Dynamic network reconfigurations during task engagement following resting state in adolescent onset schizophrenia

Understanding how functional brain networks in resting state configurations reorganize to perform cognitive tasks is critical for uncovering the nature and mechanisms underlying network dysconnectivity in psychiatric disorders. We applied energy landscape analysis (ELA), a statistical physics-based computational approach, to functional MRI data from 23 adolescent-onset schizophrenia (AOS) and 44 healthy control (HC) subjects, acquired during rest followed by executive function task. ELA maps brain activity into distinct network states and quantifies how the brain transitions among them, capturing differences in stability of network states and transition complexity across conditions. AOS and HC showed markedly different condition-dependent patterns of brain state organization and dynamics. At rest, AOS exhibited reduced dynamical complexity compared to HC (7 vs. 14 stable states) that reversed during the task with more than 2-fold increase in accessible but rarely occupied brain states, while HC showed an opposite pattern. These results suggest that cognitive demands unmask latent fragmentation of the energy landscape, comprising a proliferation of accessible but rarely occupied states not apparent at rest, in AOS. State occupancy analysis revealed a small number of dominant states accounting for the majority of brain activity time, with AOS showing greater persistence in the fully-active DMN state during task performance compared to HC. These findings suggest that the rest-to-task transition features fundamentally different neural dynamics in AOS compared to HC. Combined analysis of resting fMRI and task-induced brain dynamics revealed neural factors that may contribute to cognitive dysfunction and psychiatric symptoms in schizophrenia, with important implications for development of biomarkers and treatment targets.