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Search Results (419)

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Keywords = brain oscillation

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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
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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36 pages, 41217 KB  
Article
Clock-Related Genes Mark a Developmental Cortical Maturation Program Associated with Stage-Resolved Responses to Prenatal Immune Activation
by Yilin Wang, Shanshan Li and Xin Jin
Genes 2026, 17(9), 1107; https://doi.org/10.3390/genes17091107 - 12 Sep 2026
Viewed by 112
Abstract
Background/Objectives: Sleep and circadian disturbances are common in neurodevelopmental conditions, yet the developmental cortical programs linking clock-related transcriptional regulators to disease vulnerability remain unclear. Methods: Here, we integrated human developmental brain transcriptomes, weighted gene co-expression network analysis (WGCNA), human and mouse cortical single-cell [...] Read more.
Background/Objectives: Sleep and circadian disturbances are common in neurodevelopmental conditions, yet the developmental cortical programs linking clock-related transcriptional regulators to disease vulnerability remain unclear. Methods: Here, we integrated human developmental brain transcriptomes, weighted gene co-expression network analysis (WGCNA), human and mouse cortical single-cell atlases, prenatal immune activation transcriptomes, and ASD postmortem brain datasets to characterize the developmental architecture of BrainSpan-derived cortical programs and examine their behavior in perturbational and disease contexts. Results: In the BrainSpan frontal cortex, canonical clock-related genes followed structured but heterogeneous developmental trajectories rather than behaving as a coordinated oscillator-like unit. WGCNA identified a postnatal-rising BrainSpan-derived primary developmental module that was strongly associated with developmental age and enriched for synaptic signaling, neurotransmitter transport, ion transport, membrane excitability, cellular respiration, metabolic regulation, and proteostatic processes. Network analysis placed multiple canonical clock-related and clock-regulatory genes, including NPAS2, BHLHE40, BHLHE41, PER family members, RORA, NR1D1/2, and CLOCK, within a broader neuronal and homeostatic co-expression architecture, although their module-membership strengths varied substantially. Projection onto a human cortical developmental single-cell atlas revealed a non-uniform distribution of the corrected BrainSpan-derived developmental signature, with relatively higher scores in excitatory and inhibitory neuronal populations and lower scores in neuroblast and radial glial populations. A mouse cortical developmental single-cell atlas provided a comparative view of the stage- and cell-type-dependent expression of clock-related genes and the transferred developmental signature during corticogenesis. In a Poly(I:C)-based maternal immune activation dataset, litter-aware reanalysis identified stage-resolved genome-wide transcriptional responses following E12.5 exposure. However, neither the aggregate core clock-gene expression score nor the independently transferred BrainSpan-derived developmental signature showed a significant overall treatment effect or collection-stage-by-treatment interaction, indicating that this bulk dataset provides a perturbational context rather than evidence for selective disruption of the developmental program. An exploratory region-stratified analysis of GSE28521 yielded near-null effects for the BrainSpan-derived developmental signature, with confidence intervals crossing zero across all examined regions. These ASD postmortem findings were therefore treated as a boundary assessment rather than evidence of ASD-specific convergence. Conclusions: Collectively, these findings position clock-related genes as components of a developmentally regulated cortical maturation program enriched for neuronal signaling, synaptic maturation, metabolic regulation, and stress-response processes. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
26 pages, 1411 KB  
Review
From Oscillations to Brain States: Real-Time EEG-TMS for Adaptive Neuromodulation
by Melissa Null, Elena Mongiardini, Chiara Leu, Giulia Liberati and Paolo Belardinelli
Bioengineering 2026, 13(9), 1054; https://doi.org/10.3390/bioengineering13091054 - 10 Sep 2026
Viewed by 379
Abstract
Transcranial magnetic stimulation (TMS) enables non-invasive, focal modulation of cortical circuits by inducing electric currents in the brain through electromagnetic induction, thereby influencing neuronal excitability and synaptic plasticity. High inter- and intra-individual variability has led, however, to moderate efficacy and reproducibility of stimulation [...] Read more.
