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Recruiting Not applicable NCT03836976

Detection and Amelioration of Gamma Oscillation Abnormalities in Blast-Related Brain Injury

No applicable phase (e.g. observational)
Conditions: mTBI

Sponsor: VA Office of Research and Development

trial.available_in: БГ
Overview
Combat Veterans of post-9/11 conflicts have experienced serious cognitive and emotional problems resulting from exposure to blasts. Recent work suggests that a critical factor influencing the consequences of blast exposure is distance from the blast, rather than the presence or absence of concussion symptoms. Exposure to blasts from a distance of \<10 m has been associated with significantly greater cognitive and neural problems than exposure to blasts from \>10 m. So far, the effects of blast-related brain injury on the brain are poorly understood, as to date the effects of blast exposure have received little research focus. The investigators propose to use oscillations in the gamma band (30-100 Hz) of the electroencephalogram (EEG; brain waves) to detect and remediate neural circuit dysfunction related to blast injury in Veterans. If successful, this project could lead to new approaches to detect and remediate the effects of blast exposure on Veterans and aid in their functional recovery.
Description
Veterans of recent conflicts have experienced serious cognitive and emotional problems resulting from exposure to blasts. Recent work suggests that a critical factor in the sequelae of blast exposure is distance from the blast, rather than the presence or absence of concussion symptoms. Exposure to blasts from a distance of \<10 m has been associated with significantly greater cognitive and neural disturbances than exposure to blasts from \>10 m. The neural correlates of blast-related brain injury are poorly understood, as to date this type of brain injury has received little research focus. The investigators propose to use oscillations in the gamma band (30-100 Hz) of the electroencephalogram (EEG) to detect and remediate neural circuit dysfunction related to blast injury in Veterans. Gamma band oscillations have been shown to be involved in several brain functions, including visual perception, selective attention, working memory, long term memory, and motor control. Recent studies in animal models have linked the effects of traumatic brain injury to parvalbumin-expressing (PV+) inhibitory interneurons, which are a critical element of the cortical circuitry that generates gamma oscillations. PV+ interneuron dysfunction is associated with deficits in evoked gamma oscillations and increased power of broadband gamma "noise", as well as cognitive deficits. It has also recently been shown that stimulation of PV+ interneurons by patterned stimuli in the gamma band can improve the function of these interneurons, as well as cognitive function, in animal models of neuropsychiatric disorders. Hence, the investigators believe that gamma oscillations and stimulation provide promising targets for investigation in Veterans who suffer from blast-related brain injury. The investigators will investigate gamma band activity and stimulation in 50 Veterans who will be recruited from the participant pool of the VA Translational Research Center for TBI and Stress Disorders (TRACTS) at the VA Boston Healthcare System. * Aim 1: To assess whether evoked gamma deficits and increased gamma noise are present in individuals exposed to Close (\<10 m) vs. Far (\>10 m) blasts. The investigators predict that evoked gamma will be reduced in power and phase synchrony, while gamma noise will be increased in power, in Close compared to Far blast groups. * Aim 2: To determine whether gamma oscillation abnormalities associated with close blast exposure can be remediated by non-invasive patterned sensory stimulation in the gamma band. The investigators will administer 6 min of auditory steady-state stimulation at 40 Hz. The investigators predict that gamma conditioning will increase evoked gamma oscillations elicited by tones at the conditioned vs. unconditioned frequency, while gamma noise will be decreased. These effects will be greater in the Close compared to the Far blast groups. This project also has 2 exploratory aims: * 1\) To investigate whether resting state delta-band (1
Who can participate
Inclusion Criteria: * Research participants will be 50 veterans * Ages 18-65 years * Have experienced blast exposure * Recruited from the VA Translational Research Center for TBI and Stress Disorders (TRACTS) at the VA Boston Healthcare System (VABHS) * Half of the participants will have experienced blast exposure from a Close distance (\<10 m) * Half of the participants will have experienced blast exposure from a Far distance (\>10 m) * These groups will be matched on age and female/male ratio Exclusion Criteria: Initial exclusion criteria for TRACTS are: * History of neurological illness * Huntington's * Parkinson's * dementia, etc * History of seizure disorders unrelated to head injury * Current diagnosis of schizophrenia, bipolar, or other psychotic disorder * Self-reported severe depression or anxiety requiring hospitalization overnight, or current active homicidal and/or suicidal ideation with intent requiring crisis intervention * Cognitive disorder due to general medical condition other than TBI * Unstable psychological diagnosis (suspected psychotic or personality disorder) that would interfere with accurate data collection, determined by consensus of at least three doctoral-level psychologists. Additional exclusion criteria for participants in the present project will be: * Current alcohol or drug dependence, or abuse within the last 6 months (DSM-IV criteria) * Hearing impairments as assessed by audiometry
Interventions
Auditory gamma sensory stimulation
OTHER
Locations 1
United States (1)
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Boston , Massachusetts
Technical details
Status
Recruiting
Phase
Not applicable
Study type
INTERVENTIONAL
Sex
Male and female
Minimum age
18 Years
Maximum age
65 Years
Healthy volunteers
No
Start date
02.12.2019
Completion date
30.06.2028
Registry ID
NCT03836976
Source
clinicaltrials.gov
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