Changes in the Effective Connectivity of the Social Brain When Making Inferences About Close Others vs. the Self.

Previous research showed that the ability to make inferences about our own and other's mental states rely on common brain pathways; particularly in the case of close relationships (e.g., romantic relationships). Despite the evidence for shared neural representations of self and others, less is known about the distributed processing within these common neural networks, particularly whether there are specific patterns of internode communication when focusing on other vs. self. This study aimed to characterize context-sensitive coupling among social brain regions involved in self and other understanding. Participants underwent an fMRI while watching emotional video vignettes of their romantic partner and elaborated on their partner's (other-condition) or on their own experience (self-condition). We used dynamic causal modeling (DCM) to quantify the associated changes in effective connectivity (EC) in a network of brain regions involved in social cognition including the temporoparietal junction (TPJ), the posterior cingulate (PCC)/precuneus and middle temporal gyrus (MTG). DCM revealed that: the PCC plays a central coordination role within this network, the bilateral MTG receives driving inputs from other nodes suggesting that social information is first processed in language comprehension regions; the right TPJ evidenced a selective increase in its sensitivity when focusing on the other's experience, relative to focusing on oneself.

Using resting-state DMN effective connectivity to characterize the neurofunctional architecture of empathy.

Neuroimaging studies in social neuroscience have largely relied on functional connectivity (FC) methods to characterize the functional integration between different brain regions. However, these methods have limited utility in social-cognitive studies that aim to understand the directed information flow among brain areas that underlies complex psychological processes. In this study we combined functional and effective connectivity approaches to characterize the functional integration within the Default Mode Network (DMN) and its role in self-perceived empathy. Forty-two participants underwent a resting state fMRI scan and completed a questionnaire of dyadic empathy. Independent Component Analysis (ICA) showed that higher empathy scores were associated with an increased contribution of the medial prefrontal cortex (mPFC) to the DMN spatial mode. Dynamic causal modelling (DCM) combined with Canonical Variance Analysis (CVA) revealed that this association was mediated indirectly by the posterior cingulate cortex (PCC) via the right inferior parietal lobule (IPL). More specifically, in participants with higher scores in empathy, the PCC had a greater effect on bilateral IPL and the right IPL had a greater influence on mPFC. These results highlight the importance of using analytic approaches that address directed and hierarchical connectivity within networks, when studying complex psychological phenomena, such as empathy.

Brain circuits involved in understanding our own and other's internal states in the context of romantic relationships.

Social interactions require the capacity to understand both our and other's internal states. These semi-independent skills, the ability to understand oneself and others, seem to rely on the same type of representations and recruit similar brain areas. In this study, we looked at the neural basis of self and other processing in the context of an interaction with a significant other. Fourty-two participants in a monogamous relationship completed an fMRI task in which they watched a set of video-vignettes of his/her romantic partner expressing emotional contents. Participants were asked to elaborate on his/her spouse´s experience (other condition) and on his/her own experience when watching the video-vignettes (self-condition). The results showed a significant overlap in the brain activation for both conditions (e.g. anterior insula, posterior cingulate/precuneus, inferior frontal gyrus, inferior parietal lobule). In addition, the self-condition recruited brain areas associated with interoceptive processing and affect sharing (e.g., posterior insula), whereas the other-condition engaged brain areas involved in the cognitive representation of another's internal states and self-other distinction (e.g., fusiform, supramarginal gyrus, angular gyrus and temporoparietal junction).

Quantification of mutant E-cadherin using bioimaging analysis of in situ fluorescence microscopy. A new approach to CDH1 missense variants.

Missense mutations result in full-length proteins containing an amino acid substitution that can be neutral or deleterious, interfering with the normal conformation, localization, and function of a protein. A striking example is the presence of CDH1 (E-cadherin gene) germline missense variants in hereditary diffuse gastric cancer (HDGC), which represent a clinical burden for genetic counseling and surveillance of mutation carriers and their families. CDH1 missense variants can compromise not only the function of E-cadherin but also its expression pattern. Here, we propose a novel method to characterize E-cadherin signature in order to identify cases with E-cadherin deregulation and functional impairment. The strategy includes a bioimaging pipeline to quantify the expression level and characterize the distribution of the protein from in situ immunofluorescence images. The algorithm computes 1D (dimension intensity) radial and internuclear fluorescence profiles to generate expression outlines and 2D virtual cells representing a typical cell within the populations analyzed. Using this new approach, we verify that cells expressing mutant forms of E-cadherin display fluorescence profiles distinct from those of the wild-type cells. Mutant proteins showed a significantly decrease of fluorescence intensity at the membrane and often abnormal expression peaks in the cytoplasm, reflecting the underlying molecular mechanism of trafficking deregulation. Our results suggest employing this methodology as a complementary approach to evaluate the pathogenicity of E-cadherin missense variants. Moreover, it can be applied to a wide range of proteins and, more importantly, to diseases characterized by aberrant protein expression or trafficking deregulation.