Brain Sciences

14 pages, 863 KB

Open AccessPerspective

Aquatic Therapy as a Programmable Multisensory Environment for Arousal and Postural Control After Severe Acquired Brain Injury: A Perspective

by Andrea Calderone, Rosaria De Luca, Alessio Currò, Alessio Mirabile, Marco Piccione and Rocco Salvatore Calabrò

Brain Sci. 2026, 16(3), 344; https://doi.org/10.3390/brainsci16030344 - 22 Mar 2026

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Abstract

Background/Objectives: Severe acquired brain injury (sABI) disrupts early rehabilitation because arousal fluctuates, trunk control is fragile, and agitation limits therapy tolerance; land-based practice is frequently constrained by fall risk and staffing. We aim to reframe aquatic therapy as a programmable multisensory environment [...] Read more.

Background/Objectives: Severe acquired brain injury (sABI) disrupts early rehabilitation because arousal fluctuates, trunk control is fragile, and agitation limits therapy tolerance; land-based practice is frequently constrained by fall risk and staffing. We aim to reframe aquatic therapy as a programmable multisensory environment to stabilize arousal and support axial alignment before conventional impairment targets are feasible. Here, programmable denotes the deliberate titration and reporting of water depth, turbulence or perturbation, temperature, body orientation, and flotation and manual support as intervention inputs. Methods: This perspective integrates principles from neurobehavioral assessment, motor control, and immersion physiology to propose the Arousal–Alignment–Action loop as a falsifiable model and to define manipulable aquatic inputs (water depth, turbulence or perturbation, temperature, body orientation, and flotation and manual support) as dosing parameters. We outline a pragmatic testing ladder (within-session micro-experiments, feasibility studies, and embedded evaluations) and a minimal outcomes and confounder set to support cumulative evidence. Results: The framework links state regulation to alignment and goal-directed behavior, specifies predictions that can fail, and highlights boundary conditions (sedation, autonomic instability, pain, recent surgery or wounds, and cervical or cardiopulmonary constraints). A minimal outcome package spanning arousal/responsiveness, trunk control, behavioral dysregulation, participation/tolerance, and basic physiology is proposed, with optional objective adjuncts for mechanism-oriented studies. Conclusions: Treating water as a measurable and titratable medium, rather than a generic modality, may reduce early intensity bottlenecks and improve implementability and comparability of aquatic neurorehabilitation research in medically stable sABI; however, the model is intended as hypothesis-generating until supported by stronger direct clinical evidence. Full article

(This article belongs to the Topic Advances in Neurorehabilitation)

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11 pages, 424 KB

Open AccessBrief Report

Outcome of People with Parkinson’s Disease Treated with Levodopa-Entacapone-Carbidopa Intestinal Gel Who Failed Previous Subcutaneous Foslevodopa/Foscarbidopa

by Diego Santos García, Inés Legarda, Tamara M. González Fernández, Ana Rodríguez Sanz, Maria Isabel Morales-Casado, Alejandro Peral, Nuria Caballol, María Álvarez Sauco, Iria Campos Rodríguez, Déborah Alonso Modino, Lydia López Manzanares, Jesús Olivares Romero and Alberto Blanco Ollero

Brain Sci. 2026, 16(3), 343; https://doi.org/10.3390/brainsci16030343 - 22 Mar 2026

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Abstract

Introduction: The clinical outcome of switching to levodopa-entacapone-carbidopa intestinal gel (LECIG) after failure of subcutaneous foslevodopa/foscarbidopa (fLD/fCD) is unknown. We analyze it in people with Parkinson’s disease (PwP) treated in Spain. Methods: Retrospective analysis of PwP who had previously received fLD/fCD but dropped [...] Read more.

Introduction: The clinical outcome of switching to levodopa-entacapone-carbidopa intestinal gel (LECIG) after failure of subcutaneous foslevodopa/foscarbidopa (fLD/fCD) is unknown. We analyze it in people with Parkinson’s disease (PwP) treated in Spain. Methods: Retrospective analysis of PwP who had previously received fLD/fCD but dropped out for different reasons and started before this LECIG in Spain up to 30 November 2025. Non-parametric tests were applied to evaluate the changes between the pre- (Vpre) and post-treatment (Vpost) (LECIG) periods. Results: Data about 14 patients (57.1% males; 66.6 ± 8.6 years old) from 12 hospitals out of a total of 15 who were treated with LECIG were included. The mean time with fLD/fCD was 98.6 ± 92.3 days, with 92.9% and 57.1% experiencing side effects and lack of response, respectively. Specifically, significant subcutaneous nodules were reported in up to 64.3% of the patients. LECIG was a direct switch from fLD/fCD in 35.7% of the patients. LECIG was well tolerated, with only one dropout due to complications related to dementia. Adverse events were reported in 28.6% and 35.7% of the patients in the optimization and final follow-up evaluation (mean follow-up of 233.7 ± 157.4 days) phases, respectively. From Vpre to Vpost, “Off” time was reduced in 2.9 ± 1.9 h (p = 0.002) and motor symptoms burden improved significantly (p = 0.013), whereas a trend of significance was found for non-motor symptoms burden (p = 0.050) and quality of life (p = 0.126). Conclusions: LECIG could be an alternative therapeutic option in PwP who failed fLD/fCD. Full article

(This article belongs to the Special Issue Advances in Parkinson's Disease and Movement Disorders)

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20 pages, 1284 KB

Open AccessArticle

Acute Effects of High-Velocity Interval Cycling Versus Continuous Moderate-Intensity Cycling on Cognitive Function in Patients with Mild Cognitive Impairment

by Mari Bardopoulou, Costas Chryssanthopoulos, Evgenia D. Cherouveim, Evangelia Tzeravini, Evangelia Stanitsa, Maria Koustimpi, Eirini Chatzinikita, Irini Patsaki, Stelios Poulos, John Papatriantafyllou, Theodoros Vassilakopoulos, Maria Maridaki, Christos Consoulas, Sokratis G. Papageorgiou, Michael Koutsilieris and Anastassios Philippou

Brain Sci. 2026, 16(3), 342; https://doi.org/10.3390/brainsci16030342 - 22 Mar 2026

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Abstract

Background/Objectives: Physical exercise has emerged as a promising non-pharmacological intervention for cognitive dysfunction; however, the most effective mode of exercise remains unclear. This study aimed to investigate the acute effects of two cycling exercise protocols, (a) continuous aerobic/moderate-intensity (CA) and (b) high-velocity/low-resistance (high-cadence) [...] Read more.

Background/Objectives: Physical exercise has emerged as a promising non-pharmacological intervention for cognitive dysfunction; however, the most effective mode of exercise remains unclear. This study aimed to investigate the acute effects of two cycling exercise protocols, (a) continuous aerobic/moderate-intensity (CA) and (b) high-velocity/low-resistance (high-cadence) interval (HVI), on cognitive and executive performance in patients with mild cognitive impairment (MCI). Methods: Seventeen patients (10 females and 7 males, age: 65.5 ± 8.85 years) diagnosed with MCI or early-stage Alzheimer’s disease (13 MCI and 4 eAD) participated in a random order in three different conditions: CA, HVI, and control/no exercise (CON). Cognitive parameters were assessed acutely before and after the completion of each condition. Results: Significant condition × time interactions were observed for both Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB) (p < 0.01). Higher scores (p < 0.01) for MoCA and FAB post-intervention were found compared to baseline in both exercise bouts, whereas no changes occurred in CON. Interestingly, when post-intervention scores were compared between conditions, cognitive performance was improved only in HVΙ compared to CON in MoCA (p < 0.01) and FAB (p < 0.001), revealing a stronger acute effect of HVI. Conclusions: A single bout of high-velocity, low-resistance (high-cadence) interval cycling acutely enhanced global cognition and executive function in individuals with MCI, exerting greater improvement compared to continuous aerobic exercise or control condition. These findings emphasize the potential utilization of HVI as an effective non-pharmacological intervention to acutely enhance cognitive performance in older adults with MCI. Full article

(This article belongs to the Special Issue Advances in the Relationship Among Brain, Physical Function, and Exercise Performance)

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23 pages, 1473 KB

Open AccessArticle

Associations Between Language, Speech Sound, and Learning Disorders

by Chiara Valeria Marinelli, Emiliano Pizzicannella, Marinella De Salvatore, Daniela Sarti, Vincenza Tommasi, Pierluigi Zoccolotti, Luca Andreoli and Elisa Granocchio

Brain Sci. 2026, 16(3), 341; https://doi.org/10.3390/brainsci16030341 - 21 Mar 2026

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Abstract

Background and Objectives: Children with specific learning disorders (SLD) often present a history of speech and language deficits. However, systematic evidence on the co-occurrence among distinct learning and communication disorders remains limited. This study aimed to describe the associations among reading, spelling, and [...] Read more.

