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Brain Markers of Improvements in Cognitive Functioning

Primary Purpose

TBI (Traumatic Brain Injury), Brain Injuries, Stress

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
State regulation skill training
Treatment-as-usual
Sponsored by
VA Office of Research and Development
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for TBI (Traumatic Brain Injury) focused on measuring cognitive rehabilitation, EEG, TBI, brain networks, attention, memory, executive function

Eligibility Criteria

21 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Veterans
  • History of TBI (as defined by the American Congress of Rehabilitation Medicine and VA, with reported plausible mechanism of head injury, loss of consciousness with some period of posttraumatic alteration in cognition), in the chronic, stable phase of recovery (>6 months from injury)
  • On stable psychoactive medications (> 30 days)
  • Able and willing to participate in EEG, training and, assessments

Exclusion Criteria:

  • Severely apathetic/abulic, aphasic, or other reasons for being unable or unwilling to participate with the training tasks
  • Severe cognitive dysfunction
  • History of neurodevelopmental abnormalities
  • Ongoing illicit drug or alcohol abuse
  • Schizophrenia
  • Bipolar disorder
  • History of other neurological disorders
  • Current medical illnesses that may alter mental status or disrupt participation in the study
  • Active psychotropic medication changes
  • There will be no restriction in regard to gender, race, and socioeconomic status

Sites / Locations

  • VA Northern California Health Care System, Mather, CA

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

State regulation skill training

Treatment-as-usual

Arm Description

This arm utilizes a training system designed to strengthen goal-directed cognitive-emotional state regulation skills. The emphasis is on practice and active application of skills across a range of challenge contexts. Digital scenarios provide experiential learning opportunities, allowing Veterans to apply skills to tackle challenges that are calibrated to maximize learning. Coaches guide learning for successful application of skills to challenges in personal life.

In this arm, participants receive clinical care as usual in VA and other clinics.

Outcomes

Primary Outcome Measures

Composite Score of Attention and Executive Functioning From a Neurocognitive Test Battery
The investigators created a composite score based upon standardized performance on the following neurocognitive measures of attention and executive functions: Wechsler Adult Intelligence Test - 4th Edition- letter number sequence; Auditory Consonant Trigrams - 9, 18, 36 second conditions; Digit Vigilance Test - Total Errors; Delis-Kaplan Executive Function System Color-Word Interference Trials 3 and 4 - Time and Total Errors; & Trails B - Time. Performance on each measure was scored using populations norms, and these scores are then standardized (Z-scored) and averaged to create a composite outcome (the unit measure being Z-score). A Z-score reflects the number of standard deviations a given score is away from the population mean: A Z-score of 0 is equal to the population mean, with positive and negative values reflecting performances above and below the population mean, respectively.
Composite Score of Attention and Executive Functioning From a Neurocognitive Test Battery
The investigators created a composite score based upon standardized performance on the following neurocognitive measures of attention and executive functions: Wechsler Adult Intelligence Test - 4th Edition- letter number sequence; Auditory Consonant Trigrams - 9, 18, 36 second conditions; Digit Vigilance Test - Total Errors; Delis-Kaplan Executive Function System Color-Word Interference Trials 3 and 4 - Time and Total Errors; & Trails B - Time. Performance on each measure was scored using populations norms, and these scores are then standardized (Z-scored) and averaged to create a composite outcome (the unit measure being Z-score). A Z-score reflects the number of standard deviations a given score is away from the population mean: A Z-score of 0 is equal to the population mean, with positive and negative values reflecting performances above and below the population mean, respectively. Change will be analyzed for this data as change from before to after the intervention period.

Secondary Outcome Measures

Change in Event-Related Potential (ERP) Related to Memory Retrieval (Measured in uV)
Electroencephalography (EEG) will be collected during tasks that require attention and working memory. The old/new ERP effect (difference between brain responses to correctly remembered studied items vs. correctly rejected unstudied items) will be analyzed for this data as change from before to after the intervention period.
Event-Related Potential (ERP) Related to Memory Retrieval (Measured in uV)
Electroencephalography (EEG) will be collected during tasks that require attention and working memory. The old/new ERP effect (difference between brain responses to correctly remembered studied items vs. correctly rejected unstudied items) will be analyzed for this data prior to the intervention period.
Network Modularity From EEG
EEG will be collected during a focused rest condition. Network modularity will be estimated from a matrix of connections between electrodes based on phase coherence, a unit-less measure of correlation between phase angles of EEG signals in the theta (4-8 Hz) frequency range. The modularity metric reflects the strength of modular network organization by summing the difference between the fraction of within-module connections to the total fraction of connections across modules, thus ranging from 0 (random) to 1 (completely modular). Change in network modularity will be analyzed for this data as change from before to after the intervention period.

