Search Results (89)

Anesthesia in older patients is challenging and requires a range of skills in various techniques, both during surgery and in the post-operative period. Post-operative delirium is one of the most common cognitive dysfunctions after surgery, and elderly patients are at the highest risk. The pathophysiology of post-operative delirium remains incompletely understood. Several mechanisms (vascular, neurodegenerative, neuroimmune, neuroinflammation, drug-induced, stress-induced, and monoaminergic) have been considered to play a role. The type of anesthesia—general (gas, total intravenous), regional, or combined—was identified as a predictive factor. However, numerous prospective and retrospective studies have failed to determine which anesthetic technique is the best for preventing post-operative delirium. The type of surgery appears to be more critical than the type of anesthesia. However, the development of post-operative cognitive dysfunction could be linked to the depth of anesthesia. Dexmedetomidine displayed promising therapeutic potential for the efficient prevention or treatment of hyperactive post-operative delirium. The management of hypoactive post-operative delirium still requires further investigations, particularly in elderly patients. Full article

Aquatic species are exposed to several long-chain per- and polyfluoroalkyl substances (PFASs) in the environment but their potential toxicity is not well studied. In this study, we assessed the effects of perfluoroundecanoic acid (PFUnDA) exposure on developing zebrafish. To do this, we investigated the potential for oxidative stress and neurotoxicity by measuring reactive oxygen species, apoptosis, gene expression, and locomotor activity. Mortality was evident in fish exposed to 1000 µg/L PFUnDA, and apoptosis was indicated in fish exposed to 100 µg/L PFUnDA via an increase in casp3 transcription. No change in reactive oxygen species in 7-day-old larval fish exposed to 0.01 up to 1000 µg/L PFUnDA was detected. Visual motor response analysis revealed hypoactivity in different light–dark periods that occurred in a concentration-specific manner. At the transcriptional level, several neurotoxicity-related genes (casp3, bdnf, gfap, gmfb, nkx2-2a) were significantly upregulated, further supporting neurotoxic effects. Overall, these findings indicate that PFUnDA disrupts neurodevelopment and behavior in zebrafish larvae, raising concerns for this long-chain PFAS. Full article

Critically ill patients are predisposed to developing cognitive dysfunction, excessive daytime sleepiness (EDS), and fatigue during their stay in the intensive care unit (ICU). Modafinil, a wakefulness-promoting agent, has demonstrated potential benefits in enhancing alertness, cognitive performance, and activity levels in various clinical populations. The present narrative review aims to systematically evaluate the existing literature regarding the administration of modafinil for the treatment of EDS and fatigue in the ICU context. A comprehensive literature search was performed using the Embase, MEDLINE, Web of Science, and Google Scholar databases, covering publications up to 20 June 2025. Studies investigating the use of modafinil to improve wakefulness in ICU patients were identified. A total of nine relevant studies were included, comprising two randomized controlled trials (RCTs), two case series, and five retrospective cohort studies (n = 950 patients). Four of these studies focused on patients with traumatic brain injury or post-stroke conditions, whereas the remaining studies addressed heterogeneous ICU populations. Preliminary evidence indicates that modafinil may enhance wakefulness in selected critically ill patients and potentially facilitate their participation in rehabilitative interventions, such as physical therapy. Nonetheless, robust conclusions regarding efficacy and safety remain limited by the small sample sizes and methodological constraints of the available studies. Consequently, further large-scale RCTs are warranted to elucidate the therapeutic role of modafinil in the management of EDS and hypoactivity among ICU patients. Full article

Postoperative neurocognitive disorders (PNDs) encompass a spectrum of cognitive dysfunction in the perioperative period. PNDs can present with hypoactive symptoms such as lethargy, hyperactive symptoms such as confusion and disorientation or a mix of both. PNDs can affect patients of all ages; however, the incidence of PNDs increases significantly as patients age. It is important to promptly recognize PNDs as patients can have higher morbidity and mortality, longer hospital stays, higher readmissions rates, and additional testing/treatment after discharge. In this review, we explore the molecular basis involved in brain aging as well as the mechanisms involved in anesthesia exposure and the development of PNDs. Understanding the mechanisms behind brain aging and the parallels to the pathophysiology of PNDs such as neuroinflammation, oxidative stress, mitochondrial dysfunction, and synaptic disruption are integral to mitigating the incidence and severity of PNDs. Current research suggests possible clinical targets for management such as dexmedetomidine and NSAIDs due to their abilities to combat harmful neuroinflammatory effects. Additionally, EEG-guided anesthesia, careful choice of anesthetics, and supportive measures can aid in mitigating PNDs. By understanding the mechanisms of brain aging, the risk factors for and pathophysiology of PNDs, we can better tailor our management of PNDs. Full article

