Abstract

Understanding how practice mediates the transition of brain-behavior networks between early and later stages of learning is constrained by the common approach to analysis of fMRI data. Prior imaging studies have mostly relied on a single scan, and parametric, task-related analyses. Our experiment incorporates a multisession fMRI lexicon-learning experiment with multivariate, whole-brain analysis to further knowledge of the distributed networks supporting practice-related learning in schizophrenia (SZ). Participants with SZ were compared with healthy control (HC) participants as they learned a novel lexicon during two fMRI scans over a several day period. All participants were trained to equal task proficiency prior to scanning. Behavioral-Partial Least Squares, a multivariate analytic approach, was used to analyze the imaging data. Permutation testing was used to determine statistical significance and bootstrap resampling to determine the reliability of the findings. With practice, HC participants transitioned to a brain-accuracy network incorporating dorsostriatal regions in late-learning stages. The SZ participants did not transition to this pattern despite comparable behavioral results. Instead, successful learners with SZ were differentiated primarily on the basis of greater engagement of perceptual and perceptual-integration brain regions. There is a different spatiotemporal unfolding of brain-learning relationships in SZ. In SZ, given the same amount of practice, the movement from networks suggestive of effortful learning toward subcortically driven procedural one differs from HC participants. Learning performance in SZ is driven by varying levels of engagement in perceptual regions, which suggests perception itself is impaired and may impact downstream, "higher level" cognition.

Highlights

  • Learning impairments in schizophrenia (SZ) are widespread, impact functional outcome, and may mediate response to various types of cognitive rehabilitation strategies

  • Our results suggest that aberrant functional thalamic engagement impacts practice-related lexicon-learning processes in SZ, but further connectivity analyses are needed to fully characterize the relationship

  • Learning performance in SZ is driven by varying levels of engagement in perceptual regions, which suggests perception itself is impaired and may impact downstream, “higher level” cognition

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Summary

Introduction

Learning impairments in schizophrenia (SZ) are widespread, impact functional outcome, and may mediate response to various types of cognitive rehabilitation strategies. Prior practice-related neuroimaging experiments in SZ have relied primarily on single scanning sessions and univariate, task-related (vs behavior-related) analyses [3,4,5,6,7,8]. Brain substrates associated with practice-related learning are dynamic and widely distributed in space and time. To measure these substrates using fMRI, one should use multivariate whole-brain imaging analytic techniques, a direct brain–behavior (vs brain– task) approach to analysis, and multiple scanning sessions with sufficient in-scanner practice to measure the unfolding of brain changes in vivo. Understanding how practice mediates the transition of brain–behavior networks between early and later stages of learning is constrained by the common approach to analysis of fMRI data. Our experiment incorporates a multisession fMRI lexicon-learning experiment with multivariate, whole-brain analysis to further knowledge of the distributed networks supporting practice-related learning in schizophrenia (SZ)

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