Search Results (948)

Chronic pain is a significant and complex health condition characterized by persistent or recurrent pain lasting more than three months. Exercise-based rehabilitation is an effective non-pharmacological intervention, yet its underlying mechanisms have not been fully elucidated. This review systematically maps the molecular pathways of exercise-induced analgesia onto the pathophysiological cascades of chronic pain, aiming to fill a key gap in the current literature. It explores the molecular and cellular mechanisms underpinning the pathophysiology of chronic pain, indicating that the persistence of chronic pain stems from peripheral sensitization driven by inflammatory mediators and central sensitization involving glial cell activation and N-methyl-D-aspartate (NMDA) receptor-mediated neuroplasticity. Exercise can interrupt these pathological cascades through multi-system adaptations, including activation of the endogenous opioid and serotonergic systems activation and anti-inflammation. However, a significant gap remains in translating this mechanistic understanding of chronic pain into optimized, personalized exercise prescriptions, requiring future research into different exercise modalities, sex-specific responses, and the impact of comorbidities. Full article

In recent years, the bidirectional regulatory mechanism of the bone-brain axis has become a hotspot for interdisciplinary research. In this paper, we systematically review the anatomical and functional links between bone and the central nervous system, focusing on the regulation of brain function by bone-derived signals and their clinical translational potential. At the anatomical level, the blood–brain barrier permeability mechanism and the unique structure of the periventricular organs establish the anatomical basis for bone-brain information transmission. Innovative discoveries indicate that the bone cell network (bone marrow mesenchymal stem cells, osteoblasts, osteoclasts, and bone marrow monocytes) directly regulates neuroplasticity and the inflammatory microenvironment through the secretion of factors such as osteocalcin, lipid transporter protein 2, nuclear factor κB receptor-activating factor ligand, and fibroblast growth factor 23, as well as exosome-mediated remote signaling. Clinical studies have revealed a bidirectional vicious cycle between osteoporosis and Alzheimer’s disease: reduced bone density exacerbates Alzheimer’s disease pathology through pathways such as PDGF-BB, while AD-related neurodegeneration further accelerates bone loss. The breakthrough lies in the discovery that anti-osteoporotic drugs, such as bisphosphonates, improve cognitive function. In contrast, neuroactive drugs modulate bone metabolism, providing new strategies for the treatment of comorbid conditions. Additionally, whole-body vibration therapy shows potential for non-pharmacological interventions by modulating bone-brain interactions through the mechano-osteoclast signaling axis. In the future, it will be essential to integrate multiple groups of biomarkers to develop early diagnostic tools that promote precise prevention and treatment of bone-brain comorbidities. This article provides a new perspective on the mechanisms and therapeutic strategies of neuroskeletal comorbidities. Full article

Background/Objectives: Post-stroke cognitive impairment significantly impacts long-term functional outcomes, particularly in instrumental activities of daily living (IADLs). Working memory training (WMT) has emerged as a potential cognitive rehabilitation strategy; however, its transfer to real-world functionality remains unclear. This study evaluated whether adaptive computerized WMT enhances IADLs performance compared to a non-adaptive control condition in chronic stroke survivors. Methods: A single-blind, randomized controlled trial was conducted with 50 adults aged 50–79 years, ≥12 months post-ischemic stroke, and diagnosed with a mild neurocognitive disorder. Participants were randomized to adaptive WMT or non-adaptive cognitive training, each completing 25 home-based sessions over 12 weeks via a standardized online platform. Primary outcomes included the Lawton and Brody IADL Scale and the Working Memory Questionnaire (WMQ); secondary outcomes included the Working Memory Index (WMI) from the WAIS-IV. Analyses included frequentist and Bayesian methods. Results: Both groups showed significant pre–post improvements in IADL independence and WMI (p < 0.05; BF₁₀ > 10), with no significant between-group differences on overall IADL outcomes. The adaptive WMT group demonstrated specific gains in WMQ—Storing (p = 0.033; BF₁₀ = 3.83), while the control group improved in WMQ—Attention and IADL—Assistance Required (p = 0.004–0.035; BF₁₀ > 6). Bayesian ANOVA indicated that these effects were primarily driven by the interventions, with minimal influence from depressive symptoms or global cognition. Conclusions: Adaptive WMT yielded domain-specific cognitive benefits but did not enhance IADL performance beyond non-adaptive training. These findings highlight the limited far transfer of WMT and the importance of designing ecologically valid, multimodal rehabilitation strategies post-stroke. Full article

