Brain Sciences

19 pages, 1113 KB

Open AccessArticle

Optic Nerve Sheath Diameter and Transcranial Doppler Pulsatility Index for Non-Invasive ICP Assessment in Acute Intracerebral Hemorrhage

by Nguyen Van Tuyen, Nguyen Hoang Ngoc, Nguyen Thị Cuc and Nghiem Xuan Hoan

Brain Sci. 2026, 16(6), 553; https://doi.org/10.3390/brainsci16060553 (registering DOI) - 22 May 2026

Abstract

Background: Intracranial hypertension is a critical complication of acute intracerebral hemorrhage (ICH), contributing to high early mortality and poor functional outcomes. Invasive intracranial pressure (ICP) monitoring remains the gold standard but carries procedural risks and is resource-intensive. This study evaluated the diagnostic and [...] Read more.

Background: Intracranial hypertension is a critical complication of acute intracerebral hemorrhage (ICH), contributing to high early mortality and poor functional outcomes. Invasive intracranial pressure (ICP) monitoring remains the gold standard but carries procedural risks and is resource-intensive. This study evaluated the diagnostic and prognostic utility of optic nerve sheath diameter (ONSD) ultrasonography and transcranial Doppler (TCD)-derived pulsatility index (PI) as non-invasive ICP surrogates in patients with severe ICH. Methods: A prospective observational study was conducted in 42 patients with acute ICH who underwent concurrent invasive ICP monitoring and serial ONSD/PI measurements at 10 time points (T0–T9) between October 2021 and August 2024. Diagnostic performance was assessed using measurement-level receiver operating characteristic (ROC) curve analysis. Exploratory early mortality prediction was evaluated using random forest machine learning models incorporating ONSD, PI, age, and sex. Results: A total of 274 paired ONSD–PI–ICP measurements were obtained. Both ONSD and PI showed moderate positive correlations with invasive ICP (rho = 0.49 and 0.43, respectively; p < 0.001). ONSD demonstrated superior diagnostic accuracy for detecting ICP ≥ 20 mmHg (AUC = 0.83; optimal threshold: 5.88 mm; sensitivity: 81%; specificity: 82%) compared to PI (AUC = 0.75). In exploratory random forest analyses, the combined ONSD–PI model showed high apparent discrimination for elevated ICP detection (AUC = 0.98), while the model incorporating ONSD, PI, age, and sex showed promising but potentially optimistic discrimination for early mortality prediction (AUC = 0.95). These machine learning results should be interpreted cautiously because of the small sample size, repeated-measurement structure, measurement-level data partitioning, and limited number of early deaths. Conclusions: ONSD ultrasonography and TCD-derived PI showed promising performance as non-invasive ICP markers in severe acute ICH. However, because of the small sample size, repeated-measurement design, measurement-level analyses, and exploratory nature of the machine learning models, these findings require validation in larger external cohorts before routine clinical implementation. Full article

(This article belongs to the Topic Neurological Updates in Neurocritical Care)

24 pages, 1086 KB

Open AccessSystematic Review

Effects of Brain-Computer Interface-Controlled Hand Robot Training on Post-Stroke Recovery of Upper Limb Motor Functions: A Meta-Analysis of Dose-Matched Randomized Controlled Trials

by Song Hu, Fengjiao Wang, Xiaoxue Gao, Yong Zhi and Daehee Kim

Brain Sci. 2026, 16(6), 552; https://doi.org/10.3390/brainsci16060552 - 22 May 2026

Abstract

Objective: To systematically evaluate the rehabilitation effect of brain-computer interface (BCI)-controlled hand robot training on post-stroke motor functions, especially upper limb functions. Methods: PubMed, Embase, Web of Science, Cochrane Library, CNKI, SinoMed, WanFang Data, and VIP Database were searched from inception [...] Read more.

Objective: To systematically evaluate the rehabilitation effect of brain-computer interface (BCI)-controlled hand robot training on post-stroke motor functions, especially upper limb functions. Methods: PubMed, Embase, Web of Science, Cochrane Library, CNKI, SinoMed, WanFang Data, and VIP Database were searched from inception to 13 March 2026. Randomized controlled trials (RCTs) with dose-matched designs were included, where the test group underwent BCI-controlled hand robot training and the control group received either pure hand robot training or routine rehabilitation. Meta-analysis was performed on RevMan 5.4. Results: Totally 11 RCTs involving 380 patients were included. Compared with hand robot training alone, BCI-controlled hand robot training significantly improved Fugl-Meyer Assessment for Upper Extremity (FMA-UE) scores (MD = 4.87, 95% CI: 1.04 to 8.69) and FMA-UE proximal scores (MD = 4.44, 95% CI: 0.15 to 8.74), and significantly reduced finger flexor spasticity (MD = −0.44, 95% CI: −0.68 to −0.21), but showed no significant difference in distal upper limb motor function or Action Research Arm Test (ARAT) scores. Compared with routine rehabilitation, BCI-controlled hand robot training significantly improved FMA-UE scores (MD = 6.55, 95% CI: 3.49 to 9.61). Conclusions: BCI-controlled hand robot training can effectively improve overall upper limb and proximal motor function after stroke and alleviate finger flexor spasticity, but the evidence for distal hand function and long-term efficacy remains limited. Full article

(This article belongs to the Special Issue Robot and Brain–Computer Interface Therapies for Neurorehabilitation: Current State of the Art and Applications)

36 pages, 4323 KB

Open AccessSystematic Review

A Systematic Review of Lifestyle Interventions for Neuropathy and Neuropathic Pain: Alcohol Consumption and Avoidance

by Michael Klowak, Ezra J. Bado, Aquilla Reid-John, Rumaysa Dawood, Candice Madakadze and Andrea K. Boggild

Brain Sci. 2026, 16(6), 551; https://doi.org/10.3390/brainsci16060551 - 22 May 2026

Abstract

Background: Neuropathy and neuropathic pain (NP) are globally prevalent, remain difficult to manage, and are often exacerbated by underlying lifestyle factors. Alcohol use, particularly in the context of chronic consumption or dependence, is a recognized contributor to peripheral nerve damage, yet its [...] Read more.

