Frontiers in Neuroscience最新文献

Cognitive impairment is a prevalent non-motor symptom of Parkinson's disease (PD), increasing the risk of dementia as the disease progresses. Despite its clinical significance, the etiology of cognitive impairment in PD remains unclear. Apolipoprotein E4 (APOE4), a well-known genetic risk factor of Alzheimer's disease, has been studied for its potential role in PD-related cognitive impairment. However, findings have been conflicting and thus inconclusive, highlighting a need to critically evaluate the current research. Several studies using neuroimaging modalities have explored the brains of individuals with PD and atypical parkinsonian disorders who have APOE4. Some of these studies have identified distinct neuropathological changes that have been previously reported to be associated with cognitive impairments in those with Parkinsonisms. Here, we review the role of APOE4 on cognitive impairment in PD and atypical Parkinsonisms using neuroimaging evidence. We will examine how APOE4 may contribute to pathological changes within the brain and its association with cognitive impairment.

Audiovisual cross-modal correspondences (CMCs) refer to the brain's inherent ability to subconsciously connect auditory and visual information. These correspondences reveal essential aspects of multisensory perception and influence behavioral performance, enhancing reaction times and accuracy. However, the impact of different types of CMCs-arising from statistical co-occurrences or shaped by semantic associations-on information processing and decision-making remains underexplored. This study utilizes the Implicit Association Test, where unisensory stimuli are sequentially presented and linked via CMCs within an experimental block by the specific response instructions (either congruent or incongruent). Behavioral data are integrated with EEG measurements through neurally informed drift-diffusion modeling to examine how neural activity across both auditory and visual trials is modulated by CMCs. Our findings reveal distinct neural components that differentiate between congruent and incongruent stimuli regardless of modality, offering new insights into the role of congruency in shaping multisensory perceptual decision-making. Two key neural stages were identified: an Early component enhancing sensory encoding in congruent trials and a Late component affecting evidence accumulation, particularly in incongruent trials. These results suggest that cross-modal congruency primarily influences the processing and accumulation of sensory information rather than altering decision thresholds.

Introduction: The locus coeruleus (LC)-noradrenaline (NA) system plays a crucial role in modulating neuronal excitability and plasticity. In epilepsy, the LC-NA system plays an important role in regulating seizure thresholds and severity, with elevated NA release mediating the seizure-suppressing effects of vagus nerve stimulation (VNS). We investigated whether chemogenetic LC activation is able to increase hippocampal NA release and affect hippocampal electrophysiology in anesthetized rats.

Methods: 22 male Sprague-Dawley rats were injected with the viral vector AAV9-hSyn-NE2m in the hippocampus to induce expression of the GRAB_NE2m biosensor to locally measure changes in extracellular NA. 15/22 rats were injected with the CAV2-PRSx8-hM3Dq hSyn-mCherry viral vector in the LC to express the excitatory DREADD hM3Dq, allowing LC activation with deschloroclozapine (DCZ), and 7/22 with CAV2-PRSx8-GtACR2 as a control. A perforant path stimulation electrode and a dentate gyrus (DG) recording electrode were implanted for local field potential (LFP) and evoked potential (EP) recording as well as a DG optical fiber for GRAB_NE2m fluorescence measurement.

Results: In a significant number of rats (7/15) we found an increase in hippocampal NA release, field excitatory post synaptic potential (fEPSP) slope and population spike (PS) amplitude, indicating an increase in excitatory neurotransmission and neuronal output. 4/15 rats showed a decrease in NA release without changes in fEPSP slope or PS amplitude, and 4/15 showed no change in NA release.

Discussion: These findings indicate that chemogenetic activation of the LC-NA system can modulate hippocampal evoked responses, supporting further exploration of its role in health and disease, such as in epilepsy.

Background: Fall risk prediction is crucial for preventing falls in patients with cerebral small vessel disease (CSVD), especially for those with gait disturbances. However, research in this area is limited, particularly in the early, asymptomatic phase. Wearable sensors offer an objective method for gait assessment. This study integrating wearable sensors and machine learning, aimed to predict fall risk in patients with covert CSVD.