Background/Objectives—The personalisation agenda—matching the correct psychological therapy to diverse and comorbid mental disorders—is an unanswered dilemma in the worldwide literature which has far reaching consequences for public health. This hypothesis article addresses the question: can a biomedical approach resolve the personalisation agenda? Methods—Narrative review drawing on clinical psychology, translational psychiatry, and biomedical science literature. Results—Diverse attempts to resolve the personalisation agenda have not yet succeeded. Randomised controlled trials are uniquely biased due to unwanted placebo effects; network meta-analysis cannot address adequately which psychological therapy to use; new methodologies have not yet produced data; and neuroscientific analysis cannot yet explain how trauma-based therapies work. However, a biomedical model which divides psychological therapy into low, medium and high intensity interventions can resolve the personalisation agenda. Conclusions—Combining low intensity (placebo), with medium intensity (cognitive behavioural techniques) and high intensity interventions (trauma-based therapies) are theoretically synergistic if combined with psychosocial treatments/exercise, and used in sequence in the correct order. A biomedical model based on recent advances in placebo studies and neuroplasticity can resolve the personalisation agenda, and improve outcomes for mental disorder. Full article

(1) Background: Recent decades have seen growing interest in neuroplasticity and the activity-dependent mechanisms that allow Brain Networks to adapt functionally. Among the various stimuli, physical exercise has emerged as a key modulator of brain plasticity. This narrative review aims to synthesize evidence on the structural and functional effects of physical exercise on the brain in healthy individuals aged 18–80 years. Exercise modalities were categorized into Cardiovascular, Strength, and Mixed Training. Each was further classified by intensity (Light-to-Moderate vs. Vigorous) and duration (Short- vs. Long-Term). A total of 25 interventions were analyzed to evaluate how these variables influence Brain Networks. Findings indicate that exercise type, intensity, and duration collectively modulate neuroplastic responses. Notably, physical training induces structural and functional changes in major Brain Networks, including the Default Mode Network, Salience Network, Central Executive Network, Visuospatial Network, Sensorimotor Network, and Language and Auditory Networks. These results underscore the potential of physical exercise as an effective non-pharmacological strategy to enhance brain health and plasticity across the adult lifespan. This narrative review aims to highlight the effects of physical exercise in changing the brain either functionally or structurally. Moreover, the most relevant exercise training modalities that may improve/change neural networks in healthy populations (18–80 years) were discussed. (2) Methods: Three different types of exercise were considered: (i) Cardiovascular, (ii) Strength, and (iii) Mixed Exercise. For each of them, two levels of intensity (Light-to-Moderate and Vigorous) and two durations (Short-Term and Long-Term Effects) were included. By analyzing 25 interventions, indications about the effects on the brain considering the three factors (type of exercises, intensities, and durations) were provided. (3) Results: The findings suggest that the type of exercises, intensities, and durations could to lead neural modification over time. Specifically, exercise intervention contributes to both structural and functional changes in brain regions located in key Brain Networks, including the Default Mode Network, Salience Network, Central Executive Network, Visuospatial Network, Sensorimotor Network, and Language and Auditory Networks. (4) Conclusions: In conclusion, the evidence presented herein underscores the beneficial effects of physical exercise on the structural and functional integrity of the brain, highlighting its importance as a non-pharmacological intervention to improve brain plasticity. Full article

Recent advances in psychedelic research have renewed interest in their therapeutic potential for psychiatric disorders characterized by cognitive and behavioral rigidity. This review examines the rationale for using serotonergic psychedelics—particularly 5-HT₂A receptor agonists such as psilocybin—in the treatment of eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). The paper contextualizes these interventions within the broader serotonin hypothesis of EDs, emphasizing serotonergic dysregulation and impaired cognitive flexibility as central features of these conditions. Drawing from animal models, human neuroimaging studies, and emerging clinical trials, the authors outline how psychedelics may promote neuroplasticity and psychological insight through modulation of 5-HT₂A signaling. Preliminary evidence from open-label studies suggests psilocybin may improve ED symptoms and quality of life, though findings are early and methodologically limited. The paper also reviews data on ayahuasca, MDMA, and non-psychedelic serotonergic agents, highlighting both the promise and complexity of psychedelic-assisted therapy in EDs. The authors conclude that while further controlled trials are needed to clarify efficacy, safety, and optimal treatment parameters, psychedelics offer a novel, mechanistically distinct avenue for addressing entrenched ED psychopathology. Full article

