The purpose of this study is to explicitly and aggressively drive an optimal response to neuroplasticity- based cognitive remediation in schizophrenia in order to maximize treatment response. We will investigate factors that have generally been ignored in computer-based cognitive remediation programs-those related to social cognition-- and will delineate their relationship to motivation, functional outcome, and the neural substrates of reward anticipation and emotion processing. Current research indicates that, unless we fully understand and harness these factors, we will not achieve meaningful treatment gains for individuals with schizophrenia.
Our specific aims are: 1. To perform an RCT in which 100 schizophrenia subjects are assigned to either 60 hours of neuroplasticity- based computerized targeted cognitive training (TCT) that focuses exclusively on """"""""cold cognition"""""""" (a program which trains early sensory processing, attention, working memory and cognitive control in auditory and visual domains), or to 60 hours of training that combines the TCT program with 20 minutes per day of adaptive computerized social cognition training (SCT) exercises. 2. To compare the outcomes of these two groups of subjects on measures of neurocognition, social cognition, motivation, and functional outcome. 3. To assess subjects six months after the intervention to determine the durability of training effects. 4. To identify changes in brain activation patterns in key neural regions as a result of TCT alone vs. TCT+SCT: during reward anticipation, and during emotion recognition. The timeliness of this approach is supported by recent evidence demonstrating only weak associations between traditional cognitive remediation approaches and functional outcome in schizophrenia, but a strong, direct relationship between social cognition and functional outcome. Thus we must now examine the clinical, functional, and neural effects of a well-designed state-of-the-art cognitive training program that combines neurocognition with social cognition training. Public Health Relevance Statement (Narrative) This research is relevant to public health in that it will: 1) determine whether the addition of social cognition training exercises to neuroplasticity-based cognitive training of auditory and visual processing improves outcome for people with schizophrenia;2) help to identify neuroplasticity-based cognitive remediation strategies for schizophrenia that provide the maximal benefit in terms of helping patients to achieve meaningful improvements in motivation and social and occupational functioning.

Public Health Relevance

) This research is relevant to public health in that it will: 1) determine whether the addition of social cognition training exercises to neuroplasticity-based cognitive training of auditory and visual processing improves outcome for people with schizophrenia;2) help to identify neuroplasticity-based cognitive remediation strategies for schizophrenia that provide the maximal benefit in terms of helping patients to achieve meaningful improvements in motivation and social and occupational functioning.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH082818-04
Application #
8246427
Study Section
Interventions Committee for Disorders Related to Schizophrenia, Late Life, or Personality (ITSP)
Program Officer
Vitiello, Benedetto
Project Start
2009-08-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
4
Fiscal Year
2012
Total Cost
$579,874
Indirect Cost
$200,845
Name
Northern California Institute Research & Education
Department
Type
DUNS #
613338789
City
San Francisco
State
CA
Country
United States
Zip Code
94121
Subramaniam, Karuna; Kothare, Hardik; Mizuiri, Danielle et al. (2018) Reality Monitoring and Feedback Control of Speech Production Are Related Through Self-Agency. Front Hum Neurosci 12:82
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
Fisher, Melissa; Nahum, Mor; Howard, Elizabeth et al. (2017) Supplementing intensive targeted computerized cognitive training with social cognitive exercises for people with schizophrenia: An interim report. Psychiatr Rehabil J 40:21-32
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
Biagianti, Bruno; Fisher, Melissa; Howard, Lisa et al. (2017) Feasibility and preliminary efficacy of remotely delivering cognitive training to people with schizophrenia using tablets. Schizophr Res Cogn 10:7-14
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
Subramaniam, Karuna; Gill, Jeevit; Slattery, Patrick et al. (2016) Neural Mechanisms of Positive Mood Induced Modulation of Reality Monitoring. Front Hum Neurosci 10:581
Subramaniam, Karuna; Hooker, Christine I; Biagianti, Bruno et al. (2015) Neural signal during immediate reward anticipation in schizophrenia: Relationship to real-world motivation and function. Neuroimage Clin 9:153-63
Keshavan, Matcheri S; Vinogradov, Sophia; Rumsey, Judith et al. (2014) Cognitive training in mental disorders: update and future directions. Am J Psychiatry 171:510-22
Subramaniam, Karuna; Luks, Tracy L; Fisher, Melissa et al. (2012) Computerized cognitive training restores neural activity within the reality monitoring network in schizophrenia. Neuron 73:842-53

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