Background: Neuropathy and neuropathic pain (NP) are globally prevalent, remain difficult to manage, and are often exacerbated by underlying lifestyle factors. Alcohol use, particularly in the context of chronic consumption or dependence, is a recognized contributor to peripheral nerve damage, yet its association with neuropathy/NP has not been systematically evaluated. This systematic review synthesizes the current evidence on alcohol exposure, including quantity, frequency, and dependency, and its association with the incidence, prevalence, and severity of neuropathy/NP. Methods: This systematic review included observational studies assessing alcohol consumption patterns or dependence in relation to neuropathy/NP outcomes and was conducted in accordance with PRISMA guidelines. Exposure types were analyzed independently, and pooled odds ratios and relative risks were generated when sufficient data were available. The review was registered with PROSPERO number CRD42023484158. Results: Following de-duplication and exclusions, 76 studies were included, comprising cohort (n = 15), case–control (n = 12), and cross-sectional (n = 49) designs. While associations varied by study design and exposure category, alcohol dependence and consumption were more consistently linked with increased neuropathy incidence and severity, including electrophysiological evidence of compromised function. Notably, in studies examining alcohol cessation, abstinence was linked to clinical improvements in neuropathy/NP symptoms such as hypoesthesia and muscle weakness. While heterogeneity and risk of bias were present, largely due to the subjective classification of alcohol exposure and a lack of universally applied objective neuropathy measurement tools, multiple pooled estimates reached statistical significance. Conclusions: Evidence from observational studies supports an association between alcohol use, especially dependence, and the development and progression of neuropathy/NP, although causality remains unproven. Abstinence may offer therapeutic benefit, though further abstinence- and/or harm reduction-related interventional studies are required to clarify causality and guide low-cost, adjunctive strategies for alcohol-related neuropathy/NP. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Neuropathic Pain)

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31 pages, 470 KB

Open AccessSystematic Review

Biomarkers for Predicting Clinical Deterioration in Schizophrenia-Spectrum Disorders: A Systematic Review

by Valerio Ricci, Alessandro Sarni, Marialuigia Barresi, Lorenzo Remondino, Giovanni Martinotti and Giuseppe Maina

Brain Sci. 2026, 16(6), 550; https://doi.org/10.3390/brainsci16060550 - 22 May 2026

Abstract

Background/Objectives: Psychotic relapse affects over 80% of individuals with schizophrenia-spectrum disorders, driving long-term disability and hospitalization. Clinical relapse management relies on symptomatic monitoring without objective neurobiological tools to guide individualized antipsychotic decisions. Methods: This systematic review synthesizes evidence on neurophysiological, blood-based, molecular, neuroimaging, [...] Read more.

Background/Objectives: Psychotic relapse affects over 80% of individuals with schizophrenia-spectrum disorders, driving long-term disability and hospitalization. Clinical relapse management relies on symptomatic monitoring without objective neurobiological tools to guide individualized antipsychotic decisions. Methods: This systematic review synthesizes evidence on neurophysiological, blood-based, molecular, neuroimaging, and digital biomarkers for relapse prediction in schizophrenia-spectrum disorders. Results: Following the PRISMA 2020 guidelines, five databases were searched through March 2026 for longitudinal biomarker studies. Quality was assessed using the Newcastle-Ottawa Scale and PROBAST; findings were synthesized narratively due to substantial heterogeneity. From the 6812 citations screened, 21 studies were included across clinical high-risk, first-episode, and established illness populations. Conclusions: Mismatch negativity and P300 event-related potential (P300) showed the most consistent associations with relapse vulnerability, with mismatch negativity demonstrating relative independence from antipsychotic effects. Inflammatory and neuroendocrine markers—interleukin-6, C-reactive protein, and cortisol awakening response—predicted poor treatment response in multiple longitudinal investigations. Peripheral blood gene expression profiling identified TCF4 network dysregulation as a candidate molecular marker of impending relapse. Neuroimaging models did not outperform standard clinical variables. Digital phenotyping showed ecological promise but remains methodologically nascent. No single biomarker achieves sufficient accuracy for clinical implementation. Neurophysiological and inflammatory markers are the most tractable candidates for monitoring protocols. Future research should prioritize multimodal longitudinal designs, external validation, and systematic antipsychotic confounding control. Among the biomarkers reviewed, mismatch negativity and the interleukin-6/cortisol awakening response combination represent the most tractable candidates for pilot clinical implementation, particularly in specialized early psychosis services and antipsychotic dose-reduction research contexts; no biomarker currently achieves sufficient accuracy for routine use in maintenance treatment decisions. Full article

(This article belongs to the Special Issue Pharmacological and Psychopathological Clinical Studies on Psychotic and Mood Disorders)

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17 pages, 13027 KB

Open AccessArticle

Electrophysiological Changes in Resting-State EEG Following REAC BWO-G_B Neurobiological Modulation in Healthy Adults: A Spectral and Multivariate Exploratory Study

by Sergio Brasil, Alessandra Renck, Sigride Thome-Souza, Jean Faber, Arianna Rinaldi, Vania Fontani, Wellingson Silva Paiva and Salvatore Rinaldi

Brain Sci. 2026, 16(6), 549; https://doi.org/10.3390/brainsci16060549 - 22 May 2026

Abstract

Background: Radio Electric Asymmetric Conveyer (REAC) neurobiological modulation is proposed as an approach designed to interact with endogenous bioelectrical processes involved in cortical regulation. However, its electrophysiological correlates in physiologically preserved neural systems remain insufficiently characterized. The present study explored whether a standardized [...] Read more.