Methods: We employed soft robotic exoskeleton (SRE) to acquire gait characteristics and surface electromyography (sEMG) system to collect sEMG features, constructing three datasets: gait-only, sEMG-only, and their combination. Using Support Vector Machine (SVM), Random Forest (RF), Gradient Boosting Decision Tree (GBDT), and Neural Network (NN) algorithms, we developed twelve predictive models. Furthermore, we integrated the selected baseline data and imaging markers with the three original datasets to create three new integrated datasets, and constructed another twelve optimized predictive models using the same methods. A total of 117 participants were enrolled in the study.

Results: Of the 28 features, ANOVA identified 10 significant indicators. The Gait & sEMG integration dataset, analyzed using the SVM algorithm, demonstrated superior performance compared to other models. This model exhibited an area under the curve (AUC) of 0.986, along with a sensitivity of 0.909 and a specificity of0.923, reflecting its robust discriminatory capability.

Conclusion: This study highlights the essential role of gait characteristics, electromyographic features, baseline data, and imaging markers in predicting fall risk. It also successfully developed an SVM-based model integrating these features. This model offers a valuable tool for early detection of fall risk in CSVD patients, potentially enhancing clinical decision-making and prognosis.

Introduction: The infralimbic cortex (IL), a critical subregion within the ventromedial prefrontal cortex (vmPFC), modulates emotion, memory, and social functions via robust projections to the basolateral amygdala (BLA). However, the afferent brain regions that innervate BLA-projecting IL neurons (IL-BLA PNs) and their efferent targets have not been systematically characterized.

Methods: We employed tracing techniques integrating adeno-associated virus (AAV) and monosynaptic rabies to systematically investigate the presynaptic inputs and axonal outputs of IL-BLA PNs.

Results: Our findings revealed widespread synaptic inputs to IL-BLA PNs from subcortical areas, with the strongest inputs originating from the dorsomedial thalamus (MD) and anterior medial thalamus (AM) in the thalamic region, as well as from the ventral hippocampus (vHPC) and piriform cortex (Pir) in the limbic system. Sparse labeling of the virus demonstrated that IL-BLA PNs collateralize to innervate various subcortical regions, including the horizontal diagonal band (HDB), lateral preoptic area (LPO), ventral pallidum (VP), and lateral hypothalamus (LH).

Discussion: This work establishes essential theoretical frameworks for the functional investigation and targeted intervention in neurological disorders.

Introduction: The gut microbiota composition and the expression profiles of microRNAs (miRNAs) in the brain tissue, cerebrospinal fluid, and blood of patients with Alzheimer's disease (AD) differ significantly from those with normal cognition function. The study aimed to initially explore the relationship between plasma exosomal microRNAs, gut microbiota, and cognitive impairment, providing insights into the pathogenesis and treatment of AD.

Methods: The study enrolled 8 participants with AD and 8 participants with normal cognition. The Mini-Mental State Examination (MMSE) was utilized to evaluate cognitive function. High-throughput sequencing was used to identify differentially expressed miRNAs in plasma exosomes, while metagenomic sequencing was employed to detect differences in the abundance of gut microbiota. Furthermore, the associations among them were analyzed.

Results: Four exosomal miRNAs and 14 microbiota taxa, which exhibited differential expression and abundance, respectively, in comparison between AD group and normal cognition group, were identified to be significantly associated with MMSE scores. Notably, the abundance of potential probiotics, including Faecalibacterium prausnitzii, Roseburia intestinalis and Roseburia inulinivorans, which was decreased in AD patients, exhibited positive correlations with specific exosomal miRNAs: Roseburia intestinalis correlated with miR-3120-3p and miR-6529-5p; Roseburia inulinivorans correlated with miR-3120-3p, miR-6529-5p and miR-124-3p; Faecalibacterium prausnitzii correlated with miR-3120-3p.

