Reduced Amygdala and Ventral Striatal Activity to Happy Faces in PTSD Is Associated with Emotional Numbing

There has been a growing recognition of the importance of reward processing in PTSD, yet little is known of the underlying neural networks. This study tested the predictions that (1) individuals with PTSD would display reduced responses to happy facial expressions in ventral striatal reward networks, and (2) that this reduction would be associated with emotional numbing symptoms. 23 treatment-seeking patients with Posttraumatic Stress Disorder were recruited from the treatment clinic at the Centre for Traumatic Stress Studies, Westmead Hospital, and 20 trauma-exposed controls were recruited from a community sample. We examined functional magnetic resonance imaging responses during the presentation of happy and neutral facial expressions in a passive viewing task. PTSD participants rated happy facial expression as less intense than trauma-exposed controls. Relative to controls, PTSD participants revealed lower activation to happy (-neutral) faces in ventral striatum and and a trend for reduced activation in left amygdala. A significant negative correlation was found between emotional numbing symptoms in PTSD and right ventral striatal regions after controlling for depression, anxiety and PTSD severity. This study provides initial evidence that individuals with PTSD have lower reactivity to happy facial expressions, and that lower activation in ventral striatal-limbic reward networks may be associated with symptoms of emotional numbing.     

Lipopolysaccharide-Induced Striatal Nitrosative Stress and Impaired Social Recognition Memory Are Not Magnified by Paraquat Coexposure

Systemic inflammation triggered by lipopolysaccharide (LPS) administration disrupts blood–brain barrier (BBB) homeostasis in animal models. This event leads to increased susceptibility of several encephalic structures to potential neurotoxicants present in the bloodstream. In this study, we investigated the effects of alternate intraperitoneal injections of LPS on BBB permeability, social recognition memory and biochemical parameters in the striatum 24 h and 60 days after treatments. In addition, we investigated whether the exposure to a moderate neurotoxic dose of the herbicide paraquat could potentiate LPS-induced neurotoxicity. LPS administration caused a transient disruption of BBB integrity, evidenced by increased levels of exogenously administered sodium fluorescein in the striatum. Also, LPS exposure caused delayed impairment in social recognition memory (evaluated at day 38 after treatments) and increase in the striatal levels of 3-nitrotyrosine. These events were observed in the absence of significant changes in motor coordination and in the levels of tyrosine hydroxylase (TH) in the striatum and substantia nigra. PQ exposure, which caused a long-lasting decrease of striatal mitochondrial complex I activity, did not modify LPS-induced behavioral and striatal biochemical changes. The results indicate that systemic administration of LPS causes delayed social recognition memory deficit and striatal nitrosative stress in adult mice and that the coexposure to a moderately toxic dose of PQ did not magnify these events. In addition, PQ-induced inhibition of striatal mitochondrial complex I was also not magnified by LPS exposure, indicating the absence of synergic neurotoxic effects of LPS and PQ in this experimental model.

     

Examining Event-Related Potential (ERP) Correlates of Decision Bias in Recognition Memory Judgments

Memory judgments can be based on accurate memory information or on decision bias (the tendency to report that an event is part of episodic memory when one is in fact unsure). Event related potentials (ERP) correlates are important research tools for elucidating the dynamics underlying memory judgments but so far have been established only for investigations of accurate old/new discrimination. To identify the ERP correlates of bias, and observe how these interact with ERP correlates of memory, we conducted three experiments that manipulated decision bias within participants via instructions during recognition memory tests while their ERPs were recorded. In Experiment 1, the bias manipulation was performed between blocks of trials (automatized bias) and compared to trial-by-trial shifts of bias in accord with an external cue (flexibly controlled bias). In Experiment 2, the bias manipulation was performed at two different levels of accurate old/new discrimination as the memory strength of old (studied) items was varied. In Experiment 3, the bias manipulation was added to another, bottom-up driven manipulation of bias induced via familiarity. In the first two Experiments, and in the low familiarity condition of Experiment 3, we found evidence of an early frontocentral ERP component at 320 ms poststimulus (the FN320) that was sensitive to the manipulation of bias via instruction, with more negative amplitudes indexing more liberal bias. By contrast, later during the trial (500–700 ms poststimulus), bias effects interacted with old/new effects across all three experiments. Results suggest that the decision criterion is typically activated early during recognition memory trials, and is integrated with retrieved memory signals and task-specific processing demands later during the trial. More generally, the findings demonstrate how ERPs can help to specify the dynamics of recognition memory processes under top-down and bottom-up controlled retrieval conditions.     

