Brain Sciences

22 pages, 7800 KB

Open AccessArticle

A Cross-Subject Band-Power Complexity Metric for Detecting Mental Fatigue Through EEG

by Ang Li, Zhenyu Wang, Tianheng Xu, Ting Zhou, Xi Zhao, Honglin Hu and Marc M. Van Hulle

Brain Sci. 2026, 16(2), 199; https://doi.org/10.3390/brainsci16020199 (registering DOI) - 7 Feb 2026

Background/Objectives: Electroencephalography (EEG) is a promising modality for fatigue detection because it directly reflects neural states; however, it is hindered by the need for subject-specific calibration and its reliance on unstable labeling. Moreover, classical EEG features are sensitive to intrinsic brain rhythm [...] Read more.

Background/Objectives: Electroencephalography (EEG) is a promising modality for fatigue detection because it directly reflects neural states; however, it is hindered by the need for subject-specific calibration and its reliance on unstable labeling. Moreover, classical EEG features are sensitive to intrinsic brain rhythm variations, causing pronounced domain shifts that degrade performance across sessions and subjects. Methods: Motivated by the biological fatigue rebound mechanism, we propose a robust cross-subject metric which we name Short-Term Second-Order Differential Entropy (ST-SODE). ST-SODE effectively suppresses the interference of background brain rhythms, enhancing robustness to cross-domain drift; consequently, its one-dimensional output can provide an indication of fatigue states without additional model training. Results: ST-SODE is validated on the public driving fatigue regression dataset SEED-VIG and on a private Vigilance classification dataset based on the N-Back task. ST-SODE achieves a correlation coefficient of 0.56 on SEED-VIG dataset (vs. 0.4 for differential entropy, DE) and a binary classification accuracy of 93.75% on the Vigilance dataset, outperforming other EEG-based fatigue metrics. Conclusions: ST-SODE offers a reliable solution for deployment in fields such as driving, manufacturing, and healthcare, where it could reduce safety incidents caused by fatigue. Full article

(This article belongs to the Section Computational Neuroscience, Neuroinformatics, and Neurocomputing)

22 pages, 1982 KB

Open AccessArticle

Perceptual Decision Advantages in Open-Skill Athletes Emerge near the Threshold of Awareness: Behavioral, Computational, and Electrophysiological Evidence

by Xudong Liu, Shiying Gao, Yanglan Yu and Anmin Li

Brain Sci. 2026, 16(2), 198; https://doi.org/10.3390/brainsci16020198 (registering DOI) - 7 Feb 2026

Abstract

Background/Objectives: Perceptual awareness and decision formation unfold gradually as sensory evidence increases. Near the threshold of awareness, small differences in neural processing efficiency can be amplified into marked behavioral variability. Open-skill athletes are trained to make rapid decisions under dynamic and uncertain [...] Read more.

Background/Objectives: Perceptual awareness and decision formation unfold gradually as sensory evidence increases. Near the threshold of awareness, small differences in neural processing efficiency can be amplified into marked behavioral variability. Open-skill athletes are trained to make rapid decisions under dynamic and uncertain conditions, yet it remains unclear whether their perceptual advantage reflects enhanced early sensory sensitivity or more efficient late-stage evidence accumulation. This study aimed to identify the processing stage at which open-skill sports expertise exerts its influence. Methods: Twenty-five open-skill athletes and twenty-three non-athlete controls completed a visual orientation discrimination task with eight graded levels of stimulus visibility, ranging from subliminal to clearly visible. Behavioral performance was analyzed together with hierarchical drift–diffusion modeling to estimate latent decision parameters. Event-related potentials (ERPs) were recorded using a 64-channel EEG system during an active decision task and a passive viewing task, focusing on early (N2, P2) and late (P3) components. ERP–behavior correlations were examined across visibility levels. Results: No group differences were observed at the lowest visibility levels. Group differences emerged selectively at intermediate to high visibility levels, where athletes showed higher accuracy and a tendency toward faster responses. Drift–diffusion modeling revealed that this advantage was driven by higher drift rates in athletes, with no group differences in non-decision time, boundary separation, or starting point. Early ERP components (N2, P2) were strongly modulated by stimulus visibility but showed no consistent group differences. In contrast, the P3 component exhibited earlier and more pronounced differentiation across visibility levels in athletes. In the passive viewing task, group differences were substantially reduced. ERP–behavior analyses showed stronger and earlier P3–behavior coupling in athletes. Conclusions: Open-skill sports expertise selectively optimizes late-stage evidence accumulation and its translation into behavior, rather than enhancing unconscious or early sensory processing. Full article

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

13 pages, 7811 KB

Open AccessArticle

Astrocytes in the Ventral Tegmental Area Are Involved in Cotinine Self-Administration in Male Wistar Rats

by Xiaoying Tan and Zheng-Ming Ding

Brain Sci. 2026, 16(2), 197; https://doi.org/10.3390/brainsci16020197 (registering DOI) - 7 Feb 2026

Abstract

Background: Our recent studies indicate that astrocytes in a key mesocorticolimbic region play an important role in nicotine reinforcement. Nicotine self-administration elevated the astrocyte marker glial fibrillary acidic protein (GFAP) in the nucleus accumbens (NAc) core. Metabolic inhibition of astrocytes in the NAc [...] Read more.