Full Information

First Posted
November 9, 2017
Last Updated
March 6, 2020
Sponsor
VA Office of Research and Development
Collaborators
VA Northern California Health Care System
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1. Study Identification

Unique Protocol Identification Number
NCT03490110
Brief Title
Brain Markers of Improvements in Cognitive Functioning
Official Title
EEG Markers of Training-Induced Improvements in Cognitive Functioning
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
October 1, 2017 (Actual)
Primary Completion Date
March 1, 2019 (Actual)
Study Completion Date
June 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development
Collaborators
VA Northern California Health Care System

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Some of the most common, persistent, and disabling consequences of traumatic brain injury affect an individual's ability to achieve personal goals. Interventions that strengthen abilities such as being able to concentrate, remember, stay calm and overcome challenges, could have far reaching benefits for Veterans. One challenge in rehabilitation is that response to training can be highly variable, and a better understanding of the neural bases for this variability could inform care. This pilot project will test the clinical behavioral effects of a cognitive skill training intervention and explore to what extent changes in markers of the brain's electrical activity (using the non-invasive technique of electroencephalograms, EEG) can explain differences in responses to skill training.
Detailed Description
Detailed Description: Traumatic brain injuries (TBI) can impair cognitive functioning long after the initial trauma. Some of the most common, persistent, and disabling consequences of traumatic brain injury are deficits in higher order cognitive functions that direct more basic processes based on an individual's goals. Symptoms such as distractibility and difficulty holding goal-relevant information in memory can affect achievement of personal and professional goals. These cognitive problems can be exacerbated by post-traumatic stress (PTS) symptoms, commonly observed in the Veteran population. Interventions that strengthen goal-directed regulation of cognitive-emotion states could have far reaching benefits for Veterans. One challenge in rehabilitation is that response to training can be highly variable, and a better understanding of the neural bases for this variability could inform patient care. Investigators have developed a system for training neurocognitive skills that can be used in rehabilitation neuroscience studies to elucidate the neural bases of improvements in cognitive functioning. The training system is designed to help patients improve goal-directed brain state regulation, and preliminary work has investigated brain network parameters that may predict response to training. Electroencephalography (EEG) potentially provides easily accessible markers for the neural bases of improvements with training. Objectives in this pilot study are to investigate the potential of EEG markers to: (1) explain differential responses to attention regulation training; and (2) predict responses to training.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
TBI (Traumatic Brain Injury), Brain Injuries, Stress, Attention Deficit, Executive Dysfunction
Keywords
cognitive rehabilitation, EEG, TBI, brain networks, attention, memory, executive function

