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1.
《Journal of Physiology》2013,107(6):434-440
Phencyclidine (PCP) is a psychotomimetic drug that induces schizophrenia-like symptoms in healthy individuals and exacerbates pre-existing symptoms in patients with schizophrenia. PCP also induces behavioral and cognitive abnormalities in non-human animals, and PCP-treated animals are considered a reliable pharmacological model of schizophrenia. However, the exact neural mechanisms by which PCP modulates behavior are not known. During the last decade several studies have indicated that disturbed activity of the prefrontal cortex (PFC) may be closely related to PCP-induced psychosis. Systemic administration of PCP produces long-lasting activation of medial PFC (mPFC) neurons in rats, almost in parallel with augmentation of locomotor activity and behavioral stereotypies. Later studies have showed that such PCP-induced behavioral abnormalities are ameliorated by prior administration of drugs that normalize or inhibit excess excitability of PFC neurons. Similar activation of mPFC neurons is not induced by systemic injection of a typical psychostimulant such as methamphetamine, even though behavioral hyperactivity is induced to almost the same level. This suggests that the neural circuits mediating PCP-induced psychosis are different to those mediating methamphetamine-induced psychosis. Locally applied PCP does not induce excitation of mPFC neurons, indicating that PCP-induced tonic excitation of mPFC neurons is mediated by inputs from regions outside the mPFC. This hypothesis is strongly supported by experimental results showing that local perfusion of PCP in the ventral hippocampus, which has dense fiber projections to the mPFC, induces tonic activation of mPFC neurons with accompanying augmentation of behavioral abnormalities. In this review we summarize current knowledge on the neural mechanisms underlying PCP-induced psychosis and highlight a possible involvement of the PFC and the hippocampus in PCP-induced psychosis.  相似文献   

2.
It has been reported that reality evaluation and recognition are impaired in patients with schizophrenia and these impairments are related to the severity of psychotic symptoms. The current study aimed to investigate the neural basis of impairments in reality evaluation and recognition and their relationships with cognitive insight in schizophrenia. During functional magnetic resonance imaging, 20 patients with schizophrenia and 20 healthy controls performed a set of reality evaluation and recognition tasks, in which subjects judged whether scenes in a series of drawings were real or unreal and whether they were familiar or novel. During reality evaluation, patients showed decreased activity in various regions including the inferior parietal lobule, retrosplenial cortex and parahippocampal gyrus, compared with controls. Particularly, parahippocampal gyrus activity was correlated with the severity of positive symptoms in patients. During recognition, patients also exhibited decreased activity in various regions, including the dorsolateral prefrontal cortex, inferior parietal lobule and posterior cingulate cortex. Particularly, inferior parietal lobule activity and posterior cingulate cortex activity were correlated with cognitive insight in patients. These findings provide evidence that neural impairments in reality evaluation and recognition are related to psychotic symptoms. Anomalous appraisal of context by dysfunctions in the context network may contribute to impairments in the reality processing in schizophrenia, and abnormal declarative memory processes may be involved in cognitive insight in patients with schizophrenia.  相似文献   

3.

Background

In a previous report we showed that cognitive training fostering auditory-verbal discrimination and working memory normalized magnetoencephalographic (MEG) M50 gating ratio in schizophrenia patients. The present analysis addressed whether training effects on M50 ratio and task performance are mediated by changes in brain oscillatory activity. Such evidence should improve understanding of the role of oscillatory activity in phenomena such as M50 ratio, the role of dysfunctional oscillatory activity in processing abnormalities in schizophrenia, and mechanisms of action of cognitive training.

Methodology/Principal Findings

Time-locked and non-time-locked oscillatory activity was measured together with M50 ratio in a paired-click design before and after a 4-week training of 36 patients randomly assigned to specific cognitive exercises (CE) or standard (comparison) cognitive training (CP). Patient data were compared to those of 15 healthy controls who participated in two MEG measurements 4 weeks apart without training. Training led to more time-locked gamma-band response and more non-time-locked alpha-band desynchronization, moreso after CE than after CP. Only after CE, increased alpha desynchronization was associated with normalized M50 ratio and with improved verbal memory performance. Thus, both types of cognitive training normalized gamma activity, associated with improved stimulus encoding. More targeted training of auditory-verbal discrimination and memory additionally normalized alpha desynchronization, associated with improved elaborative processing. The latter presumably contributes to improved auditory gating and cognitive function.