Background: Our recent studies indicate that astrocytes in a key mesocorticolimbic region play an important role in nicotine reinforcement. Nicotine self-administration elevated the astrocyte marker glial fibrillary acidic protein (GFAP) in the nucleus accumbens (NAc) core. Metabolic inhibition of astrocytes in the NAc core with fluorocitrate attenuated nicotine self-administration and disrupted local extracellular glutamate and dopamine transmission. Cotinine is the major neuroactive metabolite of nicotine, demonstrating its own reinforcing effects and contributing to the development of nicotine reinforcement. Mechanisms underlying cotinine reinforcement remain underexplored. The objective of this study was to investigate the potential involvement of astrocytes in cotinine reinforcement. Methods: GFAP protein expression was measured in key mesocorticolimbic regions with a Western blot following chronic cotinine self-administration. The effects of fluorocitrate on cotinine self-administration and extracellular glutamate and dopamine levels were determined. Results: GFAP protein levels were higher in rats undergoing chronic cotinine self-administration than in those with saline self-administration within the ventral tegmental area (VTA) but not the nucleus accumbens or the medial prefrontal cortex. Intra-VTA microinjection of fluorocitrate inhibited the maintenance of cotinine self-administration. Perfusion of fluorocitrate in the VTA reduced local extracellular levels of glutamate and dopamine. Conclusions: These results indicate that cotinine self-administration augmented GFAP expression in the VTA and that metabolic inhibition of VTA astrocytes attenuated cotinine self-administration and impaired extracellular dopamine and glutamate transmission. Overall, these findings suggest that astrocytes in the VTA may play an important role in cotinine reinforcement, potentially through regulation of local extracellular glutamate and dopamine transmission. Full article

(This article belongs to the Section Behavioral Neuroscience)

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11 pages, 225 KB

Open AccessArticle

Narrative Experiences of Esketamine-Induced Dissociation in Patients with Treatment-Resistant Depression: A Qualitative Exploratory Study

by Miriam Olivola, Tiziano Prodi, Giada Versaci, Chiara Angeletti, Kevin La Monica, Fabiola Raffone, Nicolaja Girone, Natascia Brondino, Roberta Anniverno, Vassilis Martiadis, Giovanni Martinotti and Bernardo Dell’Osso

Brain Sci. 2026, 16(2), 196; https://doi.org/10.3390/brainsci16020196 (registering DOI) - 7 Feb 2026

Abstract

Background/Objectives: Esketamine-related dissociation is a transient, pharmacologically induced altered state that differs from the trait-like pathological dissociation typically observed in trauma-related conditions. While most studies have quantified these effects using the Clinician-Administered Dissociative States Scale (CADSS), patients’ subjective phenomenology and meaning-making remain [...] Read more.

Background/Objectives: Esketamine-related dissociation is a transient, pharmacologically induced altered state that differs from the trait-like pathological dissociation typically observed in trauma-related conditions. While most studies have quantified these effects using the Clinician-Administered Dissociative States Scale (CADSS), patients’ subjective phenomenology and meaning-making remain underexplored. This qualitative exploratory study investigated how patients narrate, interpret, and integrate dissociative experiences occurring during intranasal esketamine treatment for treatment-resistant depression (TRD). Methods: We conducted semi-structured interviews with 36 adults with TRD who were receiving intranasal esketamine in outpatient settings in Northern Italy (2022–2024). Interviews focused on the most salient dissociative experiences during treatment. Transcripts were anonymized and analyzed using inductive thematic analysis. Two researchers coded the data independently; discrepancies were resolved by consensus, and recruitment continued until thematic saturation was reached. Results: Four experiential domains emerged: sensory alteration and perceptual flow (10/36, 27.8%), time suspension and chronological drift (21/36, 58.3%), body and space alteration (20/36, 55.6%), and psychic distance from suffering (30/36, 83.3%). While a minority described transient distress or loss of control, most narratives framed dissociation as neutral or subjectively meaningful, often associated with a temporary reduction in ruminative self-focus and depressive distress. Conclusions: A narrative, phenomenological lens complements quantitative research by clarifying what esketamine-induced dissociation feels like to patients and how it is appraised in context. The findings do not imply a causal or mediating role in antidepressant efficacy. Rather, they suggest that dissociation functions as a transitional subjective state, the clinical relevance of which depends on anticipation, framing, monitoring, and integration. These results support the use of structured psychoeducation, in-session support, and post-session integration within real-world esketamine programs. Full article

(This article belongs to the Section Neuropsychiatry)

24 pages, 5480 KB

Open AccessArticle

Leveraging Cross-Subject Transfer Learning and Signal Augmentation for Enhanced RGB Color Decoding from EEG Data

by Metin Kerem Öztürk and Dilek Göksel Duru

Brain Sci. 2026, 16(2), 195; https://doi.org/10.3390/brainsci16020195 - 6 Feb 2026

Abstract

Objectives: Decoding neural patterns for RGB colors from electroencephalography (EEG) signals is an important step towards advancing the use of visual features as input for brain–computer interfaces (BCIs). This study aims to overcome challenges such as inter-subject variability and limited data availability [...] Read more.

Objectives: Decoding neural patterns for RGB colors from electroencephalography (EEG) signals is an important step towards advancing the use of visual features as input for brain–computer interfaces (BCIs). This study aims to overcome challenges such as inter-subject variability and limited data availability by investigating whether transfer learning and signal augmentation can improve decoding performance. Methods: This research introduces an approach that combines transfer learning for cross-subject information transfer and data augmentation to increase representational diversity in order to improve RGB color classification from EEG data. Deep learning models, including CNN-based DeepConvNet (DCN) and Adaptive Temporal Convolutional Network (ATCNet) using the attention mechanism, were pre-trained on subjects with representative brain responses and fine-tuned on target subjects to parse individual differences. Signal augmentation techniques such as frequency slice recombination and Gaussian noise addition improved model generalization by enriching the training dataset. Results: The combined methodology yielded a classification accuracy of 83.5% for all subjects on the EEG dataset of 31 previously studied subjects. Conclusions: The improved accuracy and reduced variability underscore the effectiveness of transfer learning and signal augmentation in addressing data sparsity and variability, offering promising implications for EEG-based classification and BCI applications. Full article

