Dysconnectivity of the Nucleus Accumbens and Amygdala in Youths with Thought Problems: A Dimensional Approach

Background: Youths with thought problems (TP) are at risk to develop psychosis and obsessive-compulsive disorder (OCD). Yet, the pathophysiological mechanisms underpinning TP are still unclear. Functional magnetic resonance imaging (fMRI) studies have shown that striatal and limbic alterations are associated with psychosis-like and obsessive-like symptoms in individuals at clinical risk for psychosis, schizophrenia, and OCD. More specifically, nucleus accumbens (NAcc) and amygdala are mainly involved in these associations. The current study aims to investigate the neural correlates of TP in youth populations using a dimensional approach and explore potential cognitive functions and neurotransmitters associated with it.Methods: Seed-to-voxels functional connectivity analyses using NAcc and amygdala as regions-of-interest were conducted with resting-state fMRI data obtained from 1360 young individuals, and potential confounders related to TP such as anxiety and cognitive functions were included as covariates in multiple regression analyses. Replicability was tested in using an adult cohort. In addition, functional decoding and neurochemical correlation analyses were performed to identify the associated cognitive functions and neurotransmitters.Results: The altered functional connectivities between the right NAcc and posterior parahippocampal gyrus, between the right amygdala and lateral prefrontal cortex, and between the left amygdala and the secondary visual area were the best predictors of TP in multiple regression model. These functional connections are mainly involved in social cognition and reward processing.Conclusions: The results show that alterations in the functional connectivity of the NAcc and the amygdala in neural pathways involved in social cognition and reward processing are associated with severity of TP in youths. Impact Statement Taking thought problems (TP) as a dimension, the multivariate linear regression model showed that the altered functional connectivity of the nucleus accumbens and amygdala is correlated to the severity of TP in youths. The replicability of identified connectivity was tested using an adult cohort. Functional characterization analyses revealed that these functional connectivities are involved in cognition (cognitive control), face detection (social cognition), and motivation/reward. Findings of the altered functional connectivity, related brain regions, and cognitive functions associated with TP can be a stepping stone to understanding the underlying pathophysiological mechanisms.