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Neuroplasticity in TBI and Schizophrenia

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

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03995368
Acronym
NVEST
Enrollment
93
Registered
2019-06-24
Start date
2020-11-09
Completion date
2023-04-19
Last updated
2024-09-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Schizophrenia, Traumatic Brain Injury

Keywords

Schizophrenia, Traumatic Brain Injury, Neuroplasticity, EEG

Brief summary

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

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.

Interventions

OTHERElectroencephalography

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.

Sponsors

VA Office of Research and Development
Lead SponsorFED

Study design

Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE

Intervention model description

All participants will have the same tasks delivered in the same manner.

Eligibility

Sex/Gender
ALL
Age
25 Years to 55 Years
Healthy volunteers
Yes

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

Design outcomes

Primary

MeasureTime frameDescription
Mismatch Negativity (MMN) Amplitudes in Microvolts1 DayElectroencephalography (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, a more positive value indicates a stronger Repetition Positivity (RP) to the Standard stimuli, and a more negative value indicates a stronger Deviant Negativity (DN) to the Deviant stimuli. The investigators examined the deviant negativity, repetition positivity, and the MMN (which is defined as the difference between the standard-deviant), at three different standard tone repetition sequences (2, 6, or 36). In each case, the RP, DN, and MMN get stronger (i.e., larger amplitude) as the number of standard repetitions (2, 6, 36) increase.
Visual Long-Term Potentiation (LTP) Task1 DayThis LTP task compares visual evoked potentials (VEPs) derived from the EEG before and after a period of extended visual stimulation (tetanization). We measured VEP amplitudes to two different checkerboard patterns before (pre-) and at three time points after (post-) a 10-minute prolonged tetanization checkerboard. VEPs were measured to tetanized (i.e., the same stimuli used in the 10-minute tetanization) or not tetanized (a different checkerboard pattern than the one used in tetanization) stimuli, prior to baseline (pre-), and at 5- (Post 1), 10- (Post 2), and 15- (Post 3) minutes after tetanization. This resulted in 4 VEP measurements for each tetanized and non-tetanized checkerboard. We focused on relative changes from baseline for evidence of plasticity and input specificity (i.e., tetanized vs. non-tetanized stimuli) at each of the 3 post-tetanization time points.

Secondary

MeasureTime frameDescription
Neurocognition1 DayThe MATRICS 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. The range of T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better overall cognitive functioning.
Empathic Accuracy1 DayParticipants 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.
Community Integration1 DayCommunity integration will be assessed by administering the Community Integration Questionnaire, which has 3 sub-scores (home, social, and activities). A higher score indicates better community integration.
Ekman Facial Affect Identification1 DayParticipants 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. Scores range from 0-56, with 56 indicating 100% accurate facial affect identification.

Countries

United States

Participant flow

Participants by arm

ArmCount
People With Schizophrenia
People who have been diagnosed with schizophrenia and meet the investigators' research criteria for symptoms indicative of schizophrenia within their lifetime. Electroencephalography: 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.
26
People With TBI
People who have been diagnosed with a mild or moderate traumatic brain injury (TBI) and meet research criteria indicative of TBI within their lifetime. Electroencephalography: 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.
23
Healthy Controls
People without a history of psychiatric illness or TBI and who do not meet research criteria for a psychiatric illness or TBI. Electroencephalography: 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.
26
Total75

Withdrawals & dropouts

PeriodReasonFG000FG001FG002
Overall StudyDid not meet inclusion criteria163
Overall StudyLost to Follow-up141
Overall StudyWithdrawal by Subject011

