d'Angelo Camilla, Eagle Dawn M, Coman Cristina-M, Robbins Trevor W
Department of Psychology, University of Cambridge, Cambridge, UK.
Behavioural and Clinical Neuroscience Institute (BCNI), University of Cambridge, Cambridge, UK.
Brain Neurosci Adv. 2017 Sep 27;1:2398212817733403. doi: 10.1177/2398212817733403. eCollection 2017.
Excessive checking is a common, debilitating symptom of obsessive-compulsive disorder. To further examine cognitive processes underpinning checking behaviour, and clarify how and why checking develops, we designed a novel operant paradigm for rats, the observing response task. The present study used the observing response task to investigate checking behaviour following excitotoxic lesions of the medial prefrontal cortex, nucleus accumbens core and dorsal striatum, brain regions considered to be of relevance to obsessive-compulsive disorder.
In the observing response task, rats pressed an 'observing' lever for information (provided by light onset) about the location of an 'active' lever that provided food reinforcement. Following training, rats received excitotoxic lesions of the regions described above and performance was evaluated post-operatively before histological processing.
Medial prefrontal cortex lesions selectively increased functional checking with a less-prominent effect on non-functional checking and reduced discrimination accuracy during light information periods. Rats with nucleus accumbens core lesions made significantly more checking responses than sham-lesioned rats, including both functional and non-functional checking. Dorsal striatum lesions had no direct effect on checking per se, but reduced both active and inactive lever presses, and therefore changed the relative balance between checking responses and instrumental responses.
These results suggest that the medial prefrontal cortex and nucleus accumbens core are important in the control of checking, perhaps via their role in processing uncertainty of reinforcement, and that dysfunction of these regions may therefore promote excessive checking behaviour, possibly relevant to obsessive-compulsive disorder.
过度检查是强迫症常见的、使人衰弱的症状。为了进一步研究支撑检查行为的认知过程，并阐明检查行为如何以及为何发展，我们为大鼠设计了一种新颖的操作性范式——观察反应任务。本研究使用观察反应任务来探究内侧前额叶皮质、伏隔核核心区和背侧纹状体兴奋性毒性损伤后（这些脑区被认为与强迫症相关）的检查行为。
在观察反应任务中，大鼠按压一个“观察”杠杆以获取关于提供食物强化的“活动”杠杆位置的信息（由灯光亮起提供）。训练后，大鼠接受上述区域的兴奋性毒性损伤，并在术后进行组织学处理前评估其表现。
内侧前额叶皮质损伤选择性地增加了功能性检查，对非功能性检查的影响较小，并降低了灯光信息期的辨别准确性。伏隔核核心区损伤的大鼠比假手术损伤的大鼠做出了显著更多的检查反应，包括功能性和非功能性检查。背侧纹状体损伤本身对检查没有直接影响，但减少了活动和非活动杠杆的按压次数，因此改变了检查反应与工具性反应之间的相对平衡。
这些结果表明，内侧前额叶皮质和伏隔核核心区在控制检查行为方面很重要，可能是通过它们在处理强化不确定性方面的作用，因此这些区域的功能障碍可能会促进过度检查行为，这可能与强迫症有关。
