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Search Results (1,936)

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Keywords = brain functional network

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21 pages, 7860 KB  
Article
D-SFANet: Application of a Multimodal Fusion Framework Based on Attention Mechanisms in ADHD Identification and Classification
by Li Zhang, Guangcheng Dongye and Ming Jing
Mathematics 2026, 14(5), 851; https://doi.org/10.3390/math14050851 (registering DOI) - 2 Mar 2026
Abstract
The diagnosis of attention-deficit/hyperactivity disorder (ADHD) has long relied on subjective scales, lacking objective neuroimaging biomarkers. Static functional connectivity (sFC) and dynamic functional connectivity (dFC), as commonly used metrics in resting-state functional magnetic resonance imaging (rs-fMRI) analysis, provide important perspectives for related research. [...] Read more.
The diagnosis of attention-deficit/hyperactivity disorder (ADHD) has long relied on subjective scales, lacking objective neuroimaging biomarkers. Static functional connectivity (sFC) and dynamic functional connectivity (dFC), as commonly used metrics in resting-state functional magnetic resonance imaging (rs-fMRI) analysis, provide important perspectives for related research. However, existing unimodal approaches struggle to effectively integrate the spatiotemporal characteristics of functional connectivity. To address this, this paper proposes the multimodal fusion framework D-SFANet, which synergistically models the static and dynamic features of brain functional connectivity through an attention mechanism: in the static path, it integrates a multi-scale convolutional network with phenotypic information extraction to extract hierarchical topological features; in the dynamic path, it combines graph theory with a bidirectional long short-term memory network (BiLSTM) to capture key state transition patterns in brain networks. Experimental validation demonstrates that D-SFANet achieves significantly higher classification accuracy than existing mainstream methods, robustly validating the effectiveness of its spatiotemporal fusion strategy. Full article
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13 pages, 250 KB  
Review
Mild Traumatic Brain Injury and Functional Amnesia: When Concussion Becomes a Gateway to Functional Cognitive Disorder
by Ioannis Mavroudis, Foivos Petridis, Alin Ciobica, Sotirios Papagiannopoulos and Dimitrios Kazis
Brain Sci. 2026, 16(3), 278; https://doi.org/10.3390/brainsci16030278 - 28 Feb 2026
Viewed by 6
Abstract
Mild traumatic brain injury (mTBI) is typically associated with transient cognitive disturbance, particularly involving attention and new learning, with most patients demonstrating full recovery within weeks. Memory impairment in uncomplicated mTBI generally reflects reversible neurometabolic dysfunction and is limited to a brief period [...] Read more.
Mild traumatic brain injury (mTBI) is typically associated with transient cognitive disturbance, particularly involving attention and new learning, with most patients demonstrating full recovery within weeks. Memory impairment in uncomplicated mTBI generally reflects reversible neurometabolic dysfunction and is limited to a brief period of post-traumatic amnesia and restricted retrograde loss surrounding the injury. However, a subset of patients develop persistent and disproportionate autobiographical memory disturbance that exceeds expected neuroanatomical limits and lacks structural correlates on neuroimaging. In rare but clinically challenging cases, this presentation may resemble extensive retrograde or identity-related amnesia. This review examines functional (dissociative) amnesia emerging after mTBI and proposes that concussion may act as a gateway condition facilitating the development of Functional Cognitive Disorder (FCD) in vulnerable individuals. We differentiate expected post-traumatic memory patterns from atypical selective impairment of autobiographical retrieval and clarify how distinct memory systems—episodic, autobiographical, semantic, and procedural—are differentially affected. We expand the two-hit hypothesis by integrating contemporary neurobiological evidence. The first hit comprises concussion-induced neurometabolic disturbance, glial activation, oxidative imbalance, and transient fronto-limbic dysregulation. The second hit may involve psychological stress, identity threat, maladaptive metacognitive processes, or persistent neuroinflammatory signalling, collectively resulting in functional inhibition of autobiographical memory retrieval despite preserved memory storage. Functional amnesia is conceptualised as a severe phenotype within the spectrum of functional cognitive disorder. We introduce a structured clinician-administered interview (SIFRA) to operationalise diagnostic features and support systematic assessment. This integrative framework reconciles neurological vulnerability with functional network dysregulation and provides a coherent basis for diagnosis and multidisciplinary management of persistent memory disturbance after mTBI. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
26 pages, 2801 KB  
Article
A Deep Learning-Based Decision Support System for Sensory Evaluation: A Predictive Framework for Functional Product Taste Assessment in Neuromarketing
by Jesús Jaime Moreno Escobar, Verónica de Jesús Pérez Franco, Mauro Daniel Castillo Pérez, Ana Lilia Coria Páez, Erika Yolanda Aguilar del Villar and Hugo Quintana Espinosa
Appl. Sci. 2026, 16(5), 2368; https://doi.org/10.3390/app16052368 - 28 Feb 2026
Viewed by 39
Abstract
This study aims to investigate the relationship between consumer neuroscience and neuromarketing using a multivariate methodology. Tools such as Principal Component Analysis (PCA) and deep learning neural networks were employed to interpret consumer responses to functional products. To this end, EEG signals were [...] Read more.