Evidence supporting the clinical use of neuroprotective drugs for cerebral ischemia remains limited. Spatial and temporal disorientation, along with cognitive dysfunction, are among the most prominent long-term consequences of hippocampal neurodegeneration following cerebral ischemia. Cannabigerol (CBG), a non-psychotomimetic constituent of Cannabis sativa, has demonstrated neuroprotective effects in experimental models of cerebral injury. This study investigated the neuroprotective mechanisms of CBG in mitigating memory impairments caused by transient global cerebral ischemia in C57BL/6 mice using the bilateral common carotid artery occlusion (BCCAO) model. Mice underwent sham or BCCAO surgeries and received intraperitoneal (i.p.) injections of either a vehicle or CBG (1, 5, or 10 mg/Kg), starting 1 h post-surgery and continuing daily for 7 days. Spatial memory performance and depression-like behaviors were assessed using the object location test (OLT) and tail suspension test (TST), respectively. Additional analyses examined neuronal degeneration, neuroinflammation, and neuronal plasticity markers in the hippocampus. CBG attenuated ischemia-induced memory deficits, reduced neuronal loss in the hippocampus, and enhanced neuronal plasticity. These findings suggest that CBG’s neuroprotective effects against BCCAO-induced memory impairments may be mediated by reductions in neuroinflammation and modifications in neuroplasticity within the hippocampus. Full article

Substance use disorders (SUDs) remain a major public health challenge, with existing pharmacotherapies offering limited long-term efficacy. Traditional treatments focus on dopaminergic systems but often overlook the complex interplay between metabolic signals, neuroplasticity, and conditioned behaviors that perpetuate addiction. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed for type 2 diabetes and obesity, have recently emerged as promising modulators of reward-related brain circuits. This review synthesizes current evidence on the role of glucagon-like peptide-1 (GLP-1) and its receptor in modulating craving and substance-seeking behaviors. We highlight how GLP-1 receptors are expressed in addiction-relevant brain regions, including the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC), where their activation influences dopaminergic, glutamatergic, and GABAergic neurotransmission. In addition, we explore how GLP-1 signaling affects reward processing through gut–brain vagal pathways, hormonal crosstalk, and neuroinflammatory mechanisms. Preclinical studies demonstrate that GLP-1RAs attenuate intake and relapse-like behavior across a range of substances, including alcohol, nicotine, and cocaine. Early-phase clinical trials support their safety and suggest potential efficacy in reducing craving. By integrating findings from molecular signaling, neurocircuitry, and behavioral models, this review provides a translational perspective on GLP-1RAs as an emerging treatment strategy in addiction medicine. We propose that targeting gut–brain metabolic signaling could provide a novel framework for understanding and treating SUDs. Full article

Understanding patterns of interhemispheric asymmetry is crucial for monitoring neuroplastic changes during post-stroke motor rehabilitation. However, conventional laterality indices often pose computational challenges when applied to functional near-infrared spectroscopy (fNIRS) data due to the bidirectional hemodynamic responses. In this study, we analyze fNIRS recordings from 15 post-stroke patients undergoing motor imagery brain–computer interface training across multiple sessions. We compare traditional laterality coefficients with a novel task response asymmetry coefficient (TRAC), which quantifies differential hemispheric involvement during motor imagery tasks. Both indices are calculated for oxygenated and deoxygenated hemoglobin responses using general linear model coefficients, and their day-to-day dynamics are assessed with linear regression. The proposed TRAC demonstrates greater sensitivity than conventional measures, revealing significantly higher oxygenated hemoglobin TRAC values (0.18 ± 0.19 vs. −0.05 ± 0.20, p < 0.05) and lower deoxygenated hemoglobin TRAC values (−0.15 ± 0.27 vs. 0.04 ± 0.23, p < 0.05) in lesioned compared to intact hemispheres. Among patients who exhibit substantial motor recovery, distinct daily TRAC dynamics were observed, with statistically significant temporal trends. Overall, the novel TRAC metric offers enhanced discrimination of interhemispheric asymmetry patterns and captures temporal neuroplastic changes not detected by conventional indices, providing a more sensitive biomarker for tracking rehabilitation progress in post-stroke brain–computer interface applications. Full article

