Gamma Wave Therapy for Traumatic Brain Injury

(DAGABBI Trial)

Overseen By Kevin M Spencer, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Neurological illness, Seizure disorders, Schizophrenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 minutes per session

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using sound waves to aid veterans with cognitive and emotional issues after exposure to explosions. The goal is to determine if these sound waves can enhance brain function and aid recovery. Veterans exposed to blasts from less than 10 meters away or more than 10 meters away might qualify to participate. The researchers aim to develop better treatments for blast-related brain injuries. As an unphased study, this trial offers veterans a unique chance to contribute to groundbreaking research that could improve recovery methods for such injuries.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that auditory gamma sensory stimulation is safe for treating traumatic brain injury?

Research has shown that using sound waves, known as auditory gamma sensory stimulation, is generally safe. In studies with healthy adults, participants listened to sounds at frequencies such as 40 Hz and 60 Hz, and these studies found no significant harmful effects. Similar methods have improved thinking skills in people with dementia, further supporting its safety. Although more research is needed to fully understand its effects, current evidence suggests that this type of sound therapy is well-tolerated, with few side effects reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about auditory gamma sensory stimulation for traumatic brain injury because it offers a novel, non-invasive approach to treatment. Unlike standard care options, which may include medications to manage symptoms or therapies to support recovery, this method leverages sound waves to stimulate brain activity. By targeting gamma waves, which are thought to play a role in brain repair and cognitive functions, this therapy could potentially enhance healing and improve outcomes for patients in a way that current treatments do not.

What evidence suggests that auditory gamma sensory stimulation is effective for traumatic brain injury?

Research shows that sound waves, specifically at 40 Hz, might improve brain function. Studies have found that this sound can create brain wave patterns linked to enhanced thinking and memory. Another study found that this sound helps different parts of the brain work together more effectively. In some cases, using these sound waves over time has been linked to maintaining mental sharpness and improving mood. While researchers are still learning about its effects on brain injuries from blasts, these findings suggest that this sound therapy, provided to all participants in this trial as auditory gamma sensory stimulation, could assist Veterans with cognitive and emotional challenges following such injuries. ^{2 3 6 7 8}

Who Is on the Research Team?

Kevin M. Spencer, PhD

Principal Investigator

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Are You a Good Fit for This Trial?

This trial is for post-9/11 combat veterans aged 18-65 who have experienced blast exposure and are part of the VA Boston Healthcare System. It includes those exposed to blasts from less than or more than 10 meters away, with groups matched by age and gender. Veterans must not have severe mental health issues, neurological illnesses, substance abuse problems, or hearing impairments.

Inclusion Criteria

You have been exposed to a sudden, intense burst of energy or pressure, like from an explosion.

Half of the participants have been close to an explosion within 10 meters.

Recruited from the VA Translational Research Center for TBI and Stress Disorders (TRACTS) at the VA Boston Healthcare System (VABHS)

Exclusion Criteria

I have a cognitive disorder not caused by traumatic brain injury.

I have severe depression or anxiety that required hospitalization or have had serious thoughts of harming myself or others.

This means there are more rules about who can't join the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive auditory gamma sensory stimulation to assess and remediate gamma oscillation abnormalities

6 minutes per session

Multiple sessions

Follow-up

Participants are monitored for changes in gamma power and cognitive function after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Auditory gamma sensory stimulation

Trial Overview The study tests auditory gamma sensory stimulation as a potential treatment for cognitive and emotional problems caused by blast-related brain injuries in veterans. The focus is on detecting and improving abnormalities in brain wave patterns known as gamma oscillations.

How Is the Trial Designed?

Group I: All participants Experimental Treatment 1 Intervention

All participants receive auditory gamma sensory stimulation.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

In a study involving six anesthetized macaque monkeys, gamma oscillations (over 40 Hz) were induced in the auditory cortex by tone bursts, showing that these oscillations are dependent on the frequency of the stimulus and the preferred frequency of the neurons.

