Search Results (852)

Background: Complex Regional Pain Syndrome (CRPS) is a chronic pain condition that usually affects a limb following injury or surgery and is characterized by severe pain accompanied by sensory, motor, autonomic, and trophic disturbances. Methods: This systematic review aimed to synthesize the available evidence on the effectiveness of physical exercise and neurocognitive interventions grounded in cognitive–behavioral therapy (CBT) principles for the management of CRPS. A comprehensive search was conducted in Medline (via Ovid), LILACS, ScienceDirect, PEDro, OTseeker, and the Cochrane Central Register of Controlled Trials (CENTRAL). Eligible studies included clinical trials, cohort studies, and cross-sectional studies, whereas case reports, pediatric populations, and animal studies were excluded. Fifteen studies met the inclusion criteria. Results: The findings indicated that aerobic exercise was consistently associated with pain reduction and functional improvement. Neurocognitive interventions informed by CBT principles, such as mirror therapy and graded exposure, also demonstrated efficacy in decreasing pain and enhancing functional independence. Most studies supported the effectiveness of these approaches in the management of CRPS. Overall, both physical exercise and neurocognitive interventions grounded in CBT principles produced positive effects on pain modulation, physical function, and daily activity performance. Conclusions: These findings highlight the therapeutic potential of combining physical and psychologically informed interventions for the treatment of CRPS. Full article

Depression is a prevalent and disabling psychiatric disorder, characterized by persistent disturbances in mood, cognition, and physiological processes, which collectively lead to substantial impairments in daily functioning and quality of life. This review provides a comprehensive overview of the biological mechanisms implicated in the pathophysiology of depression, including neurotransmitter dysregulation, oxidative stress, inflammatory processes, hypothalamic-pituitary-adrenal (HPA) axis dysfunction, mitochondrial impairment, and alterations in the gut-brain axis. Furthermore, it explores the role of diet in both the prevention and management of depression, with particular emphasis on Mediterranean, anti-inflammatory, and ketogenic dietary patterns, while contrasting these with the detrimental impact of a Western dietary pattern. Specific nutrients-such as n-3 polyunsaturated fatty acids (PUFAs), B-complex vitamins, vitamins D and E, zinc, selenium, and polyphenols-are highlighted for their potential roles in modulating neurotransmission, attenuating inflammation, and supporting gut microbiota homeostasis. Despite growing scientific interest in nutrition-based interventions, current evidence on the comparative efficacy of different dietary approaches remains limited. Future research is warranted to elucidate the therapeutic potential of dietary strategies as adjuncts to conventional treatments for depression and to facilitate the development of evidence-based nutritional recommendations for clinical practice. Full article

Parkinson’s disease (PD) is a progressive, irreversible neurodegenerative disorder characterized by motor impairments and a wide spectrum of non-motor symptoms, including gastrointestinal dysfunction, sleep disturbances, depression, and cognitive decline. These manifestations arise from disturbances across multiple systems—gastrointestinal, neuroendocrine, immune, enteric, and central nervous systems. Alterations in the gut microbiota may play a causal role in PD onset and frequently accompany disease progression. The gut–brain axis, particularly the vagus nerve, is increasingly recognized as a key communication pathway whose dysregulation contributes to systemic dysfunction and the breakdown of homeostasis, ultimately driving PD pathology. Currently, there is no cure for PD, and existing treatments primarily target symptom relief. Effective management of PD requires a comprehensive approach that integrates multiple pharmacologically active agents aimed at restoring impaired organ functions and, when possible, neutralizing toxic factors that accelerate disease progression. One promising therapeutic avenue lies in functional gut bacteria, which form the basis for developing live biotherapeutic products, postbiotics, and bacterial vesicles. In this review, we summarize current data on the effects of probiotics in PD, drawing on both animal models and clinical studies. We highlight the role of probiotics in modulating PD pathophysiology and discuss their potential as adjunctive therapeutic agents. To provide a broader perspective, we also include sections describing the clinical manifestations of PD, gut microbiota alterations associated with the disease, and the role of artificial intelligence, particularly machine learning, in constructing functional models of PD. Full article

