Brain Sciences最新文献

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and the presence of intracellular α-synuclein (αSyn) aggregates known as Lewy bodies (LB). αSyn, a presynaptic protein, is believed to play a crucial role in synaptic function, neurotransmitter release, and neuronal plasticity. However, its misfolding and aggregation are thought to be central to PD pathogenesis. This review provides a comprehensive analysis of αSyn's role in PD, exploring its normal physiological functions, pathological mechanisms, and therapeutic potential. The pathological transformation of αSyn involves structural alterations that promote oligomerization and fibrillization, leading to toxic gain-of-function effects. These aggregates disrupt cellular homeostasis through mechanisms including mitochondrial dysfunction, oxidative stress, lysosomal impairment, and endoplasmic reticulum stress. Furthermore, pathogenic αSyn is thought to exacerbate neurodegeneration via prion-like spread along interconnected neuronal circuits. Emerging evidence highlights the frequent co-occurrence of other proteinopathies, such as tau and amyloid-β, which may synergistically accelerate disease progression. Targeting αSyn has emerged as a potential therapeutic strategy. Approaches such as immunotherapy, small-molecule inhibitors, gene silencing, and modulation of protein degradation pathways (e.g., autophagy and proteasomal systems) are actively being explored. Additionally, lifestyle-based interventions, particularly exercise, have shown neuroprotective effects, potentially mediated by irisin-a myokine implicated in protein clearance and synaptic resilience-underscoring the importance of multimodal strategies in PD management.

Chronic pain has been increasingly recognized not only as a sensory disorder but also as a condition that profoundly disrupts affective and motivational processes. Preclinical research indicates that persistent nociceptive input drives maladaptive changes in brain reward circuits, particularly within the mesocorticolimbic dopamine system. These alterations contribute to anhedonia, diminished motivation, and aberrant reward valuation, core symptoms frequently observed in patients with chronic pain. In this review, we synthesize evidence from rodent models demonstrating how chronic pain impairs the hedonic experience and motivational aspects of reward through disrupted dopaminergic signaling, neuroinflammatory pathways, and opioid system dysregulation. We also highlight the temporal dynamics in the emergence of hedonic deficits, the sex-dependent mechanisms, and the interplay between pain and drug-seeking behaviors. Finally, we discuss how these findings inform the search for and predict early biomarkers and therapeutic targets aimed at restoring hedonic tone. A deeper understanding of the neurobiological basis of reward dysfunction in chronic pain may provide critical insights for developing more effective, mechanism-based interventions.

Background/Objectives. Despite the importance of organization-in-time ability for adults' daily performance, knowledge about this ability in adults with attention-deficit/hyperactivity disorder (ADHD) remains limited. This study aims to compare organization-in-time abilities and quality of life (QoL) in adults with ADHD versus controls and examine the association and predictive relationship between this population's organization-in-time and executive function (EF) abilities and their QoL. Methods. Participants were 69 adults with ADHD and at least one EF deficit according to the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) and 52 matched neurotypical controls. Besides the BRIEF-A and demographic questionnaire, all participants completed the Time Organization and Participation Scale and Adult ADHD QoL questionnaire. The study was approved by the institutional ethics committee, with written informed consent obtained from all participants. Results. Compared with controls, adults with ADHD demonstrated significantly poorer organization-in-time ability and QoL. Within the ADHD group, significant correlations were found between organization-in-time and EF abilities (r = -0.39 to -0.50, p < 0.01). The group (ADHD vs. control) explained 51.7% of the variance in total QoL. Beyond this, metacognitive abilities (BRIEF-A Metacognitive Index) accounted for an additional 15.1%, and organization-in-time domains contributed 10.8% of the variance in predicting total QoL. Conclusions. Identifying deficits in time-organization abilities and EFs and their association with lower QoL among adults with ADHD has empirical and clinical implications. Such identification and the development of targeted intervention programs are essential for improving QoL in this population.

