Behavioral and Brain Functions最新文献

Background: This study aims to investigate the differences in neural network connectivity within the prefrontal cortex (PFC) among elderly individuals with normal cognition (NC), mild cognitive impairment (MCI), and Alzheimer's disease (AD) using functional near-infrared spectroscopy (fNIRS).

Results: Significant differences in functional connectivity (FC) strength were observed between the NC, MCI, and AD groups in several Brodmann areas (BA) pairs, including BA46.L-BA45.R and BA9.L-BA1.L. The most pronounced FC strength differences between the NC and MCI groups occurred at the 2nd -minute mark in BA45.R, while differences between the MCI and AD groups peaked at the 5th-minute mark in BA1.L. Additionally, the NC and MCI groups displayed FC strength differences during the first 2 minutes and first 3 minutes, again with BA45.R being central. FC strength between BA46.L-BA45.R was negatively correlated with Neuropsychiatric Inventory and Clinical Dementia Rating scores.

Conclusions: FC strength in the left dorsolateral PFC, where BA46.L and BA9.L are located, emerged as a key region for cortical dysfunction in cognitive impairment. Moreover, there were differences in FC across levels of cognitive impairment, and significant correlations between differences in FC strength in BA brain regions and cognitive level.

Social ties critically influence individual health and well-being, raising important questions about why some individuals occupy advantageous social network positions. While social cognition is known to play a key role, it remains unclear whether neural differences during social information processing is associated with variability in the social network structure. Using the Prisoner's Dilemma Game (PDG) combined with multilayered social network analysis, brain network analysis, and machine learning, we investigated how neural activation patterns relate to individual social network structures. The results revealed that individuals with a larger social network size were associated with (1) heightened nodal efficiency in the midcingulate cortex (MCC), (2) reduced efficiency in the inferior occipital gyrus (IOG), (3) enhanced functional connectivity between the anterior cingulate cortex-supplementary motor area (ACC-SMA) and olfactory-somatosensory regions, and (4) significantly negative predictive effects of nodal efficiency in both the IOG and hippocampus (as identified through machine learning). These findings demonstrate that efficient brain network organization, characterized by optimized integration in the cingulate cortex with a conflict monitoring function and selective suppression of visual attention and memory processing, is related to real-world social adaptation. Our study offers novel neurobiological insights into social networks, highlighting the crucial role of neural efficiency in social resource acquisition.

Background: Opioid use disorder is driven by neurobehavioral adaptations where environmental cues trigger relapse. Consequently, extinction therapy (ET) aims to modify drug-associated memories but has limited long-term efficacy. Recently, evidence suggested that glial cells may contribute to neuroplasticity phenomena in addiction. In this sense, this study examined whether aversive memories of morphine withdrawal and their extinction induce transcriptional changes in glial markers (gfap, aif1, itgam, klf4) in key memory-related regions: the basolateral amygdala (BLA) and hippocampus (dentate gyrus [DG] and CA1).

Results: Using the conditioned place aversion (CPA) paradigm in rats, we assessed avoidance behavior after naloxone-precipitated withdrawal and its extinction. Transcriptional analyses did not reveal major changes in the BLA. However, in CA1, downregulation of microglial markers cooccurred with aversive memory retrieval and restored after extinction. Moreover, one of the microglial markers, klf4, was reduced concomitantly with extinction memory retrieval in the DG. Correlation analyses showed negative associations between microglial markers and aversive memory strength, suggesting glial involvement in withdrawal-related learning.

Conclusions: These findings might indicate that microglial activity in CA1 plays a role in opioid withdrawal-associated memories, and extinction training might be returning these effects to basal levels. Therefore, targeting glial responses could provide new therapeutic strategies to prevent relapse.

Background: A common magnitude system-consistently involving the right intraparietal sulcus (IPS)-has been proposed to support the representation of space, time and numerosity. While shared mechanisms are acknowledged, domain-specific contributions have also been suggested. Among these, the role of the right precuneus remains debated, with inconclusive evidence regarding its involvement in spatial and temporal processing. Translating this question into the language domain and within a grounded cognition framework, we investigated the causal contribution of the IPS and precuneus to the processing of spatial and temporal concepts (e.g., circuit, eternity) using a state-dependent Transcranial Magnetic Stimulation (TMS) priming paradigm. Twenty healthy participants received stimulation over the IPS and precuneus, and a sham stimulation over the control site (vertex).

