NeuroSci

Behavior is not a mere sequence of responses to stimuli but the dynamic expression of internal processes such as planning, prediction, valuation, and inference. These functions arise from distributed and metabolically costly neural systems and are best understood by considering behavior and neural activity together. This article presents a narrative and conceptual review of the neuroscience of behavior, integrating biological, environmental, and computational perspectives. We synthesize evidence from motor control, neural population dynamics, predictive processing, and spontaneous behavior, showing that behavior cannot be explained without the neural systems that generate it, and that neural activity gains meaning only through detailed behavioral models. Neural dynamics correlate with latent variables, such as intention and prediction error, that structure adaptive action across timescales. Recent advances in behavioral analysis, dimensionality reduction, and computational modeling enable the analysis of neural and behavioral data with comparable complexity, revealing shared computational architectures that link population activity with the organization of action. Our methodology involved a targeted literature search in PubMed and Web of Science (1919–2025), supplemented by seminal earlier works. By combining mechanistic and functional analysis, we outline a unified framework that explains how brains, bodies, and environments together generate flexible, adaptive behavior. Full article

Atypical parkinsonian disorders—progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA)—are rare, rapidly progressive neurodegenerative syndromes characterized by distinct molecular pathologies, heterogeneous clinical phenotypes, and limited therapeutic options. Accurate diagnosis remains a major clinical challenge, especially during early and prodromal phases, due to overlap with Parkinson’s disease (PD), phenotypic evolution, and the absence of reliable stand-alone biomarkers. Misclassification delays prognosis, impairs patient care, and hinders clinical trial design. This review synthesizes advances from 2015 to 2025 in clinical, imaging, and biomarker-based diagnosis of PSP, CBD, and MSA. We examine their phenotypic spectra, neuropathological substrates, and epidemiological trends, and critically evaluate the diagnostic performance and translational potential of emerging tools—including quantitative MRI morphometry, second-generation tau and α-synuclein PET ligands, neurophysiological markers such as video-oculography and autonomic testing, and fluid biomarkers such as neurofilament light chain. Persistent diagnostic barriers are identified, from phenotypic mimicry and pathological pleomorphism to the limited specificity of molecular assays and inequitable access to advanced technologies. We propose tiered, multimodal diagnostic algorithms that integrate structured clinical phenotyping with quantitative imaging, molecular diagnostics, systemic risk profiling, and autopsy-linked validation. Such biology-anchored approaches could enable diagnosis years before classical features emerge, improve patient stratification for disease-modifying trials, and lay the foundation for precision medicine in atypical parkinsonian disorders. A paradigm shift from descriptive nosology to mechanistically grounded frameworks is essential to accelerate early intervention and transform the clinical management of these devastating diseases. Full article

Stimulator of interferon genes (STING) is a cytosolic DNA sensor that activates type I interferon (IFN) signaling, which plays a key role in neuroinflammation. Although the role of STING in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), remains debated, its involvement in the development of CNS lesions, particularly within localized pathology, modeled here by targeting the corpus callosum, has yet to be explored. Using a focal EAE model, we compared the induction of lesions in wild-type and STING-deficient (STING^gt/gt) mice. Lesions were analyzed by immunohistochemistry, flow cytometry, and transcriptomics. STING-deficient mice had significantly larger demyelinated lesions, reduced ISG expression, and modified immune cell infiltration. STING signaling limits lesion severity in focal EAE by promoting IFN responses and regulating immune infiltration. These findings position STING as a potential target for MS therapy. Full article

Since its introduction, the construct of executive functions (EFs) has been associated with a set of tests to assess these functions and a brain network centered in the associative frontal brain regions. While the majority of perspectives have endorsed these associations, some studies have started casting doubts on them. In this article, the association between the construct of EFs, the tests used to assess them, and the involvement of frontal regions is examined. A sample of 28 patients with brain injuries was divided into three subgroups according to the region of the injury (anterior, posterior, antero-posterior). Patients were assessed with a battery of tests, including 25 measures of EFs and 6 control measures. A series of regression models revealed no significant differences in performance across the three groups. Findings indicate that the EF tests are not specific enough to differentiate EFs and brain injuries. The alleged reference of EFs to the frontal areas of the brain should attribute a higher role to other associative areas. The present study provides recommendations about how the EFs concept could be improved through methodological refinements and/or its dissemination. Full article

