Brain Sciences

15 pages, 1475 KiB

Open AccessArticle

A New Multi-Parametric MRI-Based Scoring System for Degenerative Cervical Myelopathy: The Severity on Imaging Myelopathy Score (SIMS)

by Alexis Morgado, Julien Berthiller, Fabien Subtil, Donato Creatura, Gildas Patet, Nathalie André-Obadia and Cédric Yves Barrey

Brain Sci. 2025, 15(6), 557; https://doi.org/10.3390/brainsci15060557 (registering DOI) - 23 May 2025

Abstract

Background/Objectives: Degenerative cervical myelopathy (DCM) is the leading cause of functional disabilities of spinal origin in people over 50 years old. The objective of the present study was to establish a multi-parametric weighted scoring system that is easy to use in daily [...] Read more.

Background/Objectives: Degenerative cervical myelopathy (DCM) is the leading cause of functional disabilities of spinal origin in people over 50 years old. The objective of the present study was to establish a multi-parametric weighted scoring system that is easy to use in daily practice, based on the most significant MRI signs and correlated as strongly as possible with the clinical presentation (mJOA)—we call this system the SIMS or Severity on Imaging Myelopathy Score. Methods: Ninety-nine patients who underwent clinical and radiological evaluation by mJOA and MRI between January 2015 and March 2021 were retrospectively included. The variables included in the score were the Fujiwara ratio, the T2-weighted intramedullary hyperintensity, the aspect of the peri-medullary fluid cisterns, the Torg–Pavlov ratio, the local kyphosis and the number of stenotic levels. Each variable was first correlated to the mJOA score for each patient, making it possible to construct the final SIMS at the end, and validate it by comparison with mJOA scores. Results: The variables that were significantly correlated with one another were the T2-weighted intramedullary hyperintensity, the reduction in peri-medullary fluid spaces and the number of stenotic levels (p < 0.05). Then, points were assigned to each variable according to their relative importance and made it possible to construct the definitive SIMS. The final Spearman correlation coefficient between the SIMS and the mJOA score was −0.747. Conclusions: This work showed that this new multi-parametric MRI-based scoring system represents a consistent means to characterize the degree of severity of degenerative cervical myelopathy. Full article

(This article belongs to the Section Neurosurgery and Neuroanatomy)

19 pages, 834 KiB

Open AccessArticle

Association of Health Disparities with Glioblastoma Treatment and Outcomes: Insights from a 15-Year National Cohort (2005–2020)

by Zouina Sarfraz, Diya Jayram, Ahmad Ozair, Lydia Hodgson, Shreyas Bellur, Arun Maharaj, Alireza Mansouri and Manmeet S. Ahluwalia

Brain Sci. 2025, 15(6), 556; https://doi.org/10.3390/brainsci15060556 - 23 May 2025

Abstract

Background: Despite advances in glioblastoma (GBM) management, median overall survival (mOS) remains poor, and multi-modal disparities persist. We sought to evaluate trends in GBM treatment and survival outcomes from 2005–2020, with a focus on sociodemographic and geographic disparities. Methods: We conducted a retrospective [...] Read more.

Background: Despite advances in glioblastoma (GBM) management, median overall survival (mOS) remains poor, and multi-modal disparities persist. We sought to evaluate trends in GBM treatment and survival outcomes from 2005–2020, with a focus on sociodemographic and geographic disparities. Methods: We conducted a retrospective US-based cohort study using the National Cancer Database (NCDB), stratifying study period into four intervals (2005–2008, 2009–2012, 2013–2016, and 2017–2020). Logistic regression was used to identified predictors of receipt of combination surgery, radiation, and chemotherapy (Sx+RT+Chemo). Kaplan–Meier and multivariable Cox proportional hazards approaches were used to assess mOS. Results: A total of 111,955 adults with GBM were included. From 2005–2008 to 2017–2020, mOS increased from 7.8 to 9.5 months, with geographically unequal gains in survival across the US. In multivariable logistic regression model adjusting for known confounders, combined Sx+RT+Chemo was less likely to be received by female patients (OR 0.90, 95%CI 0.88–0.92) vs. male, non-White patients (OR 0.90, 95%CI 0.86–0.94) vs. White, patients treated at community hospitals (OR: 0.78, 95%CI 0.76–0.80) vs. academic centers, publicly-insured patients (OR 0.74, 95%CI 0.71–0.76) or uninsured patients (OR 0.54, 95%CI 0.50–0.58) vs. privately-insured, and patients living in the South (OR 0.88, 95%CI 0.85–0.91), Midwest (OR 0.83, 95% CI 0.80–0.86), and West (OR 0.85, 95%CI 0.81–0.88) compared to the Northeast. In multivariable Cox regression, significantly poorer survival was seen amongst non-metropolitan patients, community-based hospital patients, and publicly-insured and uninsured patients (vs. privately-insured), despite adjusting for prognostic factors. Conclusions: Only modest improvement in mOS of GBM patients has occurred across 2005–2020, with persistent disparities linked to sociodemographic and structural factors, whose redressal warrants multi-pronged efforts. Full article

(This article belongs to the Special Issue Editorial Board Collection Series: Advances in Neuro-Oncology)

17 pages, 1263 KiB

Open AccessArticle

Is CT Still the Gold Standard in Semicircular Canal Dehiscence? Diagnostic Value of MRI in Poschl and Stenver Planes

by Cagatay Bolgen and Birsen Unal Daphan

Brain Sci. 2025, 15(6), 555; https://doi.org/10.3390/brainsci15060555 - 23 May 2025

Abstract

Background/Objectives: The primary aim of this study was to investigate whether magnetic resonance imaging (MRI) of the superior and posterior semicircular canals (SCs) in cases with and without dehiscence gives results similar to those of CT. As a novel contribution, the secondary aim [...] Read more.

