Abstract
Executive dysfunctions in early psychosis (EP) are subtle but persistent, hindering recovery. We asked whether changes in the cognitive control system (CCS) disrupt the response to increased cognitive load in persons with EP. In all, 30 EP and 30 control participants undertook multimodal MRI. Computational models of structural and effective connectivity amongst regions in the CCS were informed by cortical responses to the multi-source interference task, a paradigm that selectively introduces stimulus conflict. EP participants showed greater activation of CCS regions, including the superior parietal cortex, and were disproportionately slower at resolving stimulus conflict in the task. Computational models of the effective connectivity underlying this behavioral response suggest that the normative (control) group resolved stimulus conflict through an efficient and direct modulation of gain between the visual cortex and the anterior insula (AI). In contrast, the EP group utilized an indirect path, with parallel and multi-region hops to resolve stimulus conflict at the AI. Individual differences in task performance were dependent on initial linear gain modulations in the EP group versus a single nonlinear modulation in the control group. Effective connectivity in the EP group was associated with reduced structural integration amongst those connections critical for task execution. CCS engagement during stimulus conflict is hampered in EP owing to inefficient use of higher-order network interactions, with high tonic gain impeding task-relevant (phasic) signal amplification.
Highlights
Assertive early intervention usually yields considerable symptomatic and functional improvement in early psychosis (EP) [1]
The peak age-ofonset of psychosis from late adolescence to early adulthood suggests that childhood neurodevelopment may proceed unremarkably, but a destabilization occurs in the late-maturing cognitive control system (CCS) proximal to psychosis onset [2, 7]
We hypothesized that the “cognitive stressor” of stimulus conflict would uncover network mechanisms of activation, effective connectivity, and behavior that differ between EP participants and matched controls
Summary
Assertive early intervention usually yields considerable symptomatic and functional improvement in early psychosis (EP) [1]. Research suggests that low cognitive loads can be supported by cortical systems despite deficits in connectivity, these systems cannot transition to the configuration required for high cognitive demands [15] This is consistent with the picture of good treatment outcomes, yet persistent executive deficits. We hypothesized that the “cognitive stressor” of stimulus conflict would uncover network mechanisms of activation, effective connectivity, and behavior that differ between EP participants and matched controls. These were assessed using a generative framework (Dynamic Causal Supplementary Table S1). All procedures in this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with
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