Search Results (115)

Chronic neck pain is a multifactorial condition involving physical, psychological, and neurological dimensions. This case report describes the clinical course of a 25-year-old female with chronic neck pain and recurrent headaches who underwent a 6-week integrative intervention consisting of manual therapy and pain neuroscience-based sensorimotor retraining, administered three times per week. Outcome measures included the Headache Impact Test-6 (HIT-6), Neck Pain and Disability Scale (NPDS), Pain Catastrophizing Scale (PCS), Fear-Avoidance Beliefs Questionnaire (FABQ), pressure pain threshold (PPT), cervical range of motion (CROM), and functional near-infrared spectroscopy (fNIRS) to assess brain activity. Following the intervention, the patient demonstrated marked reductions in pain and psychological distress: HIT-6 decreased from 63 to 24 (61.9%), NPDS from 31 to 4 (87.1%), FABQ from 24 to 0 (100%), and PCS from 19 to 2 (89.5%). Improvements in PPT and CROM were also observed. fNIRS revealed decreased dorsolateral prefrontal cortex (DLPFC) activation during pain stimulation and movement tasks, suggesting a possible reduction in central sensitization burden. These findings illustrate that an integrative approach targeting biopsychosocial pain mechanisms may be beneficial in managing chronic neck pain, improving function, and modulating cortical responses. This report provides preliminary evidence in support of the clinical relevance of combining manual therapy with neurocognitive retraining in similar patients. Full article

Intracranial tumors such as gliomas, meningiomas, and brain metastases induce complex alterations in brain function beyond their focal presence. Modern connectomic and neuroimaging approaches, including resting-state functional MRI (rs-fMRI) and diffusion MRI, have revealed that these tumors disrupt and reorganize large-scale brain networks in heterogeneous ways. In adult patients, diffuse gliomas infiltrate neural circuits, causing both local disconnections and widespread functional changes that often extend into structurally intact regions. Meningiomas and metastases, though typically well-circumscribed, can perturb networks via mass effect, edema, and diaschisis, sometimes provoking global “dysconnectivity” related to cognitive deficits. Therefore, this review synthesizes interdisciplinary evidence from neuroscience, oncology, and neuroimaging on how intracranial tumors disrupt functional brain connectivity pre- and post-surgery. We discuss how functional heterogeneity (i.e., differences in network involvement due to tumor type, location, and histo-molecular profile) manifests in connectomic analyses, from altered default mode and salience network activity to changes in structural–functional coupling. The clinical relevance of these network effects is examined, highlighting implications for pre-surgical planning, prognostication of neurocognitive outcomes, and post-operative recovery. Gliomas demonstrate remarkable functional plasticity, with network remodeling that may correlate with tumor genotype (e.g., IDH mutation), while meningioma-related edema and metastasis location modulate the extent of network disturbance. Finally, we explore future directions, including imaging-guided therapies and “network-aware” neurosurgical strategies that aim to preserve and restore brain connectivity. Understanding functional heterogeneity in brain tumors through a connectomic lens not only provides insights into the neuroscience of cancer but also informs more effective, personalized approaches to neuro-oncologic care. Full article

As climate change continues to endanger a sustainable global condition, a growing literature investigates how to pursue green practices to fight its effects. Individuals are the essential starting point for such bottom-up attempts, with their attitudes towards sustainability driving pro-environmental behaviors (PEBs). Objectives: Based on the available relevant literature, this scoping review aims to delve into the processes underlying people’s sustainable decision-making (SDM) associated with PEBs. Methods: A scientific literature search was performed through (a) an active database search and (b) the identification of studies via reference and citation tracking. Results were screened and selected in Rayyan. Results: Included articles (n = 30) heterogeneously reported cognitive and neural aspects of SDM shaping PEBs. These proved to (a) recruit brain areas involved in mentalizing and moral cognition (likely because of their role in processing the interplay between personal and contextual factors rather than moral considerations in themselves); (b) undergo the same modulatory influences shaping other kinds of prosocial/cooperative behaviors; and (c) include brain areas involved in attentional/monitoring and emotional/motivational processes, alongside those consistently associated with decision-making processes. Conclusions: These results help interpret the available evidence on the neuro-cognitive bases of SDM while focusing on potential interventions to foster better practices and mitigate the adverse repercussions of climate change on human and global health. Full article

