Introduction: There is an urgent need for objective biomarkers to facilitate early diagnosis and dynamic monitoring of Alzheimer's Disease (AD). Event-Related Potential (ERP), as a neuroelectrophysiological technique with high temporal resolution, shows great promise in addressing this demand. However, the macro-level developmental trajectory, research status, and frontier directions within this field remain to be systematically elucidated. This study employs bibliometric methods to delineate the development trends, knowledge structures, and research frontiers of ERP applications in AD, thereby offering a novel perspective for early diagnosis, dynamic monitoring, and efficacy assessment. Method: Publications related to ERP and AD were retrieved and screened from the Web of Science Core Collection. A comprehensive quantitative and visual analysis was conducted using Microsoft Excel, CiteSpace, VOSviewer, and the bibliometrix package in R. The analysis covered publication trends, national/institutional collaboration networks, author co-occurrence, core journals, reference and keyword co-occurrence, and clustering. Results: The number of annual publications in this field continued to grow. The United States, China, and Italy were the most productive countries, whereas the cooperation network among institutions and authors was decentralized. Keyword clustering identified six major research topics: P300/N200, Mismatch Negativity (MMN), N170, N400, Olfactory Event-Related Potential (OERP), and Electroencephalography (EEG). Discussion: An analysis of the global research landscape reveals that ERP research has developed from an exploratory tool in the field of AD to an active research field of neuroscience. Journal and citation analysis indicate that the field has distinct clinical problem-driven features; keyword cluster analysis revealed six major themes corresponding to classical cognitive assessment, early sensory memory, and social cognition. Thematic analysis revealed that MMN and other ERP components that are sensitive to early abnormalities may become future research hotspots; however, the overall cooperation in this field still shows a certain degree of geographical concentration and institutional dispersion. In the future, it is necessary to build a closer international and interdisciplinary cooperation network, establish a standardized ERP evaluation scheme, and embed it throughout the entire process of early identification, staging, and monitoring of the effect of intervention in AD. Conclusion: This research systematically presents the current state of research, hotspots, and evolutionary trends in ERP in the field of AD. The results suggest that in the future, a closer international and interdisciplinary cooperation network and further prospective clinical validation are needed to clarify the diagnostic performance and practical application value of ERP, thereby promoting its clinical application.
Abstract: Mental disorders are among the leading causes of non-fatal health loss worldwide and are associated with significant individual, social, and economic burdens. On the other hand, neuropathic pain affects approximately 7-8% of the world's adult population and is a leading reason for medical consultations. A bidirectional relationship between depression and pain has been widely documented. Depression is associated with increased pain perception, while chronic pain may predispose or exacerbate depressive symptoms. The complexity of these two pathologies and the limited efficacy of their current treatments call for research into alternative substances with greater therapeutic success. In this sense, psilocybin has aroused interest in Western medicine since it has been found to have great potential in the treatment of disorders such as depression, anxiety, and pain, among others. In this narrative review, a visualization analysis was conducted to assess the current landscape of psilocybin and psilocin research, spanning from its potential for depression treatment to its potential for pain management. Furthermore, the mechanisms of action of these compounds are analyzed, as are their possible implications in the therapeutics of inflammation and pain, including their participation in the default mode network and the fundamental role of the mystical experiences they generate.
Abstract: Environmental exposure to lead (Pb), manganese (Mn), and cadmium (Cd) damages the Blood-Brain Barrier (BBB) and the Neurovascular Unit (NVU) through a combination of pathways, including endothelial and astrocyte remodeling, transport dysregulation, oxidative and inflammatory signaling, and altered astrocyte-pericyte control of capillary tone. These changes lead to impaired neurovascular coupling and reduced cerebral blood flow. We collated and synthesized mechanistic evidence from experimental and clinical studies conducted over the 30 years from 1995 to 2025, focusing on studies that reported quantitative environmental exposure data and measured neuroimaging correlates of NVU/BBB injury. Cognitive deficits are associated with low-level blood lead levels (<5-10 μg/dL); blood manganese (Mn) levels of 4-15 μg/L are associated with neurodegeneration. Cadmium (Cd) is a cumulative neurotoxicity biomarker linked to cognitive deficits. Hair Mn tracks chronic inhalation exposure more closely than blood Mn does, and the gap between the two measures suggests that cerebral targets receive more manganese than systemic concentrations imply. Neuroimaging corroborates these mechanistic pathways, documenting region-specific cortical and subcortical volume loss, altered brain perfusion, and changes consistent with inflammatory signaling and with endothelial and astrocyte remodeling. Pallidal T1-weighted MRI and Arterial Spin-Labeling (ASL) perfusion MRI both perform well as neuroimaging biomarkers. Multimetal exposure biomarkers are more indicative of the mixture effect than single metal biomarkers. Longitudinal, mechanistic, and quantitative analyses indicate potential to develop interventions in exposed populations.