Objective: To explore the value of multimodal molecular imaging in diagnosing and differentiating dementia with Lewy bodies (DLB). Methods: A retrospective analysis was conducted on clinical data and multimodal molecular imaging of 40 probable DLB patients treated at Peking Union Medical College Hospital (August 2017-December 2024). All 40 had ¹⁸F-FDG PET/CT; 15 had ¹³¹I-MIBG imaging; 11 had ¹⁸F-FP-CIT PET/CT. A total of 12 patients with poor cognition or atypical ¹⁸F-FDG PET/CT underwent ¹⁸F-AV45 PET/CT (2 also had ¹⁸F-PM-PBB3 imaging). A sex- and age-matched control group (cognitively normal, same-period health checkup ¹⁸F-FDG PET/CT) was included. ¹⁸F-FDG PET/CT images were visually and semi-quantitatively analyzed (ROI, SPM). ¹⁸F-AV45 PET/CT was assessed both visually and semi-quantitatively; ¹³¹I-MIBG imaging and ¹⁸F-FP-CIT PET/CT were visually evaluated. Results: The 40 DLB patients (29 males, 11 females; mean age 72 years) had distinct initial symptoms: 8 (20%) presented with cognitive decline as the first symptom, 23 (57.5%) with parkinsonian symptoms as the first symptom, and 9 (22.5%) with both symptoms occurring simultaneously. Mean intervals: 16.25 months from initial cognitive decline to parkinsonian symptoms, and 24.43 months from initial parkinsonian symptoms to cognitive decline. All had parkinsonian symptoms and cognitive impairment; 38 (95%) had visual hallucinations; and 26 (65%) had REM sleep behavior disorder. ¹⁸F-FDG PET/CT: 30(75%) showed typical occipital hypometabolism and posterior cingulate island sign; 10 (25%) had atypical findings. ¹³¹I-MIBG (15/15, 100%): cardiac sympathetic denervation. ¹⁸F-FP-CIT (10/11, 90.9%): basal ganglia dopaminergic damage. ¹⁸F-AV45 (9/12, 81.8%): positive. Semi-quantitative ¹⁸F-FDG analysis revealed parietal, occipital, and lateral temporal hypometabolism in DLB (left more severe than right). Conclusions: Dementia with Lewy bodies (DLB) presents with pre-onset parkinsonism and cognitive impairment, plus high rates of visual hallucinations and sleep disorders. Key imaging features-occipital hypometabolism/island sign on ¹⁸F-FDG PET/CT, cardiac sympathetic denervation on ¹³¹I-MIBG, and basal ganglia dopaminergic damage on ¹⁸F-FP-CIT-aid DLB diagnosis. ¹⁸F-AV45 PET/CT detects Aβ pathology in severely cognitively impaired patients, suggesting these DLB patients may have underlying AD pathology beyond DLB.

Objectives: This systematic review seeks to provide an in-depth overview of current research on tele-music interventions in supportive cancer care and identifies key areas where further research is warranted. Methods: A comprehensive search was conducted across four electronic databases (Scopus, Embase, Web of Science, and PubMed) without any data restrictions and according to the PRISMA guidelines. The primary outcome measure was the effect of tele-music interventions on psychosocial functioning. Results: Of the 2.043 articles initially identified, nine studies met the inclusion criteria and were selected for qualitative analysis. Among the music interventions, considerable variation was observed regarding delivery format and techniques employed. Most interventions were delivered remotely through Zoom, and in all but one study, a music therapist was involved. Outcome measures addressed various psychosocial and physical symptoms, most frequently anxiety, for which findings were mixed: three studies reported significant reductions, whereas two others observed no or only limited improvement. Conclusions: The results suggest that tele-music interventions are effective in reducing a range of cancer-related symptoms, including stress, anxiety, depression, and pain. However, the heterogeneity in study designs and methodological limitations hampered direct comparison and overall effectiveness assessment. Additionally, digital technologies hold considerable potential for the accessible and cost-effective delivery of music interventions.

Taking a cognitive perspective on emotions as generally exemplified by appraisal theories, I suggest that attempts to "define" emotions is a theoretical exercise whose goal should be to specify necessary and jointly sufficient conditions for something to be an emotion. To this end, I advance arguments in support of the proposal that genuine emotions have the five necessary characteristics of being (i) intentional (i.e., about something), (ii) personally significant, (iii) valenced, (iv) consciously experienced, and (v) insuppressible. Collectively, these properties distinguish emotions from other kinds of mental states. I also argue that attempts to define emotions should resist the temptation to incorporate into definitions characteristics of emotions that are not always present, even though, when they are present, those characteristics may be typical and highly salient. It is suggested that two characteristics that are routinely taken to be constitutive of emotions-bodily changes and facial expression-are just such characteristics; they are typical and salient but not in fact necessary as evidenced by the fact that many (especially low intensity) emotions occur without them.

Chronic pain is a pervasive global health issue that significantly impairs quality of life and remains inadequately managed by current therapeutic options. Traditional pharmacological treatments often offer limited relief and are associated with significant side effects, highlighting the urgent need for safer and more effective alternatives. Among emerging strategies, mesenchymal stem cell (MSC)-derived secretome, an acellular product composed of bioactive molecules such as cytokines, growth factors and extracellular vesicles, has gained increasing attention for its potent anti-inflammatory, neuroprotective and immunomodulatory properties. Unlike whole-cell therapies, secretome-based interventions offer advantages, including lower immunogenicity, higher safety and easier standardization and storage. Preclinical studies demonstrated that MSC secretome effectively alleviates pain-like behavior across various models of neuropathic, inflammatory and degenerative pain, primarily through neuroimmune modulation and glial cell reprogramming. In vitro experiments confirm its role in promoting neuronal survival, regulating opioid receptor expression and modulating (neuro)inflammatory responses. Preliminary clinical evidence supports its analgesic efficacy in conditions such as osteoarthritis, chronic low back pain and post-surgical pain, with a favorable safety profile and promising therapeutic outcomes. However, challenges remain, including variabilities in secretome composition, lack of standardized production protocols and absence of large-scale clinical trials. Despite these limitations, MSC secretome therapy represents a transformative approach in pain medicine. Continued research efforts are essential to optimize formulation, dosing and delivery strategies, as well as to clarify the regulatory landscape. With further validation, the MSC secretome could emerge as a novel, scalable and clinically viable solution for the management of chronic pain, bridging critical gaps in current treatment paradigms.