Background/Objectives: The primary aim of this study was to investigate whether magnetic resonance imaging (MRI) of the superior and posterior semicircular canals (SCs) in cases with and without dehiscence gives results similar to those of CT. As a novel contribution, the secondary aim was to assess the diagnostic correlation between CT and MRI sequences obtained primarily in Poschl and Stenver planes, instead of reformatted images, for detecting superior and posterior semicircular canal dehiscence. Methods: A total of 103 patients were retrospectively evaluated based on CT scans, and 27 of them, with the appearance or suspicion of at least one SCD and/or thinner-than-normal canal roof bone, were prospectively examined with MRI. Results: With CT as a reference, MRI had a 78% detection rate and 92% specificity for the detection of dehiscence in the superior SCs. For posterior SCs, the dehiscence detection rate and specificity of MRI were 70% and 97%, respectively. CT and MRI examinations showed a significant agreement in the diagnosis of SCD (κ = 0.71, p < 0.001 for superior SCD; κ = 0.73, p < 0.001 for posterior SCD). The agreement values of MRIs obtained in Poschl and Stenver planes with CT in the detection of dehiscence were calculated as κ = 0.43 in Poschl and κ = 0.51 in Stenver for superior SCD; κ = 0.45 in Poschl and κ = 0.46 in Stenver for posterior SCD. Conclusions: The MRI results demonstrated similar diagnostic precision to CT when identifying SCD. In patients presenting with vertigo, nystagmus, and hearing loss, normal MRI findings may be sufficient to exclude semicircular canal dehiscence (SCD), thereby potentially obviating the need for additional CT imaging. The newly introduced Poschl and Stenver plane MRI sequences demonstrate a moderate relationship with CT for SCD diagnosis. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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12 pages, 824 KiB

Open AccessArticle

Evaluating Repetitive Transcranial Magnetic Stimulation for Refractory Chronic Cluster Headache Prevention: Insights from a Randomized Crossover Pilot Trial

by Leonardo Portocarrero-Sánchez, Cristian Rizea, Exuperio Díez-Tejedor, Moisés León-Ruiz and Javier Díaz-de-Terán

Brain Sci. 2025, 15(6), 554; https://doi.org/10.3390/brainsci15060554 - 23 May 2025

Abstract

Background/Objectives: Cluster headache (CH) is a debilitating primary headache disorder characterized by severe unilateral pain attacks. Chronic CH (CCH) poses significant treatment challenges, especially in refractory cases. Neuromodulation, including repetitive transcranial magnetic stimulation (rTMS), offers a potential alternative; however, evidence for its [...] Read more.

Background/Objectives: Cluster headache (CH) is a debilitating primary headache disorder characterized by severe unilateral pain attacks. Chronic CH (CCH) poses significant treatment challenges, especially in refractory cases. Neuromodulation, including repetitive transcranial magnetic stimulation (rTMS), offers a potential alternative; however, evidence for its efficacy in CCH is lacking. Methods: A randomized, double-blind, placebo-controlled, crossover pilot study was conducted. Eligibility criteria included patients with refractory CCH (rCCH), who were then randomized to receive two treatment sequences: A, rTMS followed by sham stimulation, or B, sham followed by rTMS, separated by a one-month washout, with a follow-up period of 3 months. The primary endpoint was to analyze efficacy by assessing the change in the number of attacks per week (APW). Secondary endpoints included treatment tolerability and changes in intensity, duration, and use of rescue medication. The trial was registered with ClinicalTrials.gov (NCT06917144). Results: Eight patients were enrolled and randomized with a 50% probability of assignment to either treatment arm. Despite this, five patients were allocated to sequence A and three to sequence B. Three patients completed the entire study; five received treatment with rTMS and six with sham. The APW change during rTMS showed a change of (mean ± SD) +2.2 (10.8) attacks per week (p = 0.672). Two patients achieved complete remission during the rTMS phase, though symptoms returned by the washout period. In comparison with sham, the difference was also not statistically significant. No significant changes were observed in secondary endpoints. Side effects (two cases) were mild and transient. Conclusions: This pilot study suggests that rTMS may provide clinical benefits for rCCH in selected cases, though its effects seem transient. Adherence to treatment remains a critical challenge. Full article

(This article belongs to the Special Issue Neuromodulation for Pain Management: Evidence of Safety and Efficacy)

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4 pages, 151 KiB

Open AccessEditorial

Advances in Tinnitus and Hearing Disorders

by Alessandra Fioretti

Brain Sci. 2025, 15(6), 553; https://doi.org/10.3390/brainsci15060553 - 23 May 2025

Abstract

Tinnitus is generally defined as the perception of sound in the absence of a corresponding external acoustic stimulus [...] Full article

(This article belongs to the Special Issue Advances in Tinnitus and Hearing Disorders)

16 pages, 585 KiB

Open AccessArticle

Psychopathological Implications of Behavioral Patterns in Obsessive–Compulsive Rituals: A Hierarchical Analysis

by Luca Gambolò, Anna Di Donna, Rebecca Ottoni, Stefano Parmigiani, Carlo Marchesi and Matteo Tonna

Brain Sci. 2025, 15(6), 552; https://doi.org/10.3390/brainsci15060552 - 23 May 2025

Abstract

Background/Objectives: Compulsive rituals in Obsessive–Compulsive Disorder (OCD) are characterized by a specific motor structure, built upon the fragmentation of action flow, obtained through act repetitions and the intrusion of non-functional acts. No study to date has adopted a hierarchical analysis to subtype [...] Read more.

