Abstract
Two decades of studies suggest that computerized cognitive training (CCT) has an effect on cognitive improvement and the restoration of brain activity. Nevertheless, individual response to CCT remains heterogenous, and the predictive potential of neuroimaging in gauging response to CCT remains unknown. We employed multivariate pattern analysis (MVPA) on whole-brain resting-state functional connectivity (rsFC) to (neuro)monitor clinical outcome defined as psychosis-likeness change after 10-hours of CCT in recent onset psychosis (ROP) patients. Additionally, we investigated if sensory processing (SP) change during CCT is associated with individual psychosis-likeness change and cognitive gains after CCT. 26 ROP patients were divided into maintainers and improvers based on their SP change during CCT. A support vector machine (SVM) classifier separating 56 healthy controls (HC) from 35 ROP patients using rsFC (balanced accuracy of 65.5%, P < 0.01) was built in an independent sample to create a naturalistic model representing the HC-ROP hyperplane. This model was out-of-sample cross-validated in the ROP patients from the CCT trial to assess associations between rsFC pattern change, cognitive gains and SP during CCT. Patients with intact SP threshold at baseline showed improved attention despite psychosis status on the SVM hyperplane at follow-up (p < 0.05). Contrarily, the attentional gains occurred in the ROP patients who showed impaired SP at baseline only if rsfMRI diagnosis status shifted to the healthy-like side of the SVM continuum. Our results reveal the utility of MVPA for elucidating treatment response neuromarkers based on rsFC-SP change and pave the road to more personalized interventions.
Highlights
Neuroplasticity-based computerized cognitive training (CCT) has frequently been used as a supplementary treatment in psychotic illness [1, 2]
We employed a model that was built on an independent sample of LMU recent onset psychosis (ROP) patients not undergoing the intervention, providing us with a quantifiable clinical outcome measure of psychosis-likeness change across the healthy controls (HC)-ROP continuum with a balanced accuracy (BAC) of 65.54%
We used Emotion Matching Task (EMT) as a proxy for sensory processing and created two patient groups based on the median split of sensory processing change (SPC)
Summary
Neuroplasticity-based computerized cognitive training (CCT) has frequently been used as a supplementary treatment in psychotic illness [1, 2]. CCT implements learning-based neuroplasticity principles to restore neuromodulatory processes underlying the structure, function, and connections in the brain that support perceptual, cognitive, social, and motor abilities often disturbed in psychotic illness [3, 4]. This therapeutic approach received evidence in circumventing cognitive deficits [5,6,7] and poor functional outcome in psychosis [8, 9]. Previous meta-analyses indicate that cognitive remediation has a small to moderate effect on multiple cognitive domains including attention, working memory, executive functioning, and social cognition in the treatment of schizophrenia [6, 7, 10]. The underlying mechanism of neuroplasticity-based CCT is meant to induce widespread changes in both cortical and subcortical representations and may not be captured by singleregion activation maps measured by task-based MRI [3, 20, 21]
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