This study aims to investigate the relationship between consumer neuroscience and neuromarketing using a multivariate methodology. Tools such as Principal Component Analysis (PCA) and deep learning neural networks were employed to interpret consumer responses to functional products. To this end, EEG signals were collected, recorded, and analyzed from 83 participants aged 20 to 29 to identify significant neural markers related to food consumption decisions. Key factors influencing decision making were identified, including low beta and gamma frequency bands. Participants’ levels of attention and reflection also played a role. The findings validate the effectiveness of the proposed method, demonstrating its applicability in various fields requiring accurate and reliable classification. Furthermore, some possible applications of this topic are mentioned in the food industry section, with the aim of enabling them to develop personalized nutritional strategies based on the results obtained from the brain activity of consumers. Full article
(This article belongs to the Special Issue Deep Learning and Machine Learning in Information Systems)
36 pages, 12470 KB  
Review
Fluorescent Labeling Methods for Brain Structure Research
by Chunguang Yin, Jiangcan Li, Keyu Meng, Jiade Zhang, Meihe Chen, Ruibing Chen, Yuyang Hu, Shuodong Wang and Sheng Xie
Molecules 2026, 31(5), 817; https://doi.org/10.3390/molecules31050817 (registering DOI) - 28 Feb 2026
Viewed by 33
Abstract
The brain is a complex structural network. The employment of fluorescent labeling techniques in conjunction with advanced imaging methodologies facilitates comprehensive analysis of multiscale brain anatomy, thereby offering insights into fundamental principles of function and addressing neurological disorders. This review summarizes technological advances [...] Read more.
The brain is a complex structural network. The employment of fluorescent labeling techniques in conjunction with advanced imaging methodologies facilitates comprehensive analysis of multiscale brain anatomy, thereby offering insights into fundamental principles of function and addressing neurological disorders. This review summarizes technological advances in fluorescent labeling methods in the field of neuroscience, and their applications in neural circuit analysis, cerebrovascular imaging, neuronal activity monitoring, and fluorescence-guided treatment of brain tumors. A challenging trend in integrating smart fluorescent labeling with tissue clearing, wide-field 3D imaging, artificial intelligence-assisted data processing/reconstruction, and multimodal information fusion is highlighted and discussed. The future direction of combining high-resolution, low-damage, dynamic imaging with big data analysis is envisioned, providing tools for understanding brain structure and function and their roles in disease. Full article
(This article belongs to the Special Issue Fluorescent Molecular Tools for Neuroscience Research)
15 pages, 2381 KB  
Article
Interhemispheric Functional Hypoconnectivity Is an Early Marker of Cortical Epileptogenesis
by Tatiana M. Medvedeva and Lyudmila V. Vinogradova
Biomedicines 2026, 14(3), 549; https://doi.org/10.3390/biomedicines14030549 (registering DOI) - 28 Feb 2026
Viewed by 51
Abstract
Background: Epilepsy is a network disorder, and network-based approaches to its diagnostics and therapies attract growing attention. Identification of prognostic markers of epileptogenesis and long-term risk for developing epilepsy after brain insults is an urgent, unresolved problem. We examined whether intracortical connectivity patterns [...] Read more.
