Disrupting Fear-based Memory Consolidation

NCT05560113 | Recruiting DMC

• 1 other identifier: STUDY00004510
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 2

Brief Summary

This project represents a unique collaborative opportunity to pursue the essential proof-of-principle demonstration that non-invasive interference of sensory cortical memory consolidation shortly after an emotional experience can attenuate the cued fear response and potentially reduce the risk of developing post-traumatic stress disorder (PTSD). If successful, the study results would anchor a potential advance in the treatment of patients after a traumatic event and seed future animal and clinical studies of emotional sensory cortical memory consolidation to reduce the prevalence and negative sequelae of PTSD.

Conditions

Post-Traumatic Stress Disorder

Keywords

Fear; Transcranial Magnetic Stimulation; Memory

Outcome Measures

Primary Outcomes (2)

• Changes in Neural Connections: Functional network connectivity

  Preprocessing of neuroimaging data will be conducted using fMRI prep. Pre-processed neuroimaging data will undergo first and second level modeling in Statistical Parametric Mapping. First level analysis include an event-related model with the onset and duration of each event included for each condition, and motion included as a regressor. A high-pass filter of 128s will be applied to account for low-frequency drifts. Amygdala regions of interest (ROIs) will be defined anatomically using California Institute of Technology (CIT168) Subcortical Atlas. Primary sensory cortex ROI \& seed coordinates will be defined utilizing voxels within a V1 region mask showing maximal functional connectivity with the amygdala during conditioning.

  Study Day 30 and Day 31

• Changes in Neural Connections: Regional activation

  Preprocessing of neuroimaging data will be conducted using fMRI prep. Pre-processed neuroimaging data will undergo first and second level modeling in Statistical Parametric Mapping. First level analysis include an event-related model with the onset and duration of each event included for each condition, and motion included as a regressor. A high-pass filter of 128s will be applied to account for low-frequency drifts. Whole-brain analysis of changes in local regions of activity will be measured by change in blood-oxygen-level-dependent (BOLD) signal from resting activity. Multiple comparisons using permutation-based methods to control the false positive rate to p\<.05.

  Study Day 30 and 31

Secondary Outcomes (4)

• Changes in Measures of skin conductive response

  Study Day 30 and Day 31

• ECG

  Study Day 31

• Acoustic Startle response

  Study Day 31

• Changes in Fear conditioning and extinction task

  Study Day 30 and Day 31

Study Arms (2)

cTBS: Inhibitory Transcranial magnetic stimulation (TMS) to sensory Cortex

EXPERIMENTAL

Participants will undergo a Functional magnetic resonance imaging (fMRI) scan while performing a fear conditioning/extinction task at the Center for Systems Imaging- Emory University Hospital (CSI-EUH) and then either stay at CSI-EUH or relocate to the Neural Plasticity Research Laboratory at Emory Rehabilitation Hospital. Participants will then be randomly assigned to either receive active or sham continuous theta burst stimulation (cTBS) to transiently disrupt neural activity in the targeted sensory cortex region specifically during the sensory memory consolidation window.

Other: Continuous theta burst stimulation (cTBS)

Sham cTBS

PLACEBO COMPARATOR

Participants will undergo a Functional magnetic resonance imaging (fMRI) scan while performing a fear conditioning/extinction task at CSI-EUH and then either stay at CSI-EUH or relocate to the Neural Plasticity Research Laboratory at Emory Rehabilitation Hospital. Participants will then be randomly assigned to either receive active or sham continuous theta burst stimulation (cTBS) to transiently disrupt neural activity in the targeted sensory cortex region specifically during the sensory memory consolidation window.

Other: Sham continuous theta burst stimulation (cTBS)

Interventions

Continuous theta burst stimulation (cTBS) OTHER

cTBS, a patterned form of TMS, (80% active motor threshold intensity, 3 pulses at 50Hz, 200ms interval, 600 pulses, 40s duration applied over the targeted sensory cortical region using real-time neuronavigation to focally and transiently inhibit neural activity

cTBS: Inhibitory Transcranial magnetic stimulation (TMS) to sensory Cortex

Sham continuous theta burst stimulation (cTBS) OTHER

This will be a sham intervention. An active/sham stimulating coil will be used for double-blinding of stimulation condition. cTBS is safe and has established safety guidelines that will be strictly adhered to during study conduction.

Sham cTBS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide informed consent
• Willingness to participate in study
• No history of musculoskeletal impairment or neurological disease
• Clinical diagnosis of PTSD for individuals in the PTSD group.

You may not qualify if:

• Any participant outside the age range
• Participants that show signs of dementia (score \< 20 on the Montreal Cognitive Assessment)
• Participants that have a history of major head trauma, a neurodegenerative disorder, or recent (\<6 months) substance abuse;
• Participants that had a recent history of Central Nervous System (CNS) active drugs that may influence cortical excitability or learning; or
• Participants that report contraindications to TMS or MRI - if participating in the TMS/MRI experiments
• Current psychoactive medication usage
• Current symptoms of psychosis or bipolar disorder (as indicated by study staff through a clinical interview as part of that study).
• The study will exclude adults unable to consent, individuals who are not yet adults, pregnant women and prisoners on scientific grounds and to minimize risk.

Sponsors & Collaborators

• Emory University: lead

Study Sites (2)

Emory Rehabilitation Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

Emory University Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Study Officials

• Michael Borich, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael Borich, PhD

CONTACT

404-712-5512; michael.borich@emory.edu

Jennifer Stevens, PhD

CONTACT

404-778-1698; jswils4@emory.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 15, 2022
• First Posted: September 29, 2022
• Study Start: November 28, 2022
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: October 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be made available after completion of primary data analyses.
• Access Criteria: : Data will be made publicly available using a data archive (e.g., IPD Sharing Statement LONI Laboratory of Neuro Imaging (LONI), ida.loni.usc.edu) for potential big data analyses as well as reproducibility analyses

Locations

US (2)