Ventromedial‐frontopolar prefrontal cortex atrophy correlates with insight loss in frontotemporal dementia and Alzheimer's disease

Abstract

Loss in insight is a major feature of frontotemporal dementia (FTD) but has been investigated relatively little. More importantly, the neural basis of insight loss is still poorly understood. The current study investigated insight deficit profiles across a large cohort of neurodegenerative patients (n = 81), including FTD and Alzheimer's disease (AD) patients. We employed a novel insight questionnaire, which tapped into changes across different domains: social interaction, emotion, diagnosis/treatment, language, and motivation. FTD subtypes varied considerably for insight loss, with the behavioral variant worst and the progressive non-fluent variant least affected. All other subtypes and AD showed milder but consistent insight loss. Voxel-based morphometry analysis revealed that overall insight loss correlated with ventromedial and frontopolar prefrontal atrophy, with exception of social interaction and emotion insight loss, which additionally correlated with lateral temporal and amygdala atrophy, respectively. Our results show that patients with neurodegenerative conditions show variable loss of insight, with ventromedial and frontopolar cortex regions appearing to be particularly important for insight.

Self-awareness in neurodegenerative disease relies on neural structures mediating reward-driven attention

“…Our findings both converge and diverge from previous voxelbased morphometry studies in patients with neurodegenerative disease that have demonstrated involvement of specific prefrontal regions in self-awareness Hornberger et al, 2014). Compared with previous studies, in the current study we had a substantially larger sample size, and used a psychometrically validated instrument for measuring self-awareness that has previously been confirmed useful in anosognostic patients.…”

“…These regions were previously implicated in studies of impaired self-awareness in neurodegenerative diseases, even in studies investigating diverse objects of self-awareness such as movement, emotion, and cognition (Salmon et al, 2006;Shibata et al, 2008;Hornberger et al, 2014). Interestingly, self-awareness of abnormal movements is more impaired in patients with Huntington's disease than those with Parkinson's disease, a difference attributed to the greater pathology of orbitofrontal-limbic regions in Huntington's disease (Sitek et al, 2011).…”

“…While some studies point to medial-orbital involvement (Shibata et al, 2008;Rosen et al, 2010;Hornberger et al, 2014), others point to dorsolateral PFC involvement (Reed et al, 1993). As highlighted by a recent review, studies measuring awareness for cognitive test-performance report more frontal involvement, whereas studies measuring awareness for personality and behavioural changes pointed to lateral temporal-parietal involvement (Zamboni and Wilcock, 2011).…”

Feeling, learning from and being aware of inner states: interoceptive dimensions in neurodegeneration and stroke

“…Although this metacognitive dimension has not been examined in neurological populations, impaired awareness and diminished insight are core features of dementia [30,31]. Thus, we predicted that bvFTD and AD would be worse than controls at estimating self-performance.…”

Does dysfunction of the mirror neuron system contribute to symptoms in amyotrophic lateral sclerosis?

“…In particular, findings in behavioral variant of frontotemporal dementia (bvFTD), which shows severe loss of empathy even recognized in the diagnostic criteria (Piguet et al , 2011, Rascovsky et al , 2011, report that loss of empathy is more attributed to atrophy in the ventral medial prefrontal cortex (vMPFC), including anterior cingulate regions and not the MNS system per se (Shamay-Tsoory et al , 2004, Lough et al , 2006. Interestingly, similar vMPFC atrophy in bvFTD has been attributed to emotional blunting (Berenbaum et al , 1987, Rosen et al , 2002 and loss of insight (Hornberger et al , 2014), highlighting the critical function of this region in affective perspective-taking (i.e. putting yourself in someone else's shoes), which is required for empathy to occur.…”