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Combined transcranial electrical stimulation (tES) and cognitive training (CT) for cognitive impairment: Evidence from clinical applications and basic research. 联合经颅电刺激(tES)和认知训练(CT)治疗认知障碍:来自临床应用和基础研究的证据。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-02-02 DOI: 10.1016/j.bbr.2026.116078
Shu Xing, Yuan Yuan, Ping Ren, Zhuangfei Chen, Yu Fu

Cognitive impairment is a serious pathological feature of neuropsychiatric disorders, making the exploration of effective treatments urgent. Recent research shows that combined transcranial electrical stimulation (tES) and cognitive training (CT) can reduce cognitive deficits. This review summarizes studies on neurological disorders that use both clinical patients and rodent models to highlight the underlying neural mechanisms. In patients, this combined approach improves cognitive domains such as attention, working memory, and executive function. Improvements have been observed in patients with mild cognitive impairment (MCI), dementia (e.g., Alzheimer's disease (AD)), Parkinson's disease (PD), stroke, traumatic brain injury (TBI), multiple sclerosis, schizophrenia, attention deficit hyperactivity disorder (ADHD) and depression, as well as in healthy populations. In contrast, studies on the combined intervention are lacking in rodent models of disease. However, tES and CT separately improve spatial learning and memory in AD, TBI, schizophrenia, ADHD, and healthy animals, as well as in models of vascular dementia and cerebral ischemia. The combined intervention regulates and remodels functional connectivity in brain networks, and improves cerebrovascular microcirculation and glutamatergic neurotransmission. Importantly, tES and CT may enhance each other through cooperative and complementary effects. In addition, some studies have reported the limited efficacy or negative outcomes of combined and single interventions, which may be due to suboptimal parameters or techniques that fail to target key pathologies. Future clinical trials should explore tES-CT combination strategies targeting disease-specific brain regions. Furthermore, animal studies must be strengthened to elucidate the potential mechanisms and interactions of tES and CT.

认知障碍是神经精神疾病的严重病理特征,迫切需要探索有效的治疗方法。最近的研究表明,经颅电刺激(tES)和认知训练(CT)相结合可以减少认知缺陷。本文综述了神经系统疾病的研究,包括临床患者和啮齿动物模型,以突出潜在的神经机制。在患者中,这种综合方法可以改善认知领域,如注意力、工作记忆和执行功能。在轻度认知障碍(MCI)、痴呆症(如阿尔茨海默病(AD))、帕金森病(PD)、中风、创伤性脑损伤(TBI)、多发性硬化症、精神分裂症、注意缺陷多动障碍(ADHD)和抑郁症患者以及健康人群中都观察到改善。相比之下,在啮齿动物疾病模型中缺乏联合干预的研究。然而,tES和CT分别改善了AD、TBI、精神分裂症、ADHD和健康动物以及血管性痴呆和脑缺血模型的空间学习和记忆。联合干预调节和重塑脑网络功能连接,改善脑血管微循环和谷氨酸能神经传递。重要的是,tES和CT可以通过合作和互补效应来相互促进。此外,一些研究报告了联合干预和单一干预的有限疗效或负面结果,这可能是由于次优参数或未能针对关键病理的技术。未来的临床试验应探索针对疾病特异性脑区域的tES-CT联合策略。此外,必须加强动物研究,以阐明tES和CT的潜在机制和相互作用。
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引用次数: 0
Targeting the prefrontal-supplementary motor network with online and offline tDCS to modulate disgust: A single-blind and sham-controlled study. 在线和离线tDCS针对前额叶-辅助运动网络调节厌恶:单盲和假对照研究。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-02-02 DOI: 10.1016/j.bbr.2026.116077
Parastoo Soltani, Zekrollah Morovati, Majid Yousefi Afrashteh, Jakob Fink-Lamotte, Jaber Alizadehgoradel

