Effect of Transcranial Magnetic Stimulation to the Frontoparietal Attention Network on Anxiety Potentiated Startle

NCT03027414 | Completed Results FDA Device

• 2 other identifiers: 17004217-M-0042
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Researchers want to better understand brain processes related to fear and anxiety. They want to find out if transcranial magnetic stimulation (TMS), a type of brain stimulation, can reduce anxiety. Objective: To see how TMS affects fear and anxiety through memory and attention tasks. Eligibility: Healthy people ages 18-50 who are right-handed Design: Participants will be screened through another protocol. Participants in the pilot study will have 1 visit. This includes: Urine tests Questionnaires about mood and thinking Shock and startle workup: Electrodes are taped to the wrists or fingers. Participants will be shocked to find out what level of shock is uncomfortable but tolerable. They will hear loud, sudden noises through headphones. TMS: A coil is held on the scalp. A magnetic field stimulates the brain. Sometimes they might receive fake TMS. This feels the same as real TMS. They will perform simple tasks. Participants in the main study will have 2 visits within 2 weeks. The first visit includes: Urine tests Questionnaires about mood and thinking MRI: Participants lie on a table that slides into a scanner. They will be in the scanner about 1 hour. A computer screen in the scanner will tell them to perform simple tasks. The second visit includes: Shock and startle workup TMS

Conditions

Healthy Volunteers

Keywords

Anxiety; Startle; Dorsolateral Prefrontal Cortex; Transcranial Magnetic Stimulation (TMS); Working Memory

Outcome Measures

Primary Outcomes (2)

• Anxiety-potentiated Startle

  Electromyography Facial electromyography (EMG) startle responses were recorded from the left orbicularis oculi muscle at 2000 Hz using a Biopac MP160 unit (Biopac; Goleta, CA) via 15 × 20 mm hydrogel coated vinyl electrodes (Rhythmlink #DECUS10026; Columbia, SC). Startle EMG was bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses were scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores with a mean of 50 and a standard deviation of 10 (tx = \[Zx × 10\] + 50). Greater t-scores mean larger blinks, which could be associated with greater anxiety, however there is no clinically relevent threshold. Noisy trials (baseline SD \> 2x run SD) were excluded, and "no blink" (peak \< baseline range) trials were coded as 0. To calculate APS, we subtracted the response during the neutral ITI from the response during the unpredictable ITI.

  Pre and post stimulation

• Working Memory (WM) Related Anxiety Downregulation While Performing the Sternberg WM Task Under Threat of Shock.

  Sternberg Task: Expose subjects to active or sham TMS to a region of the frontoparietal attention network during the Sternberg WM task. Subjects will have to maintain a series of letters in WM for a brief interval during blocks of safety and threat of shock. Electromyography Facial electromyography (EMG) startle responses are recorded from the left orbicularis oculi muscle at 2000 Hz. Startle EMG is bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses are scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores (tx = \[Zx × 10\] + 50). Noisy trials (baseline SD \> 2x run SD) are excluded, and "no blink" (peak \< baseline range) trials are coded as 0. These t scores are then averaged across trials within each condition, and threat-safe contrasts are calculated independently for each level of load (low vs. high) and timing (maintenance vs. ITI).

  Pre and post stimulation

Study Arms (3)

Substudy 1 Active and Sham

EXPERIMENTAL

HVs that receive TMS over the right dlPFC

Drug: Transcranial Magnetic Stimulation Sham; Device: Transcranial Magnetic Stimulation

Substudy 2 Active and Sham

EXPERIMENTAL

HVs that receive TMS over the right dlFPC

Drug: Transcranial Magnetic Stimulation Sham; Device: Transcranial Magnetic Stimulation

Substudy 3 Active and Sham

EXPERIMENTAL

HVs will receive offline TMS to the lest IPS (FPN)

Drug: Transcranial Magnetic Stimulation Sham; Device: Transcranial Magnetic Stimulation

Interventions

Transcranial Magnetic Stimulation Sham DRUG

TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.