Background and Objectives: Children with specific learning disorders (SLD) often present a history of speech and language deficits. However, systematic evidence on the co-occurrence among distinct learning and communication disorders remains limited. This study aimed to describe the associations among reading, spelling, and math disorders and their relationships with clinically diagnosed speech sound and language disorders and speech sound disorders in a large, well-characterized clinical sample. Methods: 235 3rd- to 8th-grade Italian children with SLD participated in the study. They were categorized in terms of learning (reading, spelling, and math) and comorbid communication disorders (speech sound, and language disorders), according to established diagnostic criteria. Prevalence rates were assessed for each of the resulting subgroups. Results: Comorbidity between the three learning disorders was very frequent; 75.4% of children showed different forms of multiple SLDs, with 47.7% presenting a combined reading, spelling, and math disorder. Communication disorders were reported in 40.4% of the sample. Both language and speech sound disorders frequently co-occurred with spelling disorders, whereas associations with isolated reading or math disorders were more infrequent. Additionally, speech sound disorders frequently co-occurred with isolated spelling disorders, whereas language disorders frequently co-occurred with comorbid spelling disorders. Conclusions: Consistent with previous evidence, the study shows that learning disorders are highly comorbid with communication disorders. Critically, speech and language disorders are most frequently comorbid with spelling disorder, independent of reading and math deficits, highlighting spelling as a potential key interface between phonology, language, and learning. Full article

(This article belongs to the Special Issue Beyond Boundaries: Current Advances in Developmental Learning Disorders)

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28 pages, 4715 KB

Open AccessArticle

Probiotic Bacillus subtilis, but Not a Lactobacillus spp., Ameliorates Cognitive Impairment in a Mouse Model of LPS and Zidovudine-Induced Neuroinflammation

by Olga Murgina, Ksenia Stafeeva, Sofya Karaulova, Alena Vostrikova, Sofya Kononova, Daria Chursina, Svetlana Pozdeeva, Anastasia Makogonova, Inna Burakova, Svetlana Pogorelova, Polina Morozova, Yulia Smirnova, Mikhail Syromyatnikov, Viktor Shutikov, Evgeny Mikhailov and Artem Gureev

Brain Sci. 2026, 16(3), 340; https://doi.org/10.3390/brainsci16030340 - 21 Mar 2026

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Abstract

Background/Objectives: The gut–brain axis is increasingly recognized as a critical modulator of cognitive function. This study investigated the neurotoxic effects of combined exposure to bacterial lipopolysaccharide (LPS) and the antiretroviral drug zidovudine (ZDV) in a mouse model, and evaluated the protective potential of [...] Read more.

Background/Objectives: The gut–brain axis is increasingly recognized as a critical modulator of cognitive function. This study investigated the neurotoxic effects of combined exposure to bacterial lipopolysaccharide (LPS) and the antiretroviral drug zidovudine (ZDV) in a mouse model, and evaluated the protective potential of two probiotic interventions: Bacillus subtilis and a mixture of lactobacilli. Methods: Cognitive function was assessed using the Morris water maze (MWM). Gut microbiota composition was analyzed by 16S rRNA sequencing, and intestinal morphology was examined histologically. Gene expression of neuroinflammatory markers and mitophagy-related genes in brain tissue was quantified by RT-PCR. Plasma levels of cell-free mitochondrial DNA (cf-mtDNA) were measured as a marker of mitochondrial damage. Results: Combined LPS + ZDV exposure induced systemic inflammation, impaired spatial memory, damaged the intestinal mucosa, and caused dysbiosis characterized by an increase in pro-inflammatory Muribaculaceae. In the brain, LPS + ZDV significantly upregulated Tnfa expression, confirming neuroinflammation. Bacillus subtilis administration prevented cognitive deficits, maintained Tnfa at control levels, and significantly reduced Il1b and Il6 expression compared to the LPS + ZDV group. This was accompanied by activation of the PINK1/PTEN-dependent mitophagy pathway, prevention of cf-mtDNA release, and restoration of gut microbial diversity. In contrast, the Lactobacilli mixture not only failed to improve outcomes but was associated with exacerbated intestinal damage, more pronounced cognitive dysfunction, and no reduction in neuroinflammatory markers. Conclusions: Combined exposure to LPS and ZDV induces gut–brain axis dysfunction characterized by neuroinflammation, cognitive impairment, intestinal damage, and dysbiosis. Bacillus subtilis effectively preserves cognitive function through activation of PINK1/PTEN-dependent mitophagy and suppression of neuroinflammation, highlighting its potential as a therapeutic candidate for cognitive impairments associated with gut–brain axis dysfunction. The contrasting effects of the lactobacilli mixture underscore the critical importance of strain-specificity in probiotic interventions. Full article

(This article belongs to the Section Behavioral Neuroscience)

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22 pages, 1935 KB

Open AccessCase Report

Combined tDCS and Neuropsychological Treatment for Adult ADHD: A Single-Case Feasibility Study on Cognitive and Emotional Outcomes

by Pablo Rodríguez-Prieto, Julia Soler-Vázquez and Joaquín A. Ibáñez-Alfonso

Brain Sci. 2026, 16(3), 339; https://doi.org/10.3390/brainsci16030339 - 21 Mar 2026

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Abstract

Background/Objectives: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood and it tends to remain during adulthood. It not only affects cognitive abilities and behavior but also often presents emotional disturbances and alterations in the perceived [...] Read more.

Background/Objectives: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood and it tends to remain during adulthood. It not only affects cognitive abilities and behavior but also often presents emotional disturbances and alterations in the perceived quality of life. These symptoms are primarily related to dysfunctions in the ventromedial and dorsolateral prefrontal network. The main objective was to evaluate the feasibility and explore the initial outcomes of an integrated protocol combining neuropsychological treatment and transcranial direct current stimulation (tDCS). Methods: This study presents a single-case experimental A-B design of a 21-year-old woman, diagnosed with predominantly inattentive ADHD, treated at the University Psychology Clinic of Loyola Andalucía University. The treatment was carried out twice a week for 5 weeks (10 sessions in total), with 20 min of anodal tDCS at F3 and cathodal tDCS at F4 (2 mA), while digital neurorehabilitation exercises and psychotherapeutic support were provided. Results: An overall significant improvement was observed in cognitive functions (p = 0.008), with clinically significant gains in cognitive flexibility, visual working memory, and planning. Mixed results were found in inhibition, with improvement in interference control but no change in response inhibition. No significant changes were observed in sustained attention, auditory working memory, or processing speed. In terms of emotional state, an overall improvement was noted (p = 0.046), particularly in depression symptoms and perceived quality of life related to physical and psychological health. However, no significant changes were observed in anxiety symptoms or in areas related to the environment and social relationships. These findings reflect pilot-level evidence of clinical change within a feasibility framework. Conclusions: The combined treatment was found to be safe and feasible, showing promising preliminary improvements in cognitive and emotional domains. As a single-case study, these results serve as hypothesis-generating evidence for future controlled trials. 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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14 pages, 979 KB

Open AccessArticle

Seasonal Changes in Psychomotor Abilities of Male Handball Players

by Maciej Śliż, Wojciech Paśko, Francisco Martins, Rafał Krupa, Élvio Rubio Gouveia, Hugo Sarmento and Krzysztof Przednowek

Brain Sci. 2026, 16(3), 338; https://doi.org/10.3390/brainsci16030338 - 21 Mar 2026

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Abstract

Background/Objectives: Reaction time, hand–eye coordination, spatial orientation, and attention play a key role in handball, which is characterized by high intensity as well as high cognitive and motor demands. The level of these abilities may change during the season, potentially reflecting training adaptations [...] Read more.