Neural Correlates of the In-Group Memory Advantage on the Encoding and Recognition of Faces

People have a memory advantage for faces that belong to the same group, for example, that attend the same university or have the same personality type. Faces from such in-group members are assumed to receive more attention during memory encoding and are therefore recognized more accurately. Here we use event-related potentials related to memory encoding and retrieval to investigate the neural correlates of the in-group memory advantage. Using the minimal group procedure, subjects were classified based on a bogus personality test as belonging to one of two personality types. While the electroencephalogram was recorded, subjects studied and recognized faces supposedly belonging to the subject’s own and the other personality type. Subjects recognized in-group faces more accurately than out-group faces but the effect size was small. Using the individual behavioral in-group memory advantage in multivariate analyses of covariance, we determined neural correlates of the in-group advantage. During memory encoding (300 to 1000 ms after stimulus onset), subjects with a high in-group memory advantage elicited more positive amplitudes for subsequently remembered in-group than out-group faces, showing that in-group faces received more attention and elicited more neural activity during initial encoding. Early during memory retrieval (300 to 500 ms), frontal brain areas were more activated for remembered in-group faces indicating an early detection of group membership. Surprisingly, the parietal old/new effect (600 to 900 ms) thought to indicate recollection processes differed between in-group and out-group faces independent from the behavioral in-group memory advantage. This finding suggests that group membership affects memory retrieval independent of memory performance. Comparisons with a previous study on the other-race effect, another memory phenomenon influenced by social classification of faces, suggested that the in-group memory advantage is dominated by top-down processing whereas the other-race effect is also influenced by extensive perceptual experience.     

Activation of Midbrain and Ventral Striatal Regions Implicates Salience Processing during a Modified Beads Task

Introduction

Metacognition, i.e. critically reflecting on and monitoring one’s own reasoning, has been linked behaviorally to the emergence of delusions and is a focus of cognitive therapy in patients with schizophrenia. However, little is known about the neural processing underlying metacognitive function. To address this issue, we studied brain activity during a modified beads task which has been used to measure a “Jumping to Conclusions” (JTC) bias in schizophrenia patients.

Methods

We used functional magnetic resonance imaging to identify neural systems active in twenty-five healthy subjects when solving a modified version of the “beads task”, which requires a probabilistic decision after a variable amount of data has been requested by the participants. We assessed brain activation over the duration of a trial and at the time point of decision making.

Results

Analysis of activation during the whole process of probabilistic reasoning showed an extended network including the prefronto-parietal executive functioning network as well as medial parieto-occipital regions. During the decision process alone, activity in midbrain and ventral striatum was detected, as well as in thalamus, medial occipital cortex and anterior insula.

Conclusions

Our data show that probabilistic reasoning shares neural substrates with executive functions. In addition, our finding that brain regions commonly associated with salience processing are active during probabilistic reasoning identifies a candidate mechanism that could underlie the behavioral link between dopamine-dependent aberrant salience and JTC in schizophrenia. Further studies with delusional schizophrenia patients will have to be performed to substantiate this link.     

哺乳期棕色田鼠对配偶的识别记忆

观察了分娩后哺乳雌性棕色田鼠（Microtus mandarinus）与配偶分离7d、14d、21d后对配偶与陌生雄鼠的行为反应。结果发现,在频次和持续时间上,与配偶分离7d、14d、21d的雌鼠对配偶的攻击行为显著低于陌生雄鼠（P〈0．05）;对配偶的嗅闻及友善行为显著高于陌生雄鼠（P〈0．05）。处于哺乳前、中、后期不同阶段的雌鼠对陌生雄鼠攻击水平没有显著性差异（P〉0．05）。这些结果说明,在整个哺乳期,雌鼠能够识别配偶,对配偶的记忆不因分离时间的增加而减弱,而且对陌生鼠的攻击水平不会因哺乳阶段的变化而变化,维持高水平的攻击可能与其较强的母性行为有关。     