Background: Epilepsy is a network disorder, and network-based approaches to its diagnostics and therapies attract growing attention. Identification of prognostic markers of epileptogenesis and long-term risk for developing epilepsy after brain insults is an urgent, unresolved problem. We examined whether intracortical connectivity patterns reflect early epileptogenic changes in the cortex. Methods: We used the audiogenic kindling model, in which cortical epileptogenesis is initiated by repetition of reflex subcortically-driven seizures. Two measures of functional connectivity—mutual information and mean phase coherence—were applied to electrocorticographic recordings obtained from homotopical sites of parietal cortex during interictal and immediate postictal periods in awake rats. Interhemispheric connectivity and synchrony in non-kindled and slightly kindled rats were compared. Cortical spreading depolarization (SD), the first manifestation of growing cortical excitability in several models of epileptogenesis, was used as an electrographic marker of the earliest kindling stage. Results: In kindled animals, baseline levels of hemispheric connectivity and gamma band synchrony were significantly lower compared to seizure-naive rats. Before kindling, subcortical seizures elicited mild postictal depression of cortical gamma oscillations without changes in interhemispheric functional connectivity. Early in kindling, seizures produced wideband postictal depression of cortical activity and a striking drop in hemispheric connectivity. Conclusions: Primary network alterations during epileptogenesis involve hemispheric decoupling and reduced synchronization, both sustained (between seizures) and transient (postictal). Breakdown of long-range intracortical communication may reflect homeostatic plasticity and an active attempt to restrict epileptogenic reorganization of neural networks. We think that resting-state hemispheric hypocoupling could be an early marker of epileptogenesis. Seizure-induced SD contributes to the generation of postictal events. Full article
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17 pages, 4382 KB  
Article
Modulation of Different Salinity Conditions on Transcriptional Signature of Metabotropic Serotonin and Dopamine Receptors in Nile Tilapia (Oreochromis niloticus)
by Ming-Yuan Wu, Pichayapa Meekuan, Zhuo-Hang Feng, Zheng-Xiang Zhang, Ya-Xin Wang, Yue-Yan Sun, Zhi-Shuai Hou and Zhen-Fa Qin
Fishes 2026, 11(3), 142; https://doi.org/10.3390/fishes11030142 - 27 Feb 2026
Viewed by 58
Abstract
As freshwater resources become increasingly limited, exploiting brackish and marine waters for aquaculture is viewed as a promising alternative. Nile tilapia (Oreochromis niloticus), although considered euryhaline, shows relatively restricted tolerance to salinity compared with other tilapia species, making it an ideal [...] Read more.
As freshwater resources become increasingly limited, exploiting brackish and marine waters for aquaculture is viewed as a promising alternative. Nile tilapia (Oreochromis niloticus), although considered euryhaline, shows relatively restricted tolerance to salinity compared with other tilapia species, making it an ideal model to study adaptive responses to osmotic stress. Serotonin (5-HT) and dopamine (DA) are key modulators of stress responses through their activation of metabotropic G protein-coupled receptors (GPCRs). In this study, we investigated the transcriptional profiles of metabotropic serotonin and dopamine receptors across the brain, intestine, and liver of Nile tilapia reared in different salinity conditions (0 ppt, 16 ppt, 30 ppt). The results showed both dopamine and serotonin metabotropic receptors were duplicated with potential neofunctionalization, contributing to osmoregulatory capacity. Nile tilapia showed altered brain drd1, htr1 and htr7 subtypes in response to salt change. Meanwhile, the drd3 subtype showed pronounced alterations in the intestine and liver under elevated salinity. Notable transcriptional alterations in htr4 subtypes were observed in both brain and liver, suggesting their potential involvement in modulating energy balance and stress adaptation. Correlation network analyses further demonstrated coordinated regulation among receptor paralogues in the brain. These findings provide potential targets, such as ligand analog additives or genetic enhancement, for future functional validation and for improving salinity tolerance in Nile tilapia culture. Full article
(This article belongs to the Special Issue Physiological and Behavioral Studies in Aquaculture)
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20 pages, 6109 KB  
Article
Binaural Beat Stimulation Enhances Cognitive Function in Alzheimer’s Disease via Temporal Lobe Activation: An sLORETA Study
by Muhammad Danish Mujib, Nayab Mubashir, Ahmad Zahid Rao, Nisha Nasir, Ayesha Ikhlaq, Syeda Sehar Hussain, Fizza Zia, Ghulam Mohiuddin Asim, Ahmad O. Alokaily, Mohamed A. Almadi, Saad Ahmed Qazi and Muhammad Abul Hasan
Biomedicines 2026, 14(3), 540; https://doi.org/10.3390/biomedicines14030540 - 27 Feb 2026
Viewed by 119
Abstract
Background: The global prevalence of Alzheimer’s disease (AD) has reached 55.2 million. AD is characterized by progressive deterioration in cognition and working memory (WM), which are essential for attention, reasoning, and learning. These impairments are associated with pathological changes in cortical and [...] Read more.
