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Brain Sciences
Volume 16
Issue 9
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Brain Sci., Volume 16, Issue 9 (September 2026) – 103 articles

Cover Story (view full-size image): Autism and the psychosis spectrum are increasingly viewed as disorders of brain circuitry, yet four decades of connectivity findings were gathered under evolving diagnostic criteria. This review returns to the cerebellum, specifically to vermal lobules VI and VII, first reported as hypoplastic in autistic disorder in 1988, as a candidate source of altered cerebral connectivity. Prenatal deviation of these lobules is proposed to alter cerebello–thalamo–cortical drive during sensitive periods, reshaping cortical integration, predictive processing, and early language and social learning. With autistic disorder as the focal case, this hypothesis is examined in relation to Joubert, fragile X, Rett, Williams and schizophrenia cohorts and framed as a testable hypothesis rather than an established mechanism. View this paper
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18 pages, 1879 KB  
Review
Beyond Biomarkers: Reclaiming the Central Role of Clinical Neurophysiology in Neuromuscular Disorders
by Marilena Mangiardi
Brain Sci. 2026, 16(9), 999; https://doi.org/10.3390/brainsci16090999 - 21 Sep 2026
Viewed by 294
Abstract
Over the past two decades, advances in molecular genetics, immunology, neuroimaging, fluid biomarkers, and artificial intelligence have substantially transformed the diagnosis, classification, and treatment of neuromuscular disorders. However, increasing biological precision has also highlighted an important distinction between identifying disease mechanisms and characterizing [...] Read more.
Over the past two decades, advances in molecular genetics, immunology, neuroimaging, fluid biomarkers, and artificial intelligence have substantially transformed the diagnosis, classification, and treatment of neuromuscular disorders. However, increasing biological precision has also highlighted an important distinction between identifying disease mechanisms and characterizing their functional expression. Clinical neurophysiology occupies a specific position within this evolving diagnostic landscape by directly assessing nervous system function and providing objective information on impulse conduction, neuromuscular transmission, motor unit integrity, physiological reserve, and disease activity. Consequently, neurophysiological assessment contributes not only to diagnosis but also to differential diagnosis, longitudinal monitoring, prognostic assessment, and therapeutic evaluation. In this critical review, I examine the factors that have progressively shifted clinical neurophysiology from an interpretative clinical discipline toward a more procedural role. Using representative examples from myasthenia gravis, immune-mediated neuropathies, myopathies, and amyotrophic lateral sclerosis, I discuss how physiological information complements molecular, serological, imaging, and other biological biomarkers. I further examine the emerging role of artificial intelligence, including its potential for automated signal analysis and quantitative assessment, as well as current limitations related to generalizability, validation, and overreliance on pattern recognition. I propose a complementary conceptual framework in which biological and molecular approaches characterize disease mechanisms, while clinical neurophysiology defines their functional expression and clinical relevance in the individual patient. Within this framework, clinical neurophysiology should not be considered an alternative to precision medicine, but an integrated physiological dimension of it, connecting biological characterization with clinically actionable functional information. Full article
(This article belongs to the Section Systems Neuroscience)
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30 pages, 1152 KB  
Review
Pediatric Mild Traumatic Brain Injury and Concussion: Modern Pathophysiological Insights, Diagnostic Advances, and Active Management Protocols
by Mirjana Raicevic and Srdjan S. Nikolovski
Brain Sci. 2026, 16(9), 998; https://doi.org/10.3390/brainsci16090998 - 21 Sep 2026
Viewed by 330
Abstract
Traumatic brain injury and pediatric concussion represent major global public health concerns. This narrative review aims to provide an updated overview of pediatric concussion by integrating current evidence regarding pathophysiology, diagnostic advances, neuroimaging, biomarkers, and evidence-based management strategies. Concussion pathophysiology involves a complex [...] Read more.
Traumatic brain injury and pediatric concussion represent major global public health concerns. This narrative review aims to provide an updated overview of pediatric concussion by integrating current evidence regarding pathophysiology, diagnostic advances, neuroimaging, biomarkers, and evidence-based management strategies. Concussion pathophysiology involves a complex neurometabolic cascade characterized by ionic imbalance, mitochondrial dysfunction, cerebral blood flow alterations, diffuse axonal injury, and neuroinflammation. In pediatric populations, unique neurodevelopmental vulnerabilities (higher head-to-torso ratio, weaker cervical musculature, ongoing myelination) magnify these disturbances. Contemporary management has evolved from prolonged rest to early active recovery, incorporating brief initial rest (24–48 h) followed by sub-symptom threshold aerobic exercise, structured return-to-learn accommodations, and stepped return-to-sport protocols. Emerging diagnostic tools include the Child SCAT6/Child SCOAT6, vestibular/ocular motor screening, and blood biomarkers (GFAP, UCH-L1, NfL). Future research should focus on standardizing pediatric biomarker thresholds and validating multimodal diagnostic algorithms through prospective multicenter studies. Full article
(This article belongs to the Section Neuropharmacology and Neuropathology)
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17 pages, 465 KB  
Article
Efficacy and Safety of Microvascular Decompression in Patients with Trigeminal Neuralgia Previously Treated with Gamma Knife Stereotactic Radiosurgery
by Sebastian Dzierzęcki, Grzegorz Turek, Michał Turek, Zenon Mariak, Wojciech Czyżewski, Jan Gajewski, Jakub Litak, Magdalena Rybaczek, Mateusz Ząbek, Aleksandra Giba, Patrycja Zabrocka and Mirosław Ząbek
Brain Sci. 2026, 16(9), 997; https://doi.org/10.3390/brainsci16090997 - 21 Sep 2026
Viewed by 338
Abstract
Background/Objectives: Gamma Knife stereotactic radiosurgery (GKS) controls classical trigeminal neuralgia (TN) in 70–90% of patients, but pain recurs in a substantial minority, and these patients are then considered for microvascular decompression (MVD). Whether radiation-induced arachnoid thickening, vessel–nerve adhesion and nerve atrophy compromise [...] Read more.
Background/Objectives: Gamma Knife stereotactic radiosurgery (GKS) controls classical trigeminal neuralgia (TN) in 70–90% of patients, but pain recurs in a substantial minority, and these patients are then considered for microvascular decompression (MVD). Whether radiation-induced arachnoid thickening, vessel–nerve adhesion and nerve atrophy compromise the safety or efficacy of subsequent MVD remains unresolved, and the available series are small. The objective of this study was to determine whether prior GKS alters the efficacy or the safety of subsequent MVD. Methods: We performed a retrospective, two-center cohort study of consecutive patients with classical TN who underwent MVD between 2015 and 2025. Of more than 1571 patients treated with GKS for TN during this period, 35 subsequently underwent MVD for insufficient pain relief (GKS+); they were compared with 60 consecutive patients who underwent primary MVD without prior radiosurgery (GKS−). The primary outcome was pain control on the Barrow Neurological Institute (BNI) scale at last follow-up, dichotomized as good (BNI I–III) or poor (BNI IV–V). Secondary outcomes were postoperative adverse events, medication-free status, intraoperative findings, intradural operative time and length of stay. Results: Good long-term pain control was achieved in 31 of 35 GKS+ patients (88.6%) and 55 of 60 GKS− patients (91.7%; p = 0.725) over a mean follow-up of 31.2 and 39.7 months, respectively. Radiation-related intraoperative changes—most often arachnoid thickening (62.9%)—were present in all GKS+ patients. Composite adverse events occurred in 31.4% of GKS+ and 36.7% of GKS− patients (p = 0.660), but the majority were trigeminal sensory disturbances (22.9% and 25.0%, respectively); non-sensory complications occurred in 3 GKS+ patients (8.6%) and 7 GKS− patients (11.7%; p = 0.741). At long-term follow-up, 48.6% of GKS+ and 60.0% of GKS− patients were medication-free (p = 0.294). There were no major neurological deficits and no surgery-related deaths in either cohort. Conclusions: Prior Gamma Knife radiosurgery did not reduce the efficacy or the safety of subsequent microvascular decompression, despite consistently more demanding intraoperative conditions. MVD remains an appropriate rescue option for persistent or recurrent trigeminal neuralgia after failed radiosurgery. Full article
(This article belongs to the Special Issue The Evolving Landscape of Trigeminal Neuralgia: From Bench to Bedside and Beyond)
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17 pages, 1959 KB  
Article
Transcutaneous Auricular Vagus Nerve Stimulation Selectively Improves Executive Control and Cognitive Flexibility Following Sustained High Cognitive Load: A Randomized, Single-Blind, Sham-Controlled Study
by Haixu Lyu, Haiyan Liu, Yifan Yang, Wanying Xing, Tingwei Feng and Xufeng Liu
Brain Sci. 2026, 16(9), 1001; https://doi.org/10.3390/brainsci16091001 - 21 Sep 2026
Viewed by 288
Abstract
Objectives: Acute exposure to sustained high cognitive load rapidly depletes executive functions, yet rapid, field-compatible countermeasures remain scarce. This study examined whether transcutaneous auricular vagus nerve stimulation (taVNS) improves cognitive functions across multiple domains—including the attention networks, cognitive flexibility, and working memory—following sustained [...] Read more.
