including non-motor symptoms, cognitive decline, functional dependence, psychosocial consequences, caregiver burden, frailty, and biological heterogeneity. We argue that APD is best understood as a multidimensional state reflecting cumulative neurodegeneration and its lived, functional, and therapeutic consequences, rather than a single stage, motor phenotype, or treatment milestone. This narrative review reframes APD through five interconnected axes: clinical symptom burden; perceived disease impact; functional consequences and participation restriction; therapeutic complexity, refractoriness, and treatment-related complications; and markers associated with disease progression. We propose that APD is a multidimensional clinical state that emerges as PD progresses, when cumulative burden across these five domains exceeds the capacity of patients and caregivers to compensate, adapt, and maintain independence, resulting in progressive disability and reduced quality of life. This framework distinguishes DAT-eligible PD, late-stage PD, and overlapping intermediate phenotypes, while accommodating emerging markers without replacing clinical judgement. By making the name APD correspond more closely to clinical reality, this framework may support earlier recognition, appropriate referral, patient-centred therapeutic planning, and more consistent research stratification.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease. Despite advances in the understanding of the genetics of AD, environmental risk factors are still under investigation, and the etiology is still not completely understood. The environmental component of AD, which we explore in the first part of this review, takes on greater importance with more advanced disease onset. Moreover, genetics does not explain all of AD. Environmental risk factors are divided into modifiable and nonmodifiable risk factors. Among the modifiable risk factors, nutrition seems to play a predominant role. One-carbon metabolism (OCM) is involved in this food-related component, notably through B vitamins. Homocysteine, a sulfur-containing amino acid, is at the crossroads of OCM. Abnormal increases in homocysteine levels (hyperhomocysteinemia) are associated with deleterious effects on cognition. Various mechanisms can lead to hyperhomocysteinemia, including genetic factors associated with different polymorphisms, dietary deficiencies targeting vitamins B9 and B12, and renal insufficiency. The second part of the review details OCM and the role of homocysteine. Finally, part 3 highlights the numerous studies in the literature describing the association between hyperhomocysteinemia and cognitive decline. However, the mechanistic links between hyperhomocysteinemia and cognitive decline in AD are poorly understood. Several hypotheses have been proposed in the literature. The toxic effects of homocysteine could be mediated by N-homocysteinylation, a nonenzymatic reaction leading to the irreversible accumulation of N-homocysteinylated proteins. Finally, we detail some therapeutic trials targeting one-carbon metabolism in AD, notably vitamin B9 and B12 supplementation.

Alexithymia is associated with a lack of flexibility at several stages of emotion regulation. Additionally, previous studies associated higher alexithymia with particularities in emotional facial expression perception, and with lower executive performance. The objective of the study was to explore the cognitive factors that may underlie the lack of flexibility associated with emotion regulation in alexithymia. One hundred and twenty-six non-clinical adults underwent Go/no-Go tasks with neutral and emotional material (positive and negative emotional facial expressions of low vs. high arousal levels). The results first show that emotional stimuli had an effect on inhibition that was differentiated according to both valence and arousal levels. Alexithymia scores were never associated with executive performance in neutral blocks but moderated the effect of emotional stimuli depending on the valence and arousal combination in emotional blocks. Most of the moderation effects led to higher performances: higher alexithymia scores moderated the effect of emotional stimuli on inhibitory and perceptual performances, but direction of effects, facets and emotional stimuli involved are not consistent. We discuss the implications of these findings in terms of emotional salience effects on cognition and their potential role in alexithymia.

Pathogenic variants in AUTS2 are associated with neurodevelopmental disorders, commonly characterized by intellectual disability and autism spectrum disorder. Epilepsy in AUTS2-related syndromes has been reported only in a limited number of patients, usually with scant information on the electroclinical features and longitudinal outcome. We report a proband with AUTS2-related syndrome and performed a narrative literature review. The electroclinical features of our case fall within the spectrum of a developmental/epileptic encephalopathy with spike-wave activation in sleep. This case highlights the importance of a detailed electroclinical characterization of epilepsy in AUTS2-related syndrome and underscores the need for systematic EEG and cognitive monitoring to improve clinical management.

Pragmatic competence is crucial for effective social interaction and well-being, and yet it tends to decline with age. While most research has focused on basic linguistic skills, the multimodal nature of communication and the cognitive processes that support it have often been overlooked. The present study aims to address these gaps by assessing pragmatic-communicative ability in aging - including linguistic, extralinguistic, and paralinguistic expressive means - and examining the cognitive mechanisms underlying this decline, in particular Executive Functions (EFs), Theory of Mind (ToM), and Cognitive Reserve (CR). We analyzed communicative-pragmatic ability in 84 healthy adults in three age groups (20-40, 65-75, 76-86&#xa0;years) using the Assessment Battery for Communication (ABaCo). A comprehensive neuropsychological battery enabled the assessment of basic cognitive functions, EFs, ToM, and CR. The results show that older adults demonstrate lower performance in both pragmatic and cognitive domains. EFs emerged as predictors of communicative-pragmatic competence, while ToM appeared to play a less important role. Noteworthy, CR, particularly as reflected in educational background, attenuated age-related decline in pragmatic ability. This study extends our understanding of the cognitive factors contributing to pragmatic decline, as well as protective mechanisms involved. It also emphasizes the need for targeted cognitive and communicative interventions to promote effective communication in older adults.