Melanocortin receptors (MCRs) are responsible for various functions ranging from skin pigmentation, regulation of appetite, stress response and cognition, steroid synthesis, and energy balance to cellular regeneration and immunomodulation. The genetic polymorphism with tissue distribution ranging from the brain, limbic system, and adrenal cortex to neutrophils, monocytes, and macrophages is evident in MCRs. The mutations in MC1R, MC2R, MC3R, and MC4R genes are associated with risk of melanoma, familial glucocorticoid deficiency, obesity, and type 2 diabetes mellitus, respectively. Meanwhile, MC1R, MC2R, and MC5R genes are involved in the risk of major depressive disorder. Melanocortin receptors are involved in different inflammatory disorders, i.e., atopic dermatitis, autoimmune uveitis, sarcoidosis, respiratory diseases, multiple sclerosis, scleroderma, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer’s disease, arthritis, and reperfusion injury. Several newer therapeutic agents related to MCRs have numerous advantages over the current anti-inflammatory drugs, demonstrating therapeutic relevance. Among them, α-MSH analogs play a role in atopic dermatitis and scleroderma, and MC1R agonist Dersimelagon has shown effectiveness in systemic sclerosis. The FDA has recently approved the repository corticotropin injection (RCI) to treat sarcoidosis. The FDA has also approved various melanocortin agonists, i.e., Bremelanotide, Afamelanotide, and Setmelanotide, for the treatment of hypoactive sexual desire disorder, Erythropoietic protoporphyria, and obesity, due to pro-opiomelanocortin and leptin receptor deficiency, respectively. Therefore, this review aims to summarize the function and genetic polymorphism of melanocortin receptors, regulatory pathways involving MCRs, and the existing evidence of the prime effect of MCRs on inflammatory responses via different mechanisms and their potential therapeutic use in inflammatory diseases. Full article

Bacterial meningitis is one of the most serious infections. Salmonella meningitis is associated with a high prevalence of long-term adverse outcomes, often linked to acute complications and a broad range of potential neurological sequelae following the infection. Acute complications such as brain abscesses and chronic complications such as hearing loss and developmental delay. In this report, we present a case of a 2-month-old male patient with seizures, hypoactivity and respiratory symptoms, who was found to have Salmonella bacteremia complicated by Salmonella and Human Herpes Virus-6 (HHV-6) meningitis, as well as rhinovirus bronchiolitis, along with follow-up findings. The patient’s data, including demographics, presenting symptoms, physical examination findings, and whole exome sequence results, as well as investigations such as complete blood count (CBC), cerebrospinal fluid (CSF) analysis, liver enzyme levels, and imaging findings, were collected from the electronic medical record system using a case report form. In addition, immunological workups were performed, as serious Salmonella infections were more common in immunocompromised patients. In the literature, there was no clear correlation between Salmonella and HHV-6 meningitis, rhinovirus bronchiolitis, and the complications that developed in this infant. This case report provides valuable insights into the clinical spectrum and long-term outcomes of patients with Salmonella meningitis. Full article

This study investigates the effects of Bisphenol A (BPA)—a ubiquitous endocrine disruptor—on the swimming behavior of the rotifer Brachionus plicatilis. Across a 0–40 ppm gradient, a biphasic response was observed, with swimming speed peaking at 20 ppm (100.42 ± 12.17 µm/s) and then significantly declining by 43% to 57.58 ± 30.59 µm/s at 40 ppm (Tukey, p < 0.05). Speed–frequency plots revealed co-existing hyper- and hypoactive sub-populations at 10–30 ppm, whereas severe inhibition dominated at 40 ppm. Additionally, temporal analysis confirmed that BPA effects were both concentration- and time-dependent, with the mean speed at 10 ppm declining only slightly over time (slope ≈ −0.8), whereas at 40 ppm, the decrease was an order of magnitude steeper (slope ≈ −16.9). Additionally, BPA exposure also triggered a sharp rise in abrupt turns (582.53 ± 477.55 events) and greater path sinuosity, consistent with neuromuscular disturbance. These findings demonstrate that rotifer locomotion provides an early and sensitive indicator of environmental BPA exposure. Full article