Introduction: Transcutaneous auricular Vagus Nerve Stimulation (taVNS) may improve cognition in Mild Cognitive Impairment (MCI), but its electrophysiological correlates remain unclear. We explored whether parietal delta-band changes were associated with cognitive changes following taVNS. Methods: This exploratory secondary analysis included 26 participants with MCI from a randomized, double-blind, sham-controlled trial (taVNS, n = 14; sham, n = 12) who had valid resting-state EEG data at baseline and Week 24. Absolute and relative 1–3 Hz delta power at Pz, P1, P2, and P5 were analyzed using repeated-measures ANOVA and EEG–cognitive correlations with Benjamini–Hochberg FDR correction. Results: Absolute delta power showed significant time effects at all four electrodes after FDR correction (all q = 0.008). Relative delta power at Pz showed an uncorrected group effect (F = 5.007, p = 0.035; q = 0.218). In the taVNS group, MoCA-B improvement was positively associated with relative delta-power changes at P1, P2, and P5 (r = 0.629–0.652, p = 0.012–0.016), whereas AVLTN7 improvement was negatively associated with absolute delta-power changes across Pz, P1, P2, and P5 (coefficients = −0.418 to −0.613, p = 0.020–0.048). Although these correlations did not reach statistical significance after correction for multiple comparisons, they showed a relatively consistent direction across multiple electrodes. Discussion: Relative and absolute delta power may reflect complementary aspects of spectral modulation. The convergent cross-electrode associations provide preliminary EEG evidence linked to cognitive response to taVNS. Conclusion: Parietal delta-band power may represent a candidate electrophysiological marker of cognitive change following taVNS in MCI. These exploratory findings support further validation of predefined EEG biomarkers in larger, prospectively powered studies. Clinical trial registration: http://www.chictr.org.cn (ID: ChiCTR2000038868).
Introduction: The endocannabinoid (eCB) system plays fundamental roles in both physiological and pathological aspects of brain function. Activation of type 1 cannabinoid (CB1) receptors in astrocytes by eCBs elevates their intracellular calcium through a signaling pathway that involves activation of Gq/11 proteins, phospholipase C, and IP3R2 to mobilize calcium. Hippocampal astrocytes have been proposed to integrate synaptic information through nonlinear interactions between glutamate and acetylcholine in eliciting calcium responses. However, whether similar integrative interactions occur among other neurotransmitter receptors, namely CB1, glutamate, GABA, and dopamine, and in other brain regions remains unknown. Methods: Here, we investigated whether CB1 receptor activation in astrocytes interacts with signaling pathways of other neurotransmitter receptor systems known to be coupled to Gq/11, Gs, and Gi/o proteins. We monitored astrocytic calcium dynamics in the basolateral amygdala (BLA), a region with prominent integrative functions across multiple neurotransmitter systems, in response to independent or simultaneous receptor activation. Results: We found that simultaneous activation of CB1 receptors with glutamate (Glu), dopamine, or GABA receptors elicited calcium signals that were significantly smaller than the linear summation of responses evoked by each receptor alone. This attenuation was observed in both astrocytic arborizations and somas and was independent of the distance of the domain from the soma. In contrast, the simultaneous activation of Glu and GABA receptors produced calcium responses comparable to the linear sum of their individual effects. Discussion: Our results extend the current understanding of endocannabinoid signaling by revealing that astrocytic CB1 receptor activation can dynamically interact with other neurotransmitter system receptors to generate nonlinear astrocyte calcium signaling outcomes in BLA astrocytes. The integrative signaling capabilities of astrocytes may be particularly relevant in the BLA, suggesting that astrocytes participate directly in shaping amygdala circuit function. Conclusion: Together, these findings demonstrate that neurotransmitter-evoked calcium signaling in BLA astrocytes exhibits receptor-specific nonlinear interactions, supporting a role for astrocytes as integrative elements within local neural circuits.