Objectives: Acute exposure to sustained high cognitive load rapidly depletes executive functions, yet rapid, field-compatible countermeasures remain scarce. This study examined whether transcutaneous auricular vagus nerve stimulation (taVNS) improves cognitive functions across multiple domains—including the attention networks, cognitive flexibility, and working memory—following sustained high cognitive load. Methods: Healthy young men completed a 1 h dual task combining spatial 1-back and color–word Stroop judgments (the BS task) to induce a high-cognitive-load state; 65 participants were randomized to receive 30 min of active taVNS (left cymba conchae; 25 Hz; 500-μs pulse width; 30 s on/30 s off) or sham stimulation under a single-blind design, and 62 provided complete data and were analyzed. Cognitive performance was assessed with the Attention Network Test, Cued Switching Task, and spatial 2-back task immediately after the intervention and after 1, 2, 4, and 8 h; baseline-corrected change scores were analyzed with linear mixed-effects models. Results: The induction task reliably increased subjective workload and degraded task accuracy. Immediately after the intervention, taVNS significantly reduced the conflict effect relative to sham (b = −16.43 ms, 95% CI [−32.03, −0.82], F(1, 127.5) = 4.34, p = 0.039, d = 0.64) and the switch cost (b = −59.79 ms, 95% CI [−109.66, −9.92], F(1, 81.8) = 5.69, p = 0.019, d = 0.53); both immediate effects remained significant after Holm correction. Group × time interactions were nonsignificant, and the temporal course of the between-group differences should therefore be interpreted cautiously. No significant effects were observed for alerting, orienting, or working memory. Conclusions: These findings indicate that taVNS selectively and immediately improves executive control and cognitive flexibility following sustained high cognitive load, supporting its potential as a portable, rapid-acting cognitive countermeasure for high-demand operational settings. Full article
(This article belongs to the Section Behavioral Neuroscience)
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16 pages, 789 KB  
Article
Anodal Transcranial Direct Current Stimulation (TDCS) at Fp3–Fp2 Reduces the Face Inversion Effect: Evidence Against an Expectancy Account
by Ciro Civile
Brain Sci. 2026, 16(9), 1000; https://doi.org/10.3390/brainsci16091000 - 21 Sep 2026
Viewed by 247
Abstract
Background: Anodal transcranial direct current stimulation (tDCS) delivered through the Fp3–Fp2 montage reduces the face inversion effect (FIE), a result now used to argue that perceptual expertise underlies face recognition. Because beliefs about brain stimulation can change behaviour in the absence of any [...] Read more.
Background: Anodal transcranial direct current stimulation (tDCS) delivered through the Fp3–Fp2 montage reduces the face inversion effect (FIE), a result now used to argue that perceptual expertise underlies face recognition. Because beliefs about brain stimulation can change behaviour in the absence of any current, the literature rests on a premise that has never been examined: its sham condition provides a neutral baseline. The objective of this study was to test that premise, by establishing whether taking part in a tDCS study, as against no such study, changes performance in this paradigm. Methods: Participants (n = 96, 32 per group) completed an old/new recognition task with upright and inverted faces. The anodal and sham groups were run under a double-blind procedure, so that participants in both knew they might be receiving active stimulation; a third, no-tDCS group completed the identical task on the same timetable, with no electrodes applied and no mention of stimulation. Results: Anodal tDCS halved the FIE relative to both control groups (M = 0.23 vs. 0.55 and 0.56), where F(2, 93) = 9.99, p < 0.001, and ηp2 = 0.18, through impaired recognition of upright faces, where p < 0.001; sensitivity to inverted faces was unaffected, where p = 0.983. The sham and no-tDCS groups were equivalent on every measure taken, and every Bayes factor for that comparison favoured the null (BF = 0.18–0.27). Conclusions: Within the paradigm and procedure employed here, the beliefs that accompany taking part in a tDCS study did not change performance. The reduction in the FIE by anodal tDCS at Fp3–Fp2 is therefore unlikely to be an expectancy effect, and the sham control used throughout this literature study can be treated as a valid baseline. Full article
(This article belongs to the Section Neurotechnology and Neuroimaging)
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19 pages, 1769 KB  
Article
Temporal Dynamics of Ensemble Face Representations Under Magnocellular- and Parvocellular-Biased Visual Inputs: A Time-Resolved EEG Decoding Study
by Tianbo Li, Huanxiang Sun, Yi Jiang and Xiuling Zhang
Brain Sci. 2026, 16(9), 996; https://doi.org/10.3390/brainsci16090996 - 20 Sep 2026
Viewed by 288
Abstract
Background/Objectives: Ensemble perception enables the visual system to rapidly extract summary statistics from multiple objects. However, the temporal dynamics of ensemble average representations and their dependence on magnocellular-biased (M-biased) and parvocellular-biased (P-biased) visual information remain unclear. This study examined when ensemble face-gender information [...] Read more.
Background/Objectives: Ensemble perception enables the visual system to rapidly extract summary statistics from multiple objects. However, the temporal dynamics of ensemble average representations and their dependence on magnocellular-biased (M-biased) and parvocellular-biased (P-biased) visual information remain unclear. This study examined when ensemble face-gender information could be decoded under these two stimulus conditions. Methods: Twenty-four healthy adults performed a two-alternative forced-choice gender judgment task with neutral face ensembles and single faces. M-biased stimuli were low-luminance-contrast grayscale faces, whereas P-biased stimuli were isoluminant red–green faces. Time-resolved multivariate pattern analysis, temporal generalization, and cross-condition generalization characterized gender-related EEG dynamics. Results: Behaviorally, responses were faster for P-biased than M-biased stimuli and for single faces than ensembles, with no significant accuracy differences. Balanced Integration Scores were significantly higher for P-biased than M-biased stimuli in both ensemble and single-face conditions. M-biased ensemble gender information was reliably decodable during early (95–300 ms) and late processing (775–930 ms), with significant early temporal generalization. P-biased face ensembles showed no significant cluster-corrected time-resolved decoding but exhibited significant temporal generalization during middle-to-late processing. Under M-biased stimulation, ensemble gender information generalized to single-face judgments from 690–995 ms. Conclusions: Ensemble face-gender information showed a multistage temporal organization. M-biased ensemble information became decodable early. Late cross-condition generalization further indicated that ensemble and single-face judgments shared gender-discriminative task information. These findings characterize the temporal evolution of ensemble gender information under pathway-biased visual stimulation and provide a temporal perspective on ensemble perception. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
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38 pages, 4796 KB  
Review
Sexual Dysregulation After Traumatic Brain Injury and Stroke: A Critical Narrative Review of Neurobiology, Clinical Phenotypes, and Management
by Rocco Salvatore Calabrò, Rosaria De Luca, Riccardo Raul Ruberto, Andrea Calderone, Demetrio Milardi and Francesco Tomaiuolo
Brain Sci. 2026, 16(9), 995; https://doi.org/10.3390/brainsci16090995 - 19 Sep 2026
Viewed by 354
Abstract
Background/Objectives: Acquired brain injury (ABI) can disturb sexual regulation, but the literature does not support a single lesion-to-behavior relationship. This critical narrative review evaluates hypersexuality, sexual disinhibition, and rare acquired paraphilic manifestations after traumatic brain injury (TBI) and stroke, and asks how sparse, [...] Read more.
Background/Objectives: Acquired brain injury (ABI) can disturb sexual regulation, but the literature does not support a single lesion-to-behavior relationship. This critical narrative review evaluates hypersexuality, sexual disinhibition, and rare acquired paraphilic manifestations after traumatic brain injury (TBI) and stroke, and asks how sparse, heterogeneous evidence can inform proportionate clinical care. Methods: PubMed/MEDLINE, Scopus, and Web of Science were searched up to 6 August 2026. Two reviewers independently screened records and full texts. Evidence appraisal considered methodological quality, directness, and competing explanations. Thirteen English-language case-based publications were assessed, with neurological observations distinguished from pharmacological comparators. Results: Sexual dysfunction is common after ABI, whereas dysregulated sexual behavior is less frequent and poorly quantified. TBI primarily supports a distributed vulnerability model involving diffuse axonal injury and disruption of frontal regulatory connections. Stroke can nominate strategic candidate nodes, but lesion-network effects and clinical context remain decisive. Clinical observations associate inappropriate sexual behavior with broader behavioral difficulties, without establishing a uniform syndrome. Recent guidelines support individualized sexuality care, while contemporary imaging studies strengthen network plausibility without directly establishing sexual-dysregulation mechanisms. Conclusions: A phenotype-first framework separates dysfunction from dysregulation and distinguishes direct clinical evidence from mechanistic extrapolation. Assessment should establish what changed and whether reversible contributors explain the behavior before assigning a persistent phenotype. Management should match the dominant clinical problem, preserve consensual intimacy, and use the least restrictive targeted strategy. Explicit monitoring should determine whether benefit justifies continued treatment. Case-based evidence and language-restricted selection limit generalizability; prospective studies require standardized phenotypes and repeated observation across settings. Full article
(This article belongs to the Special Issue Sexual Behaviours and Mental Health)
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33 pages, 3284 KB  
Systematic Review
Nonconvulsive and Electrographic Status Epilepticus in Comatose Adult Survivors of Cardiac Arrest: A Systematic Review and Meta-Analysis of Prevalence, EEG-Based Diagnosis, Treatment, and Neurological Outcomes
by Vivek Gupta and Viswanath Vasudevan
Brain Sci. 2026, 16(9), 994; https://doi.org/10.3390/brainsci16090994 - 19 Sep 2026
Viewed by 285
Abstract
Objectives: This systematic review and meta-analysis aimed to estimate the prevalence of nonconvulsive status epilepticus (NCSE), electrographic status epilepticus (ESE), post-anoxic status epilepticus (PSE), and electrographic seizures in comatose adult survivors of cardiac arrest and to summarize associated diagnostic approaches, treatment strategies, [...] Read more.