Transcranial magnetic stimulation (TMS) enables non-invasive, focal modulation of cortical circuits by inducing electric currents in the brain through electromagnetic induction, thereby influencing neuronal excitability and synaptic plasticity. High inter- and intra-individual variability has led, however, to moderate efficacy and reproducibility of stimulation and treatment protocols, motivating a shift toward brain-state-dependent stimulation. Over the past decade, real-time phase-triggered EEG-TMS has established the oscillatory phase—particularly focusing on the sensorimotor mu rhythm—as a key determinant of cortical excitability and plasticity modulation. The field, however, remains largely confined to univariate, sensor-space analyses of local mu-rhythm phase, missing large-scale network dynamics. Recent advances in online EEG source reconstruction and multivariate machine and deep learning (ML/DL) approaches have begun to move beyond local phase toward whole-brain, network-level state estimation, achieving encouraging preliminary accuracies in predicting trial-by-trial cortical excitability, with promising applications in network-dysregulation conditions such as chronic pain. Integrating source-space reconstruction and individual biological variability, and adaptive ML/DL pipelines into closed-loop frameworks promises to move beyond generic stimulation protocols toward selective, network-targeted neuromodulation tailored to the individual’s dynamic brain state. Against this background, this review provides a critical overview of current achievements and limitations, while highlighting emerging methodological directions toward fully brain-state-adaptive and network-targeted EEG-TMS. We further present an illustrative use case of adaptive EEG-TMS for pain modulation, where treatment responses remain heterogeneous and the relevant dynamics are distributed across networks, and which therefore stands to gain most from individualized, network-targeted protocols. Full article
(This article belongs to the Special Issue Recent Advances in Brain Stimulation Technology)
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46 pages, 1792 KB  
Systematic Review
Iron Deficiency and Human Brain Electrophysiology Across the Lifespan: A Systematic and Mechanistic Review of Resting EEG, Event-Related Potentials, and Treatment Responsiveness
by James Chmiel, Jolanta Góral-Półrola, Patrycja Leśnicka and Marta Kopańska
Nutrients 2026, 18(18), 2955; https://doi.org/10.3390/nu18182955 - 9 Sep 2026
Viewed by 306
Abstract
Introduction: Iron is essential for cerebral energy metabolism, neurotransmitter synthesis, myelination, and neural development. Iron deficiency may therefore impair brain function even before overt anemia develops. This systematic and mechanistic review synthesized EEG findings associated with iron deficiency across the lifespan and evaluated [...] Read more.
Introduction: Iron is essential for cerebral energy metabolism, neurotransmitter synthesis, myelination, and neural development. Iron deficiency may therefore impair brain function even before overt anemia develops. This systematic and mechanistic review synthesized EEG findings associated with iron deficiency across the lifespan and evaluated electrophysiological changes following iron treatment. Materials and Methods: PubMed/MEDLINE, Scopus, Web of Science, Embase, PsycINFO, and Google Scholar were searched from inception to July 2026. Human studies examining iron deficiency or iron-deficiency anemia using EEG, quantitative EEG, task-related oscillations, event-related potentials, or cortical-evoked potentials formed the core evidence base. Two additional studies of chronic kidney disease-related or mixed-etiology anemia were retained as contextual evidence to help distinguish iron-specific electrophysiological effects from abnormalities associated more generally with anemia severity and reduced oxygen-carrying capacity. Risk of bias was assessed using RoB 2 and ROBINS-I. Because of substantial heterogeneity, findings were synthesized narratively. Results: Thirty reports were retained for narrative synthesis, covering participants from the neonatal period to adulthood. Twenty-eight formed the core iron-specific evidence base, whereas two were analyzed separately as contextual anemia evidence. Iron deficiency was commonly associated with increased slow-wave activity, reduced alpha activity, delayed sensory and cognitive processing, prolonged P300 and N2 latencies, altered frontal alpha asymmetry, and impaired differentiation between relevant and irrelevant stimuli. Reductions in P300 amplitude were less consistent but were observed in severe anemia, demanding cognitive tasks, and after infantile iron-deficiency anemia. Iron supplementation improved several spectral and ERP outcomes, although recovery was variable and some abnormalities persisted after hematological correction. Interpretation was limited by heterogeneous diagnostic criteria, small samples, inconsistent EEG methods, residual confounding, variable risk of bias, and the partial non-independence of reports arising from overlapping longitudinal cohorts or parent trials. Findings from the contextual anemia studies were not interpreted as direct evidence of an effect of iron deficiency. Conclusions: Iron deficiency may disrupt the timing, synchronization, and maturation of neural activity through impaired energy metabolism, neurotransmission, myelination, and synaptic development. EEG may be useful for detecting functional brain alterations and monitoring treatment response, but no specific electrophysiological biomarker can currently be established. Full article
(This article belongs to the Special Issue Nutrition, Stress, and Psychological Well-Being Across the Lifespan)
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26 pages, 2635 KB  
Article
Machine-Learning-Based Localization of Cortical Hyperexcitability Zones from Background EEG Activity in Epilepsy
by Anton E. Malkov, Albina V. Lebedeva, Artem A. Sharkov, Lev A. Smirnov, Tatiana A. Levanova and Alexander N. Pisarchik
Technologies 2026, 14(9), 537; https://doi.org/10.3390/technologies14090537 - 30 Aug 2026
Viewed by 473
Abstract
Background rhythmic activity in routine EEG recordings of epilepsy patients contains extensive information about brain function under pathological conditions, far exceeding the duration of epileptiform and interictal discharges. However, clinical interpretation remains predominantly focused on detecting conspicuous pathological patterns, such as seizures and [...] Read more.