Background: Radio Electric Asymmetric Conveyer (REAC) neurobiological modulation is proposed as an approach designed to interact with endogenous bioelectrical processes involved in cortical regulation. However, its electrophysiological correlates in physiologically preserved neural systems remain insufficiently characterized. The present study explored whether a standardized REAC Brain Wave Optimization Gamma (BWO-G_B) protocol is associated with measurable changes in resting-state EEG activity in healthy adults. Methods: Nine neurologically healthy participants completed a standardized REAC BWO-G_B protocol consisting of 18 sessions administered over six consecutive days. Resting-state EEG recordings were obtained before and after the intervention. Spectral power was analyzed across the 1–100 Hz range. Multivariate organization of cortical activity was explored using Principal Component Analysis (PCA) and Canonical Discriminant Analysis (CDA), with CDA used only as a descriptive visualization of within-dataset multivariate organization. Cross-correlation analysis was applied to evaluate changes in inter-regional temporal synchronization. Individual-level non-parametric testing (Wilcoxon signed-rank test) was conducted only to characterize within-subject directional spectral modulation across the recorded montage. Results: Post-intervention EEG recordings showed a consistent redistribution of spectral power across cortical regions, predominantly within frequencies below approximately 20 Hz. This pattern was observed across subjects at the individual level. Multivariate analysis revealed a dissociation between PCA, which showed partial overlap between conditions, and CDA, which descriptively showed within-dataset separability between baseline and post-intervention cortical states. Cross-correlation analysis indicated a spatially differentiated redistribution of temporal synchronization across cortical regions. At the individual level, descriptive Wilcoxon analyses indicated broadband spectral differences in seven of nine participants (p < 0.05), with consistent directional trends across all subjects; these p-values should not be interpreted as confirmatory statistical evidence. Conclusions: The findings indicate the presence of a reproducible electrophysiological pattern observed after completion of the REAC BWO-G_B protocol in healthy adults. The observed combination of spectral redistribution, descriptive multivariate organization, and changes in temporal synchronization is consistent with a structured post-intervention modification of cortical activity organization within the present dataset. However, given the exploratory design, small sample size, absence of a control condition, and absence of objective vigilance monitoring, these results should be interpreted cautiously and should not be considered as evidence of intervention-specific effects. Further controlled studies are required to determine specificity, underlying mechanisms, and potential functional relevance. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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15 pages, 917 KB

Open AccessSystematic Review

Neuroimmune Dysregulation and the Role of IL-10 in Depression: A Systematic Review

by José Luis Cortes-Altamirano, Alfonso Alfaro-Rodríguez, Angélica González-Maciel, Beatriz Pérez-Guille, Rosa Eugenia Soriano-Rosales, Herlinda Bonilla-Jaime, Alberto Ávila-Luna, Antonio Bueno-Nava, Pedro Sánchez-Aparicio and Ana Lilia Dotor-Llerena

Brain Sci. 2026, 16(6), 548; https://doi.org/10.3390/brainsci16060548 - 22 May 2026

Abstract

Background: Treatment-resistant depression (TRD) represents a major clinical challenge and is increasingly associated with persistent neuroinflammatory processes. Evidence suggests that dysregulation of the immune system, particularly the imbalance between pro-inflammatory and anti-inflammatory cytokines, contributes to poor therapeutic response. In this context, interleukin-10 (IL-10) [...] Read more.

Background: Treatment-resistant depression (TRD) represents a major clinical challenge and is increasingly associated with persistent neuroinflammatory processes. Evidence suggests that dysregulation of the immune system, particularly the imbalance between pro-inflammatory and anti-inflammatory cytokines, contributes to poor therapeutic response. In this context, interleukin-10 (IL-10) has emerged as a key mediator in regulating the inflammatory response. Objective: To systematically analyze the evidence on neuroimmune dysregulation in depression, with an emphasis on TRD, and to evaluate the potential role of IL-10 as a biomarker and modulator of therapeutic response. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Fourteen studies were included, comprising randomized clinical trials, longitudinal studies, a prospective cohort study, and exploratory designs. Methodological quality was assessed using the RoB 2 tool and complementary approaches. Data were integrated through a qualitative analysis focused on inflammatory biomarkers and clinical outcomes. Results: The studies consistently showed an association between elevated levels of pro-inflammatory cytokines, such as IL-6 and TNF-α, and the severity of depressive symptoms, as well as reduced response to conventional treatments. Immunomodulatory interventions, including ketamine, pentoxifylline, and minocycline, were associated with clinical improvement, particularly in patients with elevated baseline inflammation. IL-10 appears to be involved in counter-regulatory neuroimmune processes associated with inflammatory balance. Conclusions: Neuroinflammation plays a central role in TRD. IL-10 may serve as a relevant biomarker and a potential target for personalized therapeutic strategies informed by immune profiles, through modulation of neuroinflammatory pathways. Full article

(This article belongs to the Special Issue The Interplay Between the Brain, Behavior and Immunity)

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13 pages, 1635 KB

Open AccessArticle

Delayed Correlations Between Geomagnetic Activity and Human EEG Alpha and Theta Oscillations: Evidence from Archival and Experimental Data

by Carlee D. Chezzi, Kevin S. Saroka, Kate S. Branigan, Samuel J. Levac and Blake T. Dotta

Brain Sci. 2026, 16(6), 547; https://doi.org/10.3390/brainsci16060547 - 22 May 2026

Abstract

Neural oscillations in the alpha and theta bands have been linked to environmental factors, including geomagnetic disturbances, yet the temporal dynamics of these interactions remain poorly understood. This study examined the relationship between geomagnetic activity, quantified by the Kp index, and brain activity [...] Read more.

