Neuroplasticity in TBI and Schizophrenia

NCT03995368 | Completed Results

• 1 other identifier: D3171-P
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia; Traumatic Brain Injury

Keywords

Schizophrenia; Traumatic Brain Injury; Neuroplasticity; EEG

Outcome Measures

Primary Outcomes (2)

• 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.

  1 Day

• 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.

  1 Day

Secondary Outcomes (4)

• Neurocognition

  1 Day

• Empathic Accuracy

  1 Day

• Community Integration

  1 Day

• Ekman Facial Affect Identification

  1 Day

Study Arms (3)

People with Schizophrenia

EXPERIMENTAL

People who have been diagnosed with schizophrenia and meet the investigators' research criteria for symptoms indicative of schizophrenia within their lifetime.

Other: Electroencephalography

People with TBI

EXPERIMENTAL

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

Healthy Controls

EXPERIMENTAL

People without a history of psychiatric illness or TBI and who do not meet research criteria for a psychiatric illness or TBI.

Other: Electroencephalography

Interventions

Electroencephalography OTHER

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.

Also known as: EEG

Healthy Controls; People with Schizophrenia; People with TBI

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, 90073-1003, United States

Location

Related Links

• The Green Lab

MeSH Terms

Conditions

Schizophrenia; Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Limitations and Caveats

Limitations mainly revolved around the study being interrupted and participant flow by the COVID-19 pandemic. However, the investigators largely met recruitment goals and successfully completed the study.

Results Point of Contact

• Title: Dr. Jonathan K. Wynn
• Organization: VA Greater Los Angeles Healthcare System

Jonathan.Wynn@va.gov

3104783711

Study Officials

• Jonathan Wynn, PhD

  VA Greater Los Angeles Healthcare System, West Los Angeles, CA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: All participants will have the same tasks delivered in the same manner.

Study Record Dates

• First Submitted: June 14, 2019
• First Posted: June 24, 2019
• Study Start: November 9, 2020
• Primary Completion: April 19, 2023
• Study Completion: April 19, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)