Background/Objectives: Reaction time, hand–eye coordination, spatial orientation, and attention play a key role in handball, which is characterized by high intensity as well as high cognitive and motor demands. The level of these abilities may change during the season, potentially reflecting training adaptations and increasing physical fatigue. The aim of the study was to compare the level of psychomotor abilities in professional handball players before the start of the competition round and after the end of the league season. The study included 77 handball players playing in the Polish Handball Super League (average age: 25.6 ± 5.2 years). The players were divided according to position: pivot, center, and wing. Methods: Psychomotor abilities were assessed using the Test2Drive computer system, employing tests of simple and choice reaction time, eye–hand coordination, spatial orientation, perception and attention, and movement anticipation. Results: At the end of the season, a statistically significant reduction in reaction time was observed in the choice reaction (p = 0.001), eye–hand coordination (p = 0.002), and spatial orientation tests (p = 0.003). In terms of motor skills, an increase in time was observed in the SIRT test (p = 0.003), CHORT (p = 0.005) and HECOR (p = 0.011) tests, while the time in the PUT test was shortened for both neutral (p = 0.002) and critical (p = 0.025) stimuli. Positional analysis showed that after the season, the pivot player achieved higher effectiveness in the CHORT test than the wing player (p = 0.020). Additionally, statistically significant differences were observed for correct responses in the SPANT test (p = 0.032). In terms of correct answers in the PAMT test, the pivot player had the lowest effectiveness. Conclusions: Participation in the full season of competition coincided with significant changes in the psychomotor profile of handball players, with a simultaneous improvement in reaction speed and deterioration in movement time parameters. Full article

(This article belongs to the Special Issue Mind in Motion: Exploring Neuropsychophysiological Aspects of Sports Performance, Health and Physical Activity: 2nd Edition)

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21 pages, 802 KB

Open AccessSystematic Review

Eye Tracking for Rehabilitation and Training in Paediatric Neurodevelopmental Disorders: A Systematic Review

by Guido Catalano, Sara Abbondio, Roberta Nicotra, Valentina Berselli, Marta Guarischi, Valentina Vezzali and Sabrina Signorini

Brain Sci. 2026, 16(3), 337; https://doi.org/10.3390/brainsci16030337 - 21 Mar 2026

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Abstract

Background: Eye-tracking (ET) devices are gaining attention in technology-based paediatric rehabilitation through their intrinsic ability to assess patients’ engagement and visual attention within motivating, technology-based environments. We conducted a systematic review of available evidence from 2004 to 2025 on the implementation of ET [...] Read more.

Background: Eye-tracking (ET) devices are gaining attention in technology-based paediatric rehabilitation through their intrinsic ability to assess patients’ engagement and visual attention within motivating, technology-based environments. We conducted a systematic review of available evidence from 2004 to 2025 on the implementation of ET in rehabilitative trainings targeting paediatric populations with neurological and neurodevelopmental disorders. This paper aims to outline the rehabilitative outcomes pursued in the clinical populations considered. Methods: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three electronic databases (PubMed, Web of Science, and Scopus) were consulted to summarise the state of the art of the last 20 years. Selected articles were categorised according to the type of treated disorder and the rehabilitated function. Results: ET devices have been increasingly integrated into paediatric rehabilitation with promising results across multiple neurodevelopmental conditions (e.g., ASD, ADHD, cerebral palsy). These systems have proven effective not only in training gaze control, but also in enhancing executive functions, social cognition, communication, and participation. Furthermore, they promote personalised and data-driven solutions and support high levels of engagement, feasibility, and user satisfaction. Conclusions: ET represents a promising frontier for paediatric rehabilitation, addressing various neurodevelopmental disorders. The gaze-contingent protocols employed have demonstrated potential effects in promoting adaptive behaviour across multiple developmental areas. Further research is warranted to provide shared guidance and to strengthen practice recommendations. Full article

(This article belongs to the Special Issue Eye-Tracking Monitoring of Neurological and Psychiatric Conditions Across Life Span)

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19 pages, 3640 KB

Open AccessArticle

Effects of Sex Differences on Conditioned Fear Extinction and Safety Learning in C57BL/6J Mice

by Zhuoqun Liu, Haoxuan Pan, Huimeng Lei and Xiaohong Sun

Brain Sci. 2026, 16(3), 336; https://doi.org/10.3390/brainsci16030336 - 21 Mar 2026

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Abstract

Objectives: Females are often underrepresented in preclinical fear research due to concerns over estrous cycle related variability. This study examined whether there were differences between female and male C57BL/6J mice in terms of fear extinction and safety learning, aiming to verify the inclusion [...] Read more.

Objectives: Females are often underrepresented in preclinical fear research due to concerns over estrous cycle related variability. This study examined whether there were differences between female and male C57BL/6J mice in terms of fear extinction and safety learning, aiming to verify the inclusion of both sexes in fear regulation research. Methods: Mice underwent a 5-day fear conditioning and extinction protocol, with recent (Day 6) and remote (Day 13) retrieval tests. A separate cohort received unpaired tone-shock safety conditioning over two days, followed by recent and remote retrieval. Freezing percentage and locomotor distance, among other measures, were quantified to compare behavioral responses between sexes. Results: During fear acquisition and extinction, females and males showed comparable conditioned fear and progressive extinction, with no sex differences in freezing percentage, bout counts, or locomotor distance. Freezing remained low during both recent and remote retrieval in both sexes. In the safety-conditioning task, the safety cue reduced freezing relative to contextual baseline, contextual freezing declined from recent to remote retrieval, and no sex differences were observed across measures. Conclusions: Female and male C57BL/6J mice exhibit equivalent performance in auditory fear conditioning, extinction, retrieval, and safety learning under matched conditions. These findings support equitable inclusion of both sexes in preclinical fear-regulation studies, enhancing translational relevance without added behavioral variability. Full article

(This article belongs to the Section Behavioral Neuroscience)

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18 pages, 4131 KB

Open AccessArticle

Neural Oscillatory and Network Signatures of Age-Related Cognitive Decline Under Motor-Cognitive Dual-Task Conditions

by Miaomiao Guo, Qi Wang, Mengfan Li, Liang Sun, Tian Wang, Guizhi Xu and Lei Wang

Brain Sci. 2026, 16(3), 335; https://doi.org/10.3390/brainsci16030335 - 21 Mar 2026

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Abstract

Background: Against the backdrop of global population aging, understanding the mechanisms of age-related cognitive decline has become crucial for improving the health and quality of life in older adults. Methods: This study employed a multimodal approach to investigate the neural modulations [...] Read more.

Background: Against the backdrop of global population aging, understanding the mechanisms of age-related cognitive decline has become crucial for improving the health and quality of life in older adults. Methods: This study employed a multimodal approach to investigate the neural modulations induced by a motor cognitive dual task and their relationship with age-related decline. By integrating behavioral assessments, electroencephalography (EEG), and body composition analysis, we comprehensively evaluated performance and neural correlates in 19 younger and 18 older adults. Specifically, EEG analyses focused on comparing pre-task and post-task resting-state recordings to investigate the immediate impact of a single acute cognitive-motor dual-task session on neural oscillations and brain network organization. Results: Key findings include: (1) older adults exhibited significantly inferior performance in task accuracy, reaction time, and composite performance score compared to younger adults (p < 0.001); (2) neural oscillatory analysis of resting-state data revealed a localized increase in gamma-band power at posterior-temporal sites (PO4/T6) in older adults following the dual-task, while younger adults exhibited widespread multi-band (delta to beta) power modulation across frontal, central, and temporal regions in younger adults; (3) brain network analysis demonstrated synergistic enhancement of multi-band (Theta, Alpha, Beta, Gamma) connectivity and optimized topological organization in younger adults post-task, contrasting with network rigidity and localized compensatory patterns in older adults; (4) correlation analyses indicated significant associations between dual-task performance and MoCA-B scores in older adults (r = 0.861, p < 0.001). Conclusions: This study innovatively elucidates the neurophysiological characteristics of brain aging. The motor-cognitive dual-task paradigm proves to be a sensitive tool for capturing early cognitive changes, holding significant promise for clinical screening. Full article

(This article belongs to the Section Behavioral Neuroscience)

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15 pages, 1115 KB

Open AccessArticle

Alzheimer’s Disease Classification Using Population-Referenced Brain Volumetric Percentiles

by Jae Hyuk Shim and Hyeon-Man Baek

Brain Sci. 2026, 16(3), 334; https://doi.org/10.3390/brainsci16030334 - 20 Mar 2026

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Abstract

Background/Objectives: Translating brain volumetric biomarkers to individual-level Alzheimer’s disease (AD) diagnosis remains challenging due to difficulty interpreting raw volumes without longitudinal monitoring or matched controls. We tested a classification model using population-referenced volumetric percentiles to distinguish AD from cognitively normal (CN) subjects [...] Read more.