In certain individuals, disgust experience is abnormally high. This heightened sensitivity serves as a cognitive component that can lead to dysfunction in neural circuits related to emotion processing and psychological disorders such as contamination-based obsessive-compulsive disorder. In this single-blind study, 36 individuals with high disgust sensitivity were randomly assigned to three groups: online, offline, and sham. The online group received intensified and repetitive transcranial direct current stimulation (tDCS) while performing a disgust image watching task, whereas the offline and sham groups performed the task at two time points: immediately before (pre-test) and immediately after (post-test) the stimulation session. The offline group received active tDCS, whereas the sham group received placebo tDCS to control for the interval duration. Anodal and cathodal stimulation was applied to the left dorsolateral prefrontal cortex (l-DLPFC; F3) and pre-supplementary motor area (pre-SMA; FC2), respectively. The intervention consisted of 10 sessions of tDCS (2 sessions per day) over 5 days, with a stimulation intensity of 2mA for 20minutes and a 20-minute interval between sessions. The results showed a significant decrease in disgust experience in the online group compared to the offline group, while there was no significant difference between the online and sham groups. Although these findings suggest potential effects of tDCS combined with a task, further studies are necessary to confirm its efficacy.

在某些个体中,厌恶体验异常高。这种高度的敏感性作为一种认知成分,可能导致与情绪处理和心理障碍(如基于污染的强迫症)相关的神经回路功能障碍。在这项单盲研究中,36名高厌恶敏感性的人被随机分为三组:在线组、离线组和假组。在线组在执行厌恶图像观看任务时接受强化和重复的经颅直流电刺激(tDCS),而离线组和假组在两个时间点执行任务:刺激之前(测试前)和之后(测试后)。离线组接受主动tDCS,而假手术组接受安慰剂tDCS来控制间隔时间。分别对左背外侧前额叶皮层(l-DLPFC; F3)和前辅助运动区(pre-SMA; FC2)施加阳极和阴极刺激。干预包括10次tDCS(每天2次),持续5天,刺激强度为2mA,每次20分钟,每次之间间隔20分钟。结果显示,与离线组相比,在线组的厌恶体验显著减少,而在线组和假组之间没有显著差异。尽管这些发现表明tDCS与任务相结合的潜在影响,但需要进一步的研究来证实其有效性。
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引用次数: 0
Polygenic modulations of decoy and compromise effects by dopaminergic and serotonergic systems 多巴胺能和血清素能系统诱骗和妥协效应的多基因调节
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-02-02 DOI: 10.1016/j.bbr.2026.116072
Yao Xiao , Min Yang , Yuling Huang , Han Li , Na Zhao , Chenjin Qiao , Pingyuan Gong
Decoy effect and compromise effect are context-dependent choice biases in which adding an option shift preference without changing the original alternatives. The decoy effect increases a preference for a target by introducing an inferior comparison, whereas the compromise effect reflects a tendency to choose intermediate options. Given the established roles of dopaminergic and serotonergic pathways in reward motivation and behavioral inhibition, this study investigated whether polygenic risk scores (PRSs) within these neurotransmitter pathways could predict these two effects. Two independent samples of Chinese university students were recruited from Luoyang (Sample 1: N = 647) and Xi’an (Sample 2: N = 569), providing demographically homogeneous populations for assessing genetic contributions to decision biases. In the serotonergic system, the PRS significantly predicted compromise effect in both samples (Sample 1: β = 0.093, p = 0.017; Sample 2: β = 0.094, p = 0.026) and decoy effect in Sample 2 (β = 0.122, p = 0.003). In the dopaminergic system, the PRS only significantly predicted compromise effect in Sample 2 (β = 0.132, p = 0.002), while it significantly predicted decoy effect in both samples (Sample 1: β = 0.132, p = 0.001; Sample 2: β = 0.126, p = 0.003). Combined-sample analyses confirmed a unique contribution of dopaminergic PRS to the compromise effect and showed that the decoy effect was jointly influenced by dopaminergic and serotonergic pathways. These results show that the decoy and compromise effects arise from distinct genetic mechanisms: dopamine amplifies relative reward signals driving the decoy choices, whereas serotonin promotes safer, intermediate preferences underlying the compromise decisions.
诱饵效应和妥协效应是一种情境依赖的选择偏差,即在不改变原有选择的情况下,增加一个选项会改变人们的偏好。诱饵效应通过引入劣势比较来增加对目标的偏好,而妥协效应则反映了选择中间选项的倾向。鉴于多巴胺能和血清素能通路在奖励动机和行为抑制中的作用,本研究探讨了这些神经递质通路中的多基因风险评分(PRSs)是否可以预测这两种作用。从洛阳(样本1:N = 647)和西安(样本2:N = 569)招募了两个独立的中国大学生样本,为评估遗传对决策偏差的影响提供了人口统计学上同质的群体。在血清素能系统中,PRS显著预测了两个样本的妥协效应(样本1:β = 0.093, p = 0.017;样本2:β = 0.094, p = 0.026)和诱饵效应(样本2:β = 0.122, p = 0.003)。在多巴胺能系统中,PRS仅在样本2中显著预测妥协效应(β = 0.132, p = 0.002),而在两个样本中显著预测诱饵效应(样本1:β = 0.132, p = 0.001;样本2:β = 0.126, p = 0.003)。联合样本分析证实了多巴胺能PRS对妥协效应的独特贡献,并表明诱饵效应受多巴胺能和血清素能途径的共同影响。这些结果表明,诱饵效应和妥协效应来自不同的遗传机制:多巴胺放大了驱动诱饵选择的相对奖励信号,而血清素促进了妥协决定背后更安全的中间偏好。
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引用次数: 0
Beak wiping stereotypies are correlated with neophobia and lack of enrichment in captive house sparrows (Passer domesticus). 在圈养的家麻雀(Passer domesticus)中,擦喙刻板印象与新事物恐惧症和缺乏富集相关。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-01-31 DOI: 10.1016/j.bbr.2026.116075
Danna F Masri, William J Frazier, Melanie G Kimball, Christine R Lattin