Background/Objectives: Cognitive Disengagement Syndrome (CDS) is a clinical condition primarily characterized by inattention, hypoactivity, and mind-wandering, which has not yet been recognized as an official diagnostic category. Although there are overlaps between CDS and ADHD, evidence supports the semi-independence of CDS from the ADHD-Inattentive subtype. Importantly, while the impact of ADHD on parenting styles has been studied, no previous research has investigated the potential influence of CDS difficulties on parenting behaviors. Both CDS and ADHD are associated with internalizing and externalizing symptoms, which are influenced by negative parenting styles. The severity of ADHD is known to predict the use of dysfunctional parenting patterns; however, no studies have yet investigated how CDS difficulties might affect parenting styles. Due to the similarities between CDS and ADHD, it is reasonable to hypothesize a similar relationship. This study aims to examine the potential mediating role of parenting styles—both negative and positive—in the relationship between CDS difficulties and internalizing and externalizing symptoms. Methods: The sample is composed of 369 Italian school-aged children (9.38 ± 2.34 years old). Parents reported on their children’s psychopathology, CDS difficulties, and their own parenting strategies. Results: Analyses conducted using Hayes’ PROCESS tool indicated that only negative parenting styles partially mediated the relationship between CDS difficulties and parent-reported youth anxiety, depression, and oppositional defiant disorder. Conclusions: These findings highlight the importance of interventions aimed at both addressing CDS in children and improving parenting strategies to enhance youth psychopathological outcomes. Full article

Background and aim of this review: The ongoing opioid epidemic underscores the urgent need for innovative pharmacological and behavioral interventions to mitigate the impact of opioid use disorder (OUD). This review aims to explore theoretical overlaps between the neurobiological mechanisms underlying OUD development and the pharmacodynamic profile of methylphenidate (MPH). Particular attention is given to the potential shared molecular targets, safety considerations, and therapeutic implications of MPH use in this clinical context. Main finding: In the development of opioid dependence, the negative reinforcement of the dopaminergic transmission of the mesocorticolimbic pathway induced by the supraspinal action of opioid receptor agonists plays a major role. The induced state of hypodopaminergic and hyperadrenergic modulates the underlying disease process by affecting cognitive control, affective regulation, and motivational drive. MPH, acting as a dopamine reuptake inhibitor and modulator of vesicular monoamine transporter 2 (VMAT-2), increases extracellular dopamine availability and enhances dopaminergic signaling, suggesting potential utility in restoring dopaminergic tone in OUD. Additionally, MPH has shown efficacy in hypoactive delirium in patients with terminal cancer, improving both cognitive function and psychomotor drive. Conclusions and future perspectives: There appear to be converging neurobiological mechanisms between the action of MPH and the pathophysiology of OUD, particularly within the dopaminergic system. However, well-designed clinical trials are essential to identify the patient subgroups that may benefit from adjunctive MPH treatment, to evaluate its efficacy in this setting, and to assess the long-term safety and risk profile of stimulant use in individuals with OUD. Full article

Background: Delirium is a common, underdiagnosed neuropsychiatric syndrome in older adults, associated with high mortality and functional decline. Given its multifactorial nature and overlap with frailty, radiological markers may improve risk stratification in the emergency department (ED). Methods: We conducted a retrospective study on a small sample of 30 patients diagnosed with delirium in the emergency department who had recently undergone brain, thoracic, or abdominal CT scans for unrelated clinical indications. Using post-processing software, we analyzed radiological markers, including coronary artery calcifications (to estimate vascular age), cerebral atrophy (via the Global Cortical Atrophy scale), and cachexia (based on abdominal fat and psoas muscle volumetry). Results: Five domains were identified as significant predictors of 12-month mortality in univariate Cox regression: vascular age, delirium etiology, cerebral atrophy, delirium subtype (hyperactive vs. hypoactive), and cachexia. Based on these domains, we developed an exploratory 10-point delirium score. This score demonstrated acceptable diagnostic accuracy for mortality prediction (sensitivity 0.93, specificity 0.73, positive predictive value 0.77, negative predictive value 0.91) in this limited cohort. Conclusions: While preliminary and based on a small, retrospective sample of 30 patients, this multidimensional approach integrating clinical and radiological data may help improve risk stratification in elderly patients with delirium. Radiological phenotyping, particularly in terms of vascular aging and sarcopenia/cachexia, offers objective insights into patient frailty and could inform more personalized treatment pathways from the ED to safe discharge home, pending further validation. Full article