Conclusions/Significance

Results suggest that dysfunctional interplay of ocillatory activity that may contribute to auditory processing disruption in schizophrenia can be modified by targeted training.  相似文献   

4.

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.  相似文献   

5.
Social exclusion is an influential concept in politics, mental health and social psychology. Studies on healthy subjects have implicated the medial prefrontal cortex (mPFC), a region involved in emotional and social information processing, in neural responses to social exclusion. Impairments in social interactions are common in schizophrenia and are associated with reduced quality of life. Core symptoms such as delusions usually have a social content. However little is known about the neural underpinnings of social abnormalities. The aim of this study was to investigate the neural substrates of social exclusion in schizophrenia. Patients with schizophrenia and healthy controls underwent fMRI while participating in a popular social exclusion paradigm. This task involves passing a 'ball' between the participant and two cartoon representations of other subjects. The extent of social exclusion (ball not being passed to the participant) was parametrically varied throughout the task. Replicating previous findings, increasing social exclusion activated the mPFC in controls. In contrast, patients with schizophrenia failed to modulate mPFC responses with increasing exclusion. Furthermore, the blunted response to exclusion correlated with increased severity of positive symptoms. These data support the hypothesis that the neural response to social exclusion differs in schizophrenia, highlighting the mPFC as a potential substrate of impaired social interactions.  相似文献   

6.
《Journal of Physiology》2013,107(6):448-451
Schizophrenia affects about 1% of the world population and is a major socio-economical problem in ours societies. Cognitive symptoms are particularly resistant to current treatments and are believed to be closely related to an altered function of prefrontal cortex (PFC). Particularly, abnormalities in the plasticity processes in the PFC are a candidate mechanism underlying cognitive symptoms, and the recent evidences in patients are in line with this hypothesis. Animal pharmacological models of cognitive symptoms, notably with non-competitive NMDA receptor antagonists such as MK-801, are commonly used to investigate the underlying cellular and molecular mechanisms of schizophrenia. However, it is still unknown whether in these animal models, impairments in plasticity of PFC neurons are present. In this article, we briefly summarize the current knowledge on the effect of non-competitive NMDA receptor antagonist MK-801 on medial PFC (mPFC) neuronal activity and then introduce a form of plasticity found after acute exposure to MK-801, which was accompanied by cognitive deficits. These observations suggest a potential correlation between cognitive deficits and the aberrant plasticity in the mPFC in the animal model of schizophrenia.  相似文献   

7.
Stone tools provide some of the most abundant, continuous, and high resolution evidence of behavioral change over human evolution, but their implications for cognitive evolution have remained unclear. We investigated the neurophysiological demands of stone toolmaking by training modern subjects in known Paleolithic methods (“Oldowan”, “Acheulean”) and collecting structural and functional brain imaging data as they made technical judgments (outcome prediction, strategic appropriateness) about planned actions on partially completed tools. Results show that this task affected neural activity and functional connectivity in dorsal prefrontal cortex, that effect magnitude correlated with the frequency of correct strategic judgments, and that the frequency of correct strategic judgments was predictive of success in Acheulean, but not Oldowan, toolmaking. This corroborates hypothesized cognitive control demands of Acheulean toolmaking, specifically including information monitoring and manipulation functions attributed to the "central executive" of working memory. More broadly, it develops empirical methods for assessing the differential cognitive demands of Paleolithic technologies, and expands the scope of evolutionary hypotheses that can be tested using the available archaeological record.  相似文献   

8.

Background

The CogState Schizophrenia Battery (CSB), a computerized cognitive battery, covers all the same cognitive domains as the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery but is briefer to conduct. The aim of the present study was to evaluate the criterion and construct validity of the Japanese language version of the CSB (CSB-J) in Japanese patients with schizophrenia.

Methodology/Principal Findings

Forty Japanese patients with schizophrenia and 40 Japanese healthy controls with matching age, gender, and premorbid intelligence quotient were enrolled. The CSB-J and the Brief Assessment of Cognition in Schizophrenia, Japanese-language version (BACS-J) were performed once. The structure of the CSB-J was also evaluated by a factor analysis. Similar to the BACS-J, the CSB-J was sensitive to cognitive impairment in Japanese patients with schizophrenia. Furthermore, there was a significant positive correlation between the CSB-J composite score and the BACS-J composite score. A factor analysis showed a three-factor model consisting of memory, speed, and social cognition factors.