Objectives: This systematic review and meta-analysis aimed to estimate the prevalence of nonconvulsive status epilepticus (NCSE), electrographic status epilepticus (ESE), post-anoxic status epilepticus (PSE), and electrographic seizures in comatose adult survivors of cardiac arrest and to summarize associated diagnostic approaches, treatment strategies, neurological outcomes, and mortality. Methods: PubMed/MEDLINE, MEDLINE Core, Cochrane CENTRAL, Web of Science, and Scopus were searched from inception to May 2026. Eligible studies included adult comatose survivors of cardiac arrest who underwent EEG monitoring and reported NCSE, ESE, PSE, electrographic seizures, or related rhythmic/periodic EEG patterns. Random-effects meta-analysis of proportions was performed, separating strict NCSE/ESE/PSE constructs from broader electrographic seizure/status and epileptiform/IIC constructs. Results: Seventeen studies were included. In the primary analysis of four non-overlapping EEG-monitored cohorts, strict NCSE/ESE/PSE occurred in 112 of 457 patients; the pooled prevalence was 22% (95% CI, 10–41%; 95% prediction interval, 4–64%; I2 = 77.8%). The expanded sensitivity analysis including selected, historical, or restricted cohorts yielded a similar pooled prevalence of 22% (95% CI, 16–31%). Broad electrographic seizure/status prevalence was 10% (95% CI, 2–33%; I2 = 94.7%), and broad epileptiform/ictal–interictal continuum pattern prevalence was 29% (95% CI, 7–70%; I2 = 86.0%); these analyses represented distinct EEG constructs. Poor neurological outcome and mortality were frequent, with pooled estimates of 91% (95% CI, 85–94%) and 87% (95% CI, 78–93%), respectively. Conclusions: The pooled prevalence of NCSE/ESE/PSE was 22% among EEG-monitored comatose survivors of cardiac arrest, although the exact prevalence remains uncertain across settings. Poor neurological outcome and mortality were frequent, but recovery occurred in selected patients with continuous EEG background, later SE onset, fewer multimodal poor-outcome markers, or electrographic cessation. These findings support multimodal, phenotype-guided interpretation rather than reliance on EEG status alone. Future studies should use standardized EEG definitions, consistent denominators, and phenotype-enriched randomized designs. Full article
(This article belongs to the Section Neurotechnology and Neuroimaging)
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53 pages, 2723 KB  
Systematic Review
Psychosocial Interventions, Recovery, and Mediating Mechanisms in Schizophrenia-Spectrum Disorders: A Systematic Review and Meta-Analysis of Longitudinal Studies
by Evgenia Gkintoni, Ignatia Farmakopoulou, Maria Theodoratou and Maria Panagioti
Brain Sci. 2026, 16(9), 993; https://doi.org/10.3390/brainsci16090993 - 19 Sep 2026
Viewed by 384
Abstract
Background/Objectives: Recovery from schizophrenia-spectrum disorders is increasingly recognized as achievable, yet no synthesis has simultaneously examined long-term outcome rates, intervention effectiveness, cognitive predictors, social determinants, personal-recovery trajectories, and mediating mechanisms within a unified framework. This systematic review aimed to address these six [...] Read more.
Background/Objectives: Recovery from schizophrenia-spectrum disorders is increasingly recognized as achievable, yet no synthesis has simultaneously examined long-term outcome rates, intervention effectiveness, cognitive predictors, social determinants, personal-recovery trajectories, and mediating mechanisms within a unified framework. This systematic review aimed to address these six domains and to propose an integrative theoretical model of functional recovery, applying meta-analysis where the evidence permitted and structured narrative synthesis elsewhere. Methods: Seven databases (PubMed/MEDLINE, PsycINFO, Embase, Cochrane CENTRAL, Web of Science, Scopus, CINAHL) were searched through December 2025 following PRISMA 2020 and MOOSE guidance. We extracted eligible records (longitudinal designs, ≥6 months, adults with schizophrenia-spectrum disorders reporting functional outcomes) into two structured databases, then consolidated and de-duplicated them, yielding 467 unique papers. After topical screening and a duplicate audit, we retained 368 studies (1980–2025) and grouped them into six thematic clusters. A pre-specified rule pooled only clusters with at least five independent primary studies. Proportions were pooled with the Freeman–Tukey transformation and associations with Fisher’s z under DerSimonian–Laird random-effects models; certainty was appraised with GRADE. Results: Three pools met the threshold. Long-term functional recovery was 35.4% (95% CI 22.6–49.4; k = 11) and symptomatic remission 39.6% (95% CI 29.3–50.5; k = 7), both with very high heterogeneity (I2 = 92–98%) and low certainty. The pooled association between psychological mediators and functional outcome was weak and imprecise (r = 0.23; 95% CI −0.09–0.51; k = 7; very low certainty), reflecting facilitators (positive mental health, social support, self-efficacy, hope) and barriers (internalized stigma, substance-use comorbidity, longer duration of untreated psychosis, persistent negative symptoms) acting in opposite directions. The questions concerning specific interventions, cognitive prediction, rehabilitation, and personal recovery were synthesized narratively: structured psychosocial and combined interventions and integrated rehabilitation were associated with small-to-medium functional gains; cognition, particularly social cognition and motivation, predicted later functioning; and personal recovery followed a course partly independent of clinical status. Conclusions: Recovery and remission are attainable for a substantial minority but remain heterogeneous and modestly certain. The proposed Multi-Pathway Dynamic Recovery Model organizes the evidence into five testable principles—an ordered recovery hierarchy, social-cognitive mediation of the cognition–function link, an early-phase intervention window, social-ecological embedding, and self-reinforcing feedback loops, offered as a hypothesis-generating framework rather than a validated structure. Services should prioritize comprehensive early intervention, target social cognition and stigma, and address structural determinants to optimize long-term recovery. Full article
(This article belongs to the Special Issue Long-Term Course and Outcomes of Schizophrenia and Other Psychotic Disorders)
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9 pages, 219 KB  
Brief Report
Perception of Vowel Segments by Children and Adults: A Preliminary Study of Segment Duration
by Mark Hedrick, Kelly Yeager and Cary Springer
Brain Sci. 2026, 16(9), 992; https://doi.org/10.3390/brainsci16090992 - 19 Sep 2026
Viewed by 231
Abstract
Background/Objectives: Children’s perception of phonemes differs from that of adults. Our purpose was to examine whether children’s perception of vowels differs from that of adults because of differential emphasis on vowel segments (steady-state or transition), degree of coarticulation, or amount of information [...] Read more.
Background/Objectives: Children’s perception of phonemes differs from that of adults. Our purpose was to examine whether children’s perception of vowels differs from that of adults because of differential emphasis on vowel segments (steady-state or transition), degree of coarticulation, or amount of information to make a perceptual judgment of the vowel. Methods: A, between-group cross-sectional design was employed. Twenty-four children aged four to nine years and 17 adults (aged 18 to 53) participated. Stimuli were three naturally produced syllables (/bɑ/, /bi/ and /bu/), presented in the sound field in entirety or segmented to isolate the formant transition or the vowel static formant center. Participants selected the vowel presented by choosing from corresponding pictures on a computer screen. Results: The data from children showed consistently less accuracy for vowel identification than adults for whole syllable and all segments except full transitions. Conclusions: Children were more attuned to acoustic change or contrast to enable vowel perception than adults, yet needed more extensive change before reaching adult performance. Full article
(This article belongs to the Section Behavioral Neuroscience)
19 pages, 1574 KB  
Review
Dynamic Contrast-Enhanced MRI in Neuro-Oncology: A Narrative and Translational Review
by Francesca Bozzetti, Ana Ramos-González, Alessandro Leonetti, Chiara Tommasi, Marcello Tiseo, Francesco Salaroli, Giovanni Ceccon, Ilaria Renna, Marco Galaverni, Nicola Sverzellati and Daniele Corbo
Brain Sci. 2026, 16(9), 991; https://doi.org/10.3390/brainsci16090991 - 19 Sep 2026
Viewed by 395
Abstract
Background/Objectives: Dynamic contrast-enhanced MRI (DCE-MRI) is emerging as a key technique in neuro-oncologic imaging by enabling quantitative assessment of vascular permeability and blood–brain barrier integrity, two central features of tumor progression and treatment-related tissue injury. Its clinical relevance is particularly evident in the [...] Read more.
Background/Objectives: Dynamic contrast-enhanced MRI (DCE-MRI) is emerging as a key technique in neuro-oncologic imaging by enabling quantitative assessment of vascular permeability and blood–brain barrier integrity, two central features of tumor progression and treatment-related tissue injury. Its clinical relevance is particularly evident in the post-treatment setting, where conventional MRI lacks specificity and entities such as tumor progression, pseudoprogression, and radiation necrosis frequently overlap. Methods: This narrative review focuses on the role of DCE-MRI in differentiating treatment-related alterations from true tumor progression, primarily in gliomas and, secondarily, in brain metastases and primary CNS lymphoma. Results: We review quantitative and semiquantitative parameters, their biological interpretation, and their diagnostic performance in gliomas, metastases, and primary CNS lymphoma. We further discuss the role of DCE-MRI within multiparametric imaging workflows and highlight emerging contributions from artificial intelligence, radiomics, and automated pharmacokinetic modeling. Conclusion: As a narrative, translational review, this work aims to contextualize DCE-MRI within contemporary neuro-oncologic practice and research. Its clinical translation, however, remains limited by methodological heterogeneity and the lack of standardized acquisition and analysis protocols, highlighting the need for harmonization and prospective multicenter validation. Full article
(This article belongs to the Section Neuro-oncology)
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26 pages, 643 KB  
Article
When Alexithymia Matters: Distinct Schema–Emotion Processing Profiles of Narcissistic Admiration and Rivalry
by Dawid Konrad Ścigała, Matteo Angelo Fabris and Elżbieta Zdankiewicz-Ścigała
Brain Sci. 2026, 16(9), 990; https://doi.org/10.3390/brainsci16090990 - 18 Sep 2026
Viewed by 365
Abstract
Background/Objectives: Alexithymia may constrain emotion regulation, but its relevance may differ across personality configurations. This study examined whether narcissistic Admiration and Rivalry are embedded in distinct early maladaptive schema and alexithymia profiles. Methods: A non-clinical adult sample (N = 311) completed the Narcissistic [...] Read more.
