Neuroscience最新文献

Humans primarily rely on bodily sensations to experience emotions. Alexithymia, however, alters individuals' emotional experiences. Despite this, limited research has examined whether individuals with different levels of alexithymia experience the same emotions when exposed to identical bodily sensations. The present studies aimed to explore the altered representation of interoceptive sensations in individuals with alexithymia. In Study 1, we measured how participants associated interoceptive sensations with emotion categories using a computer mouse. In Study 2, event-related potentials (ERPs) were recorded simultaneously while participants performed the same task. Mouse trajectories and the N400 component were analyzed, and ANOVA was conducted to examine the differences in both mouse trajectories and N400 amplitudes. In Study 1, we found that individuals with high alexithymia (HA) exhibited less direct and more curved mouse trajectories compared to those with low alexithymia (LA). Study 2 confirmed these behavioral findings and further revealed that HA individuals exhibited greater N400 amplitudes than LA individuals. Our findings suggest that HA individuals experience deficits in the representation of interoceptive sensations, with the N400 serving as a potential index of these deficits in individuals with alexithymia.

Abnormal activity within supplementary motor area (SMA) has been associated with impaired speech and limb movement in neurological conditions. Normalizing aberrant neural activity through non-invasive neuromodulation techniques over SMA has demonstrated promising effects in ameliorating motor and non-motor functions. However, there is limited research on the application of transcranial electrical stimulation (tES) over the left SMA as a potential non-invasive protocol to improve speech production. In this study, we examined the effects of several tES protocols, including high-definition transcranial alternating current stimulation (HD-tACS), transcranial random noise stimulation (tRNS), and direct current stimulation (HD-tDCS), targeting the left SMA in neurotypical adults, on speech and limb reaction times. In a sham-controlled dual-experiment design, two groups of neurologically intact adult participants underwent multiple stimulation sessions: Experiment 1) sham HD-tACS, HD-tACS tuned to each individual's frequency of maximal SMA beta activity (15-30 Hz) during speech (tuned-to-speech) or limb (tuned-to-limb), or HD-tRNS; Experiment 2) sham, anodal or cathodal HD-tDCS. Following the stimulation, the participants were instructed to perform a speech-limb interleaved task. Personalized beta HD-tACS and HD-tRNS - but not HD-tDCS - over the left SMA significantly improved reaction times for both speech and limb movement compared to sham. There was no difference in reaction times between HD-tACS and HD-tRNS for either speech or limb movement. These findings demonstrate comparable neuromodulatory effects of HD-tACS and HD-tRNS in improving speech and limb reaction times in younger adults. This study is exploratory and warrants replication with a larger sample within a single-group design.

Early life stress (ELS) is a significant factor in the development of eating disorders (ED), not as a single cause, but as a powerful influence that creates a vulnerability across an individual's biology and psychology. This review explains how various forms of ELS, such as trauma, neglect, and chronic adversity, can permanently alter brain systems. For example, chronic stress hormone exposure can dysregulate the hypothalamic-pituitary-adrenal (HPA) axis, leading to abnormal cortisol levels and impaired stress self-regulation later in life. This dysregulation can lead to difficulties in managing emotions and coping with stress later in life. Furthermore, ELS impacts the brain's neurochemical systems, including serotonin, dopamine, and norepinephrine, which are responsible for mood, reward, and impulse control. Lasting changes to these systems can explain why some people use food to cope with distress, leading to behaviors like binge eating or extreme restriction. ELS also leaves a biological memory via epigenetic modifications, notably DNA methylation, altering gene expression without changing the DNA sequence to link early experiences to long-term risk. From a psychological perspective, ELS often leads to low self-esteem, self-criticism, and an impaired ability to regulate emotions. These psychological traits, along with a person's neurobiological profile, can make them more susceptible to developing an eating disorder as a way to gain a sense of control over their lives. By integrating genetic, epigenetic, neurobiological, and psychosocial factors, this review clarifies how ELS acts as a multifaceted embedder of vulnerability, contributing to the onset and persistence of EDs.

Background: Alzheimer's disease (AD) is increasingly recognized as a multifactorial network disorder in which amyloid and tau pathology interact with mitochondrial dysfunction, neuroinflammation, metabolic impairment, vascular dysregulation, and synaptic failure. This review provides an integrative, systems-level synthesis of these mechanisms with emphasis on diagnostic and therapeutic implications.

Methods: A structured narrative review was conducted using PubMed, Scopus, Web of Science, and Embase (2010-2025). Eligible studies included clinical trials, biomarker validation studies, cohort analyses, and mechanistic investigations. Evidence was synthesized by mechanistic domain with focus on cross-system interactions and translational relevance.

Findings: Convergent data indicate that soluble Aβ species, tau propagation, glial dysregulation, insulin resistance, mitochondrial bioenergetic failure, lipid imbalance, and BBB dysfunction form a self-reinforcing neurodegenerative network. Diagnostic advances-including plasma p-tau181/217, Aβ42/40 ratio, GFAP, sTREM2, neuronal exosomes, and multimodal machine-learning models-enable earlier staging and refinement of therapeutic selection. Therapeutic development is shifting from linear amyloid removal to multi-target strategies incorporating anti-tau agents, glial-modulating compounds, metabolic and microbiome interventions, medical nutrition, and multidomain lifestyle programs. Across trials, combined strategies targeting interacting mechanisms demonstrate stronger biomarker and cognitive effects than single-axis approaches.

Conclusions: AD management requires a systems-oriented therapeutic architecture in which interventions are selected based on mechanistic dominance, biomarker stage, and potential synergy. We outline a multi-target strategy integrating amyloid/tau modulation, neuroimmune regulation, metabolic-vascular stabilization, and synaptic support. Future work should prioritize biomarker-guided stratification, treatment sequencing, and prevention-oriented combination designs.

Acute pain processing emerges from complex interactions among multiple brain regions, with local ion channels critically shaping neuronal communication. To better understand the role of HCN4 channels during acute pain in mice, a genetic brain-specific HCN4-KO was compared with pharmacological inhibition by the selective HCN4 channel blocker EC18. Stimulus-driven BOLD-fMRI measurements using graded peripheral thermal stimulation allowed brain-wide investigation of both discriminative and suppressive processes within ascending and descending pain pathways. Classical BOLD parameters and graph-theoretical analyses revealed that compared to controls, HCN4-KO showed a significant increase in brain activity in regions responsible for discriminative tasks, emotional pain processing and pain suppression including sensory cortex, amygdala and hypothalamus across both high and low thermal stimulation intensities. In striking contrast, acute inhibition of HCN4 with EC18 decreased activity in these same regions compared with both KO and control mice. Furthermore, comparing pre- and post-stimulation resting-state measurements revealed that HCN4-KO and controls exhibited a stimulation-induced increase in functional connectivity, whereas EC18-treated mice demonstrated a connectivity decrease. Taken together, genetic loss of HCN4 produced a hypersensitive phenotype in thermal pain processing, whereas acute pharmacological inhibition of the channel elicited an opposing hyposensitive phenotype.