In search of autobiographical memories: A PET study in the frontal variant of frontotemporal dementia.

Patients suffering from frontal variant of frontotemporal dementia (fv-FTD) undergo autobiographical amnesia encompassing all time periods. We previously demonstrated in a group of 20 fv-FTD patients that this impairment involved deficits in executive function and semantic memory for all periods as well as new episodic learning and behavioural changes for the most recent period covering the last 12 months [Matuszewski, V., Piolino, P., de la Sayette, V., Lalevée, C., Pélerin, A., Dupuy, B., et al. (2006). Retrieval mechanisms for autobiographical memories: Insights from the frontal variant of frontotemporal dementia, Neuropsychologia, 44, 2386-2397]. The aim of the present study was to unravel the neural bases of this impairment by mapping in a subgroup of patients correlations between resting-state brain glucose utilization measured by FDG-PET and measures of autobiographical memory (AM) using the TEMPau task which is designed to gauge personal event recollection across five life time periods. Like in our previous report, the group of patients was impaired regardless of time periods compared to healthy subjects providing generic memories instead of event specific sensory-perceptual-affective details, i.e., episodic memories. New data showed that the patients were also impaired in sense of reliving and self-perspective during retrieval. The cognitivo-metabolic correlations between the AM score and resting normalized FDG-Uptake were computed using statistical parametric mapping (SPM2) and controlling for age and dementia severity. They revealed that AM deficits were mainly subserved by the dysfunction of left-sided orbitofrontal and also temporal neocortical areas whatever the period. Additional analysis showed that specific memories were associated with left orbitofrontal areas whereas generic memories were mainly associated with the left temporal pole. This study supports the view that fv-FTD patients undergo a breakdown of generative processes which relies regardless of the remoteness on the left orbitofrontal cortex and temporal neocortex to gain access to AM.