Conclusions/Significance

This study suggests that the CSB-J is a useful and rapid automatically administered computerized battery for assessing broad cognitive domains in Japanese patients with schizophrenia.  相似文献   

9.
Alterations in oscillatory brain activity are strongly correlated with cognitive performance in various physiological rhythms. The present study investigated whether the directionality of neural information flow (NIF) could be used to characterize the synaptic plasticity in thalamocortical (TC) pathway, and examined which frequency field oscillations were mostly related to the cognitive deficiency in depression. Two novel algorithms were employed to determine the coupling interaction between the LD thalamus and medial prefrontal cortex (mPFC) in five frequency bands, using the phase signals of local field potentials (LFP) in these two regions. The results showed that the power of neural activity in mPFC was increased in delta, theta and beta frequency bands in depression. However, the nonlinear characteristics of LFP activity were weakened in depression by means of sample entropy measurements. In the analysis of phase dynamics, the phase synchronization values were reduced in theta rhythm in stressed rats. Importantly, the coupling direction index d and the unidirectional influence from LD thalamus to mPFC were significantly reduced at the theta rhythm in rats in depression, and increased after memantine treatment, which were associated with the LTP alterations and cognitive impairment in our previous report. Moreover, the fact that the reduced entropy value was only found in mPFC might implicate postsynaptic effect involved in synaptic plasticity alteration in the depression model. The results suggest that the effects of depression on cognitive deficits are mediated via profound alterations in information flow in the TC pathway, and the directional index at theta rhythm could be used as a measurement of synaptic plasticity.  相似文献   

10.

Study Objectives

To investigate the effect of an eight-week, home-based, personalized, computerized cognitive training program on sleep quality and cognitive performance among older adults with insomnia.

Design

Participants (n = 51) were randomly allocated to a cognitive training group (n = 34) or to an active control group (n = 17). The participants in the cognitive training group completed an eight-week, home-based, personalized, computerized cognitive training program, while the participants in the active control group completed an eight-week, home-based program involving computerized tasks that do not engage high-level cognitive functioning. Before and after training, all participants'' sleep was monitored for one week by an actigraph and their cognitive performance was evaluated.

Setting

Community setting: residential sleep/performance testing facility.

Participants

Fifty-one older adults with insomnia (aged 65–85).

Interventions

Eight weeks of computerized cognitive training for older adults with insomnia.

Results

Mixed models for repeated measures analysis showed between-group improvements for the cognitive training group on both sleep quality (sleep onset latency and sleep efficiency) and cognitive performance (avoiding distractions, working memory, visual memory, general memory and naming). Hierarchical linear regressions analysis in the cognitive training group indicated that improved visual scanning is associated with earlier advent of sleep, while improved naming is associated with the reduction in wake after sleep onset and with the reduction in number of awakenings. Likewise the results indicate that improved “avoiding distractions” is associated with an increase in the duration of sleep. Moreover, the results indicate that in the active control group cognitive decline observed in working memory is associated with an increase in the time required to fall asleep.

Conclusions

New learning is instrumental in promoting initiation and maintenance of sleep in older adults with insomnia. Lasting and personalized cognitive training is particularly indicated to generate the type of learning necessary for combined cognitive and sleep enhancements in this population.

Trial Registration

ClinicalTrials.gov NCT00901641http://clinicaltrials.gov/ct2/show/NCT00901641  相似文献   

