Tang Yingying, Xia Wei, Yu Xiaofeng, Zhou Bo, Wu Xintong, Lui Su, Luo Chunyan, Huang Xiaoqi, Ouyang Luo, Chen Qin, Gong Qiyong, Zhou Dong
Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Epilepsy Behav. 2016 Jun;59:98-104. doi: 10.1016/j.yebeh.2016.03.013. Epub 2016 Apr 26.
Topiramate (TPM) is well recognized for its negative effects on language in healthy volunteers and patients with epilepsy. The aim of this study was to investigate the brain activation and deactivation patterns in TPM-treated patients with epilepsy with language impairment and their dynamic alteration during TPM withdrawal using functional magnetic resonance imaging (fMRI) with the verb generation task (VGT).
Twelve patients with epilepsy experiencing subjective language disfluency after TPM add-on treatment (TPM-on) and thirty sex- and age-matched healthy controls (HCs) were recruited. All subjects received a battery of neuropsychological tests and an fMRI scan with the VGT. Withdrawal of TPM was attempted in all patients. Only six patients reached complete withdrawal without seizure relapses (TPM-off), and these patients underwent a reassessment of neuropsychological and neuroimaging tests.
The neuropsychological tests demonstrated objective language impairments in TPM-on patients. Compared with the HCs, the bilateral medial prefrontal cortex and the posterior midline and lateral parts of the default mode network (DMN) (including the bilateral posterior cingulate cortex (PCC), the right medial prefrontal cortex, the right angular gyrus, the right inferior temporal gyrus, and the bilateral supramarginal gyrus) in TPM-on patients failed to deactivate during the VGT. Their task-induced activation patterns were largely similar to those of the HCs. After TPM withdrawal, partial improvement of both task-induced deactivation of the DMN (the left parahippocampal gyrus and the bilateral PCC) and task-related activation of the language network (the right middle frontal gyrus and the left superior occipital gyrus) was identified along with partial improvement of neuropsychological tests.
Task-induced deactivation is a more sensitive neuroimaging biomarker for the impaired language performance in patients administered TPM than task-induced activation. Disruption and reorganization of the balance between the DMN and the cortical language networks are found along with reversible TPM-related language impairment. These results may suggest an underlying brain mechanism by which TPM affects cognitive function.
托吡酯（TPM）对健康志愿者和癫痫患者语言功能的负面影响已得到充分认识。本研究旨在使用功能磁共振成像（fMRI）及动词生成任务（VGT），探究接受TPM治疗且有语言障碍的癫痫患者的脑激活和失活模式，以及TPM撤药期间它们的动态变化。
招募了12例在加用TPM治疗后出现主观语言不流畅的癫痫患者（TPM治疗组）和30名年龄及性别匹配的健康对照者（HCs）。所有受试者均接受了一系列神经心理学测试以及VGT的fMRI扫描。所有患者均尝试停用TPM。只有6例患者完全停药且无癫痫复发（TPM停药组），这些患者接受了神经心理学和神经影像学测试的重新评估。
神经心理学测试显示TPM治疗组患者存在客观语言障碍。与HCs相比，TPM治疗组患者在VGT期间双侧内侧前额叶皮质以及默认模式网络（DMN）的后中线和外侧部分（包括双侧后扣带回皮质（PCC）、右侧内侧前额叶皮质、右侧角回、右侧颞下回和双侧缘上回）未能失活。他们的任务诱导激活模式与HCs基本相似。TPM撤药后，DMN（左侧海马旁回和双侧PCC）的任务诱导失活以及语言网络（右侧额中回和左侧枕上回）的任务相关激活均有部分改善，同时神经心理学测试也有部分改善。
对于接受TPM治疗的患者，任务诱导失活是比任务诱导激活更敏感的语言功能受损神经影像学生物标志物。发现DMN与皮质语言网络之间的平衡被破坏和重新组织，同时伴有与TPM相关的可逆性语言障碍。这些结果可能提示了TPM影响认知功能的潜在脑机制。
