Effects of Connectivity-based rTMS and State-Dependency on Amygdala Activation (ConnecTMS)

Posttraumatic stress disorder (PTSD) is a highly debilitating disease with response rates to pharmacological treatment rarely exceeding 60%. Preliminary attempts have been made to use repetitive transcranial magnetic stimulation (rTMS) as a non-pharmacological treatment alternative, but thus far rTMS approaches have demonstrated only modest efficacy. A major factor contributing to these limited effects stems from the depth penetration of TMS, which is not sufficient to directly modulate deep subcortical structures, such as the amygdala, that are affected in PTSD. Moreover, while rTMS effects have been shown to be state-dependent, (i.e. vary substantially according to the neural state during stimulation), this important factor is rarely considered during the clinical application of rTMS. The current study addresses both of these limitations to improve the therapeutic efficacy of rTMS for PTSD. Here we will develop a protocol to test if connectivity-based rTMS is able to modulate amygdala activity through the functional connections with medial prefrontal cortex, taking advantage of state-dependency to enhance rTMS effects by actively engaging the amygdala through a fear perception task. BOLD activation in the amygdala and its connectivity with the frontal cortex will constitute the primary outcomes to test rTMS efficacy. Heart rate variability and skin galvanic responses, acquired during the presentation of fearful faces, will be used as continuous moderators of task engagement during rTMS. If successful, this study will pave the way for a large-scale study to investigate whether state-dependent, connectivity-based rTMS of the amygdala can improve rTMS efficacy as a clinical treatment for PTSD.

Study Overview

• Status: Completed
• Conditions: Amygdala Activation
• Intervention / Treatment: Device: repetitive transcranial magnetic stimulation; Device: Sham repetitive transcranial magnetic stimulation

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age Restrictions: Young Group (from 18 to 35 years old)
• Use of effective method of birth control for women of childbearing capacity.
• Willing to provide informed consent.

Exclusion Criteria:

• Current or recent (within the past 6 months) history of substance abuse or dependence.
• Current serious medical illness.
• History of seizure, epilepsy, stroke, brain surgery, head injury, cranial metal implants, known structural brain lesion, devices that may be affected by rTMS or MRI (pacemaker, medication pump, cochlear implant, implanted brain stimulator)
• Inability or unwilling to give informed consent.
• Diagnosed any Axis I DSM-IV disorder (MINI, DSM-IV).
• Clinically defined neurological disorder.
• Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure, or currently taking medication that lowers the seizure threshold.
• Claustrophobia (MRI scanner).
• Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Repetitive TMS (rTMS); excitatory rTMS applied over the medial prefrontal cortex (fMRI-guided)	Device: repetitive transcranial magnetic stimulation; excitatory 5Hz rTMS will be used
Sham Comparator: Sham repetitive TMS (rTMS); electrical sham coil applied over the medial prefrontal cortex (fMRI-guided)	Device: Sham repetitive transcranial magnetic stimulation; an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Effect of a rTMS Session on Brain Activation as Measured by the Cerebral Blood Flow (Blood Oxygenation Level Dependent Signal)	Blood oxygenation level dependent (BOLD) will be assessed to evaluate the acute effect of rTMS applied over the medial prefrontal cortex on the amygdala activation. This outcome (expressed a z-score) represents the amygdala activation, either after active rTMS or after sham rTMS. Higher z-scores for active than for sham rTMS indicates that amygdala activity increases after active rTMS compared to sham rTMS, on the other hand lower z-score after active rTMS vs. after Sham rTMS indicated that the amygdala activity would have been reduced with active rTMS.	right after the rTMS session, up to one hour

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Lysianne Beynel, PhD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2019
• Primary Completion (Actual): January 31, 2020
• Study Completion (Actual): January 31, 2020

Study Registration Dates

• First Submitted: November 16, 2018
• First Submitted That Met QC Criteria: November 16, 2018
• First Posted (Actual): November 19, 2018

Study Record Updates

• Last Update Posted (Actual): December 10, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: Pro00101172

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No