Background/Objectives: Alexithymia may constrain emotion regulation, but its relevance may differ across personality configurations. This study examined whether narcissistic Admiration and Rivalry are embedded in distinct early maladaptive schema and alexithymia profiles. Methods: A non-clinical adult sample (N = 311) completed the Narcissistic Admiration and Rivalry Questionnaire, the Young Schema Questionnaire–Short Form 3, and the Toronto Alexithymia Scale–20. Analyses examined 18 schemas and three alexithymia components—Difficulty Identifying Feelings (DIF), Difficulty Describing Feelings (DDF), and Externally Oriented Thinking (EOT)—using zero-order correlations, within-domain regressions, hierarchical regressions, and structural equation models. Results: Admiration was associated mainly with Approval/Recognition Seeking and Unrelenting Standards and with lower Social Isolation/Alienation, Defectiveness/Shame, Failure, Subjugation, Emotional Inhibition, and Insufficient Self-Control. Rivalry showed a threat-related profile involving Defectiveness/Shame, Subjugation, Emotional Inhibition, Negativity/Pessimism, and Insufficient Self-Control. Entitlement/Grandiosity was positively associated with both dimensions and did not reliably differentiate them. Alexithymia was essentially unrelated to Admiration and did not improve its schema model. In contrast, adding DIF, DDF, and EOT increased explained variance in Rivalry by 5.5%, a small-to-moderate increment; DIF and EOT made independent contributions, whereas DDF did not. A parsimonious Rivalry structural model reproduced these associations but showed mixed global fit. Conclusions: These cross-sectional findings indicate a modest, dimension-specific contribution of alexithymic processing to Rivalry rather than a general association with narcissistic self-regulation. The EOT findings require particular caution because of the subscale’s limited reliability. Longitudinal and experimental studies are needed to test the proposed vulnerability–stress process. Full article
(This article belongs to the Special Issue New Insights on Emotion Regulation)
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17 pages, 633 KB  
Article
Walkbot-Based Robot-Assisted Gait Training and Phase-Specific Lower-Limb Torque in Parkinson’s Disease: A Retrospective Comparative Study
by Gokhan Ozkocak and Rocco Salvatore Calabrò
Brain Sci. 2026, 16(9), 989; https://doi.org/10.3390/brainsci16090989 - 18 Sep 2026
Viewed by 229
Abstract
Gait impairment, postural instability, and freezing of gait are major contributors to mobility limitations in Parkinson’s disease (PD). Robot-assisted gait training (RAGT) has emerged as a promising rehabilitation strategy; however, its association with phase-specific lower-limb kinetic outcomes remains insufficiently characterized. This study compared [...] Read more.
Gait impairment, postural instability, and freezing of gait are major contributors to mobility limitations in Parkinson’s disease (PD). Robot-assisted gait training (RAGT) has emerged as a promising rehabilitation strategy; however, its association with phase-specific lower-limb kinetic outcomes remains insufficiently characterized. This study compared Walkbot-based RAGT and conventional rehabilitation in terms of Walkbot-derived phase-specific lower-limb torque, functional balance, self-reported freezing-related gait impairment, and health-related quality of life in individuals with PD. This retrospective comparative study included 60 individuals with idiopathic PD (Hoehn and Yahr stages II–III) who received either Walkbot-based RAGT (n = 30) or conventional rehabilitation (n = 30). Both groups completed 30 supervised sessions over 6 weeks. Biomechanical outcomes comprised Walkbot-derived lower-limb torque during the stance and swing phases for the clinically more affected and contralateral limbs. Clinical outcomes included the Berg Balance Scale (BBS), Freezing of Gait Questionnaire (FOG-Q), and Parkinson’s Disease Questionnaire-39 (PDQ-39). Between-group post-treatment differences were evaluated using analysis of covariance (ANCOVA), adjusting each outcome for its corresponding baseline value. After baseline adjustment, post-treatment phase-specific lower-limb torque was higher in the RAGT group for the more affected limb during swing (adjusted difference, 0.057 Nm/kg; 95% CI, 0.019–0.096; p = 0.004) and stance (0.145 Nm/kg; 95% CI, 0.098–0.193; p < 0.001), and for the contralateral limb during swing (0.051 Nm/kg; 95% CI, 0.006–0.096; p = 0.027) and stance (0.205 Nm/kg; 95% CI, 0.088–0.321; p = 0.001). The RAGT group also had higher baseline-adjusted BBS scores (adjusted difference, 5.78 points; 95% CI, 3.86–7.69; p < 0.001) and lower FOG-Q scores (−0.94 points; 95% CI, −1.27 to −0.61; p < 0.001). No significant between-group difference was observed for PDQ-39 (0.77 points; 95% CI, −0.16 to 1.69; p = 0.102). Walkbot-based RAGT was associated with more favorable baseline-adjusted phase-specific lower-limb torque, functional balance, and self-reported freezing-related gait impairment than conventional rehabilitation, whereas disease-specific quality of life did not differ significantly between groups. These findings highlight the potential value of integrating Walkbot-derived phase-specific kinetic assessment with clinical outcomes to provide a more quantitative characterization of rehabilitation-related locomotor changes in PD. Prospective randomized studies are needed to confirm these associations and establish the clinical utility of Walkbot-derived phase-specific lower-limb torque as an outcome measure. Full article
(This article belongs to the Section Neurodegenerative Diseases)
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20 pages, 4486 KB  
Article
Application of Shear Wave Elastography in Assessing Peripheral Neuropathy in Parkinson’s Disease
by Yifan Song, Shuai Zheng, Lijuan Du, Hongxia Zhang, Wei Zhang and Wen He
Brain Sci. 2026, 16(9), 988; https://doi.org/10.3390/brainsci16090988 - 17 Sep 2026
Viewed by 274
Abstract
Background/Objectives: Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, and its comorbid peripheral neuropathy (PN) severely worsens patient prognosis. The diagnostic gold standard, nerve electrophysiological examination, has critical limitations, including invasiveness. This study aimed to explore the diagnostic value of high-frequency ultrasound combined [...] Read more.
Background/Objectives: Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, and its comorbid peripheral neuropathy (PN) severely worsens patient prognosis. The diagnostic gold standard, nerve electrophysiological examination, has critical limitations, including invasiveness. This study aimed to explore the diagnostic value of high-frequency ultrasound combined with shear wave elastography (SWE) for PD-associated PN. Methods: Intra- and inter-observer reproducibility of ultrasound parameters (cross-sectional area [CSA], shear wave velocity [SWV]) of the median and common peroneal nerves was validated in 30 PD patients. A case–control study was conducted in 40 PD patients (stratified into PD-alone and PD-PN groups via the electrophysiological gold standard) and 40 healthy controls. Correlation analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis were performed to assess diagnostic efficacy. Results: All measured parameters showed good reproducibility (intraclass correlation coefficient [ICC] > 0.855). Median nerve longitudinal SWV and common peroneal nerve SWV increased sequentially across the control, PD-alone, and PD-PN groups (after age adjustment using analysis of covariance (ANCOVA), p < 0.001), and showed weak-to-moderate statistically significant correlations with median nerve motor conduction latencies after Bonferroni correction for multiple comparisons. Age and common peroneal nerve SWV were identified as independent risk factors for PD-PN, while median nerve longitudinal SWV showed a positive but non-significant association in the multivariable model. A combined model incorporating age, median nerve longitudinal SWV, and common peroneal nerve SWV achieved an area under the ROC curve (AUC) of 0.938 (sensitivity 93.75%, specificity 91.67%; bootstrap-corrected AUC = 0.906). Conclusions: SWE-derived SWV has favorable diagnostic value for PD-associated PN with good reproducibility. The combination of age and multi-nerve SWV further improves diagnostic efficiency, providing a reliable non-invasive imaging biomarker for early PD-PN diagnosis. However, given the observational design and significant age imbalance between groups, residual confounding cannot be fully excluded, and prospective studies with age-matched cohorts are needed for definitive confirmation. Full article
(This article belongs to the Special Issue Clinical Research on Parkinson’s Disease: Opportunities and Challenges (2nd Edition))
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60 pages, 1621 KB  
Review
When Development Falls out of Sync: A Developmental Timing Framework for Learning Disabilities
by Gerry Leisman
Brain Sci. 2026, 16(9), 987; https://doi.org/10.3390/brainsci16090987 - 17 Sep 2026
Viewed by 422
Abstract
Learning disabilities are traditionally conceptualized as domain-specific disorders arising from deficits in reading, attention, or numerical processing. Although these approaches have substantially advanced understanding of dyslexia, attention-deficit/hyperactivity disorder (ADHD), and dyscalculia, they do not fully explain the marked heterogeneity, developmental variability, frequent comorbidity, [...] Read more.
