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

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.

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