11.
Impaired mental state attribution is a core social cognitive deficit in schizophrenia. With functional magnetic resonance imaging (fMRI), this study examined the extent to which the core neural system of mental state attribution is involved in mental state attribution, focusing on belief attribution and emotion attribution. Fifteen schizophrenia outpatients and 14 healthy controls performed two mental state attribution tasks in the scanner. In a Belief Attribution Task, after reading a short vignette, participants were asked infer either the belief of a character (a false belief condition) or a physical state of an affair (a false photograph condition). In an Emotion Attribution Task, participants were asked either to judge whether character(s) in pictures felt unpleasant, pleasant, or neutral emotion (other condition) or to look at pictures that did not have any human characters (view condition). fMRI data were analyzing focusing on a priori regions of interest (ROIs) of the core neural systems of mental state attribution: the medial prefrontal cortex (mPFC), temporoparietal junction (TPJ) and precuneus. An exploratory whole brain analysis was also performed. Both patients and controls showed greater activation in all four ROIs during the Belief Attribution Task than the Emotion Attribution Task. Patients also showed less activation in the precuneus and left TPJ compared to controls during the Belief Attribution Task. No significant group difference was found during the Emotion Attribution Task in any of ROIs. An exploratory whole brain analysis showed a similar pattern of neural activations. These findings suggest that while schizophrenia patients rely on the same neural network as controls do when attributing beliefs of others, patients did not show reduced activation in the key regions such as the TPJ. Further, this study did not find evidence for aberrant neural activation during emotion attribution or recruitment of compensatory brain regions in schizophrenia.  相似文献   

12.
Adhikari A  Topiwala MA  Gordon JA 《Neuron》2011,71(5):898-910
The medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC) functionally interact during innate anxiety tasks. To explore the consequences of this interaction, we examined task-related firing of single units from the mPFC of mice exploring standard and modified versions of the elevated plus maze (EPM), an innate anxiety paradigm. Hippocampal local field potentials (LFPs) were simultaneously monitored. The population of mPFC units distinguished between safe and aversive locations within the maze, regardless of the nature of the anxiogenic stimulus. Strikingly, mPFC units with stronger task-related activity were more strongly coupled to theta-frequency activity in the vHPC LFP. Lastly, task-related activity was inversely correlated with behavioral measures of anxiety. These results clarify the role of the vHPC-mPFC circuit in innate anxiety and underscore how specific inputs may be involved in the generation of behaviorally relevant neural activity within the mPFC.  相似文献   

13.
Zika virus (ZIKV) infection during pregnancy is linked to various developmental brain disorders. Infants who are asymptomatic at birth might have postnatal neurocognitive complications. However, animal models recapitulating these neurocognitive phenotypes are lacking, and the circuit mechanism underlying behavioral abnormalities is unknown. Here, we show that ZIKV infection during mouse pregnancy induces maternal immune activation (MIA) and leads to autistic‐like behaviors including repetitive self‐grooming and impaired social memory in offspring. In the medial prefrontal cortex (mPFC), ZIKV‐affected offspring mice exhibit excitation and inhibition imbalance and increased cortical activity. This could be explained by dysregulation of inhibitory neurons and synapses, and elevated neural activity input from mPFC‐projecting ventral hippocampus (vHIP) neurons. We find structure alterations in the synaptic connections and pattern of vHIP innervation of mPFC neurons, leading to hyperconnectivity of the vHIP‐mPFC pathway. Decreasing the activity of mPFC‐projecting vHIP neurons with a chemogenetic strategy rescues social memory deficits in ZIKV offspring mice. Our studies reveal a hyperconnectivity of vHIP to mPFC projection driving social memory deficits in mice exposed to maternal inflammation by ZIKV.  相似文献   

14.
精神分裂症患者普遍存在视觉信息处理异常,这些视知觉功能紊乱涉及视通路的高级以及低级视区,表明在部分精神分裂症患者中,视觉系统早期或晚期的不同信息处理阶段均可能存在损伤.阐明这些感知觉信息处理紊乱的神经机制对理解精神分裂症神经病理生理学机制有重大意义.视觉周边抑制(surround suppression)是一种广泛存在的视觉现象,指在神经生理水平或视知觉水平上外周对中央视觉目标的抑制作用.精神分裂症的视觉周边抑制发生异常改变,然而其损伤状况并不完全一致,且其具体神经机制目前仍不清楚.本文以周边抑制为对象,从精神分裂症周边抑制改变状况及其神经机制两个层面简述了国内外精神分裂症视觉周边抑制的研究进展.未来研究方向需要系统全面地调查精神分裂症周边抑制损伤状况,综合脑科学研究技术共同探究精神分裂症患者周边抑制异常的具体神经环路.  相似文献   

