Autobiographical memory paradigms have been increasingly used to study the behavioral and neuroanatomical correlates of human remote memory. Although there are numerous functional neuroimaging studies on this topic, relatively few studies of patient samples exist, with heterogeneity of results owing to methodological variability. In this study, fronto-temporal lobar degeneration (FTLD), a form of dementia affecting regions crucial to autobiographical memory, was used as a model of autobiographical memory loss. We emphasized the separation of episodic (recollection of specific event, perceptual, and mental state information) from semantic (factual information unspecific in time and place) autobiographical memory, derived from a reliable method for scoring transcribed autobiographical protocols, the Autobiographical Interview [Levine, B., Svoboda, E., Hay, J., Winocur, G., & Moscovitch, M. Aging and autobiographical memory: Dissociating episodic from semantic retrieval. Psychology and Aging, 17, 677–689, 2002]. Patients with the fronto-temporal dementia (FTD) and mixed fronto-temporal and semantic dementia (FTD/SD) variants of FTLD were impaired at reconstructing episodically rich autobiographical memories across the lifespan, with FTD/SD patients generating an excess of generic semantic autobiographical information. Patients with progressive nonfluent aphasia were mildly impaired for episodic autobiographical memory, but this impairment was eliminated with the provision of structured cueing, likely reflecting relatively intact medial-temporal lobe function, whereas the same cueing failed to bolster the FTD and FTD/SD patients' performance relative to that of matched comparison subjects. The pattern of episodic, but not semantic, autobiographical impairment was enhanced with disease progression on 1- to 2-year follow-up testing in a subset of patients, supplementing the cross-sectional evidence for specificity of episodic autobiographical impairment with longitudinal data. This behavioral pattern covaried with volume loss in a distributed left-lateralized posterior network centered on the temporal lobe, consistent with evidence from other patient and functional neuroimaging studies of autobiographical memory. Frontal lobe volumes, however, did not significantly contribute to this network, suggesting that frontal contributions to autobiographical episodic memory may be more complex than previously appreciated.

The issue of whether the hippocampus and related structures in the medial-temporal lobe (MTL) play a temporary or permanent role in autobiographical episodic memory remains unresolved. One long-standing belief is that autobiographical memory (AM), like semantic memory, is initially dependent on the MTL but ultimately can be retained and recovered independently of it. However, evidence that hippocampal amnesia results in severe loss of episodic memory for a lifetime of personally experienced events suggests otherwise. To test the opposing views, we conducted detailed investigations of autobiographical episodic memory in people with amnesia resulting from MTL lesions of varying extent. By combining precise quantification of MTL and neocortical volumes with sensitive measures of recollection of one's personal past, we show that the severity of episodic, but not semantic, AM loss is best accounted for by the degree of hippocampal damage and less likely related to additional neocortical compromise.

Recent research suggests that the hippocampus is not needed for the maintenance and recovery of extensively used environments learned long ago. Instead, a network of neo-cortical regions differentially supports memory for location-navigation knowledge and visual appearance of well-known places. In this study, we present a patient, S. B., who was diagnosed with probable Alzheimer's disease long after retiring from his 40 years as a taxi driver in downtown Toronto, a place that he has visited rarely, if ever, in the last decade. His performance was compared to that of two other retired taxi drivers, L. R., who developed encephalitis after retirement, and I. L., who is without neurological illness, and a group of eight healthy control participants who were never taxi drivers but all of whom worked or lived in downtown Toronto until at least 10 years ago. Despite S. B.'s widespread atrophy, which has affected mainly his hippocampus and part of his occipitotemporal cortex, he performed at least as well as all other participants on remote memory tests of spatial location and mental navigation between well-known Toronto landmarks. Unlike the comparison populations, however, he was unable to discriminate between the appearances of landmarks that he had visited frequently in his many years as a taxi driver from unknown buildings. This profound deficit extended to famous world landmarks but not to famous faces and does not appear to be semantic in nature. These findings add further support to the claim that the hippocampus is not necessary for mental navigation of old environments and suggest that expertise is not sufficient to protect against landmark agnosia.