Maternal Immune Activation (MIA) is a phenomenon of pathophysiological stimulation of the maternal immune system during gestation which potentially leads to functional and structural disturbances of fetal neurogenesis. It occurs due to the alteration of paracrine signals between the maternal organism and the developing nervous system of the fetus. Any disturbances in the brain at embryonic and early postnatal stages might compromise its natural developmental trajectory, which could potentially increase the risk of developing neuropsychiatric disorders, such as schizophrenia, autistic spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), major depressive and bipolar disorders, etc. Presumably, all these conditions could initiate the development of age-related cognitive impairment in late ontogenesis, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and others. As the main immune cell population in the CNS, microglia both mediate its proper development and receive pathological stimuli from the maternal organism. This could lead to microglia premature activation and could become a part of the mechanisms of the fetal CNS development alterations. In this review, we discuss the role of prenatal activation of microglia in neuropsychiatric disorders and neurodegenerative disease development. We highlight approaches to modeling MIA, as well as sex differences in the morphological and functional state of microglia in the context of physiological conditions. There is a hypothesis discussed regarding the contribution of these distinctions to neuropsychiatric disorders and neurodegenerative disease incidence, prevalence, and progression in males and females. Full article

In recent years, animal welfare scientists working in professionally managed settings have increasingly focused on promoting resilience to enhance the quality of life of individual animals. Resilience—defined as an animal’s capacity to be minimally affected by a disturbance or to rapidly return to the physiological, behavioral, cognitive, health, affective, and production states that pertained before exposure to a disturbance—involves various systems and dynamic processes. There is evidence that resilience can be measured using a suite of species-specific indicators, including both behavioral measures and physiological biomarkers. These indicators should be tracked for individuals of the same species over time and across various conditions, events, and experiences. Large-scale, multi-institutional studies allow welfare scientists to collect cross-sectional data to identify “resilient phenotypes” for the species of interest. Ultimately, the focus should be on improving outcomes for individual animals as they face particular stressors, challenges, and environmental disturbances over their lifetime. Animal care specialists play a crucial role in helping animals build resilience by providing opportunities to engage in cognitive challenges, stimulating environments, and species-appropriate social interactions. This review defines resilience for animal welfare scientists, as well as discusses how to measure and promote resilience in animals residing in zoos and aquariums. Full article

Fibromyalgia syndrome (FMS) is a chronic disorder marked by widespread musculoskeletal pain, fatigue, mood disturbances, and cognitive impairments. Current treatments primarily focus on symptom management. Ashwagandha (Withania somnifera), a traditional Ayurvedic herb, is known for its adaptogenic and neuroprotective properties. This study evaluated the protective effects of the methanolic root extract of Ashwagandha (ARE) in a reserpine-induced fibromyalgia model in male Swiss albino mice. Mice received oral ARE (100 mg/kg) for 17 days and reserpine (0.5 mg/kg, subcutaneously) for three consecutive days to induce fibromyalgia-like symptoms. Behavioral assessments included Von Frey, tail suspension, rotarod, and Y-maze tests. Histological analysis was conducted on the hippocampus and thalamus; however, neurochemical analysis focused on markers such as serotonin, norepinephrine, IL-1β, TNFα, MDA, and NO. Results indicated that ARE significantly reduced pain and depressive-like behavior and improved motor function (p < 0.0001); however, no significant changes were observed in open-field locomotion. Histological examination revealed protection of Ashwagandha against neurodegeneration and improved hippocampal integrity, accompanied by increased serotonin and norepinephrine levels and decreased pro-inflammatory cytokines. These findings suggest that Ashwagandha root extract may offer therapeutic benefits for managing fibromyalgia symptoms. Full article

Background: Juvenile fibromyalgia (JFM) is a chronic pain disorder characterised by widespread musculoskeletal pain, functional impairment, fatigue, and mood disturbances. Treatment remains challenging, considering the multifactorial nature of the condition and the limited high-quality evidence supporting pharmacological or non-pharmacological interventions. Objectives: This review aimed to critically appraise level I evidence from randomised controlled trials assessing the efficacy and safety of pharmacological and non-pharmacological treatments for adolescents with JFM. Methods: Seven published peer-reviewed clinical trials were examined, including studies investigating duloxetine, milnacipran, pregabalin, cognitive-behavioural therapy (CBT), and the integrated Fibromyalgia Integrative Training Teens (FIT) program, which combines CBT with neuromuscular training. Outcomes of interest included pain intensity, functional disability, depression symptoms, physical activity, and adverse events. Results: Pharmacological agents such as duloxetine, milnacipran, and pregabalin demonstrated modest improvements in pain, but failed to produce consistent benefits in function or mood, and were associated with a high incidence of adverse effects. CBT significantly improved functional disability and depression symptoms, yet it had a limited impact on pain reduction or objectively measured activity levels. The FIT Teens program showed superior outcomes in pain intensity and biomechanical function compared to CBT alone, suggesting a synergistic effect of combining psychological and physical reconditioning strategies. Conclusions: Current evidence supports the use of multimodal treatment approaches in JFM. Non-pharmacological interventions, particularly when integrated with structured exercise, offer meaningful benefits with minimal safety concerns. Larger, methodologically rigorous trials are needed to establish optimal treatment pathways and long-term outcomes for this complex and underserved paediatric population. Full article