Background/Objectives: Compulsive rituals in Obsessive–Compulsive Disorder (OCD) are characterized by a specific motor structure, built upon the fragmentation of action flow, obtained through act repetitions and the intrusion of non-functional acts. No study to date has adopted a hierarchical analysis to subtype OCD according to specific behavioral patterns, nor has a possible association between motor profiles and psychopathology been investigated. Methods: This study involved 31 OCD patients (11 female, 35%) and 31 healthy controls (11 female, 35%). The participants were asked to provide videotapes of their behaviors (OCD compulsions for patients and corresponding normal behaviors for healthy controls). BORIS software version 2.84.1 was adopted to analyze the recorded videos. Psychopathology was assessed through the Yale–Brown Obsessive–Compulsive Scale, the Childhood Trauma Questionnaire, the Frankfurt Complaint Questionnaire, and the Social and Occupational Functioning Assessment Scale. Results: Hierarchical analysis revealed three behavioral clusters based on motor profile: Cluster 1 included OCD compulsions structurally characterized by act repetitions (“iterative” rituals); Cluster 2 was represented by OCD compulsions mainly built upon non-functional acts (“idiosyncratic” rituals); and Cluster 3 comprised routinized and normative behaviors, without behavioral ritualization (no act repetitions and few non-functional acts). No significant differences were found in age, age at onset, and OCD severity between “iterative” and “idiosyncratic” rituals. However, patients with “iterative” rituals showed both more severe pre-psychotic symptoms and childhood trauma experiences than patients with “idiosyncratic” rituals. Conclusions: These findings may have significant clinical implications as they hint at a relationship between specific behavioral patterns of OCD compulsions and different underlying psychopathologies and/or vulnerabilities. Full article

(This article belongs to the Section Neuropsychiatry)

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21 pages, 1391 KiB

Open AccessArticle

The Key Role of Personality Functioning in Understanding the Link Between Adverse Childhood Experiences and Loneliness: A Cross-Sectional Mediation Analysis

by Jeff Maerz, Roberto Viviani and Karin Labek

Brain Sci. 2025, 15(6), 551; https://doi.org/10.3390/brainsci15060551 - 23 May 2025

Abstract

Background and Aims: Loneliness represents a critical public health concern, significantly affecting mental and physical health. Adverse childhood experiences (ACEs) have been recognized as predictors of loneliness, yet the underlying mechanisms remain unclear. The level of personality functioning, determined by self- and interpersonal [...] Read more.

Background and Aims: Loneliness represents a critical public health concern, significantly affecting mental and physical health. Adverse childhood experiences (ACEs) have been recognized as predictors of loneliness, yet the underlying mechanisms remain unclear. The level of personality functioning, determined by self- and interpersonal impairments, has been proposed as a potential mediator but has not been empirically explored in this context. This study examined whether personality functioning mediates the relationship between cumulative and specific types of ACEs and loneliness using a cross-sectional design. Methods: An online survey of 334 participants (mean age = 25.96; 65% female) were assessed for ACEs using a modified version of the KERF-40-I scale, their personality functioning using the Level of Personality Functioning Scale (LPFS-BF), and loneliness using the revised UCLA Loneliness Scale. Results: Higher ACE exposure was significantly associated with loneliness and greater impairments in overall personality functioning and self-functioning. After controlling for other ACE subtypes, emotional neglect remained associated with the overall level of personality functioning, while emotional neglect and sexual violence were associated with self-functioning impairments. Mediation analyses indicated that the overall level of personality functioning was consistent with a full mediation model of the ACE–loneliness association, accounting for 64% of the total effect. When examining self-functioning separately, an indirect effect accounted for 78% of the total association. In models testing specific ACE types, self-functioning fully mediated the associations between emotional neglect, sexual violence, and loneliness. Conclusions: The findings highlight self-functioning impairments as a key mechanism linking both cumulative and specific ACEs and loneliness, suggesting a need for a targeted focus on self-related impairments. Longitudinal studies are needed to clarify the developmental trajectories. Full article

(This article belongs to the Special Issue State of the Art in Human Attachment)

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18 pages, 3090 KiB

Open AccessArticle

Microelectrode Implantation in Human Insula: Technical Challenges and Recording Insights

by Daphné Citherlet, Sami Heymann, Maya Aderka, Katarzyna Jurewicz, B. Suresh Krishna, Manon Robert, Alain Bouthillier, Olivier Boucher and Dang Khoa Nguyen

Brain Sci. 2025, 15(6), 550; https://doi.org/10.3390/brainsci15060550 - 23 May 2025

Abstract

Background/Objectives: Intracranial macroelectrode implantation is a pivotal clinical tool in the evaluation of drug-resistant epilepsy, allowing further insights into the localization of the epileptogenic zone and the delineation of eloquent cortical regions through cortical stimulation. Additionally, it provides an avenue to study [...] Read more.

Background/Objectives: Intracranial macroelectrode implantation is a pivotal clinical tool in the evaluation of drug-resistant epilepsy, allowing further insights into the localization of the epileptogenic zone and the delineation of eloquent cortical regions through cortical stimulation. Additionally, it provides an avenue to study brain functions by analyzing cerebral responses during neuropsychological paradigms. By combining macroelectrodes with microelectrodes, which allow recording the activity of individual neurons or smaller neural clusters, recordings could provide deeper insights into neuronal microcircuits and the brain’s transitions in epilepsy and contribute to a better understanding of neuropsychological functions. In this study, one or two hybrid macro-micro electrodes were implanted in the anterior-inferior insular region in patients with refractory epilepsy. We report our experience and share some preliminary results; we also provide some recommendations regarding the implantation procedure for hybrid electrodes in the insular cortex. Methods: Stereoelectroencephalography was performed in 13 patients, with one or two hybrid macro-microelectrodes positioned in the insular region in each patient. Research neuropsychological paradigms could not be implemented in two patients for clinical reasons. In total, 23 hybrid macro-microelectrodes with eight microcontacts each were implanted, of which 20 were recorded. Spiking activity was detected and assessed using WaveClus3. Results: No spiking neural activity was detected in the microcontacts of the first seven patients. After iterative refinement during this process, successful recordings were obtained from 13 microcontacts in the anterior-inferior insula in the last four patients (13/64, 20.3%). Hybrid electrode implantation was uneventful with no complications. Obstacles included the absence of spiking activity signals, unsuccessful microwire dispersion, and the interference of environmental electrical noise in recordings. Conclusions: Human microelectrode recording presents a complex array of challenges; however, it holds the potential to facilitate a more comprehensive understanding of individual neuronal attributes and their specific stimulus responses. Full article

