Detection and Amelioration of Gamma Oscillation Abnormalities in Blast-Related Brain Injury_523_Spencer

NIH RePORTER · VA · I21 · · view on reporter.nih.gov ↗

Abstract

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. We 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, we believe that gamma oscillations and stimulation provide promising targets for investigation in veterans who suffer from blast-related brain injury. We 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. We 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. We will administer 6 min of auditory steady-state stimulation at 40 Hz. We 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 incr...

Key facts

NIH application ID
10427116
Project number
5I21RX003162-03
Recipient
VA BOSTON HEALTH CARE SYSTEM
Principal Investigator
KEVIN M SPENCER
Activity code
I21
Funding institute
VA
Fiscal year
2021
Award amount
Award type
5
Project period
2019-08-01 → 2022-07-31