Concussion Symptom Treatment Using Acoustic Stimulation
In the U.S. military, over 370,000 service members have had mild traumatic brain injuries (mTBI) or concussions since 2000, possibly more due to underreporting. While most recover within 7–30 days, about 15% face persistent postconcussive symptoms (PPCS) for at least 3 months. Despite the end of combat in Iraq and Afghanistan, it’s anticipated that over 20,000 new non-deployed TBI cases will occur annually.
Military veterans with ongoing TBI symptoms report a lower quality of life. Both military personnel and civilians may be at a higher risk for addiction-related disorders after TBI. Without effective treatment, mTBI symptoms may persist, emphasizing the need for safe and effective interventions.
Current mTBI treatment focuses on education, symptom management, and graded return to activity (<30 days). For PPCS, a multidisciplinary approach is used, addressing common symptoms like headaches, cognitive issues, and emotional disturbances, along with comorbid conditions such as sleep disturbances and psychological distress. Novel therapies targeting potential physiological underpinnings for PPCS are needed.
The autonomic nervous system (ANS), regulating physiological balance, is often disrupted after mTBI. Interventions targeting ANS dysfunction show promise for PPCS. Recent research explores the bihemispheric autonomic model (BHAM), suggesting that mTBI induces dysregulation through asymmetrical activity in the cerebral hemispheres. Restoring balance in interventions may aid recovery.
Neurotechnologies like Cereset ResearchTM (CR) impact brain activity. CR, an upgraded version of HIRREMâ, uses a closed-loop paradigm to echo brainwaves as audible tones, showing potential in reducing symptoms persisting at least 3 months post-injury.
The Study
Effective interventions are essential for addressing postconcussive symptoms. The study reports the outcomes of a randomized, sham-controlled trial of CeresetResearchTM Standard Operating Procedures (CR-SOP), a noninvasive, closed-loop, allostatic, acoustic stimulation neurotechnology previously demonstrated to improve insomnia.
Methods
Participants
In this multisite, randomized controlled trial, participants were recruited from Uniformed Services University/Walter Reed National Military Medical Center in Bethesda, MD, and Womack Army Medical Center at Fort Bragg (now Fort Liberty), NC. They included active duty service members, retired veterans, or military dependents with a history of traumatic brain injury (TBI) occurring at least 3 months but no more than 10 years prior. This timeframe aimed to exclude those in the acute TBI recovery period and cover TBIs likely during military service while avoiding a significant focus on childhood or adolescent TBIs.
All participants were eligible for care in the Department of Defense healthcare system, potentially addressing concerns about socioeconomic status and access to care. They needed to show likely persistent postconcussive symptoms (PPCS) with a score of ≥23 on the Neurobehavioral Symptom Inventory (NSI), and TBI history was confirmed through the Ohio State University TBI Identification Method Interview.
Inclusion criteria also required participants to abstain from alcohol or recreational drugs during the intervention phase and for at least 3 weeks afterward. They were instructed to discontinue specific medications before the study, including benzodiazepines, opioids, antipsychotics, mood stabilizers, anticonvulsants, non-benzodiazepine sleep aids, prescribed sedative-hypnotics, and medical marijuana or cannabinoid medication. Initiation of these medications was also to be avoided during the study period.
Exclusion criteria included a history of moderate or severe TBI, a diagnosis of a psychotic disorder, severe depression (PHQ-9 score ≥20), bipolar disorder, current alcohol or substance use disorder, or active suicidal or homicidal ideation. Individuals with hearing difficulties that impaired normal conversational volume were also excluded. Recruitment at USUHS/Walter Reed and Fort Bragg occurred through various means, including informational tables, physician referrals, word of mouth, social media, and local news stories.
Study Design
This prospective double-blind, two-arm, randomized controlled clinical trial involved participants who were randomly assigned to either the intervention or a random tones control group. The randomization was done using blocked randomization with a block size of 4, and the scheme was created by an investigator with no participant contact. All research staff, except the Technologist, were blinded to group assignments. Participants remained blind to treatment groups until the final follow-up assessment.
Fifty participants received CR-SOP with acoustic stimulation linked to brainwaves (LB, intervention), while 54 received CR-SOP with random engineered tones not linked to brainwaves (NL, control). The target enrollment, after potential attrition, was at least 42 per group to achieve 80% power, based on pilot studies and a priori power analyses. All study procedures were approved by the Uniformed Services University Institutional Review Board (IRB), with secondary approval from Walter Reed’s IRB and Womack Army Medical Center’s Human Research Protection Program.
Sessions began 0–14 days following the initial enrollment visit, with each participant receiving 10 sessions over 1–5 weeks. Although participants were encouraged to complete sessions close together for optimal benefit, sessions were scheduled at participants’ convenience, considering COVID-19-related disruptions in 2020. Assessments were repeated at 0–14 days (V2), 3 months (V3, the primary endpoint), and 6 months (V4) post-intervention. Due to pandemic-related closures, some in-person study activities were disrupted, leading to breaks, withdrawals, and delayed or remote assessments, limited to questionnaires for some participants.
Results
Results of the study showed that out of 118 subjects assessed for eligibility, 106 eligible participants consented and enrolled, with two dropping out before randomization. The randomization of 104 participants revealed no significant differences between the two groups at baseline. The mean age of participants was 37.2 years, with 21% being women. Demographic factors, military status, history, clinical comorbidities, and prior therapeutic modalities were similar between the groups, reflecting characteristics of the overall military population.
Most traumatic brain injuries (TBIs) in this cohort resulted from explosions, fights, falls, and/or crashes. The time taken to complete sessions and intervals to data collection points were comparable for both groups. There were no significant differences in the total days for completing the intervention, in-office days receiving sessions, days between the initial visit and the start of sessions, the number of breaks in sessions, or days between the last session and the primary endpoint assessment at 3 months.
Both groups reported similar rates of relaxation and falling asleep during sessions (LB: 92%, NL: 93%). COVID-19 restrictions and lost data affected both groups similarly, with adjusted protocols for data collection in virtual visits. For participants under COVID-19 adjusted protocols, questionnaire data were obtained, but physical measures were not collected. Recordings for heart rate variability (HRV) analysis compared to baseline were adequate for 68 participants at the 3-month assessment and 56 at the 6-month assessment.
Final Thoughts
Participation in a study involving approximately 10 cumulative hours of resting comfortably in a zero-gravity chair, with eyes closed and exposure to computer-generated acoustic stimulation, is well-tolerated. This approach is linked to significant improvements in postconcussive symptoms, both clinically and statistically. However, the study results do not suggest that, in a primarily active-duty group experiencing postconcussive symptoms, listening to acoustic stimulation based on one’s own brain electrical activity reduces symptoms or enhances brain function or heart rate variability more than randomly generated, computer-engineered acoustic stimulation.
Ongoing research suggests that combining acoustic stimulation with micro-electrical stimulation of the scalp, also based on brain electrical activity, may have a greater impact on improving postconcussive symptoms.
Future studies will explore whether the gains observed in this study can be enhanced, such as achieving greater symptom improvement with fewer treatment sessions, through the combination of acoustic and micro electrical stimulation in a similar noninvasive neurotechnology intervention.
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