Baseline characteristics

CharacteristicPeople With SchizophreniaTotalHealthy ControlsPeople With TBI
Age, Continuous52.5 years
STANDARD_DEVIATION 9.8
48.4 years
STANDARD_DEVIATION 12.4
49.1 years
STANDARD_DEVIATION 12.9
42.9 years
STANDARD_DEVIATION 12.9
Ethnicity (NIH/OMB)
Hispanic or Latino
6 Participants19 Participants7 Participants6 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
20 Participants56 Participants19 Participants17 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants3 Participants1 Participants2 Participants
Race (NIH/OMB)
Asian
0 Participants1 Participants1 Participants0 Participants
Race (NIH/OMB)
Black or African American
14 Participants36 Participants15 Participants7 Participants
Race (NIH/OMB)
More than one race
0 Participants4 Participants1 Participants3 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
12 Participants31 Participants8 Participants11 Participants
Region of Enrollment
United States
26 Participants75 Participants26 Participants23 Participants
Sex: Female, Male
Female
6 Participants7 Participants1 Participants0 Participants
Sex: Female, Male
Male
20 Participants68 Participants25 Participants23 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 260 / 230 / 26
other
Total, other adverse events
0 / 260 / 230 / 26
serious
Total, serious adverse events
0 / 260 / 230 / 26

Outcome results

Primary

Mismatch Negativity (MMN) Amplitudes in Microvolts

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, a more positive value indicates a stronger Repetition Positivity (RP) to the Standard stimuli, and a more negative value indicates a stronger Deviant Negativity (DN) to the Deviant stimuli. The investigators examined the deviant negativity, repetition positivity, and the MMN (which is defined as the difference between the standard-deviant), at three different standard tone repetition sequences (2, 6, or 36). In each case, the RP, DN, and MMN get stronger (i.e., larger amplitude) as the number of standard repetitions (2, 6, 36) increase.

Time frame: 1 Day

ArmMeasureGroupValue (MEAN)Dispersion
People With SchizophreniaMismatch Negativity (MMN) Amplitudes in MicrovoltsStandard20.04 microvoltsStandard Deviation 1.53
People With SchizophreniaMismatch Negativity (MMN) Amplitudes in MicrovoltsDeviant36-0.98 microvoltsStandard Deviation 1.69
People With SchizophreniaMismatch Negativity (MMN) Amplitudes in MicrovoltsStandard360.16 microvoltsStandard Deviation 1.02
People With SchizophreniaMismatch Negativity (MMN) Amplitudes in MicrovoltsStandard6-0.15 microvoltsStandard Deviation 1.39
People With SchizophreniaMismatch Negativity (MMN) Amplitudes in MicrovoltsMMN2-0.59 microvoltsStandard Deviation 2.38
People With SchizophreniaMismatch Negativity (MMN) Amplitudes in MicrovoltsDeviant6-0.80 microvoltsStandard Deviation 1.44
People With SchizophreniaMismatch Negativity (MMN) Amplitudes in MicrovoltsMMN36-1.14 microvoltsStandard Deviation 1.92
People With SchizophreniaMismatch Negativity (MMN) Amplitudes in MicrovoltsMMN6-0.65 microvoltsStandard Deviation 2.01
People With SchizophreniaMismatch Negativity (MMN) Amplitudes in MicrovoltsDeviant2-0.54 microvoltsStandard Deviation 1.82
People With TBIMismatch Negativity (MMN) Amplitudes in MicrovoltsStandard6-0.40 microvoltsStandard Deviation 1.23
People With TBIMismatch Negativity (MMN) Amplitudes in MicrovoltsMMN2-1.19 microvoltsStandard Deviation 1.88
People With TBIMismatch Negativity (MMN) Amplitudes in MicrovoltsMMN6-1.87 microvoltsStandard Deviation 1.98
People With TBIMismatch Negativity (MMN) Amplitudes in MicrovoltsMMN36-3.13 microvoltsStandard Deviation 2.42
People With TBIMismatch Negativity (MMN) Amplitudes in MicrovoltsStandard2-0.46 microvoltsStandard Deviation 1.43
People With TBIMismatch Negativity (MMN) Amplitudes in MicrovoltsStandard360.08 microvoltsStandard Deviation 1.34
People With TBIMismatch Negativity (MMN) Amplitudes in MicrovoltsDeviant2-1.66 microvoltsStandard Deviation 1.36
People With TBIMismatch Negativity (MMN) Amplitudes in MicrovoltsDeviant6-2.26 microvoltsStandard Deviation 1.6
People With TBIMismatch Negativity (MMN) Amplitudes in MicrovoltsDeviant36-3.05 microvoltsStandard Deviation 1.9
Healthy ControlsMismatch Negativity (MMN) Amplitudes in MicrovoltsMMN36-2.90 microvoltsStandard Deviation 2.86
Healthy ControlsMismatch Negativity (MMN) Amplitudes in MicrovoltsMMN2-0.41 microvoltsStandard Deviation 1.89
Healthy ControlsMismatch Negativity (MMN) Amplitudes in MicrovoltsDeviant2-1.32 microvoltsStandard Deviation 1.73
Healthy ControlsMismatch Negativity (MMN) Amplitudes in MicrovoltsMMN6-1.75 microvoltsStandard Deviation 2.11
Healthy ControlsMismatch Negativity (MMN) Amplitudes in MicrovoltsDeviant36-2.55 microvoltsStandard Deviation 2.19
Healthy ControlsMismatch Negativity (MMN) Amplitudes in MicrovoltsStandard60.34 microvoltsStandard Deviation 1.15
Healthy ControlsMismatch Negativity (MMN) Amplitudes in MicrovoltsStandard2-0.91 microvoltsStandard Deviation 1.27
Healthy ControlsMismatch Negativity (MMN) Amplitudes in MicrovoltsDeviant6-1.40 microvoltsStandard Deviation 2
Healthy ControlsMismatch Negativity (MMN) Amplitudes in MicrovoltsStandard360.35 microvoltsStandard Deviation 1.44
Primary