A Key Role for Nectin-1 in the Ventral Hippocampus in Contextual Fear Memory

Nectins are cell adhesion molecules that are widely expressed in the brain. Nectin expression shows a dynamic spatiotemporal regulation, playing a role in neural migratory processes during development. Nectin-1 and nectin-3 and their heterophilic trans-interactions are important for the proper formation of synapses. In the hippocampus, nectin-1 and nectin-3 localize at puncta adherentia junctions and may play a role in synaptic plasticity, a mechanism essential for memory and learning. We evaluated the potential involvement of nectin-1 and nectin-3 in memory consolidation using an emotional learning paradigm. Rats trained for contextual fear conditioning showed transient nectin-1—but not nectin-3—protein upregulation in synapse-enriched hippocampal fractions at about 2 h posttraining. The upregulation of nectin-1 was found exclusively in the ventral hippocampus and was apparent in the synaptoneurosomal fraction. This upregulation was induced by contextual fear conditioning but not by exposure to context or shock alone. When an antibody against nectin-1, R165, was infused in the ventral-hippocampus immediately after training, contextual fear memory was impaired. However, treatment with the antibody in the dorsal hippocampus had no effect in contextual fear memory formation. Similarly, treatment with the antibody in the ventral hippocampus did not interfere with acoustic memory formation. Further control experiments indicated that the effects of ventral hippocampal infusion of the nectin-1 antibody in contextual fear memory cannot be ascribed to memory non-specific effects such as changes in anxiety-like behavior or locomotor behavior. Therefore, we conclude that nectin-1 recruitment to the perisynaptic environment in the ventral hippocampus plays an important role in the formation of contextual fear memories. Our results suggest that these mechanisms could be involved in the connection of emotional and contextual information processed in the amygdala and dorsal hippocampus, respectively, thus opening new venues for the development of treatments to psychopathological alterations linked to impaired contextualization of emotions.     

Lipovitellin is a Non-Self Recognition Receptor with Opsonic Activity

Lipovitellin (Lv), a glycolipoprotein, is a major component of the egg yolk, which is usually regarded as an energy reserve of nutrients essential for growth and development. We have purified Lv from ovulated eggs of the rosy barb Puntius conchonius by two-step chromatography and characterized it by staining with periodic acid/Schiff reagent and Sudan black B, amino acid composition analysis, and peptide mass fingerprinting. The results of ligand and bacterial binding assays, an enzyme-linked immunosorbent assay (ELISA), and the phagocytosis test revealed, for the first time, that the purified native form of P. conchonius Lv acts as a pattern recognition molecule with multiple specificities capable of identifying pathogen-associated molecular patterns (PAMPs), including those of lipopolysaccharide, lipoteichoic acid, and peptidoglycan, rather than self components and that it can bind Gram-negative and -positive bacteria, such as Escherichia coli and Staphylococcus aureus. These tests also showed that the P. conchonius Lv functions as an opsonin capable of enhancing macrophage phagocytosis. Taken together, these characteristics suggest that in developing embryos/larvae of P. conchonius, the native form of Lv may be physiologically involved in the sensing of invading pathogens via interaction with PAMPs and in the recruitment of the primitive macrophages that appear in early embryos to phagocytose and digest the pathogens, thereby protecting them from pathogenic attacks.     

RNase Activity Decreases following a Heat Shock in Wheat Leaves and Correlates with Its Posttranslational Modification

Heat shock results in a coordinate loss of translational efficiency and an increase in mRNA stability in plants. The thermally mediated increase in mRNA half-life could be a result of decreased expression and/or regulation of intracellular RNase enzyme activity. We have examined the fate of both acidic and neutral RNases in wheat seedlings that were subjected to a thermal stress. We observed that the activity of all detectable RNases decreased following a heat shock, which was a function of both the temperature and length of the heat shock. In contrast, no reduction in nuclease activity was observed following any heat-shock treatment. Antibodies raised against one of the major RNases was used in western analysis to demonstrate that the RNase protein level did not decrease following a heat shock, and the data suggest that the observed decrease in RNase activity in heat-shocked leaves may be due to modification of the protein. Two-dimensional gel/western analysis of this RNase revealed three isoforms. The most acidic isoform predominated in control leaves, whereas the most basic isoform predominated in leaves following a heat shock and correlated with the heat-shock-induced reduction in RNase activity and increase in mRNA half-life. These data suggest that RNase activity may be regulated posttranslationally following heat shock as a means to reduce RNA turnover until recovery ensues.     

