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

Trial Summary

What is the purpose of this trial?

Combat Veterans of post-9/11 conflicts have experienced serious cognitive and emotional problems resulting from exposure to blasts. Recent work suggests that a critical factor influencing the consequences 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 problems than exposure to blasts from \>10 m. So far, the effects of blast-related brain injury on the brain are poorly understood, as to date the effects of blast exposure have received little research focus. The investigators propose to use oscillations in the gamma band (30-100 Hz) of the electroencephalogram (EEG; brain waves) to detect and remediate neural circuit dysfunction related to blast injury in Veterans. 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.

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 data supports the effectiveness of the treatment Auditory gamma sensory stimulation for Traumatic Brain Injury?

Research shows that gamma-band auditory stimulation, particularly at 60 Hz, may improve certain cognitive functions like executive functions in healthy adults. Additionally, structured auditory sensory stimulation programs have shown positive recovery outcomes in patients with severe traumatic brain injury, suggesting potential benefits of auditory stimulation in this context. ^{1 2 3 4 5}

Is Gamma Wave Therapy safe for humans?

There is no evidence of hearing loss in humans due to transcranial magnetic stimulation, which is similar to gamma wave therapy, suggesting it is generally safe for human use. ^{6 7 8 9 10}

How does Gamma Wave Therapy differ from other treatments for traumatic brain injury?

Gamma Wave Therapy is unique because it uses transcranial alternating current stimulation (tACS) to specifically target gamma brain waves, which are involved in brain functions like memory and attention. This approach is different from traditional treatments as it aims to modulate brain activity non-invasively by synchronizing and enhancing gamma oscillations, potentially improving cognitive functions affected by traumatic brain injury. ^{1 2 6 11 12}

Research Team

Kevin M. Spencer, PhD

Principal Investigator

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Modulation of auditory gamma-band responses using transcranial electrical stimulation. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Gamma (60 Hz) auditory stimulation improves intrusions but not recall and working memory in healthy adults. [2023]

3. Brazil pubmed.ncbi.nlm.nih.gov

Behavioral and electrophysiological auditory processing measures in traumatic brain injury after acoustically controlled auditory training: a long-term study. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Cognitive-behavioral recovery in comatose patients following auditory sensory stimulation. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Novel sensory paradigms for neuromodulation in disorders of consciousness in traumatic brain injury. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Auditory field reduction in human following head trauma. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Pinprick-induced gamma-band oscillations are not a useful electrophysiological marker of pinprick hypersensitivity in humans. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Acquired Central Auditory Processing Disorder in Service Members and Veterans. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Hearing complaints among veterans following traumatic brain injury. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

No evidence of hearing loss in humans due to transcranial magnetic stimulation. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Stimulus-related gamma oscillations in primate auditory cortex. [2017]

12. United States pubmed.ncbi.nlm.nih.gov

Multi-sensory Gamma Stimulation Ameliorates Alzheimer's-Associated Pathology and Improves Cognition. [2020]