Visual Long-Term Potentiation (LTP) Task

This LTP task compares visual evoked potentials (VEPs) derived from the EEG before and after a period of extended visual stimulation (tetanization). We measured VEP amplitudes to two different checkerboard patterns before (pre-) and at three time points after (post-) a 10-minute prolonged tetanization checkerboard. VEPs were measured to tetanized (i.e., the same stimuli used in the 10-minute tetanization) or not tetanized (a different checkerboard pattern than the one used in tetanization) stimuli, prior to baseline (pre-), and at 5- (Post 1), 10- (Post 2), and 15- (Post 3) minutes after tetanization. This resulted in 4 VEP measurements for each tetanized and non-tetanized checkerboard. We focused on relative changes from baseline for evidence of plasticity and input specificity (i.e., tetanized vs. non-tetanized stimuli) at each of the 3 post-tetanization time points.

Time frame: 1 Day

ArmMeasureGroupValue (MEAN)Dispersion
People With SchizophreniaVisual Long-Term Potentiation (LTP) TaskPost-NonTetanized 30.325 microvoltStandard Deviation 0.857
People With SchizophreniaVisual Long-Term Potentiation (LTP) TaskPost-tetanization 20.677 microvoltStandard Deviation 1.489
People With SchizophreniaVisual Long-Term Potentiation (LTP) TaskPost-tetanization 30.475 microvoltStandard Deviation 1.803
People With SchizophreniaVisual Long-Term Potentiation (LTP) TaskPost-NonTetanized 20.465 microvoltStandard Deviation 0.951
People With SchizophreniaVisual Long-Term Potentiation (LTP) TaskPost-tetanization 11.215 microvoltStandard Deviation 1.601
People With SchizophreniaVisual Long-Term Potentiation (LTP) TaskPre-NonTetanized0.207 microvoltStandard Deviation 0.664
People With SchizophreniaVisual Long-Term Potentiation (LTP) TaskPre-tetanization0.295 microvoltStandard Deviation 1.758
People With SchizophreniaVisual Long-Term Potentiation (LTP) TaskPost-NonTetanized 10.557 microvoltStandard Deviation 0.978
People With TBIVisual Long-Term Potentiation (LTP) TaskPost-tetanization 11.145 microvoltStandard Deviation 1.217
People With TBIVisual Long-Term Potentiation (LTP) TaskPost-NonTetanized 10.197 microvoltStandard Deviation 1.217
People With TBIVisual Long-Term Potentiation (LTP) TaskPost-NonTetanized 20.364 microvoltStandard Deviation 1.515
People With TBIVisual Long-Term Potentiation (LTP) TaskPost-NonTetanized 30.705 microvoltStandard Deviation 1.303
People With TBIVisual Long-Term Potentiation (LTP) TaskPre-tetanization0.201 microvoltStandard Deviation 1.53
People With TBIVisual Long-Term Potentiation (LTP) TaskPost-tetanization 20.360 microvoltStandard Deviation 1.563
People With TBIVisual Long-Term Potentiation (LTP) TaskPost-tetanization 30.226 microvoltStandard Deviation 1.722
People With TBIVisual Long-Term Potentiation (LTP) TaskPre-NonTetanized0.155 microvoltStandard Deviation 1.378
Healthy ControlsVisual Long-Term Potentiation (LTP) TaskPost-NonTetanized 30.142 microvoltStandard Deviation 1.054
Healthy ControlsVisual Long-Term Potentiation (LTP) TaskPost-NonTetanized 10.508 microvoltStandard Deviation 1.271
Healthy ControlsVisual Long-Term Potentiation (LTP) TaskPre-tetanization0.274 microvoltStandard Deviation 1.554
Healthy ControlsVisual Long-Term Potentiation (LTP) TaskPost-tetanization 11.149 microvoltStandard Deviation 1.316
Healthy ControlsVisual Long-Term Potentiation (LTP) TaskPost-tetanization 20.662 microvoltStandard Deviation 1.319
Healthy ControlsVisual Long-Term Potentiation (LTP) TaskPost-tetanization 30.540 microvoltStandard Deviation 1.508
Healthy ControlsVisual Long-Term Potentiation (LTP) TaskPre-NonTetanized0.049 microvoltStandard Deviation 1.203
Healthy ControlsVisual Long-Term Potentiation (LTP) TaskPost-NonTetanized 20.334 microvoltStandard Deviation 1.408
Secondary