Learning disabilities are traditionally conceptualized as domain-specific disorders arising from deficits in reading, attention, or numerical processing. Although these approaches have substantially advanced understanding of dyslexia, attention-deficit/hyperactivity disorder (ADHD), and dyscalculia, they do not fully explain the marked heterogeneity, developmental variability, frequent comorbidity, or changing learning trajectories observed across children. This conceptual review proposes a developmental timing framework in which learning disabilities emerge, in many cases, from maturational asynchrony among interacting neural, cognitive, linguistic, sensorimotor, and executive systems rather than from isolated deficits within a single domain. Drawing on evidence from developmental neuroscience, cognitive psychology, neuroeducation, developmental systems theory, and learning sciences, we synthesize research on the developmental coordination of language, executive function, attention, motor control, working memory, symbolic learning, and numerical cognition across childhood. Within this framework, dyslexia, ADHD-related learning difficulties, dyscalculia, and mixed learning profiles are interpreted as distinct developmental expressions of differing patterns of cross-system asynchrony interacting with the increasing cognitive demands of formal education. We distinguish maturational asynchrony from related concepts, including developmental variability, developmental cascades, and multiple-deficit models, and propose measurable indicators through which the framework may be empirically evaluated. The framework further generates testable predictions concerning longitudinal developmental trajectories, educational transitions, developmental fit, and timing-sensitive intervention. Rather than replacing established cognitive accounts of learning disabilities, the developmental timing framework provides an integrative developmental architecture within which existing theories can be understood while offering a basis for future longitudinal and intervention research. This perspective highlights the importance of aligning educational expectations and instructional practices with children’s evolving neurodevelopmental readiness rather than chronological age alone. Full article
(This article belongs to the Special Issue Neuroeducation: Bridging Cognitive Science and Classroom Practice)
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20 pages, 7102 KB  
Article
Quantitative Navigated Transcranial Magnetic Stimulation Motor Mapping and nTMS-Guided Corticospinal Tractography in Healthy Individuals and Patients with Motor-Eloquent Brain Tumors
by Evangelia Chatzikyriakou, Ioannis Vlachos, Konstantinos Pastiadis, Nikolaos Foroglou, Konstantinos Kouskouras, Georgios Feretos, Christos Frantzidis, Ioannis Patsalas, Vasileios Papaliagkas, Dimitris Kugiumtzis and Vasilios K. Kimiskidis
Brain Sci. 2026, 16(9), 986; https://doi.org/10.3390/brainsci16090986 - 17 Sep 2026
Viewed by 305
Abstract
Background/Objectives: Navigated transcranial magnetic stimulation (nTMS) enables presurgical motor mapping, while nTMS-seeded diffusion tensor imaging (DTI) delineates the corticospinal tract (CST). We compared cortical and tractography measures between healthy individuals and patients with motor-eloquent brain tumors and between patient hemispheres. Methods: Twenty healthy [...] Read more.
Background/Objectives: Navigated transcranial magnetic stimulation (nTMS) enables presurgical motor mapping, while nTMS-seeded diffusion tensor imaging (DTI) delineates the corticospinal tract (CST). We compared cortical and tractography measures between healthy individuals and patients with motor-eloquent brain tumors and between patient hemispheres. Methods: Twenty healthy volunteers and 18 patients underwent first dorsal interosseous (FDI) mapping at 110% resting motor threshold (rMT). Motor map metrics, maximum FDI motor-evoked potential (MEP) amplitude, and nTMS-seeded CST measures were analyzed; hotspot and center-of-gravity (CoG) dispersion were assessed in common space. DTI metrics were available for 13 healthy volunteers and 13 patients. Results: Consistent with previous nTMS literature, patients showed impaired motor performance and suprathreshold corticospinal output, with lower grip strength, maximum FDI MEP amplitude, and map volume than controls. rMT did not differ significantly, indicating that threshold excitability may be unrevealing despite motor system dysfunction. Notably, the contralateral patient hemisphere also differed from controls in grip strength, maximum FDI MEP amplitude, reconstructed CST fiber length, and mean axial diffusivity, while these measures did not differ significantly between the ipsilateral and contralateral patient hemispheres. CoG dispersion was greater in patients, whereas hotspot dispersion was not. Conclusions: The study confirms tumor-associated impairment of motor performance and suprathreshold corticospinal output while identifying two potentially novel observations: abnormalities extending to the apparently unaffected hemisphere and increased heterogeneity of the amplitude-weighted motor map center. Notably, contralateral abnormalities may reflect bilateral network changes or patient-related factors, rather than isolated contralateral CST pathology. Independent healthy controls may therefore provide information not captured by within-patient hemispheric comparisons. Full article
(This article belongs to the Special Issue Noninvasive Neuromodulation Applications in Research and Clinics—2nd Edition)
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25 pages, 505 KB  
Hypothesis
Focal Task-Specific Dystonia Beyond M1: Network Adaptations and a Causal-Architecture Taxonomy of Dystonia
by Norman Lu and Rodrigo F. O. Pena
Brain Sci. 2026, 16(9), 985; https://doi.org/10.3390/brainsci16090985 - 17 Sep 2026
Viewed by 561
Abstract
Focal task-specific dystonia (FTSD) is associated with abnormalities across primary motor cortex (M1), basal ganglia, cerebellum, primary somatosensory cortex (S1), and spinal circuits, but their causal ordering is unresolved. Starting from the companion M1-centered framework, we ask whether repeated expression of a task-specific [...] Read more.
Focal task-specific dystonia (FTSD) is associated with abnormalities across primary motor cortex (M1), basal ganglia, cerebellum, primary somatosensory cortex (S1), and spinal circuits, but their causal ordering is unresolved. Starting from the companion M1-centered framework, we ask whether repeated expression of a task-specific motor synergy (TSMS) with a proposed M1 excitation–inhibition imbalance could produce task-linked adaptations elsewhere in the motor system. We propose candidate mechanisms linking abnormal M1 output to reweighting of striatal dopamine signaling and direct- and indirect-pathway function, recalibration of cerebellar teaching and corrective output, reduced functional separability of S1 sensory populations, and use-dependent weakening of spinal reciprocal inhibition. Reported FTSD findings serve as empirical constraints; these intermediate cellular and circuit links remain hypotheses rather than established causal sequences. Extra-M1 changes could later reinforce or help maintain the dystonic state, compensate for it, or interact bidirectionally with the cortical abnormality. The M1-primary claim concerns causal initiation rather than anatomical exclusivity and predicts that task-specific abnormalities of M1 recruitment and rapid inhibitory control should precede or closely track the proposed extra-M1 adaptations. We also propose a provisional causal-architecture taxonomy distinguishing typical neuroplastic, atypical neuroplastic, and non-neuroplastic dystonias by the process hypothesized to dominate symptom generation and persistence. The TSMS framework, including the symptom-threshold, overreaching sequence, a proposed state of task-specific output limitation termed true weakness, and below- or at-threshold retraining (BATR), is advanced for FTSD rather than assumed to generalize unchanged across dystonias. Longitudinal, intervention-based, and experimental-model tests are outlined to distinguish the proposed sequence from basal ganglia-primary, cerebellar-primary, sensory-primary, concurrent, and distributed alternatives and to test whether retraining-related improvement follows the predicted physiological route. Full article
(This article belongs to the Special Issue Brain Plasticity and Motor Control—3rd Edition)
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24 pages, 645 KB  
Article
From Clipping to Coiling and Beyond: Mapping the Evolution and Future Directions of Intracranial Aneurysm Research
by Jure Pešak and Andrej Kastrin
Brain Sci. 2026, 16(9), 984; https://doi.org/10.3390/brainsci16090984 - 16 Sep 2026
Viewed by 362
Abstract
Background/Objectives: Intracranial aneurysm (IA) management has evolved from surgical treatment of ruptured lesions into a multidisciplinary field integrating diagnostics, neurocritical care, endovascular techniques, and individualized risk assessment. As the literature has grown beyond the scope of traditional narrative synthesis, bibliometric methods are [...] Read more.
Background/Objectives: Intracranial aneurysm (IA) management has evolved from surgical treatment of ruptured lesions into a multidisciplinary field integrating diagnostics, neurocritical care, endovascular techniques, and individualized risk assessment. As the literature has grown beyond the scope of traditional narrative synthesis, bibliometric methods are needed to characterize the field’s development. We used co-word analysis to map the conceptual structure and thematic evolution of IA research over nearly eight decades. Methods: We analyzed 22,061 publications indexed in PubMed between 1946 and 2023. Co-word analysis of Medical Subject Headings tracked thematic development across six subperiods grouped into eras. Within each thematic network, topics were classified by centrality and density as motor, niche (highly developed but isolated), emerging or declining, or basic themes. Results: Four historical eras were delineated as an interpretative synthesis of the six subperiods. The open-surgery era (1946–1980) centered on ruptured aneurysms and refinement of operative techniques. The transitional era (1981–1990) was marked by proactive vasospasm management and emerging neurocritical care. The endovascular era (1991–2010) reflected the rise of evidence-based medicine and endovascular therapy. The multidisciplinary era (2011–2023) shifted toward unruptured aneurysms, molecular research, biomechanics, and individualized risk stratification. Recent themes, including hemodynamics, flow diversion, and precision medicine, reflect a growing research emphasis on predictive and personalized approaches to aneurysm management. Conclusions: IA research has evolved from descriptive, technique-oriented studies toward a data-driven landscape increasingly focused on predictive assessment and management of unruptured lesions. Its thematic evolution highlights the growing prominence of molecular and computational approaches, although their clinical and translational impact cannot be directly inferred from the present analysis. Full article
(This article belongs to the Special Issue Advances in Intracranial Aneurysms)
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46 pages, 55677 KB  
Hypothesis
RIFT: A Fractal-Holographic Theory of Consciousness and Autopoietic Control
by Erhard Bieberich
Brain Sci. 2026, 16(9), 983; https://doi.org/10.3390/brainsci16090983 - 16 Sep 2026
Viewed by 603
Abstract
Background/Objectives: Consciousness remains poorly understood as a causative force. Existing theories describe neural correlates or information processing but do not explain how a unified inner experiential space is physically generated or acts back upon its substrate. Recurrent Integration Fractal Theory (RIFT) proposes a [...] Read more.