Neural oscillations in the alpha and theta bands have been linked to environmental factors, including geomagnetic disturbances, yet the temporal dynamics of these interactions remain poorly understood. This study examined the relationship between geomagnetic activity, quantified by the Kp index, and brain activity in low alpha (7–10 Hz) and theta (4–7 Hz) bands using two complementary approaches. In Experiment 1, archival EEG data from 238 subjects collected over four years were analyzed for correlations between daily Kp values and band power across a ±90-day window. Significant positive correlations (p < 0.01) emerged in both bands, with a spatially coherent peak in caudal regions occurring 19 days prior to EEG measurement. In Experiment 2, an independent sample of 22 participants was exposed to a simulated geomagnetic storm, and EEG was recorded at baseline and 19 days post-exposure. Paired-samples t-tests revealed significant within-subject reductions in theta, low alpha, and high alpha power over frontal and parietal regions, consistent with a delayed neural response. Together, these findings provide converging correlational and experimental evidence for a lagged influence of geomagnetic activity on human brain oscillations. The 19-day delay observed in both datasets suggests that geomagnetic disturbances may exert residual effects on neural dynamics well beyond immediate exposure, warranting further investigation into underlying mechanisms and potential behavioral relevance. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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8 pages, 468 KB

Open AccessArticle

Incidences of Concussion in the United States: A Review of Health Insurance Claims

by Alyssa M. Lickfeld, Elizabeth V. Castro, Ava Ferreira, Jazlyn M. Edwards, Alissa Patel, John J. Leddy and Mohammad N. Haider

Brain Sci. 2026, 16(6), 546; https://doi.org/10.3390/brainsci16060546 - 22 May 2026

Abstract

Background: Mild traumatic brain injuries (mTBIs) are a significant public health concern in the US. Understanding incidence and demographic patterns is essential for developing targeted prevention and intervention strategies. The most recent study using national healthcare records to examine incidence utilized data [...] Read more.

Background: Mild traumatic brain injuries (mTBIs) are a significant public health concern in the US. Understanding incidence and demographic patterns is essential for developing targeted prevention and intervention strategies. The most recent study using national healthcare records to examine incidence utilized data from 2016, highlighting the need for updated estimates that reflect current trends. Methods: The MarketScan^® Database was used for this study which includes person-specific clinical utilization, expenditures, and enrollment across different services. A query for mTBIs (S06.0x.xx) or post-concussion syndrome (F07.89) from January–December 2023 was performed for patients aged 0–64. Patients with the same diagnosis codes for the prior 12 months (i.e., chronic diagnosis), moderate to severe TBIs (S06.2–9), skull fractures (S02.xx), and/or brain hemorrhages (S06.3x) were excluded. Results: Out of 11,737,855 insured members with data in 2023, 43,213 new mTBIs were recorded (incidence rate = 0.37%), with the highest rate in adolescents (incidence rate = 1.27%). From the ages of 0–14 years, males had a higher incidence of concussion, but from 15 to 65 years, females had a higher incidence. Minimal differences were seen between urban and rural zip codes. Conclusions: Concussion incidence in adolescents is higher than other age groups, which may reflect increased participation in sports or heightened vulnerability during development. Males had a higher incidence than females during childhood, but females did later in life. These differences may reflect true disparities in injury risk, variations in reporting patterns, or a combination of both. Further research is warranted to understand the underlying mechanisms and to inform age- and sex-specific prevention efforts. Full article

(This article belongs to the Special Issue Accessing Treatment and Rehabilitation for Underserved Survivors of Brain Injury)

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8 pages, 336 KB

Open AccessCase Report

Opicapone as Add-On Therapy to Continuous Subcutaneous Foslevodopa/Foscarbidopa Infusion: Clinical Improvement and Wearable Sensor-Based Gait Analysis

by Paolo Solla, Carla Masala, Gianluca Martinez, Raffaele Galiero, Valentina Floris, Elisa Ogana, Valentina Canu, Francesco Loy and Tommaso Ercoli

Brain Sci. 2026, 16(5), 545; https://doi.org/10.3390/brainsci16050545 - 21 May 2026

Abstract

Background/Objectives: Continuous subcutaneous foslevodopa/foscarbidopa infusion (CSFLI) improves motor fluctuations in advanced Parkinson’s disease (PD), but some patients continue to experience residual motor and non-motor fluctuations despite optimized infusion parameters. We describe two patients receiving CSFLI in whom the addition or reintroduction of opicapone [...] Read more.