Substudy 1 Active and Sham; Substudy 2 Active and Sham; Substudy 3 Active and Sham

Transcranial Magnetic Stimulation DEVICE

TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.

Substudy 1 Active and Sham; Substudy 2 Active and Sham; Substudy 3 Active and Sham

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Ages 18-50
• Subjects able to give their consent
• Right handed

You may not qualify if:

• Non-English speaking individual
• Any significant medical or neurological problems (e.g. cardiovascular illness, respiratory illness, neurological illness, seizure, etc.)
• Current or past Axis I psychiatric disorder(s) as identified with the Structured Clinical Interview for DSM-IV, non-patient edition (SCID-np)
• Active or history of active suicidal ideation.
• Evidence of a first-degree relative with history of psychosis or bipolar disorder; specifically, participant will know diagnosis or treatment in order to confirm presence of disorder.
• Alcohol/drug problems in the past year or lifetime alcohol or drug dependence according to the Structured Clinical Interview for DSM-IV.
• Current use of medications that act on histamine (i.e. diphenhydramine), dopamine (methylphenidate), norepinephrine (buproprion), serotonin (sertraline), or acetylcholine (amitryptiline) receptors. Subjects will be excluded on this basis if they either 1) take these medications on a chronic basis, or 2) if they have taken the drug within 5 half-lives of the drug metabolism, determined by the medical professional at the time of screening.
• History of seizure (childhood febrile seizures are acceptable and these subjects may be included in the study),
• History of epilepsy in self or first degree relatives, stroke, brain surgery, head injury, cranial metal implants, known structural brain lesion.
• Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or currently taking medication that lowers the seizure threshold (table below).
• Pregnancy, or positive pregnancy test.
• Neurological syndrome of the arm (e.g., carpal tunnel syndrome, cubital tunnel syndrome, etc.)
• Positive urine toxicology screen during the screening visit.
• IQ \<80
• Employee or staff of NIMH or are an immediate family member of a NIMH employee, staff, or NIMH contractors.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Balderston NL, Quispe-Escudero D, Hale E, Davis A, O'Connell K, Ernst M, Grillon C. Working memory maintenance is sufficient to reduce state anxiety. Psychophysiology. 2016 Nov;53(11):1660-1668. doi: 10.1111/psyp.12726. Epub 2016 Jul 19.

  PMID: 27434207 BACKGROUND

• Schmitz A, Grillon C. Assessing fear and anxiety in humans using the threat of predictable and unpredictable aversive events (the NPU-threat test). Nat Protoc. 2012 Feb 23;7(3):527-32. doi: 10.1038/nprot.2012.001.

  PMID: 22362158 BACKGROUND

• Slotema CW, Blom JD, Hoek HW, Sommer IE. Should we expand the toolbox of psychiatric treatment methods to include Repetitive Transcranial Magnetic Stimulation (rTMS)? A meta-analysis of the efficacy of rTMS in psychiatric disorders. J Clin Psychiatry. 2010 Jul;71(7):873-84. doi: 10.4088/JCP.08m04872gre. Epub 2010 Mar 9.

  PMID: 20361902 BACKGROUND

• Balderston NL, Roberts C, Beydler EM, Deng ZD, Radman T, Luber B, Lisanby SH, Ernst M, Grillon C. A generalized workflow for conducting electric field-optimized, fMRI-guided, transcranial magnetic stimulation. Nat Protoc. 2020 Nov;15(11):3595-3614. doi: 10.1038/s41596-020-0387-4. Epub 2020 Sep 30.

  PMID: 33005039 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anxiety Disorders

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Results Point of Contact

• Title: Nicholas Balderston
• Organization: University of Pennsylvania

nicholas.balderston@pennmedicine.upenn.edu

2157463058

Study Officials

• Christian Grillon, Ph.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2017
• First Posted: January 23, 2017
• Study Start: January 23, 2017
• Primary Completion: July 19, 2019
• Study Completion: June 29, 2020
• Last Updated: May 17, 2022
• Results First Posted: May 17, 2022

Record last verified: 2020-06

Locations

US (1)