Results: Results showed that stimulation of the IPS abolished the priming effect observed under the sham control condition for both spatial and temporal concepts, whereas stimulation of the precuneus selectively disrupted priming for temporal concepts only.

Conclusions: These findings support the role of the right IPS as a key area for magnitude processing in language, while also highlighting a more specific contribution of the precuneus-particularly its ventral portion-to temporal concepts.

Cognitive functions are critical to everyday life, and enhancing cognitive abilities has significant implications for both individual development and societal advancement. However, there remains no consensus on whether cognitive capacities can be systematically improved through behavioral interventions, commonly known as cognitive training. Recent advancements in large-scale neural recordings offer unprecedented insights into the brain's cognitive mechanisms, presenting new opportunities to rigorously assess the effectiveness of cognitive training. In this review, we examine the core neural substrates underlying cognitive processes and explore generalized mechanisms of neuroplasticity associated with cognitive training. Integrating findings from animal models and human research, we emphasize the role of emerging schematic neural representations as potential mediators of cognitive transfer. Finally, we discuss future directions that could shed light on the mechanistic foundations of transfer after training, aiming to bridge the gap between experimental findings and real-world cognitive enhancement.

This study aimed to investigate the sex-dependent behavioral effects of tamoxifen, commonly used to induce Cre recombination in transgenic systems, across three developmental stages (adult, adolescent, and neonatal) and two CreERT2 mouse lines (CaMKIIα-CreERT2 and Aldh1l1-CreERT2). Both male and female mice, including wild-type C57BL/6J and CreERT2 transgenic lines, were subjected to tamoxifen treatment followed by behavioral tests assessing locomotion, anxiety-like behavior (open field test and elevated plus maze), social interaction, recognition memory (new object recognition), sucrose preference, and depression-like behavior (forced swimming test) at least 4 weeks post-treatment. We found that adult tamoxifen treatment increased depression-like behavior specifically in males, while adolescent treatment increased sucrose preference only in males, yet impaired recognition memory and increased depression-like behavior in both sexes. Neonatal treatment caused pervasive impairments, reducing locomotion and increasing anxiety- and depression-like behavior in both sexes, while enhancing social interaction only in males. Furthermore, effects differed in adult CaMKIIα-CreERT2 and Aldh1l1-CreERT2 mice. In the former, tamoxifen treatment impaired locomotion, increased anxiety-like behavior, and reduced recognition memory specifically in females, while increasing sucrose preference in males. In the latter, tamoxifen treatment impaired recognition memory in both sexes but increased sucrose preference only in males. These results demonstrate that tamoxifen alone induced long-lasting, sex-specific behavioral alterations dependent on developmental exposure. Furthermore, interactions of tamoxifen with CreERT2 expression introduced additional complexity, potentially confounding genetic studies. These findings emphasize the necessity of including appropriate controls (vehicle, tamoxifen-only, Cre-only) and both sexes in studies using the tamoxifen-inducible CreERT2-loxP system.

Background: Essential tremor (ET) is a common movement disorder characterized by persistent limb tremors. Currently, no effective treatment for ET exists. Natural plant-derived compounds, like the flavonoid, quercetin may provide therapeutic benefits, particularly when delivered in nanoemulsion formulations that enhance bioavailability and efficacy. This study evaluated the neuroprotective potential of quercetin nanoemulsion (Que-NE) in a harmaline-induced mouse model of ET.

Methods: Thirty-two male Swiss mice were randomly divided into four groups (n = 8 each): Control, Harmaline (10 mg/kg, i.p., on days 3, 5, and 7), Que-NE (20 mg/kg, i.p., for 7 days), and Harmaline + Que-NE. Harmaline was used to reliably induce tremor via olivocerebellar hyperexcitability. Behavioral performance was assessed using the open field, elevated plus maze, tail suspension, wire grip, rotarod, and passive avoidance tests. Expression of NF-κB, TNF-α, IL-1β, IL-6, NMDA receptor, and Lingo-1 was determined by RT-PCR.

Results: Que-NE significantly reduced harmaline-induced tremor severity (p < 0.0001), decreased immobility time in the tail suspension test (p = 0.0003), and improved open field anxiety-like behaviors compared with harmaline alone (P = 0.0012). Que-NE downregulated pro-inflammatory mediators (P < 0.0001) and reduced Lingo-1 gene expression (P < 0.0001). However, Que-NE showed limited efficacy in severe motor coordination tasks (rotarod, wire grip) and passive avoidance memory.