The serotonergic system, originating in the raphe nuclei, differentially modulates the dorsal and ventral hippocampus, which are implicated in cognition and emotion, respectively. Emerging evidence from rodent models (e.g., neonatal ventral hippocampal lesion, pharmacological NMDA receptor antagonist exposure) and human postmortem studies indicates dorsoventral serotonergic alterations in schizophrenia. These data include elevated 5-HT1A receptor expression in the dorsal hippocampus, linking serotonergic hypofunction to cognitive deficits, and hyperactive 5-HT2A/3 receptor signaling and denser serotonergic innervation in the ventral hippocampus driving local hyperexcitability associated with psychosis and stress responsivity. These dorsoventral serotonergic alterations are shown to disrupt the excitation–inhibition balance, impair synaptic plasticity, and disturb network oscillations, as established by in vivo electrophysiology and functional imaging. Synthesizing these multi-level findings, we propose a novel “dorsoventral serotonin imbalance” model of schizophrenia, in which ventral hyperactivation predominantly contributes to psychotic symptoms and dorsal hypoactivity underlies cognitive deficits. We further highlight promising preclinical evidence that selective targeting of region- and receptor-specific targeting, using both pharmacological agents and emerging delivery technologies, may offer novel therapeutic opportunities enabling symptom-specific strategies in schizophrenia. Full article

Background: Borderline personality disorder (BPD) is a severe psychiatric condition characterised by emotional instability, impulsivity, interpersonal dysfunction, and self-injurious behaviours. Despite growing clinical interest, the neuropsychological mechanisms underlying these symptoms are still not fully understood. This review aims to summarise findings from neuroimaging, psychophysiological, and neurodevelopmental studies in order to clarify the neurobiological and physiological basis of BPD, with a particular focus on emotional dysregulation and implications for the treatment of adolescents. Methods: A narrative review was conducted, integrating results from longitudinal neurodevelopmental studies, functional and structural neuroimaging research (e.g. FMRI and PET), and psychophysiological assessments (e.g., heart rate variability and cortisol reactivity). Studies were selected based on their contribution to understanding the neural correlates of BPD symptom dimensions, particularly emotion dysregulation, impulsivity, interpersonal dysfunction, and self-harm. Results: Findings suggest that early reductions in amygdala volume, as early as age 13 predict later BPD symptoms. Hyperactivity of the amygdala, combined with hypoactivity in the prefrontal cortex, underlies deficits in emotion regulation. Orbitofrontal abnormalities correlate with impulsivity, while disruptions in the default mode network and oxytocin signaling are related to interpersonal dysfunction. Self-injurious behaviour appears to serve a neuropsychological function in regulating emotional pain and trauma-related arousal. This is linked to disruption of the hypothalamic-pituitary-adrenal (HPA) axis and structural brain alterations. The Unified Protocol for Adolescents (UP-A) was more effective to Mentalization-Based Therapy for Adolescents (MBT-A) at reducing emotional dysregulation compared, though challenges in treating identity disturbance and relational difficulties remain. Discussion: The reviewed evidence suggests that BPD has its in early neurodevelopmental vulnerability and is sustained by maladaptive neurophysiological processes. Emotional dysregulation emerges as a central transdiagnostic mechanism. Self-harm may serve as a strategy for regulating emotions in response to trauma-related neural dysregulation. These findings advocate for the integration of neuroscience into psychotherapeutic practice, including the application of neuromodulation techniques and psychophysiological monitoring. Conclusions: A comprehensive understanding of BPD requires a neuropsychologically informed framework. Personalised treatment approaches combining pharmacotherapy, brain-based interventions, and developmentally adapted psychotherapies—particularly DBT, psychodynamic therapy, and trauma-informed care—are essential. Future research should prioritise interdisciplinary, longitudinal studies to further bridge the gap between neurobiological findings and clinical innovation. Full article

