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脑功能连接与精神分裂症的病理生理学

Brain functional connectivity and the pathophysiology of schizophrenia.

作者信息

Angelopoulos E

机构信息

1st Psychiatric Department, University of Athens , University Mental Health Research Institute, Athens, Greece.

出版信息

Psychiatriki. 2014 Apr-Jun;25(2):91-4.

Abstract

In the last decade there is extensive evidence to suggest that cognitive functions depending on coordination of distributed neuronal responses are associated with synchronized oscillatory activity in various frequency ranges suggesting a functional mechanism of neural oscillations in cortical networks. In addition to their role in normal brain functioning, there is increasing evidence that altered oscillatory activity may be associated with certain neuropsychiatric disorders, such as schizophrenia. Consequently, disturbances in neural synchronization may represent the functional relationship of disordered connectivity of cortical networks underlying the characteristic fragmentation of mind and behavior in schizophrenia. In recent studies the synchronization of oscillatory activity in the experience of characteristic symptoms such as auditory verbal hallucinations and thought blocks have been studied in patients with schizophrenia. Studies involving analysis of EEG activity obtained from individuals in resting state (in cage Faraday, isolated from external influences and with eyes closed). In patients with schizophrenia and persistent auditory verbal hallucinations (AVHs) observed a temporary increase in the synchronization phase of α and high θ oscillations of the electroencephalogram (EEG) compared with those of healthy controls and patients without AVHs . This functional hyper-connection manifested in time windows corresponding to experience AVHs, as noted by the patients during the recording of EEG and observed in speech related cortical areas. In another study an interaction of theta and gamma oscillations engages in the production and experience of AVHs. The results showed increased phase coupling between theta and gamma EEG rhythms in the left temporal cortex during AVHs experiences. A more recent study, approaches the thought blocking experience in terms of functional brain connectivity. Thought blocks (TBs) are characterized by regular interruptions of the flow of thought. Outward signs are abrupt and repeated interruptions in the flow of conversation or actions while subjective experience is that of a total and uncontrollable emptying of the mind. In the very limited bibliography regarding TB, the phenomenon is thought to be conceptualized as a disturbance of consciousness that can be attributed to stoppages of continuous information processing due to an increase in the volume of information to be processed. In an attempt to investigate potential expression of the phenomenon on the functional properties of electroencephalographic (EEG) activity, an EEG study was contacted in schizophrenic patients with persisting auditory verbal hallucinations (AVHs) who additionally exhibited TBs. Phase synchronization analyses performed on EEG segments during the experience of TBs showed that synchrony values exhibited a long-range common mode of coupling (grouped behavior) among the left temporal area and the remaining central and frontal brain areas. These common synchrony-fluctuation schemes were observed for 0.5 to 2 s and were detected in a 4-s window following the estimated initiation of the phenomenon. The observation was frequency specific and detected in the broad alpha band region (6-12 Hz). The introduction of synchrony entropy (SE) analysis applied on the cumulative synchrony distribution showed that TB states were characterized by an explicit preference of the system to be functioned at low values of synchrony, while the synchrony values are broadly distributed during the recovery state. The results indicate that during TB states, the phase locking of several brain areas were converged uniformly in a narrow band of low synchrony values and in a distinct time window, impeding thus the ability of the system to recruit and to process information during this time window. The results of this study seem to have greater importance on neuronal correlation of consciousness. The brain is a highly distributed system in which numerous operations are executed in parallel and that lacks a single coordinating center. This raises the question of how the computations occurring simultaneously in spatially segregated processing areas are coordinated and bound together to give rise to coherent percepts and actions. One of the coordinating mechanisms appears to be the synchronization of neuronal activity by phase locking of self-generated network oscillations. This led to the hypothesis that the cerebral cortex might exploit the option to synchronize the discharges of neurons with millisecond ` theoretical formulations of the binding-by-synchrony hypothesis were proposed earlier by Milner (1974), but the Singer lab in the 1990s was the first to obtain experimental evidence supporting the potential role of synchrony as a relational code. The results concerning the functional connectivity of the brain during TBs further support the hypothesis of phase synchronization as a key mechanism for neuronal assemblies underlying mental representations in the human brain.

摘要

在过去十年中,有大量证据表明,依赖于分布式神经元反应协调的认知功能与各种频率范围内的同步振荡活动相关,这表明皮层网络中神经振荡存在一种功能机制。除了在正常脑功能中发挥作用外,越来越多的证据表明,振荡活动的改变可能与某些神经精神疾病有关,如精神分裂症。因此,神经同步紊乱可能代表了精神分裂症患者思维和行为特征性碎片化背后皮层网络连接紊乱的功能关系。在最近的研究中,已经对精神分裂症患者特征性症状(如幻听和思维中断)体验中的振荡活动同步性进行了研究。研究涉及对处于静息状态(在法拉第笼中,与外界影响隔离且闭眼)的个体所获得的脑电图(EEG)活动进行分析。与健康对照者和无幻听的患者相比,患有精神分裂症和持续性幻听(AVH)的患者观察到脑电图(EEG)的α和高θ振荡同步相位暂时增加。这种功能性超连接在与幻听体验相对应的时间窗口中表现出来,正如患者在脑电图记录期间所指出的,并在与言语相关的皮层区域中观察到。在另一项研究中,θ和γ振荡的相互作用参与了幻听的产生和体验。结果显示,在幻听体验期间,左颞叶皮层中θ和γ脑电节律之间的相位耦合增加。一项更新的研究从功能性脑连接的角度探讨了思维中断体验。思维中断(TB)的特征是思维流的规律性中断。外在表现是对话或行动流中的突然和反复中断,而主观体验是思维完全且无法控制地清空。在关于思维中断的非常有限的文献中,该现象被认为可概念化为一种意识障碍,这可归因于由于待处理信息量增加导致连续信息处理的停止。为了研究该现象在脑电图(EEG)活动功能特性上的潜在表现,对患有持续性幻听(AVH)且额外表现出思维中断的精神分裂症患者进行了一项脑电图研究。在思维中断体验期间对脑电图片段进行的相位同步分析表明,同步值在左颞叶区域与其余中央和额叶脑区之间表现出一种长程共模耦合(分组行为)。这些共同的同步波动模式在0.5至2秒内被观察到,并在该现象估计开始后的4秒窗口内被检测到。该观察结果具有频率特异性,且在宽α波段区域(6 - 12赫兹)被检测到。对累积同步分布应用同步熵(SE)分析表明,思维中断状态的特征是系统明显倾向于在低同步值下运行,而在恢复状态下同步值分布广泛。结果表明,在思维中断状态期间,几个脑区的相位锁定在一个狭窄的低同步值带内且在一个特定的时间窗口内统一收敛,从而在这个时间窗口内阻碍了系统募集和处理信息的能力。这项研究的结果似乎对意识的神经元相关性具有更大的重要性。大脑是一个高度分布式的系统,其中许多操作并行执行,且缺乏一个单一的协调中心。这就提出了一个问题,即在空间上分离的处理区域中同时发生的计算是如何被协调并结合在一起以产生连贯的感知和行动的。一种协调机制似乎是通过自生成网络振荡的相位锁定来实现神经元活动的同步。这导致了这样一种假设,即大脑皮层可能利用这种选择来使神经元放电同步,精确到毫秒级。同步绑定假说的理论公式较早前由米尔纳(1974年)提出,但辛格实验室在20世纪90年代首次获得了支持同步作为一种关系编码潜在作用的实验证据。关于思维中断期间大脑功能连接的结果进一步支持了相位同步作为人类大脑中精神表征基础的神经元集合的关键机制这一假说。

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