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
training in brain state regulation compared to treatment-as-usual
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
State regulation skill training
Arm Type
Experimental
Arm Description
This arm utilizes a training system designed to strengthen goal-directed cognitive-emotional state regulation skills. The emphasis is on practice and active application of skills across a range of challenge contexts. Digital scenarios provide experiential learning opportunities, allowing Veterans to apply skills to tackle challenges that are calibrated to maximize learning. Coaches guide learning for successful application of skills to challenges in personal life.
Arm Title
Treatment-as-usual
Arm Type
Active Comparator
Arm Description
In this arm, participants receive clinical care as usual in VA and other clinics.
Intervention Type
Behavioral
Intervention Name(s)
State regulation skill training
Intervention Description
Participants complete seven supervised training sessions. Training sessions last 2 hours, and participants are requested to complete approximately 2.5 hours of additional skill practice over the course of each week outside of session (total ~4.5 hours per week).
Intervention Type
Other
Intervention Name(s)
Treatment-as-usual
Intervention Description
Participants receive clinical care as usual over a matched time period.
Primary Outcome Measure Information:
Title
Composite Score of Attention and Executive Functioning From a Neurocognitive Test Battery
Description
The investigators created a composite score based upon standardized performance on the following neurocognitive measures of attention and executive functions: Wechsler Adult Intelligence Test - 4th Edition- letter number sequence; Auditory Consonant Trigrams - 9, 18, 36 second conditions; Digit Vigilance Test - Total Errors; Delis-Kaplan Executive Function System Color-Word Interference Trials 3 and 4 - Time and Total Errors; & Trails B - Time. Performance on each measure was scored using populations norms, and these scores are then standardized (Z-scored) and averaged to create a composite outcome (the unit measure being Z-score). A Z-score reflects the number of standard deviations a given score is away from the population mean: A Z-score of 0 is equal to the population mean, with positive and negative values reflecting performances above and below the population mean, respectively.
Time Frame
Week 1, before intervention period (baseline)
Title
Composite Score of Attention and Executive Functioning From a Neurocognitive Test Battery
Description
The investigators created a composite score based upon standardized performance on the following neurocognitive measures of attention and executive functions: Wechsler Adult Intelligence Test - 4th Edition- letter number sequence; Auditory Consonant Trigrams - 9, 18, 36 second conditions; Digit Vigilance Test - Total Errors; Delis-Kaplan Executive Function System Color-Word Interference Trials 3 and 4 - Time and Total Errors; & Trails B - Time. Performance on each measure was scored using populations norms, and these scores are then standardized (Z-scored) and averaged to create a composite outcome (the unit measure being Z-score). A Z-score reflects the number of standard deviations a given score is away from the population mean: A Z-score of 0 is equal to the population mean, with positive and negative values reflecting performances above and below the population mean, respectively. Change will be analyzed for this data as change from before to after the intervention period.
Time Frame
Week 8, after the intervention period
Secondary Outcome Measure Information:
Title
Change in Event-Related Potential (ERP) Related to Memory Retrieval (Measured in uV)
Description
Electroencephalography (EEG) will be collected during tasks that require attention and working memory. The old/new ERP effect (difference between brain responses to correctly remembered studied items vs. correctly rejected unstudied items) will be analyzed for this data as change from before to after the intervention period.
Time Frame
Week 8, after the intervention period
Title
Event-Related Potential (ERP) Related to Memory Retrieval (Measured in uV)
Description
Electroencephalography (EEG) will be collected during tasks that require attention and working memory. The old/new ERP effect (difference between brain responses to correctly remembered studied items vs. correctly rejected unstudied items) will be analyzed for this data prior to the intervention period.
Time Frame
Week 1, before the intervention period
Title
Network Modularity From EEG
Description
EEG will be collected during a focused rest condition. Network modularity will be estimated from a matrix of connections between electrodes based on phase coherence, a unit-less measure of correlation between phase angles of EEG signals in the theta (4-8 Hz) frequency range. The modularity metric reflects the strength of modular network organization by summing the difference between the fraction of within-module connections to the total fraction of connections across modules, thus ranging from 0 (random) to 1 (completely modular). Change in network modularity will be analyzed for this data as change from before to after the intervention period.
Time Frame
Week 8, after the intervention period

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Veterans History of TBI (as defined by the American Congress of Rehabilitation Medicine and VA, with reported plausible mechanism of head injury, loss of consciousness with some period of posttraumatic alteration in cognition), in the chronic, stable phase of recovery (>6 months from injury) On stable psychoactive medications (> 30 days) Able and willing to participate in EEG, training and, assessments Exclusion Criteria: Severely apathetic/abulic, aphasic, or other reasons for being unable or unwilling to participate with the training tasks Severe cognitive dysfunction History of neurodevelopmental abnormalities Ongoing illicit drug or alcohol abuse Schizophrenia Bipolar disorder History of other neurological disorders Current medical illnesses that may alter mental status or disrupt participation in the study Active psychotropic medication changes There will be no restriction in regard to gender, race, and socioeconomic status
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anthony Chen, MD MA
Organizational Affiliation
VA Northern California Health Care System, Mather, CA
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Northern California Health Care System, Mather, CA
City
Sacramento
State/Province
California
ZIP/Postal Code
95655
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Brain Markers of Improvements in Cognitive Functioning

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