Top-Down Executive Control in Traumatic Brain Injury (TBI), PTSD and Combined

Top-Down Executive Control in TBI, PTSD and Combined TBI/PTSD

This research investigates processes involved with one being able to focus on relevant information and ignore non-relevant information in veterans with PTSD and those with a history of traumatic brain injury. In addition, this study evaluates whether there is an additive effect of having both PTSD and history of TBI on ability to focus attention and inhibit distracting information.

Study Overview

• Status: Completed
• Conditions: PTSD; TBI (Traumatic Brain Injury)

Detailed Description

Traumatic brain injury (TBI) and PTSD both are characterized by deficits in attention, yet it is unclear as to whether this is related to an inability to focus on relevant information or ignore non-relevant information. History of TBI and PTSD are common to returning soldiers from OEF/OIF and thus is highly relevant to veteran health care. It is unclear how TBI and PTSD separately, and together, affect one's ability to focus attention versus inhibit distracting stimuli. This research investigates this issue by use of a working memory paradigm with functional magnetic resonance imaging (fMRI) that entails the subject being instructed to ignore some stimuli and remember other stimuli resulting in discrete biomarkers of (1) task-related enhancement of neural processes as well as (2) suppression of task-irrelevant neural processes. In this way, the specific aspect of attention in TBI and PTSD will be elucidated in addition to exploring whether PTSD and TBI have an additive, or even synergist, effect when combined.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• United States
  • California
    • Martinez, California, United States, 94553
      • Martinez Outpatient Clinic and Community Living Center, Martinez, CA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

OEF/OIF Veterans enrolled in the Northern California Health Care System

Description

Inclusion Criteria:

• All subjects will be between 18 and 40 years of age.
• In order to be included in the mTBI group, participants must have sustained between 1 and 3 mild TBIs. The criteria for TBI will be consistent with what the VA currently uses (i.e., American Congress of Rehabilitative Medicine).

• More specifically, patients will have sustained a traumatically induced physiologic disruption of brain function as indicated by at least one of the following:

  • any period of loss of consciousness,
  • any loss of memory for events immediately before or after the accident,
  • any alteration in mental status at the time of the accident, and
  • focal neurologic deficits.

• Additional criteria for TBI include:

  • TBI must have been sustained during OEF or OIF and
  • TBI must consist of less than 30 minutes loss of consciousness, posttraumatic amnesia of less than 1 hour, and no positive CT/MRI findings.
• For PTSD group inclusion, psychiatric diagnoses will be established via the PTSD Clinical Checklist- Military (PCL-M) and the Clinician Administered PTSD Scale (CAPS).
• For PTSD/mTBI group inclusion, the above criteria must be met for both PTSD and mTBI.
• Control subjects will be OEF/OIF veterans with a history of exposure to combat without current or previous diagnosis of PTSD and no history of TBI.

Exclusion Criteria:

• Subjects who meet diagnostic criteria for drug abuse/dependence over the past year will be excluded.
• Individuals will be excluded if they have neurological confounds (e.g., baseline history of a CNS opportunistic infection, CNS neoplasm, neurosyphilis, current seizure disorder, demyelinating diseases), learning disorder, or current psychiatric disorders involving psychosis (schizophrenia, bipolar disorder with psychosis).
• Patients will also be excluded from the study if they are claustrophobic or are taking cardiovascular medications as these are contraindications for fMRI.
• All 4 subject groups will be matched for age and education.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Control Group; Control group without traumatic brain injury (TBI) or post-traumatic stress disorder (PTSD)
PTSD Group; PTSD (not TBI)
TBI Group; TBI (no PTSD)
TBI+PTSD Group; Combined TBI history and PTSD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Magnetic Resonance Imaging (fMRI) Correlation	Functional magnetic resonance imaging (fMRI) is used to measure neural activity in participants during attentional task, specifically measured as a bold signal change from rest to attention task. We then calculate the correlation between the bold signal (fMRI) and the PTSD CheckList questionnaire score. (The bold signal from fMRI indirectly reflects the brain's use of glucose, the brain's main energy source.) Correlations are reflected in an R-value, and R-values can range from 0-1, where 0 means there is no correlation (or relationship) between the two measures (here, the two measures are the fMRI brain signal and the PTSD score) and 1 means there is a perfect correlation between the two measures. A high correlation in this study would suggest that the more severe a patient's PTSD symptoms are, the harder their brain is having to work to accomplish the attention task. Separate correlations were analyzed for each group, and the overall R-value for each group is reported below.	These are chronic patients and controls who will only be tested at one time point, which corresponds to their entry into the study (after signing consent forms). Data collected at this single time point will be reported.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychodiagnostic Testing: Post-traumatic Stress Disorder Check List (PCL) Measures the Level of Post-traumatic Stress Disorder (PTSD) Symptoms	The PCL is a 17-item questionnaire that measures PTSD symptoms on a scale that ranges from 17-85 points. The total severity score is reported below. A higher score means a higher level of PTSD symptoms.	These are chronic patients and controls who will only be tested at one time point, which corresponds to their entry into the study (after signing consent forms). Data collected at this single time point will be reported.
Neuropsychological Testing (Wechsler Test of Adult Reading)	This test provides an estimate of pre-morbid IQ, which is important to report so that the patient sample can be compared to other similar studies for comparable IQ level and so that pre-morbid IQ can be considered as a potential variable. There are 50 items that are each given a score of 1, so the range of scores is 0-50. The raw score is then converted into an estimated IQ score based on age and education. The scores reported below reflect this estimated IQ score, where normal IQ scores range from 75 as low average to 125 as high average.	These are chronic patients and controls who will only be tested at one time point, which corresponds to their entry into the study (after signing consent forms). Data collected at this single time point will be reported.

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: University of California, Berkeley
• Investigators: Principal Investigator: Juliana V. Baldo, PhD, Martinez Outpatient Clinic and Community Living Center, Martinez, CA

Publications and helpful links

General Publications

• Sozda CN, Muir JJ, Springer US, Partovi D, Cole MA. Differential learning and memory performance in OEF/OIF veterans for verbal and visual material. Neuropsychology. 2014 May;28(3):347-352. doi: 10.1037/neu0000043. Epub 2013 Nov 18.

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2011
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): April 21, 2017

Study Registration Dates

• First Submitted: February 18, 2010
• First Submitted That Met QC Criteria: February 18, 2010
• First Posted (Estimate): February 19, 2010

Study Record Updates

• Last Update Posted (Actual): September 12, 2017
• Last Update Submitted That Met QC Criteria: August 11, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: PTSD; fMRI; attention; TBI (Traumatic Brain Injury)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: D7031-W

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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