European Journal of Neuroscience最新文献

Pupil dilation (PD) is more pronounced during the correct recognition of previously encountered target items than during the correct rejection of novel, previously unseen foils. This phenomenon, known as the pupil old/new effect, has been interpreted in several ways—one prominent account suggests that it reflects a bottom-up attentional orienting response triggered by activated mnemonic information. Given that the magnitude of an orienting response to a stimulus is influenced by its task relevance, we tested in two experiments whether task instructions modulate the pupil old/new effect. Participants were presented with previously encoded material intermixed with novel items and were instructed to categorize the items as animate/inanimate (nonmnemonic task) and then to make an old/new recognition judgment on a subset of the items (mnemonic task). When the items had strong memory representations, an old/new effect emerged in the nonmnemonic task condition (i.e., when no explicit memory decision was required). In contrast, this effect could not be consistently demonstrated for weakly encoded items. Moreover, when the encoded stimuli were not overlearned, the old/new effect was more pronounced in the mnemonic than in the nonmnemonic task, suggesting that the effect is driven by attentional orientation modulated by task relevance. The pattern of our results thus suggests that strong memory representations can automatically trigger increased PD (i.e., without explicit memory instruction), and that the pupil old/new effect reflects an attentional orienting response toward activated mnemonic information.

The temporal and spatial characteristics of the nociceptive system have been previously investigated to understand pain mechanisms. One way to evaluate the combined temporospatial integration of sensory information is by directional discrimination. Since directional discrimination is a perceptual ability, it may be improved through perceptual learning. Perceptual learning improves the ability to perceive and recognize stimuli through practice but has rarely been investigated in the nociceptive system. The aim of this study was to investigate if perceptual learning affects nociceptive directional discrimination using moving temperature-controlled laser stimuli. Twenty-eight healthy subjects participated in a crossover study on two different days. On each day, subjects went through either supervised (i.e., with feedback) or unsupervised (i.e., without feedback) training to discriminate the direction of the moving stimulus in the right forearm. The noxious stimulus was displaced across the skin in four directions (distal, proximal, lateral, and medial) and five different displacement lengths. The subjects had to indicate the perceived stimulus direction and the degree of certainty in the discriminated direction. The results showed that there was a significant increase in the correctness of the indicated directions and certainty following supervised training. In the lateral–medial direction, the supervised training decreased the directional discrimination threshold (DDT, where 50% of directions were correctly discriminated), which was not observed for the unsupervised training. In conclusion, it was found that only supervised training improves the performance of directional discrimination. While the percentage of correct answers increased following supervised training, the estimated DDT did not decrease in all directions.

Emerging evidence in ischemic stroke indicates that imbalances in serotonin and dopamine are linked to motor deficits in stroke survivors. Nevertheless, the spatial relationships between the biological mechanisms underlying stroke and the observed imaging changes remain poorly understood. This study aimed to explore neuroplasticity alterations in chronic subcortical ischemic stroke patients before and after 1-month pharmacological intervention, as well as to assess the spatial connections between the underlying biology and imaging changes. In the present study, all patients underwent two T1-weighted scans and resting-state functional magnetic resonance imaging sessions, spaced 1 month apart. Key assessments focused on gray matter (GM) volume, voxel-mirrored homotopic connectivity (VMHC), and the spatial distribution correlations of neurotransmitters. Longitudinal analysis demonstrated significant reductions in the right precuneus, left calcarine cortex, and left cerebellum, while increases in the left middle cingulate cortex (MCC), left supplementary motor area (SMA), and right precentral gyrus after intervention. Similarly, longitudinal analyses of VMHC showed substantial increases in the inferior parietal lobe, precentral gyrus, middle temporal gyrus, SMA, postcentral gyrus, MCC, and cerebellum. Both neuroimaging metrics in the SMA and precentral gyrus regions exhibited significant correlations with clinical outcomes. Additionally, a notable connection was observed between neuroimaging measures (GM volume and VMHC) and the spatial distribution of neurotransmitter systems, including serotonergic systems and vesicular acetylcholine transporter. Taken together, these results highlight the evolving neuroimaging changes that occur after an ischemic stroke and provide novel insights into the underlying neurological processes driving these longitudinal alterations in stroke patients.

The blood–brain barrier (BBB) is an essential protective structure that preserves the homeostasis of the central nervous system (CNS) by controlling the transfer of chemicals and infections from the bloodstream into the tissues of the brain. The BBB is primarily composed of brain microvascular endothelial cells (BMECs), which are closely linked by tight junction (TJ) proteins, including occludin, claudins and junctional adhesion molecules (JAMs). However, certain bacterial infections, such as those caused by Escherichia coli (E. coli), Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae (H. influenzae), have developed strategies to compromise these TJs, facilitating their invasion of the CNS and resulting in meningitis. These bacteria utilise several virulence factors, including outer membrane proteins, pili and toxins, to modify host cell signalling pathways, compromise the BBB and facilitate their translocation across barriers. This study aims to clarify the molecular processes employed by these pathogens to penetrate the BBB, with an emphasis on their effects on TJ integrity. A comprehension of these mechanisms is essential for formulating effective medicines to prevent and cure bacterial meningitis by safeguarding or restoring BBB integrity.

Parkinson's disease (PD) is a neurodegenerative disorder with rapidly increasing prevalence, characterized by dopaminergic neuronal loss and α-synuclein aggregation. Current therapies provide only symptomatic benefit and do not alter the disease course. MicroRNAs (miRNAs), small noncoding RNAs that regulate gene expression, are increasingly recognized as key modulators of PD pathogenesis, influencing oxidative stress, mitochondrial dysfunction, neuroinflammation, and proteostasis. Therapeutic modulation of miRNAs in PD has centered on two complementary approaches: miRNA inhibitors (antagomiRs), which silence pathogenic miRNAs, and miRNA mimics (agomiRs), which restore the activity of protective ones. This review integrates current insights into miRNA dysregulation in PD and evaluates the hurdles limiting therapeutic translation. Specific miRNAs such as miR-7, miR-153, and miR-34b/c directly regulate SNCA expression, whereas others influence clearance pathways and stress responses. Although miRNA-based therapeutics offer considerable promise, their clinical utility remains constrained by challenges of delivery, specificity, and standardization. This review highlights strategies to harness miRNA modulation as a targeted therapeutic avenue in PD.