(This article belongs to the Section Computational Neuroscience, Neuroinformatics, and Neurocomputing)

15 pages, 2353 KB

Open AccessArticle

Higher Purity of Phosphatidylserine Improves Human Cortical Neuron Function by Modulating SIRT1-PGC-1α Pathways

by Sung-Min Jeon, Stanley Cho, Yoon-Seob Lee, Ji-Yu Lee, Eunice J. Kang, Tommy D. Kim, Jayna Shin, Heejin Jo and Sung-Ung Kang

Brain Sci. 2026, 16(2), 194; https://doi.org/10.3390/brainsci16020194 - 6 Feb 2026

Abstract

While phosphatidylserine (PS) is recognized for its neuroprotective properties, the effects of PS purity on human cortical neurons remain unexplored. This study investigates the effects of three different PS purities (15 µM of 50%, 70%, and 80%) on neuronal health using human-embryonic-stem-cell-derived cortical [...] Read more.

While phosphatidylserine (PS) is recognized for its neuroprotective properties, the effects of PS purity on human cortical neurons remain unexplored. This study investigates the effects of three different PS purities (15 µM of 50%, 70%, and 80%) on neuronal health using human-embryonic-stem-cell-derived cortical neurons. Our findings reveal that higher PS purity enhances the expression of key regulatory proteins Sirtuin 1 (SIRT1) and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), known for their roles in neuroprotection and mitochondrial function. Specifically, 80% PS purity significantly increases SIRT1 and PGC-1α levels, suggesting that PS purity strengthens neuroprotective pathways and improves mitochondrial quality control. Through SIRT1 knockdown experiments, we demonstrate that PS-induced upregulation of PGC-1α is SIRT1 dependent, highlighting a SIRT1-PGC-1α regulatory axis that enhances mitochondrial health. In an amyloid-beta 1–42 (Aβ₄₂)-induced Alzheimer’s disease (AD) model, PS treatment reduced cytotoxicity and countered the Aβ₄₂-induced downregulation of SIRT1 and PGC-1α, particularly at 70% and 80% PS purity, indicating PS’s role in preserving neuronal viability and combating AD-like pathology. These results suggest that the biological activity of PS preparations in vitro can depend on purity, motivating future studies to define compositional determinants and bioavailability relevant to translational applications. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms Regulating Neuronal Function, Homeostasis, and Disease)

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17 pages, 651 KB

Open AccessArticle

Evaluation of Relationship Between Neuromuscular Fatigue and Manual Dexterity in Physiotherapists: An Observational Study

by Gianluca Libiani, Francesco Sartorio, Ilaria Arcolin, Stefano Corna, Marco Godi and Marica Giardini

Brain Sci. 2026, 16(2), 193; https://doi.org/10.3390/brainsci16020193 - 6 Feb 2026

Abstract

Background/Objectives: Neuromuscular fatigue (NMF) can impair manual dexterity and strength in healthcare professionals. Due to their high physical and cognitive workloads, physiotherapists (PTs) are particularly susceptible to NMF. This study investigated whether NMF, expressed as changes in manual dexterity and grip strength, occurs [...] Read more.

Background/Objectives: Neuromuscular fatigue (NMF) can impair manual dexterity and strength in healthcare professionals. Due to their high physical and cognitive workloads, physiotherapists (PTs) are particularly susceptible to NMF. This study investigated whether NMF, expressed as changes in manual dexterity and grip strength, occurs over a workday and across a workweek in PTs, and explored its relationship with stress and sleep quality. Methods: A total of 43 full-time PTs (25 female, mean age 37.72 ± 11.94 years) were recruited. Manual dexterity was assessed using the Functional Dexterity Test (FDT), while maximal grip strength (MGS) was measured by a hand dynamometer. Reliability was evaluated on a subgroup using Intraclass Correlation Coefficients (ICC_3,1) and Standard Error of Measurement (SEM). Evaluations were conducted at the beginning and at the end of the work shift, on Monday and Friday. Subjective fatigue, perceived stress, and sleep quality were also recorded. Results: The FDT showed excellent intra-rater reliability (ICC > 0.93; SEM < 0.94 s). FDT performance was significantly slower on Friday evening compared to all other time points (p < 0.01), exceeding the minimal detectable change thresholds. No significant changes were observed in MGS across the week. Perceived stress was strongly correlated with fatigue levels on Monday (ρ = 0.731) and Friday (ρ = 0.612) evenings. Sleep quality and professional experience did not correlate with performance changes. Conclusions: PTs experience a significant decline in manual dexterity by the end of the workweek, suggesting an accumulation of NMF. While MGS remains stable, fine motor control is more sensitive to fatigue. Psychosocial stress appears to be a major driver of perceived fatigue in this population. Full article

(This article belongs to the Special Issue Outcome Measures in Rehabilitation)

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14 pages, 3289 KB

Open AccessBrief Report

iTBS Stimulation of the Bilateral IFG/IPL Alters the Oscillatory Pattern in ASD

by Mitra Assadi, Reza Koiler, Ryan Ally, Richard Fischer and Rodney Scott

Brain Sci. 2026, 16(2), 192; https://doi.org/10.3390/brainsci16020192 - 6 Feb 2026

Abstract

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by impairments in social communication, reciprocity, and adaptive behavior. Converging neurobiological evidence suggests that these clinical features arise from aberrant connectivity and dysregulated neuronal oscillations across distributed brain networks. In particular, dysfunction within [...] Read more.