Background rhythmic activity in routine EEG recordings of epilepsy patients contains extensive information about brain function under pathological conditions, far exceeding the duration of epileptiform and interictal discharges. However, clinical interpretation remains predominantly focused on detecting conspicuous pathological patterns, such as seizures and interictal events, which is labor-intensive and requires expert evaluation. Recent advances in rhythmic EEG analysis combined with machine learning (ML) have enabled reliable differentiation between healthy individuals and epilepsy patients. Building on this momentum, the present study introduces a novel ML framework for the automated analysis and localization of cortical hyperexcitability foci, using only background EEG oscillations in the absence of detectable interictal discharges or seizure events. Leveraging publicly available EEG data, we demonstrate that Random Forest and CatBoost algorithms can effectively predict the approximate localization of interictal discharge foci at the level of major cortical regions. In a cohort of 48 patients (782 one-minute background epochs, five localization classes), Random Forest achieved an accuracy of 0.92 with a macro F1-score of 0.90 under patient-wise cross-validation. These findings establish background EEG activity as a promising clinically relevant biomarker for focal epilepsy diagnosis and highlight the feasibility of developing automated, expert-independent localization tools, addressing a critical unmet need in clinical neurophysiology. Full article
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13 pages, 801 KB  
Systematic Review
Objective Sleep Architecture Alterations and Sleep-Dependent Brain Clearance Dysfunction Across the Early Alzheimer’s Disease Continuum: A Systematic Review
by Sonja Cabarkapa, Courtney Shelton, Philippe Faucie and Jérôme Murgier
J. Clin. Med. 2026, 15(16), 6454; https://doi.org/10.3390/jcm15166454 - 20 Aug 2026
Viewed by 733
Abstract
Background: Sleep-dependent glymphatic clearance has emerged as a potential mechanism linking sleep disruption with Alzheimer’s Disease (AD) pathology. However, the relationship between objectively measured sleep and glymphatic function across the AD continuum remains unclear. Methods: Four databases (PubMed, Embase, Cochrane Library, and PsycINFO) [...] Read more.
Background: Sleep-dependent glymphatic clearance has emerged as a potential mechanism linking sleep disruption with Alzheimer’s Disease (AD) pathology. However, the relationship between objectively measured sleep and glymphatic function across the AD continuum remains unclear. Methods: Four databases (PubMed, Embase, Cochrane Library, and PsycINFO) were systematically searched for studies assessing objective sleep metrics and glymphatic-related biomarkers or clearance measures in humans across the AD continuum. Following peer review of the search strategy, supplementary searches of PubMed and Embase using expanded glymphatic and sleep electrophysiology terminology were undertaken to maximize sensitivity. The final database searches identified 416 records. After removal of 72 duplicates, 344 records were screened, 64 reports underwent full-text assessment, and four studies met the inclusion criteria. Results: Four studies involving participants across the AD continuum were included. Objective sleep assessment was performed using polysomnography or electroencephalography, while brain clearance was evaluated using direct or surrogate imaging measures including diffusion tensor image analysis along the perivascular space (DTI-ALPS), perivascular space burden, blood oxygen level-dependent–cerebrospinal fluid (BOLD-CSF) coupling, or direct tracer-based clearance imaging. Across studies, better preserved slow-wave sleep, slow-wave activity, and sleep oscillatory coupling were generally associated with more favorable glymphatic function or glymphatic-related biomarkers. Conversely, disrupted sleep architecture, reduced sleep efficiency, and altered sleep oscillatory coupling were associated