Background/Objectives: Consciousness remains poorly understood as a causative force. Existing theories describe neural correlates or information processing but do not explain how a unified inner experiential space is physically generated or acts back upon its substrate. Recurrent Integration Fractal Theory (RIFT) proposes a three-step mechanism that reconstructs the spatial relationships of the outer world (exospace) within the experiential space of the Self (endospace) and enables autopoietic feedback. Methods: RIFT was examined through six computational modules representing successive transformations from recurrent network activity to endospace generation and feedback. Recurrent loops through fractal dendritic trees generated temporally organized excitatory postsynaptic potentials (EPSPs) and dynamic information integration. Coincident EPSPs programmed somatic multifractals composed of ion channels and membrane lipid domains, producing a fractal Self-attractor (fractal enfolding, Step 1). Coherent point sources derived from this attractor generated a holographic endospace that preserved exospace relationships (holographic unfolding, Step 2), and the reconstructed field modulated lipid-channel coupling and channel opening (autopoietic feedback, Step 3). Generational Fractal Mapping (GFM), in which new EPSPs are mapped onto the compressed fractal seed of the prior state, enables incremental updating, temporal continuity, and Self-attractor transfer. Results: The architecture was validated computationally against three properties specified by RIFT as requirements of consciousness: irreducibility, information integration, and holographic encoding. The simulations also reproduced signatures consistent with conscious access and low-dimensional volitional control. Conclusions: RIFT provides a testable computational framework linking neural activity, endospace generation, and feedback. It predicts effects of lipid-substrate disruption in Alzheimer’s disease, fractal signatures of conscious states, and structural criteria for artificial consciousness. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
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30 pages, 1458 KB  
Review
Psychological Issues Among Caregivers of Children with Neurodevelopmental Disorders: A Scoping Review
by Gerald Agyapong-Opoku, Ejemai Eboreime, Andrew J. Greenshaw and Belinda Agyapong
Brain Sci. 2026, 16(9), 982; https://doi.org/10.3390/brainsci16090982 - 16 Sep 2026
Viewed by 423
Abstract
Background: Caring for children with neurodevelopmental disorders can be challenging and is normally associated with a heightened risk of psychological challenges among caregivers. Objective: This scoping review aims to synthesize the existing literature on the prevalence and correlates of stress, anxiety, and depression [...] Read more.
Background: Caring for children with neurodevelopmental disorders can be challenging and is normally associated with a heightened risk of psychological challenges among caregivers. Objective: This scoping review aims to synthesize the existing literature on the prevalence and correlates of stress, anxiety, and depression among caregivers of children with neurodevelopmental disorders. Methods: This scoping review was conducted following the methodological framework outlined by Arksey and O’Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-ScR) extension for scoping reviews. A comprehensive literature search was conducted in PubMed, PsycINFO, Scopus, Web of Science, and CINAHL. Results: A total of 56 studies were included in this review. Factors associated with caregivers’ psychological issues include the age of the child, daily stress from own needs and the child’s care needs, and co-morbidity in the child. Articles utilized different screening tools and diverse diagnostic classifications to determine symptoms of stress, anxiety, and depression, leading to variations in prevalence estimates. The lowest prevalence of stress reported was 7.9%, while the highest reported caregiver moderate-to-severe stress was 94.6%. Similarly, the prevalence of anxiety and depression varied from 6.0% to 85.8% and from 5.2% to 85.1%, respectively. This substantial variability is likely attributable to the heterogeneity of assessment tools and inconsistencies in the use of classificatory terminology, such as “severe,” “clinical range,” and “high”, which may limit the generalizability of the findings. Conclusions: Caregivers of children with neurodevelopmental disabilities experience an immense psychological burden. Expanding access to sustainable psychosocial and social protection interventions is a vital step toward improving their well-being. This will indirectly improve the overall outcomes for the children. Government and policymakers should prioritize the implementation of measures such as social support allocated to this cohort to enhance their quality of life and improve their overall well-being. Full article
(This article belongs to the Section Developmental Neuroscience)
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29 pages, 386 KB  
Review
Supporting Visual Working Memory in Healthy Aging: A Review of Current Interventions and Perspectives on Future Approaches
by Virginia Tronelli, Alessandra Barbon and Veronica Mazza
Brain Sci. 2026, 16(9), 981; https://doi.org/10.3390/brainsci16090981 - 16 Sep 2026
Viewed by 364
Abstract
Visual working memory (vWM) undergoes age-related decline, affecting storage capacity, representational precision, feature binding, and inhibitory control, with consequences for everyday functioning. Nevertheless, accumulating evidence indicates that the aging brain retains substantial plasticity, providing an opportunity of intervention. This review synthesizes current evidence [...] Read more.
Visual working memory (vWM) undergoes age-related decline, affecting storage capacity, representational precision, feature binding, and inhibitory control, with consequences for everyday functioning. Nevertheless, accumulating evidence indicates that the aging brain retains substantial plasticity, providing an opportunity of intervention. This review synthesizes current evidence on approaches to improving vWM in healthy older adults, including classic and game-based cognitive training, non-invasive brain stimulation (NIBS), and multimodal protocols that combine cognitive training with physical exercise or brain stimulation. Across the literature, process-based cognitive training produces improvements on trained and closely related tasks, whereas evidence for durable far-transfer remains limited. NIBS demonstrates promising neurophysiological effects, particularly when targeting frontoparietal networks, although behavioral outcomes remain heterogeneous and appear to depend on stimulation parameters and individual characteristics. Emerging findings further suggest that combining interventions may enhance selected aspects of vWM, highlighting the importance of personalized approaches. Despite these advances, intervention effects are often modest, task-specific, and resource-intensive. As a complementary approach, the review proposes placebo and nocebo effects as a theoretically grounded hypothesis that warrants empirical investigation for potentially complementing existing interventions and promoting healthy cognitive aging rather than confounds. Full article
(This article belongs to the Special Issue Ageing and Visual Working Memory: Cognitive and Neural Perspectives)
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18 pages, 842 KB  
Article
FastSurfer-Based Brain Morphometry and Machine-Learning Classification Across the Alzheimer’s Disease Spectrum
by Sinem Nur Altun and Hurriyet Cetinok
Brain Sci. 2026, 16(9), 980; https://doi.org/10.3390/brainsci16090980 - 16 Sep 2026
Viewed by 280
Abstract
Background: This study aimed to quantitatively assess structural changes in the hippocampus, amygdala, entorhinal cortex, lateral ventricles, precuneus, and posterior cingulate using deep-learning-based FastSurfer morphometry and evaluate their contribution to classification across the Alzheimer’s disease (AD) spectrum. Methods: Three-dimensional T1-weighted MRI [...] Read more.
Background: This study aimed to quantitatively assess structural changes in the hippocampus, amygdala, entorhinal cortex, lateral ventricles, precuneus, and posterior cingulate using deep-learning-based FastSurfer morphometry and evaluate their contribution to classification across the Alzheimer’s disease (AD) spectrum. Methods: Three-dimensional T1-weighted MRI data from the AD Neuroimaging Initiative (ADNI) were analyzed using FastSurfer. The study included 791 participants (425 female and 366 male): 365 cognitively normal (CN), 273 with mild cognitive impairment (MCI), and 153 with AD. Morphometric measures included hippocampal and amygdala volumes, lateral ventricular volume, entorhinal cortical thickness and surface area, and precuneus and posterior cingulate thickness and folding index. Volumetric measures were normalized to estimated total intracranial volume (eTIV). Principal morphometric comparisons were additionally adjusted for age, sex, and education. Six machine-learning classifiers were evaluated using participant-level training (n = 632) and held-out test (n = 159) sets, with an additional MMSE-ablation analysis. Results: Hippocampal and amygdala volumes were significantly lower and lateral ventricular volume was significantly higher in AD than in CN (all p < 0.001), with these differences persisting after eTIV normalization and remaining significant after adjustment for age, sex, and education (all adjusted p < 0.001). MCI generally showed intermediate volumetric values between CN and AD. Mini-Mental State Examination (MMSE) scores correlated positively with total hippocampal (r = 0.495) and amygdala (r = 0.462) volumes and negatively with lateral ventricular volume (r = −0.256) (all p < 0.001). For three-class CN/MCI/AD classification, Logistic Regression with ElasticNet achieved a mean macro-F1 score of 0.706 ± 0.017 in five-fold cross-validation and a held-out macro-F1 score of 0.705 with MMSE included. Excluding MMSE reduced the held-out macro-F1 score to 0.531 and ROC-AUC to 0.735, compared with 0.857 when MMSE was included. Performance was higher for binary CN-versus-AD classification, with a held-out test macro-F1 score of 0.919 and ROC-AUC of 0.990. Conclusions: FastSurfer-based morphometry demonstrated medial temporal atrophy and lateral ventricular enlargement across the CN–MCI–AD spectrum, with the principal volumetric differences remaining robust after adjustment for age, sex, and education. The intermediate morphometric profile of MCI and the associations between medial temporal volumes and cognitive performance support the relevance of these structural measures. Machine-learning performance improved substantially when MMSE was incorporated, indicating that the combined models reflect integrated morphometric, demographic, genetic, and cognitive information rather than morphometry alone. External validation in independent cohorts is required before clinical application. Full article
(This article belongs to the Section Neurotechnology and Neuroimaging)
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21 pages, 716 KB  
Review
Awakening the Vagus: Transcutaneous Auricular Vagus Nerve Stimulation—A Narrative Review
by Lara Portincaso, Gaia Chiara Santi, Nicole Villa and Davide Antonio Di Pietro
Brain Sci. 2026, 16(9), 979; https://doi.org/10.3390/brainsci16090979 - 16 Sep 2026
Viewed by 451
Abstract
Disorders of consciousness (DoC), including unresponsive wakefulness syndrome/vegetative state (UWS/VS) and minimally conscious state (MCS), remain a major challenge in clinical neurology. Therapeutic options are limited, and prognosis is often uncertain. Transcutaneous stimulation of the auricular branch of the vagus nerve (taVNS) is [...] Read more.