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by impairments in social communication, reciprocity, and adaptive behavior. Converging neurobiological evidence suggests that these clinical features arise from aberrant connectivity and dysregulated neuronal oscillations across distributed brain networks. In particular, dysfunction within the mirror neuron regions, concentrated in the inferior frontal gyrus (IFG) and inferior parietal lobule (IPL), has been implicated in deficits of imitation, empathy, and social cognition in ASD. Non-invasive neuromodulation using repetitive transcranial magnetic stimulation (rTMS) has shown modest behavioral benefits in ASD. However, most studies apply the conventional protocols targeting the dorsolateral prefrontal cortex. The effects of intermittent theta-burst stimulation (iTBS), a potent excitatory rTMS protocol targeting the mirror neuron regions, on the oscillatory dynamics in ASD remain largely unexplored. Objective: To investigate whether iTBS targeting the bilateral IFG and IPL modulates EEG-derived oscillatory activity in adolescents with ASD and to explore the relationship between oscillatory changes and social reciprocity. Methods: Six adolescents with Level I or II ASD (ages 13–18) underwent bilateral iTBS targeting the IFG and IPL using a figure-of-eight coil and standardized theta-burst parameters. Participants were randomized to receive either 18 active iTBS sessions or a waitlist-controlled crossover design (9 sham followed by 9 active sessions). Standard 21-channel EEG recordings were obtained during the first (EEG-1) and final (EEG-2) active stimulation sessions, including pre- and post-stimulation epochs. Power spectral analyses were conducted across frequency bands (delta through gamma). Behavioral outcomes were assessed using the Childhood Autism Rating Scale, Second Edition (CARS2), administered pre- and post-intervention. Results: All participants tolerated the intervention without adverse effects. Behavioral analysis demonstrated a significant reduction in CARS2 scores following iTBS and is reported in detail in our prior clinical outcomes manuscript, consistent with improved social reciprocity (p < 0.001). EEG analysis revealed an immediate post-stimulation increase in gamma-band power during EEG-1 in five of six participants, whereas lower-frequency bands exhibited variable responses. In contrast, EEG-2 showed no consistent post-stimulation gamma enhancement. Net comparisons between EEG-1 and EEG-2 demonstrated attenuation of the initial gamma response in the same five participants. At the group level, gamma percent change did not reach statistical significance at EEG-1 (p = 0.12) or EEG-2 (p = 0.66), and exploratory comparisons between the 9-active versus 18-active arms did not reach statistical significance. While ipsi-directional changes in gamma power and CARS2 scores were observed in four participants, correlation was not identified in this pilot sample. Conclusions: Bilateral iTBS targeting the IFG and IPL induces a transient enhancement of gamma oscillations in adolescents with ASD that attenuates with repeated stimulation. This pattern is consistent with adaptive homeostatic plasticity (metaplasticity) within excitatory–inhibitory circuits, potentially mediated by GABAergic interneurons. These findings support the feasibility of EEG as an objective biomarker of neuromodulatory engagement in ASD and highlight the importance of network-level and oscillatory mechanisms in interpreting therapeutic responses. Larger, sham-controlled studies incorporating multimodal biomarkers are warranted to clarify clinical relevance and optimize personalized neuromodulation strategies. Full article

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

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26 pages, 2410 KB

Open AccessStudy Protocol

In-Phase Bilateral Upper Limb Exercises Improve Cognitive and Motor Functions in Progressive Multiple Sclerosis: A Pilot Randomized Controlled Trial

by Dimitris Sokratous, Charalambos Costa Charalambous, Marios Pantzaris, Kyriaki Michailidou and Nikos Konstantinou

Brain Sci. 2026, 16(2), 191; https://doi.org/10.3390/brainsci16020191 - 5 Feb 2026

Abstract

Background and Purpose: Progressive multiple sclerosis impairs cognitive and motor functions and reduces quality of life. Complex goal-directed movements are challenging due to cognitive deficits, whereas in-phase bilateral exercises require less attentional demand and cognitive effort. This type of exercise may therefore improve [...] Read more.

Background and Purpose: Progressive multiple sclerosis impairs cognitive and motor functions and reduces quality of life. Complex goal-directed movements are challenging due to cognitive deficits, whereas in-phase bilateral exercises require less attentional demand and cognitive effort. This type of exercise may therefore improve both cognitive and motor functions. Previous studies in people with progressive multiple sclerosis suggested a strong association between cognitive and upper limb functions; however, the effects of in-phase bilateral exercises remain unclear. Objectives: To evaluate the effects of in-phase bilateral upper limb exercise on cognitive processing, motor functions, and quality of life in people with progressive multiple sclerosis. Methods: Twenty participants (11 females, mean age = 55.8 years) were randomized (1:1) to an experimental or active control group for a 12-week intervention. The experimental group performed in-phase bilateral upper limb exercises while the active control group performed conventional exercises. ANOVA was conducted to determine the effect of intervention on information processing speed, motor function, fatigue, and quality of life. Results: Post hoc analyses revealed that the experimental group demonstrated significantly greater improvements than the active control group in information processing speed (t(18) = 8.6, p < 0.05), as well as across all exploratory secondary outcome measures (all p < 0.05). Conclusions: This pilot randomized controlled trial suggests that in-phase bilateral exercises, which demand less cognitive effort than other forms of bilateral coordination, are associated with improvements in information processing speed, motor functions, fatigue, and quality of life in people with progressive multiple sclerosis. Full article

(This article belongs to the Special Issue Assessment and Rehabilitation of Cognitive Function in Neurological Disorders)

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25 pages, 1165 KB

Open AccessReview

Multiple Roles of Cannabinoids in the Olfactory System

by Thomas Heinbockel and Edward A. Brown

Brain Sci. 2026, 16(2), 190; https://doi.org/10.3390/brainsci16020190 - 5 Feb 2026

Abstract

The endocannabinoid system is a ubiquitous neuromodulatory network that links internal physiological state to neural circuit function across the brain. While its roles in memory, reward, pain, and motor control are well established, its contribution to olfactory processing has only recently gained attention. [...] Read more.

