Hypothesis for the pathophysiology of delirium: Role of baseline brain network connectivity and changes in inhibitory tone
Hypothesis for the pathophysiology of delirium: Role of baseline brain network connectivity and changes in inhibitory tone
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DOI：
10.1016/j.mehy.2011.03.048
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发表时间：
2011-07-01
影响因子：
4.7
通讯作者：
Sanders, Robert D.
中科院分区：
文献类型：
--
作者：
Sanders, Robert D.
高度组织和互连的结构促进了正常的大脑功能，允许感觉信息和运动反应的复杂整合。谵妄的急性混乱状态的特征是意识、觉醒水平和认知记忆的波动性障碍；因此，谵妄代表着信息整合和适当处理的失败。这种认知瓦解的发病机制尚不清楚。本文提出了一种假设，即谵妄是由大脑内网络连接的严重故障引起的。该假设预测网络连接中断的程度取决于两个因素：（i）大脑内的基线连接和（ii）抑制音调的水平。基线连接是指在突然的侮辱引发谵妄之前大脑内神经网络的连接。许多不可改变的谵妄危险因素会影响基线连通性，例如年龄、认知障碍、痴呆和抑郁。据推测，引发谵妄的突发事件（可改变的危险因素）会通过增加大脑内的抑制张力来进一步、急剧地破坏网络连接。可改变的危险因素包括炎症、代谢异常、睡眠不足和苯二氮卓类药物等药物。 GABA 能神经传递的一个重要作用涉及增加抑制性音调以产生谵妄。该理论解释了各种形式的谵妄，包括活动减退、活动过度和混合性谵妄。随之而来的谵妄的形式将取决于网络崩溃的方式和程度（取决于个体的基线网络连接性和产生的抑制音调的变化程度）。 (C) 2011 Elsevier Ltd. 保留所有权利。
Normal brain function is facilitated by a highly organized and interconnected structure allowing complex integration of sensory information and motor responses. The acute confusional state of delirium is characterized by a fluctuating disturbance in consciousness, arousal level and cognition-memory; as such, delirium represents a failure in the integration and appropriate processing of information. The pathogenesis of this cognitive disintegration is unclear; herein a hypothesis is proposed that delirium results from an acute breakdown in network connectivity within the brain. The hypothesis predicts that the extent to which the network connectivity breaks down is dependent on two factors: (i) the baseline connectivity within the brain and (ii) the level of inhibitory tone. Baseline connectivity is the connectivity of neural networks within the brain before the precipitating insult provoking delirium. Many non-modifiable risk factors for delirium influence baseline connectivity such as age, cognitive impairment, dementia and depression. Precipitant events that provoke delirium (modifiable risk factors) are hypothesized to further, and acutely, breakdown network connectivity by increasing inhibitory tone within the brain. Modifiable risk factors include inflammation, metabolic abnormalities, sleep deprivation and medication such as benzodiazepines. An important role for GABAergic neurotransmission is implicated in increasing the inhibitory tone to produce delirium. This theory accounts for the various forms of delirium, hypoactive, hyperactive and mixed. The form of delirium that ensues will depend upon how and which networks breakdown (dependent on both the individual's baseline network connectivity and the degree change in inhibitory tone produced). (C) 2011 Elsevier Ltd. All rights reserved.