Background/Objectives: Continuous subcutaneous foslevodopa/foscarbidopa infusion (CSFLI) improves motor fluctuations in advanced Parkinson’s disease (PD), but some patients continue to experience residual motor and non-motor fluctuations despite optimized infusion parameters. We describe two patients receiving CSFLI in whom the addition or reintroduction of opicapone was associated with improvement in persistent fluctuations. In one patient, clinical findings were further explored using wearable sensor monitoring. Methods: Two patients with advanced PD treated with CSFLI and residual fluctuations received add-on opicapone. Clinical evaluation included neurological examination, assessment of motor fluctuations, and documentation of antiparkinsonian therapy before and after opicapone introduction. In one patient, motor performance was additionally evaluated with wearable sensor monitoring during the Timed Up and Go test and the 6-minute walk test before (T0) and three months after opicapone introduction (T1). Results: In both cases, opicapone 50 mg once daily was associated with rapid improvement in residual motor and non-motor fluctuations during CSFLI therapy. In the first patient, freezing episodes and unpredictable akinesia resolved. In the second patient, the reintroduction of opicapone improved morning slowness, axial symptoms, and dorsal pain. Wearable sensor analysis showed increased walking distance during the 6-minute walk test, higher walking speed, reduced Timed Up and Go duration, increased step length, and reduced step length variability. Conclusions: These preliminary observations suggest that opicapone may deserve further investigation as a potential adjunctive strategy in selected patients receiving CSFLI who continue to experience residual fluctuations despite optimized infusion therapy. Wearable sensor monitoring may provide objective support for treatment assessment in this setting. Full article

(This article belongs to the Special Issue New Approaches in the Exploration of Parkinson’s Disease: 2nd Edition)

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13 pages, 4923 KB

Open AccessArticle

The Psychological and Behavioural Correlates of Workplace Victimization

by Amelia Rizzo, Maria Grazia Maggio, Martina Barbera, Francesca Bruno, Gabriele Giorgi, Luca Di Giampaolo, Murat Yildirim, Lucasz Szarpak, Giuseppe Ferrari, Raffaela Maione, Rocco Salvatore Calabrò and Francesco Chirico

Brain Sci. 2026, 16(5), 544; https://doi.org/10.3390/brainsci16050544 - 21 May 2026

Abstract

Background: Workplace victimization is a form of repeated and systematic psychological violence that can severely affect both mental and physical health. From a psychological perspective, it impacts mood states, defense mechanisms, and personality functioning. Methods: This cross-sectional study investigated the psychological [...] Read more.

Background: Workplace victimization is a form of repeated and systematic psychological violence that can severely affect both mental and physical health. From a psychological perspective, it impacts mood states, defense mechanisms, and personality functioning. Methods: This cross-sectional study investigated the psychological and behavioural correlates of workplace victimization in a sample of 33 workers from various professional sectors, using a multidimensional assessment including standardized measures of personality traits, mood states, and defense mechanisms. Results: The MMPI-2 profile revealed elevated scores in Hypochondriasis (Hs: 72.00), Depression (D: 70.21), Hysteria (Hy: 67.61), and Paranoia (Pa: 68.76), indicating somatic symptoms, depressive features, and suspiciousness. The POMS showed increased Tension–Anxiety (T: 65.06), Depression–Dejection (D: 68.21), Anger–Hostility (A: 68.15), and Fatigue–Inertia (F: 65.24), alongside reduced Vigor–Activity (V: 43.18). The DMI analysis highlighted a high Reversal score (REV: 65.91), suggesting a predominant use of defense mechanisms such as altruism and idealization to cope with distress. Conclusions: In this selected sample of adults referred for psychological evaluation for suspected or documented workplace victimization, participants showed a clinically relevant psychological burden, including depressive symptoms, somatic concerns, Anger–Hostility, fatigue, reduced vigor, and specific defensive patterns. Given the cross-sectional design, small sample size, and absence of a control group, these findings should be interpreted as preliminary and cannot establish causality or the specificity of this profile to workplace victimization. Full article

(This article belongs to the Special Issue Social and Emotional Processes in Interpersonal Contexts)

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4 pages, 166 KB

Open AccessEditorial

New Advances in the Development of New Drugs and Treatment Targets for Brain Cancers (2nd Edition)

by Luis Exequiel Ibarra, Laura Natalia Milla Sanabria and Nuria Arias-Ramos

Brain Sci. 2026, 16(5), 543; https://doi.org/10.3390/brainsci16050543 - 21 May 2026

Abstract

Primary tumors of the central nervous system (CNS) represent a major clinical challenge worldwide due to their high morbidity, aggressive biological behavior, and limited therapeutic options [...] Full article

(This article belongs to the Special Issue New Advances in the Development of New Drugs and Treatment Targets for Brain Cancers (2nd Edition))

11 pages, 959 KB

Open AccessReview

Modulation of the PI3K/AKT/mTOR and AMPK/TSC2/mTOR Pathways by N-Acetyl-L-Cysteine as a Protector of Embryonic Bodies from the Toxic Effect of Methylmercury

by Júlia Leão Batista Simões, Geórgia de Carvalho Braga, Charles Elias Assmann and Margarete Dulce Bagatini

Brain Sci. 2026, 16(5), 542; https://doi.org/10.3390/brainsci16050542 - 21 May 2026

Abstract

Methylmercury (MeHg) is a potent environmental contaminant primarily ingested through seafood consumption. Gestational exposure induces profound neurological and developmental deficits in the fetus that often persist throughout childhood. This developmental vulnerability arises from the immature state of the blood–brain barrier and a limited [...] Read more.