Background: Physical exercise has been linked to improvements in motor and cognitive functions as well as to the modulation of neurotrophic and inflammatory factors, particularly in older adults. This aim of this study was to investigate the effects of a 12-week multimodal exercise program on cognitive function, motor performance, and plasma levels of brain-derived neurotrophic factor (BDNF) and cytokines in elderly individuals with Alzheimer’s disease (AD). Methods: A non-randomized controlled trial design was employed, involving 23 participants aged 62 to 85 years diagnosed with mild to moderate AD. The intervention group (n = 7) attended 60-minute sessions three times per week, incorporating aerobic, strength, flexibility, and motor coordination exercises, while the control group (n = 8) maintained usual activities. Methods: A non-randomized controlled trial design was used, involving 23 participants aged 62 to 85 years. Of these, 15 had a clinical diagnosis of mild to moderate AD and were allocated to either an intervention group (n = 7) or and AD control group (n = 8). The remaining eight participants were cognitively healthy and formed a control group matched for age and sex, used exclusively for baseline comparisons. The intervention group participated in 60-minute sessions three times per week, including aerobic, strength, flexibility, and motor coordination exercises. The AD control group (n = 8) maintained their usual daily routines. Results: Compared to baseline, the intervention group demonstrated significant improvements in executive and attentional functions, as measured by the Frontal Assessment Battery (FAB) and Clock Drawing Test (CDT); mobility, balance, gait speed, and lower limb strength also improved (p < 0.05). Additionally, plasma BDNF levels increased significantly, and interleukin-2 (IL-2) levels decreased. Conclusions: In conclusion, the multimodal exercise program resulted in cognitive and motor benefits and positively modulated biomarkers related to neuroplasticity and inflammation, supporting its potential as a complementary intervention in elderly individuals with AD. Full article

The maturation of brain regions involved in emotion regulation—particularly the amygdala and prefrontal cortex—from fetal life to age two is a dynamic process shaped by genetic and environmental factors. Early experiences, especially responsive caregiving, promote the growth of neural circuits supporting emotional expression and regulation. In contrast, early adversity such as neglect or chronic stress may disrupt these circuits and increase vulnerability to emotional difficulties. Elevated levels of placental CRH are linked to alterations in fetal brain development related to emotion. Neurodevelopmental processes like synaptic pruning and myelination, active during the first years, further shape emotional circuitry. These findings underscore the importance of early caregiving and timely interventions in fostering healthy emotional development. The present article proposes an integrative conceptual framework for early emotional and cognitive development, combining neurobiological models with contemporary theories in developmental psychology. Full article

Tau protein is essential for the structural stability of neurons, particularly through its role in microtubule assembly and axonal transport. However, when abnormally hyperphosphorylated or cleaved, Tau can aggregate into insoluble forms that disrupt neuronal function, contributing to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). Emerging evidence suggests that similar Tau-related alterations may occur in individuals with chronic exposure to psychoactive substances. This review compiles experimental, clinical, and postmortem findings that collectively indicate a substance-specific influence on Tau dynamics. Alcohol and opioids, for instance, promote Tau hyperphosphorylation and fragmentation through the activation of kinases such as GSK-3β and CDK5, as well as proteases like caspase-3, leading to neuroinflammation and microglial activation. Stimulants and dissociatives disrupt insulin signaling, increase oxidative stress, and impair endosomal trafficking, all of which can exacerbate Tau pathology. In contrast, cannabinoids and psychedelics may exert protective effects by modulating kinase activity, reducing inflammation, or enhancing neuroplasticity. Psychedelic compounds such as psilocybin and harmine have been demonstrated to decrease Tau phosphorylation and facilitate cognitive restoration in animal models. Although the molecular mechanisms differ across substances, Tau consistently emerges as a convergent target altered in substance-related cognitive disorders. Understanding these pathways may provide not only mechanistic insights into drug-induced neurotoxicity but also identify Tau as a valuable biomarker and potential therapeutic target for the prevention or treatment of cognitive decline associated with substance use. Full article