Community Integration

Community integration will be assessed by administering the Community Integration Questionnaire, which has 3 sub-scores (home, social, and activities). A higher score indicates better community integration.

Time frame: 1 Day

Population: A higher score indicates better functioning. CIQ-home ranges from 0-10, CIQ-social ranges from 0-12, and CIQ-activities ranges from 0-17.

ArmMeasureGroupValue (MEAN)Dispersion
People With SchizophreniaCommunity IntegrationCIQ-social7.24 score on a scaleStandard Error 2.332
People With SchizophreniaCommunity IntegrationCIQ-home5.88 score on a scaleStandard Error 3.046
People With SchizophreniaCommunity IntegrationCIQ-activities3.00 score on a scaleStandard Error 1.581
People With TBICommunity IntegrationCIQ-social8.45 score on a scaleStandard Error 2.385
People With TBICommunity IntegrationCIQ-home6.05 score on a scaleStandard Error 2.87
People With TBICommunity IntegrationCIQ-activities4.36 score on a scaleStandard Error 1.56
Healthy ControlsCommunity IntegrationCIQ-home6.67 score on a scaleStandard Error 2.461
Healthy ControlsCommunity IntegrationCIQ-activities3.96 score on a scaleStandard Error 1.574
Healthy ControlsCommunity IntegrationCIQ-social8.96 score on a scaleStandard Error 2.116
Secondary

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. Scores range from 0-56, with 56 indicating 100% accurate facial affect identification.

Time frame: 1 Day

ArmMeasureValue (MEAN)Dispersion
People With SchizophreniaEkman Facial Affect Identification42.4 score on a scale (total out of 56)Standard Deviation 7.1
People With TBIEkman Facial Affect Identification46.4 score on a scale (total out of 56)Standard Deviation 5.9
Healthy ControlsEkman Facial Affect Identification44.6 score on a scale (total out of 56)Standard Deviation 5.7
Secondary

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.

Time frame: 1 Day

Population: We are unable to analyze the data due to an error in the scoring script that is not fixable.

Secondary

Neurocognition

The MATRICS 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. The range of T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better overall cognitive functioning.

Time frame: 1 Day

ArmMeasureValue (MEAN)Dispersion
People With SchizophreniaNeurocognition35.13 t-scoreStandard Deviation 15.18
People With TBINeurocognition45.32 t-scoreStandard Deviation 11.34
Healthy ControlsNeurocognition46.29 t-scoreStandard Deviation 12.42

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026