Methylmercury (MeHg) is a potent environmental contaminant primarily ingested through seafood consumption. Gestational exposure induces profound neurological and developmental deficits in the fetus that often persist throughout childhood. This developmental vulnerability arises from the immature state of the blood–brain barrier and a limited endogenous antioxidant capacity in the developing CNS. Postnatal exposure via breastfeeding further compromises neurodevelopment, specifically impairing visuospatial processing and memory. While fetal and placental mercury accumulation correlates with gestational age, the specific mechanisms of transplacental transport remain poorly defined. Mechanistically, MeHg predominantly accumulates in fetal renal tissue, followed by the brain and liver. This review aims to elucidate MeHg-induced oxidative stress and autophagic collapse mediated by the PI3K/AKT/mTOR and AMPK/TSC2/mTOR pathways. Furthermore, we evaluate neuroprotective candidates, specifically N-acetyl-L-cysteine (NAC) and CCL chemokine modulation, as strategies to mitigate fetal impairment and the associated cellular damage. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms Regulating Neuronal Function, Homeostasis, and Disease (2nd Edition))

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38 pages, 6120 KB

Open AccessArticle

Paper to Pixels: Enhancing Unilateral Neglect Assessment Using the New Computer Vision-Based Tool CANDO

by Lisa Beckmann, Rylan Donohoe, Doris Schmid, Ines C. Kiphuth, Karin Ludwig and Thomas Schenk

Brain Sci. 2026, 16(5), 541; https://doi.org/10.3390/brainsci16050541 - 21 May 2026

Abstract

Background/Objectives: The main aim of this article is to introduce a novel tool that allows the automatic scoring of many of the subtests from the conventional subpart of the Behavioural Inattention Test (BIT) and its German adaptation, the Neglect Test (NET). BIT [...] Read more.

Background/Objectives: The main aim of this article is to introduce a novel tool that allows the automatic scoring of many of the subtests from the conventional subpart of the Behavioural Inattention Test (BIT) and its German adaptation, the Neglect Test (NET). BIT and NET are standard test batteries used in the diagnosis of neglect. Our article has two parts. First, we examine the shortcomings of manual scoring, and secondly, we introduce our computer vision tool and evaluate its diagnostic validity and efficacy. Methods: In Part 1, diagnostic consistency was examined across raters with varying expertise using selected BIT and NET tasks, with repeated assessments conducted under controlled evaluation conditions. In Part 2, a computer vision-based tool (CANDO) was developed to automate scoring using a deterministic computer vision pipeline designed to reproducibly apply scoring criteria across tasks. The performance of CANDO was compared with ground truth across cancellation, line bisection, and copying tasks. Results: Manual scoring showed high overall agreement between and within raters under ideal conditions. However, diagnostic classification still differed across raters and repeated assessments. These inconsistencies were primarily driven by drawing and copying tasks. CANDO achieved very high accuracy for cancellation and line bisection tasks and strong agreement for copying tasks, while reducing variability associated with subjective judgment, time pressure, and oversight. The remaining discrepancies between computer vision and human raters had limited impact on diagnostic outcomes. Conclusions: Manual assessment of unilateral neglect is vulnerable to inconsistencies arising from subjective evaluation and the structural limitations of scoring systems. Computer vision-based automation can reduce diagnostic variability, improve reproducibility, and increase assessment efficiency, while preserving clinically relevant information. The presented framework provides a practical tool to support higher-quality neglect assessment. Full article

(This article belongs to the Special Issue Advanced Study in Stroke and Stroke Rehabilitation)

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20 pages, 5511 KB

Open AccessArticle

Neural and Kinematic Characteristics of Reaching in Autistic Children During Movement Observation, Execution, and Synchronization: An fNIRS Study

by Wan-Chun Su, Daisuke Tsuzuki and Anjana Bhat

Brain Sci. 2026, 16(5), 540; https://doi.org/10.3390/brainsci16050540 - 20 May 2026

Abstract

Background/Objectives: Children with Autism Spectrum Disorder (ASD, here on termed autistic children) exhibit motor difficulties in social and non-social contexts. Although previous studies have reported behavioral and neural characteristics, their relationship remains largely unexplored. The current study aimed to investigate the behavioral and [...] Read more.

Background/Objectives: Children with Autism Spectrum Disorder (ASD, here on termed autistic children) exhibit motor difficulties in social and non-social contexts. Although previous studies have reported behavioral and neural characteristics, their relationship remains largely unexplored. The current study aimed to investigate the behavioral and neural mechanisms underlying interpersonal synchrony in autistic children using simultaneous kinematic and Functional Near-Infrared Spectroscopy (fNIRS) recordings. Methods: Fifty-eight autistic or non-autistic children participated (mean age = 10.1, standard error = 0.3). fNIRS and an inertial measurement unit were used simultaneously to record the neural activity over frontotemporal and parietal regions and arm movement kinematics during a reach-to-clean-up task across three conditions: Watch—the child observed the tester clean up the blocks; Do—the child cleaned up the blocks independently; and Together—the child and tester cleaned up the blocks synchronously. Results: Behaviorally, autistic children demonstrated longer movement displacement, higher average velocity and acceleration, and a greater number of movement units. In terms of cortical activation, autistic children showed hypoactivation in the bilateral precentral gyrus and right inferior parietal lobe, along with hyperactivation in the right middle frontal gyrus, left inferior frontal gyrus, and left inferior parietal lobule. Correlations between kinematic and neural measures suggest that autistic children rely more on online/feedback control to compensate for reduced feedforward control. Conclusions: This study reveals unique compensatory strategies in autistic children, highlighting the connections between neural and behavioral characteristics. These findings have strong potential to inform the development of ASD screening tools and to guide targeted intervention strategies. Full article

(This article belongs to the Section Developmental Neuroscience)

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13 pages, 1478 KB

Open AccessReview

Sympathetic Activation and Sleep-Related Movements: Integrating Autonomic, Dopaminergic, and Iron Deficiency Mechanisms

by Gulcin Benbir Senel and Lourdes M. DelRosso

Brain Sci. 2026, 16(5), 539; https://doi.org/10.3390/brainsci16050539 - 20 May 2026

Abstract

Objective: Recent research has expanded the understanding of the potential role of sympathetic nervous system activation in the implications of sleep-related movement disorders, particularly in the mechanisms of dopaminergic dysfunction and iron deficiency. This multifactorial perspective aims to provide insights into disease mechanisms [...] Read more.

