Anxiety
Conditions
Keywords
anxiety, transcranial magnetic stimulation
Brief summary
Aim 1: Active cTBS to IPS will disrupt arousal-dependent temporal memory, reflected in reduced relative order discrimination accuracy and expanded temporal distance estimates, relative to sham. Aim 2: Active iTBS to IPS will enhance arousal-dependent temporal memory, reflected in improved relative order discrimination accuracy and compressed temporal distance estimates, relative to sham. Aim 3: Baseline physiological arousal, trait anxiety (STAI), Beck Anxiety Inventory (BAI), trauma symptoms (PCL-5), and individualized E-field strength will predict the magnitude of TBS-induced behavioral changes in temporal memory.
Detailed description
Aim 1 (cTBS): Behavioral outcomes will include relative order discrimination and temporal distance estimation. Data will be analyzed using linear mixed-effects models with fixed effects of stimulation condition (cTBS vs. Sham-cTBS), session (Week 2 vs. Week 4) within the cTBS group, counterbalanced across active and sham sessions, and their interaction, and random intercepts and slopes for participants to account for repeated measures. Continuous physiological arousal (heart rate) and subjective arousal ratings during encoding will be included as covariates. Neural analyses will focus on baseline fMRI collected during high-arousal movie clips. Regions of interest (ROIs) include the intraparietal sulcus, amygdala subregions (basolateral and central-medial), anterior and posterior hippocampus, and perirhinal cortex. IPS-linked network connectivity at baseline will be modeled as a predictor of behavioral sensitivity to cTBS, rather than measuring post-TBS changes. Multiple comparisons will be controlled using false discovery rate (FDR) correction at q \< .05. Aim 2 (iTBS): Analyses will mirror Aim 1, substituting iTBS versus Sham-iTBS as the primary contrast. Behavioral indices of temporal memory and physiological arousal (heart rate, continuous ratings) during encoding will serve as primary outcomes. Baseline IPS connectivity measures will be used to examine individual susceptibility to iTBS modulation of behavior. ROI-level analyses will apply FDR correction (q \< .05). Voxelwise exploratory analyses of baseline functional connectivity may be conducted, with AFNI 3dLME modeling and cluster correction via 3dClustSim (voxelwise p \< 0.001, cluster α = 0.05). Aim 3 - Individual Differences and Exploratory Contrasts: Individual difference analyses will incorporate baseline arousal indices, self-report measures (STAI, BAI, PCL-5), and participant-specific electric field (E-field) estimates from SimNIBS (individualized modeling software) as continuous moderators. Mixed-effects models will examine condition × moderator interactions to determine whether baseline physiology, self-report anxiety measures, or E-field strength predict differential behavioral sensitivity to cTBS or iTBS. Session order will be included as a covariate to account for potential practice or carryover effects. FDR correction (q \< .05) will be applied across all behavioral and ROI-level analyses.
Interventions
DEVICEActive TMS
Theta Burst Stimulation (TBS): TBS will be delivered using a MagVenture MagPro X100 stimulator with a Cool-B65 A/P coil. One session of 600 pulses will be delivered per visit.
DEVICESham TMS
Theta Burst Stimulation (TBS): TBS will be delivered using a MagVenture MagPro X100 stimulator with a Cool-B65 A/P coil. One session of 600 pulses will be delivered per visit.
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Active and sham TMS will be delivered in a double-blind manner.
Intervention model description
This study uses a mixed design: between-subjects for stimulation type (cTBS group vs. iTBS group) and within-subjects for stimulation condition (active vs. sham), counterbalanced across visits. Healthy adult volunteers will be assigned to either cTBS or iTBS. Each participant completes one active and one sham TBS session, separated by a washout period. Week 1 - Baseline MRI/Behavior: Structural and functional MRI to identify individualized IPS targets during arousal-inducing movie clips. Week 2 - Condition A (Active or Sham TBS): TBS delivered immediately prior to encoding six pseudo-randomized emotionally arousing movie clips. Behavioral testing follows encoding (relative order discrimination and temporal distance estimation). Active or sham assignment is counterbalanced within each group. Week 3 - Washout: No visits or stimulation. Ensures independence between Condition A and Condition B. Week 4 - Condition B (Opposite TBS Condition).
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Able to provide informed consent * Right-handed (to ensure consistency in motor threshold determination)
Exclusion criteria
* Non-English speaking * Significant medical problems * Current or past psychiatric disorder * Active or history of suicidal ideation * Alcohol or drug problems in the past year, or lifetime alcohol or drug dependence * Medications affecting the central nervous system * History of seizure, epilepsy, or other neurological problems * Any increased risk for seizure * Pregnancy * Medical conditions that increase risk for fMRI or TMS * Metal in the body that makes MRI unsafe * Medical implants * Claustrophobia * Orthostatic hypotension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Order Discrimination | Task will be administered immediately following TBS or sham stimulation at Weeks 2 and 4. | Participants will view sequences of emotionally arousing movie clips and judge the chronological order in which specific events occurred. Accuracy in determining sequential order will serve as a primary measure of temporal memory. |
| Temporal Distance Estimation | Task will be administered immediately following TBS or sham stimulation at Weeks 2 and 4. | Following each clip sequence, participants will estimate the perceived temporal distance between events. These estimates will capture subjective distortions in the encoding of elapsed time under arousal. |
Contacts
CONTACTNicholas Balderston
PRINCIPAL_INVESTIGATORNicholas L Balderston
University of Pennsylvania
Outcome results
None listed