Anterior cruciate ligament reconstruction (ACLR) results in prolonged muscle weakness, impaired neuromuscular control, and delayed return to sport. Cross-education (CE), unilateral training of the uninjured limb, has been proposed as an adjunct therapy to promote bilateral adaptations. This scoping review evaluated the functional and neuroplastic effects of CE rehabilitation post-ACLR. Following PRISMA-ScR and JBI guidelines, PubMed, Scopus, Web of Science, and PEDro were searched up to February 2025. A bibliometric analysis was also conducted to report keyword co-occurrence and identify trends in this line of research. Of 333 screened references, 14 studies (price index: 43% and low-to-moderate risk of bias) involving 721 participants (aged 17–45 years) met inclusion criteria. CE protocols (6–12 weeks; 2–5 sessions/week) incorporating isometric, concentric, and eccentric exercises demonstrated strength gains (10–31%) and strength preservation, alongside improved limb symmetry (5–14%) and dynamic balance (7–18%). There is growing interest in neuroplasticity and corticospinal excitability, although neuroplastic changes were assessed heterogeneously across studies. Findings support CE as a feasible and low-cost strategy to complement early-stage ACLR rehabilitation, especially when direct loading of the affected limb is limited. Standardized protocols for clinical intervention and neurophysiological assessment are needed. Full article

Kinesthetic motor imagery (KMI), the mental rehearsal of a motor task without its actual performance, constitutes one of the most common techniques used for brain–computer interface (BCI) control for movement-related tasks. The effect of neural injury on motor cortical activity during execution and imagery remains under investigation in terms of activations, processing of motor onset, and BCI control. The current work aims to conduct a post hoc investigation of the event-related potential (ERP)-based processing of KMI during BCI control of anthropomorphic robotic arms by spinal cord injury (SCI) patients and healthy control participants in a completed clinical trial. For this purpose, we analyzed 14-channel electroencephalography (EEG) data from 10 patients with cervical SCI and 8 healthy individuals, recorded through Emotiv EPOC BCI, as the participants attempted to move anthropomorphic robotic arms using KMI. EEG data were pre-processed by band-pass filtering (8–30 Hz) and independent component analysis (ICA). ERPs were calculated at the sensor space, and analysis of variance (ANOVA) was used to determine potential differences between groups. Our results showed no statistically significant differences between SCI patients and healthy control groups regarding mean amplitude and latency (p < 0.05) across the recorded channels at various time points during stimulus presentation. Notably, no significant differences were observed in ERP components, except for the P200 component at the T8 channel. These findings suggest that brain circuits associated with motor planning and sensorimotor processes are not disrupted due to anatomical damage following SCI. The temporal dynamics of motor-related areas—particularly in channels like F3, FC5, and F7—indicate that essential motor imagery (MI) circuits remain functional. Limitations include the relatively small sample size that may hamper the generalization of our findings, the sensor-space analysis that restricts anatomical specificity and neurophysiological interpretations, and the use of a low-density EEG headset, lacking coverage over key motor regions. Non-invasive EEG-based BCI systems for motor rehabilitation in SCI patients could effectively leverage intact neural circuits to promote neuroplasticity and facilitate motor recovery. Future work should include validation against larger, longitudinal, high-density, source-space EEG datasets. Full article

Electrophysiological studies reveal significant organizational and functional differences in the cortex of blind individuals compared to sighted individuals. These differences result from the nervous system’s reorganization to adapt to new sensory modalities used in daily life. Cortical visual prostheses offer a means to restore visual sensations in blind individuals by generating phosphenes, luminous perceptions that provide information about their surroundings. This study investigates the cortical changes associated with the use of a visual neuroprosthesis, focusing on how the brain adapts to the restored visual input. Our findings aim to contribute to understanding neuroplasticity in sensory restoration processes. Full article