Background: The global prevalence of Alzheimer’s disease (AD) has reached 55.2 million. AD is characterized by progressive deterioration in cognition and working memory (WM), which are essential for attention, reasoning, and learning. These impairments are associated with pathological changes in cortical and subcortical regions. Binaural beats (BBs), a non-invasive auditory neuromodulation technique, have demonstrated cognitive enhancement effects in healthy individuals; however, their impact on WM in patients with AD remains largely unexplored. Methods: This study investigated the effects of BB stimulation on WM and cognitive function in the temporal lobe of patients with AD using standardized Low-Resolution Electromagnetic Tomography (sLORETA). Twenty-five patients with AD were randomly assigned to either an experimental group (n = 15) that received BB stimulation or a control group (n = 10) that received standard auditory stimulation. EEG recordings were obtained before and after the intervention. Results: Paired t-tests conducted on timeframe and frequency-wise sLORETA images revealed significant increases (p < 0.05) in theta, alpha1, and alpha2 frequency bands in the experimental group. Activated regions included the inferior, middle, superior, and transverse temporal gyri; Brodmann areas (BA) 20, 21, 22, 40, and 42; as well as networks associated with working memory and cognition. Conclusions: These findings suggest that BB stimulation induces temporal lobe activation, thereby enhancing working memory and cognitive function in patients with AD. Full article
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21 pages, 591 KB  
Review
Mood and Cognitive Disorders Following Hearing Loss: Impact of Hearing Aid Timing
by Giuseppe Alberti, Sabrina Loteta, Daniele Portelli, Cosimo Galletti, Francesco Galletti, Bruno Galletti, Mario Lentini, Salvatore Ronsivalle, Salvatore Maira, Jérôme René Lechien, Stephane Gargula and Antonino Maniaci
Audiol. Res. 2026, 16(2), 32; https://doi.org/10.3390/audiolres16020032 - 26 Feb 2026
Viewed by 95
Abstract
Background: Hearing loss is one of the most common yet often overlooked sensory deficits worldwide, with consequences extending well beyond auditory function. Mounting evidence highlights the complex interrelationships among hearing loss, cognitive decline, and psychosocial well-being. Neural mechanisms underlying this association include increased [...] Read more.
Background: Hearing loss is one of the most common yet often overlooked sensory deficits worldwide, with consequences extending well beyond auditory function. Mounting evidence highlights the complex interrelationships among hearing loss, cognitive decline, and psychosocial well-being. Neural mechanisms underlying this association include increased cognitive load, cortical reorganisation, and social isolation, which mediate the impact of auditory deprivation on the brain and mental health. Furthermore, hearing impairment is consistently associated with a higher risk of depression and anxiety, particularly when the duration of untreated deafness is prolonged. Methods: This narrative review summarises recent longitudinal and neuroimaging studies investigating the effects of hearing loss and the timing of intervention with hearing aids. The review focuses on evidence addressing cognitive, psychological, and neural outcomes in relation to early versus delayed amplification. Results: Across multiple studies, early adoption of hearing aids within a limited timeframe after diagnosis is linked to better cognitive performance, lower depressive symptom scores, and more preserved neural network integrity. Experimental evidence supports the existence of sensitive periods for auditory intervention, during which brain plasticity allows for optimal reorganisation and recovery of function. Conversely, delayed amplification may lead to irreversible cortical changes and persistent psychosocial distress. Despite this, several barriers—healthcare accessibility, patient attitudes, and economic constraints—continue to delay timely intervention. Conclusions: Early identification and management of hearing loss are critical to preserve cognitive and emotional health. An integrated approach addressing both hearing and cognitive well-being, supported by patient education and personalised care strategies, may maximise the benefits of amplification and improve overall quality of life. Full article
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22 pages, 4017 KB  
Article
The Effect of Music Stimulation on Resting-State Brain Functional Networks Following Exhaustive Endurance Exercise: An EEG Study
by Jing Fan, Bohan Li, Fujie Liu, Fanghao Jiao, Aiping Chi and Shuqi Yao
Brain Sci. 2026, 16(3), 258; https://doi.org/10.3390/brainsci16030258 - 25 Feb 2026
Viewed by 176
Abstract
Objective: The purpose of this research is to examine how motivational music immediately impacts the brain’s functional connectivity patterns in male athletes following a single session of intense endurance exercise, utilizing resting-state electroencephalography (EEG) and brain network analysis methods. Methods: The study involved [...] Read more.