The endocannabinoid system is a ubiquitous neuromodulatory network that links internal physiological state to neural circuit function across the brain. While its roles in memory, reward, pain, and motor control are well established, its contribution to olfactory processing has only recently gained attention. This review synthesizes the current knowledge on the anatomical, cellular, and functional interactions between the endocannabinoid system and the olfactory pathway, from the olfactory epithelium and main olfactory bulb to higher order cortical targets. We highlight how endocannabinoid signaling, primarily via cannabinoid receptor type 1 (CB1), shapes synaptic transmission within olfactory bulb microcircuits, modulates centrifugal feedback, and adjusts sensory gain in a state-dependent manner, particularly in relation to hunger, feeding behavior, stress, and reward. In addition, we review evidence that the endocannabinoid system regulates olfactory neurodevelopment and adult neurogenesis by influencing neural stem cell proliferation, migration, and integration into existing circuits. Emerging links between endocannabinoid signaling, olfactory dysfunction, neuropsychiatric disease, metabolic disorders, and neurodegeneration underscore the translational relevance of this system. We also discuss methodological challenges inherent to studying endocannabinoid signaling and outline future directions, including circuit-specific targeting and intranasal delivery strategies. Together, these findings position the olfactory system as a powerful and accessible model for understanding how endocannabinoids couple internal state to perception and behavior, with important implications for therapeutic development. Full article

(This article belongs to the Special Issue Brain Plasticity in Health and Disease: From Molecules to Circuits)

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12 pages, 693 KB

Open AccessArticle

Neurotransmitter Mechanisms of Ketamine and Ketamine–Magnesium Sulfate-Induced Hypothermia: Evidence for Serotonergic and Adrenergic Involvement Without GABA_A Contributions

by Katarina Savić Vujović, Sonja Vučković, Lara Samardžić, Branislava Medić, Dragana Srebro, Ana Jotić and Ivana Ćirković

Brain Sci. 2026, 16(2), 189; https://doi.org/10.3390/brainsci16020189 - 4 Feb 2026

Abstract

Background: Ketamine and magnesium sulfate are commonly used perioperatively to prevent shivering, a frequent and clinically relevant complication of spinal and general anesthesia. Although their hypothermic effects are well documented, the neurotransmitter mechanisms underlying these effects remain insufficiently understood. This study examines whether [...] Read more.

Background: Ketamine and magnesium sulfate are commonly used perioperatively to prevent shivering, a frequent and clinically relevant complication of spinal and general anesthesia. Although their hypothermic effects are well documented, the neurotransmitter mechanisms underlying these effects remain insufficiently understood. This study examines whether serotonergic, adrenergic (α₂), and GABAergic (GABA_A) systems contribute to hypothermia induced by ketamine and a ketamine–magnesium sulfate combination. Methods: Body temperature was measured in Wistar rats after administration of ketamine (10 mg/kg) or the ketamine (5 mg/kg)–magnesium sulfate (5 mg/kg) combination. To assess neurotransmitter involvement, animals received yohimbine (α₂ antagonist), methysergide (non-selective 5-HT antagonist), or bicuculline (GABA_A antagonist) prior to ketamine or the drug combination. Data were analyzed using two-way repeated measures ANOVA followed by Tukey’s post hoc test. Results: Yohimbine at 0.5 and 1 mg/kg significantly potentiated ketamine-induced hypothermia, while only 3 mg/kg enhanced the effect of the ketamine–magnesium sulfate combination. Methysergide had a bidirectional influence: 1 mg/kg methysergide deepened ketamine-induced hypothermia, whereas 0.5 mg/kg methysergide attenuated the hypothermic effect of the ketamine–magnesium sulfate combination. Bicuculline (1–2 mg/kg) did not alter the hypothermic responses to ketamine or the combination. Conclusions: These findings indicate that ketamine- and ketamine–magnesium sulfate-induced hypothermia is primarily modulated by serotonergic and adrenergic mechanisms, whereas GABA_A receptor-dependent pathways do not appear to play a major role under the experimental conditions used. These results provide new mechanistic insights into NMDA antagonist–related thermoregulation and may help inform anesthetic strategies for shivering prevention and maintenance of perioperative thermal stability. Full article

(This article belongs to the Section Neuropharmacology and Neuropathology)

7 pages, 293 KB

Open AccessEditorial

‘Molecular and Cellular Neuroscience’: Impacts of Eight Highly Cited Articles Published in This Section of Brain Sciences in 2024

by Swapan K. Ray

Brain Sci. 2026, 16(2), 188; https://doi.org/10.3390/brainsci16020188 - 4 Feb 2026

Abstract

This year, the selection criteria for highly cited articles in the ‘Molecular and Cellular Neuroscience’ section of Brain Sciences were focused on publications that achieved a citation count of 10 or more during 2024. Applying this metric, the Editorial Office, in collaboration with [...] Read more.