with impaired glymphatic clearance or glymphatic dysfunction. Conclusions: Current evidence suggests that objectively measured sleep architecture, particularly slow-wave sleep and sleep oscillatory dynamics, may be associated with biomarkers of brain clearance across the AD continuum. However, the available evidence remains preliminary, is predominantly cross-sectional, and relies largely on indirect measures of brain clearance. Larger longitudinal studies incorporating standardized sleep assessment and validated measures of cerebral clearance are required to clarify temporal relationships, establish causality, and determine whether sleep-targeted interventions influence brain clearance or disease progression. Summary of findings: Preliminary evidence suggests that preserved slow-wave sleep and sleep oscillatory activity are associated with more favorable biomarkers of brain clearance, whereas disrupted sleep architecture is associated with less favorable clearance-related measures. Full article
(This article belongs to the Section Clinical Neurology)
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12 pages, 2603 KB  
Brief Report
Photopharmacological Cholinergic Modulation of Cortical Activity in Human Brain Slices
by Jose Manuel Sanchez-Sanchez, Joana Covelo, Estefania Conde, Pedro Roldán, Jordi Rumià, Mar Carreño, Fabio Riefolo, Carlo Matera, Pau Gorostiza and Maria V. Sanchez-Vives
Brain Sci. 2026, 16(8), 822; https://doi.org/10.3390/brainsci16080822 - 31 Jul 2026
Viewed by 392
Abstract
Background/Objectives: Understanding the unique properties of human neurons is crucial for advancing knowledge of brain function and facilitating clinical translation. This study explores the use of photopharmacology, specifically a photoswitchable ligand, Phthalimide-Azo-Iperoxo (PAI), to modulate cortical activity in human brain slices. Methods: Human [...] Read more.
Background/Objectives: Understanding the unique properties of human neurons is crucial for advancing knowledge of brain function and facilitating clinical translation. This study explores the use of photopharmacology, specifically a photoswitchable ligand, Phthalimide-Azo-Iperoxo (PAI), to modulate cortical activity in human brain slices. Methods: Human cortical tissue was obtained from patients undergoing resective neurosurgery for pharmacoresistant epilepsy. The inactive cis isomer of PAI (200 nM) was bath-applied to brain slices exhibiting slow-oscillatory activity, producing no effect on the ongoing network activity. Subsequent illumination of the slices with white light induced photoconversion to trans-PAI, the active form of the compound. Results: Photoactivation of PAI selectively activated M2 muscarinic acetylcholine receptors, resulting in a significant increase in oscillatory frequency accompanied by reductions in both Up-state and Down-state durations. Conclusions: In this proof-of-concept study, our findings provide preliminary evidence that photopharmacology can selectively modulate slow oscillations in human cortical circuits, highlighting its potential as a tool for investigating human cortical dynamics. By extending observations previously made in animal models to human tissue, this work establishes the feasibility of photopharmacological modulation in human cortical tissue and provides a foundation for future translational research. Full article
(This article belongs to the Section Systems Neuroscience)
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19 pages, 954 KB  
Review
Effects of 40 Hz Brain Stimulation Across Modalities: A Comparative Narrative Review
by Eugen Kvašňák
Brain Sci. 2026, 16(8), 808; https://doi.org/10.3390/brainsci16080808 - 30 Jul 2026
Viewed by 820
Abstract
Gamma-band oscillations centered around 40 Hz play an important role in cortical communication, and their disruption has been documented as a neurophysiological feature of several neurodegenerative and neuropsychiatric disorders. This narrative review synthesizes preclinical and early-phase clinical evidence for 40 Hz non-invasive brain [...] Read more.
