Recent advances in the integrative neurosciences have led to an increased understanding of brain plasticity mechanisms underlying perceptual and cognitive skill learning. The purpose of this study is to apply these principles to the neuroscience-guided training-based remediation of specific cognitive deficits in schizophrenia. Based on a working model of the consequences of impaired cortical neuronal network processing efficiency and attentional deficits in schizophrenia, we will employ a set of novel, intensive, computer-based cognitive training exercises that specifically target neurocognitive processing efficiency (speed and accuracy in the perception and ? response to targets), using an adaptive training procedure. We will examine the effects of this neuroscience-guided training strategy on cognitive performance, symptom profile, quality of life, and social cue recognition in subjects with schizophrenia as compared to schizophrenic subjects who undergo a control intervention (graphics-based computer games). We will also examine to what degree the effects of this intervention endure six months beyond the initial training. The study design will be a controlled clinical trial with 80 schizophrenic subjects randomly assigned in matched pairs to 100 hours of either active training or a control computer-games intervention, for 40 completed subjects per matched group. Three different sets of both verbal and visuo-spatial cognitive training exercises will be used based on the principles of the self-adjusted neuroadaptive psychophysical training tools initially developed by Merzenich et al. for language disabilities (1998). Exercises will directly target a core domain of neurocognitive impairment in schizophrenia--verbal and visuo-spatial processing efficiency-- which is known to be relevant to clinical and psychosocial outcome, while secondarily training attention and executive control.
The specific aims are: 1. To employ a neuroscience-based cognitive training strategy for the remediation of impaired neurocognitive processing efficiency in schizophrenia and to compare the effects of this training to a control intervention. 2. To evaluate the degree to which remediation of this specific cognitive impairment generalizes to improvements in other, higher-order cognitive deficits in schizophrenia. 3. To evaluate whether this targeted training reduces subjects' symptom severity and improves complex psychosocial functions, including social cue recognition and quality of life. 4. To determine whether the effects of training persist 6 months beyond the training period. 5. To examine factors that influence the response to training: -- Individual subject differences at study entry (cognitive and clinical status)-- Pharmacologic status (serum anticholinergicity and plasma neuroleptic levels). ? ?

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Interventions Research Review Committee (ITV)
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Heinssen, Robert K
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Northern California Institute Research & Education
San Francisco
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Subramaniam, Karuna; Gill, Jeevit; Fisher, Melissa et al. (2018) White matter microstructure predicts cognitive training-induced improvements in attention and executive functioning in schizophrenia. Schizophr Res 193:276-283
Kantrowitz, Joshua T; Swerdlow, Neal R; Dunn, Walter et al. (2018) Auditory System Target Engagement During Plasticity-Based Interventions in Schizophrenia: A Focus on Modulation of N-Methyl-D-Aspartate-Type Glutamate Receptor Function. Biol Psychiatry Cogn Neurosci Neuroimaging 3:581-590
Subramaniam, Karuna; Ranasinghe, Kamalini G; Mathalon, Daniel et al. (2017) Neural mechanisms of mood-induced modulation of reality monitoring in schizophrenia. Cortex 91:271-286
Dale, Corby L; Brown, Ethan G; Fisher, Melissa et al. (2016) Auditory Cortical Plasticity Drives Training-Induced Cognitive Changes in Schizophrenia. Schizophr Bull 42:220-8
Biagianti, Bruno; Fisher, Melissa; Neilands, Torsten B et al. (2016) Engagement with the auditory processing system during targeted auditory cognitive training mediates changes in cognitive outcomes in individuals with schizophrenia. Neuropsychology 30:998-1008
Vinogradov, Sophia; Herman, Alexander (2016) Psychiatric Illnesses as Oscillatory Connectomopathies. Neuropsychopharmacology 41:387-8
Subramaniam, Karuna; Gill, Jeevit; Slattery, Patrick et al. (2016) Neural Mechanisms of Positive Mood Induced Modulation of Reality Monitoring. Front Hum Neurosci 10:581
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Subramaniam, Karuna; Luks, Tracy L; Garrett, Coleman et al. (2014) Intensive cognitive training in schizophrenia enhances working memory and associated prefrontal cortical efficiency in a manner that drives long-term functional gains. Neuroimage 99:281-92

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