This year, the selection criteria for highly cited articles in the ‘Molecular and Cellular Neuroscience’ section of Brain Sciences were focused on publications that achieved a citation count of 10 or more during 2024. Applying this metric, the Editorial Office, in collaboration with myself as Associate Editor of the ‘Molecular and Cellular Neuroscience’ section of the journal, identified eight articles that not only exemplified the mission of this section but also made significant scientific contributions by advancing our current understanding of the molecular and cellular mechanisms underlying major and rare neurological disorders. These articles encompass miscellaneous topics, including Alzheimer’s disease (AD), chronic alcoholism, glioblastoma multiforme (GBM), amyotrophic lateral sclerosis (ALS), cognitive impairment, cerebrovascular disease, and Rett syndrome (RTT). Importantly, several contributions highlight experimental therapeutic strategies aimed at mitigating pathogenic mechanisms, offering promising avenues for translational research and future clinical applications. Full article

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

17 pages, 994 KB

Open AccessReview

MAC/MAB–RCS: An Integrative Regulatory Control Framework for Risk Stratification and Personalized Intervention in Addiction Psychiatry

by Anna Makarewicz, Remigiusz Recław, Anna Grzywacz, Jolanta Chmielowiec and Krzysztof Chmielowiec

Brain Sci. 2026, 16(2), 187; https://doi.org/10.3390/brainsci16020187 - 3 Feb 2026

Abstract

Objectives: Addiction disorders remain a major challenge in contemporary psychiatry due to high relapse rates and significant individual and societal burden. Despite advances in addiction neurobiology, current diagnostic frameworks and dominant models offer limited tools for early risk identification and dynamic support of [...] Read more.

Objectives: Addiction disorders remain a major challenge in contemporary psychiatry due to high relapse rates and significant individual and societal burden. Despite advances in addiction neurobiology, current diagnostic frameworks and dominant models offer limited tools for early risk identification and dynamic support of clinical decision-making across the course of treatment. The aim of this narrative review is to introduce the MAC/MAB–RCS model as an integrated conceptual framework for risk stratification and personalized intervention in addiction psychiatry. Methods: The proposed model integrates evidence from four complementary domains: genetic, epigenetic, and stress-axis biomarkers; functional brain network organization; and psychological/psychiatric dimensions relevant to addictive behaviors. These domains are synthesized into a unified conceptual structure designed to capture dynamic regulatory processes underlying addiction vulnerability. Results: At the core of the model lies the Regulatory Control State (RCS), a latent higher-order construct representing an individual’s dynamic regulatory capacity through the integration of cognitive control, emotional regulation, and motivational drive modulation. Disruption of the RCS is conceptualized as a shared transdiagnostic mechanism driving craving escalation, compulsive behavior, and relapse vulnerability, independent of substance class or specific addictive behavior. Conclusions: The MAC/MAB–RCS model aligns with the principles of precision psychiatry by offering a pragmatic, clinically oriented translational framework with potential applicability across clinical settings, bridging neurobiological research and clinical practice. The review discusses its relationship to existing models, potential clinical and systemic applications, key limitations, and priorities for future validation studies. Full article

(This article belongs to the Special Issue Risks and Mechanisms in Addiction Neuroscience Informing Treatment)

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18 pages, 330 KB

Open AccessArticle

Moderating Role of Cigarette Smoking on the Efficacy of tDCS in the Treatment of Negative and Cognitive Symptoms of Schizophrenia: Results from a Randomized Clinical Trial

by Jacopo Lisoni, Gabriele Nibbio, Mattia Ardesi, Antonio Baglioni, Lorenzo Bertoni, Francesco Bezzi, Camilla Agnese Carolina Cicolari, Federica Frigerio, Michela Gregorelli, Paola Miotto, Giacomo Deste, Stefano Barlati and Antonio Vita

Brain Sci. 2026, 16(2), 186; https://doi.org/10.3390/brainsci16020186 - 3 Feb 2026

Abstract

Background: Transcranial Direct Current Stimulation (tDCS) has shown potential in improving negative symptoms (NS) and Cognitive Impairment Associated with Schizophrenia (CIAS). However, heterogeneity in stimulation protocols and sample characteristics limit definitive conclusions regarding tDCS effectiveness in schizophrenia. Given the detrimental effects of cigarette [...] Read more.

Background: Transcranial Direct Current Stimulation (tDCS) has shown potential in improving negative symptoms (NS) and Cognitive Impairment Associated with Schizophrenia (CIAS). However, heterogeneity in stimulation protocols and sample characteristics limit definitive conclusions regarding tDCS effectiveness in schizophrenia. Given the detrimental effects of cigarette smoking, particularly on cognition, this study explored the role of cigarette smoking as a modifiable individual factor potentially contributing to methodological heterogeneity by evaluating tDCS effects on NS and CIAS in Smoker (SM) and Non-Smoker (NoSM) patients. Methods: Post hoc analyses of a double-blind RCT were performed on 50 patients, randomized to 2 mA active or sham-tDCS (15 weekday sessions) with bilateral bipolar-nonbalanced prefrontal placement. The sample was divided according to the smoking status, consisting of 28 SM and 22 NoSM. Separate one-way analyses of covariance (ANCOVA) were performed within each subgroup to assess changes over time between treatment conditions. Clinical outcomes included Positive and Negative Symptoms Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), Clinical Global Impression (CGI) and Calgary Depression Scale for Schizophrenia (CDSS) total scores. Results: SM exhibited baseline lower cognitive scores in verbal memory, motor speed and working memory domains. NS improved in both SM and NoSM with large effect size. Significant improvement in CIAS, specifically in working memory and verbal fluency, were found exclusively in NoSM. Conclusions: Cigarette smoking appeared to limit tDCS effectiveness in improving CIAS but not NS in schizophrenia. We suggested that the neurotoxic milieu linked to chronic exposure to neurotoxins of cigarette smoking could be responsible for these effects, counterbalancing the neuroprotective effects of tDCS. Further studies are warranted to replicate these findings. Full article

(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd Edition)

