AIMS Neuroscience最新文献

Background: Alzheimer's disease (AD) and mild cognitive impairment (MCI) are widely recognized for their hallmark cognitive deficits, typically characterized by progressive cognitive deterioration. However, neuropsychiatric symptoms (NPS), including depression, apathy, anxiety, irritability, and sleep disturbances, are increasingly prevalent in the early stages of these conditions and significantly influence the disease trajectory and patient outcomes. Importantly, neuropsychiatric symptoms often precede overt memory loss by several years, with subtle mood and behavioral disturbances serving as early pre-diagnostic markers of an underlying Alzheimer's pathology. Their presence complicates the diagnosis, accelerates the disease progression, and intensifies the caregiver burden. However, distinguishing NPS arising from neurodegeneration and primary psychiatric disorders remains a profound diagnostic challenge, thus delaying timely intervention and obscuring early disease recognition.

Objective: This structured narrative review examines the diagnostic complexities, clinical impact, and current management of NPS in early-stage Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI), alongside the biological underpinnings, clinical relevance, diagnostic challenges, and treatment perspectives. We argue that understanding and managing NPS is essential to improve the clinical outcomes, reduce the caregiver burden, and guide therapeutic innovation.

Methods: A structured narrative review of peer-reviewed studies published between 2012 and 2025 was conducted using PubMed, MEDLINE, Scopus, PsycINFO, Google Scholar, and CINAHL. The included studies investigated NPS prevalence, neurobiological correlations, and management strategies in individuals with AD or MCI.

Findings: NPS affects up to 80% of individuals with early AD or MCI, often preceding cognitive decline. The current management strategies heavily rely on non-pharmacological interventions such as caregiver support, behavioral activation, and structured routines, while pharmacological options remain limited by modest efficacy and safety concerns.

Discussion: Advancing knowledge of NPS and their association with cognitive decline is critical to establish more precise diagnostic criteria and to inform personalized therapeutic approaches. Future research should emphasize biomarker-driven diagnostics and the development of novel, targeted interventions that simultaneously address cognitive and neuropsychiatric domains to optimize outcomes for patients and caregivers. This study contributes to the field by reframing NPS as potential early biomarkers in the trajectory of MCI and dementia progression.

Computational modeling of excitatory/inhibitory (E/I) balance offers transformative insights into the neurobiological underpinnings of autism spectrum disorder (ASD). In this review, we examined the integration of neurotransmitter dynamics and genetic factors into multiscale computational frameworks to elucidate the mechanisms driving E/I dysregulation in ASD. We explored the pivotal roles of glutamate and GABA, the primary excitatory and inhibitory neurotransmitters, and the modulatory impact of serotonin and dopamine (DA), in shaping neural circuit stability, behavioral outcomes, and ASD core symptoms. Genetic mutations affecting synaptic proteins such as SHANK3, GRIN2A, and GABRB3 were highlighted for their capacity to disturb synaptic scaffolding and glutamatergic and GABAergic signaling, thereby shifting the E/I ratio. Computational approaches, ranging from detailed neuronal simulations to neural mass and spiking network models, captured the heterogeneous manifestations of E/I imbalance and aligned with molecular, neuroimaging, and electrophysiological findings in ASD. We discussed how these models informed individualized diagnostic strategies, enabled prediction of treatment responses, and offered targets for precision medicine. Major challenges included methodological inconsistencies, neurochemical measurement discrepancies, polygenic interactions, and the translation of model predictions into clinical practice. We concluded that the integration of neurotransmitter and genetic data within advanced computational models represents a significant advance toward unraveling ASD pathophysiology, with the promise of developing dynamic, personalized interventions. Ongoing efforts should emphasize longitudinal data, multiomic integration, sex-specific trajectories, and cross-disciplinary collaboration to further the clinical applicability and translational potential of computational E/I balance modeling in autism research.

When becoming a parent, caregivers undergo complex, and sometimes permanent, neurobiological alterations, and this area of neurobiology has been extensively studied for decades. Due to ethical concerns and experimental limitations, the first parental neurobiology experiments were exclusively performed using rodent animal model systems, such as mice, rats, and voles. More recent technological advancements, such as the functional MRI (fMRI) scan, have become widely adopted and led to great insight into the impact of parenting on human neurobiology. In this thematic literature review, we present key studies that provide insight into the relationship of pregnancy and parturition on maternal caregiving behavior and the relationship of postpartum on all parents. First, we examine the relationship of endocrine hormones such as estrogen, progesterone, oxytocin, and testosterone with the neurobiological development of a parent. Next, we describe the significant transformation of subcortical maternal circuit components that occur during pregnancy, and the changes in the volume of grey and white matter generated during the postpartum. These brain structure alterations contribute to the development of parental nurturing behaviors.