Background: Neural efficiency theory proposes that expert athletes optimize brain resource allocation and functioning. Beta band oscillations are associated with attention, motor preparation, and emotional control, reflecting adaptive patterns of reduced cortical energy expenditure (absolute power) and greater temporal precision (peak frequency). Slow cortical potential (SCP) neurofeedback has emerged as a method to train voluntary cortical regulation, yet its application in sports—particularly in precision-demanding disciplines such as golf—remains underexplored. The aim of this study was to evaluate the effects of SCP neurofeedback on beta band activity in competitive golfers. Methods: Forty-two golfers were randomly assigned to either an intervention group (n = 21), which completed 16 SCP neurofeedback sessions (2560 trials), or a control group (n = 21). SCP activity was measured during activation and deactivation trials, while EEG beta oscillations were analyzed in terms of peak frequency and absolute power at C3, O2, F8, and T5. These sites were chosen for their relevance to golf: C3 (motor execution), O2 (visual processing), F8 (inhibitory and emotional control), and T5 (visuospatial integration). Results: The intervention group showed significant increases in positive SCP trials, reflecting improved voluntary cortical inhibition. Peak frequency increased in Beta 1 (C3) and Beta 2 (O2), while absolute power decreased at F8 and T5, which seems to indicate a reduced cortical overload and enhanced visuospatial integration. Conclusions: SCP neurofeedback modulated beta activity in golfers, enhancing neural efficiency and supporting its potential as an innovative tool to optimize performance in precision sports. Full article

Introduction: Multiple sclerosis (MS) is a chronic neurodegenerative disease that entails high costs, progressive disability, and reduced quality of life (QoL). Telerehabilitation (TR), supported by new technologies, is emerging as an alternative or complement to in-person rehabilitation, potentially lowering socioeconomic impact and improving QoL. Aim: The objective of this study was to evaluate the effect of TR on the QoL of people with MS compared with in-person rehabilitation or no intervention. Materials and methods: A systematic review of randomized clinical trials was conducted (March–May 2025) following PRISMA guidelines. Searches were run in the PubMed-Medline, EMBASE, PEDro, Web of Science, and Dialnet databases. Methodological quality was assessed with the CASP scale, risk of bias with the Risk of Bias 2 tool, and evidence level and grade of recommendation with the Oxford Classification. The protocol was registered in PROSPERO (CRD420251110353). Results: Of the 151 articles initially found, 12 RCTs (598 total patients) met the inclusion criteria. Interventions included (a) four studies employing video-controlled exercise (one involving Pilates to improve fitness, another involving exercise to improve fatigue and general health, and two using exercises focused on the pelvic floor muscles); (b) three studies using a monitoring app to improve manual dexterity, symptom control, and increased physical activity; (c) two studies implementing an augmented reality system to treat cognitive deficits and sexual disorders, respectively; (d) one platform with a virtual reality headset for motor and cognitive training; (e) one study focusing on video-controlled motor imagery, along with the use of a pain management app; (f) a final study addressing cognitive training and pain reduction. Studies used eight different scales to assess QoL, finding similar improvements between groups in eight of the trials and statistically significant improvements in favor of TR in four. The included trials were of good methodological quality, with a moderate-to-low risk of bias and good levels of evidence and grades of recommendation. Conclusions: TR was more effective in improving the QoL of people with MS than no intervention, was as effective as in-person treatment in patients with EDSS ≤ 6, and appeared to be more effective than in-person intervention in patients with EDSS between 5.5 and 7.5 in terms of QoL. It may also eliminate some common barriers to accessing such treatments. Full article

