Decker Franziska Maria, Jelinek Jonas, Fogaing Kamgaing Franck, Alam Mesbah, Al-Afif Shadi, Krauss Joachim K, Schwabe Kerstin, Hermann Elvis J
Department of Neurosurgery, Hannover Medical School, 30625 Hannover, Germany.
Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany.
Brain Sci. 2025 Aug 13;15(8):862. doi: 10.3390/brainsci15080862.
Cerebellar cognitive affective syndrome (CCAS) is a well-recognized postoperative complication in children following resection of brain tumors involving cerebellar midline structures. The fastigial nucleus is regarded as relevant, but the underlying neural mechanisms remain incompletely understood. This study uses an oddball paradigm designed to model attentional and learning processes relevant to CCAS to investigate how early-life lesions of the fastigial nucleus in rats affect cognitive performance and neural information processing in the medial prefrontal cortex (mPFC) in adulthood. Fastigial lesions were induced stereotaxically in 23-day-old male Sprague Dawley rats [ = 9]. Naïve [ = 9] and sham-lesioned rats [ = 6] served as controls. As adults, all rats were trained in an oddball paradigm requiring discrimination of a rare target tone from a rare distractor and a frequent standard tone. Local field potentials (LFPs) were recorded from electrodes implanted in the mPFC during oddball testing and event-related potentials (ERPs) were analyzed. Rats with fastigial lesions required significantly more training days to reach ≥70% correct performance criterion. In fully trained rats, analysis of neural recordings during behavioral testing revealed reduced ERP amplitudes and prolonged latencies of late ERP components after target stimuli. Developmental fastigial lesions lead to lasting deficits in cognitive learning capacity and neural mPFC processing, highlighting the integrative role of cerebellar midline structures in higher-order cognitive function and sensory discrimination. This rodent model provides a valuable translational platform for further investigating the neural basis of CCAS and may inform neurosurgical strategies aimed at minimizing cognitive sequelae in children undergoing cerebellar tumor resection.
小脑认知情感综合征（CCAS）是儿童脑肿瘤切除术后累及小脑中线结构时一种公认的并发症。顶核被认为与之相关，但其潜在的神经机制仍未完全明确。本研究采用一种oddball范式，旨在模拟与CCAS相关的注意力和学习过程，以研究大鼠幼年时顶核损伤如何影响成年内侧前额叶皮质（mPFC）的认知表现和神经信息处理。对23日龄雄性Sprague Dawley大鼠（n = 9）进行立体定位诱导顶核损伤。未处理的大鼠（n = 9）和假损伤大鼠（n = 6）作为对照。成年后，所有大鼠均接受oddball范式训练，要求区分罕见的目标音、罕见干扰音和频繁出现的标准音。在oddball测试期间，从植入mPFC的电极记录局部场电位（LFP），并分析事件相关电位（ERP）。顶核损伤的大鼠达到≥70%正确表现标准所需的训练天数显著更多。在训练充分的大鼠中，行为测试期间的神经记录分析显示，目标刺激后ERP振幅降低，晚期ERP成分潜伏期延长。发育性顶核损伤导致认知学习能力和神经mPFC处理的持久缺陷，突出了小脑中线结构在高阶认知功能和感觉辨别中的整合作用。这种啮齿动物模型为进一步研究CCAS的神经基础提供了一个有价值的转化平台，并可能为旨在尽量减少小脑肿瘤切除儿童认知后遗症的神经外科策略提供参考。