Disorders of consciousness (DoC), including unresponsive wakefulness syndrome/vegetative state (UWS/VS) and minimally conscious state (MCS), remain a major challenge in clinical neurology. Therapeutic options are limited, and prognosis is often uncertain. Transcutaneous stimulation of the auricular branch of the vagus nerve (taVNS) is a non-invasive neuromodulation technique that has gained increasing interest as a potential strategy to promote recovery of consciousness. This narrative review summarizes the anatomical and functional rationale of taVNS, compares invasive and non-invasive vagus nerve stimulation techniques, reviews the biological mechanisms underlying its effects, discusses established clinical applications, technological innovations, and available clinical trial evidence. Current data suggest that taVNS is safe and well-tolerated, with preliminary evidence of applicability in DoC, particularly in patients with MCS. However, heterogeneity in stimulation protocols and the limited number of large-scale randomized controlled trials highlight the need for further standardized research. Full article
(This article belongs to the Special Issue Modern Aspects of Neurorehabilitation)
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13 pages, 2160 KB  
Article
Early Risk Stratification and Time-to-Cure Analysis in Patients with Residual Hemifacial Spasm After Microvascular Decompression
by Siyi Liu, Tao Du, Feng Hou, Zaiying Jiang, Liu He, Yunjian Huang, Bing Ni, Xueyuan Wang, Yunpeng Wang and Hongwei Zhu
Brain Sci. 2026, 16(9), 978; https://doi.org/10.3390/brainsci16090978 - 16 Sep 2026
Viewed by 245
Abstract
Background/Objectives: Microvascular decompression (MVD) is an effective treatment for hemifacial spasm (HFS), but some patients have residual spasms after surgery. Some later achieve delayed cure, whereas others have persistent HFS, making reoperation planning difficult. This study aimed to develop a prediction model for [...] Read more.
Background/Objectives: Microvascular decompression (MVD) is an effective treatment for hemifacial spasm (HFS), but some patients have residual spasms after surgery. Some later achieve delayed cure, whereas others have persistent HFS, making reoperation planning difficult. This study aimed to develop a prediction model for early risk stratification in patients with residual HFS after MVD. Methods: We retrospectively analyzed 500 consecutive patients with primary HFS who underwent MVD between November 2021 and August 2023. Among them, 140 patients with residual HFS at 24 h postoperatively were included. Clinical variables, intraoperative abnormal muscle response, Cohen grade at 24 h after surgery (Cohen-post), and Immediate Subjective Improvement Rate (ISIR) were collected. A multivariable logistic regression model was developed and presented as a nomogram, with bootstrap internal validation. Cox regression and Kaplan–Meier analyses were used to assess time to cure. Results: Mean follow-up was 21.9 months. Delayed cure occurred in 102 patients (72.9%), whereas 38 (27.1%) had persistent HFS. The final model included ISIR, Cohen-post, and offending artery status. The nomogram showed good discrimination (area under the curve 0.901). Patients with higher ISIR and lower Cohen-post recovered faster. Among patients with delayed cure, median time to cure was 30 days, and 95% achieved cure within 300 days after surgery. Conclusions: In patients with residual HFS at 24 h after MVD, a nomogram incorporating ISIR, Cohen-post, and offending artery status may help distinguish delayed cure from persistent HFS and may provide useful information on the likelihood of further recovery. Full article
(This article belongs to the Special Issue New Trends and Technologies in Modern Neurosurgery: 2nd Edition)
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15 pages, 1087 KB  
Article
Evaluation of Clusterin, Sestrin-2, Oxidative Stress, and Inflammatory Indices in Patients with Alzheimer’s Disease Dementia
by Nida Aslan Karakelle, Safiye Göçer, Esra Eruyar, Yasemin Atıcı and Müge Coşkun Yıldırım
Brain Sci. 2026, 16(9), 977; https://doi.org/10.3390/brainsci16090977 - 15 Sep 2026
Viewed by 234
Abstract
Introduction: Alzheimer’s disease dementia (AD dementia) is a progressive neurodegenerative disorder associated with cognitive decline. Oxidative stress and inflammation may contribute to its pathophysiology, with clusterin (CLU) and sestrin-2 (SESN2) emerging as potential biomarkers. This study evaluated oxidative stress markers, inflammatory indices, and [...] Read more.
Introduction: Alzheimer’s disease dementia (AD dementia) is a progressive neurodegenerative disorder associated with cognitive decline. Oxidative stress and inflammation may contribute to its pathophysiology, with clusterin (CLU) and sestrin-2 (SESN2) emerging as potential biomarkers. This study evaluated oxidative stress markers, inflammatory indices, and serum CLU and SESN2 levels in patients with AD dementia. Methods: A total of 48 patients with AD dementia and 39 healthy controls in a broadly comparable age range were enrolled from a neurology outpatient clinic. AD dementia was diagnosed according to internationally accepted clinical criteria. Cognitive function was assessed using Mini-Mental State Examination (MMSE) scores obtained at diagnosis. Serum malondialdehyde (MDA), glutathione (GSH), CLU, and SESN2 were measured, with MDA and GSH analyzed spectrophotometrically and CLU and SESN2 concentrations determined using the enzyme-linked immunosorbent assay (ELISA). Inflammatory indices were calculated from routine hematological and biochemical parameters. Results: A multivariable logistic regression model including age, MDA, and GSH showed excellent discriminatory performance for distinguishing patients with AD dementia from healthy controls. Patients with AD dementia had significantly lower SESN2 levels (p < 0.001) and higher CLU levels (p < 0.001) than controls. No significant associations were observed between inflammatory indices and the investigated clinical or biochemical variables in the AD dementia group (p > 0.05). Conclusions: Oxidative stress and altered SESN2 and CLU levels may be associated with AD dementia, whereas the inflammatory indices showed limited utility. Larger prospective studies are needed to validate these findings and clarify their clinical significance. Full article
(This article belongs to the Section Neurodegenerative Diseases)
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15 pages, 7209 KB  
Article
Resting-State 40 Hz EEG Activity Before and After Single-Session Non-Flickering 40 Hz Light Stimulation in Cognitively Normal Older Adults: An Uncontrolled Pilot Study
by Chia-Hsiung Cheng and Hsinjie Lu
Brain Sci. 2026, 16(9), 976; https://doi.org/10.3390/brainsci16090976 - 15 Sep 2026
Viewed by 346
Abstract
Background: Forty-hertz sensory stimulation has emerged as a potential approach for modulating neural activity relevant to Alzheimer’s disease. However, electrophysiological changes following non-flickering 40 Hz light stimulation in older adults remain unclear. This study investigated whether a single-session intervention of non-flickering 40 [...] Read more.
Background: Forty-hertz sensory stimulation has emerged as a potential approach for modulating neural activity relevant to Alzheimer’s disease. However, electrophysiological changes following non-flickering 40 Hz light stimulation in older adults remain unclear. This study investigated whether a single-session intervention of non-flickering 40 Hz light stimulation would be associated with increased resting-state 40 Hz oscillations in cognitively normal older adults. Methods: In this uncontrolled single-arm pilot study, 16 cognitively normal older adults underwent a 60 min session of non-flickering 40 Hz light stimulation. Resting-state EEG was recorded immediately before and after stimulation. Relative power within 38–42 Hz was analyzed across six predefined scalp regions and the whole-brain measure using one-tailed Wilcoxon signed-rank tests with Benjamini–Hochberg false discovery rate (FDR) correction. Exploratory real-time EEG recordings during stimulation were available in 10 participants. Results: After FDR correction, resting-state 38–42 Hz relative power was higher post-stimulation in the central (FDR = 0.045, effect size = 0.555) and right temporal (FDR = 0.014, effect size = 0.724) regions. In the absolute-power sensitivity analysis, only the right temporal increase remained significant after FDR correction (FDR = 0.042). Exploratory during-stimulation analysis showed a nominally increased 38–42 Hz signal-to-noise ratio in the right temporal region (p = 0.026). One participant reported very mild fatigue; no other adverse responses were reported. Conclusions: This pilot study suggests regional increases in resting-state 38–42 Hz activity after non-flickering 40 Hz light stimulation, with additional absolute-power support for the right temporal finding. These findings remain preliminary given the uncontrolled design and small sample. Full article
(This article belongs to the Section Behavioral Neuroscience)
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38 pages, 4510 KB  
Article
Cognitive Control and Metacognition: The Effect of Interference, Working-Memory Load, and Shifting on Confidence in Response Correctness and Partial Error
by Patryk Guzda, Marta Siedlecka and Aleksandra Gruszka
Brain Sci. 2026, 16(9), 975; https://doi.org/10.3390/brainsci16090975 - 15 Sep 2026
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Abstract
Background/Objectives: Confidence is typically studied in simple perceptual decisions, although everyday decisions also require cognitive control and monitoring of action. Across two experiments, we examined whether response conflict, stimulus complexity, and sequence affect task performance and retrospective metacognitive judgments concerning different aspects of [...] Read more.