Background/Objectives: Translating brain volumetric biomarkers to individual-level Alzheimer’s disease (AD) diagnosis remains challenging due to difficulty interpreting raw volumes without longitudinal monitoring or matched controls. We tested a classification model using population-referenced volumetric percentiles to distinguish AD from cognitively normal (CN) subjects and evaluated its generalization across independent cohorts. Methods: Brain volumes from 95 regions were extracted using an automated segmentation pipeline and converted to age and sex adjusted percentiles using a reference population (N = 1833). A logistic regression classifier was trained on ADNI subjects (N = 873; AD = 183, CN = 690) split into training (60%), validation (20%), and test (20%) sets. The model was evaluated on two independent validation datasets: the held-out ADNI validation set and an external Korean cohort (N = 72; AD = 36, CN = 36) acquired with different scanner protocols and demographic characteristics. Results: The model achieved excellent discrimination across all evaluation sets: ADNI validation (AUC = 0.963, accuracy = 90.3%), ADNI test (AUC = 0.960, accuracy = 89.7%), and Korean external validation (AUC = 0.981, accuracy = 87.5%). The minimal validation gap (0.018) demonstrated robust generalization. Positive coefficients for ventricular regions reflected AD-associated atrophy patterns, while negative coefficients for medial temporal structures indicated their contribution within multivariate patterns distinguishing AD from normal aging. Conclusions: Population-referenced brain volumetric percentiles enable accurate AD classification with robust generalization across populations and scanner protocols. By contextualizing individual brain structure relative to normative populations while accounting for age and sex, this approach demonstrates potential for clinical translation as an accessible neuroimaging-based diagnostic tool. Full article

(This article belongs to the Special Issue Alzheimer’s Disease: Symptoms, Early Diagnosis, Treatment, and Prevention)

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15 pages, 7457 KB

Open AccessArticle

Parietal Alpha-ERD and Theta-ERS Serve as Neuroelectrical Indices for Working Memory Impairment Following Total Sleep Deprivation

by Wenbin Sheng, Zihan Gang, Liwei Zhang, Yongcong Shao and Qianxiang Zhou

Brain Sci. 2026, 16(3), 333; https://doi.org/10.3390/brainsci16030333 - 20 Mar 2026

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Abstract

Background/Objectives: Acute total sleep deprivation (TSD) is known to impair working memory capacity. However, the specific relationship between alterations in the brain’s electrical power spectrum following TSD and working memory deficits remains poorly understood. Methods: In this study, 30 healthy young adults (14 [...] Read more.

Background/Objectives: Acute total sleep deprivation (TSD) is known to impair working memory capacity. However, the specific relationship between alterations in the brain’s electrical power spectrum following TSD and working memory deficits remains poorly understood. Methods: In this study, 30 healthy young adults (14 males and 16 females) were enrolled, and 28 participants were finally included in the analysis after excluding EEG data with excessive noise, who underwent a verbal working memory task under two conditions: baseline sleep (BL) and 36 h of TSD. EEG data were recorded concurrently. Results: We observed a significant decrease in working memory accuracy and a significant prolongation of reaction time after TSD. Furthermore, TSD led to a significant enhancement of parietal alpha-ERD (at electrodes P3/Pz/P4) and theta-ERS, accompanied by a reduction in N2 and P3 wave amplitudes. Conclusions: These findings suggest that TSD may impair working memory by weakening parietal alpha-ERD and early conflict monitoring and late attention evaluation processes. The enhanced theta-ERS might represent a compensatory mechanism. Full article

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

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18 pages, 1632 KB

Open AccessArticle

Leuprolide Acetate Promotes Sensory Recovery and Modulates Dorsal Root Ganglion Responses After Sciatic Nerve Transection in Rats

by Irma Hernández-Jasso, Denisse Calderón-Vallejo, José Ávila-Mendoza, David Epardo, Jerusa E. Balderas-Márquez, Carlos Arámburo, J. Luis Quintanar and Carlos G. Martínez-Moreno

Brain Sci. 2026, 16(3), 332; https://doi.org/10.3390/brainsci16030332 - 20 Mar 2026

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Abstract

Background/Objectives: Sciatic nerve injuries are among the most common classes of peripheral nerve harm and have a strong impact on quality of life, as well as a significant negative economic impact for patients, society, and governments, since they represent a frequent cause [...] Read more.

Background/Objectives: Sciatic nerve injuries are among the most common classes of peripheral nerve harm and have a strong impact on quality of life, as well as a significant negative economic impact for patients, society, and governments, since they represent a frequent cause of work-related disabilities and sick leave applications. Following nerve injury, neurons, Schwann, and satellite cells undergo marked changes in phenotype, metabolic activity, neuronal survival, nervous transmission, and an exacerbated activation of the inflammatory response. Leuprolide acetate (LA), a clinically available agonist of gonadotropin-releasing hormone (GnRH), has shown clear neurotrophic properties and is considered a novel potential candidate for treating neural injuries, including sciatic nerve pathologies. This study aimed to analyze the effect of LA treatment on sensory function and dorsal root ganglia (DRG) changes in a rat sciatic nerve full-transection (SNT) model. Methods: Variations in cold and heat sensitivity were assessed using the thermal plate test, while DRG tissue sections were examined for modifications in reactive gliosis by immunofluorescence analysis, and axonal transport using a retrograde tracer. Also, changes in the expression of pro-regenerative genes Stat3, Socs3, Fos, Jun, Atf4, and Limk1 were quantified by qPCR. Results: Our results showed that LA treatment exerted a distinct neurotrophic effect, since it promoted the specific recovery of cold sensitivity, improved axonal transport, regulated the inflammatory response, and modulated the exacerbated expression of pro-regenerative genes in the SNT model. Conclusions: These findings indicate that LA therapy may have the potential to improve sensory recovery in patients with sciatic nerve injuries. Full article

(This article belongs to the Section Molecular and Cellular Neuroscience)

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2 pages, 1837 KB

Open AccessCorrection

Correction: Tong et al. Reduced Apoptotic Injury by Phenothiazine in Ischemic Stroke Through the NOX-Akt/PKC Pathway. Brain Sci. 2019, 9, 378

by Yanna Tong, Kenneth B. Elkin, Changya Peng, Jiamei Shen, Fengwu Li, Longfei Guan, Yu Ji, Wenjing Wei, Xiaokun Geng and Yuchuan Ding

Brain Sci. 2026, 16(3), 331; https://doi.org/10.3390/brainsci16030331 - 20 Mar 2026

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Abstract

In our article “Reduced Apoptotic Injury by Phenothiazine in Ischemic Stroke Through the NOX-Akt/PKC Pathway” [...] Full article

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22 pages, 1509 KB

Open AccessArticle

ICTD: Combination of Improved CNN–Transformer and Enhanced Deep Canonical Correlation Analysis for Eye-Movement Emotion Classification

by Cong Zhang, Xisheng Li, Jiannan Chi, Ming Cao, Qingfeng Gu and Jiahui Liu

Brain Sci. 2026, 16(3), 330; https://doi.org/10.3390/brainsci16030330 - 19 Mar 2026

Viewed by 290

Abstract

Background/Objectives: Emotion classification based on eye-movement features has become a widely adopted approach due to the simplicity of data acquisition and the strong association between ocular responses and emotional states. However, several challenges remain with regard to existing emotion recognition methods, including [...] Read more.

Background/Objectives: Emotion classification based on eye-movement features has become a widely adopted approach due to the simplicity of data acquisition and the strong association between ocular responses and emotional states. However, several challenges remain with regard to existing emotion recognition methods, including the relatively weak correlation between eye-movement features and emotional labels and the fact that the key features are not prominently presented. Methods: To address abovelimitations, this study proposes an improved CNN-transformer combined with enhanced deep canonical correlation analysis network (ICTD). The proposed method first performs preprocessing and reconstruction of raw eye-movement signals to extract informative features. Subsequently, convolutional neural networks (CNNs) and transformer architectures are employed to capture local and global feature, respectively. In addition, an incremental feature feedforward network is incorporated to enhance the transformer, enabling the model to assign higher importance to salient feature information. Finally, the extracted representations are processed through deep canonical correlation analysis based on cosine similarity in order to generate classification outcomes. Results: Experiments conducted on the SEED-IV, SEED-V, and eSEE-d datasets demonstrate that the proposed ICTD framework consistently outperforms baseline approaches and attains optimal classification results. (1) On the eSEE-d dataset, the results of three-category arousal and valence classification reach 81.8% and 85.2%, respectively; (2) on the SEED-IV dataset, the emotion four-category classification result reaches 91.2%; (3) finally, on the SEED-V dataset, the emotion five-category classification result reaches 85.1%. Conclusions: The proposed ICTD framework effectively improves feature representation and classification performance, showing strong potential for practical emotion recognition and physiological signal analysis. Full article

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

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11 pages, 2646 KB

Open AccessArticle

Assessment of Patterns of Infiltration and Relapse of Patients with Glioblastoma of the Occipital Lobe

by Michal Schulenkowski, Chun Khai Loh and Michael Back

Brain Sci. 2026, 16(3), 329; https://doi.org/10.3390/brainsci16030329 - 19 Mar 2026

Viewed by 247

Abstract

Background: Current target volume delineation protocols for glioblastoma utilise uniform or isotropic expansion around the surgical cavity and residual tumour, without considering specific sites at risk for infiltration. Tumours arising in different neuroanatomical sites may demonstrate distinct patterns of infiltration. This study aims [...] Read more.