Objective: Recent research has expanded the understanding of the potential role of sympathetic nervous system activation in the implications of sleep-related movement disorders, particularly in the mechanisms of dopaminergic dysfunction and iron deficiency. This multifactorial perspective aims to provide insights into disease mechanisms and opportunities for targeted interventions that address both neurological and autonomic contributors to sleep-related movements. Methods: To synthesize the current evidence on the role of sympathetic activation in sleep-related movement disorders, we conducted a review of the literature to identify studies exploring the intersection of autonomic nervous system activity and motor phenomena during sleep. Results: Studies indicate that sympathetic activation may contribute directly to the initiation and propagation of motor events during sleep. Evidence from electrophysiological studies and heart rate variability analyses in patients with sleep-related movement disorders shows that sympathetic bursts often precede or coincide with leg movements and arousals, suggesting a causal rather than reactive role. Moreover, iron deficiency appears to exacerbate both dopaminergic and autonomic dysfunction, providing a unifying mechanism that bridges these pathways. Conclusions: These findings support a shift from viewing sympathetic activity as a secondary response to arousal to recognizing it as a possible primary trigger of sleep-related motor events. Full article

(This article belongs to the Section Sleep and Circadian Neuroscience)

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17 pages, 12081 KB

Open AccessReview

Surgical Management of Traumatic Brain Injury Based on Intracranial Compliance: Toward Personalized Decision-Making

by Santiago Cardona-Collazos, Laura M. Loaiza-Cardona, Andres Salazar-Restrepo, Luigi Valentino Berra and Andres M. Rubiano

Brain Sci. 2026, 16(5), 538; https://doi.org/10.3390/brainsci16050538 - 20 May 2026

Abstract

Traditional surgical decision-making in traumatic brain injury (TBI) has relied on static intracranial pressure (ICP) thresholds and fixed volumetric criteria, an approach that inadequately reflects the dynamic physiological nature of secondary brain injury. These conventional metrics fail to capture the critical determinant of [...] Read more.

Traditional surgical decision-making in traumatic brain injury (TBI) has relied on static intracranial pressure (ICP) thresholds and fixed volumetric criteria, an approach that inadequately reflects the dynamic physiological nature of secondary brain injury. These conventional metrics fail to capture the critical determinant of clinical deterioration: the progressive loss of intracranial compliance, the brain’s capacity to buffer additional volume without harmful pressure escalation. This manuscript proposes a practical, compliance-based framework for selecting precise, personalized surgical strategies using real-time physiological, imaging, and neuromonitoring indicators. Based on the Intracranial Compartment Syndrome (ICCS) model, this approach translates the loss of compensatory reserve into actionable operative decisions. Compliance is assessed through multimodal tools, including ICP waveform morphology, cerebral oxygenation, and complementary noninvasive neuromonitoring. ICCS staging delineates three operative contexts: Stage 1, preserved compliance; Stage 2, compliance failure with maintained oxygenation requiring physiology-guided interventions to restore buffering capacity; and Stage 3, global decompensation with lost of compliance plus oxygenation failure requiring immediate, aggressive intervention for partial or total brain tissue survival. By shifting surgical reasoning from fixed anatomical thresholds to a physiology-centered assessment of intracranial compliance, this framework aims to enhance the timing, selection, and overall effectiveness of neurosurgical interventions in TBI. Full article

(This article belongs to the Section Systems Neuroscience)

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15 pages, 335 KB

Open AccessArticle

Investigating Treatment Response in Obsessive–Compulsive Disorder Through Neuromodulation and Patient-Derived Induced Pluripotent Stem Cell Models: Preliminary Clinical Observations from a Translational Study

by Beatrice Benatti, Matteo Marcatili, Rodolfo Leuzzi, Massimo Clerici, Luciano Conti, Massimo Gennarelli, Carlo Sala, Federico Bernoni d’Aversa, Valentina Casati, Michele Castiglioni, Camilla Gesi, Nicolaja Girone, Luca Larini, Alessandra Minelli, Emma Rinaldi, Matteo Vismara and Bernardo Dell’Osso

Brain Sci. 2026, 16(5), 537; https://doi.org/10.3390/brainsci16050537 - 19 May 2026

Abstract

Background: Treatment-resistant obsessive–compulsive disorder (OCD) is a heterogeneous and clinically challenging condition. Growing evidence suggests alterations in glutamatergic signaling within cortico–striatal–thalamo–cortical circuits, including those involving medium spiny neurons (MSNs), as well as genetic factors affecting synaptic organization, although the biological mechanisms underlying differential [...] Read more.

