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Self-referential processing relies mainly on the medial prefrontal cortex (MPFC) and enhances memory encoding (i.e., Self-Reference Effect, SRE) as it improves the accuracy and richness of remembering in both young and older adults. However, studies on age-related changes in the neural correlates of the SRE on the subjective (i.e., autonoetic consciousness) and the objective (i.e., source memory) qualitative features of episodic memory are lacking. In the present fMRI study, we compared the effects of a self-related (semantic autobiographical memory task) and a non self-related (general semantic memory task) encoding condition on subsequent episodic memory retrieval. We investigated encoding-related activity during each condition in two groups of 19 younger and 16 older adults. Behaviorally, the SRE improved subjective memory performance in both groups but objective memory only in young adults. At the neural level, a direct comparison between self-related and non self-related conditions revealed that SRE mainly activated the cortical midline system, especially the MPFC, in both groups. Additionally, in older adults and regardless of the condition, greater activity was found in a fronto-parietal network. Overall, correlations were noted between source memory performance and activity in the MPFC (irrespective of age) and visual areas (mediated by age). Thus, the present findings expand evidence of the role of the MPFC in self-referential processing in the context of source memory benefit in both young and older adults using incidental encoding via semantic autobiographical memory. However, our finding suggests that its role is less effective in aging.

Autobiographical memory (AM) comprises representation of specific (episodic) and generic personal information (semantic). Depression is characterized by a shift from episodic to semantic AM retrieval (overgeneralization). Theoretical models have proposed that this effect could be linked to reduced executive resources. Moreover, overgeneral memories, accompanied by a negativity bias in depression, lead to a pervasive negative self-representation. Even in non clinical populations executive functions and AM specificity are closely linked, and overgeneral memories could result in depressive emotional responses. We made the hypothesis that healthy subjects showing a rigid negative self-image would mimic the neurocognitive profile of patients. We measured executive functions and the self-image in young healthy subjects, and recorded their brain activity, by means of fMRI, while they retrieved episodic AMs. We report that a more rigid negative self-image corresponds to lower executive functions and less vivid specific memories. Moreover, higher negative self-image is accompanied by attenuated activity in the left ventrolateral prefrontal and in the anterior cingulate cortex, that have been repeatedly shown to exhibit altered functionality in depression. Activity in these regions, on the contrary, positively correlates with executive and memories performances, in agreement with their role in executive functions and AM retrieval. We claim that rigid negative self-image could represent a marker or a vulnerability trait of depression that is linked to reduced executive functions efficiency and to episodic AM decline. Our results are encouraging for psychotherapeutic approaches promoting cognitive flexibility in depression and other psychiatric disorders.