Neuroplasticity in TBI and Schizophrenia

Study Overview
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Brief Summary
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This proposal will examine measures of neuroplasticity (the brain's ability to alter its function or structure in response to changes in the environment or novel experiences) in Veterans with schizophrenia or traumatic brain injury (TBI). Both conditions are associated with impaired cognition (for example, attention, memory, learning), which is in turn associated with poor community functioning and integration. However, the two disorders differ in their origins: schizophrenia is a neurodevelopmental disorder appearing usually in late adolescence while TBI is an acquired disorder as the result of an injury to the head. Understanding of the root causes of complex cognitive impairments associated with these disorders remains limited. Neuroplasticity is a fundamental brain process that underlies cognitive functioning and may give insight into the causes of cognitive dysfunction in TBI and schizophrenia. Neuroplasticity will be measured using electroencephalography (EEG) by placing small electrodes on the scalp that record the brain's electrical activity. Participants will listen to simple auditory tones and view simple visual patterns while their EEG is recorded. Additionally, participants will have measures of cognition and clinical interviews for diagnosis of a disorder as well as any current levels of symptoms.

Detailed Description
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EEG recording: In this procedure, the participant's brain function will be recorded while listening to auditory tones or viewing simple visual stimuli. Participants will respond with a button press to specific tones or images. Participants will have all tasks clearly described to them and will practice each task prior to beginning the experiments. While performing these tasks, the brain's electrical activity (commonly referred to as brain waves) will be recording using electroencephalography (EEG). Participant's will wear a cap that contains several electrodes (small, metal discs that are able to pick up electrical activity). A small amount of gel will be applied to the scalp underneath each electrode. These electrodes simply rest on the surface of the scalp and above and below the left eye. It takes approximately 15 minutes to place and prepare the electrodes. The entire recording session will last approximately 90 minutes (including setup). Before having EEG recorded it is important to wash the hair and scalp and not use conditioners or products in the hair as these may interfere with the electrical signal. The gel used is simply washed out of the hair with running water. During the auditory task, participants will listen to a series of tones while watching a silent movie. Participants do not need to pay attention to the tones. During the visual task, participants will view a series of images on a computer screen that consist of a checkerboard pattern. Periodically, they will be asked to respond with a button press if one of the images is different than the others. Interviews: There will be interviews conducted by trained staff that ask questions about participants' demographics (age, gender, education). A clinical interview will be given to all participants to determine if participants have either schizophrenia, a history of a traumatic brain injury, or have no psychiatric illness. All participants will be asked questions about how they are feeling. In addition, participants will answer questions about their family and friends and how they have been getting along with people in their lives. Behavioral testing: Participants will have measures of cognition assessed using various computer-based tasks and pen-and-pencil questionnaires. These tests assess aspects of cognition including memory, attention, language, and motor skills. Participants will also be asked to view a series of pictures of faces and identify the emotion depicted on the face. Finally, participants will be asked to view a series of short videos consisting of a person telling a personal story. Participants will continuously rate how they think that person in the video is feeling (happy, sad, angry, etc.) while telling their story. Additional Information: It may sometimes be necessary to contact a participant's physician to inquire about their medical history or diagnosis. Permission will be sought from participant's in order for contact to be made with their physician.

Official Title
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New Applications of Neuroplasticity Biomarkers in Veterans With Traumatic Brain Injury or Schizophrenia

Conditions
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Schizophrenia, Traumatic Brain Injury

Intervention / Treatment
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* Other: Electroencephalography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Veterans with a diagnosis of schizophrenia or a history of mild or moderate traumatic brain injury (TBI) Veterans without a psychiatric diagnosis and no history of TBI (healthy control participants) will also be recruited No other neurological or medical condition interfering with providing informed consent or valid assessment No current depression based on the Structured Clinical Interview for DSM-5 (SCID-I) or depressive symptoms rated moderate or higher a rating of 13 or higher on the Hamilton Depression Rating Scale No DSM-V substance use disorder greater than mild severity in the past 3 months No form of cognitive remediation in the 6 months prior to testing An 8th grade reading level assessed with the Wide Range Achievement Test (WRAT) Normal or corrected-to-normal vision and hearing Exclusion Criteria: Exclusion criteria for all patient participants include: changes in medication dosage or type 3 months prior to testing hospitalization for psychiatric health in the 3 months prior to testing changes in housing status in the 6 months prior to testing

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: All participants will have the same tasks delivered in the same manner.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: People with Schizophrenia<br>People who have been diagnosed with schizophrenia and meet the investigators' research criteria for symptoms indicative of schizophrenia within their lifetime. | Other: Electroencephalography<br>* The investigators will use EEG combined with measures of cognition and clinical interviews to explore connections between these measures and electrical activity in the brain in Veterans with a diagnosis of schizophrenia or TBI, and healthy controls.<br>* Other names: EEG;|
| Experimental: People with TBI<br>People who have been diagnosed with a mild or moderate traumatic brain injury (TBI) and meet research criteria indicative of TBI within their lifetime. | Other: Electroencephalography<br>* The investigators will use EEG combined with measures of cognition and clinical interviews to explore connections between these measures and electrical activity in the brain in Veterans with a diagnosis of schizophrenia or TBI, and healthy controls.<br>* Other names: EEG;|
| Experimental: Healthy Controls<br>People without a history of psychiatric illness or TBI and who do not meet research criteria for a psychiatric illness or TBI. | Other: Electroencephalography<br>* The investigators will use EEG combined with measures of cognition and clinical interviews to explore connections between these measures and electrical activity in the brain in Veterans with a diagnosis of schizophrenia or TBI, and healthy controls.<br>* Other names: EEG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mismatch Negativity (MMN) | Electroencephalography (EEG) measures the brain's activity while viewing simple visual stimuli or listening to simple auditory tones. MMN is measured while listening to a series of auditory tones, and is derived as the difference in responses to common stimuli minus rare stimuli (e.g., stimuli presented 90% of the time minus stimuli presented 10% of the time). A more negative value indicates stronger MMN. | 1 Day | 
| Visual Long-Term Potentiation (LTP) Task | Electroencephalography (EEG) measures the brain's activity while viewing simple visual stimuli or listening to simple auditory tones. This LTP task compares visual evoked potentials (VEPs) derived from the EEG before and after a period of extended visual stimulation. | 1 Day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurocognition | The MATRIC Consensus Cognitive Battery (MCCB) measures cognition in seven different domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition) and provides a SINGLE summary t-score (age and gender corrected) of overall cognitive functioning. | 1 Day | 
| Empathic Accuracy | Participants watch 9, short video clips of a person recounting a personal story. The participant must continuously rate how the person in the video is feeling while telling the story. The participant's ratings are then correlated with the ratings of the person who was in the video rating how they felt recounting their story. The average correlation for the 9 videos is the dependent variable, with higher positive correlations indicating higher empathic accuracy. | 1 Day | 
| Community Integration | Community integration will be assessed by administering three separate scales (the Lubben Social Network Scale, the Role Functioning Scale, and the Community Integration Questionnaire). A single summary score (comprised of norming scores from each questionnaire and averaging over those normalized scores) is provided. A higher score indicates better community integration. | 1 Day | 
| Ekman Facial Affect Identification | Participants view a series of 56 faces depicting one of seven different emotions (happy, sad, surprised, angry, afraid, disgusted, and neutral). The total number correctly identified faces is the outcome measure, with higher scores indicating better performance. | 1 Day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Traumatic Brain Injury, Neuroplasticity, EEG