Conclusions: Que-NE exerts measurable anti-inflammatory, anxiolytic, and antidepressant-like effects in the harmaline model of ET. The impact of Que-NE on improving motor deficits, reducing inflammatory markers, and suppressing inhibitors of synaptic plasticity highlights the potential of Que-NE as a disease-modifying strategy. However, dose-response, protein-level, and long-term studies are needed to evaluate the therapeutic potential of Que-NE for ET management.

Heat Shock Protein Family A Member 1B (Hspa1b) is an RNA binding protein that regulates transcriptional and post transcriptional processes. Previous studies have suggested its protective role in stress adaptation and post injury depression, as well as its potential therapeutic effects following antidepressant treatment in major depressive disorder (MDD). However, its direct involvement in MDD remains unclear. In this study, a mouse model with hippocampal Hspa1b overexpression was established. Integrated RNA immunoprecipitation sequencing (RIP seq) and RNA sequencing (RNA seq) were performed to investigate Hspa1b mediated transcriptional regulation and alternative splicing. Overexpression of Hspa1b resulted in 401 differentially expressed genes (DEGs), including downregulation of several neuroinflammatory genes such as Lcn2, Ccl5, and Cd52, upregulation of oxytocin/neurophysin I prepropeptide (Oxt), and downregulation of intercellular adhesion molecule 1 (Icam1), which are all associated with depression pathogenesis. In addition, 1,397 significantly altered Hspa1b regulated alternative splicing events were identified. RT qPCR confirmed splicing changes in six genes, including Spata13 and Ptpro, among others linked to depression and neuronal functions. These findings demonstrate that hippocampal Hspa1b overexpression is associated with transcriptional and splicing alterations in genes related to immune, neuronal, and HPA axis pathways, which are key mechanisms implicated in MDD. Based on these alterations, Hspa1b may act as a double-edged regulator in MDD, warranting further investigation of its causal role and therapeutic potential.

Research into memory mechanisms has predominantly centered on adult male rodents, often overlooking the influences of sex and developmental stage. Memory processes vary significantly between juveniles and adults, with sex acting as a critical determinant. Oxytocin (OXT) has emerged as a key modulator of fear responses and extinction in a sex-dependent manner, with prepubertal females displaying OXT-dependent contextual extinction patterns akin to adult males. These differences likely stem from diverse trajectories of hippocampal and prefrontal cortex maturation. This study examines the CA1 region's involvement in object location memory (OLM), social recognition memory (SRM), and synaptic plasticity among juvenile male and female rats, focusing on OXT's role. Results reveal that, in juvenile (postnatal day -PND 27) protein synthesis inhibition or OXT receptor blockade with OXT receptor antagonist (OXTR-Ant) in CA1 impairs OLM and impairs long-term potentiation (LTP) uniquely in males. These findings correlate with a greater increase in CA1 c-Fos expression following OLM in juvenile males compared to females. The SRM impairment was uniform across sexes under these treatments. In adults (PND 69), OXTR-Ant caused OLM impairment solely in females. These findings underscore pronounced sex- and age-specific variations in CA1-dependent memory and synaptic plasticity, shedding light on distinct neurobiological mechanisms that emerge pre-puberty and evolve throughout development.

Cognitive flexibility-the ability to adaptively shift between different mental processes-is essential for human functioning. This meta-analysis examines age-related changes in neural correlates of cognitive flexibility using two common assessments: the Wisconsin Card Sorting Test (rule-discovery) and Task-Switching Paradigm (rule-retrieval). We synthesized findings from 85 articles comprising 118 experiments with 2246 participants across young, middle-age, and older adult groups. Activation Likelihood Estimation analyses revealed an age-related decrease in neural involvement, particularly in posterior regions, with an anterior shift in older adults. Younger adults exhibited bilateral activation patterns while older adults showed left-dominant activity, indicating neural circuit redistribution. Rule-retrieval tasks consistently engaged left-lateralized frontoparietal regions across all age groups, with middle-age adults additionally recruiting the right cerebellum and medial frontal gyrus. For rule-discovery tasks, age-related changes were observed in bilateral frontoparietal regions, with older adults showing unique activation in the left inferior frontal gyrus. These findings highlight differential aging trajectories for rule-retrieval versus rule-discovery processes, reflecting changes in neural mechanisms with aging. Furthermore, middle-age adults recruited additional regions related to conflict monitoring, whereas older adults relied more on planning-related areas, suggesting strategy differences. Our study provides critical insights into the neural underpinnings of cognitive flexibility and its age-related changes, emphasizing the need for research on mechanisms and task-specific age trajectories.