18 pages, 853 KB

Open AccessArticle

Intraindividual Variability in Perceptual-Motor Performance Measured with Virtual Reality Among Military Veterans

by Scott L. Bruce, Michael Cooper, Carly Farmer, Audrey Folsom, Melanie Fulton, Jana Haskins, Cheryl Knight, Carlitta M. Moore, Johnathon A. Mullins, Amy Shollenbarger, Rashele Wade, Stacy Walz, Rebbecca Wellborn, Rachel Wilkins and Kendall Youngman

Brain Sci. 2026, 16(2), 185; https://doi.org/10.3390/brainsci16020185 - 3 Feb 2026

Abstract

Background/Objectives: Concussions produce a wide array of symptoms that are often subtle and difficult to quantify. One such symptom involves reaction or response time (RT), consisting of perceptual latency time (LT) and movement time (MT). This pilot study examined the relationship between concussion [...] Read more.

Background/Objectives: Concussions produce a wide array of symptoms that are often subtle and difficult to quantify. One such symptom involves reaction or response time (RT), consisting of perceptual latency time (LT) and movement time (MT). This pilot study examined the relationship between concussion history, mental health, and perceptual-motor performance among military veterans using a virtual reality (VR)-based assessment. The primary outcome was intraindividual variability (IIV), defined as the standard deviation of an individual’s responses across repeated trials. Methods: Of 78 veterans who volunteered, 29 (22 males, 7 females) provided complete VR data. Participants completed surveys assessing concussion and combat history, mental health issues, and suicide ideation. During VR testing, participants responded to 40 trials requiring neck rotation, arm reach, and a step toward left or right virtual targets. Associations between predictors (e.g., concussion, mental health) and VR outcomes (RT, LT, IIV) were evaluated using Receiver Operating Characteristic (ROC) Area Under the Curve (AUC) values. Results: Concussion history was the strongest predictor of performance deficits. IIV metrics were sensitive indicators of both concussion and mental health issues. Univariable analyses yielded AUC values of 0.944–0.806 all of which were statistically significant (p ≤ 0.001), and multivariable analyses produced AUCs of 0.950–0.870 all of which were also statistically significant (p ≤ 0.001). Incongruent movements and longer LT values were especially discriminative. Conclusions: Veterans with concussion and mental health histories demonstrated quantifiable perceptual-motor impairments in VR environments. Findings support VR assessment as a feasible, sensitive tool for detecting subtle residual effects of concussion. Full article

(This article belongs to the Section Sensory and Motor Neuroscience)

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7 pages, 199 KB

Open AccessEditorial

Theoretical, Clinical, and Rehabilitative Aspects of Anosognosia an Extended Editorial

by Guido Gainotti

Brain Sci. 2026, 16(2), 184; https://doi.org/10.3390/brainsci16020184 - 2 Feb 2026

Abstract

Anosognosia (from the ancient Greek—a-, “without,” nosos, “disease,” and gnōsis, “knowledge”) has been recognised as one of the most complex syndromes investigated from different theoretical and clinical perspectives in patients with brain damage since the beginning of the last century (see [...] Full article

(This article belongs to the Special Issue Anosognosia and the Determinants of Self-Awareness)

15 pages, 2724 KB

Open AccessArticle

Radiological and Clinical Outcomes After Navigated Tubular Unilateral Laminotomy for Bilateral Decompression (ULBD) for Lumbar Spinal Stenosis Among Patients with Concurrent Degenerative Scoliosis: A Short-Term Retrospective Case Series

by Mateusz Bielecki, Chibuikem A. Ikwuegbuenyi, Yizhou Xie, Jessica Berger, Catherine Mykolajtchuk, Anne Schlumprecht, Rodolfo Villalobos-Diaz, Noah Willett, Mousa K. Hamad, Galal Elsayed, Ibrahim Hussain, Osama N. Kashlan and Roger Härtl

Brain Sci. 2026, 16(2), 183; https://doi.org/10.3390/brainsci16020183 - 1 Feb 2026

Abstract

Background/Objectives: Adult degenerative scoliosis (ADS) is a spinal disease causing pain and reduced mobility, often occurring with degenerative lumbar spinal stenosis (DLSS). While fusion stabilizes the spine, it has drawbacks like loss of motion and adjacent segment degeneration. Minimally invasive techniques, such as [...] Read more.

Background/Objectives: Adult degenerative scoliosis (ADS) is a spinal disease causing pain and reduced mobility, often occurring with degenerative lumbar spinal stenosis (DLSS). While fusion stabilizes the spine, it has drawbacks like loss of motion and adjacent segment degeneration. Minimally invasive techniques, such as tubular unilateral laminotomy for bilateral decompression (tULBD), provide a less invasive alternative, but their impact on ADS with DLSS is underexplored. This study examines the short-term effects of navigated tULBD on radiological and clinical outcomes in this patient population. Methods: This retrospective single-center study analyzed patients aged ≥18 years with DLSS and ADS (Cobb angle ≥ 10°), with or without grade I spondylolisthesis, who underwent navigated tULBD between June 2019 and October 2022. Radiological parameters were assessed pre- and post-operatively using AI-powered FXA™ Version 1.33, Raylytic Software GmbH, Leipzig, Germany, while clinical outcomes were evaluated using the Oswestry Disability Index (ODI) and Numeric Rating Scale (NRS) for back and leg pain. Statistical analyses were conducted with R Studio. Results: This study included 20 patients (mean age 74.6 ± 7.6 years, body mass index [BMI] 26.08 ± 3.7 kg/m²), with a median follow-up of 2 months. Most underwent single-level decompression (45%), with a median of 2 surgical levels (IQR: 1–3). Radiological parameters showed no significant changes (p > 0.05). Clinically, the median NRS back improved from 5 (IQR: 3–9) preoperatively to 2 (IQR: 0–2) postoperatively (p = 0.009) and 1 (IQR: 0–4.5) at follow-up (p = 0.004). NRS leg scores dropped from 3.5 (IQR: 0–5) to 0 postoperatively and at follow-up (p = 0.02, p = 0.04). ODI improved from 37.8 (IQR: 29–42.5) preoperatively to 17.5 (IQR: 5–24) at follow-up (p = 0.04). There were no neurological complications. Conclusions: Navigated tULBD is a promising, minimally invasive option for mild ADS and DLSS. It provides significant pain and disability relief without adversely affecting stability and alignment. Long-term studies are needed to confirm durability and efficacy, particularly in severe cases. Full article

