The Road Not Taken: Disconnection of a Human-Unique Cortical Pathway Underlying Naturalistic Social Perception in Schizophrenia.

Background: Efficient processing of complex and dynamic social scenes relies on intact connectivity of many underlying cortical areas and networks, but how connectivity anomalies affect the neural substrates of social perception remains unknown. Here we measured these relationships using functionally based localization of social perception areas, resting-state functional connectivity, and movie-watching data. Methods: In 42 participants with schizophrenia (SzPs) and 41 healthy control subjects, we measured the functional connectivity of areas localized by face-emotion processing, theory-of-mind (ToM), and attention tasks. We quantified the weighted shortest path length between visual and medial prefrontal ToM areas in both populations to assess the impact of these changes in functional connectivity on network structure. We then correlated connectivity along the shortest path in each group with movie-evoked activity in a key node of the ToM network (posterior temporoparietal junction [TPJp]). Results: SzPs had pronounced decreases in connectivity in TPJ/posterior superior temporal sulcus (TPJ-pSTS) areas involved in face-emotion processing (t81 = 4.4, p = .00002). In healthy control subjects, the shortest path connecting visual and medial prefrontal ToM areas passed through TPJ-pSTS, whereas in SzPs, the shortest path passed through the prefrontal cortex. While movie-evoked TPJp activity correlated with connectivity along the TPJ-pSTS pathway in both groups (r = 0.43, p = .002), it additionally correlated with connectivity along the prefrontal cortex pathway only in SzPs (rSzP = 0.56, p = .003). Conclusions: These results suggest that connectivity along the human-unique TPJ-pSTS pathway affects both the network architecture and functioning of areas involved in processing complex dynamic social scenes. These results demonstrate how focal connectivity anomalies can have widespread impacts across the cortex.

Brain connectivity at rest predicts individual differences in normative activity during movie watching.

When exposed to the same sensory event, some individuals are bound to have less typical experiences than others. Previous research has investigated this phenomenon by showing that the typicality of one's sensory experience is associated with the typicality of their stimulus-evoked brain activity (as measured by intersubject correlation, or ISC). Individual differences in ISC have recently been attributed to variability in focal neural processing. However, the extent to which these differences reflect purely intra-regional variability versus variation in the brain's baseline ability to transmit information between regions has yet to be established. Here, we show that an individual's degree and spatial distribution of ISC are closely related to their brain's functional organization at rest. Using resting state and movie watching fMRI data from the Human Connectome Project, we reveal that resting state functional connectivity (RSFC) profiles can be used to predict cortex-wide ISC. Similar region-level analyses demonstrate that the levels of ISC exhibited by brain regions during movie watching are associated with their connectivity to other regions at rest, and that the nature of these connectivity-activity relationships varies as a function of regional roles in sensory information processing. Finally, we show that an individual's unique spatial distribution of ISC, independent of its magnitude, is also related to their RSFC profile. These findings contextualize reports of localized individual differences in ISC as potentially reflecting larger, network-level alterations in resting brain function and detail how the brain's ability to process complex sensory information is linked to its baseline functional organization.

Relationships between depressive symptoms and brain responses during emotional movie viewing emerge in adolescence.

Affective disorders such as major depression are common but serious illnesses characterized by altered processing of emotional information. Although the frequency and severity of depressive symptoms increase dramatically over the course of childhood and adolescence, much of our understanding of their neurobiological bases comes from work characterizing adults' responses to static emotional information. As a consequence, relationships between depressive brain phenotypes and naturalistic emotional processing, as well as the manner in which these associations emerge over the lifespan, remain poorly understood. Here, we apply static and dynamic inter-subject correlation analyses to examine how brain function is associated with clinical and non-clinical depressive symptom severity in 112 children and adolescents (7-21 years old) who viewed an emotionally evocative clip from the film Despicable Me during functional MRI. Our results reveal that adolescents with greater depressive symptom severity exhibit atypical fMRI responses during movie viewing, and that this effect is stronger during less emotional moments of the movie. Furthermore, adolescents with more similar item-level depressive symptom profiles showed more similar brain responses during movie viewing. In contrast, children's depressive symptom severity and profiles were unrelated to their brain response typicality or similarity. Together, these results indicate a developmental change in the relationships between brain function and depressive symptoms from childhood through adolescence. Our findings suggest that depressive symptoms may shape how the brain responds to complex emotional information in a dynamic manner sensitive to both developmental stage and affective context.