Yu-Hsuan A Chang1,2, Anisa Marshall2, Naeim Bahrami1,2, Kushagra Mathur2, Sogol S Javadi2, Anny Reyes2,3, Manu Hegde4,5, Jerry J Shih6,7, Brianna M Paul4,5, Donald J Hagler2,8, Carrie R McDonald1,2,3,7. 1. Department of Psychiatry, University of California, San Diego, California. 2. Center for Multimodal Imaging and Genetics, University of California, San Diego, California. 3. San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, California. 4. Department of Neurology, University of California, San Francisco, California. 5. UCSF Comprehensive Epilepsy Center, San Francisco, California. 6. Department of Neurosciences, University of California, San Diego, California. 7. UCSD Comprehensive Epilepsy Center, San Diego, California. 8. Department of Radiology, University of California, San Diego, California.
Abstract
OBJECTIVES: Temporal lobe epilepsy (TLE) is known to affect large-scale gray and white matter networks, and these network changes likely contribute to the verbal memory impairments observed in many patients. In this study, we investigate multimodal imaging patterns of brain alterations in TLE and evaluate the sensitivity of different imaging measures to verbal memory impairment. METHODS: Diffusion tensor imaging (DTI), volumetric magnetic resonance imaging (vMRI), and resting-state functional MRI (rs-fMRI) were evaluated in 46 patients with TLE and 33 healthy controls to measure patterns of microstructural, structural, and functional alterations, respectively. These measurements were obtained within the white matter directly beneath neocortex (ie, superficial white matter [SWM]) for DTI and across neocortex for vMRI and rs-fMRI. The degree to which imaging alterations within left medial temporal lobe/posterior cingulate (LMT/PC) and left lateral temporal regions were associated with verbal memory performance was evaluated. RESULTS: Patients with left TLE and right TLE both demonstrated pronounced microstructural alterations (ie, decreased fractional anisotropy [FA] and increased mean diffusivity [MD]) spanning the entire frontal and temporolimbic SWM, which were highly lateralized to the ipsilateral hemisphere. Conversely, reductions in cortical thickness in vMRI and alterations in the magnitude of the rs-fMRI response were less pronounced and less lateralized than the microstructural changes. Both stepwise regression and mediation analyses further revealed that FA and MD within SWM in LMT/PC regions were the most robust predictors of verbal memory, and that these associations were independent of left hippocampal volume. SIGNIFICANCE: These findings suggest that microstructural loss within the SWM is pronounced in patients with TLE, and injury to the SWM within the LMT/PC region plays a critical role in verbal memory impairment. Wiley Periodicals, Inc.
OBJECTIVES:Temporal lobe epilepsy (TLE) is known to affect large-scale gray and white matter networks, and these network changes likely contribute to the verbal memory impairments observed in many patients. In this study, we investigate multimodal imaging patterns of brain alterations in TLE and evaluate the sensitivity of different imaging measures to verbal memory impairment. METHODS: Diffusion tensor imaging (DTI), volumetric magnetic resonance imaging (vMRI), and resting-state functional MRI (rs-fMRI) were evaluated in 46 patients with TLE and 33 healthy controls to measure patterns of microstructural, structural, and functional alterations, respectively. These measurements were obtained within the white matter directly beneath neocortex (ie, superficial white matter [SWM]) for DTI and across neocortex for vMRI and rs-fMRI. The degree to which imaging alterations within left medial temporal lobe/posterior cingulate (LMT/PC) and left lateral temporal regions were associated with verbal memory performance was evaluated. RESULTS:Patients with left TLE and right TLE both demonstrated pronounced microstructural alterations (ie, decreased fractional anisotropy [FA] and increased mean diffusivity [MD]) spanning the entire frontal and temporolimbic SWM, which were highly lateralized to the ipsilateral hemisphere. Conversely, reductions in cortical thickness in vMRI and alterations in the magnitude of the rs-fMRI response were less pronounced and less lateralized than the microstructural changes. Both stepwise regression and mediation analyses further revealed that FA and MD within SWM in LMT/PC regions were the most robust predictors of verbal memory, and that these associations were independent of left hippocampal volume. SIGNIFICANCE: These findings suggest that microstructural loss within the SWM is pronounced in patients with TLE, and injury to the SWM within the LMT/PC region plays a critical role in verbal memory impairment. Wiley Periodicals, Inc.
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