Auditory Stimulation During Sleep for Schizophrenia

Overseen By Dara Manoach, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must be taking: APDs

Must not be taking: Psychotropic medications

Disqualifiers: Neurological disorders, Chronic conditions, others

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

Compensation: Varies

Number of Visits: 2

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you have schizophrenia and are on a stable dose of antipsychotic drugs, you can continue taking them. However, if you are a healthy adult, you cannot participate if you are currently using psychotropic medications or medications that affect sleep or thinking.

What data supports the effectiveness of the treatment Closed loop auditory stimulation during sleep for schizophrenia?

Research shows that auditory stimulation during sleep can increase certain brain activities related to sleep in people with schizophrenia, similar to healthy individuals. Although this did not improve memory in the study, it suggests potential for treating sleep-related issues in schizophrenia. ^{1 2 3 4 5}

Is auditory stimulation during sleep safe for humans?

Auditory stimulation during sleep, such as closed-loop auditory stimulation, is generally considered safe for humans. Studies have shown it can influence brain activity during sleep without significant adverse effects, although more research is needed to confirm its safety across different conditions. ^{1 3 4 6 7}

How does the treatment of auditory stimulation during sleep for schizophrenia differ from other treatments?

This treatment is unique because it uses sound to enhance brain activity during sleep, specifically targeting slow waves and sleep spindles, which are often disrupted in schizophrenia. Unlike traditional medications, this non-invasive approach aims to improve sleep-related brain functions without drugs. ^{1 2 4 7 8}

What is the purpose of this trial?

In this research study the investigators will use sleep headbands to measure brain rhythms and to improve their coordination across brain regions. The headbands will be worn at home for multiple nights. On some nights the headbands will play soft sounds at specific times during sleep. The investigators are interested in learning whether this timed auditory stimulation may be a strategy to improve the coordination of sleep rhythms across brain regions, improve network communication, and as a result, improve memory. The investigators will study 30 adults aged 18-45 with schizophrenia and 30 demographically matched healthy controls. Participants will first have a daytime MRI scan, during which they will complete a finger tapping motor sequence task (MST), followed by a week of sleep at home with a sleep headband. They will also do the MST at home on two of the nights. On the final day of the study, participants will return for a second MRI scan.

Eligibility Criteria

This trial is for adults aged 18-45 who have been diagnosed with schizophrenia. Participants will use a sleep headband at home to test if auditory stimulation during sleep can improve brain coordination and memory. They must be able to undergo MRI scans and perform a motor sequence task.

Inclusion Criteria

Additional inclusion for Adults with schizophrenia: DSM-V confirmed diagnosis of schizophrenia

Fluent in English

I have schizophrenia and am not on medication or have been on a stable dose.

Exclusion Criteria

Additional Exclusion Criteria for Healthy adults: History of mental illness

IQ <85

I have a neurological condition or seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline Assessment

Participants undergo a daytime MRI scan and complete a finger tapping motor sequence task (MST)

1 day

1 visit (in-person)

Home Sleep Monitoring

Participants wear sleep headbands at home for multiple nights, with auditory stimulation on some nights

5 nights

Follow-up Assessment

Participants return for a second MRI scan and complete post-stimulation assessments

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in hippocampal microstructural integrity and functional connectivity

1 week

Treatment Details

Interventions

• Closed loop auditory stimulation during sleep

Trial Overview The study tests whether soft sounds played through a sleep headband during specific times in the night can enhance brain network communication in individuals with schizophrenia, potentially leading to improved memory.

Participant Groups

Group I: Schizophrenia Experimental Treatment 1 Intervention

Adult outpatients with a diagnosis of schizophrenia.

Group II: Healthy Controls Active Control 1 Intervention

Adult participants screened to exclude a personal history of mental illness, family history of schizophrenia spectrum disorder, and psychoactive medication use.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Findings from Research

In a study involving 18 patients with schizophrenia, real-time auditory stimulation during sleep successfully increased slow wave and sleep spindle activity, similar to responses seen in healthy individuals.

Despite the positive electrophysiological changes, the auditory stimulation did not lead to any improvement in memory performance, indicating that while the approach shows promise, it currently does not enhance memory consolidation in patients with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auditory stimulation in-phase with slow oscillations to enhance overnight memory consolidation in patients with schizophrenia? Weinhold, SL., Lechinger, J., Timm, N., et al.[2022]

A novel auditory closed-loop stimulation technique was successfully used to manipulate theta activity during REM sleep in a study involving 16 healthy young adults, demonstrating the ability to entrain EEG activity to 5 Hz.

The stimulation led to an initial increase in theta power followed by a prolonged suppression, along with an increase in beta power, suggesting potential for further research into the effects of REM sleep on behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase-locked auditory stimulation of theta oscillations during rapid eye movement sleep. Harrington, MO., Ashton, JE., Ngo, HV., et al.[2021]

In a pilot study involving 18 patients with schizophrenia and refractory auditory hallucinations, low-frequency deep transcranial magnetic stimulation (TMS) was administered, but results showed no significant difference in improvement between the active treatment and sham groups.

Despite initial encouraging results, the study concluded that this specific TMS protocol did not have a statistically significant effect on reducing auditory hallucinations or improving other clinical symptoms in the patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep transcranial magnetic stimulation add-on for the treatment of auditory hallucinations: a double-blind study. Rosenberg, O., Gersner, R., Klein, LD., et al.[2022]

Closed-loop auditory stimulation can enhance sleep rhythms, specifically increasing delta, theta, and sigma power during non-rapid eye movement (NREM) sleep, which is crucial for brain recovery and memory consolidation.

The study found that this stimulation specifically improved the coupling between delta and sigma activity in the right parietal area, suggesting a targeted approach to enhance sleep-dependent neuroplasticity in specific brain regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in cross-frequency coupling following closed-loop auditory stimulation in non-rapid eye movement sleep. Krugliakova, E., Volk, C., Jaramillo, V., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Neuromodulation of sleep rhythms in schizophrenia: Towards the rational design of non-invasive brain stimulation. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Auditory stimulation in-phase with slow oscillations to enhance overnight memory consolidation in patients with schizophrenia? [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Sleep disturbances in patients with schizophrenia : impact and effect of antipsychotics. [2022]

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

Phase-locked auditory stimulation of theta oscillations during rapid eye movement sleep. [2021]

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

Deep transcranial magnetic stimulation add-on for the treatment of auditory hallucinations: a double-blind study. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

A psychophysiological investigation of the long-term effects of clozapine upon sleep patterns of normal young adults. [2019]

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

Examining the optimal timing for closed-loop auditory stimulation of slow-wave sleep in young and older adults. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Changes in cross-frequency coupling following closed-loop auditory stimulation in non-rapid eye movement sleep. [2021]