15.
H Lee  D Dvorak  HY Kao  AM Duffy  HE Scharfman  AA Fenton 《Neuron》2012,75(4):714-724
Brain abnormalities acquired early in life may cause schizophrenia, characterized by adulthood onset of psychosis, affective flattening, and cognitive impairments. Cognitive symptoms, like impaired cognitive control, are now recognized to be important treatment targets but cognition-promoting treatments are ineffective. We hypothesized that cognitive training during the adolescent period of neuroplastic development can tune compromised neural circuits to develop in the service of adult cognition and attenuate schizophrenia-related cognitive impairments that manifest in adulthood. We report, using neonatal ventral hippocampus lesion rats (NVHL), an established neurodevelopmental model of schizophrenia, that adolescent cognitive training prevented the adult cognitive control impairment in NVHL rats. The early intervention also normalized brain function, enhancing cognition-associated synchrony of neural oscillations between the hippocampi, a measure of brain function that indexed cognitive ability. Adolescence appears to be a critical window during which prophylactic cognitive therapy may benefit people at risk of schizophrenia.  相似文献   

16.
Pavlovian fear conditioning is often used in combination with functional magnetic resonance imaging (fMRI) in humans to investigate the neural substrates of associative learning 1-5. In these studies, it is important to provide behavioral evidence of conditioning to verify that differences in brain activity are learning-related and correlated with human behavior. Fear conditioning studies often monitor autonomic responses (e.g. skin conductance response; SCR) as an index of learning and memory 6-8. In addition, other behavioral measures can provide valuable information about the learning process and/or other cognitive functions that influence conditioning. For example, the impact unconditioned stimulus (UCS) expectancies have on the expression of the conditioned response (CR) and unconditioned response (UCR) has been a topic of interest in several recent studies 9-14. SCR and UCS expectancy measures have recently been used in conjunction with fMRI to investigate the neural substrates of aware and unaware fear learning and memory processes 15. Although these cognitive processes can be evaluated to some degree following the conditioning session, post-conditioning assessments cannot measure expectations on a trial-to-trial basis and are susceptible to interference and forgetting, as well as other factors that may distort results 16,17 .Monitoring autonomic and behavioral responses simultaneously with fMRI provides a mechanism by which the neural substrates that mediate complex relationships between cognitive processes and behavioral/autonomic responses can be assessed. However, monitoring autonomic and behavioral responses in the MRI environment poses a number of practical problems. Specifically, 1) standard behavioral and physiological monitoring equipment is constructed of ferrous material that cannot be safely used near the MRI scanner, 2) when this equipment is placed outside of the MRI scanning chamber, the cables projecting to the subject can carry RF noise that produces artifacts in brain images, 3) artifacts can be produced within the skin conductance signal by switching gradients during scanning, 4) the fMRI signal produced by the motor demands of behavioral responses may need to be distinguished from activity related to the cognitive processes of interest. Each of these issues can be resolved with modifications to the setup of physiological monitoring equipment and additional data analysis procedures. Here we present a methodology to simultaneously monitor autonomic and behavioral responses during fMRI, and demonstrate the use of these methods to investigate aware and unaware memory processes during fear conditioning. Download video file.(83M, mov)  相似文献   

17.
Kim J  Park S  Blake R 《PloS one》2011,6(5):e19971

Background

Anomalous visual perception is a common feature of schizophrenia plausibly associated with impaired social cognition that, in turn, could affect social behavior. Past research suggests impairment in biological motion perception in schizophrenia. Behavioral and functional magnetic resonance imaging (fMRI) experiments were conducted to verify the existence of this impairment, to clarify its perceptual basis, and to identify accompanying neural concomitants of those deficits.

Methodology/Findings

In Experiment 1, we measured ability to detect biological motion portrayed by point-light animations embedded within masking noise. Experiment 2 measured discrimination accuracy for pairs of point-light biological motion sequences differing in the degree of perturbation of the kinematics portrayed in those sequences. Experiment 3 measured BOLD signals using event-related fMRI during a biological motion categorization task.Compared to healthy individuals, schizophrenia patients performed significantly worse on both the detection (Experiment 1) and discrimination (Experiment 2) tasks. Consistent with the behavioral results, the fMRI study revealed that healthy individuals exhibited strong activation to biological motion, but not to scrambled motion in the posterior portion of the superior temporal sulcus (STSp). Interestingly, strong STSp activation was also observed for scrambled or partially scrambled motion when the healthy participants perceived it as normal biological motion. On the other hand, STSp activation in schizophrenia patients was not selective to biological or scrambled motion.