Introduction: Speech perception relies on integrating auditory and visual information, shaped by both perceptual and cognitive factors. Musical training has been shown to affect multisensory processing, whereas cognitive processes, such as recalibration derived from a perceptual history, influence neural responses to upcoming sensory inputs. To investigate these influences, we evaluated cortical activity associated with the McGurk illusion focusing specifically on how musical training and perceptual history affect multisensory speech perception.

Methods: Musicians and age-matched nonmusicians participated in electroencephalogram experiments using a McGurk task. We analyzed five conditions on the basis of stimulus type and participants' responses and quantified the rate of illusory percepts and cortical alpha power between groups using dynamic imaging of coherent sources.

Results: No differences in McGurk susceptibility were detected between musicians and nonmusicians. Source-localized alpha, however, revealed group-specific patterns: musical training was associated with frontal alpha modulation during integration, a finding consistent with enhanced top-down control, whereas nonmusicians relied more on sensory-driven processing. Additionally, illusory responses occurred in auditory-only trials. Follow-up analyses revealed no significant alpha modulation clusters in musicians, but temporal alpha modulations in nonmusicians depending on preceding audiovisual congruency.

Conclusions: These findings suggest that musical training may influence the neural mechanisms of audiovisual integration during speech perception. Specifically, musicians appear to employ enhanced top-down control involving frontal regions, whereas nonmusicians rely more on sensory-driven processing mediated by parietal and temporal regions. Furthermore, perceptual recalibration may be more prominent in nonmusicians, whereas musicians appear to focus more on current sensory input, reducing their reliance on perceptual history.

Objective: Substance use in patients with mental disorders is often associated with worse outcomes, increased risks, and impaired decision-making. Therefore, the evaluation of mental capacity in patients with coexisting mental illness and substance use disorder (dual diagnosis) is necessary to improve clinical outcomes and mitigate risks to self and others.

Design: A retrospective inspection of electronic records for patients admitted between March 2017 and August 2020 in two London inpatient facilities was conducted. Capacity was assessed using the principles set out in the Mental Capacity Act 2005.

Results: A capacity assessment was recorded in 34.9% of admissions. Only 6.2% of admissions whose primary diagnosis was mental and behavioral changes due to the use of substances had a recorded mental capacity assessment. Capacity to understand the negative impact of substances was assessed in 2.1% of total admissions.

Conclusions: This study indicates very low rates of mental capacity assessment across acute psychiatric admissions, with very few relating to capacity to understand the risks associated with using substances. Further research on the capacity of patients with dual diagnosis is needed. This may help to manage certain risks in this patient population.

Objectives: Existing motor imagery electroencephalography (MI-EEG) decoding approaches are constrained by their reliance on sole representations of brain connectivity graphs, insufficient utilization of multi-scale information, and lack of adaptability. Methods: To address these constraints, we propose a novel Local-Partition-Global Graph learning Network (LPGGNet). The Local Learning module first constructs functional adjacency matrices using partial directed coherence (PDC), effectively capturing causal dynamic interactions among electrodes. It then employs two layers of temporal convolutions to capture high-level temporal features, followed by Graph Convolutional Networks (GCNs) to capture local topological features. In the Partition Learning module, EEG electrodes are divided into four partitions through a task-driven strategy. For each partition, a novel Gaussian median distance is used to construct adjacency matrices, and Gaussian graph filtering is applied to enhance feature consistency within each partition. After merging the local and partitioned features, the model proceeds to the Global Learning module. In this module, a global adjacency matrix is dynamically computed based on cosine similarity, and residual graph convolutions are then applied to extract highly task-relevant global representations. Finally, two fully connected layers perform the classification. Results: Experiments were conducted on both the BCI Competition IV-2a dataset and a laboratory-recorded dataset, achieving classification accuracies of 82.9% and 87.5%, respectively, which surpass several state-of-the-art models. The contribution of each module was further validated through ablation studies. Conclusions: This study demonstrates the superiority of integrating multi-view brain connectivities with dynamically constructed graph structures for MI-EEG decoding. Moreover, the proposed model offers a novel and efficient solution for EEG signal decoding.