Behavioural syndromes are suites of correlated behaviours at the population or species level that can affect how wild animals respond to their environments, including potentially stressful situations such as captivity. In this study, we assessed whether beak wiping, a stereotyped anxiety-linked behaviour where birds wipe their beaks on a perch in a "windshield wiper" motion, was correlated with another anxiety-linked behaviour, neophobia towards novel objects presented with food, in captive house sparrows (Passer domesticus). We predicted that more neophobic sparrows would also exhibit more beak-wiping stereotypies. We analyzed 1 h long control videos (when sparrows were presented with a normal food dish only; n = 54) from three previous neophobia studies to assess beak wiping frequency, mean beak wiping bout duration, and total bout duration. Sparrows' reluctance to feed in the presence of novel objects was significantly correlated with the mean duration of beak wiping bouts during control trials. We also found that simple enrichment (rubber perches, manzanita branch perches, and/or artificial pine branches) decreased both the frequency and duration of beak wiping. These findings suggest that high neophobia and high levels of stereotypy may arise due to similar neuroendocrine mechanisms and reflect a "high anxiety" behavioural syndrome. This work also highlights the importance of providing species-appropriate environmental enrichment to decrease the prevalence of stereotypic behaviours in captive songbirds.

行为综合症是种群或物种水平上的一系列相关行为,可影响野生动物对环境的反应,包括圈养等潜在压力情况。在这项研究中,我们评估了擦嘴是否与另一种焦虑相关的行为有关,即鸟类在“雨刷”运动中在栖木上擦嘴,这是一种与焦虑相关的行为,即对带有食物的新物体的新恐惧症,这是笼养的麻雀(Passer domesticus)的行为。我们预测,更多的恐新麻雀也会表现出更多擦喙的刻板印象。我们分析了之前三个新恐惧症研究的1小时长的对照视频(当麻雀只提供正常食物盘时,n=54),以评估擦喙频率,平均擦喙时间和总时间。在对照试验中,麻雀在新物体面前不愿进食与擦喙次数的平均持续时间显著相关。我们还发现,简单的富集(橡胶枝、manzanita枝和/或人工松枝)减少了擦拭喙的频率和持续时间。这些发现表明,高度的新恐惧症和高度的刻板印象可能是由于相似的神经内分泌机制而产生的,反映了一种“高度焦虑”的行为综合征。这项工作还强调了提供适合物种的环境丰富以减少圈养鸣禽刻板行为盛行的重要性。
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引用次数: 0
Male paternal exposure to predatory risk during adolescence alters offspring antipredator behavior and basal HPA axis activity in Brandt's voles. 雄性父亲在青春期暴露于捕食风险会改变后代的反捕食行为和基础下丘脑轴活动。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-01-31 DOI: 10.1016/j.bbr.2026.116073
Ping Wang, Taoxiu Zhou, Yinyue Gu, Xinyi Lan, Wanhong Wei, Ruiyong Wu

