Movement disorders:去甲肾上腺素能活动,对焦虑诱发的冻结步态,有何影响?

2022-06-18 Freeman MedSci原创

与焦虑有关的交感神经唤醒可以促进分布式皮质网络之间的 "交叉对话 "增加,最终表现为阵发性的步态冻结发作。

最近人们认识到焦虑是诱发步态冻结(FOG)的一个重要因素。据报道,情绪紊乱,如惊恐发作,在FOG之前和期间都会发生。焦虑的生理标志物(如心率和皮肤电导的升高)已被发现在FOG发作前增加。此外,当使用沉浸式虚拟现实(VR)木板任务诱发焦虑时,FOG患者在浏览高架木板时,与地面上的木板相比,表现出更频繁和更严重的冻结发作。尽管有这些行为观察,但对于支撑焦虑和FOG之间关系的神经机制仍有猜测。尽管对PD焦虑的神经机制还不是很了解,但焦虑已与网络层面的异常相联系,这与唤醒系统的过度参与相一致。然而,需要更深入地了解这些网络层面的异常如何与肢体间协调和冻结的改变相关。

图1: 论文封面图

尽管众所周知,帕金森病(PD)患者有多巴胺能系统的功能障碍,而且多巴胺通常被认为能促进大脑中有效的系统级功能,但服用多巴胺能药物只能部分改善FOG,这表明非多巴胺能病理生理学的突出作用。有充分的证据表明,PD患者的上升性唤醒系统内存在病理学,与威胁反应和焦虑密切相关。一个有希望的候选者是蓝斑核(LC),它是中枢神经系统中去甲肾上腺素能神经元的主要枢纽。已知LC协调唤醒和自律神经的平衡,导致广泛分布在整个皮层的目标处的去甲肾上腺素释放升高。除了这些强直效应外,去甲肾上腺素的下游阶段性效应与网络水平整合的增加有关,这反过来又被证明有助于高阶认知功能(如工作记忆)所需的动态皮质互动(即串扰)。


与这些有益的认知效果相反,增强的强直性LC活动被认为与压力反应有关,通过其在更广泛的交感神经回路中的连接,共同产生生理和神经传递反应的急性变化。 通过这些联系,LC被认为在焦虑的病理生理学中起着突出的作用。尽管上升的去甲肾上腺素系统的招募对于对威胁的正常反应至关重要,但有人认为,LC的过度活动与适应不良的威胁反应和长期的焦虑有关。


此外,LC还与其他PD症状的加重有关。例如,与压力相关的去甲肾上腺素唤醒系统的激活已经参与了震颤的表现。与这一概念一致,FOG与一些表明交感神经唤醒的措施有关,这表明了一种新的机理解释,即焦虑如何通过将大脑转移到更容易受到交叉对话干扰的状态而为FOG的发生 "创造条件"。

这些证据产生了这样的假设:LC的过度活动可能导致FOG患者的焦虑加剧。继发于焦虑的去甲肾上腺素的增加会提高整个网络中皮质区域的反应增益,本质上促进运动、认知和边缘网络之间的交叉对话。


藉此,悉尼大学的Natasha L. Taylor等人,使用了一个虚拟现实步态范式,该范式已被验证可以通过让参与者浏览一个虚拟plank来引起焦虑,同时收集特发性PD患者的基于任务的fMRI,并确认步态的冻结。

他们发现:与非威胁性条件相比,威胁性条件引发了更多的冻结。

图2:论文结果图


通过使用动态连接分析,他们确定了威胁条件下运动、边缘和认知网络内部和之间 "交叉对话 "的增加模式。

此外,威胁条件与高度的网络整合有关。他们证实了这一现象的交感性,因为在一个辅助实验中,在虚拟现实步态范式的焦虑诱导条件下,瞳孔扩张增加。

该发现代表了一种神经生物学的机制途径,通过这种途径,与焦虑有关的交感神经唤醒可以促进分布式皮质网络之间的 "交叉对话 "增加,最终表现为阵发性的步态冻结发作。

 

原文出处:
Taylor NL, Wainstein G, Quek D, Lewis SJG, Shine JM, Ehgoetz Martens KA. The Contribution of Noradrenergic Activity to Anxiety‐Induced Freezing of Gait. _Movement Disorders_. Published online April 5, 2022:mds.28999. doi:[10.1002/mds.28999](https://doi.org/10.1002/mds.28999)

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    2023-01-13 anminleiryan
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encodeId=5d5020e7698bb, content=<a href='/topic/show?id=67cc600242' target=_blank style='color:#2F92EE;'>#disorder#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6002, encryptionId=67cc600242, topicName=disorder)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3fc52500170, createdName=12498cbcm00(暂无昵称), createdTime=Mon Jul 11 21:27:22 CST 2022, time=2022-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1284953, encodeId=b4851284953d7, content=<a href='/topic/show?id=b67d8244123' target=_blank style='color:#2F92EE;'>#肾上腺素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82441, encryptionId=b67d8244123, topicName=肾上腺素)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=325a197, createdName=amyloid, createdTime=Thu Jun 16 02:27:22 CST 2022, time=2022-06-16, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1895258, encodeId=d4781895258a3, content=<a href='/topic/show?id=ce478241e0b' target=_blank style='color:#2F92EE;'>#肾上腺#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82417, encryptionId=ce478241e0b, topicName=肾上腺)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8dba135, createdName=xuyong523, createdTime=Thu Oct 13 06:27:22 CST 2022, time=2022-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1878540, encodeId=b97818e854020, content=<a href='/topic/show?id=c157696175' target=_blank style='color:#2F92EE;'>#ERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6961, encryptionId=c157696175, topicName=ERS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e93e105, 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16 02:27:22 CST 2022, time=2022-06-16, status=1, ipAttribution=)]
  6. 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encodeId=5d5020e7698bb, content=<a href='/topic/show?id=67cc600242' target=_blank style='color:#2F92EE;'>#disorder#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6002, encryptionId=67cc600242, topicName=disorder)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3fc52500170, createdName=12498cbcm00(暂无昵称), createdTime=Mon Jul 11 21:27:22 CST 2022, time=2022-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1284953, encodeId=b4851284953d7, content=<a href='/topic/show?id=b67d8244123' target=_blank style='color:#2F92EE;'>#肾上腺素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82441, encryptionId=b67d8244123, topicName=肾上腺素)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=325a197, createdName=amyloid, createdTime=Thu Jun 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    2022-12-15 xxxx1061
  7. 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  8. 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