Gamma-band oscillations centered around 40 Hz play an important role in cortical communication, and their disruption has been documented as a neurophysiological feature of several neurodegenerative and neuropsychiatric disorders. This narrative review synthesizes preclinical and early-phase clinical evidence for 40 Hz non-invasive brain stimulation across five delivery modalities: (1) auditory stimulation, which leverages the 40 Hz auditory steady-state response (ASSR) to probe parvalbumin-positive (PV+) interneuron circuits and serves as a validated neurophysiological biomarker in schizophrenia; (2) visual stimulation, using luminance or invisible spectral flicker to induce steady-state visually evoked potentials (SSVEPs) and, in animal models, to activate microglial phagocytosis; (3) transcranial alternating current stimulation (tACS), which delivers sinusoidal sub-threshold membrane polarization at gamma frequency, with preliminary case-series evidence suggesting tau burden reduction and EEG-based biomarker changes in Alzheimer’s disease; (4) repetitive transcranial magnetic stimulation (rTMS), offering focal cortical entrainment that, when combined with tACS in phase-synchronized protocols, produces sustained gamma enhancement in the dorsolateral prefrontal cortex; and (5) multisensory combined stimulation, which engages multiple convergent pathways and currently represents the approach with the most promising early translational signal, including cognitive stabilization and hippocampal volume preservation in small AD trials. While single-session entrainment does not reliably yield cognitive gains, multi-week applications have shown neurophysiological and preliminary biomarker-level changes in selected populations. It should be emphasized, however, that the human evidence base remains early-phase and largely derived from small, often uncontrolled studies; 40 Hz stimulation should accordingly be regarded as a biologically plausible and well-tolerated investigational approach rather than an established therapeutic intervention. Adequately powered, randomized, sham-controlled trials are required before clinical conclusions can be drawn. Full article
(This article belongs to the Section Neurorehabilitation)
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24 pages, 1411 KB  
Review
Bidirectional Mechanisms Linking Circadian Rhythm Disruption and Parkinson’s Disease: Chronobiomarkers and Therapeutic Implications
by Xinyue Zhang, Weina Shen, You Wu, Wei Zhang and Qing Ye
Int. J. Mol. Sci. 2026, 27(15), 6719; https://doi.org/10.3390/ijms27156719 - 28 Jul 2026
Viewed by 728
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder in which circadian rhythm disruption (CRD) emerges as both a prodromal feature and a potential pathogenic driver. Elucidating the bidirectional interplay between PD and CRD is essential for identifying early biomarkers and developing chronotherapeutic strategies. [...] Read more.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder in which circadian rhythm disruption (CRD) emerges as both a prodromal feature and a potential pathogenic driver. Elucidating the bidirectional interplay between PD and CRD is essential for identifying early biomarkers and developing chronotherapeutic strategies. We narratively synthesized literature published over the past two decades in PubMed, Web of Science, and CNKI, focusing on molecular mechanisms, clinical manifestations, biomarker development, and interventional studies addressing the PD–CRD interface. In the CRD-PD direction, circadian disruption accelerates dopaminergic neurodegeneration through four convergent mechanisms: (i) REV-ERBα–mediated dysregulation of dopamine biosynthesis and NF-κB/NLRP3-driven neuroinflammation; (ii) impaired sleep-dependent glymphatic clearance of α-synuclein (α-syn); (iii) NAD+–SIRT1–BMAL1–PGC-1α axis dysfunction leading to mitochondrial bioenergetic failure; and (iv) C/EBPβ-dependent autophagic rhythm disruption coupled with pro-inflammatory microglial activation, collectively establishing a dual pro-inflammatory–autophagy-suppressive milieu permissive for α-syn aggregation. In the reverse PD-CRD direction, PD pathology destabilizes the circadian system via Braak-stage degeneration of rhythm-regulatory nuclei, retinal dopaminergic denervation attenuating SCN photic entrainment, pineal–melatonin axis suppression, iatrogenic effects of dopaminergic pharmacotherapy, and gut microbiota dysbiosis propagated through the microbiota–gut–brain axis. Emerging multi-modal chronobiomarkers—including peripheral clock gene expression profiles, melatonin secretion patterns, tryptophan–kynurenine metabolites, and gut microbial oscillation signatures—show promise for prodromal diagnosis and disease subtyping. Circadian-targeted precision interventions—encompassing timed bright light therapy, exogenous melatonin, and chronopharmacological interventions—represent a promising translational paradigm for the early identification and management of PD. Full article
(This article belongs to the Special Issue Research on New Targets and New Drugs for Dementia)
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48 pages, 5353 KB  
Review
Dietary Polyphenols as Modulators of Redox Signalling: From the Antioxidant-Pro-Oxidant Continuum to Clinical Translation (2015–2025)
by José Manuel Pérez de la Lastra, Celia María Curieses Andrés, Elena Bustamante Munguira, Celia Andrés Juan and Eduardo Pérez Lebeña
Curr. Issues Mol. Biol. 2026, 48(7), 732; https://doi.org/10.3390/cimb48070732 - 17 Jul 2026
Viewed by 599
Abstract
Polyphenols often oscillate between antioxidant and pro-oxidant behaviours depending on structural motifs and context, yet the field still relies heavily on test-tube antioxidant assays that poorly predict cellular and clinical outcomes. This review (2015-2025) integrates chemistry, enzymology, and human data to frame polyphenols [...] Read more.