Background: Treatment-resistant obsessive–compulsive disorder (OCD) is a heterogeneous and clinically challenging condition. Growing evidence suggests alterations in glutamatergic signaling within cortico–striatal–thalamo–cortical circuits, including those involving medium spiny neurons (MSNs), as well as genetic factors affecting synaptic organization, although the biological mechanisms underlying differential treatment response remain incompletely understood. Methods: This multicenter study presents a translational research framework aimed at investigating potential molecular and cellular correlates of treatment response in a cohort of patients with OCD, stratified according to their response to pharmacological treatments and transcranial magnetic stimulation (TMS). Peripheral blood mononuclear cells from clinically defined subgroups are reprogrammed into human induced pluripotent stem cells and differentiated into MSN-enriched neuronal cultures, enabling in vitro investigation of morphological, biochemical, and transcriptomic features associated with different clinical profiles. Optogenetic and pharmacological stimulation paradigms are applied to probe selected aspects of neuronal activation in vitro, providing a controlled and simplified experimental framework to explore cellular responses under different treatment conditions. By integrating clinical phenotyping with patient-derived cellular models, this study establishes a translational platform for hypothesis generation in the investigation of treatment response in OCD. Results and Conclusions: Preliminary clinical observations from an initial cohort undergoing neuromodulation are also reported to document feasibility and early clinical implementation of the study, providing an initial characterization of the cohort. Full article

(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd Edition)

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16 pages, 1578 KB

Open AccessArticle

Sleep Quality Profiles in Youth with Eating Disorders: A Latent Profile Analysis

by Elvira Anna Carbone, Matteo Aloi, Renato de Filippis, Marianna Rania, Alessia Scordo, Claudia Procopio, Lavinia Rotella, Daria Quirino, Ettore D’Onofrio, Pasquale De Fazio and Cristina Segura-Garcia

Brain Sci. 2026, 16(5), 536; https://doi.org/10.3390/brainsci16050536 - 19 May 2026

Abstract

Background/Objectives: Sleep disturbances are highly prevalent in young individuals with eating disorders (EDs) and are associated with increased psychopathology and poorer clinical outcomes. However, sleep alterations in ED populations are heterogeneous and may reflect distinct underlying clinical profiles. The study aimed to identify [...] Read more.

Background/Objectives: Sleep disturbances are highly prevalent in young individuals with eating disorders (EDs) and are associated with increased psychopathology and poorer clinical outcomes. However, sleep alterations in ED populations are heterogeneous and may reflect distinct underlying clinical profiles. The study aimed to identify sleep quality profiles and examine their clinical correlates in youth with EDs. Methods: A total of 288 youth outpatients with EDs completed the Pittsburgh Sleep Quality Index (PSQI), along with measures of eating and general psychopathology. Latent Profile Analysis (LPA) was conducted using PSQI scores to identify distinct sleep profiles. Multinomial logistic regression models were performed to assess clinical variables of profile membership. Results: A four-profile solution was identified: (1) less impaired sleepers, (2) medication-using sleepers, (3) global poor sleepers, and (4) sleep-initiation-difficulty sleepers. Profiles differed significantly in ED severity, affective symptoms, emotion regulation difficulties, and sleep-related eating behaviors. Profiles characterized by greater sleep impairment exhibited higher levels of binge eating, night eating, and psychological distress. Multinomial logistic regression analyses indicated that night eating was the largest contributor to latent profile membership across all comparisons, significantly increasing the likelihood of belonging to more impaired sleep profiles. Conclusions: Sleep in individuals with EDs is characterized by distinct and clinically meaningful profiles rather than a uniform pattern of impairment. These findings support the clinical utility of person-centered approaches to better characterize sleep disturbances in ED populations. Full article

(This article belongs to the Special Issue Emerging Trends in Youth Mental Health)

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19 pages, 702 KB

Open AccessArticle

Linking Auditory Brainstem Neural Stability to Parent-Reported Autistic Traits in School-Age Children

by Devon Pacheco Major, Emily Cary, Erin Matsuba, Natalie Russo and Beth Prieve

Brain Sci. 2026, 16(5), 535; https://doi.org/10.3390/brainsci16050535 - 19 May 2026

Abstract

Background: Neural stability, defined as trial-by-trial fluctuations in neural responses to the repetitive sensory input, is an indicator of neural processing stability. The auditory brainstem response (ABR) can provide an electrophysiological measure of neural stability. Findings on neural stability differences between autistic and [...] Read more.

Background: Neural stability, defined as trial-by-trial fluctuations in neural responses to the repetitive sensory input, is an indicator of neural processing stability. The auditory brainstem response (ABR) can provide an electrophysiological measure of neural stability. Findings on neural stability differences between autistic and neurotypical individuals are inconsistent, potentially due to methodological differences and sample heterogeneity. This study aimed to investigate the relationship between neural stability in the brainstem and autistic traits in a group of children with and without a diagnosis of autism. We examined whether the degree of neural stability differs based on the evoking stimulus and response component analyzed, and whether neural stability relates to parent-reported autistic traits, as measured by the Autism Spectrum Quotient (AQ) and social responsiveness scale-2 (SRS-2). Methods: In total, 41 participants had usable click ABRs and 34 had usable sABRs. Neural stability was quantified using Pearson correlation analyses between binaurally evoked subaverage ABR waveforms. Parent-reported measures of autistic traits were collected. Results: Neural stability differed across ABR components, with the click ABR being significantly more stable than sABR components. Decreased neural stability is significantly related to autistic traits measured by the AQ but not the SRS-2. There was no significant response component by AQ interaction. Conclusions: Neural stability in the auditory brainstem pathway is linked to individual differences in autistic traits measured by the AQ but not the SRS, implying that early sensory processing neural stability may be related to broader features of autistic traits rather than social communication alone. Full article

(This article belongs to the Special Issue Rethinking Neurodevelopmental Disorders: Beyond One-Size-Fits-All)

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