Postdoctoral Fellow, UCSF Department of Psychiatry
neuroplasticity-based cognitive training for serious mental illness
Background: Individuals with schizophrenia have heterogeneous impairments of the auditory processing system that likely mediate differences in the cognitive gains induced by auditory training (AT). Mismatch negativity (MMN) is an event-related potential component reflecting auditory echoic memory, and its amplitude reduction in schizophrenia has been linked to cognitive deficits. Therefore, MMN may predict response to AT and identify individuals with schizophrenia who have the most to gain from AT. Furthermore, to the extent that AT strengthens auditory deviance processing, MMN may also serve as a readout of the underlying changes in the auditory system induced by AT. Methods: Fifty-six individuals early in the course of a schizophrenia-spectrum illness (ESZ) were randomly assigned to 40 hours of AT or Computer Games (CG). Cognitive assessments and EEG recordings during a multi-deviant MMN paradigm were obtained before and after AT and CG. Changes in these measures were compared between the treatment groups. Baseline and trait-like MMN data were evaluated as predictors of treatment response. MMN data collected with the same paradigm from a sample of Healthy Controls (HC; n=105) were compared to baseline MMN data from the ESZ group. Results: Compared to HC, ESZ individuals showed significant MMN reductions at baseline (p=.003). Reduced Double-Deviant MMN was associated with greater general cognitive impairment in ESZ individuals (p= .020). Neither ESZ intervention group showed significant change in MMN. We found high correlations in all MMN deviant types (rs=.59-.68, all ps<.001) between baseline and post-intervention amplitudes irrespective of treatment group, suggesting trait-like stability of the MMN signal. Greater deficits in trait-like Double-Deviant MMN predicted greater cognitive improvements in the AT group (p=.02), but not in the CG group. Conclusions: In this sample of ESZ individuals, AT had no effect on auditory deviance processing as assessed by MMN. In ESZ individuals, baseline MMN was significantly reduced relative to HCs, and associated with global cognitive impairment. MMN did not show changes after AT and exhibited trait-like stability. Greater deficits in the trait aspects of Double-Deviant MMN predicted greater gains in global cognition in response to AT, suggesting that MMN may identify individuals who stand to gain the most from AT.
Abstract: Two important paradigm shifts have occurred recently in the field of schizophrenia research. First, we now understand schizophrenia to be a neurodevelopmental disorder, one that is characterized by aberrant patterns of activation and connectivity in cortical and subcortical neural networks that are present before illness onset and that worsen as an individual progresses into later stages of the disease. Second, we now understand that these abnormalities are not immutable and fixed, but instead can respond to interventions targeting brain plasticity, particularly when delivered in the prodromal and early phases of schizophrenia. In this chapter, we will first describe some of the neurocognitive impairments that characterize schizophrenia, highlighting the developmental course of the illness. We will then briefly review salient features of currently available computerized cognitive training programs that target these impairments. Next, we will present an overview of current research findings regarding neurobiological effects of computerized cognitive training in schizophrenia and how these results shed light on the critical neuroplasticity mechanisms that support successful training. Finally, we will present recommendations for future research to optimize computerized cognitive training programs, with an aim to promoting functional recovery.
Pub.: 07 Dec '13, Pinned: 07 Jun '17
Abstract: Individuals at clinical high risk (CHR) for psychosis demonstrate cognitive impairments that predict later psychotic transition and real-world functioning. Cognitive training has shown benefits in schizophrenia, but has not yet been adequately tested in the CHR population.In this double-blind randomized controlled trial, CHR individuals (N = 83) were given laptop computers and trained at home on 40 hours of auditory processing-based exercises designed to target verbal learning and memory operations, or on computer games (CG). Participants were assessed with neurocognitive tests based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative (MATRICS) battery and rated on symptoms and functioning. Groups were compared before and after training using a mixed-effects model with restricted maximum likelihood estimation, given the high study attrition rate (42%).Participants in the targeted cognitive training group showed a significant improvement in Verbal Memory compared to CG participants (effect size = 0.61). Positive and Total symptoms improved in both groups over time.CHR individuals showed patterns of training-induced cognitive improvement in verbal memory consistent with prior observations in schizophrenia. This is a particularly vulnerable domain in individuals at-risk for psychosis that predicts later functioning and psychotic transition. Ongoing follow-up of this cohort will assess the durability of training effects in CHR individuals, as well as the potential impact on symptoms and functioning over time. Clinical Trials Number: NCT00655239. URL: https://clinicaltrials.gov/ct2/show/NCT00655239?term=vinogradov&rank=5.
Pub.: 24 Feb '16, Pinned: 07 Jun '17
Abstract: 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. 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. 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. 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
Pub.: 13 Sep '16, Pinned: 07 Jun '17