(This article belongs to the Special Issue Understanding the Role and Functions of the Insula in the Brain)

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17 pages, 1921 KiB

Open AccessArticle

Streamlining cVEP Paradigms: Effects of a Minimized Electrode Montage on Brain–Computer Interface Performance

by Milán András Fodor, Atilla Cantürk, Gernot Heisenberg and Ivan Volosyak

Brain Sci. 2025, 15(6), 549; https://doi.org/10.3390/brainsci15060549 - 23 May 2025

Abstract

(1) Background: Brain–computer interfaces (BCIs) enable direct communication between the brain and external devices using electroencephalography (EEG) signals, offering potential applications in assistive technology and neurorehabilitation. Code-modulated visual evoked potential (cVEP)-based BCIs employ code-pattern-based stimulation to evoke neural responses, which can then be [...] Read more.

(1) Background: Brain–computer interfaces (BCIs) enable direct communication between the brain and external devices using electroencephalography (EEG) signals, offering potential applications in assistive technology and neurorehabilitation. Code-modulated visual evoked potential (cVEP)-based BCIs employ code-pattern-based stimulation to evoke neural responses, which can then be classified to infer user intent. While increasing the number of EEG electrodes across the visual cortex enhances classification accuracy, it simultaneously reduces user comfort and increases setup complexity, duration, and hardware costs. (2) Methods: This online BCI study, involving thirty-eight able-bodied participants, investigated how reducing the electrode count from 16 to 6 affected performance. Three experimental conditions were tested: a baseline 16-electrode configuration, a reduced 6-electrode setup without retraining, and a reduced 6-electrode setup with retraining. (3) Results: Our results indicate that, on average, performance declines with fewer electrodes; nonetheless, retraining restored near-baseline mean Information Transfer Rate (ITR) and accuracy for those participants for whom the system remained functional. The results reveal that for a substantial number of participants, the classification pipeline fails after electrode removal, highlighting individual differences in the cVEP response characteristics or inherent limitations of the classification approach. (4) Conclusions: Ultimately, this suggests that minimal cVEP-BCI electrode setups capable of reliably functioning across all users might only be feasible through other, more flexible classification methods that can account for individual differences. These findings aim to serve as a guideline for what is currently achievable with this common cVEP paradigm and to highlight where future research should focus in order to move closer to a practical and user-friendly system. Full article

(This article belongs to the Section Computational Neuroscience and Neuroinformatics)

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18 pages, 293 KiB

Open AccessArticle

The Impact of COVID-19 in Brazil Through an Educational Neuroscience Lens: A Preliminary Study

by Camila G. Fonseca, Camila L. L. Dias, Marcus L. L. Barbosa, Maria Julia Hermida, Luiz Renato R. Carreiro and Alessandra G. Seabra

Brain Sci. 2025, 15(6), 548; https://doi.org/10.3390/brainsci15060548 - 23 May 2025

Abstract

Background: Educational neuroscience has made important contributions to show how the COVID-19 pandemic impacted schooling. In countries like Brazil, with significant educational inequality, the suspension of in-person classes worsened these disparities, as low-income families faced difficulties accessing remote learning. Methods: This study evaluated [...] Read more.

Background: Educational neuroscience has made important contributions to show how the COVID-19 pandemic impacted schooling. In countries like Brazil, with significant educational inequality, the suspension of in-person classes worsened these disparities, as low-income families faced difficulties accessing remote learning. Methods: This study evaluated executive functions (EF) and academic skills in reading, writing, and maths for 178 public school students from the first to ninth grades in São Paulo, Brazil, comparing them with pre-pandemic norms to assess possible differences. EF were assessed using the Hayling Test, Digit Span Task, and Verbal Fluency, while academic skills were measured by the School Performance Test II. To analyse differences between the sample of this study and the pre-pandemic normative samples, one-sample t-tests were performed. Due to the small sample size, segmented by school grade and age, the bootstrapping resampling method was used, and the effect size was measured with Cohen’s d. Results: A one-sample t-test showed significant differences between times, with lower post-pandemic performance in verbal fluency (9–14 years old), working memory (10–14 years old), and inhibitory control across all age groups. Writing skills were lower from the fifth to eighth grades and reading from the fourth to eight grades. Maths skills were lower in the fourth, eighth, and ninth grades. Better post-pandemic performance was seen in working memory (6 and 7 years old). Conclusions: Students in the upper grades of elementary school during the pandemic were most impacted by the suspension of in-person teaching, highlighting the importance of schooling and the need for recovery efforts at these levels. Full article

(This article belongs to the Special Issue Advances in Educational Neuroscience: Current Status and Future Directions)

14 pages, 532 KiB

Open AccessReview

Transcranial Direct Current Stimulation (tDCS) for Borderline Personality Disorder (BPD): Why and How?

by Lionel Cailhol, Kamilia Soltani, Cécilia Neige, Marine Mondino, Jérôme Brunelin and Martin Blay

Brain Sci. 2025, 15(6), 547; https://doi.org/10.3390/brainsci15060547 - 23 May 2025

Abstract

Background: Borderline Personality Disorder (BPD) is a severe psychiatric condition characterized by pervasive emotional dysregulation, impulsivity, and unstable interpersonal relationships. Affecting over 1% of the general population, BPD carries significant morbidity, frequent hospitalizations, and an increased risk of suicide. Although specialized psychotherapeutic approaches [...] Read more.

