Back to results

Disrupting Fear-based Memory Consolidation

Primary Purpose

Post-Traumatic Stress Disorder

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Continuous theta burst stimulation (cTBS)

Sham continuous theta burst stimulation (cTBS)

About this trial

This is an interventional treatment trial for Post-Traumatic Stress Disorder focused on measuring Fear, Transcranial Magnetic Stimulation, Memory

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

Emory Rehabilitation HospitalRecruiting
Emory University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

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

Sham cTBS

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Changes in Measures of skin conductive response

Skin conductance response (SCR) will be recorded during localization, conditioning, and fear retention tasks using the BIOPAC system MP150 (BIOPAC systems, Inc.) and parameters previously utilized in the lab. SCR is a validated physiological measure of sympathetic arousal, with higher SCR indicating a higher arousal response to conditioned stimuli. Change in SCR from early to late extinction is our primary indicator of the degree of extinction learning. SCR will be scored as a response to individual Conditioned Stimulus (CS)+E and CS- stimuli (maximum SC within 6 seconds post-CS onset, minus average SC over a 2-second prestimulus baseline) and will be square-root transformed for normalization. Early fear extinction will be defined as occurring within the first fear extinction run, with late fear extinction being defined as the second extinction run.

ECG

Heart rate and heart-rate variability (HRV) will be measured using the ECG module of the BIOPAC system at a sampling rate of 1 kilo Hertz (kHz). One 5mm Ag/AgCl (Silver/Silver Chloride) electrode will be placed on the chest above the right clavicle, another electrode will be placed on the chest under the left side of the ribcage.

Acoustic Startle response

The acoustic startle response (eyeblink component) will be measured via electriomyography (EMG) of the right orbicularis oculi muscle. Two 5 mm Ag/AgCl pre-gelled disposable electrodes will be positioned approximately 1 cm under the pupil and 1 cm below the lateral canthus. The startle probe (noise burst) will be a 108-decibel (dB) (A) Sound Pressure Level (SPL), 40-ms burst of broadband noise with a near instantaneous rise time . The startle probe is a white noise burst that is affectively neutral and clearly differentiable from the aversive sound used for the US.

Changes in Fear conditioning and extinction task

Participants will view pictures of animals and tools which will not be repeated. During the 1st phase, 3 categories of images will be displayed: animals, tools, and animal/tool images phase-scrambled. Blocks of 10 images of each category will be displayed 4 times, with each image displayed for 0.75 seconds with a 0.25 s delay between images and 11 s inter-block interval. This task will allow for localization of brain areas activated by animal images vs. tool images, with the phase scrambled images serving as a control. 15 animal and 15 tool images will be randomly displayed for 4.5 s with a fixation cross displayed between each image for 6, 8, or 10 seconds. For the 2nd phase, 10 of either the animal or tool images are assigned as the CS+, and paired with the US, a 1-second loud screeching sound at the end of the image presentation. The other image type, the CS-, will not be paired with the US. In the fear retention phase on Day 2, the CS+ and CS- will be presented without the US.

Full Information

NCT ID

NCT05560113

First Posted

September 15, 2022

Last Updated

September 12, 2023

Sponsor

Emory University

1. Study Identification

Unique Protocol Identification Number

NCT05560113

Brief Title

Disrupting Fear-based Memory Consolidation

Official Title

Forgetting Fear: Establishing a Novel Non-invasive Approach to Disrupt Fear-based Sensory Memory Consolidation in Humans

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 28, 2022 (Actual)

Primary Completion Date

December 2028 (Anticipated)

Study Completion Date

December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Emory University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

This mechanistic study in humans will study an unexplored precision-based approach of non-invasive neuromodulation of sensory cortex with the aim to prevent PTSD by attenuating the sensory encoding of fear memory. The objective of this project is to explore the basic science and therapeutic potential of sensory-emotional reprogramming in humans, and translate this idea into a precise, individualized treatment to reduce the risk that negative emotional sensory experiences lead to PTSD. Understanding sensory-emotional programming in humans could anchor a breakthrough 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 sequela of PTSD.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Post-Traumatic Stress Disorder

Keywords

Fear, Transcranial Magnetic Stimulation, Memory

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

66 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

Sham cTBS

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Other

Intervention Name(s)

Continuous theta burst stimulation (cTBS)

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Sham continuous theta burst stimulation (cTBS)

Intervention Description

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.

Primary Outcome Measure Information:

Title

Changes in Neural Connections: Functional network connectivity

Description

Time Frame

Study Day 30 and Day 31

Title

Changes in Neural Connections: Regional activation

Description

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.

Time Frame

Study Day 30 and 31

Secondary Outcome Measure Information:

Title

Changes in Measures of skin conductive response

Description

Time Frame

Study Day 30 and Day 31

Title

ECG

Description

Time Frame

Study Day 31

Title

Acoustic Startle response

Description

Time Frame

Study Day 31

Title

Changes in Fear conditioning and extinction task

Description

Time Frame

Study Day 30 and Day 31

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Michael Borich, PhD

Phone

404-712-5512

michael.borich@emory.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Jennifer Stevens, PhD

Phone

404-778-1698

jswils4@emory.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Borich, PhD

Organizational Affiliation

Emory University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Emory Rehabilitation Hospital

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michael Borich, PhD

Phone

404-712-0612

michael.borich@emory.edu

Facility Name

Emory University Hospital

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michael Borich, PhD

Phone

404-712-0612

michael.borich@emory.edu

First Name & Middle Initial & Last Name & Degree

Robert C Liu, PhD

Phone

404-727-5274

robert.liu@emory.edu

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Raw and preprocessed magnetic resonance imaging data as well as behavioral data.

IPD Sharing Time Frame

Data will be made available after completion of primary data analyses.

IPD Sharing 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

Learn more about this trial

Disrupting Fear-based Memory Consolidation

We'll reach out to this number within 24 hrs