Polyphenols often oscillate between antioxidant and pro-oxidant behaviours depending on structural motifs and context, yet the field still relies heavily on test-tube antioxidant assays that poorly predict cellular and clinical outcomes. This review (2015-2025) integrates chemistry, enzymology, and human data to frame polyphenols as modulators of redox signalling rather than mere radical scavengers. We first formalize the catechol/o-quinone-hydroquinone/p-quinone cycle and the role of NQO1 and Keap1/NRF2 thresholds. We then examine bioavailability, conjugation, and microbiota-derived metabolites (metabotypes), highlighting when the “active” species is a conjugate or a microbial derivative. We discuss safety through quinone speciation and adduct chemistry, and connect food processing (e.g., PPO-driven browning) with shifts in quinone pools. Contextual “levers” (pH, O2, Fe/Cu, oxidases) can flip antioxidant to pro-oxidant outputs, sometimes beneficial via hormesis and redox preconditioning. In humans, randomised trials and prospective cohorts point in a broadly consistent direction, although primary composite endpoints have often proved null, and observational associations should not be read as equivalent to trial evidence. Heterogeneous results across studies are largely explained by dose, adherence, metabotypes, matrix, and endpoint selection. We propose a practical dose-response framework and a reporting checklist to improve interpretation and translation. Recasting polyphenols as tuneable redox-signalling agents clarifies apparent contradictions across models and suggests precision-nutrition strategies (metabotype-aware) and food design approaches (PPO and quinone speciation) with potential in healthy ageing, muscle, and brain. Full article
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12 pages, 480 KB  
Review
Gamma Oscillations, Sensory Stimulation, and Glymphatic Function: Toward User-Friendly Auditory Interventions for Brain Health in Aging and Neurodegeneration
by Peter Wostyn and Piet Goddaer
Med. Sci. 2026, 14(3), 398; https://doi.org/10.3390/medsci14030398 - 17 Jul 2026
Viewed by 801
Abstract
The glymphatic system is a brain-wide clearance pathway that facilitates the removal of interstitial solutes, including amyloid-β, and plays a critical role in maintaining brain homeostasis. Impairments in glymphatic transport have been implicated in aging and neurodegenerative diseases, including Alzheimer’s disease. While glymphatic [...] Read more.
The glymphatic system is a brain-wide clearance pathway that facilitates the removal of interstitial solutes, including amyloid-β, and plays a critical role in maintaining brain homeostasis. Impairments in glymphatic transport have been implicated in aging and neurodegenerative diseases, including Alzheimer’s disease. While glymphatic activity is most pronounced during sleep, emerging evidence suggests that specific patterns of neural activity, including gamma-frequency oscillations entrained by sensory stimulation, can modulate glymphatic transport even during wakefulness. Preclinical studies further indicate that 40 Hz sensory stimulation, delivered via light, sound, or multisensory paradigms, can induce gamma oscillations, reduce pathological protein accumulation, and enhance cognitive performance in animal models of Alzheimer’s disease. Early clinical investigations similarly suggest that gamma-frequency sensory stimulation may improve blood-based biomarkers, neuroimaging measures, and cognitive outcomes in patients with Alzheimer’s disease. To translate gamma-frequency stimulation into broadly applicable preventive or therapeutic strategies, approaches must be both effective and tolerable for long-term use. Conventional auditory gamma stimulation can be perceived as acoustically rough or monotonous, reducing listener comfort and limiting acceptability for prolonged use in broader populations. User-friendly auditory formats, such as “gamma music” and the more recently introduced “immersive gamma music”, have been proposed as potentially useful approaches for delivering gamma-frequency stimulation while improving listening comfort and facilitating sustained use. Collectively, gamma-frequency sensory stimulation represents a promising approach to support healthy brain aging and mitigate neurodegenerative processes, particularly when implemented via user-friendly auditory formats that facilitate repeated and long-term use. While these findings are encouraging, further research is needed to validate these approaches and determine their clinical relevance. Full article
(This article belongs to the Section Neurosciences)
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23 pages, 992 KB  
Article
Examination of Retention and Recall of Polytheistic Versus Monotheistic Religious Concepts
by Paul Robertson, Robert Ross and Hailey Kirchner
Religions 2026, 17(7), 825; https://doi.org/10.3390/rel17070825 - 9 Jul 2026
Viewed by 493
Abstract
Polytheistic and monotheistic ideas may lead to different processing in the brain, an understudied area generally and firmly within the 4E paradigm, especially in relation to embodiment. This paper uses a recognition memory paradigm to compare electroencephalography (EEG) signals and both reaction time [...] Read more.
