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

NCT ID: NCT03836976

Last Updated: 2025-04-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-02
• Study Completion Date: 2028-06-30

Brief Summary

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.

Detailed 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 (1-4 Hz) EEG power is increased in Close relative to Far blast exposure groups, as delta power is increased in individuals who have experienced mild traumatic brain injury compared to healthy controls.
• 2) As blast exposure is associated with white matter deficits, and PV+ interneuron axons are myelinated, the investigators will examine whether gamma abnormalities are correlated with white matter deficits as assessed by diffusion tensor imaging (DTI) measures in the auditory cortex, available from the TRACTS database.

In sum, this project seeks to advance the understanding of the effects of blasts on brain function in Veterans by probing the effects of blast exposure on the neural circuits that generate gamma oscillations, and by testing whether a new type of non-invasive brain stimulation can improve brain function in Veterans exposed to blasts. 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.

Conditions

mTBI

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

All participants

All participants receive auditory gamma sensory stimulation.

Group Type: EXPERIMENTAL

Auditory gamma sensory stimulation

Intervention Type: OTHER

Gamma-conditioning stimulation will be

administered in 2 blocks of 3 min each. During each block, participants will be presented with a continuous

tone at the CF (500 or 1200 Hz) that will be amplitude modulated at 40 H

Interventions

Auditory gamma sensory stimulation

Gamma-conditioning stimulation will be

administered in 2 blocks of 3 min each. During each block, participants will be presented with a continuous

tone at the CF (500 or 1200 Hz) that will be amplitude modulated at 40 H

Intervention Type: OTHER

Eligibility Criteria

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

• 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.

• Current alcohol or drug dependence, or abuse within the last 6 months (DSM-IV criteria)
• Hearing impairments as assessed by audiometry

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kevin M. Spencer, PhD

Role: PRINCIPAL_INVESTIGATOR

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Locations

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kevin M Spencer, PhD

Role: CONTACT

Kevin.Spencer@va.gov

(774) 826-1375

Facility Contacts

Terence M Keane, PhD

Role: primary

terry.keane@va.gov

857-364-4551

Other Identifiers

I21RX003162

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N3162-P

Identifier Type: -

Identifier Source: org_study_id