Theme: Mechanisms

Project Description

Conduct disorder (CD) is characterised by a repetitive and pervasive pattern of aggressive and rule-breaking antisocial behaviour. It is one of the most common childhood psychiatric disorders, and associated with the highest burden of any mental disorder in young people. As such, understanding CD and its neurobiological correlates is a priority. Of particular importance for this project, structural MRI has demonstrated cortical and subcortical changes, including the thalamus, associated with CD. A reduced volume of the thalamus has been suggested to represent impaired information processing resulting in disrupted behaviours. However, this idea has yet to be formally tested using brain imaging data. We will test this hypothesis using a novel analytical framework that quantifies information flow, applying it directly to the thalamocortical system (TS) to quantify changes to the TS in CD.

How does the brain react optimally to behavioural challenges while managing the vast amount of information it receives from the external environment and from the constant, dynamic communication between brain regions? Synthesising evidence from the past few decades, we recently suggested that this is the role of the TS, comprising the thalamic nuclei, the thalamic reticular nucleus and the cerebral cortex. The TS generates the most prominent neuronal oscillations of wakefulness and sleep and is linked to cognition; changes in conscious state associated with sleep and anaesthesia, and is disrupted in many common neurodevelopmental, neurological and psychiatric conditions.

Although the cortex dominates human neuroscientific studies, a bias termed ‘corticocentric myopia’, behaviour critically depends on subcortical structures, including the thalamus. We will build upon our own and others’ work to quantify whole-brain, spatio-temporal dynamics of TS communication, and investigate how changes to thalamocortical communication routes and dynamics associated with CD are reflected in functional data. We will make use of existing, largescale data sets with MRI data in addition to measures of CD (e.g., the ABCD Study, ENIGMA-Antisocial Behavior Working Group). Our analytical framework uses functional (fMRI) and structural (diffusion weighted imaging, DWI) data to model brain networks as a system of dynamically interacting senders and receivers, quantifying how information travels between brain regions. Structural pathways from diffusion weighted imaging (DWI) are evaluated using measures from information and communications theory calculated from fMRI data. We will optimise our existing approach specifically to investigate TS information flow, and apply this to CD.

This project provides a new approach to understanding and characterising CD, building on novel developments in the analysis of functional brain imaging data and a new framework for understanding the role of the thalamus.