THE DUAL-SYSTEM HYPOTHESIS OF ANOSOGNOSIA: The Interplay Between Emotional Processing and Self-Monitoring in Neurodegenerative Patients

The ASSESS project is a monocenter, regionally based, study evaluating the pathophysiological/functional processes underlying anosognosia in both AD and bvFTD. The multimodal analysis will be applied to the obtained cognitive, neuroimaging and electrophysiological data in order to describe the mechanistic cascade of anosognosia and their neuronal and electrophysiological biomarkers. Importantly, it has the potential to significantly impact society by: i) addressing a fundamental scientific question towards a causal understanding on how self-awareness emerges in the human brain; and ii) developing a cognitive BCI-system, which will allow us to validated neurophenomenologically EEG biomarkers in anosognosia, and may give us access in later steps to neurofeedback applications for the improvement of self-awareness in early stages of AD and bvFTD, with major social and economic gains.

Inclusion Criteria: PATIENTS and HEALTHY CONTROLS : * French speakers\*, age ≥ 50 ≤ 85 years of age, with normal color vision or corrected-tonormal visual acuity, * Capacity to consent, * Covered by social security, * Ability to undergo MRI scanning, * The spouse / caregiver is able to accompany the subject to both visits and ready to complete questionnaires. * Already in menopause (for women) PATIENTS : 30 patients fulfilling the core diagnostic features of bvFTD; 30 patients fulfilling the core diagnostic features of AD; both in a mild to moderate cognitive and functional severity stage, as determined by: MMSE score greater than or equal to 18, and CDR global score less than or equal to 2, Grober et Buschke: TRGB \< 42 as well as clinical signs (subjective impression) of anosognosia. HEALTHY SUBJECTS (n=40) : MMSE score ≥ 27;TRGB\> 42 Education, gender-, and aged-matched controls. \* Subjects will be administered neuropsychological tests that have been validated for French speakers. Exclusion Criteria: * Illiteracy /unable to count or to read; * Having a neurological disorder, such as: epilepsy, extrapyramidal signs, brain tumour, subdural haematoma, history of head trauma followed by persistent neurological deficits (motor, sensory or cognitive); stroke that has occurred in the last three months; * Report of a present or prior major psychiatric disorder; * Potentially confounding medications, particularly beta-blockers that may have effects on the peripheral nervous system; typically, beta-blockers are used to control heart rhythm, treat angina, and reduce high blood pressure. * Person deprived of their liberty by judicial or administrative decision * Participation in a drug trial or exclusion period of another study * Inability to understand information about the protocol * Meeting brain MRI exclusion criteria (pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin, or body, claustrophobia) or refusing MRI. \* Contra-indication questionnaire to be filled in beforehand.