Adolescent stress not only exerts enduring effects on individual behavior and physiology, but also shapes offspring phenotypes through mechanisms of transgenerational inheritance. However, the transgenerational effects of predation risk, an important ecological factor, remain poorly characterized in wild, social rodents. Using male Brandt's voles (Lasiopodomys brandtii) as a model, this study systematically investigated the transgenerational effect of adolescent exposure to cat urine, rabbit urine (as a non-predator stimulus), and distilled water (as a control) for 60min daily over 18 consecutive days on the behavioral and physiological traits of future offspring. Our data showed that while male paternal adolescent cat odor (CO) exposure did not significantly alter overall parental investment by either parent, it induced significant phenotypic changes in offspring. These included an increased female ratio at weaning and reduced post-weaning weight gain. Furthermore, adolescent offspring exhibited decreased locomotor activity in the open field test, while adult offspring displayed heightened vigilant rearing and reduced head-out behavior when confronted with CO exposure. These behavioral and developmental alterations were accompanied by elevated serum levels of adrenocorticotropic hormone and corticosterone, suggesting enhanced basal activity of the hypothalamic-pituitary-adrenal axis. These findings demonstrate that male paternal experience with predation risk during adolescence can transgenerationally regulate the sex ratio, growth and development, stress response, and antipredator strategies of future offspring, independent of alterations in parental investment in wild, social rodents. This study elucidates the unique role of the paternal lineage in the transgenerational inheritance of early adversity and provides further experimental evidence for understanding how environmental stress drives adaptive phenotypic transmission across generations.

青少年压力不仅对个体的行为和生理产生持久的影响,而且通过跨代遗传机制塑造后代的表型。然而,作为一个重要的生态因素,捕食风险的跨代效应在野生社会性啮齿类动物中仍未得到充分的研究。本研究以雄性勃兰特田鼠(Lasiopodomys brandtii)为模型,系统研究了青春期连续18天每天暴露60min猫尿、兔尿(作为非捕食者刺激)和蒸馏水(作为对照)对后代行为和生理性状的跨代影响。我们的数据显示,尽管雄性父亲在青春期接触猫气味(CO)不会显著改变亲本的总体投资,但它会引起后代显着的表型变化。其中包括断奶时雌性比例增加和断奶后体重增加减少。此外,青少年后代在野外测试中表现出运动活动下降,而成年后代在面对一氧化碳暴露时表现出高度警惕的饲养和减少的头出行为。这些行为和发育改变伴随着促肾上腺皮质激素和皮质酮的血清水平升高,表明下丘脑-垂体-肾上腺轴的基础活动增强。这些发现表明,在野生社会性啮齿类动物中,雄性在青春期面临捕食风险的经历可以跨代调节后代的性别比例、生长发育、应激反应和反捕食策略,而不依赖于亲代投资的改变。本研究阐明了父系在早期逆境跨代遗传中的独特作用,并为理解环境应激如何驱动适应性表型跨代传递提供了进一步的实验证据。
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引用次数: 0
Resilient Hubs, Shifting Links: The Brain's Network Architecture During Deceptive Behavior. 弹性枢纽,移动链接:欺骗行为中的大脑网络结构。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-01-31 DOI: 10.1016/j.bbr.2026.116076
Ali Rahimi Saryazdi, Farnaz Ghassemi, Golnaz Baghdadi

Deception is one of the most enigmatic human behaviors, and understanding its neural mechanisms remains a central challenge in neuroscience. Investigating brain dynamics during deception provides insights into cognitive control and social processing. In this study, we analyzed the architecture of brain region connections, focusing on rich, feeder, and local links, using EEG signals from 22 participants performing a visual task under instructed deception. Functional connectivity matrices were computed with phase lag index, and binary networks were constructed across multiple thresholds. Results showed that brain networks are organized around stable hub regions, which remain largely unchanged during deception. However, deceptive behavior disrupted peripheral connections, with feeder and local links showing reductions relative to truthful responding, suggesting reallocation of cognitive resources. Although hub regions were consistent, hubs in the truthful condition exhibited higher connectivity than during deception in both binary and weighted networks across all percentages of rich nodes (p < 10-6), indicating more efficient hub-to-hub integration during truthful processing. Analysis of link deviations across thresholds and rich-node percentages revealed a dynamic pattern. At low percentages, rich links were stable while local links varied most. As percentages increased, rich links showed the largest deviations, local links the smallest, and feeder links maintained intermediate variability. These results indicate that deception initially disrupts local processing, while communication among core hubs is affected as network engagement grows. These findings highlight the importance of investigating the architecture of brain region connections during complex social behaviors, showing how stable hubs and flexible peripheral links support cognitive processing.

