Energy in functional brain states correlates with cognition in adolescent schizophrenia and healthy persons

Abstract

AbstractAdolescent-onset schizophrenia (AOS) is a relatively rare and under-studied form of schizophrenia with more severe cognitive impairments and poorer outcome compared to adult-onset schizophrenia. Several neuroimaging studies have reported alterations in regional activations that account for activity in individual regions (first-order model) and functional connectivity that reveals pairwise co-activations (second-order model) in AOS compared to controls. The pairwise maximum entropy model, also called the Ising model, can integrate both first-order and second-order terms to elucidate a comprehensive picture of neural dynamics and captures both individual and pairwise activity measures into a single quantity known as energy, which is inversely related to the probability of state occurrence. We applied the MEM framework to task functional MRI data collected on 23 AOS individuals in comparison with 53 healthy control subjects while performing the Penn Conditional Exclusion Test (PCET), which measures executive function that has been repeatedly shown to be more impaired in AOS compared to adult-onset schizophrenia. Accuracy of PCET performance was significantly reduced among AOS compared to controls as expected. Average cumulative energy achieved for a participant over the course of the fMRI negatively correlated with task performance, and the association was stronger than any first-order associations. The AOS subjects spent more time in higher energy states that represent lower probability of occurrence and were associated with impaired executive function suggesting that the neural dynamics may be less efficient compared to controls who spent more time in lower energy states occurring with higher probability and hence are more stable and efficient. The energy landscapes in both conditions featured attractors that corresponded to two distinct subnetworks, namely fronto-temporal and parieto-motor. Attractor basins were larger in the controls than in AOS; moreover, fronto-temporal basin size was significantly correlated with cognitive performance in controls but not among the AOS. The single trial trajectories for the AOS group also showed higher variability in concordance with shallow attractor basins among AOS. These findings suggest that the neural dynamics of AOS features more frequent occurrence of less probable states with narrower attractors, which lack the relation to executive function associated with attractors in control subjects suggesting a diminished capacity of AOS to generate task-effective brain states.