Brain Stimulation for PTSD

Overseen By Wen Li, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Florida State University

Must not be taking: Psychoactive medications, Calcium channel blockers

Disqualifiers: Major medical illness, Neurological disorder, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate pre- to post-stimulation

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this study is to develop and test a novel pathophysiology of PTSD by integrating sensory cortical (SC) and amygdala-PFC dysfunctions into a tripartite Sensory-Prefrontal-Cortex-Amygdala (SPA) model.

Will I have to stop taking my current medications?

If you are taking calcium channel blockers or alpha-blockers, you will need to stop these medications for 48 hours before the scan. For other medications, the protocol does not specify, but you should have medication stability for the past 2 months if you are taking psychotropic medications.

Is brain stimulation using tRNS and tACS safe for humans?

Transcranial random noise stimulation (tRNS) and transcranial alternating current stimulation (tACS) are non-invasive brain stimulation methods that have been used in studies on human brain function and behavior. These methods are generally considered safe, as they involve low-intensity electrical currents and have been used in various research settings without significant safety concerns. ^{1 2 3 4 5}

How does the treatment alpha-frequency tACS differ from other treatments for PTSD?

Alpha-frequency tACS is unique because it uses electrical currents to enhance brain wave patterns, specifically alpha oscillations, which are linked to relaxation and reduced anxiety. This non-invasive treatment can increase connectivity in the brain and reduce symptoms of anxiety, offering a novel approach compared to traditional PTSD treatments like medication or talk therapy. ^{1 4 6 7 8}

What data supports the effectiveness of the treatment alpha-frequency tACS for PTSD?

Research shows that alpha-frequency tACS can increase brain connectivity and reduce anxiety, which may help with PTSD. Additionally, a similar treatment, cranial electrotherapy stimulation (CES), has been reported by veterans to improve PTSD symptoms by 62.5%. ^{1 4 9 10 11}

Who Is on the Research Team?

Wen Li, PhD

Principal Investigator

Florida State University

Are You a Good Fit for This Trial?

This trial is for right-handed individuals aged 18-50 with normal vision and smell, who meet specific safety criteria. Participants must have a PTSD diagnosis and if on psychotropic meds, they should be stable for the last 2 months. Substance users must abstain for 48 hours before the experiment.

Inclusion Criteria

Right-handed

If having mild substance use disorder (for patients) or occasional substance use, abstention from use 48 hours before the experiment.

Meeting the tACS screening criteria (e.g., lack of a serious head injury or loss of consciousness)

Exclusion Criteria

Regularly drinking 3 or more alcoholic beverages a day

Concurrent Axis I diagnosis (depression, anxiety, and mild substance use disorder are allowed given their high comorbidity with PTSD)

Severe psychiatric instability or severe situational life crises, including evidence of being actively suicidal or homicidal, or any behavior that poses an immediate danger to self or others

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tACS or RNS stimulation and undergo EEG-fMRI recordings

Immediate pre- to post-stimulation

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• alpha-frequency tACS
• Random noise stimulation

Trial Overview The study tests a new theory of PTSD involving sensory cortex and amygdala-PFC dysfunctions by using two brain stimulation techniques: alpha-frequency tACS (transcranial alternating current stimulation) and random noise stimulation.

How Is the Trial Designed?

Group I: With PTSD for study Experimental Treatment 2 Interventions

80 patients with PTSD in randomized, double-blind, controlled design

Group II: Health controls for study Active Control 2 Interventions

80 healthy subjects in randomized, double-blind, controlled design

Who Is Running the Clinical Trial?

Florida State University

Lead Sponsor

Trials

234

Recruited

41,100+

Published Research Related to This Trial

In a study involving 25 participants, it was found that decreasing the intensity of transcranial alternating current stimulation (tACS) from 1.0 mA to 0.4 mA switched the effect from excitation to inhibition of cortical excitability in the primary motor cortex.

The research demonstrated that different intensities of high-frequency transcranial electrical stimulation can selectively control the enhancement or reduction of motor cortex excitability, with 140 Hz tACS producing stronger inhibition than transcranial random noise (tRNS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Close to threshold transcranial electrical stimulation preferentially activates inhibitory networks before switching to excitation with higher intensities. Moliadze, V., Atalay, D., Antal, A., et al.[2016]

Transcranial alternating current stimulation (tACS) is a promising non-invasive brain stimulation technique that can reset disturbed brain oscillations, potentially improving behavioral outcomes in psychiatric disorders, with initial studies showing no serious adverse events.

The review highlights that tACS may serve not only as a therapeutic tool but also as a diagnostic aid for psychiatric conditions, suggesting its dual role in both treatment and understanding of mental health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial alternating current stimulation (tACS): from basic mechanisms towards first applications in psychiatry. Elyamany, O., Leicht, G., Herrmann, CS., et al.[2023]

Transcranial alternating current stimulation (tACS) at alpha frequencies (8-12 Hz) applied over four days significantly enhanced long-range alpha connectivity in the brain, which lasted more than 24 hours after treatment, indicating potential for lasting neural changes.

This increase in connectivity was associated with reduced anxiety and improved perception of sensory stimuli, suggesting that tACS could be a promising intervention for psychiatric disorders linked to abnormal neural oscillations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lasting connectivity increase and anxiety reduction via transcranial alternating current stimulation. Clancy, KJ., Baisley, SK., Albizu, A., et al.[2019]

Focal brain stimulation shows promise as a treatment for PTSD, with evidence suggesting that targeting specific brain areas involved in fear response and emotion regulation can enhance treatment efficacy.