The findings suggest that gamma oscillations in the auditory cortex may play a crucial role in synchronizing neuronal activity based on the similarity of their receptive fields, which could be a mechanism for sensory integration across different areas of the cortex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stimulus-related gamma oscillations in primate auditory cortex. Brosch, M., Budinger, E., Scheich, H.[2017]

Auditory gamma entrainment (GENUS) over seven days significantly improved spatial and recognition memory while reducing amyloid levels in the auditory cortex and hippocampus of Alzheimer's disease mouse models (5XFAD mice).

Combining auditory and visual GENUS led to enhanced microglial responses and a broader reduction of amyloid plaques across the neocortex, indicating that multi-sensory stimulation can have widespread positive effects on brain pathology and cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-sensory Gamma Stimulation Ameliorates Alzheimer's-Associated Pathology and Improves Cognition. Martorell, AJ., Paulson, AL., Suk, HJ., et al.[2020]

Veterans with traumatic brain injury (TBI) are at a higher risk for hearing problems, with evidence from self-reports and behavioral studies indicating both peripheral and central auditory dysfunction.

While current treatments like hearing aids and auditory training may help, there is a need for more research to understand the impact of mental health issues on auditory function and to improve rehabilitation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hearing complaints among veterans following traumatic brain injury. Gallun, FJ., Papesh, MA., Lewis, MS.[2020]

A study comparing audiologic results before and after transcranial magnetic stimulation (TMS) in humans found no evidence of hearing loss, even after repeated exposure over several years.

The risk of hearing loss from the acoustic artifact of TMS appears to be minimal, as assessed through various audiological tests including audiograms and auditory evoked potentials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No evidence of hearing loss in humans due to transcranial magnetic stimulation. Pascual-Leone, A., Cohen, LG., Shotland, LI., et al.[2019]

Military service members and veterans are at increased risk for central auditory processing deficits due to exposure to factors like blasts, neurotrauma, hazardous noise, and ototoxicants, highlighting the need for targeted assessments.

Current clinical practices do not adequately address the unique challenges faced by military personnel, indicating a need for improved assessment and rehabilitation strategies, as well as further research to understand the mechanisms behind these auditory processing deficits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acquired Central Auditory Processing Disorder in Service Members and Veterans. Tepe, V., Papesh, M., Russell, S., et al.[2022]

In a study of 40 young adults, those who experienced minor cranial trauma showed significantly higher auditory thresholds, indicating reduced sensitivity to sound, particularly at lower frequencies (19 dB SPL at 500 Hz and 9 dB SPL at 2000 and 4000 Hz).

The trauma patients exhibited earlier BAER wave I responses compared to controls, suggesting that cranial trauma may affect central auditory processing, leading to hypersensitivity to loud sounds while simultaneously reducing sensitivity to softer sounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auditory field reduction in human following head trauma. Collet, L., Duclaux, R., Marion, P.[2019]

In a study involving 20 healthy volunteers, high-frequency electrical stimulation (HFS) increased sensitivity to mechanical pinprick stimuli, indicating a state of mechanical hypersensitivity.

However, the expected increase in scalp gamma-band oscillations (GBOs) associated with this hypersensitivity was not observed at the group level, leading to the conclusion that GBOs may not be a reliable marker for assessing pinprick hypersensitivity in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pinprick-induced gamma-band oscillations are not a useful electrophysiological marker of pinprick hypersensitivity in humans. Gousset, S., Torta, DM., Mouraux, A., et al.[2023]

Transcranial alternating current stimulation (tACS) significantly enhances gamma-band activity in response to auditory stimuli, improving both the magnitude and timing of these responses, while transcranial direct current stimulation (tDCS) does not have this effect.

Both tACS and tDCS strengthen the gamma phase connectome, which is important for synchronizing brain activity, suggesting that these noninvasive neurostimulation techniques can modify clinical biomarkers related to neurological and psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of auditory gamma-band responses using transcranial electrical stimulation. Jones, KT., Johnson, EL., Tauxe, ZS., et al.[2021]

In a study involving 36 healthy adults, gamma-band auditory stimulation at 40 Hz and 60 Hz did not significantly improve long-term verbal memory or working memory performance, suggesting limited efficacy for enhancing memory in healthy individuals.