Background/Objectives: This study aims to investigate the influence of demographic, behavioral, anthropometric, and comorbid factors on brain atrophy in people living with HIV (PLWH). Methods: We conducted a cross-sectional study involving 121 HIV-positive patients, stratified into two groups, those with and without brain atrophy (BA). For each participant, we recorded demographic data, smoking status, physical activity levels, disease and treatment duration, and comorbidities. BA was quantitatively assessed using MRI-derived volumetric measurements of 47 cerebral substructures. Results: Patients with BA exhibited significantly reduced gray matter (GM) and white matter (WM) volumes alongside increased cerebrospinal fluid volumes, both in absolute and percentage measurements. WM atrophy was most pronounced in the frontal, parietal, and temporal lobes, with relative sparing of the occipital lobe. GM atrophy predominantly affected the basal ganglia (notably, the thalamus and putamen) and cortical regions, including the hippocampus, frontal, and parietal lobes. Significant positive correlations were observed between BA and both smoking status (pack–years) and disease duration, while physical activity demonstrated an inverse relationship (higher atrophy risk in those with less than 30 min of daily continuous walking). Non-adherence to antiretroviral therapy (ART) was also associated with BA. Among comorbidities, type 2 diabetes and HIV-associated neurocognitive disorders (HAND) showed the strongest associations with BA. Conclusions: Brain atrophy in PWH is correlated with smoking, physical inactivity, and the duration of HIV infection. Comorbid conditions, such as type II diabetes and HAND, amplify the risk for BA. We consider that early lifestyle interventions and optimized ART may mitigate the neurodegeneration process. Full article

Cognitive dysfunction represents one of the most persistent and disabling features of Long COVID, yet its molecular underpinnings remain incompletely understood. This narrative review synthesizes current evidence on the pathophysiological mechanisms linking SARS-CoV-2 infection to long-term neurocognitive sequelae. Key processes include persistent neuroinflammation, blood–brain barrier (BBB) disruption, endothelial dysfunction, immune dysregulation, and neuroendocrine imbalance. Microglial activation and cytokine release (e.g., IL-6, TNF-α) promote synaptic dysfunction and neuronal injury, while activation of inflammasomes such as NLRP3 amplifies CNS inflammation. Vascular abnormalities, including microthrombosis and BBB leakage, facilitate the infiltration of peripheral immune cells and neurotoxic mediators. Hypothalamic–pituitary–adrenal axis dysfunction and reduced vagal tone further exacerbate systemic inflammation and autonomic imbalance. Biomarkers such as GFAP, NFL, IL-6, and S100B have been associated with both neuroinflammation and cognitive symptoms. Notably, transcriptomic signatures in Long COVID overlap with those observed in Alzheimer’s disease, highlighting shared pathways involving tau dysregulation, oxidative stress, and glial reactivity. Understanding these mechanisms is critical for identifying at-risk individuals and developing targeted therapeutic strategies. This review underscores the need for longitudinal research and integrative biomarker analysis to elucidate the molecular trajectory of cognitive impairment in Long COVID. Full article

Objectives: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises rare systemic vasculitides that can present with cognitive dysfunction. However, data on the screening and characterization of cognitive dysfunction in AAV remain limited. Methods: Cognitive complaints in AAV patients were screened using self-report questionnaires. Objective cognitive impairment was assessed with a standardized neurocognitive test battery. Results were compared with clinical evaluations, brain MRI findings, treatment history, and neuropsychiatric symptoms. All test results were standardized for the overall population. Results: Twelve patients (five women, seven men) with a median [IQR] age of 68 [59–71] and a median [IQR] disease duration of 92 months [55–127] were included. None of the patients showed evidence of vasculitis activity on brain MRI. Cognition was assessed using a standardized neurocognitive test battery in all patients except one. Four patients (36%) were found to have cognitive impairment, defined as three or more altered tests. The most affected functions were attentional and executive, with the d2-R (4/4), Rey–Osterrieth Complex Figure Delayed Recall (3/4), and Trail Making Test Part B (3/4) showing the most frequent deficiencies. Objective cognitive disorders were not associated with self-reported cognitive complaints. No significant association was found between cognitive impairment and vasculitis activity or sequelae, corticosteroid and immunosuppressive treatments, or neuropsychiatric symptoms. Conclusions: This study highlights the presence of cognitive impairments in AAV, predominantly affecting attentional and executive functions, which may reflect vascular involvement. Early and tailored approaches to cognitive screening and management are essential to improve patient care and quality of life. Full article