Objective: The purpose of this research is to examine how motivational music immediately impacts the brain’s functional connectivity patterns in male athletes following a single session of intense endurance exercise, utilizing resting-state electroencephalography (EEG) and brain network analysis methods. Methods: The study involved 34 healthy male athletes who were tasked with performing incremental cycling exercises until exhaustion, both with and without music. Their resting-state EEG was recorded before and after the exercise. Brain functional networks were analyzed in the theta, alpha, and beta frequency bands based on changes in phase locking value (PLV). Specifically, the study examined the central executive network (CEN), default mode network (DMN), salience network (SN), sensorimotor network (SMN), and dorsal attention network (DAN), assessing their topological properties using graph theory methods. Results: Music significantly prolonged the time to exhaustion. Across frequency bands, the music condition exhibited higher global and local efficiency compared with the no-music condition. Following exhaustion without music, beta-band connectivity significantly increased, suggesting compensatory hyper-synchronization under fatigue. In contrast, music led to reduced alpha- and beta-band global connectivity post-exercise, accompanied by selective strengthening of functionally relevant couplings, particularly between SMN and CEN, and enhanced DAN–DMN coordination. Additionally, music prevented maladaptive connectivity shifts observed under fatigue, including excessive SN–CEN coupling. Conclusions: Exhaustive exercise without music induces widespread beta-band hyper-connectivity, reflecting increased neural cost under central fatigue. Music, however, promotes a more efficient and selectively integrated network configuration, supporting the neural efficiency hypothesis. These findings provide neurophysiological evidence that music optimizes large-scale brain network organization under physical stress, thereby contributing to enhanced endurance performance. Full article
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14 pages, 255 KB  
Review
Neuroscience-Informed Creative Group Therapy for Processing Trauma and Developing Resilience During Wartime
by Sharon Vaisvaser, Yifat Shalem-Zafari, Neta Ram-Vlasov and Liat Shamri-Zeevi
J. Pers. Med. 2026, 16(3), 128; https://doi.org/10.3390/jpm16030128 - 25 Feb 2026
Viewed by 149
Abstract
Traumatic experiences can disrupt one’s sense of safety, self-efficacy, and relationships. Prolonged stress may lead to anxiety, depression, and diminished agency. The embodied, subjective manifestations of trauma call for personalized therapeutic approaches that address symptoms and foster resilience. Group Creative Arts Therapies (CATs) [...] Read more.
Traumatic experiences can disrupt one’s sense of safety, self-efficacy, and relationships. Prolonged stress may lead to anxiety, depression, and diminished agency. The embodied, subjective manifestations of trauma call for personalized therapeutic approaches that address symptoms and foster resilience. Group Creative Arts Therapies (CATs) offer relational aesthetic interventions that promote resilience and trauma recovery. Incorporating body-based methods, movement, materials and visual expression, CATs support interoceptive awareness, multisensory integration, embodiment, and emotional–cognitive processing. This article presents a review and conceptual framework of group CAT interventions during wartime, focusing on challenges related to body awareness, self-efficacy, and autobiographical memory. It examines how creative aesthetic approaches help process trauma and strengthen resilience. Drawing on predictive processing accounts of brain function, the article explores the neuropsychological impact of trauma and how creative group work may modulate related brain mechanisms. Creative techniques can foster bodily anchored self-awareness, self-efficacy and processes of traumatic memory reconsolidation. Aesthetic experiences are associated with changes in brain activation and connectivity through processes of embodiment, externalization, and meaning making. On an intrapersonal level, converging evidence highlights the role of sensory and sensorimotor processing, along with the dynamic interplay between Default Mode, Executive Control, and Salience networks, as conceptualized in the Triple Network Model. On an interpersonal level, the literature points to the dynamics of brain and body synchronization, as emerging phenomena during shared creative engagement. These neurodynamics provide a coherent framework for understanding how creative arts-based psychotherapeutic group work can support trauma processing and the cultivation of resilience. Full article
(This article belongs to the Special Issue Mental Health: Clinical Advances in Personalized Medicine)
26 pages, 2399 KB  
Review
Ayahuasca and Its Main Component N,N-Dimethyltryptamine (DMT) for the Treatment of Mental Disorders: Mechanisms of Action, Clinical Studies, and Tools to Explore the Human Mind
by Alice Melani, Giorgia Papini, Marco Bonaso, Letizia Biso, Shivakumar Kolachalam, Nicola Luigi Bragazzi, Ciro Conversano, Graziella Orrù, Biancamaria Longoni and Marco Scarselli
Biomedicines 2026, 14(3), 506; https://doi.org/10.3390/biomedicines14030506 - 25 Feb 2026
Viewed by 178
Abstract
In recent years, psychopharmacology has experienced a significant challenge, highlighting a renewed and strong scientific interest in psychedelics as breakthrough therapies for mental disorders. Psychedelics can influence cognitive and emotional processes, showing solid therapeutic potential, particularly in treatment-resistant psychiatric disorders. Amongst the most [...] Read more.
