Abstract

Background: Greater impairments in early sensory processing predict response to auditory computerized cognitive training (CCT) in patients with recent-onset psychosis (ROP). Little is known about neuroimaging predictors of response to social CCT, an experimental treatment that was recently shown to induce cognitive improvements in patients with psychosis. Here, we investigated whether ROP patients show interindividual differences in sensory processing change and whether different patterns of SPC are (1) related to the differential response to treatment, as indexed by gains in social cognitive neuropsychological tests and (2) associated with unique resting-state functional connectivity (rsFC).Methods: Twenty-six ROP patients completed 10 h of CCT over the period of 4–6 weeks. Subject-specific improvement in one CCT exercise targeting early sensory processing—a speeded facial Emotion Matching Task (EMT)—was studied as potential proxy for target engagement. Based on the median split of SPC from the EMT, two patient groups were created. Resting-state activity was collected at baseline, and bold time series were extracted from two major default mode network (DMN) hubs: left medial prefrontal cortex (mPFC) and left posterior cingulate cortex (PCC). Seed rsFC analysis was performed using standardized Pearson correlation matrices, generated between the average time course for each seed and each voxel in the brain.Results: Based on SPC, we distinguished improvers—i.e., participants who showed impaired performance at baseline and reached the EMT psychophysical threshold during CCT—from maintainers—i.e., those who showed intact EMT performance at baseline and sustained the EMT psychophysical threshold throughout CCT. Compared to maintainers, improvers showed an increase of rsFC at rest between PCC and left superior and medial frontal regions and the cerebellum. Compared to improvers, maintainers showed increased rsFC at baseline between PCC and superior temporal and insular regions bilaterally.Conclusions: In ROP patients with an increase of connectivity at rest in the default mode network, social CCT is still able to induce sensory processing changes that however do not translate into social cognitive gains. Future studies should investigate if impairments in short-term synaptic plasticity are responsible for this lack of response and can be remediated by pharmacological augmentation during CCT.

Highlights

  • Cognitive system dysfunction represents a significant risk factor for recent-onset psychosis (ROP) [1, 2] and a poor prognostic indicator [3]

  • Second-level analyses revealed a number of significant differences in whole-brain resting-state functional connectivity (rsFC) of left posterior cingulate cortex (PCC) between improver and maintainer patients that underwent SCT (Table 2)

  • Improvers showed at rest an increase in connectivity between left PCC and left superior medial frontal lobe (including supplementary motor area, frontal inferior lobe, triangularis lobe, and left thalamus (Figure 2), as well as an increase in connectivity between left PCC and right postcentral gyrus

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Summary

Introduction

Cognitive system dysfunction represents a significant risk factor for ROP (recent-onset psychosis) [1, 2] and a poor prognostic indicator [3]. Cognitive dysfunction and underlying neural system inefficiency have become primary targets for preemptive experimental interventions in ROP, including computerized cognitive training (CCT) [5]. In patients with ROP, a CCT program targeting the auditory system was found to significantly improve several domains of cognition, as well as early structural and dynamic imaging responses in auditory and prefrontal cortices [8,9,10]. Greater impairments in early sensory processing predict response to auditory computerized cognitive training (CCT) in patients with recent-onset psychosis (ROP). Little is known about neuroimaging predictors of response to social CCT, an experimental treatment that was recently shown to induce cognitive improvements in patients with psychosis. We investigated whether ROP patients show interindividual differences in sensory processing change and whether different patterns of SPC are [1] related to the differential response to treatment, as indexed by gains in social cognitive neuropsychological tests and [2] associated with unique resting-state functional connectivity (rsFC)

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