欺骗是最神秘的人类行为之一,理解其神经机制仍然是神经科学的核心挑战。研究欺骗过程中的大脑动态,可以深入了解认知控制和社会处理。在这项研究中,我们利用22名参与者在指示欺骗下执行视觉任务的脑电图信号,分析了大脑区域连接的结构,重点关注丰富、馈线和局部连接。利用相位滞后指数计算功能连通性矩阵,构建跨多个阈值的二值网络。结果表明,大脑网络是围绕稳定的中枢区域组织起来的,这些区域在欺骗过程中基本保持不变。然而,欺骗行为破坏了外围连接,支线和局部连接显示出相对于真实反应的减少,这表明认知资源的重新分配。尽管枢纽区域是一致的,但在二元和加权网络中,在所有富节点的百分比中,诚实条件下的枢纽比欺骗条件下的枢纽表现出更高的连通性(p < 10-6),表明在诚实处理过程中更有效的枢纽到枢纽集成。跨阈值和富节点百分比的链接偏差分析揭示了一种动态模式。在较低的百分比,丰富的链接是稳定的,而本地链接变化最大。随着百分比的增加,丰富链接显示出最大的偏差,局部链接最小,饲料链接保持中等变异性。这些结果表明,欺骗最初会扰乱本地处理,而核心枢纽之间的通信随着网络参与度的增加而受到影响。这些发现强调了研究复杂社会行为中大脑区域连接结构的重要性,显示了稳定的中枢和灵活的外围连接如何支持认知处理。
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引用次数: 0
The emerging neuromodulatory role of Homovanillic acid in the medial prefrontal cortex: Implications for anxiety. 高香草酸在内侧前额叶皮层中的神经调节作用:对焦虑的影响。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-01-31 DOI: 10.1016/j.bbr.2026.116074
Xiaohong Wang, Lu Sun, Zhongyu Zhang, Haowei Shen, Lei Chen, Jianmei Huang, Haifeng Zhai

Homovanillic acid (HVA), the principal terminal metabolite of dopamine, has long been considered an inactive byproduct of dopaminergic signaling. However, its potential neuromodulatory role in emotional regulation remains largely unexplored. This study investigated the neuromodulatory capacity of HVA within the medial prefrontal cortex (mPFC) and its implications for anxiety-like behavior. We employed an integrated approach in rodents, combining neurochemical profiling, stereotaxic microinfusion, and whole-cell patch-clamp electrophysiology. Rats were phenotyped for anxiety-like behavior using the elevated plus-maze (EPM), revealing a distinct neurochemical signature in the mPFC of high-anxiety individuals: significantly elevated HVA alongside reduced 3-methoxytyramine (3-MT), without alterations in dopamine, norepinephrine, serotonin, or their major metabolites. Crucially, bilateral microinjection of HVA (0.5 or 1.5 μg/side) into the mPFC of naïve rats induced dose-dependent anxiogenic effects, evidenced by reduced open-arm exploration and entries in the EPM. Electrophysiological recordings from deep-layer pyramidal neurons in mouse mPFC slices demonstrated that HVA (80 μM) suppresses calcium channel-mediated plateau potentials. Our findings reveal HVA as an active neuromodulator in the mPFC that shapes anxiety-like behaviors through inhibition of calcium channels, challenging its traditional status as a metabolic waste product.

高香草酸(HVA)是多巴胺的主要末端代谢物,长期以来被认为是多巴胺能信号的非活性副产物。然而,它在情绪调节中的潜在神经调节作用在很大程度上仍未被探索。本研究探讨了HVA在内侧前额叶皮层(mPFC)内的神经调节能力及其对焦虑样行为的影响。我们在啮齿类动物中采用了一种综合方法,结合了神经化学分析、立体定向微输液和全细胞膜片钳电生理学。使用升高的正迷宫(EPM)对大鼠进行焦虑样行为表型分析,揭示了高焦虑个体mPFC中明显的神经化学特征:HVA显著升高,3-甲氧基酪胺(3-MT)减少,多巴胺、去甲肾上腺素、血清素或其主要代谢物没有变化。至关重要的是,在naïve大鼠的mPFC中双侧微量注射HVA(0.5或1.5μg/侧)诱导了剂量依赖性的焦虑效应,这可以通过减少张开臂的探索和EPM的进入来证明。小鼠mPFC切片深层锥体神经元的电生理记录表明,HVA (80μM)抑制钙通道介导的平台电位。我们的研究结果表明,HVA在mPFC中是一种活跃的神经调节剂,通过抑制钙通道来塑造焦虑样行为,挑战了HVA作为代谢废物的传统地位。
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引用次数: 0
Second-Order Conditioning of Safety in Male and Female Rats. 雌雄大鼠的二级安全条件反射。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-01-31 DOI: 10.1016/j.bbr.2026.116059
Daniel B K Gabriel, Kaitlin R Crilow, Susan Sangha