Discussion: The study revealed a close association among gut microbiota, plasma exosomal miRNAs, and cognitive impairment in AD, and suggested that specific components of gut microbiota and exosomal miRNAs may serve as potential biomarkers and therapeutic targets for AD on the microbiota-gut-brain axis.

Adult-onset autosomal dominant leukodystrophy (ADLD) is a rare, slowly progressive, and fatal neurodegenerative disorder characterized by central nervous system white matter loss due to LMNB1 gene abnormalities encoding laminB1. However, not all LMNB1 mutations lead to ADLD. Currently, two genetic alterations have been identified in association with the pathogenesis of ADLD: LMNB1 gene tandem duplication and LMNB1 gene upstream deletions. We report a case of a 60-year-old man diagnosed with ADLD, with pyramidal tract dysfunction and autonomic abnormalities as the main clinical manifestations. MRI revealed bilateral symmetric high signal intensities in the white matter of the medulla oblongata, middle cerebellar peduncles, cerebral peduncle, periventricular white matter, centrum semi vale, and the pressure region of the corpus callosum. Whole exome sequencing results indicated 73.6Kb duplicate copy number variation signals in the 5q23.2 region of the proband's chromosome. The Multiplex ligation-dependent probe amplification (MLPA) experiment results indicate recurrent mutations across all exons (exon1-11) of the LMNB1 gene. This is the eighth ADLD pedigree from China. We conducted a literature review of all ADLD pedigrees in China and summarized the characteristics of Chinese patients with ADLD to raise awareness of ADLD disease.

Like many other vertebrates, rodents communicate via pheromones, which favors intraspecies communication. In contrast, kairomones are semiochemicals involved in interspecific communication, facilitating information between organisms of different species but advantageous for the receiver. Kairomones induce behavioral, physiological, and endocrinological changes in rodents, and have been proven to activate specific neuronal pathways in one or multiple components of the olfactory system (the main olfactory system, accessory olfactory system, and Gruenberg ganglion). The sophisticated olfactory networks help rodents innately recognize kairomones and elicit appropriate behavioral (aversive, avoidance, defense, and escape mechanisms), physiological, and endocrinological changes. Thus far, odor sources (e.g., urine, feces, hair, and body rubbings) of predators, such as felines, canines, and serpentes, have been studied in rodents. Specific kairomones have been identified, behaviorally tested, and validated for their potential to induce behavioral, neuronal, and endocrinological changes in rodents. One of the most studied kairomones is the fox odor, 2,5-dihydro 2,4,5-trimethylthiazoline, although other compounds have been reported to a limited extent. This review summarizes the current knowledge on kairomones and their effects on the behavioral, neuronal, and endocrine systems of rats and mice.

Parkinson's disease (PD), a common neurodegenerative disease, seriously impacts the quality of life of patients. In recent years, research has revealed that the GABAergic signaling pathway plays an important role in the occurrence and development of PD. GABA is an important inhibitory neurotransmitter in the central nervous system (CNS), synthesized through the alpha decarboxylation reaction of glutamate (Glu) under the action of glutamic acid decarboxylase (GAD) in GABAergic neurons. It works by binding to specific receptors (GABA _A /GABA _B ). In PD patients, the activity of GABAergic neurons in the basal ganglia (BG) changes, leading to an imbalance between direct and indirect pathways and causing motor symptoms. Meanwhile, the GABAergic signaling pathway is closely related to non-motor symptoms such as anxiety, depression, and sleep disorders. At present, the treatment methods for PD mainly include drug therapy, surgical treatment, and rehabilitation therapy. Acupuncture, as a complementary and alternative therapy, has shown promising efficacy in the clinical treatment of PD. This review comprehensively and thoroughly explores the therapeutic effect of acupuncture on PD and its mechanism of action with GABAergic signaling. By systematically summarizing relevant research results, it was found that acupuncture may exert a complex mechanism of therapeutic effect by regulating the GABAergic signaling pathway. Further clarification of these mechanisms of action will be beneficial for promoting the application and development of acupuncture in the treatment of PD and is expected to provide new targets and strategies.