Background/Objectives: The glymphatic system is a recently characterized glial-dependent waste clearance pathway in the brain, which makes use of perivascular spaces for cerebrospinal fluid exchange. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) offers a non-invasive method for estimating perivascular flow, but its biological specificity and susceptibility to methodological variation, particularly head position during MRI acquisition, remain as threats to the validity of this technique. This study aimed to assess the prevalence of current DTI-ALPS practices, evaluate the impact of head orientation on ALPS index calculation, and propose a novel computational approach to improve measurement validity. Methods: We briefly reviewed DTI-ALPS literature to determine the use of head-orientation correction strategies. We then analyzed diffusion MRI data from 172 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to quantify the influence of head orientation on ALPS indices computed using the conventional Unrotated-ALPS, a vecrec-corrected ALPS, and the new LD-ALPS method proposed within. Results: A majority of studies employed Unrotated-ALPS, which does not correct for head orientation. In our sample, Unrotated-ALPS values were significantly associated with absolute head pitch (r₁₆₉ = −0.513, p < 0.001), indicating systematic bias. This relationship was eliminated using either vecreg or LD-ALPS. Additionally, LD-ALPS showed more sensitivity to cognitive status as measured by Mini-Mental State Examination scores. Conclusions: Correcting for head orientation is essential in DTI-ALPS studies. The LD-ALPS method, while computationally more demanding, improves the reliability and sensitivity of perivascular fluid estimates, supporting its use in future research on aging and neurodegeneration. Full article

Background: The Coma Recovery Scale–Revised (CRS-R) is the gold standard for diagnosing chronic disorders of consciousness (DoC); however, its clinical utility is limited by lengthy administration and the need for specialized training. The Simplified Evaluation of Disorders of Consciousness (SECONDs) provides a faster and more user-friendly alternative. Objective: This study aims to evaluate the validity and reliability of the Argentine adaptation of the SECONDs scale in adults with chronic DoC due to acquired brain injury. Methods: Twenty-nine patients were evaluated over two consecutive days by three blinded raters. On day one, rater A administered the SECONDs (A1) and rater B administered the CRS-R (B) to assess concurrent validity. On day two, rater A repeated the SECONDs (A2), and rater C performed an additional SECONDs assessment (C), permitting evaluation of intra-rater (A1 vs. A2) and inter-rater (A vs. C) reliability. Results: The SECONDs demonstrated excellent intra-rater (ICC = 0.98) and inter-rater (ICC = 0.86) reliability. Concurrent validity with the CRS-R was strong (r = 0.73, p < 0.001). Diagnostic agreement was high between A1 and B (κ = 0.75) and between both A1-A2 and A1-C (κ = 0.82). The median administration time was significantly shorter for the SECONDs (10 vs. 15 min; p < 0.001). Conclusion: The Argentine SECONDs is a valid, reliable, and efficient tool for the clinical assessment of DoC patients in rehabilitation settings. Full article

Until recently, research on the pathobiological substrate of psychosis has been focused on neurotransmitter perturbations. However, this scope has expanded to include new fields, such as the immune/redox/metabolic/neuroendocrine/stress systems. Indeed, basic research in the stress field showed that the systems above can represent components of a general inflammatory process as tightly interconnected as a Gordian knot. Based on the inflammatory hypothesis concerning the psychosis etiopathology, the findings from psychotic cohort studies on each one of the immune/redox/metabolic/neuroendocrine/stress systems have started to accumulate. The evidence favors the involvement of these systems in the formation of the pathobiological psychotic substrate, yet little is known concerning their interplay. This review attempts to establish a frame of reference for the evidence concerning intersystemic interactions, starting with the basic research on the stress field and expanding to clinical studies with psychosis cohorts, hoping to instigate new avenues of research. Full article

This study aims to investigate whether a combined action observation–motor imagery practice may enhance the effects of conventional physical rehabilitation in a stroke survivor population. A total of 8 (7 male, 1 female) post-stroke patients with upper limb hemiparesis were enrolled into a single-blinded, randomised, study. Five times per week for three weeks, four patients experienced 60’ conventional physical therapy, while the other 4 experienced 30’ conventional physical therapy and 30’ action observation–motor imagery practice. The Fugl-Meyer Assessment-Upper Extremity and the Wolf Motor Function Test scores from the baseline and post-physiotherapy were used to evaluate upper extremity motor function. Patients who received the AO + MI alongside conventional physical rehabilitation benefitted more than those who received only conventional physical rehabilitation. However, the sample size was very small (only eight participants), which reduces both the statistical power and the ability to generalise the results. Moreover, there was no follow-up; therefore, it is unclear whether the observed improvements lasted over time. Finally, some potentially confounding factors, such as stroke type or lesion site, were not statistically controlled. Notwithstanding these limitations, our findings may serve as a basis for future large-scale, well-controlled studies on AO + MI in stroke rehabilitation. Full article