Background: Borderline Personality Disorder (BPD) is a severe psychiatric condition characterized by pervasive emotional dysregulation, impulsivity, and unstable interpersonal relationships. Affecting over 1% of the general population, BPD carries significant morbidity, frequent hospitalizations, and an increased risk of suicide. Although specialized psychotherapeutic approaches have shown efficacy, their impact is often constrained by availability, lengthy treatment durations, moderate effect sizes, and high dropout rates. Pharmacological treatments for BPD remain inadequate and are usually accompanied by adverse side effects. Objective: This narrative review seeks to explore the potential of transcranial direct current stimulation (tDCS) as a safe, cost-effective, and accessible neuromodulation intervention aimed at alleviating core BPD symptoms—namely, emotional dysregulation and impulsivity—while also addressing common comorbidities and opportunities for integration with existing therapeutic modalities. Methods: We conducted a narrative literature synthesis in accordance with the SANRA (Scale for the Assessment of Narrative Review Articles) guidelines. A PubMed/MEDLINE search was performed using keywords related to transcranial direct current stimulation (tDCS) and BPD, identifying five published randomized controlled trials on the topic. To provide a broader perspective, we also included studies from related fields examining mechanisms of action, safety and tolerability, cost-effectiveness, stimulation parameters, and clinical outcomes relevant to BPD. Results: Conventional tDCS protocols—typically involving 1–2 mA currents for 20–30 min—have demonstrated an excellent safety profile, resulting in only minimal and transient side effects without any risk of overdose or misuse, which is a key advantage for populations at high risk of suicidality. With moderately priced devices and the feasibility of home-based administration, tDCS provides a substantially more affordable alternative to both long-term pharmacotherapy and intensive psychotherapy. Neurobiologically, tDCS modulates the excitability of the dorsolateral and ventrolateral prefrontal cortex and enhances fronto-limbic connectivity, thereby strengthening top-down regulatory control over emotion and behavior. Pilot randomized controlled trials report moderate effect sizes for improvements in emotional regulation, inhibitory control, and rejection sensitivity, along with ancillary gains in executive functioning and reductions in depressive and substance-use symptoms when stimulating the left dorsolateral prefrontal cortex. Conclusions: tDCS stimulation emerges as a safe and scalable adjunctive treatment for BPD, leveraging targeted neuromodulation to address core features and common comorbidities like depression. However, variability in current protocols and the scarcity of well-powered randomized trials underscore the pressing need for standardized methodologies, longer-term follow-up, and individualized stimulation strategies to establish enduring clinical benefits. 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, 6356 KiB

Open AccessArticle

The Differential and Interactive Effects of Aging and Mental Fatigue on Alpha Oscillations: A Resting-State Electroencephalography Study

by Xiaodong Yang, Kaixin Liu, Lei Liu, Yanan Du, Hao Yu, Yongjie Yao, Yu Sun and Chuantao Li

Brain Sci. 2025, 15(6), 546; https://doi.org/10.3390/brainsci15060546 - 22 May 2025

Abstract

Background: Both aging and cognitive fatigue are significant factors influencing alpha activity in the brain. However, the interactive effects of age and mental fatigue on the alpha spectrum and functional connectivity have not been fully elucidated. Methods: Using resting-state EEG data from an [...] Read more.

Background: Both aging and cognitive fatigue are significant factors influencing alpha activity in the brain. However, the interactive effects of age and mental fatigue on the alpha spectrum and functional connectivity have not been fully elucidated. Methods: Using resting-state EEG data from an open-access dataset (younger: N = 198; older: N = 227) collected before and after a 2 h cognitive task block, we systematically examined the effects of aging and mental fatigue on alpha (8–13 Hz) oscillations via an aperiodic-corrected power spectrum, the weighted phase lag index (wPLI), and graph theory analysis. Results: In both spectral power and network efficiency, mental fatigue primarily modulates low alpha in younger individuals, while high alpha reflects stable age-related changes. The aperiodic offset and exponent decrease with age, while mental fatigue leads to an increase in the exponent. Notable interactions between age and mental fatigue are observed in low-alpha power, the aperiodic exponent, and the network efficiency of both low- and high-alpha bands. Conclusions: This study provides valuable insights into the differential modulation patterns of alpha activity by age and mental fatigue, as well as their interactions. These findings advance our understanding of how aging and mental fatigue differentially and interactively shape neural dynamics. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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12 pages, 604 KiB

Open AccessArticle

Still Relevant, Still Effective: A Retrospective Observational Cohort Study on Real-Life Use of Flunarizine in Episodic Migraine

by Devrimsel Harika Ertem, Faik Ilik and Mustafa Kemal Ilik

Brain Sci. 2025, 15(6), 545; https://doi.org/10.3390/brainsci15060545 - 22 May 2025

Abstract

Aim: New disease-specific and mechanism-based treatments for migraine that share good evidence of efficacy have recently been introduced. However, due to reimbursement problems with insurance companies and high costs, classical anti-migraine drugs continue to be used. The objective of this study was to [...] Read more.