Current research indicates that downregulating fear-related circuits (like the amygdala) and upregulating emotion regulation areas (like the prefrontal cortex) may be key to improving PTSD treatment outcomes, but more studies are needed to validate these targets and explore additional ones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defining focal brain stimulation targets for PTSD using neuroimaging. van Rooij, SJH., Sippel, LM., McDonald, WM., et al.[2022]

A survey of 152 service members and veterans revealed that cranial electrotherapy stimulation (CES) led to clinical improvements of 25% or more in anxiety (66.7%), PTSD (62.5%), insomnia (65.3%), and depression (53.9%).

Participants overwhelmingly perceived CES as safe (99.0%), and those not on prescription medications found it more effective than when combined with medication, highlighting CES as a promising noninvasive treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Military service member and veteran self reports of efficacy of cranial electrotherapy stimulation for anxiety, posttraumatic stress disorder, insomnia, and depression. Kirsch, DL., Price, LR., Nichols, F., et al.[2015]

Transcranial random noise stimulation (tRNS) is a non-invasive method that can effectively modulate perception and enhance learning in individuals, indicating its potential as a therapeutic tool.

While tRNS shows promise for improving brain function, its effects on higher cognitive processes are inconsistent, suggesting that further research is needed to understand its long-term benefits and mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using noise for the better: The effects of transcranial random noise stimulation on the brain and behavior. van der Groen, O., Potok, W., Wenderoth, N., et al.[2022]

In a study involving 22 healthy subjects, neither high-frequency nor low-frequency transcranial random noise stimulation (tRNS) produced significant changes in auditory steady state responses (ASSR) or resting state EEG activity, suggesting limited efficacy of tRNS in modulating these brain activities.

Interestingly, the sham tRNS condition led to a significant decrease in 20Hz ASSR and an increase in alpha frequency band activity, indicating that the act of stimulation itself, even without active tRNS, may influence brain activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrophysiological evaluation of high and low-frequency transcranial random noise stimulation over the auditory cortex. Schoisswohl, S., Langguth, B., Gebel, N., et al.[2021]

In a study with 15 healthy participants, both 1-mA and 2-mA transcranial direct current stimulation (tDCS) significantly increased motor cortical excitability, as measured by motor-evoked potentials, compared to baseline.

Transcranial random noise stimulation (tRNS) alone did not enhance cortical excitability, suggesting that the addition of a direct current offset is necessary for effective stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the effects of transcranial random noise stimulation and transcranial direct current stimulation on motor cortical excitability. Ho, KA., Taylor, JL., Loo, CK.[2015]

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]

Transcranial alternating current stimulation (tACS) at 10 Hz effectively increased alpha power in the brain and improved general psychopathology symptoms, particularly depression, in patients with schizophrenia, as shown in a double-blind, randomized, placebo-controlled trial involving multiple sessions over a treatment week.

While tACS did not significantly reduce auditory hallucinations, the changes in brain connectivity correlated with symptom improvement, suggesting that tACS may have broader applications in treating mood-related symptoms across different mental health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha transcranial alternating current stimulation reduces depressive symptoms in people with schizophrenia and auditory hallucinations: a double-blind, randomized pilot clinical trial. Zhang, M., Force, RB., Walker, C., et al.[2023]

Transcranial alternating current stimulation (tACS) at alpha frequency can induce lasting changes in brain oscillations, known as aftereffects, which are primarily explained by plasticity mechanisms rather than mere entrainment echoes.

In a study with 12 healthy participants, significant aftereffects were observed only with longer 8-second stimulation trains, suggesting that modifying brain oscillations with tACS could have potential clinical applications for conditions related to abnormal neural synchrony.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha Power Increase After Transcranial Alternating Current Stimulation at Alpha Frequency (α-tACS) Reflects Plastic Changes Rather Than Entrainment. Vossen, A., Gross, J., Thut, G.[2022]

Citations

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

Close to threshold transcranial electrical stimulation preferentially activates inhibitory networks before switching to excitation with higher intensities. [2016]

2. Germany pubmed.ncbi.nlm.nih.gov

Transcranial alternating current stimulation (tACS): from basic mechanisms towards first applications in psychiatry. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Lasting connectivity increase and anxiety reduction via transcranial alternating current stimulation. [2019]

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

Defining focal brain stimulation targets for PTSD using neuroimaging. [2022]

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

Military service member and veteran self reports of efficacy of cranial electrotherapy stimulation for anxiety, posttraumatic stress disorder, insomnia, and depression. [2015]

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

Using noise for the better: The effects of transcranial random noise stimulation on the brain and behavior. [2022]

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

Electrophysiological evaluation of high and low-frequency transcranial random noise stimulation over the auditory cortex. [2021]

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

Comparison of the effects of transcranial random noise stimulation and transcranial direct current stimulation on motor cortical excitability. [2015]

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

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

10. Germany pubmed.ncbi.nlm.nih.gov

Alpha transcranial alternating current stimulation reduces depressive symptoms in people with schizophrenia and auditory hallucinations: a double-blind, randomized pilot clinical trial. [2023]

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

Alpha Power Increase After Transcranial Alternating Current Stimulation at Alpha Frequency (α-tACS) Reflects Plastic Changes Rather Than Entrainment. [2022]