Preterm birth remains a significant global health challenge and is strongly associated with heightened risks of long-term neurodevelopmental impairments, including cognitive delays, behavioural disorders, and emotional dysregulation. In recent years, accumulating evidence has underscored the critical role of the gut microbiota in early brain development through the gut–brain axis. In preterm infants, microbial colonisation is frequently delayed or disrupted due to caesarean delivery, perinatal antibiotic exposure, formula feeding, and prolonged stays in neonatal intensive care units (NICUs), all of which contribute to gut dysbiosis during critical periods of neurodevelopment. This review synthesises current knowledge on the sources, temporal patterns, and determinants of gut microbiota colonisation in preterm infants. This review focuses on the gut bacteriome and uses faecal-sample bacteriome sequencing as its primary method of characterisation. We detail five mechanistic pathways that link microbial disturbances to adverse neurodevelopmental outcomes: immune activation and white matter injury, short-chain fatty acids (SCFAs)-mediated neuroprotection, tryptophan–serotonin metabolic signalling, hypothalamic–pituitary–adrenal (HPA) axis modulation, and the integrity of intestinal and blood–brain barriers (BBB). We also critically examine emerging microbiota-targeted interventions—including probiotics, prebiotics, human milk oligosaccharides (HMOs), antibiotic stewardship strategies, skin-to-skin contact (SSC), and faecal microbiota transplantation (FMT)—focusing on their mechanisms of action, translational potential, and associated ethical concerns. Finally, we identify key research gaps, including the scarcity of longitudinal studies, limited functional modelling, and the absence of standardised protocols across clinical settings. A comprehensive understanding of microbial–neurodevelopmental interactions may provide a foundation for the development of targeted, timing-sensitive, and ethically sound interventions aimed at improving neurodevelopmental outcomes in this vulnerable population. Full article

Background/Objectives: Sleep is integral to cognitive functioning, yet many college students experience poor sleep, often influenced by dysfunctional beliefs about sleep. Dysfunctional beliefs can exacerbate sleep issues and negatively impact executive functioning (EF). Distinct EF facets, including inhibition, working memory, and cognitive flexibility, may differ in their sensitivity to sleep disruptions. While research suggests links between sleep and EF, less is known about how sleep-related beliefs may moderate this relationship and how sleep can affect the various EF facets. Utilizing an undergraduate population, this study examined how sleep quality/quantity affects the different EF facets, how this relationship differs between subjective and objective measurements, and whether dysfunctional beliefs about sleep moderate the relationship. Methods: Undergraduate students (N = 212, ages 18–23) completed self-report measures assessing dysfunctional beliefs about sleep (DBAS-16), sleep quality (ISI), and sleep quantity (self-reported sleep duration). Objective EF was measured using computerized CNS Vital Signs tasks targeting inhibition (Stroop Test), working memory (4-Part Continuous Performance Test), and cognitive flexibility (Shifting Attention). Subjective EF was measured using individual subscales on the Behavioral Rating Inventory of Executive Functioning—Adult Version (BRIEF-A). Results: Moderation analyses were conducted via linear regression. When measured objectively, neither sleep quantity nor insomnia severity (sleep quality) significantly affected any EF facets, and dysfunctional beliefs about sleep did not have any significant moderation effect. When measured subjectively, insomnia severity (sleep quality), but not sleep quantity, significantly predicted inhibition and cognitive flexibility; in contrast, neither predictor significantly predicted working memory. Regarding specific predictors, dysfunctional sleep beliefs were found to exert significant effect over all three facets; this effect was diminished when insomnia severity was included in the model. Regarding moderation, dysfunctional beliefs about sleep moderated the relationship between sleep quantity and all three EF facets. Conclusions: The impact of sleep quality, sleep quantity, and dysfunctional beliefs about sleep varies depending on whether the facets of EF are measured subjectively or objectively. Dysfunctional beliefs about sleep may exacerbate the perceived effect of short sleep duration on daytime cognitive functioning. In addition, insomnia severity may account for the effects of dysfunctional sleep beliefs on perceived inhibitory control and cognitive flexibility; however, working memory may be more resistant to the effects of sleep disturbances and dysfunctional sleep beliefs. Clinical implications of these results and future directions are discussed. Full article