Aim: New disease-specific and mechanism-based treatments for migraine that share good evidence of efficacy have recently been introduced. However, due to reimbursement problems with insurance companies and high costs, classical anti-migraine drugs continue to be used. The objective of this study was to assess the clinical efficacy and tolerability of flunarizine for the preventive treatment of episodic migraine without aura in a Turkish cohort, concentrating on alterations in headache frequency, pain intensity, and migraine-related disability as measured by MIDAS scores within a practical clinical environment. Methods: Clinical and demographic data of 243 patients with episodic migraine without aura (175 females, 68 males; mean age 33.9 years) were evaluated. Headache frequency, side effects of flunarizine, pain intensity, and MIDAS scores were recorded during initial and 3-month follow-up periods. Results: After three months of flunarizine treatment, significant improvements were observed in headache parameters. The mean Numeric Pain Rating Scale (NPRS) score, the mean MIDAS score, and the monthly migraine attack frequency declined significantly (all p values < 0.001). Adverse events were reported in 21.8% of patients, most commonly weight gain and tiredness, followed by mood changes, gastrointestinal symptoms, and numbness or tingling. Patients experiencing side effects were significantly older (p = 0.023), though side effects did not impact treatment efficacy. Regression analysis identified no significant predictors of disability improvement. Conclusion: Our results demonstrated that flunarizine had considerable short-term efficacy in decreasing the frequency of migraine attacks, alleviating headache severity, and reducing migraine-related disability among patients experiencing episodic migraine without aura. Although mild to moderate side effects were fairly prevalent, especially in older individuals, they did not compromise the effectiveness of the treatment. Notably, early adverse events occurring within the first two weeks resulted in treatment discontinuation for some patients, highlighting the necessity for vigilant monitoring during the initial phase of treatment. Full article

(This article belongs to the Section Sensory and Motor Neuroscience)

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15 pages, 666 KiB

Open AccessArticle

Resting Electroencephalography Microstates and Alpha Power Modulation in Preschool-Aged Children with Autism Spectrum Disorder

by Mingxuan Ma, Ziying Yang, Leiyan Wang, Shan Lu, Junxia Han and Xiaoli Li

Brain Sci. 2025, 15(6), 544; https://doi.org/10.3390/brainsci15060544 - 22 May 2025

Abstract

Background/Objectives: Emerging evidence suggests that individuals with autism spectrum disorder (ASD) exhibit altered neural connectivity and disrupted brain network dynamics, which can be captured through EEG microstate analysis. Most research to date has focused on older children, adolescents, or adults with ASD, [...] Read more.

Background/Objectives: Emerging evidence suggests that individuals with autism spectrum disorder (ASD) exhibit altered neural connectivity and disrupted brain network dynamics, which can be captured through EEG microstate analysis. Most research to date has focused on older children, adolescents, or adults with ASD, while studies focusing on preschool-aged children with ASD remain limited. Given that early brain development is critical for understanding the onset and progression of ASD, more research targeting this age group is essential. Methods: In this study, resting EEG data were collected from 59 preschool-aged children with ASD and 59 typically developing (TD) participants. Results: The results revealed a reduction in global explained variance and coverage of microstate in children with ASD, indicating poorer social performance that was independent of alpha power after the removal of the 1/f-like aperiodic signal. These findings reflect the social symptoms commonly observed in ASD. Additionally, alpha power was found to modulate the occurrence and duration of microstates in both groups. Conclusions: Our findings highlight that atypical microstates can serve as reliable biomarkers for ASD, offering valuable insights into the neurophysiological mechanisms underlying the disorder and paving the way for future research directions. Full article

(This article belongs to the Section Developmental Neuroscience)

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8 pages, 351 KiB

Open AccessBrief Report

Screening for Post-Stroke Cognitive Impairment in Sub-Saharan Africa: A Good IDEA?

by Fode Abass Cissé, Yannick Fogoum Fogang, Male Dore and Gilles Naeije

Brain Sci. 2025, 15(6), 543; https://doi.org/10.3390/brainsci15060543 - 22 May 2025

Abstract

Background: Post-stroke cognitive impairment (PSCI) remains under-recognized in Sub-Saharan Africa (SSA), in part due to the lack of validated cognitive screening tools adapted to low-literacy populations. We aimed to validate the Identification of Dementia in Elderly Africans (IDEA) cognitive screen in SSA and [...] Read more.

Background: Post-stroke cognitive impairment (PSCI) remains under-recognized in Sub-Saharan Africa (SSA), in part due to the lack of validated cognitive screening tools adapted to low-literacy populations. We aimed to validate the Identification of Dementia in Elderly Africans (IDEA) cognitive screen in SSA and assess its utility for detecting PSCI in Guinea and Cameroon. Methods: Normative IDEA scores were derived from a control cohort of healthy older adults in Conakry (Guinea) and Bafoussam (Cameroon). The tool was then applied to consecutive stroke patients from the same hospitals within one month of stroke onset. Demographic, clinical, and vascular risk profiles were collected. Between-group comparisons were performed using Welch’s t-tests and chi-square tests. Results: Among 91 healthy controls (median age: 64), the mean IDEA score was 12 ± 2.4. A cut-off of ≤7 (2 standard deviations below the mean) was defined for cognitive impairment. Among 111 stroke patients (median age: 65; mean NIHSS: 9.9 ± 5.8), the mean IDEA score was 9.6 ± 3.2, and 31 patients (28%) had scores ≤ 7. Stroke patients had significantly higher rates of hypertension and diabetes compared to controls. Conclusions: The IDEA screen appears to be a feasible and effective tool for detecting PSCI in SSA clinical settings. The 28% prevalence of cognitive impairment aligns with data from high-income countries, supporting the broader use of the IDEA to strengthen cognitive care pathways in SSA stroke populations. Full article

(This article belongs to the Special Issue Assessment and Rehabilitation of Cognitive Function in Neurological Disorders)

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17 pages, 990 KiB

Open AccessSystematic Review

Combination of Drugs in the Treatment of Alcohol Use Disorder: A Meta-Analysis and Meta-Regression Study

by João Vitor Guimarães Mandaji, Maria Olivia Pozzolo Pedro, Kae Leopoldo, João Pini Alemar, Julio Torales, Antonio Ventriglio and João Mauricio Castaldelli-Maia

Brain Sci. 2025, 15(6), 542; https://doi.org/10.3390/brainsci15060542 - 22 May 2025

Abstract

Background: Alcohol Use Disorder (AUD) is highly prevalent among substance use disorders worldwide and is characterized by a multifactorial pathophysiology. AUD treatment is mostly based on combined pharmacotherapy and multidisciplinary clinical approaches. Nonetheless, meta-analytical studies assessing the efficacy of combination therapy are scarcely [...] Read more.