Duchenne muscular dystrophy (DMD) causes progressive muscle degeneration due to dystrophin deficiency. Dystrophin is also expressed in the brain during development and postnatally, yet a characterization of dystrophin isoform expression across brain cells and regions is lacking, limiting our understanding of the cognitive impairment affecting one-third of the patients and hampering the development of dystrophin-restoring drugs in the central nervous system (CNS). Here, we applied spatial transcriptomics to map Dmd isoforms across mouse brain regions and cell types. Mdx52 mice received exon 51-skipping therapies restoring the Dp427-sized isoform at the transcript and protein levels. We observed distinct spatial patterns: full-length isoforms localized to deeper cortical layers and CA1, while shorter isoforms were enriched in cortical layer 1 and dentate gyrus. We present evidence of isoform restoration, immune activation following treatment, and a framework to evaluate exon-skipping therapies in the CNS using spatial transcriptomics.

Amyloid-&#x3b2; (A&#x3b2;) accumulation begins many years before the onset of clinical symptoms in Alzheimer's disease (AD). Studies in humans suggest that unimpaired individuals with elevated A&#x3b2; exhibit subtle changes in cognitive trajectories over time, particularly in memory. Identifying animal models that recapitulate these early changes is critical for translational research on preclinical AD. Here, we hypothesized that aging dogs, which naturally accumulate A&#x3b2;, show similar patterns to those observed in humans. Forty-three beagles underwent longitudinal cognitive testing on tasks assessing spatial memory, landmark discrimination, and reversal learning, while A&#x3b2; burden was measured using cerebrospinal fluid A&#x3b2;42/40. Parallel analyses were conducted in cognitively unimpaired older adults from the Harvard Aging Brain Study (n&#x202f;=&#x202f;287) using A&#x3b2; PET imaging and neuropsychological assessments. Despite no baseline differences, dogs with lower CSF A&#x3b2;42/40 showed worse longitudinal trajectories on a spatial memory task. No comparable effects were observed for landmark discrimination or reversal learning. Using a data-driven approach, Low CSF A&#x3b2;42/40 dogs were more likely to be classified in the Lower trajectory group than High CSF A&#x3b2;42/40 dogs. A similar pattern emerged in humans: A&#x3b2;+ individuals showed lower memory trajectories compared to A&#x3b2;- individuals. Across species, memory deficits were characterized by reduced benefits of practice effects rather than abrupt decline. Together, these findings suggest that aging dogs show A&#x3b2;-associated memory trajectories that parallel patterns observed in cognitively unimpaired older adults and support the canine model as a valuable translational platform for studying the earliest stages of AD.

Faces and voices are some of the most salient sources of information for identifying others' emotions. However, little research has focused on how emotional prosody modulates the earliest stages of face perception at the neural level. This study investigated priming effects of emotional prosody on the time course of subsequently presented emotional faces using event-related potentials (ERPs). Auditory prosodic primes (spoken sentences filtered to remove semantic information) expressing happy, neutral, or angry emotion were presented and immediately followed by a face expressing a congruent or incongruent emotion. After each trial, participants (n = 58) rated the face on valence and arousal. ERPs time-locked to face onset were analyzed at all time points and electrodes using data-driven mass univariate statistics. A significant main effect of face emotion was found spanning the N170, P2, and early EPN components. A significant main effect of voice emotion was found from approximately 50-100 msec and 150-400 msec, interpreted as increased attention in V1 and other non-face visual areas due to arousing vocal stimuli, especially angry ones. Critically, these factors did not interact, suggesting that face-voice congruency did not affect early perceptual face processing in this context. Behavioural results, however, showed that voice emotion influenced ratings of face valence and arousal, suggesting that voice prime and face information are integrated only at later cognitive but not early perceptual stages. Thus, prosody primes influenced visual processing before and after facial expressions were decoded, but face-voice congruency did not modulate early face emotion processing.

Adolescents in low-resource settings hold positive attitudes toward sexual and reproductive health (SRH) services, yet fail to use them. This study presents a theoretical reinterpretation of mixed-methods data (N = 408 adolescents, aged 13-19) from Uganda's Busoga region, through Festinger's Cognitive Dissonance Theory. Quantitative findings showed health-seeking attitudes predicted SRH service utilization (&#x3b2; = 0.910, p < .001) and future intentions (&#x3b2; = 1.976, p < .001), but 52% of adolescents had no SRH service contact in past year, and mean uptake scores remained below 2.0 on a 5-point scale. Qualitative analysis of focus group discussions identified three dissonance-reduction strategies: avoidance of health facilities, rationalization through misinformation, and selective information-seeking from peers. The reinterpretation proposes four intervention strategies: barrier reduction, community norm campaigns, cues to action with immediate access, and targeted messaging for working and rural adolescents. Addressing psychological discomfort and structural barriers may help close the attitude-behaviour gap.