However, 60 Hz stimulation was found to reduce immediate recall intrusions, indicating a potential positive effect on executive functions, which warrants further investigation into the role of gamma oscillations in cognitive processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma (60 Hz) auditory stimulation improves intrusions but not recall and working memory in healthy adults. Manippa, V., Filardi, M., Vilella, D., et al.[2023]

A study involving six adults aged 20 to 37 with severe traumatic brain injury showed that acoustically controlled auditory training led to long-term improvements in auditory processing, as evidenced by changes in brainstem response measurements one year after training.

The training resulted in increased amplitudes and improved latencies in auditory brainstem responses, indicating enhanced auditory function, while behavioral assessments remained stable, suggesting lasting benefits from the training program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral and electrophysiological auditory processing measures in traumatic brain injury after acoustically controlled auditory training: a long-term study. Figueiredo, CC., Andrade, AN., Marangoni-Castan, AT., et al.[2018]

A structured auditory sensory stimulation program (SSP) applied to 12 male patients with severe traumatic brain injury (TBI) starting 3 days post-injury showed positive recovery effects, particularly in Glasgow Coma Scale (GCS) and cognitive functioning scores after 7 days.

The study found that SSP significantly improved recovery metrics without negatively impacting cerebral dynamics, suggesting it can be a safe and effective intervention to enhance arousal and cognitive recovery in TBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive-behavioral recovery in comatose patients following auditory sensory stimulation. Davis, AE., Gimenez, A.[2019]

Sensory stimulation is commonly used in neurorehabilitation for patients with disorders of consciousness (DoC) after traumatic brain injury (TBI), but there is limited scientific evidence supporting its effectiveness.

Recent studies suggest that using paraclinical tests can help identify signs of awareness in patients and measure the effects of sensory stimulation, indicating a need for more individualized treatment approaches in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel sensory paradigms for neuromodulation in disorders of consciousness in traumatic brain injury. Padua, L., Cuccagna, C., Pazzaglia, C.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10149720/

Gamma sensory entrainment for cognitive improvement in ... Studies have attempted to artificially induce gamma oscillations by using 40 Hz sensory entrainment stimulation.

2. nature.com nature.com/articles/s41598-024-63727-z

Auditory gamma-band entrainment enhances default mode ... This study investigates the effectiveness of entrainment in terms of promoting neural synchrony and spatial connectivity across the cortex.

3. mdpi.com mdpi.com/1660-4601/19/23/15553

Long-Term Multi-Sensory Gamma Stimulation of Dementia ... This study reports on three case studies where the use of gamma stimulation over one year contributed to maintenance of cognition and increases in mood

4. molecularneurodegeneration.biomedcentral.com molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-024-00785-x

Mystery of gamma wave stimulation in brain disorders This review provides an overview of current research progress on the potential therapeutic effects of γ oscillations in various brain disorders.

5. academic.oup.com academic.oup.com/cercor/article/30/1/283/5482276

Marked Increases in Resting-State MEG Gamma-Band Activity ... These novel findings suggest the possibility that abnormal gamma activities may be a proxy for GABA-ergic interneuron dysfunction and a promising neuroimaging ...

6. withpower.com withpower.com/trial/phase-brain-injuries-11-2019-3ae78?lat=36.65114&lng=-97.3517

Gamma Wave Therapy for Traumatic Brain Injury (DAGABBI Trial) In a study involving 36 healthy adults, gamma-band auditory stimulation at 40 Hz and 60 Hz did not significantly improve long-term verbal memory or working ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11952037/

40 Hz multisensory stimulation therapy for cognitive impairment This study explores the impact of a 40 Hz multisensory stimulation treatment on brain function, behavior, and disease progression in animal models

8. mdpi.com mdpi.com/2076-3425/14/9/857

Gamma-Band Auditory Steady-State Response and Attention In our study, we aimed to systemically review all known articles related to the attentional modulation of gamma-band ASSRs.