Hartikainen Kaisa M, Sun Lihua, Polvivaara Markus, Brause Maarja, Lehtimäki Kai, Haapasalo Joonas, Möttönen Timo, Väyrynen Kirsi, Ogawa Keith H, Öhman Juha, Peltola Jukka
a Behavioral Neurology Research Unit, Tampere University Hospital , Tampere , Finland.
J Clin Exp Neuropsychol. 2014;36(5):540-50. doi: 10.1080/13803395.2014.913554. Epub 2014 May 19.
Deep brain stimulation (DBS) of anterior thalamic nuclei (ANT) is a novel promising therapeutic method for treating refractory epilepsy. Despite reports of subjective memory impairments and mood disturbances in patients with ANT-DBS, little is known of its effects on cognitive and affective processes.
The anterior thalamus has connections to prefrontal and limbic networks important for cognitive control and emotional reactivity. More specifically, anterior cingulate cortex (ACC), linked with ANT, has been assigned roles related to response inhibition and attention allocation to threat. Thus, we hypothesized ANT-DBS to influence executive functions, particularly response inhibition, and modulate emotional reactivity to threat.
Twelve patients having undergone ANT-DBS for intractable epilepsy participated in the study. Patients performed a computer-based executive reaction time (RT) test--that is, a go/no-go visual discrimination task with threat-related emotional distractors and rule switching, while the DBS was switched ON (5/5 mA constant current) and OFF every few minutes.
ANT-DBS increased the amount of commission errors--that is, errors where subjects failed to withhold from responding. Furthermore, ANT-DBS slowed RTs in context of threat-related distractors. When stimulation was turned off, threat-related distractors had no distinct effect on RTs.
We found immediate objective effects of ANT-DBS on human cognitive control and emotion-attention interaction. We suggest that ANT-DBS compromised response inhibition and enhanced attention allocation to threat due to altered functioning of neural networks that involve the DBS-target, ANT, and the regions connected to it such as ACC. The results highlight the need to consider affective and cognitive side-effects in addition to the therapeutic effect when adjusting stimulation parameters. Furthermore, this study introduces a novel window into cognitive and affective processes by modulating the associative and limbic networks with direct stimulation of key nodes in the thalamus.
丘脑前核（ANT）的深部脑刺激（DBS）是一种治疗难治性癫痫的新的有前景的治疗方法。尽管有报道称接受ANT-DBS治疗的患者存在主观记忆障碍和情绪紊乱，但对其对认知和情感过程的影响知之甚少。
丘脑前叶与对认知控制和情绪反应很重要的前额叶和边缘网络相连。更具体地说，与ANT相连的前扣带回皮质（ACC）已被赋予与反应抑制和对威胁的注意力分配相关的作用。因此，我们假设ANT-DBS会影响执行功能，特别是反应抑制，并调节对威胁的情绪反应。
12名因顽固性癫痫接受ANT-DBS治疗的患者参与了该研究。患者进行了一项基于计算机的执行反应时间（RT）测试——即一项带有与威胁相关的情绪干扰物和规则切换的“是/否”视觉辨别任务，同时每隔几分钟将DBS打开（5/5 mA恒流）和关闭。
ANT-DBS增加了错误肯定的数量——即受试者未能抑制反应的错误。此外，在存在与威胁相关的干扰物的情况下，ANT-DBS减缓了反应时间。当刺激关闭时，与威胁相关的干扰物对反应时间没有明显影响。
我们发现ANT-DBS对人类认知控制和情绪-注意力交互有直接的客观影响。我们认为，由于涉及DBS靶点ANT及其连接区域（如ACC）的神经网络功能改变，ANT-DBS损害了反应抑制并增强了对威胁的注意力分配。结果强调在调整刺激参数时，除了治疗效果外，还需要考虑情感和认知副作用。此外，本研究通过直接刺激丘脑的关键节点来调节联合和边缘网络，为认知和情感过程引入了一个新的窗口。