In recent years, psychopharmacology has experienced a significant challenge, highlighting a renewed and strong scientific interest in psychedelics as breakthrough therapies for mental disorders. Psychedelics can influence cognitive and emotional processes, showing solid therapeutic potential, particularly in treatment-resistant psychiatric disorders. Amongst the most promising compounds, ayahuasca and its main psychoactive component, N,N-dimethyltryptamine (DMT), have received considerable attention. Ayahuasca is a psychoactive brew traditionally prepared from the liana Banisteriopsis caapi and the leaves of Psychotria viridis. Its psychoactive properties derive mainly from DMT, while β-carbolines, which act as monoamine oxidase-A (MAO-A) inhibitors, prevent the metabolic degradation of DMT, enhancing its bioavailability and allowing oral administration. In contrast, in monotherapy, DMT or its analog 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is generally administered via alternative routes, like inhalation, intranasal, or intravenous delivery. DMT is primarily a serotonin (5-HT)2A receptor partial agonist, whereas 5-MeO-DMT has a higher affinity for the 5-HT1A receptor compared to 5-HT2A, though other receptor targets are engaged, fostering neuroplasticity and a reorganization of brain networks involved in perception, cognition, and mood regulation. Despite limited clinical trials, current evidence offers an optimistic outlook on DMT and 5-MeO-DMT efficacy for treatment-resistant depression (TRD) and major depressive disorder (MDD), whereas evidence for other mental disorders studies is still preliminary. There are four phase II studies with 5-MeO-DMT and one with DMT for TRD, while there are two phase II studies with DMT fumarate for MDD. Beyond their therapeutic potential, psychedelics also represent powerful tools for exploring the human mind, offering valuable insights into brain function and mental health. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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18 pages, 5999 KB  
Article
A Two-Stage Framework for Early Detection and Subtype Identification of Alzheimer’s Disease Through Multimodal Biomarker Extraction and Improved GCN
by Junshuai Li, Wei Kong and Shuaiqun Wang
Brain Sci. 2026, 16(3), 255; https://doi.org/10.3390/brainsci16030255 - 25 Feb 2026
Viewed by 138
Abstract
Background: Imaging-transcriptomic analysis, through the integration of multimodal magnetic resonance imaging (MRI) and transcriptomic data, provides complementary structural, functional, and molecular information that is crucial for the early detection and mechanistic exploration of Alzheimer’s disease (AD). However, effectively extracting features from heterogeneous multimodal [...] Read more.
Background: Imaging-transcriptomic analysis, through the integration of multimodal magnetic resonance imaging (MRI) and transcriptomic data, provides complementary structural, functional, and molecular information that is crucial for the early detection and mechanistic exploration of Alzheimer’s disease (AD). However, effectively extracting features from heterogeneous multimodal data and capturing the associations between microscopic molecular variations and macroscopic brain alterations remain key challenges. Recent advances in deep learning and multimodal integration have enhanced the ability to model nonlinear cross-modal relationships, enabling more accurate identification of imaging-transcriptomic biomarkers and subtypes. Developing robust multimodal frameworks is therefore essential for early AD detection, subtype identification, and advancing precision medicine in neurodegenerative diseases. Methods: In this study, a two-stage method of multimodal Feature Extraction based on Association Analysis and Graph Convolutional Network with Self-Attention and Self-Expression framework (MFEAA-GCNSASE) for early diagnosis of AD and effective identification of subtypes of MCI with different progression to AD is proposed. In the first stage, the MFEAA model is applied to integrate multiple association analysis methods on sMRI, PET, and transcriptomic data to identify key multimodal biomarkers for AD and mild cognitive impairment (MCI). In the second stage, the GCNSASE model enhances classification accuracy between AD and MCI patients through self-attention and self-expression layers. Additionally, unsupervised clustering was performed on MCI samples using top multimodal biomarkers to explore subtype heterogeneity and conversion risk. Reliable MCI subtypes were also identified through a consensus clustering approach. Results: The proposed algorithm integrates sMRI, PET, and transcriptomic data, identifying robust biomarkers including the Left Hippocampus, Left Angular Gyrus, and key genes such as SLC25A5 and GABARAP. To ensure statistical robustness given the extreme class imbalance, we employed a rigorous repeated stratified cross-validation (RSCV) framework. GCNSASE achieved state-of-the-art discrimination performance with mean AUC values ranging from 0.946 to 0.961 across feature subsets (10–50%), significantly outperforming MOGONET (mean AUC: 0.844–0.875, p < 0.001) and conventional machine learning models with tighter 95% confidence