Sidhu, MK; (2015) Episodic Memory in Temporal Lobe Epilepsy. Doctoral thesis , UCL (University College London).

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Abstract

Individuals with temporal lobe epilepsy (TLE) have significant material specific episodic memory impairments with greater verbal and visual memory deficits accompanying left and right TLE respectively. More recently, however, widespread cognitive deficits have been described in patients with TLE in keeping with morphological and functional abnormalities that extend beyond the temporal lobes. Functional magnetic resonance imaging (fMRI) has demonstrated reorganisation of memory encoding networks within the temporal lobe in TLE, but little is known of the extra-temporal networks in these patients. Memory fMRI as a tool for predicting memory decline after anterior temporal lobe resection has been explored but a clinically applicable algorithm has yet to be defined. Fewer studies have described the changes in the memory encoding networks after temporal lobe surgery. This thesis presents methodological developments and novel applications to describe the pre-operative and post-operative verbal and visual memory networks in those with unilateral TLE. Pre-operatively, I investigated extra-temporal areas of memory reorganisation in left and right TLE patients, quantitatively compared to healthy controls. Novel findings include the ‘efficiency’ of extra-temporal reorganisation to successful memory formation. Next, using clinical parameters such as age at onset of epilepsy, epilepsy duration and seizure frequency as continuous regressors, I described the factors affecting verbal and visual memory reorganisation in TLE. In a separate pre-operative study, I used an alternative fMRI analysis method, multi-voxel pattern analysis (MVPA) that focuses on the patterns of activity across voxels 4 in specific brain regions that are associated with individual memory traces. I used MVPA-fMRI to assess the functional integrity of the hippocampi and other medial temporal lobe structures in patients with unilateral TLE. Next, I explored the predictive ability of temporal and extra-temporal activations in predicting post-operative verbal memory decline in left and right TLE patients and described a method of using memory fMRI as a clinically applicable tool in patients who had anterior temporal lobe resection. Finally, I explored memory encoding network plasticity four and 12 months after anterior temporal lobe resection. In this study, controls were also scanned at similar time intervals to patients. I report for the first time, dynamic changes in the memory encoding network four and 12 months after surgery, relative to changes in controls. Novel findings also include the efficiency of these post-operative networks. In this thesis, I also discuss methodological constraints, clinical applications and future directions.

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