Self-appraisal and medial prefrontal activation in early stage Alzheimer’s disease

Introduction Self-referential processing in healthy subjects is related to activation within cortical midline structures, such as the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC; Northoff et al., 2006). Little is know about the engagement of these structures during self-referential processing at different stages of Alzheimer’s disease (AD). The PCC and the MPFC have been found to be activated during a self-appraisal task of adjectives in patients at very early stage of the disease (patients with Mild Cognitive Impairment, MCI; Ries et al., 2006). In contrast, in a similar task, Ruby et al. (2009) have found that mild demented patients activated the dorsal part of the MPFC (DMPFC) to a lesser extent than healthy controls (HC). Ruby et al. did not assess depression symptoms in their patients. Yet, MPFC activations have been found to be modified during self-referential processing in depressed participants (Lemogne et al., 2012). Therefore, in this study, we examined brain correlates of self-appraisal processing in AD patients when controlling for depressive symptoms. Methods Twenty-two mild AD patients and 22 HC matched on age, level of education and gender (respectively: 76±5y; 11±3y; 12M10F) to the AD patients (respectively: 76±7y; 11±3y; 11M11F) were recruited. To control for dementia severity and depression, the participants were administrated the Mattis Dementia Rating (MDR) and the Geriatric Depression Scale (GDS). A self-appraisal task intermixed with a recognition task was administered in an fMRI experimentation. In the self-appraisal task, the participants saw adjectives and had to indicate if the trait describes them (Self-condition; SC) or the King Albert II (for men)/the Queen Fabiola (for women; Other-condition; OC). The adjectives were presented in blocks of 6 items. Participants performed 9 runs consisting in one block of SC and one block of OC followed by a recognition phase where participants were presented with the 12 adjectives that they had just previously seen randomly mixed with 12 new adjectives. They were asked to indicate for each adjective whether they had seen it in the previous task. Statistical analyses focused on the self-appraisal task. Brain activations related to the self appraisal process were isolated in each participant by subtracting brain activation related to OC items from brain activation related to SC items. Then at the group level, we examined differences between groups (HC>AD and AD>HC) and a conjunction analysis examined brain activations that were common to both groups. Preprocessing and statistical analyses were performed with SPM8 (p<.001 uncorrected with a-priori hypotheses). Results GDS scores were similar in AD (3±3) and HC (3±3; T(42) = .1; P=.9) groups. No region was found to be significantly more activated during self-appraisal process in HC than in AD and vice versa when performing direct statistical comparison. Moreover, a conjunction analysis revealed that the VMPFC was the only region commonly activated in AD and HC during self-appraisal process (Punc<.001). Conclusions Our results revealed that AD patients engaged the ventral part of the MPFC to a similar extent than HC during self-appraisal judgements. These results and the results found in patients with MCI by Ries et al. (2006) suggest that at initial stages of AD, patients engaged self-related regions when they performed judgements about themselves as HC do. The divergence with the findings by Ruby et al. (2009) may be related either to the fact that they did not controlled for depressive symptoms or to the fact that their patients showed on average lower scores at the MDR (124) than our patients (127). One can assume that engagement of the self-related regions during self-appraisal judgements in the AD patients depends on the severity of the dementia and/or depressive symptoms. In conclusion, MPFC may be engaged during self-referential processing in very mild AD patients without depressive symptoms. References: Lemogne, C., Delaveau, P., Freton, M., Guionnet, S. & Fossati, P. (2012). Medial prefrontal cortex and the self in major depression. Journal of Affective Disorders, 136, 1-11. Ries, M. L., Schmitz, T.W., Kawahara, T.N., Torgerson, B.M., Trivedi, M.A. & Johnson, S.C. (2006). Task-dependent posterior cingulated activation in mild cognitive impairment. NeuroImage, 29, 485-492. Ruby, P., Collette, F., D’Argembeau, A., Péters, F., Degueldre, C., Balteau, E., Luxen, A., Maquet, P. & Salmon, E. (2009). Perspective taking to assess self-personality: What’s modified in Alzheimer’s disease ? Neurobiology of Aging, 30(10), 1637-1651