Altered cerebral activity associated with topiramate and its withdrawal in patients with epilepsy with language impairment: An fMRI study using the verb generation task.
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.
Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Yingying
Y
Tang
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Wei
W
Xia
Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Xiaofeng
X
Yu
Department of Psychosomatic Medicine, Sichuan Province People's Hospital, Chengdu, Sichuan, China.
Bo
B
Zhou
Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Xintong
X
Wu
Huaxi MR Research Center, Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Su
S
Lui
Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Chunyan
C
Luo
Huaxi MR Research Center, Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Xiaoqi
X
Huang
Southwestern Medical Center, University of Texas, Dallas, TX, USA.
Luo
L
Ouyang
Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: chenqin8124@gmail.com.
Qin
Q
Chen
Huaxi MR Research Center, Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Division of Medical Imaging, Faculty of Medicine, University of Liverpool, Liverpool L69 3BX, United Kingdom. Electronic address: qiyonggong@hmrrc.org.cn.
Qiyong
Q
Gong
Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: zhoudong66@yahoo.de.
Dong
D
Zhou
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects; D001931:Brain Mapping / Q000379:methods; D003071:Cognition / Q000502:physiology; D004827:Epilepsy / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000187:drug effects; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives*; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000187:drug effects; D006801:Humans; D007806:Language Disorders / Q000139:chemically induced* / Q000000981:diagnostic imaging* / Q000523:psychology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009483:Neuropsychological Tests; D000077236:Topiramate; D028761:Withholding Treatment; D055815:Young Adult
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose
Epilepsy; Functional magnetic resonance imaging (fMRI); Language; Topiramate (TPM)