Background: attention-deficit/hyperactivity disorder (ADHD) and Alzheimer’s disease (AD) are distinct neurological conditions that may share genetic and molecular underpinnings. ADHD, a neurodevelopmental disorder, affects approximately 5% of children and 3% of adults globally, while AD, a neurodegenerative disorder, is the leading cause of dementia in older adults. Emerging evidence suggests potential overlapping contributors, including pathways related to synaptic plasticity, neuroinflammation, and oxidative stress. Methods: this systematic review investigated potential genetic predispositions linking Attention-Deficit/Hyperactivity Disorder (ADHD) and Alzheimer’s Disease (AD). Following PRISMA guidelines, a search was conducted in Web of Science, Embase, PsycINFO, and PubMed using keywords related to ADHD, AD, and genetic factors. Studies included were original human studies utilizing genetic analyses and ADHD polygenic risk scores (PRS), with AD confirmed using established diagnostic criteria. Exclusion criteria comprised non-original studies, animal research, and articles not addressing genetic links between ADHD and AD. Screening was conducted with Rayyan software (version 1.4.3), assessing relevance based on titles, abstracts, and full texts. Results:. The search identified 1450 records, of which 1092 were screened after duplicates were removed. Following exclusions, two studies met inclusion criteria. One study analyzed ADHD-PRS in 212 cognitively unimpaired older adults using amyloid-beta (Aβ) PET imaging and tau biomarkers. The findings revealed that ADHD-PRS was associated with progressive cognitive decline, increased tau pathology, and frontoparietal atrophy in Aβ-positive individuals, suggesting that ADHD genetic liability may exacerbate AD pathology. Another study assessed ADHD-PRS in a cohort of 10,645 Swedish twins, examining its association with 16 somatic conditions. The results showed modest risk increases for cardiometabolic, autoimmune, and neurological conditions, with mediation effects through BMI, education, tobacco use, and alcohol misuse, but no direct link between ADHD-PRS and dementia. Discussion and conclusions: this review highlights preliminary but conflicting evidence for a genetic intersection between ADHD and AD. One study suggests that ADHD genetic liability may exacerbate AD-related pathology in Aβ-positive individuals, whereas another large registry-based study finds no direct link to dementia, with associations largely mediated by lifestyle factors. The potential ADHD–AD relationship is likely complex and context-dependent, influenced by biomarker status and environmental confounders. Longitudinal studies integrating genetics, biomarkers, and detailed lifestyle data are needed to clarify this relationship. Full article

The extracranial–intracranial (EC–IC) bypass is a complex neurosurgical procedure performed for cerebral flow augmentation or flow replacement. Anesthetic management of these patients poses significant challenges due to the delicate balance required to maintain cerebral perfusion, often complicated by extensive cardiovascular comorbidities. Despite the complexity of these cases, current literature offers limited guidance on optimal anesthetic strategies. At our high-volume academic institution, we developed a standardized multimodal anesthetic protocol aimed at achieving intraoperative hemodynamic stability and facilitating timely postoperative emergence. A dedicated team of neuroanesthesiologists manages these cases in constant communication with the surgical team, ensuring real-time adjustments aligned with surgical needs and patient physiology. Our experience highlights the importance of individualized anesthetic planning and interdisciplinary coordination. Given the scarcity of published data and the specialized nature of EC–IC bypass procedures, we believe our institutional approach may serve as a useful reference for other centers, particularly those with limited exposure to this complex patient population, and lay the foundation for future prospective trials on optimal anesthetic care for this patient population. Full article