This study examined whether the Brief Observation of Social Communication Change (BOSCC) yields consistent scores when administered by parents versus professionals within the same home environment. Forty-one toddlers (73% male; mean age 28.2 months) at elevated likelihood for autism spectrum disorder completed two BOSCC sessions at home: one parent-led and one professional-led, following identical procedures. The domains, Social Communication (SC), Restricted and Repetitive Behaviours (RRB), and Other Abnormal Behaviours (OAB), were scored by independent coders. Scores were compared using paired t-tests or Wilcoxon signed-rank tests, and consistency was assessed with correlations. No significant differences were observed between parent- and professional-led sessions for Total BOSCC scores or the SC, RRB, or OAB domains (all p > .19; Cohen's d&#x2009;<&#x2009;0.15). Correlations were strong for Total (&#x3c1;&#x2009;=&#x2009;0.90), SC (&#x3c1;&#x2009;=&#x2009;0.83), and RRB (r&#x2009;=&#x2009;.78) scores, indicating high consistency. OAB scores exhibited only moderate correlation (&#x3c1;&#x2009;=&#x2009;0.33), which became non-significant following outlier exclusion. BOSCC reliably captures core autism-related behaviours (SC and RRB) irrespective of whether the session is led by a parent or a professional. Parent-led administration in the home is a valid and scalable approach for naturalistic behavioural monitoring and intervention assessment.

While the impact of prosody on sentence processing in a first language (L1) has been widely studied and is well-documented, the extent to which second language (L2) learners utilize prosodic cues remains less clear. This study investigated how prosody affects the resolution of prepositional phrase (PP) attachment ambiguity, particularly when combined with visual contextual cues, and compared the performance by native English speakers and Chinese learners of English. Participants' attachment preferences alongside their reaction time from both correct and incorrect responses were analyzed to assess differences in L1 and L2 sentence processing. The results reveal that native participants were able to make effective use of prosodic information to resolve PP-attachment ambiguity, even when the accompanying visual context biased a noun phrase attachment. In contrast, the Chinese L2 learners showed a strong and consistent preference for the verb phrase attachment. This suggests that their sentence processing relied more heavily on the structure-based parsing strategies. These contrasting patterns between L1 and L2 speakers highlight the challenges L2 learners have in coordinating multiple information sources, such as prosody and visual context, during language comprehension.

Lead is a persistent environmental heavy metal and a potent neurotoxin that continues to threaten global public health despite regulatory restrictions. Chronic and developmental exposure, particularly during early life, leads to persistent structural and functional disturbances in the central nervous system. This review provides a comprehensive analysis of the mechanisms underlying lead-induced neurotoxicity, integrating molecular, cellular, histopathological, and behavioral evidence from both rodent and zebrafish models. The review further summarizes blood-brain barrier disruption, oxidative stress, mitochondrial dysfunction, synaptic impairment, neuroinflammation, apoptosis, neurotransmitter dysregulation, and neurodevelopmental alterations associated with lead exposure in experimental animal models. Lead crosses the blood-brain barrier by mimicking essential divalent cations such as Ca2&#x207a;, Zn2&#x207a;, and Fe2&#x207a;, thereby disrupting calcium signalling and impairing neuronal communication. Once in the brain, lead induces oxidative stress through excessive reactive oxygen species generation, mitochondrial dysfunction, lipid peroxidation, DNA damage, and depletion of antioxidant defenses. Lead also impairs synaptic plasticity by altering NMDA receptor subunit composition, reducing synaptic protein expression, and dysregulating genes involved in neurodevelopment. In parallel, it activates both intrinsic and extrinsic apoptotic pathways and enhances neuroinflammatory signaling through microglial and astrocytic activation, further contributing to neuronal injury. Experimental studies demonstrate hippocampal degeneration, Purkinje cell loss, synaptic ultrastructural alterations, impaired long-term potentiation, and cognitive dysfunction in rodents. Zebrafish models reveal disrupted neurodevelopment, altered expression of gfap, huC, neurexin, and antioxidant-related genes, behavioral abnormalities, and circadian rhythm disturbances. Overall, the study indicates that lead neurotoxicity arises from interconnected mechanisms involving oxidative stress, synaptic dysfunction, apoptosis, mitochondrial impairment, and neuroinflammation. A comprehensive understanding of these pathways is essential for early risk assessment, therapeutic target identification, and the development of effective neuroprotective interventions against lead-induced brain injury.