Polytheistic and monotheistic ideas may lead to different processing in the brain, an understudied area generally and firmly within the 4E paradigm, especially in relation to embodiment. This paper uses a recognition memory paradigm to compare electroencephalography (EEG) signals and both reaction time and accuracy during the retrieval of polytheistic and monotheistic god concepts. We use EEG to analyze alpha oscillations whose de-synchronization reveals the neurological difficulty of ideas due to novelty or conceptual complexity. Word pairs of polytheistic or monotheistic ideas were presented to subjects, whose brains were analyzed during identification (polytheistic vs. monotheistic) and recall, alongside their reaction time and recall accuracy. No major support was found for different alpha oscillation levels during processing of polytheistic versus monotheistic ideas between monotheistic and religiously unaffiliated subjects. Meanwhile, a significant difference was found in reaction time during recall across both monotheistic and religiously unaffiliated subjects, as polytheistic ideas were recalled more quickly in both groups. These findings bear on dominant theories in the cognitive science of religion that privilege powerful and automatic agency detection in humans’ evolved past, alongside the cultural record where the dominant form of religious belief historically was polytheistic. It also contributes to 4E approaches to religion, shedding light on how religious ideas and concepts—here in the form of word pairs—both draw from how the brain understands embodiment and themselves are processed in embodied, neurologically specific ways. Full article
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19 pages, 17590 KB  
Article
Widespread Hyper-Coupling and Frequency-Specific Dysregulation of Phase-Amplitude Coupling in Young Children with Autism Spectrum Disorder
by Jiannan Kang, Zongbing Xiao, Zhiyuan Fan, Xiangyu Zhang, Xiaoli Li and Xing Jin
Brain Sci. 2026, 16(7), 718; https://doi.org/10.3390/brainsci16070718 - 4 Jul 2026
Viewed by 456
Abstract
Background: Autism spectrum disorder (ASD) is characterized by widespread aberrations in brain scalp-level synchronization. Phase-amplitude coupling (PAC), which reflects cross-frequency neuronal oscillatory interactions, serves as a crucial metric for assessing functional brain integration. However, the specific patterns of PAC at both intra-region and [...] Read more.
Background: Autism spectrum disorder (ASD) is characterized by widespread aberrations in brain scalp-level synchronization. Phase-amplitude coupling (PAC), which reflects cross-frequency neuronal oscillatory interactions, serves as a crucial metric for assessing functional brain integration. However, the specific patterns of PAC at both intra-region and inter-region scalp levels in young children with ASD, as well as their precise associations with clinical symptoms, remain unclear. Methods: This study enrolled 237 children with ASD aged 3–9 years and 201 age-matched typically developing (TD) children. Resting-state electroencephalography (EEG) data were acquired from all participants. The analysis systematically examined low-frequency oscillation phase (δ, θ, α) modulation of high-frequency oscillation amplitude (β and low γ) from both intra-region and inter-region dimensions. The PAC strength was quantified using the modulation index (MI). Multiple comparisons were corrected using the Bonferroni method. Finally, correlations between PAC metrics and Autism Behavior Checklist (ABC) scores were analyzed. Results: Compared to the control group, children with ASD exhibited significant frequency-specific PAC abnormalities: (1) Multi-regional γ hyper-coupling: There was a significant enhancement in the modulation of γ amplitude by δ/θ/α phase across the measured scalp regions, suggesting abnormal high-frequency synchronization. (2) Dissociated β modulation patterns: The ASD group showed increased δ–β coupling (predominantly in frontal, temporal, and occipital lobes) alongside significantly reduced α–β coupling (localized to frontal and central regions). This reflects both an abnormal locking of slow-wave activity to the β band and a diminished regulatory role of α oscillations. (3) Clinical correlation: Notably, abnormally elevated PAC strength (particularly in the δ/θ/α–γ bands) showed a negative correlation with clinical symptom severity—that is, stronger coupling was associated with lower scores on the ABC. Conclusions: Leveraging a large-sample dataset, this study characterizes the landscape of aberrant cross-frequency interactions in young children with ASD. Our findings indicate that the neuroelectrical activity in ASD goes beyond mere connectivity anomalies by demonstrating altered PAC strength at both the intra-region and inter-region levels. Notably, the strength of this aberrant intra-region PAC is correlated with clinical symptoms. Full article
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22 pages, 6676 KB  
Article
Neurophysiological Responses to Inhalation of Osmanthus fragrans Volatiles: A Combined Electronic Nose and Electroencephalogram (EEG) Study on Concentration-Dependent Effects
by Seong Jun Hong, Hyeonjin Park, Younglan Ban, Se Young Yu, Hee Sung Moon, Ji Sun Kim, Daeyong Shin, Kiseong Kim, Young Jun Kim, Jae Kyeom Kim and Eui-Cheol Shin
Plants 2026, 15(13), 2006; https://doi.org/10.3390/plants15132006 - 29 Jun 2026
Viewed by 834
Abstract
Fragrant olive (Osmanthus fragrans var. aurantiacus (O. fragrans)) extract is known to influence neurophysiological responses through inhalation, yet research on concentration-dependent effects and sex-specific variations remains insufficient. This study utilized an electronic nose (E-nose), electroencephalography (EEG), and standardized low-resolution electromagnetic [...] Read more.