Background/Objectives: Confidence is typically studied in simple perceptual decisions, although everyday decisions also require cognitive control and monitoring of action. Across two experiments, we examined whether response conflict, stimulus complexity, and sequence affect task performance and retrospective metacognitive judgments concerning different aspects of performance: confidence in response correctness and confidence that a covert partial error occurred. Methods: Participants performed a modified Stroop task in which they responded to word colour and, in compound trials, also reported the position of an accompanying line. In Experiment 1 (N = 66), participants rated confidence in the correctness of their responses. In Experiment 2 (N = 47), electromyography was used to identify covert partial errors, and participants rated confidence that a partial error had occurred. Results: Conflict reduced response accuracy, prolonged response times, and was associated with a small reduction in confidence in correct responses. In Experiment 1, the effect of sequence on confidence depended on stimulus complexity: confidence was higher in simple-repeated than in simple-switched trials, whereas the opposite pattern was observed for compound trials. In Experiment 2, partial errors occurred more frequently under conflict but less frequently in compound trials. Greater incorrect-burst surface and longer correction time were associated with higher partial-error confidence, and both relationships were weaker in compound trials. The association with incorrect-burst surface remained reliable after adjustment for response time. Exploratory analyses also showed lower metacognitive sensitivity under conflict and complexity and lower metacognitive efficiency in compound trials. Conclusions: Cognitive-control demands were associated with retrospective metacognitive judgments concerning both completed response outcomes and partial-error events occurring during response generation. Conflict was associated with a small reduction in confidence in correct responses, whereas partial-error confidence was associated with measurable characteristics of the partial-error event. The weaker relationship between EMG-derived response-process characteristics and confidence during compound processing suggests that current task demands affect how strongly internal response-related information is related to metacognitive judgments. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
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24 pages, 895 KB  
Article
Cognitive and Behavioral Functioning in Female Former Soccer Players: Results from the Head Impact and Trauma Surveillance Study (HITSS)
by Shania C. Mulayi, Anna Aaronson, Kelsey J. Goostrey, Fatima Tuz-Zahra, Yorghos Tripodis, William S. Cole-French, Matthew Roebuck, Greta Schneider, Brittany N. Pine, Joseph N. Palmisano, Brett M. Martin, Kenton H. Zavitz, Douglas I. Katz, Christopher J. Nowinski, Ann C. McKee, Thor D. Stein, R. Scott Mackin, Michael D. McClean, Jennifer Weuve, Jesse Mez, Michael W. Weiner, Rachel L. Nosheny, Michael L. Alosco and Robert A. Sternadd Show full author list remove Hide full author list
Brain Sci. 2026, 16(9), 974; https://doi.org/10.3390/brainsci16090974 - 15 Sep 2026
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Abstract
Background/Objectives: Repetitive head impacts (RHI) from contact and collision sports have been associated with later-life cognitive and neurobehavioral impairments, as well as neurodegenerative conditions such as chronic traumatic encephalopathy (CTE). RHI-associated clinical sequelae among female former soccer players, specifically, are not well understood. [...] Read more.
Background/Objectives: Repetitive head impacts (RHI) from contact and collision sports have been associated with later-life cognitive and neurobehavioral impairments, as well as neurodegenerative conditions such as chronic traumatic encephalopathy (CTE). RHI-associated clinical sequelae among female former soccer players, specifically, are not well understood. This cross-sectional study aimed to examine the relationship of RHI exposure proxies (e.g., total years of soccer play, concussion history, highest level of play, and estimated cumulative heading frequency) with clinical measures (e.g., subjective cognitive complaints, objective cognitive performance, behavioral dysregulation, and depressive symptoms) among 2732 women, aged 40 years or above, enrolled in the Head Impact and Trauma Surveillance Study (HITSS), all of whom formerly played organized soccer. Methods: HITSS participants completed an online battery that elicited self-reported cognitive and behavioral complaints and depressive symptoms and that assessed cognitive performance via computerized tests. Multivariable linear regression models estimated associations between soccer-related RHI proxies and outcome measures, adjusting for age and education. Results: Among the former soccer players, longer duration of soccer play, higher level of play, greater estimated cumulative heading frequency, and concussion history were significantly associated with worse self-reported cognitive functioning, greater behavioral dysregulation, and elevated depressive symptom severity. Apart from a single association between concussion history and visual learning and episodic memory performance, we found no other associations between RHI proxies and objective cognitive test performance. Conclusions: Among middle-aged women who played organized soccer, cumulative RHI exposure corresponded to a higher degree of subjective cognitive complaints, worse behavioral functioning, and more severe depressive symptoms. Continued monitoring of this large cohort of female former soccer players offers a more comprehensive understanding of long-term health consequences of soccer play. Full article
(This article belongs to the Special Issue Heterogeneity in Cognitive Aging: From Healthy Aging to Neurodegenerative Disease)
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18 pages, 7678 KB  
Article
Computational–Experimental Characterization of Transcranial Magneto-Acoustic Stimulation for Dose-Efficient Neural Activation
by Ruxin Tan, Fangxuan Chu, Xin Wang, Xiaoqing Zhou, Ren Ma, Tao Yin, Haojun Fan and Zhipeng Liu
Brain Sci. 2026, 16(9), 973; https://doi.org/10.3390/brainsci16090973 - 14 Sep 2026
Viewed by 309
Abstract
Background/Objectives: Transcranial magneto-acoustic stimulation (TMAS) is an emerging multiphysics neuromodulation modality that introduces magneto-acoustically induced currents into ultrasound-based neural stimulation. However, how this coupled physical input is converted into neuronal recruitment and measurable biological responses remains insufficiently understood. This study aimed to [...] Read more.
Background/Objectives: Transcranial magneto-acoustic stimulation (TMAS) is an emerging multiphysics neuromodulation modality that introduces magneto-acoustically induced currents into ultrasound-based neural stimulation. However, how this coupled physical input is converted into neuronal recruitment and measurable biological responses remains insufficiently understood. This study aimed to establish a computational–experimental framework for quantifying TMAS-induced neural activation across stimulation dose, spike timing, and calcium-related response domains. Methods: The model combined ultrasound-induced membrane mechanics, charge-based neuronal electrophysiology, pressure-dependent calcium-current modulation, and a Lorentz-force-mediated current source for TMAS. Regular-spiking excitatory neurons and low-threshold-spiking inhibitory interneurons were simulated to estimate excitation thresholds, firing latency, and spike-pattern transitions. Two model-informed stimulation conditions were examined using in vitro calcium imaging, in vivo hippocampal fiber photometry, and c-Fos/microtubule-associated protein 2 (MAP2) immunofluorescence. Results: TMAS reduced the half-maximal effective dose relative to transcranial ultrasound stimulation by 71.4–76.3% in regular spiking neurons and 51.5–58.2% in low-threshold spiking interneurons, while shortening firing latency and expanding burst-response domains. Experimentally, near-threshold TMAS produced larger peak calcium responses and greater c-Fos/MAP2 immunoreactivity than TUS. Conclusions: TMAS enhances neuronal responsiveness more efficiently than TUS by reducing excitation thresholds, improving spike-timing responses, and reshaping firing-pattern transitions. Consistent with the overall computational comparison, experimental measurements showed greater neuronal activation under TMAS than under TUS at matched ultrasound parameters. Full article
(This article belongs to the Section Computational Neuroscience, Neuroinformatics, and Neurocomputing)
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119 pages, 1984 KB  
Systematic Review
Telerehabilitation for Motor Recovery in Adults with Neurological Disorders: A Systematic Review and Meta-Analysis Across Motor Domains, Delivery Models, and Follow-Up Effects
by Rocco Salvatore Calabrò, Arnold Fredrick D’Souza, Sanaz Pournajaf, Francesca Baglio, Carl Froilan D. Leochico and Alon Kalron
Brain Sci. 2026, 16(9), 972; https://doi.org/10.3390/brainsci16090972 - 14 Sep 2026
Viewed by 348
Abstract
Background/Objectives: Telerehabilitation may extend neurorehabilitation beyond conventional settings, but comparative effects across neurological diagnoses and motor domains remain uncertain. This systematic review and meta-analysis synthesized motor outcomes while distinguishing International Classification of Functioning, Disability and Health activity domains, delivery models, and comparator questions. [...] Read more.
Background/Objectives: Telerehabilitation may extend neurorehabilitation beyond conventional settings, but comparative effects across neurological diagnoses and motor domains remain uncertain. This systematic review and meta-analysis synthesized motor outcomes while distinguishing International Classification of Functioning, Disability and Health activity domains, delivery models, and comparator questions. Methods: Five databases were searched from inception to 8 June 2026 using two database-specific Boolean search strategies. Comparative studies of adults with neurological disorders receiving active remote, digital, virtual, wearable, or hybrid rehabilitation were eligible. Random-effects models used restricted maximum likelihood estimation; Hartung–Knapp confidence intervals were primary when at least three studies were available, and DerSimonian–Laird models were sensitivity analyses. Results: Eighty-seven studies included stroke, Parkinson’s disease, multiple sclerosis, spinal cord injury, acquired brain injury, or ataxia. For walking and mobility activities versus usual care, no additional therapy, or waitlist, the point estimate favoured telerehabilitation but was imprecise and compatible with no difference (standardized mean difference 1.06, 95% confidence interval −0.23 to 2.35; three studies; 121 participants; I2 = 57.6%). Global motor-functional and activities-of-daily-living outcomes showed similar uncertainty (0.83, −0.35 to 2.00; three studies; 304 participants; I2 = 73.6%). Both findings had very-low-certainty evidence. No pooled comparison included enough studies to assess publication bias. Two-study datasets for balance-related activity/postural control and upper-limb impairment were highly heterogeneous and interpreted descriptively. Conclusions: Comparative evidence for telerehabilitation across neurological diagnoses and motor domains remains uncertain. Programme characteristics are plausible implementation considerations, not established efficacy modifiers. Small evidence sets, wide intervals, clinical heterogeneity, risk of bias, and inconsistent adverse-event ascertainment preclude conclusions about clinical importance or established safety. Full article
(This article belongs to the Section Neurorehabilitation)
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