Brain Sciences

38 pages, 4796 KB

Open AccessReview

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 (registering DOI) - 19 Sep 2026

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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36 pages, 2622 KB

Open AccessSystematic 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 (registering DOI) - 19 Sep 2026

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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Graphical abstract

53 pages, 2723 KB

Open AccessSystematic 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 (registering DOI) - 19 Sep 2026

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

Open AccessBrief 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 (registering DOI) - 19 Sep 2026

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

Open AccessReview

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 (registering DOI) - 19 Sep 2026

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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27 pages, 643 KB

Open AccessArticle

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 (registering DOI) - 18 Sep 2026

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

Open AccessArticle

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 (registering DOI) - 18 Sep 2026

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

Open AccessArticle

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

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

Open AccessReview

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

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

Open AccessArticle

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

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

Open AccessHypothesis

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

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

Open AccessArticle

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

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

Open AccessHypothesis

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

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

Open AccessReview

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

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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33 pages, 386 KB

Open AccessReview

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

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

Open AccessArticle

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

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

Open AccessReview

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

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

Open AccessArticle

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

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

Open AccessArticle

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

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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