  Although neurocognitive models have been proposed to explain anosognosia in
Alzheimer's disease (AD), the neural cascade responsible for its origin in the
human brain remains unknown. Here, we build on a mechanistic dual-path
hypothesis that brings error-monitoring and emotional processing systems as key
elements for self-awareness, with distinct impacts on the emergence of
anosognosia in AD. Proceeding from the notion of anosognosia as a dimensional
syndrome, ranging from the lack of concern about one's own deficits (i.e.,
anosodiaphoria) to the complete lack of awareness of deficits, our hypothesis
states that (i) unawareness of deficits would result from a failure in the
error-monitoring system, whereas (ii) anosodiaphoria would more likely result
from an imbalance between emotional processing and error-monitoring systems. In
the first case, a synaptic failure in the error-monitoring system, in which the
cingulate cortex plays a major role, would have a negative impact on error (or
deficits) awareness, preventing patients from becoming aware of their
condition. In the second case, an impairment in the emotional processing
system, in which the amygdala and orbitofrontal cortex play a major role, would
prevent patients from monitoring the internal milieu for relevant errors (or
deficits) and assigning appropriate value to them, thus biasing their impact on
the error-monitoring system. Our hypothesis stems from two scientific premises.
One comes from preliminary results in AD patients showing a synaptic failure in
the error-monitoring system and decline of awareness at the time of diagnosis.
Another comes from the somatic marker hypothesis, which proposes that emotional
signals are critical to adaptive behavior. Further exploration will be of great
interest to illuminate the foundations of self-awareness and improve our
understanding of the underlying mechanisms of anosognosia in AD.