Insomnia is a common and complex disorder, rooted in the dysregulation of circadian rhythms, impaired neurotransmitter function, and disturbances in sleep–wake homeostasis. While conventional hypnotics such as benzodiazepines and Z-drugs are effective in the short term, their use is limited by a high potential for dependence, cognitive side effects, and withdrawal symptoms. In contrast, melatonergic receptor agonists—melatonin, ramelteon, tasimelteon, and agomelatine—represent a pharmacologically targeted alternative that modulates MT1 and MT2 receptors, which are pivotal to the regulation of circadian timing and sleep initiation. Clinical evidence supports the efficacy of these agents in reducing sleep onset latency, extending total sleep duration, and re-aligning disrupted circadian rhythms, particularly among older individuals and patients with non-24 h sleep–wake disorders. Notably, agomelatine offers additional antidepressant properties through selective antagonism of the 5-HT_2C receptor in micromolar concentrations. In contrast, its agonistic activity at melatonergic receptors is observed in the low sub-nanomolar range, which illustrates the complexity of this drug’s interactions with the human body. All compounds reviewed demonstrate a generally favorable safety and tolerability profile. Accumulating evidence highlights that selected medicinal plants, such as chamomilla, lemon balm, black cumin, valeriana, passionflower and lavender, may exert relevant hypnotic or anxiolytic effects, thus complementing melatonergic strategies in the management of insomnia. This structured narrative review presents a comprehensive analysis of the molecular pharmacology, receptor affinity, signaling pathways, and clinical outcomes associated with melatonergic agents. It also examines their functional interplay with serotonergic, GABAergic, dopaminergic, and orexinergic systems involved in arousal and sleep regulation. Through comparative synthesis of pharmacokinetics and neurochemical mechanisms, this work aims to inform the development of evidence-based strategies for the treatment of insomnia and circadian rhythm sleep–wake disorders. Full article

Background and Objectives: Traditionally regarded as a purely motor disorder, amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of upper and lower motor neurons. However, it is increasingly recognized as a condition with a broader clinical spectrum, encompassing a variety of non-motor symptoms (NMS) that significantly impact patients’ quality of life and may influence disease progression and prognosis. Materials and Methods: The study included 44 patients diagnosed with probable or definite ALS and 35 healthy controls (HC). Functional neurological status, non-motor manifestations, and cognitive and affective domains were evaluated using the revised ALS Functional Rating Scale (ALSFRS-R), the Non-Motor Symptoms Questionnaire (NMSQuest), the Frontal Assessment Battery (FAB), and the Beck Depression Inventory (BDI), respectively. Results: A majority of ALS patients exhibited non-motor symptoms (NMS). Significant associations were identified between specific NMS domains and ALSFRS-R subdomains: sleep disturbances were associated with lower fine motor, respiratory, and total scores; digestive symptoms with lower bulbar, respiratory, and total scores; cardiovascular symptoms with lower total scores; urinary symptoms with higher bulbar subscores and a significantly slower progression rate (ΔPR); and sensory symptoms with higher gross motor subscores. BDI scores were negatively correlated with respiratory and bulbar functions, whereas FAB scores showed positive correlations with both bulbar and total ALSFRS-R scores. Conclusions: Non-motor symptoms are highly prevalent in this ALS cohort. These symptoms do not consistently correlate with greater motor impairment, as urinary and somatosensory involvement may occur independently of functional decline. Cognitive, affective, and behavioral alterations co-exist with motor symptoms and are associated with poorer overall functional performance. Full article

