Sub-optimal modulation of gain by the cognitive control system in young adults with early psychosis

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.

Cognitive Control System Gates Insula Processing of Affective Stimuli in Early Psychosis

“…In contrast, we found a significant difference in reaction time between these same groups in a more difficult task of interference without an emotional component (multi-source interference task, c.f. 14 ). Absence of differences in task performance here suggests the observed neural changes are not sufficiently disruptive to hamper the execution of this relatively simple motor inhibition task, even if they support the subtle but more pernicious psychotic phenomena experienced by our EP participants.…”

“…The participants and functional imaging protocol are as recently described. 14 The description, analysis, and modeling of the affective go/no-go task in this cohort are unique to the present study.…”

“… 11 Dysfunction in these systems and processes occurs in mood disorders such as major depression 12 , 13 and psychosis. 14 , 15 For example, altered neural activity in these regions has been found in tasks of emotion processing in psychosis. 16–18 Although computational modeling of neuroimaging data have highlighted the contribution of suboptimal top-down cognitive control to the positive symptoms of psychosis, 19 , 20 there is a paucity of theoretical and empirical work linking cognitive control to emotion deficits and related negative symptoms of psychosis.…”

Structure-function models of temporal, spatial, and spectral characteristics of non-invasive whole brain functional imaging

“…Here, the extent of perturbation was quantified by introducing a perturbation term in the coupled NMMs (Sanz Perl et al, 2021 ). A DCM approach was used to investigate modulation of gain by the cognitive control systems in early psychosis (Burgher et al, 2021 ).…”

The thalamus in psychosis spectrum disorder

“…We structure this piece into four sections. First, we outline our central hypothesis related to thalamocortical dysconnectivity and PSD symptomatology, with an overarching framing that PSD fundamentally affects computations supporting cognitive control and reasoning ( Garety et al, 2005 ; Cardella and Gangemi, 2015 ; Burgher et al, 2021 ). Second, we discuss recent animal studies that have redefined the role of the thalamus in cognitive function, laying the groundwork for how its dysfunction can contribute to cognitive control and reasoning deficits in PSD.…”