Juvenile Lesions of the Cerebellar Fastigial Nucleus Cause Lasting Cognitive Deficits and Prefrontal Cortex Dysfunction in Adult Rats: Implications for the Cerebellar Cognitive Affective Syndrome.

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.