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Brain Advance Access originally published online on August 6, 2007
Brain 2007 130(9):2327-2342; doi:10.1093/brain/awm166
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© The Author (2007). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Consequences of hippocampal damage across the autobiographical memory network in left temporal lobe epilepsy

Donna Rose Addis1,2,3, Morris Moscovitch2,3 and Mary Pat McAndrews1,2

1Toronto Western Research Institute, 2Department of Psychology, University of Toronto and 3Rotman Research Institute, Baycrest Centre for Geriatric Care, Toronto, ON, Canada

Correspondence to: Mary Pat McAndrews, Neuropsychology Clinic, 4F-409 Toronto Western Hospital, 399 Bathurst St., Toronto, ON, Canada M5T 2S8. E-mail: mcandrws{at}uhnres.utoronto.ca

Lesion and neuroimaging evidence suggests the hippocampus (HC) is a crucial node in the neural network supporting autobiographical memory (AM) retrieval, and thus focal damage to the HC may have functional consequences for structures throughout the network. Using fMRI, we examined the impact of hippocampal damage on the engagement and connectivity of the AM network in 11 patients with left temporal lobe epilepsy (mean age of onset of seizures, 24 years) with significant left hippocampal atrophy and a mild AM deficit. All investigations were completed pre-surgically. The fMRI paradigm comprised three conditions: (i) retrieving specific AMs in response to personalized cues obtained during a pre-scan interview; (ii) a sentence completion control task; and (iii) a size discrimination control task. AM-related activity (relative to the control tasks) was significantly reduced in patients compared to controls, in residual hippocampal tissue and across the AM network, including the medial prefrontal cortex, temporal poles, retrosplenial and lateral parietal cortex. Furthermore, the strength of connections involving the left HC was also reduced in patients. In contrast, connections between extra-hippocampal nodes, such as left retrosplenial and medial prefrontal cortex, were strengthened in patients, possibly reflecting a compensatory mechanism. Our findings confirm that the left HC is a crucial node in the AM network, possibly playing a dominant role in initiating the engagement of other network nodes, and its damage has significant consequences for the functional organization and connectivity of the neural network supporting AM retrieval.

Key Words: autobiographical memory; hippocampus; temporal lobe epilepsy; effective connectivity; fMRI

Abbreviations: AI, autobiographical interview; AM, autobiographical memory; BOLD, blood-oxygenation level dependent; HC, hippocampus; ICS, inter-collicular sulcus; LMPFC, left medial prefrontal cortex; LTLE, left TLE; MPC, medial parietal cortex; MTL, medial temporal lobe; PHG, parahippocampal gyrus; ROI, region of interest; tPOLE, temporal pole; TPJ, temporoparietal junction; TLE, temporal lobe epilepsy

Received March 9, 2007. Revised June 1, 2007. Accepted June 28, 2007.


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