(This article belongs to the Special Issue Novel Techniques in Spine Neurosurgery)

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16 pages, 1652 KB

Open AccessArticle

Impact of Amplification and Noise on Subjective Cognitive Effort and Fatigue in Older Adults with Hearing Loss

by Devan M. Lander and Christina M. Roup

Brain Sci. 2026, 16(2), 182; https://doi.org/10.3390/brainsci16020182 - 31 Jan 2026

Abstract

Background/Objectives: Older adults with hearing loss frequently report increased listening effort and fatigue, particularly in complex auditory environments. These subjective experiences may reflect increased cognitive resource allocation during both auditory and visual tasks, yet the impact of hearing aids on task-related effort [...] Read more.

Background/Objectives: Older adults with hearing loss frequently report increased listening effort and fatigue, particularly in complex auditory environments. These subjective experiences may reflect increased cognitive resource allocation during both auditory and visual tasks, yet the impact of hearing aids on task-related effort and fatigue remains unclear. This study examined subjective effort and fatigue in experienced older adult hearing aid users while completing cognitively demanding auditory and visual tasks in quiet and background noise, with and without hearing aids. Methods: Thirty-one adults aged 60–87 years completed a cognitive battery assessing inhibition, attention, executive function, and auditory and visual working memory across four listening conditions: aided-quiet, unaided-quiet, aided-noise, and unaided-noise. Subjective effort was measured using the NASA Task Load Index, and task-related fatigue was assessed using a situational fatigue scale. Linear mixed-effects models controlled for age and pure-tone average hearing thresholds. Results: Participants reported significantly lower effort and fatigue in quiet compared to background noise, regardless of hearing aid use. The aided-quiet condition was rated as the least effortful and fatiguing, whereas the unaided-noise condition was rated as the most demanding. Subjective effort and fatigue were moderately to strongly correlated across conditions, particularly in noise. Auditory working memory performance was significantly associated with subjective fatigue across listening conditions, while visual working memory was not associated with effort or fatigue. Hearing aid use did not produce significant reductions in effort or fatigue across conditions. Conclusions: Background noise substantially increases perceived task-related effort and fatigue during cognitively demanding auditory and visual tasks in older adults with hearing loss. While hearing aids did not significantly reduce effort or fatigue across conditions, optimal listening environments were associated with the lowest subjective reports. Auditory working memory emerged as a key factor related to fatigue, highlighting the interplay between hearing, cognition, and subjective listening experiences in older adulthood. Full article

(This article belongs to the Special Issue Advances in Speech and Language Research for Cognitive Well-Being in Aging)

24 pages, 5027 KB

Open AccessArticle

Multi-Site Classification of Autism Spectrum Disorder Using Spatially Constrained ICA on Resting-State fMRI Networks

by Talha Imtiaz Baig, Junlin Jing, Peng Hu, Bochao Niu, Zhenzhen Yang, Bharat B. Biswal and Benjamin Klugah-Brown

Brain Sci. 2026, 16(2), 181; https://doi.org/10.3390/brainsci16020181 - 31 Jan 2026

Abstract

Background/Objectives: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by differences in social communications and restricted, repetitive patterns of behaviors and interests, affecting approximately 1% of children globally. While functional magnetic resonance imaging (fMRI) has provided insights into altered brain [...] Read more.

Background/Objectives: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by differences in social communications and restricted, repetitive patterns of behaviors and interests, affecting approximately 1% of children globally. While functional magnetic resonance imaging (fMRI) has provided insights into altered brain connectivity patterns in ASD, classification based on neuroimaging remains a challenging due to the heterogeneity of the disorder and variability in imaging data across sites. This study employs a network-based approach using large-scale, multi-site rs-fMRI dataset from the Autism Brain Imaging Data Exchange (ABIDE I and II) to classify ASD and healthy controls using machine learning. Methods: A semi-blind Independent Component Analysis method, specifically the spatial constraint reference ICA, is applied to identify functional brain networks, and the ComBat harmonization technique is used to address site-specific variability across 11 independent datasets, ensuring consistency in feature representation. Support Vector Machines (SVMs) are employed for classification, focusing on three key networks: the Default Mode Network (DMN), Sensorimotor Network (SMN), and Visual Sensory Network (VSN). Results: The results demonstrate high classification accuracy, with the VSN achieving the highest performance (83.23% accuracy, 87.90% AUC), followed by the DMN (81.43% accuracy, 84.53% AUC) and the SMN (80.52% accuracy, 84.96% AUC), positioned with their recognized roles in social cognition and sensory–motor processing, respectively. Conclusions: The integration of ICA-based feature extraction with ComBat harmonization significantly improved classification accuracy compared to previous studies. These findings point out the potential of network-based approaches in ASD classification and point out the importance of integrating multi-site neuroimaging data for identifying reproduceable network-level features. Full article

(This article belongs to the Special Issue EEG and fMRI Applications in Exploring Brain Activity)

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