Conclusion

Schizophrenia is accompanied by difficulties discriminating biological from non-biological motion, and associated with those difficulties are altered patterns of neural responses within brain area STSp. The perceptual deficits exhibited by schizophrenia patients may be an exaggerated manifestation of neural events within STSp associated with perceptual errors made by healthy observers on these same tasks. The present findings fit within the context of theories of delusion involving perceptual and cognitive processes.  相似文献   

18.
Pregnancy and the postpartum period are times of profound behavioral change including alterations in cognitive function. This has been most often studied using hippocampal-dependent tasks assessing spatial learning and memory. However, less is known about the cognitive effects of motherhood for tasks that rely on areas other than the hippocampus. We have previously shown that postpartum females perform better on the extradimensional phase of an attentional set shifting task, a measure of cognitive flexibility which is dependent on the medial prefrontal cortex (mPFC). The present experiments aimed to extend this work by examining the importance of postpartum stage as well as offspring and parity in driving improved mPFC cognitive function during motherhood. We also examined whether the neuropeptide oxytocin, which plays a role in regulating numerous maternal functions, mediates enhanced cognitive flexibility during motherhood. Our results demonstrate that compared to virgin females, cognitive flexibility is enhanced in mothers regardless of postpartum stage and is not affected by parity since both first (primiparous) and second (biparous) time mothers showed the enhancement. Moreover, we found that improved cognitive flexibility in mothers requires the presence of offspring, as removal of the pups abolished the cognitive enhancement in postpartum females. Lastly, using an oxytocin receptor antagonist, we demonstrate that oxytocin signaling in the mPFC is necessary for the beneficial effects of motherhood on cognitive flexibility. Together, these data provide insights into the temporal, experiential and hormonal factors which regulate mPFC-dependent cognitive function during the postpartum period.  相似文献   

19.
Memory performance in everyday life is often far from perfect and therefore needs to be monitored and controlled by metamemory evaluations, such as judgments of learning (JOLs). JOLs support monitoring for goal-directed modification of learning. Behavioral studies suggested retrieval processes as providing a basis for JOLs. Previous functional imaging research on JOLs found a dissociation between processes underlying memory prediction, located in the medial prefrontal cortex (mPFC), and actual encoding success, located in the medial temporal lobe. However, JOL-specific neural correlates could not be identified unequivocally, since JOLs were given simultaneously with encoding. Here, we aimed to identify the neurocognitive basis of JOLs, i.e., the cognitive processes and neural correlates of JOL, separate from initial encoding. Using functional magnetic resonance imaging (fMRI), we implemented a face-name paired associative design. In general, we found that actual memory success was associated with increased brain activation of the hippocampi bilaterally, whereas predicted memory success was accompanied by increased activation in mPFC, orbital frontal and anterior cingulate cortices. Masking brain activation during predicted memory success with activation during retrieval success revealed BOLD increases of the mPFC. Our findings indicate that JOLs actually incorporate retrieval processes.  相似文献   

20.
Abnormal phospholipid metabolism has been implicated in the pathogenesis of schizophrenia, and it was reported that phospholipase C (PLC) β1 is reduced in specific brain areas of patients with schizophrenia. However, the causal relationship of the PLCβ1 gene with behavioral symptoms of schizophrenia remains unclear. To address this issue, we have examined the mutant mice lacking PLCβ1 for schizophrenia-related phenotypes by performing various behavioral tests, including general locomotor activity, sensorimotor gating, social behaviors, and learning and memory. Phospholipase C β1 knockout mice showed hyperactivities in an open field. They showed impaired prepulse inhibition of acoustic startle response, which was ameliorated by a systemic administration of an antipsychotic D2-receptor antagonist, haloperidol. In addition, they showed abnormal social behaviors, such as lack of barbering behavior, socially recessive trait and lack of nesting behavior. Furthermore, they showed impaired performance in the delayed-non-match-to-sample T-maze test. The present results show that the PLCβ1 mutant mice share some of the behavioral abnormalities that have been reported in patients with schizophrenia. Thus, the PLCβ1-linked signaling pathways may be involved in the neural system whose function is disrupted in the pathogenesis of schizophrenia.  相似文献   

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