Background: Sciatic nerve schwannomas are rare benign tumors that can develop along the nerve’s course, from the pelvis to the thigh. Giant schwannomas, defined as those exceeding 5 cm, are particularly rare and may alter the tumor’s anatomical relationship with the nerve, impacting surgical strategy. Methods: A PRISMA 2020-compliant systematic review was conducted using the terms (“sciatic” AND “schwannoma”) for publications from 2000 to October 2024. Of 166 identified articles, we excluded those lacking giant schwannoma cases or involving syndromic associations. We also report a novel case from our center. Results: Our patient, a 35-year-old woman, presented with tingling and discomfort while sitting, localized to the left thigh, without radicular pain or motor deficits. MRI revealed a 14 × 7 cm mass. This is, to our knowledge, the first reported case of a giant solitary sciatic schwannoma of these dimensions located exclusively in the thigh, resected via intracapsular dissection with nerve monitoring, that was fully documented and reported. The review yielded 22 relevant articles, most involving pelvic or pelvic–thigh junction locations, with low recurrence rates. Conclusions: Giant sciatic schwannomas may be asymptomatic and slow-growing. This case is notable for tumor’s location, large size, and successful nerve-sparing surgical outcome. Full article

Background: The consequences of median nerve compression at the carpal tunnel level require a precise diagnostic evaluation before a frequently applied surgical intervention. Positive Tinel or Phalen signs are not always related to abnormal results in electroneurographic examinations of sensory and motor nerve fibers, which are intended to confirm final diagnoses, thereby confusing both surgeons and neurophysiologists. In the face of contradictory data, this study aims to reinvestigate these correlations in a randomly chosen population of patients with a primary diagnosis of carpal tunnel syndrome (CTS). Methods: Seventy-five randomly chosen patients with clinically detected CTS underwent neurophysiological studies of median nerve sensory (SNAP) and motor (CMAP) fibers conduction at the wrist. Both the median and ulnar nerves were assessed to reduce the risk of misinterpretation related to anatomical variations. Results: This study provides evidence on the relatively high utility of Phalen’s test in the early clinical detection of CTS within a general population of patients, whose positive results moderately correlate (rho = −0.327) with abnormalities in amplitudes rather than the distal latency parameters of SNAP recordings. The axonal injury type is more distinct than slowing-down impulses at the wrist following compression of the sensory nerve fibers in the early course of CTS. Positive Tinel’s test results are useful in diagnosing CTS patients with advanced axonal and demyelinating changes in the motor fibers at the wrist, which weakly correlate with prolonged latency and decreased amplitude in SNAP recordings (rho = −0.214 and rho = −0.235, respectively), but not with abnormalities in recordings of both amplitudes and latencies in CMAP electroneurography. Conclusions: The correlations between clinical signs and neurophysiological findings in CTS indicate that provocative tests, such as Phalen’s and Tinel’s, have limited diagnostic value, demonstrating only weak-to-moderate associations with neural conduction parameters. A positive Tinel’s sign should be regarded mainly as a marker of severe or chronic sensory impairment, often accompanied by motor fibers involvement in advanced pathological stages, rather than as an indicator of motor damage alone. Nerve conduction studies remain essential for confirming CTS, assessing its severity, and guiding treatment decisions, including surgical qualification. The presented correlation of clinical and functional neurophysiological results in CTS diagnosis allows us not only to specify the source and severity of the pathology of the median nerve fibers but also may influence the personalization of physiotherapeutic and surgical treatments. Full article

Patients with Parkinson’s disease frequently suffer from complicated anxiety disorders that are entwined with their attitudes and behaviors. In regard to this population, cognitive behavioral therapy (CBT) has been attracting an increasing amount of attention as a potentially effective treatment for mental health issues like anxiety. CBT helps patients manage stress and improve their psychological well being through behavioral, relaxation, and cognitive techniques. Even though there is already evidence that cognitive behavioral therapy (CBT) can dramatically reduce psychological symptoms in Parkinson’s patients, more thorough research is required to determine its exact role in comprehensive anxiety treatment and prove its long-term efficacy. The purpose of this study is to examine the body of research on the use of cognitive behavioral therapy (CBT) to treat anxiety in patients with Parkinson’s disease, looking at its limitations and challenges as well as clinical characteristics, advantages, and possible behavioral and psychological impacts. Full article

