Patients suffering from schizophrenia and related psychotic illnesses suffer from a varied presentation of hallucinations, delusions, and disorganization. While many of these symptoms are disruptive, it is the cognitive impairments of the illness that are most strongly associated with poor psychosocial functioning. While pharmacological treatments to address cognitive impairments have shown little effect for patients with schizophrenia, cognitive remediation training has been demonstrated to offer cognitive and functional improvements. Previous imaging studies of patients who have undergone cognitive remediation have found increased prefrontal activation associated with cognitive and functional improvements, but it is unclear whether changes in neural connectivity may better characterize and predict changes in cognitive and functional ability. The current proposal will examine schizophrenia patients before and after undergoing a triple blind placebo controlled trial of cognitive remediation. I will first replicate previous findings, demonstrating hat cognitive remediation leads to improvements in prefrontal activation and functional connectivity, but further determine which of these changes best supports changes in cognitive and functional outcome. These analyses will focus on functional activation in a general linear model (GLM) and functional connectivity as measured by independent components analysis (ICA). I will also examine intrinsic connectivity, measured at rest, to determine whether neural plasticity generalizes to instances where task demands are not present. This will allow us to better understand the neural mechanisms and extent of neural plasticity from cognitive remediation. Previous findings have also identified behavioral markers in patients with schizophrenia that predict positive functional change from cognitive remediation. However, it is not yet known whether these markers may also predict neural plasticity. In the second aim of this proposal I will determine whether pre-training cognition, psychosocial functioning, and motivation are predictive of neuro-plastic changes from cognitive remediation. In a second part to this aim, I wil examine the opposite effect, determining whether pre-training neural activation is predictive of behavioral changes in cognitive, functional, or motivational status. Finally, I will use a separate set of data collected from a multi-site placebo-controlled cognitive remediation trial to replicate these results. Findings from this proposal will identify the neural mechanisms that support positive outcomes from cognitive remediation training for schizophrenia.

Public Health Relevance

Patients suffering from schizophrenia and related psychotic illnesses experience cognitive disruptions associated with poor functional outcomes. While these symptoms have been largely resistant to pharmacological treatments, cognitive remediation training has been demonstrated to improve aspects of cognition and psychosocial functioning. Currently the neural mechanisms supporting cognitive and functional change in schizophrenia are not fully understood, and an examination of factors that promote neural plasticity will serve to inform future cognitive interventions.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZMH1-ERB-B (04))
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Rubio, Mercedes
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University of Minnesota Twin Cities
Schools of Arts and Sciences
United States
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Ramsay, Ian S; Nienow, Tasha M; MacDonald 3rd, Angus W (2017) Increases in Intrinsic Thalamocortical Connectivity and Overall Cognition Following Cognitive Remediation in Chronic Schizophrenia. Biol Psychiatry Cogn Neurosci Neuroimaging 2:355-362
Ramsay, Ian S; MacDonald 3rd, Angus W (2015) Brain Correlates of Cognitive Remediation in Schizophrenia: Activation Likelihood Analysis Shows Preliminary Evidence of Neural Target Engagement. Schizophr Bull 41:1276-84