“I Know that You Know that I Know”: Neural Substrates Associated with Social Cognition Deficits in DM1 Patients

Abstract

Myotonic dystrophy type-1 (DM1) is a genetic multi-systemic disorder involving several organs including the brain. Despite the heterogeneity of this condition, some patients with non-congenital DM1 can present with minimal cognitive impairment on formal testing but with severe difficulties in daily-living activities including social interactions. One explanation for this paradoxical mismatch can be found in patients’ dysfunctional social cognition, which can be assessed in the framework of the Theory of Mind (ToM). We hypothesize here that specific disease driven abnormalities in DM1 brains may result in ToM impairments. We recruited 20 DM1 patients who underwent the “Reading the Mind in the Eyes” and the ToM-story tests. These patients, together with 18 healthy controls, also underwent resting-state functional MRI. A composite Theory of Mind score was computed for all recruited patients and correlated with their brain functional connectivity. This analysis provided the patients’ “Theory of Mind-network”, which was compared, for its topological properties, with that of healthy controls. We found that DM1 patients showed deficits in both tests assessing ToM. These deficits were associated with specific patterns of abnormal connectivity between the left inferior temporal and fronto-cerebellar nodes in DM1 brains. The results confirm the previous suggestions of ToM dysfunctions in patients with DM1 and support the hypothesis that difficulties in social interactions and personal relationships are a direct consequence of brain abnormalities, and not a reaction symptom. This is relevant not only for a better pathophysiological comprehension of DM1, but also for non-pharmacological interventions to improve clinical aspects and impact on patients’ success in life.

Neural substrates of motor and cognitive dysfunctions in SCA2 patients: A network based statistics analysis

“…Each node's mean time course was calculated as the average of the fMRI time series from all voxels within a given region. Correlation matrices were then obtained calculating the correlation between all pairs of nodes' mean signals as described by Serra et al (2016). In this way, we were able to assess differences in functional connectivity (FC) between specific cerebellar and cerebral “nodes”.…”

Functional Changes of Mentalizing Network in SCA2 Patients: Novel Insights into Understanding the Social Cerebellum

“…The "Networks-based statistics" (NBS) tool developed by Zalesky and co-authors (2010) [ In order to obtain a connectivity matrix for each participant, representing the functional network to be tested, each node's mean time course was calculated as the average of the fMRI time series from all voxels within a certain ROI. Correlation matrices were then obtained calculating the correlation between all pairs of nodes' mean signals as described by Serra and colleagues (2016) [39]. In this way, we were able to assess differences in FC between specific cerebellar and cerebral "nodes".…”

Abnormal Cortical Thickness Is Associated With Deficits in Social Cognition in Patients With Myotonic Dystrophy Type 1

“…Importantly, a strict relationship has been reported not only between structural brain abnormalities and DM1 patients' cognitive profile (e.g., executive functions, reasoning and visuospatial abilities) (7,9) but also with patients' CTG triplet expansion (6,8,13). When looking at functional brain connectivity, abnormalities in specific networks have been identified to account for DM1 patients' personality traits (14), as well as for some complex cognitive impairments (8,15) in the domain of social cognition (SC) (16). This is particularly relevant considering that higher-order neuropsychological dysfunctions, including SC, dominate the cognitive profile of DM1 patients who, conversely, perform relatively well on tests exploring single neuropsychological domains (e.g., memory, language, etc).…”