Evidence for Functional Activity of Up-Regulated Nicotine Binding Sites in Rat Striatal Synaptosomes

A number of studies have found that the chronic administration of nicotine causes an increase in the density of nicotinic binding sites in the brain, but it is not known whether these additional binding sites are functionally active receptors. In this study, the effects of 1-week administration of the potent nicotinic agonist, (+)-anatoxin-a (96 nmol/day via osmotic minipumps), was assessed on [3H]nicotine binding and [3H]dopamine uptake and release in rat striatal synaptosomes. Chronic (+)-anatoxin-a treatment resulted in a 32% increase in the Bmax of [3H]nicotine binding in anatoxin-treated animals compared to control. There was a 43% increase in the activity of 3 microM nicotine to release [3H]dopamine from synaptosomes of anatoxin-treated animals, but the release induced by 20 mM K+ depolarization was unaffected. There was no effect of chronic (+)-anatoxin-a treatment on the uptake of [3H]dopamine. A strong positive correlation (r = 0.64) was found between the density of [3H]nicotine binding sites and the nicotine-induced stimulation of [3H]dopamine release in individual animals. These results indicate that (+)-anatoxin-a, like nicotine, produces an up-regulation of nicotine binding sites following chronic administration, and that these additional sites are functional receptors capable of mediating the release of dopamine from striatal synaptosomes.     

Rat Striatal Synaptosomes as a Model System for Studying the Inhibition of Dihydropteridine Reductase Activity

Abstract

The distribution of dihydropteridine reductase between soluble and particulate fractions in synaptosomes parallels that of lactate dehydrogenase, but not monoamine oxidase. K_i and I₅₀ values for inhibitors obtained with the enzyme-rich P₂ fraction and its twice-washed fraction (P₂ W₂) were essentially the same, and were similar to those obtained with highly purified human liver enzyme. Dihydropteridine reductase inhibitory potency of multi-ring compounds containing a catechol-moiety was greater than that of single ring catecholic compounds, which in turn was greater than that of phydroxyphenolic compounds. The P₂ fraction of rat striatal synaptosomal preparations may serve as a convenient source of dihydropteridine reductase for studying the inhibition of this enzyme.     

Interplay between Affect and Arousal in Recognition Memory

Background

Emotional states linked to arousal and mood are known to affect the efficiency of cognitive performance. However, the extent to which memory processes may be affected by arousal, mood or their interaction is poorly understood.

Methodology/Principal Findings

Following a study phase of abstract shapes, we altered the emotional state of participants by means of exposure to music that varied in both mood and arousal dimensions, leading to four different emotional states: (i) positive mood-high arousal; (ii) positive mood-low arousal; (iii) negative mood-high arousal; (iv) negative mood-low arousal. Following the emotional induction, participants performed a memory recognition test. Critically, there was an interaction between mood and arousal on recognition performance. Memory was enhanced in the positive mood-high arousal and in the negative mood-low arousal states, relative to the other emotional conditions.

Conclusions/Significance

Neither mood nor arousal alone but their interaction appears most critical to understanding the emotional enhancement of memory.     

K-252a Promotes Survival and Choline Acetyltransferase Activity in Striatal and Basal Forebrain Neuronal Cultures

Abstract: The organic molecule K-252a promoted cell survival, neurite outgrowth, and increased choline acetyltransferase (ChAT) activity in rat embryonic striatal and basal forebrain cultures in a concentration-dependent manner. A two- to threefold increase in survival was observed at 75 n M K-252a in both systems. A single application of K-252a at culture initiation prevented substantial (>60%) cell death that otherwise occurred after 4 days in striatal or basal forebrain cultures. A 5-h exposure of striatal or basal forebrain cells to K-252a, followed by its removal, resulted in survival equivalent to that observed in cultures continually maintained in its presence. This is in contrast to results found with a 5-h exposure of basal forebrain cultures to nerve growth factor (NGF). Acute exposure of basal forebrain cultures to K-252a, but not to NGF, increased ChAT activity, indicating that NGF was required the entire culture period for maximum activity. Striatal cholinergic and GABAergic neurons were among the neurons rescued by K-252a. Of the protein growth factors tested in striatal cultures (ciliary neurotrophic factor, neurotrophin-3, NGF, brain-derived neurotrophic factor, interleukin-2, basic fibroblast growth factor), only brain-derived neurotrophic factor promoted survival. The enhancement of survival and ChAT activity of basal forebrain and striatal neurons by K-252a defines additional populations of neurons in which survival and/or differentiation is regulated by a K-252a-responsive mechanism. The above results expand the potential therapeutic targets for these molecules for the treatment of neurodegenerative diseases.     