Understanding how individuals interact with reward-related cues in their environment provides insight into the neural mechanisms underlying motivation and personalized behavior. While monetary rewards for self are well studied, the neural basis of socially relevant rewards-such as filial reward-remains less understood. This study investigated functional and structural brain responses to reward gained from a cognitive task performance for self or for parents (filial) using functional MRI (fMRI) and diffusion MRI (dMRI) in young adults, reflecting personalized interaction with environmental cues. Thirty-two healthy young adults (17 males, mean age = 23 ± 1 years) performed a 2-back working memory task cued for reward conditions for self and for parents during fMRI scanning, followed by dMRI acquisition. Participants were categorized based on the reward condition in which they showed the highest score in task performance. Self-reported reward responsiveness scores were also collected. Random-effects fMRI analysis revealed activation of the putamen in the self-reward condition, more than in the filial reward condition. Using this region as a seed, probabilistic tractography was conducted to compute connection probability indices (CPI) to key target areas: anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), dorsolateral and ventrolateral prefrontal cortices, anterior/posterior insula, and amygdala. The nucleus accumbens (NAcc) was included as a comparative seed. While the cue for self-reward elicited activation in the reward area putamen, with higher white matter connectivity from the right putamen to the ACC, a cue for filial reward significantly activated the right insula. Lateralization to the right insula was also seen in the structural connectivity to NAcc in the filial group. Filial reward also displayed a positive relationship between white matter connectivity of left NAcc to PCC with reward responsiveness. These results demonstrate individualized neural responses shaped by the self and social relevance of the reward.

Whole-body vibration therapy (WBVT) is increasingly recognized as an alternative exercise modality with established benefits for musculoskeletal and cardiovascular health. Its effects on cognitive performance and autonomic regulation in healthy young adults, however, remain unclear. This within-subject study investigated whether acute WBVT influences executive function and heart rate variability (HRV). Thirty-six healthy volunteers (aged 18-25 years) completed two testing sessions separated by 7 days: a baseline (no vibration) session and a single 10-min WBVT session performed in a standing posture. Cognitive performance was assessed immediately after each session using a modified Stroop test, and electrocardiographic recordings were analyzed for HRV indices, including stress index, low-frequency (LF) and high-frequency (HF) power, LF/HF ratio, and mean heart rate. Compared with baseline, WBVT was associated with faster mean reaction times for congruent and incongruent Stroop stimuli (all p < 0.001) without changes in response accuracy. The stress index increased during the Stroop task relative to baseline (p = 0.052) and returned toward baseline following WBVT, whereas LF, HF, the LF/HF ratio, and total power showed no statistically significant changes. In this cohort, acute WBVT was associated with improved processing speed without measurable alterations in standard HRV metrics. These preliminary findings suggest that WBVT may transiently facilitate attentional processing in healthy young adults, but controlled trials with sham conditions and mechanistic measures are needed to confirm and contextualize these effects.

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) affecting young adults, particularly in North America and Europe, with nearly 2.5 million individuals impacted globally. Characterized by demyelination and neuronal damage, MS involves complex immune-mediated mechanisms. In this review, we focused on the pathophysiological processes of MS, highlighting the roles of T cells, B cells, and proinflammatory cytokines in driving demyelination, which are often the main focus of treatments in the form of immunotherapy. We emphasized remyelination as a key therapeutic target that is necessary for protecting axons and restoring neural function to solve the root problem. Emerging therapies, such as high-dose supplementation with vitamin D and glutathione, appear effective in regulating immune activity and lowering oxidative burden, thus supporting remyelination and neuroprotection. Preclinical models using toxin-induced demyelination have provided valuable insights into the mechanisms of remyelination and identified potential therapeutic targets like LINGO-1 antagonists. Clinical trials, particularly those involving the anti-LINGO-1 monoclonal antibody BIIB033, have demonstrated encouraging results in enhancing remyelination and improving clinical outcomes. LINGO-1 is an inhibitory protein that impairs OPC differentiation. Integrating these innovative approaches into clinical practice could revolutionize MS management by shifting the focus from managing symptoms to promoting CNS repair and long-term recovery. Continued research into the molecular mechanisms of remyelination and the development of targeted therapies is essential for advancing MS treatment and improving the quality of life for patients.