Fragrant olive (Osmanthus fragrans var. aurantiacus (O. fragrans)) extract is known to influence neurophysiological responses through inhalation, yet research on concentration-dependent effects and sex-specific variations remains insufficient. This study utilized an electronic nose (E-nose), electroencephalography (EEG), and standardized low-resolution electromagnetic tomography (sLORETA) to characterize the volatile profiles and neurophysiological impacts of O. fragrans at 3% and 5% concentrations. E-nose analysis identified 48 volatile compounds, with chemometric modeling (PCA, HCA) showing clear discrimination between concentrations. EEG results demonstrated that inhalation induced significant concentration-dependent changes—specifically increasing sedation-related alpha waves and decreasing tension-related gamma waves—with 5% O. fragrans eliciting more widespread cortical responses than the 3% concentration. Notably, no significant sex-related differences were observed in general EEG patterns; however, sLORETA revealed that 5% inhalation specifically suppressed high beta and gamma activities in male participants within Brodmann areas 13, 21, 22, and 44, regions associated with emotional and multisensory processing. In conclusion, this study successfully quantified the relationship between volatile profiles and human brain responses using an integrated biomimetic and neurophysiological approach. These findings provide objective evidence that O. fragrans inhalation, particularly at 5%, modulates neural oscillations toward a relaxed state, offering valuable data for olfactory perception and potential applications as functional volatile compounds. Full article
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Proceeding Paper
Interactive Brain Interface for Multimodal EEG Visualization and Disease-Specific Neural Dynamics
by Souhaila Khalfallah, Alaeddine Hmidi and Kais Bouallegue
Med. Sci. Forum 2026, 46(1), 5; https://doi.org/10.3390/msf2026046005 - 26 Jun 2026
Viewed by 488
Abstract
Understanding how brain activity varies across neurological and neurodevelopmental disorders requires tools capable of revealing patterns hidden in complex electroencephalographic (EEG) data. Conditions such as epilepsy, Alzheimer’s disease, dementia, and autism exhibit distinct alterations in neural oscillations and connectivity, which remain difficult to [...] Read more.
Understanding how brain activity varies across neurological and neurodevelopmental disorders requires tools capable of revealing patterns hidden in complex electroencephalographic (EEG) data. Conditions such as epilepsy, Alzheimer’s disease, dementia, and autism exhibit distinct alterations in neural oscillations and connectivity, which remain difficult to interpret in real time; therefore, this study proposes an interactive interface for intuitive exploration and analysis of disease-specific EEG dynamics. The system integrates classical signal processing techniques and computational modeling to extract spectral features, inter-electrode coherence, and spatial activation patterns, which are visualized through spectrograms, topographic maps, and connectivity graphs that update continuously. In addition, a web-based platform is incorporated to enable clinicians and technicians to store and manage patient information, including diagnosis, severity level, number of recordings, sampling frequency, recording duration, and acquisition dates, supporting structured data organization and longitudinal monitoring. The results demonstrate that the interface captures meaningful differences between disorders, with epileptic patterns showing strong synchronization and burst activity, while neurodegenerative conditions exhibit spectral slowing and reduced connectivity. Overall, the proposed framework provides an effective and accessible tool for EEG visualization, combining interactive analysis with clinical data management to support research, education, and potential clinical applications. Full article
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