Stimuli can acquire meaning and significance indirectly by being paired with other stimuli that already have known outcomes. When a stimulus has a well-established association with either aversive or rewarding consequences, other neutral stimuli can take on similar properties simply by occurring alongside it - even if the original outcome is not presented. This process is known as second-order conditioning. Relatively few studies have examined second-order conditioning of inhibitory safety memories. Here, we examined second-order conditioning of safety in adult male and female Long-Evans rats by adapting our well-established first-order safety conditioning paradigm to include novel stimuli paired with the established safety cue. Our findings demonstrate that a second-order safety cue can attenuate fear responses to a degree comparable to that of a first-order safety cue. In contrast, a novel cue that had never been paired with a safety signal failed to produce an equivalent reduction in defensive behavior during fear cue presentation, demonstrating that the reduced fear to the second-order safety cue was a product of conditioning and not external inhibition. Developing methods to generalize safety to novel stimuli that have not been explicitly conditioned for safety holds significant promise for advancing innovative strategies aimed at mitigating maladaptive fear responses.

刺激可以通过与其他已知结果的刺激配对间接获得意义和重要性。当一个刺激与厌恶或有益的结果建立了良好的联系时,其他中性刺激可以简单地通过与它一起出现而具有类似的属性——即使原始结果没有出现。这个过程被称为二阶条件作用。相对较少的研究考察了抑制安全记忆的二级条件反射。在此,我们对成年雄性和雌性Long-Evans大鼠的二级安全条件反射进行了研究,通过调整我们已建立的一级安全条件反射范式,将新刺激与已建立的安全线索配对。我们的研究结果表明,二阶安全提示可以在一定程度上减弱恐惧反应,与一阶安全提示相当。相比之下,一个从未与安全信号配对的新线索在恐惧线索呈现期间未能产生相应的防御行为减少,这表明对二级安全线索的恐惧减少是条件反射的产物,而不是外部抑制的产物。开发方法将安全性推广到没有明确的安全条件的新刺激,对于推进旨在减轻适应不良恐惧反应的创新策略具有重要的前景。
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引用次数: 0
Transcriptomic integration nominates FOXN2 as a candidate schizophrenia risk gene. 转录组整合将FOXN2作为候选精神分裂症风险基因。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-01-28 DOI: 10.1016/j.bbr.2026.116068
Ling Yu, Jian Chen, Shanshan Du, Qing Long, Zeyi Guo, Yilin Liu, Fuyi Qin, Mengxue Wang, Raoxiang Luo, Yunqiao Zhang, Yong Zeng, Zhaowei Teng
<p><strong>Background: </strong>Schizophrenia (SCZ) is increasingly recognized as a complex, systemic disorder involving interactions between the central nervous system and peripheral biological processes. Growing evidence implicates dysregulation of the gut-brain axis in SCZ pathophysiology; however, the genetic mechanisms linking schizophrenia susceptibility to gut-related biological pathways remain poorly understood, particularly with respect to causal gene prioritization across tissues.</p><p><strong>Methods: </strong>To address this gap, we conducted a cross-tissue transcriptome-wide association study (TWAS) using FUSION across five tissues relevant to brain-gut interactions, including the hippocampus, frontal cortex (BA9), transverse colon, sigmoid colon, and whole blood. Candidate genes were further prioritized using MAGMA gene-based analysis based on schizophrenia genome-wide association study (GWAS) summary statistics from the Psychiatric Genomics Consortium and the IEU Open GWAS project. Integrative analyses combining summary-data-based Mendelian randomization (SMR) and Bayesian colocalization (PP.H4 > 0.75) were applied to refine candidate gene selection. Expression of the top candidate gene was examined by RT-qPCR in peripheral blood samples from 19 patients with SCZ and 21 healthy controls. Finally, two-sample Mendelian randomization (MR) analyses were performed to explore potential associations between the prioritized gene and 205 gut microbial metabolic pathways.