Kisspeptin (Kiss1) and kisspeptin 1 receptor (Kiss1R) are vital in regulating various functions across many species, primarily those relating to reproduction. The kisspeptin system has recently attracted clinical interest as a potential therapeutic treatment for patients with hypoactive sexual desire disorder. This study maps the distribution of Kiss1 and Kiss1R mRNA in the Syrian hamster forebrain using dual-labeled RNAscope. In our study, the distributions of kisspeptin and its receptor were mapped across adult males and females on day 1 or day 2 of their estrous cycle. Conditioned place preference was used to observe the potential effect of kisspeptin on sexual reward in female hamsters. The expression of kisspeptin was greater in females than males, with the estrous cycle having no effect on expression. A comparison of these findings to those in other species revealed that the expression in Syrian hamsters was similar to that reported for other species, demonstrating the conservation of expression. Kisspeptin did not influence sexual reward in females, nor did it affect measures of their primary sexual behavior. These findings provide additional insights into the expression and function of kisspeptin across novel species and add to ongoing research in understanding how kisspeptin may influence sexual desire in animals, including humans. Full article

Background: The occurrence (incidence or prevalence) of delirium in brain tumors is unknown, yet delirium is associated with increased morbidity and mortality and worse quality of life. We conducted a systematic review and meta-analysis to determine the occurrence of delirium in hospitalized patients with brain tumors. Methods: PubMed, Scopus, and Web of Science were systematically searched for papers from 1 January 1999 to 12 July 2024, including references from texts. Cross-sectional, prospective, and other cohort study designs were included, and individual case reports, case series, editorials, and reviews were excluded. The included papers were scored using a validated sensitivity analysis tool and tested for quality and bias using funnel plots and Egger’s test. We used random effects models for the summary estimates. We performed subgroup analyses by tumor type, tumor location, delirium subtype, and length of stay. Results: Of the 452 studies screened, 27 were included, representing 35,958 patients. The overall occurrence of delirium was 0.17 (95% CI [0.11–0.24]). Delirium occurrence in patients with low-grade gliomas, high-grade gliomas, and brain metastases was 0.10 [0.06–0.16], 0.21 [0.10–0.40], and 0.31 [0.16–0.50], respectively. Compared to the occipital lobe, there was a higher occurrence of delirium for tumors in the frontal (RR 3.08 [1.35–8.22]) and temporal lobes (RR 2.88 [1.22–7.93]). The patients were more likely to have hypoactive (RR 1.61 [1.30; 1.98]) than hyperactive delirium. Delirium was associated with 4.62 additional hospitalized days compared to those without delirium (CI [3.23–6.01]). Discussion: We confirmed high occurrence rates of delirium in patients hospitalized with brain tumors. Patients with brain metastases had a higher occurrence of delirium compared to patients with gliomas, and delirium occurrence rates were higher in patients with frontotemporal tumors. Delirium occurrence rates in the literature are very heterogeneous and point toward a need for tailored assessments in patients with brain tumors. Full article

Background/Objectives: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent condition etiologically related to suboptimal levels of dopamine (DA) and norepinephrine (NE) that is typically treated with psychostimulant medication. In individuals with ADHD, divergent thinking abilities have been shown to improve with the use of psychostimulants. Furthermore, psychostimulants affect autonomic nervous system (ANS) functioning, which can impact creative cognition. However, it is not known how DA and NE affect creative cognition in this setting and how this effect is related to autonomic activity in ADHD. Therefore, our objective was to elucidate ANS function and its relationship with divergent creativity gains related to psychostimulant treatment in ADHD. Method: Seventeen individuals diagnosed with ADHD (age 27.9 ± 6.7 sd) participated in two counterbalanced sessions—one while on their prescribed stimulant medication and another after abstaining for at least 24 h. During each session, participants completed convergent (anagrams) and divergent (Torrance Test of Creative Thinking) thinking tasks. An 8 min electrocardiogram prior to cognitive testing was taken to measure heart rate variability (HRV), which is an index of ANS functioning. Results: The hypothesized baseline pNN50 HRV measure was not predictive of enhanced creativity gains on convergent anagrams or divergent creativity on the Torrance when taking stimulants. Conclusions: In this pilot study, the relationship between baseline HRV and the impact of stimulants on anagram performance suggests the noradrenergic system may not play a role in the effect of stimulants on convergent or divergent creativity. The lack of a relationship between baseline HRV and stimulant-related changes in TTCT and anagram scores lends some support to the hypothesis that dopaminergic effects may be the predominant factor in the effect of stimulants on creativity in ADHD. Future research should further investigate the interaction between hypoactive neurotransmitter systems, particularly dopamine in divergent and norepinephrine in convergent creativity, using neuroimaging techniques to assess neurotransmitter dynamics during creativity-based tasks. Full article