New Applications of Neuroplasticity Biomarkers in Veterans with Traumatic Brain Injury or Schizophrenia

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Veterans with cognitive deficits represent a substantial service and financial burden at the Veterans Administration (VA). Importantly, even with treatment, these Veterans have severe problems with community integration, defined as the ability to return to full participation in major life roles (e.g., competitive employment, school) and supportive social/family networks. Two of the most prominent patient groups within the VA who have cognitive deficits and poor community integration are those with schizophrenia (SCZ) and traumatic brain injury (TBI). There is strong evidence that both disorders are associated with impaired neuroplasticity, which is a key cellular mechanism of cognition. Importantly, several specialized psychosocial and neurostimulation (e.g., tDCS) treatments that target neuroplasticity and cognition have recently emerged. New neuroplasticity- focused interventions that improve the cognitive deficits that lead to poor community integration in SCZ and TBI would highly valuable for the VA healthcare system. However, to evaluate the efficacy of this novel intervention approach, we need objective biomarker measures that validly assess neuroplasticity and are appropriate for use in clinical trials in these populations. These tools currently do not exist. This proposal is designed to address this key treatment development prerequisite. This proposal will adopt a translational approach and use neuroscience-based methods to objectively assess non-invasive neuroplasticity measures in Veterans with cognitive disorders (schizophrenia and TBI) and examine relationships to behavioral measures of cognition and community integration. Given the highly novel application of these electroencephalography (EEG) measures of neuroplasticity to the study of SCZ and TBI, we selected the SPiRE small pilot project mechanism. The research aims for this project are to measure short-term (STP) and long-term potentiation (LTP) using non-invasive EEG to: 1) evaluate the feasibility of recruiting Veterans with cognitive deficits (TBI and SCZ), examine tolerability of the EEG-based neuroplasticity measures, and optimize the paradigms, and 2) evaluate the statistical properties of the neuroplasticity measures, a necessary step to determine whether they will be acceptable to serve as biomarkers. In an exploratory aim, we will evaluate the relationships between the neuroplasticity measures and cognition and community integration. We will utilize paradigms translated from neuroscience studies to objectively assess neurophysiological measures of neuroplasticity. In the proposed 2-year study we will recruit a total of 75 Veterans, (25 with schizophrenia, 25 with TBI, and 25 healthy Veterans without cognitive deficits) from the VA Greater Los Angeles Healthcare system. By identifying the role of neuroplasticity as a key determinant of cognition and community integration in Veterans with cognitive disorders (i.e., schizophrenia or TBI), we will address substantial knowledge gaps in the root causes of poor community integration in Veterans that make very heavy treatment and financial demands on the national VA system. This project will help assess objective biomarkers of neuroplasticity that can be used to gauge the efficacy of interventions targeting cognition in future studies. The results from this study will help guide interventions that ultimately are aimed at improving community integration in Veterans with cognitive disorders.