Despite the success of antiretroviral therapy (ART) in suppressing viral replication in the blood, HIV persists in the central nervous system (CNS) and causes chronic neurocognitive impairment, a hallmark of HIV-associated neurocognitive disorders (HAND). This review looks at the complex interactions among HIV, the blood–brain barrier (BBB), neuroinflammation, and the roles of viral proteins, immune cell trafficking, and pro-inflammatory mediators in establishing and maintaining latent viral reservoirs in the CNS, particularly microglia and astrocytes. Key findings show disruption of the BBB, monocyte infiltration, and activation of CNS-resident cells by HIV proteins like Tat and gp120, contributing to the neuroinflammatory environment and neuronal damage. Advances in epigenetic regulation of latency have identified targets like histone modifications and DNA methylation, and new therapeutic strategies like latency-reversing agents (LRAs), gene editing (CRISPR/Cas9), and nanoparticle-based drug delivery also offer hope. While we have made significant progress in understanding the molecular basis of HIV persistence in the CNS, overcoming the challenges of BBB penetration and neuroinflammation is key to developing effective therapies. Further research into combination therapies and novel drug delivery systems will help improve outcomes for HAND patients and bring us closer to a functional cure for HIV. Full article

FKBP5 has been of special scientific interest in the behavioral sciences since it has been involved in the pathophysiology of several mental disorders. It is a gene with pleiotropic effects which encodes the protein FKBP5, a cochaperone that decreases glucocorticoid receptor (GR) affinity for glucocorticoids by competing with FKBP4, altering the GR chaperone complex, and impairing GR activation. As a key modulator of the stress response, FKBP5 plays a critical role in regulating cortisol levels in the organism. The FKBP5 gene is regulated through a combination of transcriptional, epigenetic, post-transcriptional, and environmental mechanisms, as well as genetic polymorphisms that influence its transcription and stress responsiveness. Notably, the rs1360780 T-allele in FKBP5 significantly affects FKBP5 regulation and has been linked to stress-related disorders by influencing transcription and stress responsiveness. In this narrative review, we aim to provide an overview of the role played by the single-nucleotide polymorphism rs1360780 in the FKBP5 locus in gene expression, its epigenetic regulation, and the impact of early stress in its functioning. We discuss some brain regions with differential expression of FKBP5 and some behavioral phenotypes linked to the locus. The T-allele of rs1360780 is considered a risk variant, as it leads to high FKBP5 induction, which delays negative feedback and increases GR resistance. This results in states of relative hypercortisolemia and brain morphofunctional alterations, particularly in regions sensitive to glucocorticoid activity during critical periods of neurodevelopment. Additionally, exposure to childhood maltreatment is associated with demethylation of the glucocorticoid response elements of FKBP5, further increasing its expression levels. Among the psychological dimensions analyzed in which FKBP5 is involved are neurocognition, aggression, suicidality, and social cognition. At the level of mental disorders, the gene may play a role in the pathogenesis of post-traumatic stress disorder, depression, and bipolar disorder. In psychotic disorders, its role is less clear. This knowledge enhances the understanding of disease mechanisms that operate through psychopathological dimensions, and highlights the need to design specific, person-centered psychopharmacological and environmental therapeutic interventions. Full article

Methamphetamine (METH) use is frequent among people with HIV (PWH) and appears to increase the risk of neuronal injury and neurocognitive impairment (NCI). This study explored in vivo the effects of a 12 week (long-term), low-dose METH regimen in a transgenic animal model of neuroHIV with inducible expression of HIV-1 transactivator of transcription (Tat). Seven months after transient Tat induction and five months after METH exposure ended, we detected behavioral changes in the Barnes maze (BM) spatial memory task in the Tat and METH groups but not the combined Tat + METH group. The novel object recognition (NOR) task revealed that Tat extinguished discrimination in female animals with and without METH, although METH alone slightly improved NOR. In contrast, in males, Tat, METH, and Tat + METH all compromised NOR. Neuropathological examination detected sex-dependent and brain region-specific changes of pre-synaptic terminals, neurites, and activation of astrocytes and microglia. RNA-sequencing and quantitative reverse transcription polymerase chain reaction indicated that METH and Tat significantly altered gene expression, including factors linked to Alzheimer’s disease-like NCI. In summary, chronic low-dose METH exerts long-term effects on behavioral function, neuropathology, and mRNA expression, and modulates the effects of Tat, suggesting sex-dependent and -independent mechanisms may converge in HIV brain injury and NCI. Full article

