Background: Persistent symptoms after mild traumatic brain injury (mTBI, or concussion) such as headaches, dizziness or sleep difficulties, are common and no treatment has been convincingly shown to ameliorate the symptoms in well-controlled trials. There is some evidence of that TBI is associated with an imbalance in the brain’s electrical activity, typically manifest by unilateral or bilateral increased amplitudes at various frequencies. There is preliminary evidence, but no controlled clinical trials, to indicate that translating the dominant wave forms obtained via electroencephalogram (EEG) to auditory tones and/or low-level electrical scalp stimulation could help the brain reset and improve postconcussive symptoms. We hypothesized that those randomized to ten ~1-hour sessions listening to acoustic stimulation via auditory tones that echo their own brain electrical activity in real time could achieve greater reduction in mTBI-related symptom severity than those randomized to receive randomly generated auditory tones not linked to brainwaves, and that the addition of microelectrical stimulation of the scalp could further enhance the response. Population: Participants are active duty or recently retired service members or their family members, with mTBI 3 months to 10 years prior, and subsequent persistent symptoms resulting in a Neurobehavioral Symptom Inventory (NSI) Score ≥23. The 2 study sites are Uniformed Services University/Walter Reed National Military Medical Center, Bethesda, MD, and Womack Army Medical Center, Fort Bragg, NC. Design type and procedures: The first of two studies was a double-blind, two-arm, controlled clinical trial randomizing 106 individuals with persisting symptoms after mTBI to 10 ~1-hour sessions of either auditory tones linked to brainwaves (LB) or not linked to brainwaves (NL). Sessions were completed over 1-5 weeks. Software algorithms performed real-time analysis of brain electrical activity and utilized a Fourier transformation to translate brainwaves to auditory tones played through standard earbud headphones. Both groups received the same sequence of procedures and comparable levels of social interaction from study investigators and support personnel. Both participants and outcomes assessors were blinded to treatment allocation throughout the study and its analysis. The primary outcome measure is differential change on the NSI. Secondary outcomes include the PTSD Checklist for DSM5 (PCL5), Patient Health Questionnaire-9 (PHQ-9) for depression, and heart rate variability (HRV, measured with the Faros system). The second study uses the same outcome measures to compare 10 sessions of musical notes alone vs. 5 sessions of notes plus microelectrical scalp stimulation, using the same electrodes that measure EEG, all based on measured brainwaves. Auditory tones are delivered ~1/second, electrical stimuli ~1/minute.
Results: Study 1 achieved the target of 106 participants (22% female, mean age 37.1, 2.8 deployments, 3.8 TBIs), who were randomized 1:1 basis to LB or NL. There were no significant differences between the two groups at baseline. Among all study participants, the primary outcome, NSI score, declined from baseline 41.0 to 27.2 after (p < 0.0001), and this improvement was largely sustained at 3 months (31.2) and 6 months (28.4). However, there were no significant differences between the LB (NSI declined from 39.9 at baseline to 28.2 post-intervention, 31.5 at 3 months, and 29.4 at 6 months) and NL (NSI declined from 41.5 at baseline to 26.2, 29.9, and 27.3 respectively). Similar patterns were observed for the PCL5 and PHQ-9 and there was no difference in HRV between groups. Forty-four of a target 86 participants have been enrolled in the second study, and preliminary results of this will be presented at the meeting as well.
Conclusions: Ten hours of resting comfortably in a zero gravity chair in the dark with eyes closed listening to acoustic stimulation improves postconcussive, PTSD and depression symptoms. Although prior studies demonstrated added benefit from tones linked to brainwaves, for other conditions, as administered in this protocol linking the tones to brain electrical activity did not reduce persisting post-TBI symptoms more than unlinked tones. The second study assesses whether LB microelectrical scalp stimulation can further enhance acoustic stimulation.