Background: Current target volume delineation protocols for glioblastoma utilise uniform or isotropic expansion around the surgical cavity and residual tumour, without considering specific sites at risk for infiltration. Tumours arising in different neuroanatomical sites may demonstrate distinct patterns of infiltration. This study aims to review the infiltration and progression sites for the occipital lobe glioblastoma to identify sites potentially at risk. Methods: Patients with occipital lobe glioblastoma managed according to the EORTC-NCIC protocol were identified through a prospective database. Based on MRI analysis, a qualitative description of sites of tumour infiltration and subsequent progression was performed. These were categorised into neuroanatomical subsites adjacent to the occipital lobe: level 1 related to the origin gyrus; level 2 related to adjacent gyral subsites; and level 3 related to subsites that involved distant regions. Patients could be classified in more than one level where multifocal involvement was present at diagnosis or progression. Spatial patterns were assessed in relation to three major white matter tracts: inferior longitudinal fasciculus, cingulum, and corpus callosum. Results: A total of 46 patients were analysed. At diagnosis, 20 patients (43.5%) had medial occipital lobe involvement and 26 (56.5%) had lateral involvement. Level 2 and level 3 infiltration were observed in 33 (71.7%) and 27 (58.7%) patients. Progression occurred in 43 patients (93.5%), with involvement at level 1 in 28%, level 2 in 77%, and level 3 in 98%. Lateral tumours demonstrated proportionately higher progression in the trigone (75% vs. 52.6%) and anterior temporal lobe (50% vs. 15.8%, p = 0.026), while medial tumours more frequently involved the splenium (47.3% vs. 16.7%, p = 0.046). Conclusions: Infiltration and progression of occipital lobe glioblastoma may demonstrate distinct neuroanatomical patterns, with spatial distribution corresponding to major white matter tracts. Full article

(This article belongs to the Section Neuro-oncology)

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31 pages, 4919 KB

Open AccessArticle

Comparison of Resting-State EEG and Synchronization Between Young Adults with Down Syndrome and Controls in Bipolar Montage

by Jesús Pastor, Lorena Vega-Zelaya and Diego Real de Asúa

Brain Sci. 2026, 16(3), 328; https://doi.org/10.3390/brainsci16030328 - 19 Mar 2026

Viewed by 294

Abstract

The qEEG findings of subjects with Down syndrome (DS) have not been described in the context of bipolar montage. Resting-state EEG (rsEEG) with a bipolar montage was performed in 22 young adults (26.0 ± 1.2 years) with DS but without psychiatric or neurological [...] Read more.

The qEEG findings of subjects with Down syndrome (DS) have not been described in the context of bipolar montage. Resting-state EEG (rsEEG) with a bipolar montage was performed in 22 young adults (26.0 ± 1.2 years) with DS but without psychiatric or neurological pathology and matched control subjects of the same sex and age, and the results were conventionally and numerically analyzed. Channels were grouped into frontal, parieto-occipital, and temporal lobes. For every channel, the power spectrum was calculated and used to compute the area for the delta, theta, alpha and beta bands and was log-transformed. Shannon’s spectral entropy (SSE) and coherence by bands were computed. Finally, we also calculated the peak frequency distribution of the alpha band. qEEG revealed alterations in the rsEEG that were not detected visually. Subjects with DS showed a significant generalized increase in the power of the delta and theta bands, along with a decrease in the power of the alpha band in the posterior half of the scalp. This alpha activity also exhibited features corresponding to older euploid subjects, showing interhemispheric asynchrony in one-third of the individuals. The beta band power was significantly increased in the frontal lobes and adjacent regions, such as the parietal and mid-temporal regions. Individuals with DS showed a generalized decrease in parieto-occipital synchronization associated with intelligence quotient. Left temporal synchronization was also lower. The synchronization of specific channel pairs was greater in subjects with DS in the frontal lobe and much lower in the occipital and temporal regions. These results indicate that alterations in band structure and synchronization in subjects with DS are highly specific and can aid in the clinical evaluation of these individuals. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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21 pages, 5784 KB

Open AccessArticle

Activity Patterns in Relation to Dynamic Functional Network States: A Longitudinal Feasibility Study of Brain–Behavior Associations in Young Adults

by Najme Soleimani, Maria Misiura, Ali Maan, Sir-Lord Wiafe, Jennalyn Burnette, Asia Hemphill, Vonetta M. Dotson, Rebecca Ellis, Tricia Z. King, Erin B. Tone and Vince D. Calhoun

Brain Sci. 2026, 16(3), 327; https://doi.org/10.3390/brainsci16030327 - 19 Mar 2026

Viewed by 452

Abstract

Background/Objectives: Young adulthood is a critical developmental period during which lifestyle behaviors may shape intrinsic brain network dynamics that support cognition. This pilot longitudinal intervention study examined whether variability in physical activity and sedentary behavior during an 8-week exercise and/or cognitive intervention protocol [...] Read more.

Background/Objectives: Young adulthood is a critical developmental period during which lifestyle behaviors may shape intrinsic brain network dynamics that support cognition. This pilot longitudinal intervention study examined whether variability in physical activity and sedentary behavior during an 8-week exercise and/or cognitive intervention protocol was associated with changes in intrinsic brain dynamics and cognitive and mood outcomes in undergraduate young adults. Methods: Participants (n = 32) completed resting-state functional magnetic resonance imaging (rs-fMRI) at baseline (T1) and post-intervention (T2). Dynamic functional network connectivity (dFNC) was estimated from 53 intrinsic connectivity networks derived using spatially constrained independent component analysis (ICA). Ten recurring dynamic connectivity states were identified and individualized using constrained dynamic double functional independent primitives (c-ddFIPs). State occupancy and dynamic convergence and divergence metrics were computed to characterize network flexibility. Results: Greater moderate-to-vigorous physical activity was modestly but consistently associated with increased occupancy of integrative higher-order states, particularly States 6 and 7, and reduced occupancy of more segregated configurations. More physically active individuals also demonstrated greater divergence between integrative and low-engagement states, whereas greater sedentary time corresponded to increased similarity among segregated configurations. Working memory performance showed parallel associations with more integrative and better-differentiated dynamic patterns. Conclusions: These findings suggest that dynamic functional network reconfiguration may represent a neurobiological mechanism linking lifestyle behaviors and cognitive health in young adulthood. Furthermore, they highlight the translational promise of engagement-driven, low-burden programs for college-aged young adults, showing that even modest variability in habitual physical activity corresponds to greater engagement and differentiation of integrative connectivity states linked to executive and broader cognitive functions. Full article

(This article belongs to the Special Issue Modulating Brain Network Dynamics Through Training: Impacts on Perception, Cognition, and Action in Health and Disorder)

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14 pages, 245 KB

Open AccessReview

The Fate of Borderline Pathology in Dimensional Classification Systems: A Narrative Review

by Danilo Pesic, Dusica Lecic-Tosevski, Bojana Pejuskovic, Ana Munjiza-Jovanovic and Olivera Vukovic

Brain Sci. 2026, 16(3), 326; https://doi.org/10.3390/brainsci16030326 - 19 Mar 2026

Viewed by 255

Abstract

Recent revisions of personality disorder (PD) classifications have moved from categorical diagnoses toward dimensional models, raising renewed questions about the nosological status and clinical utility of borderline personality disorder (BPD). This narrative review traces the development of the borderline construct from early descriptions [...] Read more.

Recent revisions of personality disorder (PD) classifications have moved from categorical diagnoses toward dimensional models, raising renewed questions about the nosological status and clinical utility of borderline personality disorder (BPD). This narrative review traces the development of the borderline construct from early descriptions of patients positioned between neurosis and psychosis, through its theoretical consolidation within the concept of borderline personality organization, to the operationalization of BPD in DSM-III and subsequent diagnostic revisions. A central section summarizes contemporary controversies regarding the validity and utility of BPD features. Arguments for abandoning the diagnosis emphasize the absence of a distinct borderline factor in factor analytic studies, the tendency of the construct to capture fluctuating symptoms and patterns of behaviour rather than stable maladaptive personality traits, the stigmatizing and non-selective use of the label, and the lack of disorder-specific treatment approaches. In contrast, converging evidence supports the view that core borderline symptoms frequently function as markers of general PD pathology and of the severity of impairments in self and interpersonal functioning. The paper integrates the concept of the borderline level of personality functioning, conceptualizing borderline pathology as a dynamic dimension of dysfunction with potential transient regressions, and links this concept to the Level of Personality Functioning (LPF, Criterion A) within the DSM 5 Alternative Model for Personality Disorders (AMPD). Retaining borderline pathology as a dimension may support contemporary PD assessment by offering a clinically recognizable marker of overall dysfunction, a guide for rating severity, an indicator of personality structure and need for psychotherapy, without disrupting continuity with an extensive clinical and research tradition. Full article

(This article belongs to the Special Issue Advances in Borderline Personality Disorder: From Detection to Treatment)

18 pages, 1318 KB

Open AccessSystematic Review

The Use of Non-Invasive Brain Stimulation Techniques in Subjects with Parkinson’s Disease and Mild Cognitive Impairment: A Systematic Review

by Davide Mazzara, Angelo Torrente, Paolo Alonge, Giulia Gerardi, Anna Renda and Roberto Monastero

Brain Sci. 2026, 16(3), 325; https://doi.org/10.3390/brainsci16030325 - 19 Mar 2026

Viewed by 345

Abstract

Background/Objectives: Mild cognitive impairment (MCI) is common in Parkinson’s disease (PD) and significantly impacts quality of life. Non-invasive brain stimulation (NIBS) techniques have emerged as potential therapeutic interventions. This systematic review analyzes the current evidence regarding the efficacy of Transcranial magnetic stimulation (TMS) [...] Read more.

