Abstracts

Rationale: Traditionally, working memory is considered unimpaired in temporal lobe epilepsy (TLE) but recent data show a decline in patients with hippocampal sclerosis (HS). Functional MRI (fMRI) demonstrates bilateral middle frontal gyrus (MFG) and superior parietal lobule (SPL) activation during a visuospatial working memory task with reduced activation of the right SPL seen in patients with either left or right HS. The aim of the present study was investigate the underlying structural correlates of the decline in working memory.Methods: We studied 36 patients with unilateral HS (18 left, 18 right) and 26 age matched controls. Subjects underwent structural imaging, diffusion tensor imaging, a visuospatial 'n-back' fMRI paradigm and neuropsychological assessment. A single measure of working memory was derived using a principal component analysis from in scanner performance on the n-back task and out-of-scanner performance with digit span (backwards), gesture span and motor sequencing. Voxel-Based Morphometry (VBM) and Tract-Based Spatial Statistics (TBSS) were used to determine areas of atrophy and loss of integrity in white matter tracts. The working memory score was used as a regressor in both whole-brain voxelwise analysis and TBSS analysis to determine areas where loss of structural integrity was correlated with a decline in working memory.Results: Patients with both left HS and right HS showed a decline in working memory compared to healthy controls (p=0.002, p=0.004 respectively). VBM demonstrated grey matter atrophy in left and right temporal lobes respectively in the patient groups. Grey matter atrophy was also seen in the SPL bilaterally (left HS) or on the right (right HS). VBM and TBSS showed widespread white matter atrophy and loss of integrity in both patient groups particularly in the ipsilateral hemisphere. In the left HS group, whole-brain analysis showed a decline in fractional anisotropy (FA) within the cingulum and MFG bilaterally and right temporal lobe and increases in mean diffusivity (MD) in the cingulum and SPL/supramarginal gyrus bilaterally and right temporal lobe were correlated with a decline in working memory. Regression with TBSS showed decline in FA in the cingulum, superior longitudinal fasiculus and corpus callosum bilaterally were correlated with weaker working memory. In the right HS group, only a small cluster of reduced FA in the right posterior parietal region was identified in the whole brain analysis.Conclusions: This study demonstrates that working memory is impaired in patients with HS. In both left and right HS, grey matter atrophy is seen in the right SPL, a region that is activated less in patients during working memory tasks. There is widespread loss of white matter volume and integrity in keeping with the decline in working memory which has a distributed cognitive network. However, white matter changes within the MFG and SPL bilaterally and the interconnecting white matter tracts can be demonstrated. These are the same areas identified during fMRI as important for working memory tasks, and the changes correlate with decline in performance.