Effects of 2.1 GHz Electromagnetic Radiation on Locomotor Activity,Recognition Memory,and Anxiety-Related Behavior in Rats

Neurophysiology - The effects of short-term (2 h per day for 7 days) exposures to different doses of 2.1 GHz radiofrequency electromagnetic radiation (RF-EMR) on cognition and behavior of rats were...     

吗啡和胆碱能拮抗剂联合给药对小鼠Y迷宫空间记忆提取及活动性的影响(英文）

吗啡和胆碱能系统的相互作用已在多项研究中提到,本实验想查明吗啡是否能和胆碱能拮抗剂、东莨菪碱以及阿托品共同作用对小鼠的Y迷宫空间识别记忆提取产生影响。采用测试前腹腔给药的方法,选用3种剂量的吗啡(5、1.5、0.5mg/kg),两种剂量的东莨菪碱(1、0.1mg/kg),以及两种剂量的阿托品(0.5、0.1mg/kg),剂量由高到低相配对作为联合给药的手段。其结果表明:1)0.5mg/kg低剂量吗啡与0.1mg/kg低剂量的东莨菪碱,或与0.1mg/kg低剂量的阿托品联合给药的小鼠,在记忆提取测试中,空间探查行为(各臂停留时间百分比)对新异臂没有偏好,而新奇探索行为(各臂访问次数百分比)仍保持了对新异臂的偏好,而相应剂量药物单独给药的小鼠记忆提取均没有被损害;2)吗啡能和东莨菪碱相互作用使小鼠的活动性显著增强。暗示吗啡和胆碱能拮抗剂对小鼠空间记忆提取的破坏存在一定程度的相互作用。     

成年布氏田鼠对个体气味信号的识别与记忆

将配对饲养的成年雌雄布氏田鼠分离, 通过分开单独饲养12 h , 1 d、2 d、3 d、5 d 和7 d 后雌、雄鼠对原配偶异性和陌生异性气味信号的选择实验, 探讨布氏田鼠对气味信号的识别和记忆。实验表明: 在分离12 h 和1 d 后, 雄鼠对陌生雌性气味的选择和探究行为显著多于对熟悉雌鼠气味, 而雌鼠对两种气味并未表现显著的探究差异; 布氏田鼠对气味信号的记忆维持的强度和时间随个体不同而产生差异, 雄鼠在分离后12 h、1d、2 d 中对陌生雌鼠气味均表现出差异明显的探究行为, 而后, 各项探究行为的差异均不明显。雌鼠探究行为变化比较缓慢。据此推测雄鼠对气味的记忆维持在2 d 左右。     

Electrophysiological Correlates of Vigilance During a Continuous Performance Test in Healthy Adults

The present study evaluated patterns of electrophysiological activity associated with sustained vigilance in healthy adults. Quantitative electroencephalographs (QEEG) were recorded during the performance of a Continuous Performance Test (CPT). Participants were divided into low and high vigilance groups based upon their reaction time changes between the early and late portions of the CPT. Coherence measures were calculated from the QEEG across the baseline, early CPT, and late CPT experimental conditions. Participants in the low vigilance group had higher baseline and CPT frontal to posterior coherence in the alpha and beta bands suggestive of a less vigilant state throughout the entire study. Additionally, the low vigilance group had a significantly greater beta 1 band coherence drop from baseline to the initial portion of the CPT than the high vigilance group. The combined groups had significantly lower amounts of right hemisphere frontal to posterior coherence across a number of frequency bands throughout all of the phases of the study when compared to the homologous left hemisphere sites. These interhemispheric coherence differences are consistent with vigilance network theories that implicate the right frontal and parietal lobes in the maintenance of sustained attention (M. I. Posner & M. E. Raichle, 1994).