Neurotechnology Following Traumatic Brain Injury

Persistent symptoms after concussion or mild traumatic brain injury (mTBI), such as pain and
sleep difficulties, may be related to altered patterns of brain electrical activity,
including changes in amplitude and frequency. The purpose of this study is to evaluate a
noninvasive, closed-loop, acoustic stimulation neurotechnology, High resolution, relational,
resonance-based, electroencephalic mirroring, with standard operating procedures, HIRREM-SOP.
This intervention is intended to improve symptoms by supporting self-optimization of brain
electrical activity. Put more simply, musical tones will be played to echo, or mirror one's
own brainwaves, in real time, allowing opportunity for auto-calibration, self-adjustment, and
equilibration of that brain activity. The hypothesis is that over the course of ten 90-minute
sessions, symptoms related to mTBI, will improve much more with musical tones linked to
brainwaves than with random tones.

Participants will be enrolled at Uniformed Services University/Walter Reed National Military
Medical Center in Bethesda, MD, and Womack Army Medical Center, Fort Bragg, NC. The 106
participants in the first part of the study can be active duty or recently retired service
members, or their family members, who have had a mTBI at least three months and not more than
ten years ago, with related symptoms. Participants will be randomized to either musical tones
that reflect their own brain activity, or random tones. A technologist will oversee each
session in which the tones are presented. Participants and those analyzing outcomes will be
blinded to the nature of the acoustic stimuli received. The primary outcome will be the
change in Neurobehavioral Symptom Inventory scores at three months, and the final follow-up
will occur be at six months. Changes in sleep, pain, dizziness, and general quality of life
will also be measured.

Inclusion Criteria:

- 1 Must have symptoms related to concussion or TBI, not healthy controls Age 18 years
or older.

- 2 Active duty or retired military service member, or dependent beneficiary.

- 3 History of mild TBI, confirmed by administration of the Ohio State University TBI

- Identification Method Interview.

- 4 At least three months, and no more than ten years, since their most recent TBI.

- 5 Persistent symptoms temporally related, or otherwise attributable to, the TBI, such
as

- headache or chronic pain, sensory disturbance including auditory, visual or other
sensory

- symptoms, balance difficulties, or dizziness. After obtaining informed consent,
sufficient

- severity of symptoms for entry into the study will be confirmed by administration of
the

- Neurobehavioral Symptom Inventory (NSI), with a score of 23 or higher required for

- inclusion.

- 6 Willingness to be randomly assigned to one of the two treatment groups and to
provide

- data for all study measures.

- 7 Willingness to abstain from alcohol or recreational drug use throughout the
intervention

- period and up to 3 weeks after completion of the final office-based intervention
session.

- This abstention period is intended to support the stabilization of new brain activity

- patterns that may result from the intervention.

- 8 For individuals using any of the following medication classes (either regularly
scheduled

- or PRN), a willingness both to discontinue or hold those medications at least five (5)
halflives

- prior to the initiation of study procedures, and throughout the period of
participation

- in the study, as well as to sign a release enabling contact between study staff and
their

- prescribing provider, to ensure that the prescriber deems that holding said medication

- during the study period is permissible and reasonable: benzodiazepines, opioids,
antipsychotics,

- mood-stabilizers, anti-convulsants, non-benzodiazepine sleep aids (including

- but not limited zolpidem, eszoplicone, zaleplon, trazadone, and diphenhydramine),
other

- prescribed sedative-hypnotics, or medical marijuana or cannabinoid medication.

- 9 Willingness to abstain from initiation of PRN/as needed usage of the above listed

- medications throughout the period of study participation. This criterion only applies
to

- new PRN prescription or usage. There is no requirement to abstain from a new,
regularly scheduled prescription for one of the above medications during the course of
the study, if the participant's provider

- deems such usage to be indicated. The potential impact of the initiation of any such

- medications during the study will be assessed by conducting sensitivity analyses after
the

- completion of the study.

- 10 Willingness to alert study investigators of any changes in their medication usage

- throughout the course of their study participation.

Exclusion Criteria:

- 1 Unable or unwilling to demonstrate an understanding of the nature and intent of the

- study, and/or to complete informed consent procedures.

- 2 A history of moderate or severe TBI.

- 3 The diagnosis of a psychotic disorder (including schizophrenia and schizoaffective

- disorder), severe depression (PHQ-9 score > 20), bipolar disorder, or active suicidal
or

- homicidal ideation.

- 4 Physically unable to come to the study visits, or to sit in a chair for up to two
hours.

- 5 Inability to hear and repeat a phrase spoken at normal conversational volume.

- 6 Meeting criteria for a current alcohol or substance use disorder.