Background: Healthy cognitive functioning is a primary component of well-being, independence, and successful aging. Cognitive deficits can arise from various conditions, such as brain injury, mental illness, and neurological disorders. Rehabilitation is a highly specialized service limited to patients who have access to institutional settings. In response to this unmet need, telehealth solutions are ideal for triggering the migration of care from clinics to patients’ homes. Objectives: The aim of EARLY-COGN^3 will be threefold: (1) to test the efficacy of a digital health at-home intervention (tele@cognitive protocol) as compared to an unstructured cognitive at-home rehabilitation in a cohort of patients with Chronic Neurological Diseases (CNDs); (2) to investigate its effects on the biomolecular and neurophysiological marker hypothesizing that people with CNDs enrolled in this telerehabilitation program will develop changes in biological markers and cortical and subcortical patterns of connectivity; (3) to analyze potential cognitive, neurobiological, and neurophysiological predictors of response to the tele@cognitive treatment. Method: In this single-blind, randomized, and controlled pilot study, we will assess the short- and long-term efficacy of cognitive telerehabilitation protocol (tele@cognitive) as compared to an unstructured cognitive at-home rehabilitation (Active Control Group—ACG) in a cohort of 60 people with Mild Cognitive Impairment (MCI), Subjective Cognitive Complaints (SCCs), or Parkinson’s Disease (PD). All participants will undergo a clinical, functional, neurocognitive, and quality of life assessment at the baseline (T0), post-treatment (5 weeks, T1), and at the 3-month (T2) follow-up. Neurophysiological markers and biomolecular data will be collected at T0 and T1. Conclusions: EARLY-COGN^3 project could lead to a complete paradigm shift from the traditional therapeutic approach, forcing a reassessment on how CNDs could take advantage of a digital solution. (clinicaltrials.gov database, ID: NCT06657274) Full article

Chronic intermittent hypoxia (IH) is one of the hallmark features of obstructive sleep apnea (OSA) and adversely affects neurocognitive and behavioral functioning. However, how the duration of IH correlates with its deleterious effects remains unexplored. We aimed to assess the effects of IH over a prolonged period of time mimicking untreated OSA. Male C57Bl/6J mice were exposed to IH for 96 weeks. Sleep activity was acquired using a piezoelectric system. Novel object recognition (NOR) and the elevated plus maze test (EPMT) were conducted as measures of cognitive function and anxiety, respectively. Brain inflammation was evaluated by a panel of inflammation marker assays. All tests were performed after 16 and 96 weeks of IH exposure. After 96 weeks, sleep percentages during the dark phase decreased in both IH and room air (RA) compared to 16-week exposure (RA: p = 0.0214; IH: p = 0.0188). In addition to age-dependent declines in NOR performance, the mice after 96 weeks of IH exposure had lower NOR preference scores than RA controls (p = 0.0070). The time spent in open arms of the EPMT was reduced in mice exposed to IH compared to RA. Inflammatory marker expression increased in IH-exposed mice. Thus, aging and IH induce similar alterations in sleep, cognition, and neuroinflammation. However, the effects of aging are exacerbated by concurrent IH, suggesting that OSA is a disease associated with an acceleration in biological aging. Full article

Perioperative neurocognitive disorders (PNDs), including postoperative delirium, delayed neurocognitive recovery, and long-term postoperative neurocognitive disorders, present significant challenges for older patients undergoing surgery. Inflammation is a protective mechanism triggered in response to external pathogens or cellular damage. Historically, the central nervous system (CNS) was considered immunoprivileged due to the presence of the blood–brain barrier (BBB), which serves as a physical barrier preventing systemic inflammatory changes from influencing the CNS. However, aseptic surgical trauma is now recognized to induce localized inflammation at the surgical site, further exacerbated by the release of peripheral pro-inflammatory cytokines, which can compromise BBB integrity. This breakdown of the BBB facilitates the activation of microglia, initiating a cascade of neuroinflammatory responses that may contribute to the onset of PNDs. This review explores the mechanisms underlying neuroinflammation, with a particular focus on the pivotal role of cytokines in the pathogenesis of PNDs. Full article