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation, demyelination, and neurodegeneration within the central nervous system (CNS). It predominantly affects women and young adults, with environmental and genetic factors contributing to its onset. MS presents a wide range of neurological symptoms due to the scattering of lesions in the CNS, often leading to vision, sensorimotor, and cognitive impairments. The clinical course of MS varies, with relapsing-remitting MS (RRMS) being the most common, followed by secondary progressive MS (SPMS) and primary progressive MS (PPMS). Diagnosis is based on clinical evaluation, MRI findings, and cerebrospinal fluid analysis, with the McDonald criteria playing a key role in confirming dissemination in time and space. Current treatments, such as disease-modifying therapies (DMTs) and steroids, focus on managing relapses and reducing long-term disability. Novel therapies, including remyelination and neuroprotective agents, are showing promise in advancing care. While these medications can slow progression and improve quality of life, MS remains an incurable disease that requires ongoing research to find more effective therapies. Surgical interventions are rare but can address severe symptoms like spasticity and bladder dysfunction, contributing to an overall personalized management approach.

Carnosine (β-alanyl-L-histidine) is an endogenous dipeptide widely distributed in mammalian tissues, especially skeletal and cardiac muscle cells, and, to a lesser extent, in the brain. While early interest in carnosine was given because of its role in muscle cell metabolism and athletic performance, it has more recently gained attention for its potential application in several chronic diseases. Specifically, brain aging and neurodegenerative disorders have received particular attention, as a marked reduction in carnosine levels has been described in these conditions. Carnosine exerts a wide range of biological activities, including antioxidant, anti-inflammatory, anti-glycation, metal-chelating, and neuroprotective properties. Mechanistically, it acts by inhibiting the production of advanced glycation end products (AGEs), buffering cellular pH, and regulating intracellular nitric oxide signaling and mitochondrial function. Its safety profile, the lack of toxicity, and significant side effects support its application for long-term therapeutic use. In this review, we aim to recapitulate and discuss the effects, dosages, and administration routes of carnosine in preclinical in vivo models, with a particular focus on neurodegenerative disorders where it has been shown to reduce oxidative stress, suppress neuroinflammation, modulate protein aggregation, and preserve cognitive function, all key features of neurodegeneration. Despite promising findings, there are gaps in the knowledge on how carnosine affects synaptic plasticity, neuronal remodeling, and other processes that play a central role in the pathophysiology of neurodegenerative disorders. Additionally, clinical translation remains challenging due to inconsistencies across in vivo studies in terms of dosage, treatment duration, routes of administration, and disease models, which affect reproducibility and cross-study comparability. Therefore, while carnosine emerges as a multifunctional and well-tolerated molecule, further research is needed to clarify its therapeutic relevance in human diseases. In this review, we also address future perspectives and key methodological challenges that must be overcome to effectively translate carnosine's biological potential into clinical practice.

In recent years, there has been increasing focus in neuroscience on the influence of social relationships and experience in the brain. Socioneuroscience has been created to make contributions to fully understand the social relations that influence the architecture and functioning of the brain. The scientific literature has shown the impact of the coercive dominant discourse that promotes violent relationships on neural changes that lead to negative health consequences. However, less research has been conducted on the changes produced when violent relationships are overcome and prevented. This article advances in this direction by analyzing a teacher's perception on the impact of the Zero Violence Brave Club (ZVBC) intervention on his students' wellbeing. To that end, data collection through communicative observation was gathered over five months of the ZVBC implementation in a 2nd grade primary school classroom. Our results indicated that, according to the teacher, relationships among students improved from the very first week throughout the implementation, improving the classroom climate, students' motivation, and wellbeing.

The persistent primitive trigeminal artery is the most common remnant of the embryonic carotid-basilar connection. While its anatomy is well documented, its clinical significance in strokes remains debated. Some studies suggest it predisposes ischemia through altered hemodynamics, whereas others report a protective role via collateral circulation. This review summarizes the current knowledge on the anatomy, imaging, and clinical implications of the persistent primitive trigeminal artery in strokes. A literature search of PubMed, Scopus, and Embase up to March 2025 identified relevant case reports, imaging studies, and clinical series. The artery typically arises from the cavernous segment of the internal carotid artery, courses alongside the trigeminal nerve, and terminates in the posterior circulation. Classification systems describe variations in its termination, course, and vascular supply. Magnetic resonance and computed tomography angiography are key diagnostic tools, each with their advantages and limitations. Evidence shows two opposing roles: either as a conduit for steal phenomena, turbulent flow, and thromboembolism or as a collateral channel that preserves cerebral perfusion during carotid or vertebrobasilar occlusion. Understanding this vessel's anatomy and potential hemodynamic effects are critical for accurate diagnoses, risk assessments, and treatment planning. Its dual nature highlights the importance of individualized evaluations and further research to clarify its role in strokes.