Background: Alcohol Use Disorder (AUD) is highly prevalent among substance use disorders worldwide and is characterized by a multifactorial pathophysiology. AUD treatment is mostly based on combined pharmacotherapy and multidisciplinary clinical approaches. Nonetheless, meta-analytical studies assessing the efficacy of combination therapy are scarcely available. Methods: We searched for randomized clinical trials through PubMed, ClinicalTrials.gov, Cochrane Library, SciELO, Biblioteca Virtual em Saúde, and Google Scholar databases. Original clinical trials published in English and Portuguese were selected. Data collection followed the PRISMA and MOOSE guidelines and was assessed using the Risk of Bias Tool (RoB 2). Heterogeneity was assessed using the Q test. Meta-regression was conducted using Egger’s regression method. Twelve articles were finally included in the analysis, and random-effects models were applied on aggregate trial results. Results: The meta-analysis found that combination therapies led to an average 4.045% increase in abstinence rates (95% CI: 0.415% to 7.675%) compared to monotherapies. Meta-regression showed a strong positive association between the use of naltrexone, acamprosate, and sertraline—either alone or in combination—and treatment success in AUD. The meta-regression also highlighted the impact of patients’ variables, such as gender, age, country, and psychiatric comorbidities, on their treatment outcomes. These findings may identify a potential therapeutic pathway promoting alcohol abstinence, further supported by a Number Needed to Treat (NNT) of 25, as an acceptable value for substance use disorder treatments. Conclusions: Combined pharmacotherapies are more effective than monotherapy in enhancing abstinence rates in AUD treatment, with naltrexone, acamprosate, and sertraline emerging as key adjunctive agents promoting these outcomes. These findings underscore the complexity of AUD as a multifactorial psychiatric condition and highlight the potential of combined pharmacotherapy as a promising strategy for achieving better treatment outcomes, particularly in terms of abstinence rates. Full article

(This article belongs to the Section Neuropsychiatry)

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19 pages, 2154 KiB

Open AccessArticle

A New Method for Inducing Mental Fatigue: A High Mental Workload Task Paradigm Based on Complex Cognitive Abilities and Time Pressure

by Lei Ren, Lin Wu, Tingwei Feng and Xufeng Liu

Brain Sci. 2025, 15(6), 541; https://doi.org/10.3390/brainsci15060541 - 22 May 2025

Abstract

Objectives: With the advancement of modern society, people in cognitively demanding jobs are increasingly exposed to occupational stress. Prolonged and high-intensity cognitive activities are prone to inducing mental fatigue (MF), which adversely affects both psychological and physiological well-being, as well as task [...] Read more.

Objectives: With the advancement of modern society, people in cognitively demanding jobs are increasingly exposed to occupational stress. Prolonged and high-intensity cognitive activities are prone to inducing mental fatigue (MF), which adversely affects both psychological and physiological well-being, as well as task performance. Existing methods for inducing MF often demonstrate limited effectiveness due to insufficient cognitive load from overly simplistic tasks and the potential emotional disturbance caused by prolonged task duration. This study aims to explore a comprehensive cognitive task paradigm that integrates task complexity and time pressure, thereby developing a novel and effective method for inducing MF based on high mental workload (HMW) and the effects of time on task (ToT). Methods: Using convenience sampling, university students from a medical college were recruited as participants. The study was conducted in three steps. In the first step, we constructed a 1-back Stroop (BS) task paradigm by designing tasks with varying levels of complexity and incorporating time pressure through experimental manipulation. In the second step, the efficacy of the BS task paradigm was validated by comparing it with the traditional 2-back cognitive task in inducing HMW. In the third step, an MF induction protocol was established by combining the BS task paradigm with the ToT effect (i.e., a continuous 30 min task). Effectiveness was assessed using validated subjective measures (NASA Task Load Index [NASA-TLX] and Visual Analog Scale [VAS]) and objective behavioral metrics (reaction time and accuracy). Statistical analyses were performed using analysis of variance (ANOVA) and t-tests. Results: The BS task paradigm, which integrates complex cognitive abilities such as attention, working memory, inhibitory control, cognitive flexibility, and time pressure, demonstrated significantly higher NASA-TLX total scores, as well as elevated scores in mental demand, temporal demand, performance, and frustration scales, compared to the 2-back task. Additionally, the BS task paradigm resulted in longer reaction times and lower accuracy. As the BS task progressed, participants exhibited significant increases in mental fatigue (MF), mental effort (ME), mental stress (MS), and subjective feelings of fatigue, while the overall number of correct trials and accuracy showed a significant decline. Furthermore, reaction times in the psychomotor vigilance test (PVT) were significantly prolonged, and the number of lapses significantly increased between pre- and post-task assessments. Conclusions: The BS task paradigm based on complex cognitive abilities and time pressure could effectively induce an HMW state. Combined with the ToT effect, the BS paradigm demonstrated effective MF induction capabilities. This study provides a novel and reliable method for inducing HMW and MF, offering a valuable tool for future research in related fields. Full article

(This article belongs to the Section Cognitive, Social and Affective Neuroscience)

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16 pages, 1423 KiB

Open AccessArticle

Frontal Transcranial Direct Current Stimulation in Moderate to Severe Depression: Clinical and Neurophysiological Findings from a Pilot Study

by Florin Zamfirache, Gabriela Prundaru, Cristina Dumitru and Beatrice Mihaela Radu

Brain Sci. 2025, 15(6), 540; https://doi.org/10.3390/brainsci15060540 - 22 May 2025

Abstract

Background/Objectives: Transcranial Direct Current Stimulation (tDCS) has proven to be a promising intervention for major depressive disorder (MDD). Even so, the specific neurophysiological mechanisms underlying its therapeutic effects, particularly regarding frontal EEG markers, remain insufficiently understood. This pilot study investigated both the [...] Read more.