Orexin is a neuropeptide produced in the hypothalamus that plays a key role in regulating slee—wake cycles, energy metabolism, feeding behavior, and physical activity. It exists in two forms, orexin-A and orexin-B, which bind to G protein-coupled receptors OX₁R and OX₂R with differing affinities. Orexin signaling is widespread in the brain and extends to peripheral tissues, including adipose tissue. Its involvement in hypothalamic and extrahypothalamic circuits suggests a broad role in homeostatic regulation. Dysfunctions in the orexinergic system are implicated in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and multiple sclerosis, particularly through mechanisms involving sleep disturbances and neuroinflammation. This study examines how orexin influences neural circuits related to arousal, motivation, and motor control. It also explores how physical activity stimulates orexin release, enhancing neuroplasticity and cognitive resilience. In addition, orexin’s role in reward-related feeding, genetic susceptibility to obesity, and brown adipose tissue thermogenesis is discussed. Overall, the orexinergic system represents a vital neurochemical link between physical activity, metabolism, and cognitive health. Although many of its mechanisms remain to be clarified, its central role in integrating energy balance and behavioral responses makes it a promising target for future therapeutic strategies. Full article

In an attempt to improve utilization of the frequency spectrum left vacant by license holders, cognitive radio networks (CRNs) permit secondary users (SUs) to utilize such spectrum when the license holders, known as primary users (PUs), are inactive. When a pair of SUs wants to communicate over the CRN, they need to converge simultaneously on one of the vacant channels, in a process known as rendezvous. In this work, we attempt to reduce the rendezvous time for SUs executing the well-known enhanced jump-stay (EJS) channel hopping procedure. We achieve this by modifying EJS in order to search the vacant spectrum around a specific favorite channel, instead of hopping across the whole spectrum. Moreover, the search process is carefully designed in order to accommodate the dynamic nature of CRNs, where PUs repeatedly become active and inactive, resulting in disturbances to the rendezvous process. A main feature of our proposed technique, named dynamic jump-stay (DJS), is that the SUs do not need any prior coordination over a common control channel (CCC), thereby allowing for scalable and more robust distributed CRNs. Simulations are used to quantify the resulting performance improvement in terms of expected time to rendezvous, maximum time to rendezvous, and interference on PUs. Full article

Sleep disorders are highly prevalent in children with Autism Spectrum Disorder (ASD), profoundly impacting their neurodevelopment and daily functioning. Alterations in sleep architecture and regulatory mechanisms contribute to difficulties with sleep onset, maintenance, and overall sleep quality. Sensory processing differences, commonly observed in ASD, may further exacerbate these disturbances by affecting arousal regulation and environmental responsiveness during sleep. Given the fundamental role of sleep in brain maturation, its disruption negatively impacts synaptic plasticity and neurological development, particularly during critical periods. These sleep-related alterations can influence cognitive and behavioral outcomes and may serve as early indicators of ASD, highlighting their potential value in early diagnosis and intervention. Understanding the neurobiological mechanisms linking sleep and ASD is essential for developing targeted therapeutic strategies. Ongoing research increasingly focuses on pharmacological, nutraceutical, and behavioral interventions aimed at mitigating sleep disorders and their cascading effects on neurodevelopment. Optimizing these therapeutic approaches through a multidisciplinary lens is crucial for enhancing clinical outcomes and improving overall quality of life in children with ASD. Full article

This case report describes a patient (male, 10 years old) with Autism Spectrum Disorder (ASD) and multiple comorbidities, including epilepsy, gastrointestinal and sleep disturbances, and obesity. Whole-exome sequencing (WES) identified two variants of uncertain significance (VUS) in the GRID2 gene. Mutations in this gene are associated with spinocerebellar ataxia type 18 (SCA18). However, this finding did not correlate with the clinical presentation of the patient. This study evaluates the effects of Radio Electric Asymmetric Conveyer (REAC) stimulation on the cognitive–behavioral dysfunctions of a child with severe ASD and multiple comorbidities. Two stimulation protocols—Neuro Postural Optimization (NPO) and Neuro Psychophysical Optimization (NPPO)—and REAC were performed sequentially. After five weeks of treatment, a 34.9% reduction in total scores on the Autism Treatment Evaluation Checklist (ATEC) and an 8.2% on the Autism Behavior Checklist (ABC) were observed. Assessment of the severity of ASD symptoms using the Childhood Autism Rating Scale (CARS) tool showed less pronounced improvement. The REAC intervention yielded a reduction in Social Relating impairment and an improvement in Sensory/Cognitive Awareness. Further research in this area should employ extended REAC protocols to replicate and amplify clinical responses among individuals with ASD. Full article