Engagement with the auditory processing system during targeted auditory cognitive training mediates changes in cognitive outcomes in individuals with schizophrenia

Abstract

Background: Individuals with schizophrenia who engage in targeted cognitive training (TCT) of the auditory system show generalized cognitive improvements. The high degree of variability in cognitive gains maybe due to individual differences in the level of engagement of the underlying neural system target.

Method: 131 individuals with schizophrenia underwent 40 hours of TCT. We identified target engagement of auditory system processing efficiency by modeling subject-specific trajectories of auditory processing speed (APS) over time. Lowess analysis, mixed models repeated measures analysis, and latent growth curve modeling were used to examine whether APS trajectories were moderated by age and illness duration, and mediated improvements in cognitive outcome measures.

Results: We observed significant improvements in APS from baseline to 20 hours of training (initial change), followed by a flat APS trajectory (plateau) at subsequent time-points. Participants showed interindividual variability in the steepness of the initial APS change and in the APS plateau achieved and sustained between 20 and 40 hours. We found that participants who achieved the fastest APS plateau, showed the greatest transfer effects to untrained cognitive domains.

Conclusions: There is a significant association between an individual's ability to generate and sustain auditory processing efficiency and their degree of cognitive improvement after TCT, independent of baseline neurocognition. APS plateau may therefore represent a behavioral measure of target engagement mediating treatment response. Future studies should examine the optimal plateau of auditory processing efficiency required to induce significant cognitive improvements, in the context of interindividual differences in neural plasticity and sensory system efficiency that characterize schizophrenia. (PsycINFO Database Record

Trial registration: ClinicalTrials.gov NCT01988714 NCT00694889 NCT02105779.

(c) 2016 APA, all rights reserved).

Figures

Figure 1. Applying the experimental medicine model to targeted cognitive training of auditory/verbal processing in schizophrenia

Schizophrenia is characterized by impaired feed-forward/ feedback operations in auditory working memory that are associated with cognitive dysfunction. Training is thus designed to improve the perception and temporally-detailed resolution of auditory inputs that feed forward into working memory operations and verbal encoding, while providing feedback engagement of attention and cognitive control operations. We hypothesize that engagement of this training target-- interacting feedback and feed-forward operations-- will be associated with enhanced cognitive performance, particularly in verbal learning and memory.

Figure 2. Trajectory of auditory processing speed (APS) over time, as indexed by APS scores at baseline, and after 20,30 and 40 hours of auditory TCT (n=131)

Error bars represent standard errors of the means.

Figure 3

Latent Growth Curve (LGC) model for the target engagement measure of auditory processing speed (APS) over time, conditioned for MATRICS Global Cognition (GC) scores (N = 130).