Background/Objectives: Mild cognitive impairment (MCI) is common in Parkinson’s disease (PD) and significantly impacts quality of life. Non-invasive brain stimulation (NIBS) techniques have emerged as potential therapeutic interventions. This systematic review analyzes the current evidence regarding the efficacy of Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES) on cognitive domains in patients with PD-MCI. Methods: A systematic search was conducted across the PubMed, Scopus, Web of Science, and Medline Ultimate databases up to 20 November 2025. We included studies investigating the effects of NIBS compared to sham stimulation on neuropsychological outcomes in diagnosed PD-MCI patients. Results: Eight studies involving different stimulation protocols were included. Interventions primarily used TMS or tES targeting the left dorsolateral prefrontal cortex (DLPFC). Episodic memory and global cognition were the most responsive domains, assessed with specific neuropsychological scales. Findings for executive functions and attention were heterogeneous, while visuospatial abilities generally showed limited immediate response. Conclusions: NIBS represents a promising but low-certainty-evidence adjunctive therapy for PD-MCI, with improvements found in memory and global cognition. Future research should prioritize larger sample sizes, combined interventions (NIBS plus cognitive rehabilitation), and extended follow-ups to evaluate long-term neuroplasticity. Full article

(This article belongs to the Special Issue Non-Invasive Brain Stimulation in Neurological Diseases and Neurorehabilitation)

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17 pages, 852 KB

Open AccessArticle

The Production of Clitics in Serbian Speakers with Stroke Aphasia

by Mile Vukovic and Sladjana Lukic

Brain Sci. 2026, 16(3), 324; https://doi.org/10.3390/brainsci16030324 - 19 Mar 2026

Viewed by 243

Abstract

Background/Objectives: Cross-linguistic studies show that the production of morphosyntactic elements (e.g., clitics) is problematic and often omitted in nonfluent agrammatic aphasia (NFA), with the degree of impairment varying across languages. Serbian, with its rich clitic system, provides a sensitive window into grammatical impairment. [...] Read more.

Background/Objectives: Cross-linguistic studies show that the production of morphosyntactic elements (e.g., clitics) is problematic and often omitted in nonfluent agrammatic aphasia (NFA), with the degree of impairment varying across languages. Serbian, with its rich clitic system, provides a sensitive window into grammatical impairment. This study is the first to examine the production of proclitics and enclitics in Serbian speakers with aphasia and their relationship to short-term and working memory. Methods: Forty-six individuals with stroke-induced aphasia (25 NFA and 21 fluent aphasia [FA]) and 54 healthy controls completed an experimental Serbian clitic production test. Participants were prompted to produce clitic sentences (12 proclitics, such as prepositions or conjunctions, and 18 clitics, such as pronouns or auxiliary verbs) in response to various scenarios. Performances were correlated with sentence repetition and digit span (forward/backward). Results: Both aphasia groups produced significantly fewer clitics than controls (p < 0.001). Participants with NFA produced fewer overall clitics and showed no clitic type effects (p = 0.329), whereas participants with FA produced proclitics more accurately than enclitics (p = 0.028). Clitic production correlated with performance on sentence repetition and digit span tasks, but patterns differed by aphasia group. In NFA, both enclitics and proclitics were associated with sentence repetition and digit span (p < 0.05), whereas in FA, these measures were primarily associated with enclitic production (p < 0.05). Conclusions: Clitics production distinguishes nonfluent from fluent aphasia in Serbian and is differentially supported by working and verbal memory resources. The Serbian clitic production test reveals a selective proclitic advantage that is observed only in fluent aphasia, serving as a sensitive clinical marker in this population. Full article

(This article belongs to the Section Neurolinguistics)

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16 pages, 2310 KB

Open AccessArticle

Neuro-Transcriptomic Responses to Polypharmacological Agents in Danio rerio: Implications for Translational Drug Repurposing in Neurodevelopmental Disorders

by Alexander D. Bartkowiak and Marie R. Mooney

Brain Sci. 2026, 16(3), 323; https://doi.org/10.3390/brainsci16030323 - 18 Mar 2026

Viewed by 335

Abstract

Background: Neurodevelopmental disorders span a wide spectrum of deficits, often with a known or suspected genetic basis. While some genetic determinants may indicate treatment with selective compounds, more often both the molecular cause of the disorder and the mechanism of action for [...] Read more.

Background: Neurodevelopmental disorders span a wide spectrum of deficits, often with a known or suspected genetic basis. While some genetic determinants may indicate treatment with selective compounds, more often both the molecular cause of the disorder and the mechanism of action for the therapeutic compound are more ambiguously matched. Due to the polypharmacological nature of most neuroactive compounds, measuring gene expression changes following drug perturbation could be an effective strategy to gain insight into shared therapeutic action downstream of diversity in receptor interaction. High-throughput drug discovery platforms have effectively measured changes in gene expression following drug perturbation in cell cultures, but unfortunately, these platforms often lack specificity for neuroactive compounds, fail to capture the developmental influence of cell–cell interactions, and do not accurately model drug metabolism in an intact system. Methods: In this study, we present a high-throughput, low-cost and cell-type-specific approach for capturing transcriptional changes in neural cell populations following neuroactive compound exposure through the combined use of transgenic zebrafish, cell sorting, and bulk RNA-seq. Results: Our system captures unique transcriptional profiles between neuronal and non-neuronal cell populations and demonstrates specific drug responsiveness within our neuronal cell population. We assessed two known positive allosteric modulators (PAMs) of γ-Aminobutyric acid sub-type A receptors (GABA_AR), ivermectin and propofol, as a case study to explore shared pathway and gene expression changes following drug exposure; these chemically distinct agents share a mechanistic signature that dampens the neuronal hyperexcitability characteristic of a broad spectrum of neurodevelopmental disorders. Two shared downregulated genes reflect a core expression module for modulating GABAergic tone: SRC proto-oncogene, non-receptor tyrosine kinase (SRC), and Glutamate decarboxylase 2 (GAD2). Conclusions: We provide this methodology and analysis as a framework for exploring shared changes in gene expression following neuroactive compound exposure in vivo, leading to a more complete and nuanced understanding of therapeutic effects on neurons that can aid in drug repurposing efforts for neurodevelopmental disorders. Full article

(This article belongs to the Special Issue Translational Omics in Neurodegenerative and Neurodevelopmental Disorders)

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18 pages, 1959 KB

Open AccessArticle

Predictive and Reactive Control During Interception

by Mario Treviño, Nathaly Martín, Andrea Barrera and Inmaculada Márquez

Brain Sci. 2026, 16(3), 322; https://doi.org/10.3390/brainsci16030322 - 18 Mar 2026

Viewed by 304

Abstract

Background/Objectives: Successful interception of moving targets requires combining predictive control, which anticipates future target states, and reactive control, which compensates for ongoing sensory discrepancies. How these components evolve over time and are distributed across gaze and manual behavior remains unclear. We aimed to [...] Read more.