intervals, indicating superior stability despite the limited AD sample size. Clustering analysis revealed two distinct MCI subtypes with divergent molecular landscapes: Subtype A was enriched in energy metabolism and cellular maintenance pathways, whereas Subtype B was enriched in neuroinflammatory and aberrant signaling pathways. Notably, the majority of MCI patients who subsequently converted to AD were concentrated in the immune-inflammatory Subtype B. These findings highlight that neuroinflammation coupled with bioenergetic failure constitutes a critical mechanism driving the conversion from MCI to AD. Conclusions: The proposed methods not only provide the key multimodal biomarkers and enhance the accuracy of the classification model for early AD diagnosis but also identify biologically and clinically meaningful MCI subtypes with distinct molecular signatures and conversion risks. Exploring these associated multimodal biomarkers and MCI subtypes is of great significance, as they help elucidate the heterogeneous mechanisms underlying AD onset and progression, enable the identification of high-risk individuals likely to convert to AD, and provide a foundation for targeted therapeutic strategies and individualized clinical management. These findings have important implications for understanding disease heterogeneity, discovering potential intervention targets, and advancing precision medicine in neurodegenerative diseases. Full article
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23 pages, 514 KB  
Systematic Review
Syntactic Processing in the Aging Brain: Neural Reorganization, Cognitive Scaffolding, and Implications for Language Resilience
by Xinmiao Liu and Shengqi Wu
Brain Sci. 2026, 16(3), 251; https://doi.org/10.3390/brainsci16030251 - 24 Feb 2026
Viewed by 191
Abstract
Objectives: Although behavioral studies suggest that syntactic comprehension is relatively preserved in healthy aging, the underlying neural mechanisms remain a subject of intense debate. This review aims to synthesize neuroimaging and electrophysiological evidence to clarify how the aging brain reorganizes to maintain language [...] Read more.
Objectives: Although behavioral studies suggest that syntactic comprehension is relatively preserved in healthy aging, the underlying neural mechanisms remain a subject of intense debate. This review aims to synthesize neuroimaging and electrophysiological evidence to clarify how the aging brain reorganizes to maintain language resilience. Methods: A systematic search was conducted across multiple databases such as PubMed and Web of Science. Twenty-three relevant empirical studies meeting our inclusion criteria were identified. The synthesis focused on regional activation patterns, functional connectivity, and temporal dynamics during syntactic processing in older adults compared to younger controls. Results: The review revealed four key findings. First, the core left-lateralized frontotemporal language network remains resilient during syntactic processing in older adults. Second, age-related changes in functional connectivity within the core network are heterogeneous, with evidence for both reduction and preservation. Third, right-hemisphere homologues are increasingly recruited, but its functional significance is condition-dependent, serving both compensatory and non-compensatory roles. Fourth, older adults increasingly engage domain-general cognitive control regions, such as the dorsolateral prefrontal cortex and pre-supplementary motor area, to support syntactic processing under high cognitive loads. Conclusions: On the basis of these findings, we propose the Graded Compensation and Cognitive Scaffolding (GCCS) model which posits that language resilience is maintained through a graded and condition-dependent adaptation of neural resources. This study critically evaluates the current literature and highlights the need for more methodologically rigorous studies to better understand the effects of aging on syntactic processing and its neural basis. Given the limited number of eligible studies, the findings of this review should be interpreted with caution. More well-powered, longitudinal research is needed to uncover the trajectory of neural reorganization during syntactic processing in older adults. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
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12 pages, 7312 KB  
Article
Symptom-Oriented, Connectome-Informed Deep Brain Stimulation for Asymmetric Dystonic Tremor: Unilateral Ventral Intermediate Nucleus (VIM) DBS Targeting a Tremor-Dominant Network
by Olga Mateo-Sierra, Javier Ricardo Pérez-Sánchez, Beatriz De la Casa-Fages, María Teresa Del Castillo, Pilar Fernández, Pascual Elvira, José Paz and Francisco Grandas
J. Clin. Med. 2026, 15(4), 1666; https://doi.org/10.3390/jcm15041666 - 23 Feb 2026
Viewed by 213
Abstract
Background: Deep brain stimulation (DBS) has traditionally followed diagnosis-driven, nucleus-centered targeting paradigms. Increasing evidence supports a circuit-based framework in which clinical outcomes depend on modulation of symptom-relevant networks rather than diagnostic labels alone. This approach is particularly relevant in mixed movement disorder phenotypes [...] Read more.