Postoperative neurocognitive dysfunction (PND) is a prevalent and debilitating complication in elderly surgical patients, characterized by persistent cognitive decline that negatively affects recovery and quality of life. As the aging population grows, the rising number of elderly surgical patients has made PND an urgent clinical challenge. Despite increasing research efforts, the pathophysiological mechanisms underlying PND remain inadequately characterized, underscoring the need for a more integrated framework to guide targeted interventions. To better understand the molecular mechanisms and therapeutic targets of PND, this narrative review synthesized evidence from peer-reviewed studies, identified through comprehensive searches of PubMed, Embase, Cochrane Library, and Web of Science. Key findings highlight neuroinflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalances, microvascular changes, and white matter lesions as central to PND pathophysiology, with particular parallels to encephalocele- and sepsis-associated cognitive impairments. Among these, neuroinflammation, mediated by pathways such as the NLRP3 inflammasome and blood–brain barrier disruption, emerges as a pivotal driver, triggering cascades that exacerbate neuronal injury. Oxidative stress and mitochondrial dysfunction synergistically amplify these effects, while neurotransmitter imbalances and microvascular alterations, including white matter lesions, contribute to synaptic dysfunction and cognitive decline. Anesthetic agents modulate these interconnected pathways, exhibiting both protective and detrimental effects. Propofol and dexmedetomidine demonstrate neuroprotective properties by suppressing neuroinflammation and microglial activation, whereas inhalational anesthetics like sevoflurane intensify oxidative stress and inflammatory responses. Ketamine, with its anti-inflammatory potential, offers promise but requires further evaluation to determine its long-term safety and efficacy. By bridging molecular insights with clinical practice, this review highlights the critical role of personalized anesthetic strategies in mitigating PND and improving cognitive recovery in elderly surgical patients. It aims to inform future research and clinical decision-making to address this multifaceted challenge. Full article

Background: The digital phenotyping tool has great potential for the deep characterization of neurological and quality-of-life assessments in brain tumor patients. Phone communication activities (details on call and text use) can provide insight into the patients’ sociability. Methods: We prospectively collected digital-phenotyping data from six brain tumor patients. The data were collected using the Beiwe application installed on their personal smartphones. We constructed several daily sociability features from phone communication logs, including the number of incoming and outgoing text messages and calls, the length of messages and duration of calls, message reciprocity, the number of communication partners, and number of missed calls. We compared variability in these sociability features against those obtained from a control group, matched for age and sex, selected among patients with a herniated disc. Results: In brain tumor patients, phone-based communication appears to deteriorate with time, as evident in the trend for total outgoing minutes, total outgoing calls, and call out-degree. Conclusions: These measures indicate a possible decrease in sociability over time in brain tumor patients that may correlate with survival. This exploratory analysis suggests that a quantifiable digital sociability phenotype exists and is comparable for patients with different survival outcomes. Overall, assessing neurocognitive function using digital phenotyping appears promising. Full article

Canine functional magnetic resonance imaging (fMRI) neurocognitive studies represent an emerging field that is advancing more gradually compared to progress in human fMRI research. Given the potential benefits of canine fMRI for veterinary, comparative, and translational research, this systematic review highlights significant findings, focusing on specific brain areas activated during task-related and resting state conditions in dogs. The review addresses the following question: “What brain areas in dogs are activated in response to various stimuli?”. Following PRISMA 2020 guidelines, a comprehensive search of PUBMED, Scopus, and Web of Knowledge databases identified 1833 studies, of which 46 met the inclusion criteria. The studies were categorized into themes concerning resting state networks and visual, auditory, olfactory, somatosensory, and multi-stimulations studies. In dogs, resting state networks and stimulus-specific functional patterns were confirmed as vital for brain function. These findings reveal both similarities and differences in the neurological mechanisms underlying canine and human cognition, enhance the understanding of neural activation pathways in dogs, expand the knowledge of social bonding patterns, and highlight the potential use of fMRI in predicting the suitability of dogs for assistance roles. Further studies are needed to further map human–canine similarities and identify the unique features of canine brain function. Additionally, implementing innovative human methods, such as combined fMRI–magnetic resonance spectroscopy (MRS), into canine neurocognitive research could significantly advance the field. Full article