Background/Objectives: Successful interception of moving targets requires combining predictive control, which anticipates future target states, and reactive control, which compensates for ongoing sensory discrepancies. How these components evolve over time and are distributed across gaze and manual behavior remains unclear. We aimed to explore the time-resolved dynamics of predictive control during continuous interception and to dissociate eye and hand contributions. Methods: Human participants intercepted a moving target in a two-dimensional arena using a joystick while eye movements were recorded. Target speed was systematically varied, and visual information was selectively reduced by occluding either the target or the user-controlled cursor. Predictive control was assessed using two complementary metrics: a geometric strategy index capturing moment-to-moment spatial lead or lag relative to target motion, applied separately to gaze and manual trajectories, and root mean square error (RMSE) computed relative to current and forward-shifted target positions to quantify predictive alignment. Results: Successful interception was characterized by structured, speed-dependent transitions between predictive and reactive control rather than a fixed strategy. Predictive alignment emerged early and was dynamically reweighted as temporal constraints increased. Gaze and manual behavior showed complementary but partially dissociable predictive signatures. Occluding the target decreased predictive alignment, whereas occluding the user-controlled cursor had comparatively minor effects, indicating strong reliance on internal state estimation rather than continuous visual feedback of the effector. Conclusions: Predictive and reactive control are continuously and dynamically reweighted during interception. Their interaction unfolds within single trials and depends on target dynamics and sensory availability. These findings provide quantitative evidence for time-resolved coordination between anticipatory and feedback-driven control mechanisms in goal-directed behavior. Full article

(This article belongs to the Special Issue Predictive Processing in Brain and Behavior)

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10 pages, 2287 KB

Open AccessEssay

Engineering Pareidolia: Mental Imagery, Perceptual Scaffolding, and Visual Creativity

by Alexis Demas

Brain Sci. 2026, 16(3), 321; https://doi.org/10.3390/brainsci16030321 - 17 Mar 2026

Viewed by 357

Abstract

Pareidolia is often framed as a viewer-side illusion: a tendency to perceive meaningful forms—especially faces—in ambiguous inputs. This Concept Paper argues that pareidolia can also be deliberately engineered and therefore provides a tractable entry point into the neurophysiology of visual creativity. We propose [...] Read more.

Pareidolia is often framed as a viewer-side illusion: a tendency to perceive meaningful forms—especially faces—in ambiguous inputs. This Concept Paper argues that pareidolia can also be deliberately engineered and therefore provides a tractable entry point into the neurophysiology of visual creativity. We propose a unifying construct in which engineered pareidolia functions as externally scaffolded mental imagery: minimal visual constraints recruit internally generated templates and top-down inference while remaining anchored to sensory input. To strengthen theoretical rigor, we define necessary and sufficient features that distinguish this construct from adjacent accounts (scaffolded cognition; perceptual scaffolding; bistable perception). Using Arcimboldo’s composite portraits and Dürer’s embedded face in View of the Arco Valley, plus a canonical Renaissance example (Leonardo’s Bacchus/Saint John the Baptist), we outline distinct “design regimes” that modulate cue validity, attentional release, and interpretive switching. We then connect engineered pareidolia to creativity research by linking pareidolia design and detection to measurable constructs in divergent/creative perception, including but not limited to Torrance-style domains, and we propose feasible behavioral and neurophysiological paradigms that control for artistic skill and clinical status. Finally, we distinguish benign pareidolia from hallucination, discuss clinical resonance in dementia with Lewy bodies where pareidolia can be quantified, and outline an empirically testable research program that reframes pareidolia as a bridge between imagination, perception, and creativity. Full article

(This article belongs to the Special Issue Mental Images and the Brain: From Cognitive Neuropsychology to Functional Neuroimaging)

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17 pages, 376 KB

Open AccessArticle

Cognitive Functioning in Abstinent Patients with Alcohol Use Disorder: Exploring Evidence for Premature Aging

by Jeroen Staudt, Yvonne C. M. Rensen, Hein A. De Haan, Jos I. M. Egger and Boukje A. G. Dijkstra

Brain Sci. 2026, 16(3), 320; https://doi.org/10.3390/brainsci16030320 - 17 Mar 2026

Viewed by 496

Abstract

Background/Objectives: Chronic alcohol use accelerates biological and cognitive aging, yet it remains unclear how cognitive aging progresses during abstinence in alcohol use disorder (AUD). It is also unknown to what extent this follows models such as accelerated aging or the age-related decline as [...] Read more.

Background/Objectives: Chronic alcohol use accelerates biological and cognitive aging, yet it remains unclear how cognitive aging progresses during abstinence in alcohol use disorder (AUD). It is also unknown to what extent this follows models such as accelerated aging or the age-related decline as proposed by the vulnerability hypothesis. This study examined age-related changes and cognitive recovery during abstinence in patients with AUD. Methods: A total of 197 clinically admitted patients, referred for detoxification and extensive neuropsychological examination, were included. Neuropsychological testing was administered in the second and sixth week of admission using well-normed instruments. Using both multi-assessment and cross-sectional data, relationships between age and normed cognitive outcome scores were examined. Results: After six weeks of abstinence, age-related deviations were observed for perceptual reasoning (PRI), verbal comprehension (VCI), and short-term memory (SMI) but not for ten other cognitive indices. During admission, age significantly influenced the change in belonging to a specific recovery category. Each additional year of age reduced the odds of showing no cognitive impairment by 5% and reduced the odds of cognitive recovery by approximately 4%, compared to non-improvers. Conclusions: Age-related influences appear limited to specific cognitive functions and do not follow a uniform or easily interpretable pattern. Perceptual reasoning seems negatively affected after age 60 for participants with six weeks of abstinence. Older participants showed a reduced likelihood of cognitive recovery and a reduced likelihood of having no cognitive problems at all. The findings do not support accelerated aging and are still too weak to be considered evidence for the vulnerability hypothesis. Implications for future research are discussed. Full article

(This article belongs to the Special Issue Heterogeneity in Cognitive Aging: From Healthy Aging to Neurodegenerative Disease)

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12 pages, 832 KB

Open AccessArticle

The Effect of Stress on Working Memory in Persons with Parkinson’s Disease

by Andrew Zaman, Caelia Marshall and Elizabeth L. Stegemöller

Brain Sci. 2026, 16(3), 319; https://doi.org/10.3390/brainsci16030319 - 17 Mar 2026

Viewed by 306

Abstract

Background: In addition to motor symptoms, persons with Parkinson’s disease (PD) experience several non-motor symptoms with challenges in working memory being particularly common. These cognitive challenges may worsen under stress. The purpose of this pilot study was to examine how physical stress affects [...] Read more.

Background: In addition to motor symptoms, persons with Parkinson’s disease (PD) experience several non-motor symptoms with challenges in working memory being particularly common. These cognitive challenges may worsen under stress. The purpose of this pilot study was to examine how physical stress affects working memory in persons with PD. Methods: Eight individuals with PD and 11 healthy older adults (HOAs) completed digit span forward and backward tasks following a socially evaluated cold pressor stressor and a control condition. Results: Under non-stressful conditions, persons with PD had a smaller digit span backward capacity and were slower during the digit span forward task compared to HOAs. However, during the stress condition, individuals with PD performed comparably to HOAs on the backward digit span task. Stress negatively affected response times on the backward task for both groups but did not alter capacity or response time on the forward task. Conclusions: These findings provide an initial step in understanding the effects of physical stress on working memory in PD. Since working memory supports many daily activities, understanding how stress influences this cognitive process may inform interventions that enhance stress regulation and improve cognitive and functional outcomes for individuals living with PD. Full article

(This article belongs to the Special Issue Advances in Parkinson's Disease and Movement Disorders)

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18 pages, 2976 KB

Open AccessArticle

Etiology and Risk Factors for Shunt Revision in Adult Hydrocephalus: A Single-Center Retrospective Cohort Study

by Christodoulos Komiotis, Anastasia Tasiou, Alexandros G. Brotis and Kostas N. Fountas

Brain Sci. 2026, 16(3), 318; https://doi.org/10.3390/brainsci16030318 - 17 Mar 2026

Viewed by 299

Abstract

Background/Objectives: Hydrocephalus is defined as the symptomatic accumulation of excessive cerebrospinal fluid (CSF) within the ventricular system. It has an estimated incidence of 85 cases per 100,000 population annually in adults, making it one of the most common conditions managed by neurosurgeons [...] Read more.

Background/Objectives: Hydrocephalus is defined as the symptomatic accumulation of excessive cerebrospinal fluid (CSF) within the ventricular system. It has an estimated incidence of 85 cases per 100,000 population annually in adults, making it one of the most common conditions managed by neurosurgeons globally. Many conditions may lead to ventricular dilation and hydrocephalus, such as hemorrhage, tumors, infection, trauma, and idiopathic normal-pressure hydrocephalus (iNPH). Regardless of the cause, the gold-standard treatment for hydrocephalus is CSF diversion, usually via a ventriculoperitoneal (VP) shunt. The goal of the present study is to present our experience regarding the etiology of hydrocephalus, management, and shunt failure characteristics over the last 11 years. Methods: A single-center retrospective cohort study was performed. Our cohort consisted of adult patients who were shunted or required revision surgery in our department over the last 11 years. Data regarding the etiology of hydrocephalus, management, shunt characteristics, revision status, and etiology of revision were collected and retrospectively analyzed. Univariable and multivariable logistic regression models were established in order to explore potential associations between the etiology of hydrocephalus and patient characteristics and risk of shunt revision. Revision-free survival probabilities were estimated using the Kaplan–Meier method, while shunt failure rates were also calculated. Results: Our cohort consisted of 114 patients, the median age was 59 (IQR = 26.5) years, and the male-to-female ratio was 1.04:1. The most common cause of hydrocephalus was iNPH (30.7%), followed by post-hemorrhagic (23.7%) and tumor-related hydrocephalus (21.1%). The 12-month revision rate was 13.6%, with overall revision-free survival of 86.4% at one year. Infection (43.2%) was the most common cause of shunt revision, followed by obstruction (16.2%), and mechanical disconnection and migration (18.9%). Younger age was associated with higher risk of revision, while etiology of hydrocephalus and patient sex were not. Conclusions: Our study adds to the pertinent literature data regarding hydrocephalus etiology, management strategies, and shunt failure rates across different hydrocephalus etiologies. Additionally, it serves as a foundation for future studies that could identify predictors of shunt failure, apart from the etiology of hydrocephalus, such as patient characteristics, surgical factors, or shunt types. Finally, we highlight the importance of comprehensive national and potentially continental registries, which will facilitate large-scale analyses. Full article