</p><p><strong>Results: </strong>Cross-tissue integration of TWAS, MAGMA, and SMR identified five convergent schizophrenia susceptibility genes: TVP23B, NSUN2, RPL12, FOXN2, and THAP5. Bayesian colocalization analysis highlighted FOXN2 as the most robust candidate (PP.H4 =0.995). RT-qPCR analysis demonstrated significantly lower FOXN2 expression in peripheral blood from patients with schizophrenia compared with healthy controls (mean ± SD: 0.72±0.64 vs.1.13±0.42; t = 2.34, P = 0.02). In two-sample MR analyses, genetically proxied FOXN2 expression was modestly but significantly associated with 10 gut microbial metabolic pathways after false discovery rate correction, suggesting potential links between schizophrenia risk genes and gut microbial metabolic processes.</p><p><strong>Limitations: </strong>This study relies on cis-eQTL-based transcriptomic integration and assumes a single causal variant in colocalization analyses. The number of available MR instruments was limited, and the clinical validation sample size was modest, with residual confounding not fully excluded. In addition, the GWAS and eQTL datasets were predominantly derived from populations of European ancestry, which may limit generalizability. The observed associations between FOXN2 and gut microbial metabolic pathways should therefore be considered exploratory and require further functional validation.</p><p><strong>Conclusion: </strong>Our findings suggest that FOXN2 may contribute to the genetic architectur
背景:精神分裂症(SCZ)越来越被认为是一种复杂的全身性疾病,涉及中枢神经系统和外周生物过程之间的相互作用。越来越多的证据表明肠-脑轴在SCZ病理生理中的失调;然而,将精神分裂症易感性与肠道相关生物学途径联系起来的遗传机制仍然知之甚少,特别是在组织间的因果基因优先级方面。方法:为了解决这一空白,我们使用FUSION在与脑-肠相互作用相关的五个组织中进行了跨组织转录组关联研究(TWAS),包括海马、额叶皮质(BA9)、横结肠、乙状结肠和全血。根据精神病学基因组学联盟和IEU开放GWAS项目的精神分裂症全基因组关联研究(GWAS)汇总统计数据,使用MAGMA基因分析进一步对候选基因进行优先排序。采用基于汇总数据的孟德尔随机化(SMR)和贝叶斯共定位(PP.H4 > 0.75)相结合的综合分析来优化候选基因选择。采用RT-qPCR检测了19例SCZ患者和21例健康对照者外周血中该基因的表达情况。最后,进行双样本孟德尔随机化(MR)分析,以探索优先基因与205种肠道微生物代谢途径之间的潜在关联。结果:TWAS、MAGMA和SMR的跨组织整合鉴定出5个趋同的精神分裂症易感基因:TVP23B、NSUN2、RPL12、FOXN2和THAP5。贝叶斯共定位分析显示FOXN2是最稳健的候选基因(PP.H4 =0.995)。RT-qPCR分析显示,与健康对照组相比,精神分裂症患者外周血FOXN2表达明显降低(平均±SD: 0.72±0.64 vs.1.13±0.42;t = 2.34, P = 0.02)。在两份样本的MR分析中,经过错误发现率校正后,基因代理的FOXN2表达与10种肠道微生物代谢途径存在适度但显著的关联,这表明精神分裂症风险基因与肠道微生物代谢过程之间存在潜在的联系。局限性:本研究依赖于基于顺式eqtl的转录组整合,并在共定位分析中假设一个单一的因果变异。可用MR仪器的数量有限,临床验证样本量适中,残留混淆未完全排除。此外,GWAS和eQTL数据集主要来自欧洲血统的人群,这可能限制了通用性。因此,观察到的FOXN2与肠道微生物代谢途径之间的关联应被视为探索性的,需要进一步的功能验证。结论:我们的研究结果表明FOXN2可能参与精神分裂症的遗传结构,并可能与肠-脑轴相关的代谢途径有关。这些结果为未来的实验研究提供了基础,以阐明这种关联的生物学机制。
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引用次数: 0
Amygdala-centered mechanisms of pain amplification and chronification in fibromyalgia and migraine: Narrative review 以杏仁核为中心的疼痛放大和慢性化机制在纤维肌痛和偏头痛:叙述性回顾
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-01-28 DOI: 10.1016/j.bbr.2026.116071
Nataliya Zharova , Yury Zharikov , Yane Pelicer-Marques , Vladimir Nikolenko , Vladislav Tarasenko , Elena Mikliaeva , Anastasia Mchenskaya , Sergey Ryagin , Sevak Antonyan , Denis Aniskin , André Pontes-Silva , Tatiana Zharikova