Background: Deep brain stimulation (DBS) has traditionally followed diagnosis-driven, nucleus-centered targeting paradigms. Increasing evidence supports a circuit-based framework in which clinical outcomes depend on modulation of symptom-relevant networks rather than diagnostic labels alone. This approach is particularly relevant in mixed movement disorder phenotypes such as dystonic tremor, where the most disabling symptom may not align with the conventional surgical target. Methods: We report a clinically illustrative single case treated using a symptom-oriented, connectome-informed DBS strategy. Clinical phenotype, tremor severity, functional impairment, prior medical and botulinum toxin treatments, and longitudinal outcomes were systematically reviewed. DBS target selection prioritized the dominant, treatment-refractory symptom rather than the underlying dystonia diagnosis. Surgical planning incorporated high-resolution MRI with patient-specific thalamic segmentation using Brainlab Brain Elements®, followed by postoperative lead localization and volume of tissue activated visualization with the SureTune™ platform. Results: A 54-year-old left-handed woman with long-standing cervical dystonia developed a severe, markedly asymmetric dystonic tremor predominantly affecting the left upper limb, resulting in profound functional disability. Instead of conventional bilateral globus pallidus internus DBS, unilateral right ventral intermediate nucleus (VIM) DBS was selected to engage tremor-related cerebellothalamic circuits. Rapid and marked improvement was observed, with tremor severity reduced to mild levels within 15 days after stimulation onset. At 6-month follow-up, overall tremor severity improved from 49 to 13 points on the Fahn–Tolosa–Marin Tremor Rating Scale, corresponding to a 73.5% reduction. This improvement was associated with restoration of legible handwriting, independent feeding and drinking, and recovery of bimanual fine motor function. Clinical benefit remained stable throughout follow-up, without stimulation-related adverse effects. Conclusions: This case illustrates the feasibility of a symptom-oriented, connectome-informed DBS strategy in selected patients with dystonic tremor. When symptom expression and network involvement are markedly asymmetric, selective unilateral modulation of the tremor-dominant circuit may achieve meaningful and durable functional improvement. Further studies are needed to assess the generalizability of this approach. Full article
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31 pages, 1766 KB  
Review
Opioid Receptors in Psychedelia: Indirect Serotonergic Modulation of Direct KOR Activation by Salvinorin A
by Maximiliano Ganado, Carmen Rubio, Javier Pérez-Villavicencio, Norma Serrano, Héctor Romo-Parra, Ángel Lee and Moisés Rubio-Osornio
Biomedicines 2026, 14(2), 476; https://doi.org/10.3390/biomedicines14020476 - 21 Feb 2026
Viewed by 654
Abstract
The neuropharmacology of psychedelics has traditionally focused on serotonergic mechanisms, particularly 5-HT2A receptor activation. However, this paradigm incompletely explains the diversity of neurobiological and therapeutic effects observed across psychedelic compounds. Non-classical psychedelics such as salvinorin A, the primary active constituent of Salvia divinorum [...] Read more.
The neuropharmacology of psychedelics has traditionally focused on serotonergic mechanisms, particularly 5-HT2A receptor activation. However, this paradigm incompletely explains the diversity of neurobiological and therapeutic effects observed across psychedelic compounds. Non-classical psychedelics such as salvinorin A, the primary active constituent of Salvia divinorum, challenge this framework through direct kappa opioid receptor (KOR) agonism, representing a serotonin-independent pathway to altered consciousness. This review systematically examines the role of the endogenous opioid system in mediating psychedelic effects, with emphasis on salvinorin A’s unique KOR-dependent mechanisms. We synthesized preclinical and clinical evidence from in vitro studies, genetically modified animal models, optogenetic circuit dissection, and human neuroimaging trials. Salvinorin A’s selective KOR activation is characterized by pronounced β-arrestin-biased signaling, distinguishing it from endogenous dynorphins and classical KOR agonists. This produces rapid receptor desensitization, transient functional plasticity, and profound dissociative effects mediated through thalamocortical disruption, mesolimbic dopaminergic suppression, and fragmentation of large-scale brain networks. Classical serotonergic psychedelics indirectly engage opioid systems through downstream 5-HT2A signaling, contributing to analgesic and mood-regulatory effects via secondary MOR/DOR modulation. Despite being a potent opioid agonist, salvinorin A exhibits low abuse potential due to aversive phenomenology, dopaminergic suppression, and absence of positive reinforcement in animal models. Incorporating opioid receptor pharmacology into psychedelic neuroscience expands mechanistic understanding beyond serotonin-centric models, revealing multiple neurochemical pathways capable of inducing therapeutically relevant altered states. This framework enables rational development of biased KOR ligands and establishes salvinorin A as a paradigmatic model for non-serotonergic psychedelia with applications in treatment-resistant depression, addiction, and chronic pain. Full article
(This article belongs to the Special Issue Dopamine Signaling Pathway in Health and Disease—2nd Edition)
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