Global disruption in excitation-inhibition balance can cause localized network dysfunction and Schizophrenia-like context-integration deficits.
Global disruption in excitation-inhibition balance can cause localized network dysfunction and Schizophrenia-like context-integration deficits.
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DOI：
10.1371/journal.pcbi.1008985
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发表时间：
2021-05
影响因子：
4.3
通讯作者：
Redish AD
中科院分区：
文献类型：
--
作者：
Calvin OL;Redish AD
背景整合不良是精神分裂症的一种认知症状，也就是在决策过程中整合以前和当前信息的过程。背景信息的维持被证明对兴奋-抑制(EI)平衡的变化很敏感。然而，大脑的许多区域对EI失衡很敏感，因此尚不清楚系统性操作如何影响对背景整合至关重要的特定区域。我们构建了一个多结构、生物物理现实的代理，它可以执行上下文整合，正如点模式预期任务所评估的那样。该代理包括感知网络、记忆网络和决策系统，能够成功地执行点图案预期任务。对药物的EI平衡的系统性操纵产生了记忆结构的局部性功能障碍，这导致了情境整合中的精神分裂症样缺陷。当代理人的锥体细胞不那么兴奋时，代理人专注于线索，比默认的代理人更晚开始反应，这就像人们会预测自闭症谱系上的个体会出现的缺陷一样。这个模型表明，通过在情境整合任务中增加干扰因素并仔细检查参与者的反应时间，可以在不同类型的情境整合缺陷之间进行分析。精神分裂症是一种衰弱的精神健康疾病，其根本病因目前尚不清楚。神经兴奋和抑制大脑特定区域的神经失衡被认为是导致精神分裂症症状的原因。大脑的大多数区域都有特定的兴奋-抑制平衡，这使得它们能够在信息处理中发挥作用。兴奋-抑制平衡中的系统性变化如何导致神经回路中的特定缺陷和功能障碍尚不清楚。精神分裂症患者的一个常见认知缺陷是背景整合困难，即在做出决定时成功使用以前和当前信息的能力。我们通过模拟模型代理中潜在的失衡的影响，评估了这种症状是如何由神经兴奋和抑制的失衡引起的。毒剂神经兴奋和抑制的全局失衡导致特定回路的损害。这些功能失调的回路产生了行为缺陷，就像在精神分裂症患者身上观察到的那样。这些模拟表明，兴奋或抑制的全局变化可能如何扰乱特定的神经回路，改善背景整合评估的方法，分析行为的新方法，以及为什么在自闭症谱系障碍中评估背景整合可能是有益的。
Poor context integration, the process of incorporating both previous and current information in decision making, is a cognitive symptom of schizophrenia. The maintenance of the contextual information has been shown to be sensitive to changes in excitation-inhibition (EI) balance. Many regions of the brain are sensitive to EI imbalances, however, so it is unknown how systemic manipulations affect the specific regions that are important to context integration. We constructed a multi-structure, biophysically-realistic agent that could perform context-integration as is assessed by the dot pattern expectancy task. The agent included a perceptual network, a memory network, and a decision making system and was capable of successfully performing the dot pattern expectancy task. Systemic manipulation of the agent’s EI balance produced localized dysfunction of the memory structure, which resulted in schizophrenia-like deficits at context integration. When the agent’s pyramidal cells were less excitatory, the agent fixated upon the cue and initiated responding later than the default agent, which were like the deficits one would predict that individuals on the autistic spectrum would make. This modelling suggests that it may be possible to parse between different types of context integration deficits by adding distractors to context integration tasks and by closely examining a participant’s reaction times. Schizophrenia is a debilitating mental health disorder and its underlying etiology is currently unknown. Neural imbalances in the neural excitation and inhibition of specific regions of the brain have been hypothesized to cause symptoms of schizophrenia. Most regions of the brain have specific excitation-inhibition balances that permit their functioning in the processing of information. How systemic changes in the excitation-inhibition balance cause specific deficits and dysfunction within neural circuits is unknown. A common cognitive deficit in schizophrenia is difficulty with context integration, which is the ability to successfully use previous and current information when making decisions. We assessed how this symptom could be caused by an imbalance in neural excitation and inhibition by simulating the effects of potential imbalances in a model agent. Global imbalances in the agent’s neural excitation and inhibition led to impairment of specific circuits. These dysfunctional circuits produced behavioral deficits that were like those observed in individuals with schizophrenia. These simulations suggested how specific neural circuits may be disrupted by global changes in excitation or inhibition, ways to improve the assessment of context integration, new approaches to analyzing behavior, and why it may be beneficial to assess context integration in autism spectrum disorder.
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