Objective

This review aimed to examine the role of the amygdala as a central hub in the pathophysiology of chronic pain, with a specific focus on fibromyalgia and migraine. We synthesize evidence on how structural, functional, and neurochemical alterations within amygdala-centered circuits contribute to pain amplification, emotional dysregulation, and central sensitization, and discuss their implications for circuit-based therapeutic strategies.

Methods

A comprehensive, theory-driven literature synthesis was conducted, integrating findings from neuroimaging, neuromodulation, molecular neuroscience, and clinical studies. We examined alterations in amygdala structure, function, and connectivity with cortical and brainstem regions involved in nociceptive processing, emotional regulation, and descending pain modulation. Pharmacological and non-pharmacological interventions targeting limbic–brainstem circuits were also analyzed.

Results

Converging evidence indicates that both fibromyalgia and migraine are associated with significant volumetric, functional, and connectivity-related alterations of the amygdala. These changes are characterized by limbic hyperexcitability and aberrant coupling with the prefrontal cortex, hypothalamus, periaqueductal gray (PAG), and rostral ventromedial medulla (RVM), biasing descending pain control toward facilitation rather than inhibition. This network reorganization amplifies both the sensory and affective dimensions of pain and promotes symptom persistence. Neurochemical dysregulation—encompassing glutamatergic, monoaminergic, GABAergic, and peptidergic systems—further sustains maladaptive plasticity within amygdala-centered circuits. Emerging therapeutic approaches, including cognitive-behavioral interventions, neuromodulation, pharmacological modulation, and immersive technologies, show potential to reshape dysfunctional limbic–cortical networks and attenuate pain amplification.

Conclusion

The amygdala emerges as a key integrative node linking nociceptive, emotional, and autonomic processes in fibromyalgia and migraine. Through its influence on descending pain modulatory systems, amygdala-centered circuits play a critical role in pain chronification and affective sensitization. These findings support a circuit-based framework for chronic pain, highlighting the amygdala as a promising target for individualized, multimodal therapeutic strategies aimed at restoring adaptive emotional–nociceptive integration.
目的:本综述旨在研究杏仁核在慢性疼痛病理生理学中的作用,特别是纤维肌痛和偏头痛。我们综合了杏仁核中心回路的结构、功能和神经化学改变如何导致疼痛放大、情绪失调和中枢敏感化的证据,并讨论了它们对基于回路的治疗策略的影响。方法综合神经影像学、神经调节、分子神经科学和临床研究成果,进行全面的、以理论为导向的文献综合。我们研究了杏仁核结构、功能的改变,以及与伤害性加工、情绪调节和下行疼痛调节有关的皮质和脑干区域的连通性。还分析了针对边缘-脑干回路的药物和非药物干预措施。结果越来越多的证据表明,纤维肌痛和偏头痛都与杏仁核的体积、功能和连接相关的显著改变有关。这些变化的特征是边缘高度兴奋性和与前额叶皮层、下丘脑、导水管周围灰质(PAG)和吻侧腹内侧髓质(RVM)的异常耦合,使下行疼痛控制倾向于促进而不是抑制。这种网络重组放大了疼痛的感觉和情感维度,并促进了症状的持续。神经化学失调——包括谷氨酸能、单胺能、gaba能和肽能系统——进一步维持了杏仁核中心回路的适应性不良。新兴的治疗方法,包括认知行为干预、神经调节、药理学调节和沉浸式技术,显示出重塑功能失调的边缘皮层网络和减轻疼痛放大的潜力。结论杏仁核在纤维肌痛和偏头痛中是连接伤害、情绪和自主神经过程的关键综合节点。通过对下行疼痛调节系统的影响,杏仁核中心回路在疼痛慢性化和情感敏感化中起着关键作用。这些发现支持了基于神经回路的慢性疼痛框架,强调杏仁核是一个有希望的目标,旨在恢复适应性情绪-伤害整合的个性化,多模式治疗策略。
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引用次数: 0
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Behavioural Brain Research
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