Traumatic brain injury (TBI), even when mild, has been associated with the presence of depression. Depression is a mood disorder characterized by persistent negative thoughts and sadness and is challenging to treat due to the multiple mechanisms involved in its pathophysiology, including increased nitric oxide (NO) levels. There are no completely safe and effective pharmacological strategies to treat this disorder. Mucuna pruriens (MP) has been shown to possess neuroprotective properties by regulating inflammatory responses and nitric oxide synthase activity. In this study, we evaluated the antidepressant-like effect of MP in male Wistar rats with induced mild traumatic brain injury (mTBI). MP extract (50 mg/kg i.p.) was administered immediately after mTBI and every 24 h for five days. We used the rats’ preference for sucrose consumption to assess the presence of depression-like behavior and analyzed the nitrite and nitrate levels in their cerebral cortex, striatum, midbrain, and nucleus accumbens. Untreated animals with mTBI showed a reduced preference for sucrose than those treated with MP, whose preference for sucrose was similar to that of sham animals. Increased nitrite and nitrate levels were observed in different brain regions in the TBI subjects; however, this increase was not observed in MP-treated animals. MP reduces behavior associated with depression and the brain NO levels in rats with mTBI. Full article

The antipsychotic drug haloperidol is found on the WHO list of essential drugs. In vitro, haloperidol demonstrates binding affinity for various receptors, including histamine H₂ receptors (H₂Rs). Several cardiac effects of haloperidol are known, but it remains unclear whether H₂Rs are involved. Here, the hypothesis was tested that haloperidol has the potential to act as either an agonist or an antagonist of human cardiac H₂Rs. The contractile effects of haloperidol were studied in isolated left and right atrial preparations from transgenic mice overexpressing human H₂Rs in the heart (H₂-TG), and compared to human atrial preparations from adult patients. Haloperidol reduced the histamine-stimulated force of contraction in the human atrial preparations as well as the histamine-stimulated force of contraction and beating rate in the left and right atrial preparations from the H₂-TG, respectively. Moreover, haloperidol reduced the isoprenaline-stimulated force of contraction in the human atrial preparations. In the wild-type mouse preparations, haloperidol only reduced the isoprenaline-stimulated beating rate in the right atria, but not the force in the left atria. Principally, haloperidol is capable of acting as an antagonist of both H₂Rs and β-adrenoceptors in the human heart. However, the effects are only relevant at very high doses of haloperidol, which are never or seldom achieved in practice. Full article

Background: Systemic lupus erythematosus (SLE) is reported to be the most common rheumatological disorder associated with catatonia. To date, reports on catatonia manifestations in SLE patients are uncommon in published literature, which has often favored a fragmented vision. We performed a narrative review with the aim of identifying all published reports of catatonia in SLE patients to ascertain—in a comprehensive view—its clinical characteristics and to provide useful insights for daily clinical practice. Methods: Comprehensive literature searches were carried out on 10 March 2025 (subsequently repeated ahead of draft on 6 June) in all main bibliographic databases: MEDLINE and EMBASE (OVID interface); PsycINFO (ProQuest); and PubMed, to capture within-text references. All searches combined controlled (MESH, Entree, and APA Headings) and free-text elements for both areas under observation: systemic lupus erythematosus (SLE) AND catatonia, with primary focus on case reports and series. Sets of findings were reviewed separately by the authors, and the full text of selected items was sourced. Further useful references were retrieved through citation lists. Results: 39 cases of patients with SLE and catatonia were identified (35 females and 4 males), with a mean age of 22.64 years (range 11–46). Only three patients were over the age of 40; a total of 10 had catatonia at the same time of SLE onset and 5 within a month of SLE diagnosis. Antiphospholipid and anti-ribosomal P protein antibodies were rarely identified. Almost all the patients improved following treatment with lorazepam and/or electroconvulsive therapy. Only one case of malignant catatonia was reported. Finally, a large number of patients were Asian or Afro-American, at least in the reports where ethnicity was specified. Conclusions: Catatonia can occur in patients with SLE, and it may be its first clinical manifestation, especially in young patients. Its prognosis is mostly favorable. Full article