Brain Sciences最新文献

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.

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.

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.

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.

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.

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.

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.

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.

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.