Abstracts

Rationale: Traditionally the hippocampus has not been considered as part of the neural substrate of working memory (WM), and it has been assumed that WM is preserved in Temporal Lobe Epilepsy (TLE). Recent imaging and neuropsychological data suggest this view may need revision. The aim of this study was to investigate the neural correlates of WM in TLE using functional MRI (fMRI).Methods: We used a visuo-spatial n-back paradigm to compare WM network activity in 38 unilateral hippocampal sclerosis (HS) patients (19 left, 19 right) and in 29 age matched healthy controls. Subjects were required to monitor the locations of dots at a given delay from the original occurrence. There were three 30-second active conditions (0-, 1-, and 2-back). Each active condition started with a 15-second resting baseline. Subjects also performed out-of-scanner tests of WM. Contrasts of interest were modelled to investigate the main effects and interactions of single- and multiple-item WM, and the default mode network in response to increasing task demand. In order to explore the relationship between WM competence and neural activation patterns, a single measure of WM was derived by applying a principal component analysis to the WM measures. The derived WM composite score for each subject was then entered as a regressor of interest in order to test for correlations between areas of fMRI activation and subject performance.Results: Both left and right HS groups performed less well on WM tests than controls (p=0.002 and p=0.006 respectively). The HS groups showed reduced right superior parietal lobe activity during multiple-item WM (p<0.001). No hippocampal activation was found during the n-back paradigm in any group, but the hippocampi progressively deactivated as the task demands increased. This effect was bilateral for controls, whereas the HS patients showed progressive unilateral deactivation contralateral to the side of seizure focus (Figure 1). Regression analysis revealed progressive deactivation of the contralateral hippocampus was associated with better performance in the left HS group (Small Volume Correction 8mm sphere, t = 2.28, p<0.05). Conclusions: Our findings indicate that the cognitive effect of HS impacts on WM and disrupts the underlying neural network. Unlike fMRI studies of episodic memory our data suggest it is deactivation rather than activation of the hippocampus that is the crucial process and indicates that hippocampal function needs to be progressively suppressed to maintain good performance, particularly as the WM load increases.