The dual-system hypothesis of anosognosia: the interplay between emotional processing and self-monitoring in neurodegenerative patients – NOT_AWARE

The ability to appraise our own performance is a unique component of human functioning. It is impaired in brain diseases responsible for anosognosia, resulting in poor self-appraisal of one's own deficits. Anosognosia negatively impacts on capacity issues, such as treatment compliance and the patients’ ability to deal appropriately with risk situations, with damaging consequences on their quality of life. Furthermore, it places a serious burden on the healthcare systems and may be extremely distressing for the patients’ caregivers. Although initially described after vascular brain lesions and frequently observed in neurodegenerative disorders, such as the Alzheimer's disease (AD) or the behavioral variant of frontotemporal dementia (bvFTD), anosognosia remains an intriguing phenomenon and its neural mechanisms largely unknown. There is, however, evidence in neurodegenerative disorders pointing to frontally-mediated dysfunctions as causes of anosognosia. Here, we build on a convergence of emotional and self-monitoring processes, and specifically explore their role in the emergence of anosognosia in AD and bvFTD patients, thus predicting that unawareness across domains may depend on common processes. In particular, we hypothetize that anosognosia might result from the inability to establish the linkage between emotional arousal and self-monitoring (that would normally trigger adaptive behaviors), due to critical connectivity impairments in the uncinate fasciculus in both AD and bvFTD(regardless to the nature of the deficits to which the patients are unaware). Indeed, by virtue of its connectivity, linking limbic with frontal/executive systems, one might expect that the uncinate fasciculus plays a major role in the interplay between emotional arousal and self-monitoring. Our main scientific, clinical and technological goals are: 1) To test the interplay between self-monitoring and autonomic reactivity (as a proxy of emotional arousal) and then determine whether it is disturbed in both groups of patients relative to healthy controls, and whether it correlates with the patients’ anosognosia level, as measured by standard scales (STUDY 1); 2) To test whether structural and functional damage to the uncinate fasciculus correlate with the patients’ anosognosia level, and whether it may be critical for the emergence of this neurological syndrome (STUDY 2); and 3) To establish the neurophysiological markers of anosognosia in order to further develop a cognitive Brain-computer interface (BCI) aimed at monitoring patients’ self-awareness in real time (STUDY 3). Our methodological approach will combine behavioral with advanced electrophysiological and neuroimaging methods that all tap on self-monitoring abilities and their relation to both emotional arousal and measures of self-appraisal accuracy. Importantly, recent evidence supports the brain’s ability to modify and learn even in early stages of dementia, which may thus constitute a critical window for BCI interventions in neurodegenerative patients. Typically, BCIs acquire brain waves from an EEG amplifier and then utilize the biomarkers derived from the brain signal and adapt to the user’s performance. The goal is to apply neuro-physiological regulation to foster cortical reorganization, thus promoting neural plasticity. The development of a cognitive BCI monitoring anosognosia is a necessary step to design specific neurofeedback strategies improving self-awareness. In sum, this project 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 validate 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.