(This article belongs to the Section Systems Neuroscience)

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16 pages, 751 KB

Open AccessArticle

Frontal Lobe and Subregional Volumetric Alterations Across Alzheimer’s Disease, Amnestic Mild Cognitive Impairment, and Vascular Dementia: An MRI Volumetry Study

by Stefan Stojanoski, Katarina Karher, Duško Kozić, Siniša S. Babović, Miloš Vuković and Katarina Koprivšek

Brain Sci. 2026, 16(3), 317; https://doi.org/10.3390/brainsci16030317 - 16 Mar 2026

Viewed by 401

Abstract

Background: Frontal lobe involvement represents an important but heterogeneously expressed feature across neurodegenerative and vascular cognitive disorders. While frontal atrophy has been described in Alzheimer’s disease (AD), detailed volumetric assessment of frontal subregions across Alzheimer’s disease, amnestic mild cognitive impairment (aMCI), and vascular [...] Read more.

Background: Frontal lobe involvement represents an important but heterogeneously expressed feature across neurodegenerative and vascular cognitive disorders. While frontal atrophy has been described in Alzheimer’s disease (AD), detailed volumetric assessment of frontal subregions across Alzheimer’s disease, amnestic mild cognitive impairment (aMCI), and vascular dementia (VaD) remains insufficiently characterized. The aim of this study was to evaluate frontal lobe and frontal subregional volumetric alterations across these diagnostic groups using automated MRI-based volumetry. Methods: This cross-sectional study included 120 participants divided into four groups: AD, VaD, aMCI, and cognitively healthy controls (n = 30 per group). All participants underwent standardized neuropsychological assessment and 3T brain MRI. Automated volumetric analysis of the frontal lobe and its subregions was performed using the Vol2Brain pipeline. Group differences in total intracranial volume–adjusted frontal volumes were assessed using analysis of covariance, controlling for age and sex, followed by Bonferroni-corrected post hoc comparisons. False discovery rate (FDR) correction was applied across subregional comparisons. Results: A significant main effect of diagnostic group was observed for total frontal lobe volume, with lower adjusted volumes in patients with AD compared with aMCI and cognitively healthy controls. After correction for multiple comparisons, only total frontal lobe volume remained statistically significant. At the nominal level, group differences were observed in several frontal subregions, predominantly involving prefrontal and orbitofrontal areas. However, these findings did not survive FDR correction and should be interpreted as exploratory. No consistent frontal volumetric pattern was observed in VaD. Receiver operating characteristic analysis demonstrated moderate discriminatory ability of total frontal lobe volume for distinguishing AD from cognitively healthy controls. Conclusions: Automated MRI-based volumetry revealed global frontal lobe reduction in Alzheimer’s disease, whereas subregional findings were exploratory after correction for multiple testing. Frontal volumetric measures did not demonstrate a characteristic pattern in VaD. Global frontal volume may provide complementary structural information within clinically define cognitive disorders. Full article

(This article belongs to the Special Issue Using Neuroimaging to Explore Neurodegenerative Diseases)

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8 pages, 1669 KB

Open AccessCase Report

Selection of Recipient Vessels in Double-Barrel STA-MCA Bypass Surgery with the Assistance of Intraoperative ICG Fluorescence: A Case Report and Review of the Literature

by Stefanie Bauer, Timo Kahles, Michael Diepers, Gerrit A. Schubert, Lukas Andereggen and Serge Marbacher

Brain Sci. 2026, 16(3), 316; https://doi.org/10.3390/brainsci16030316 - 16 Mar 2026

Viewed by 248

Abstract

Background/Objectives: Selection of the optimal recipient artery in superficial temporal artery to middle cerebral artery (STA–MCA) extracranial–intracranial bypass surgery is essential to ensure adequate cerebral perfusion. Various pre- and intraoperative tools for target vessel selection have been proposed. Indocyanine green fluorescence video angiography [...] Read more.

Background/Objectives: Selection of the optimal recipient artery in superficial temporal artery to middle cerebral artery (STA–MCA) extracranial–intracranial bypass surgery is essential to ensure adequate cerebral perfusion. Various pre- and intraoperative tools for target vessel selection have been proposed. Indocyanine green fluorescence video angiography (ICG-VA) enables real-time visualization of cerebral hemodynamics, facilitating recipient vessel selection and anastomotic evaluation. Here, we review the literature and present the use of qualitative ICG-VA to support intraoperative decision-making during double-barrel (DB) STA–MCA bypass surgery. Case description: We report the case of a 68-year-old patient with bilateral steno-occlusive cerebrovascular disease, who developed progressive hemodynamic compromise of the left hemisphere after prior right-sided STA-MCA bypass. Preoperative imaging demonstrated impaired perfusion and posterior-to-anterior leptomeningeal collateralization from the posterior cerebral artery. During the left-sided DB bypass surgery, intravenous ICG-VA was used to assess relative cortical perfusion. Two superficial M4 branches with the most pronounced perfusion delay were selected as recipients based on the ICG-VA and anatomical criteria. Postoperative angiography confirmed graft patency. At short-term follow-up, the patient remained neurologically stable, with complete regression of preoperative symptoms. Conclusions: This case illustrates the application of qualitative ICG-VA for perfusion-oriented recipient vessel selection in DB STA-MCA bypass for steno-occlusive disease. Real-time perfusion assessment may complement conventional anatomical criteria for recipient vessel selection in flow-augmentation procedures. Further studies incorporating quantitative hemodynamic analysis are warranted. Full article

(This article belongs to the Special Issue Advances in the Diagnosis, Visualization and Treatment of Intracranial Aneurysms and Subarachnoid Hemorrhage)

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Open AccessArticle

Inducing Lucid Dreaming Based on a Contemplative Practice of Compassion

by Daniel J. Morris, Susana G. Torres-Platas, Karen R. Konkoly, John Hirschle, Lodoe Sangpo, Thabkhe, Tenzin Legden, Lobsang Pelmo, Tenzin Pasang, Marcia Grabowecky, Robin Nusslock and Ken A. Paller

Brain Sci. 2026, 16(3), 315; https://doi.org/10.3390/brainsci16030315 - 16 Mar 2026

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Abstract

Background/Objectives: Lucid dreaming—dreaming with the awareness that one is dreaming—has been explored from many perspectives, including those of cognitive neuroscience and various ancient cultural traditions. Lucid dreaming appears within the Tibetan-Buddhist literature together with dream yoga, a set of contemplative practices aimed at [...] Read more.

Background/Objectives: Lucid dreaming—dreaming with the awareness that one is dreaming—has been explored from many perspectives, including those of cognitive neuroscience and various ancient cultural traditions. Lucid dreaming appears within the Tibetan-Buddhist literature together with dream yoga, a set of contemplative practices aimed at cultivating lucidity during dreams along with other qualities such as visual imagination, somatic awareness, and cognitive flexibility. These practices include deity visualization, which is the practice of bringing to mind a detailed image of a being whose qualities the practitioner wishes to cultivate. We examined whether it is possible to induce a lucid dream of Chenrezig, the ultimate embodiment of compassion in a Tibetan-Buddhist context. Methods: Five participants slept in the sleep laboratory for 7 overnight sessions with polysomnographic recording and auditory reminders to visualize Chenrezig during REM sleep. Results: Lucid dreams were reported by two participants. A frequent lucid dreamer with no prior Tibetan-Buddhist training experienced a lucid dream that included a visualization of Chenrezig following auditory cueing during REM sleep. A monastic participant with no prior history of lucid dreaming reported their first-ever lucid dream on the night following their laboratory session. Conclusions: This exploratory study illustrates, via collaborative research including monastic scholars trained in neuroscience, that dream content can be intentionally shaped using an approach that integrates contemplative visualization practices with modern techniques of dream engineering. Full article

(This article belongs to the Special Issue Lucid Dreaming and Psychophysiological Correlates of States of Consciousness)

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Brain Sci., Volume 16, Issue 3 (March 2026) – 95 articles

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