Background/Objectives: Transcranial Direct Current Stimulation (tDCS) has proven to be a promising intervention for major depressive disorder (MDD). Even so, the specific neurophysiological mechanisms underlying its therapeutic effects, particularly regarding frontal EEG markers, remain insufficiently understood. This pilot study investigated both the clinical efficacy and neurophysiological impact of frontal tDCS in individuals with mild to severe depression, with particular focus on mood changes and alterations in Frontal Alpha Asymmetry (FAA), Beta Symmetry, and Theta/Alpha Ratios at the F3 and F4 electrode sites. Methods: A total of thirty–one participants were enrolled and completed a standardized Flow Neuroscience tDCS protocol targeting the dorsolateral prefrontal cortex using a bilateral F3/F4 montage. The intervention included an active phase of five stimulations per week for three weeks, followed by a Strengthening Phase with two stimulations per week. Clinical outcomes were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS), while neurophysiological changes were evaluated via standardized quantitative EEG (QEEG) recordings obtained before and after the treatment course. Among the participants, fourteen individuals had a baseline MADRS score of ≥20, indicating moderate to severe depressive symptoms. Results: Following tDCS treatment, significant reductions in MADRS scores were observed across the cohort, with clinical response rates notably higher in the moderate/severe group (71.4%) compared to the mild depression group (20.0%). Neurophysiological effects were modest: no significant changes were detected in FAA or Beta Symmetry measures. However, a substantial reduction in the Theta/Alpha Ratio at F4 was found in participants with moderate to severe depression (p = 0.018, Cohen’s d = −0.72), suggesting enhanced frontal cortical activation associated with clinical improvement. Conclusions: These findings indicate that frontal tDCS is effective in reducing depressive symptoms, particularly in cases of moderate to severe depression. While improvements in FAA and Beta Symmetry were not significant, changes in the Theta/Alpha Ratio at F4 point toward dynamic neurophysiological reorganization potentially linked to therapeutic outcomes. The Theta/Alpha Ratio may serve as a promising biomarker for tracking tDCS response, whereas other EEG metrics might represent more stable trait characteristics. Future research should prioritize individualized stimulation protocols and incorporate more sensitive neurophysiological assessments, including functional connectivity analyses and task-evoked EEG paradigms, to understand the mechanisms underlying clinical improvements. Full article

(This article belongs to the Special Issue Advances in Non-Invasive Brain Stimulation)

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7 pages, 475 KiB

Open AccessCase Report

The Importance of Neuroimaging Follow-Up in Bilirubin-Induced Encephalopathy: A Clinical Case Review

by Martina Resaz, Alessia Pepe, Domenico Tortora, Andrea Rossi, Luca Antonio Ramenghi and Andrea Calandrino

Brain Sci. 2025, 15(6), 539; https://doi.org/10.3390/brainsci15060539 - 22 May 2025

Abstract

Introduction: Hyperbilirubinemia in newborns can lead to kernicterus, a severe form of neonatal encephalopathy caused by bilirubin toxicity. Despite timely interventions such as exchange transfusion, kernicterus can still develop, especially in high-risk infants. MRI is crucial for detecting early and evolving signs of [...] Read more.

Introduction: Hyperbilirubinemia in newborns can lead to kernicterus, a severe form of neonatal encephalopathy caused by bilirubin toxicity. Despite timely interventions such as exchange transfusion, kernicterus can still develop, especially in high-risk infants. MRI is crucial for detecting early and evolving signs of bilirubin-induced brain damage. Case Report: We report a term newborn who developed severe hyperbilirubinemia and kernicterus despite receiving exchange transfusion. The infant presented on day 3 of life with jaundice, hypotonia, and feeding difficulties and had a bilirubin level of 51 mg/dL. After exchange transfusion, bilirubin levels normalized, but neurotoxicity persisted. Initial MRI at one month showed mild T1 hyperintensity in the hippocampi with no changes in the basal ganglia. At two months, T1 hyperintensities in the hippocampi partially resolved. By six months, MRI revealed T2 hyperintensities in the globus pallidus and hippocampal atrophy, consistent with kernicterus. Magnetic resonance spectroscopy (MRS) showed reduced N-acetylaspartate (NAA) levels, indicating neuronal loss. Discussion: MRI is essential in monitoring bilirubin-induced brain injury. In this case, early MRI findings showed mild hippocampal T1 hyperintensity, which resolved partially. At six months, T2 hyperintensities in the globus pallidus confirmed chronic bilirubin encephalopathy. MRS demonstrated a reduction in N-acetylaspartate, indicative of neuronal loss. Susceptibility-Weighted Imaging (SWI) showed no abnormalities, likely due to the myelination process in neonates. Conclusions: This case highlights the importance of repeated MRI in detecting bilirubin-induced brain damage. Early neuroimaging enables timely interventions and improves long-term neurodevelopmental outcomes in infants with severe hyperbilirubinemia. Full article

(This article belongs to the Section Developmental Neuroscience)

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