Brain Plasticity
Conditions
Keywords
transcranial magnetic stimulation, electroencephalography
Brief summary
Aim 1: Measure local shifts in cortical spectral dynamics following aiTBS. Aim 2: Measure network-specific shifts in task performance following aiTBS. Exploratory aim: Evaluate changes to resting state spectral dynamics in absence of stimulation after aiTBS.
Detailed description
Study Design. The study design comprises a two-group (DLPFC, TPJ) two-condition (active, sham) parallel design. Order of condition will be counterbalanced across subjects. Aim 1 Outcome: Spectral Dynamics. All participants will undergo TEP measurements before and after aiTBS therapy (peri-therapeutic) at the left DLPFC and left TPJ to evaluate changes cortical excitability. We will average the results of repeated single pulse stimulation at an intensity of 120% RMT. Participants will also undergo scalp EEG recording during aiTBS sessions and while at rest. Peri-therapeutic oscillatory bands will be determined by averaging responses to across multiple baseline recording sessions using the MATLAB toolbox FieldTrip for detection of signal within the 4-8Hz spectral band. We hypothesize that theta power increases in participants after completing three days of aiTBS when compared against their respective baselines. Intra-therapeutic changes to theta oscillatory signal will also be collected as an additional primary outcome. Averages of theta oscillatory power within each day of aiTBS will be recorded and compared against baseline. Aim 2 Outcome: Task Performance. Participants will complete both a working memory and affective interference task. The primary outcome measure will be task performance as measured by response time for each subject. Values collected after aiTBS will be compared against their pre-stimulation counterparts using a paired t-test for a given task. The change in these metrics will then be compared across the two tasks using an unpaired t-test. Change in performance metrics for each task will similarly be compared against changes in metrics of the participant group receiving stimulation to the alternate site. We hypothesize performance on network-congruent tasks increase after aiTBS. Data Analyses. The primary responses will be continuously distributed, and we will compare the active to sham conditions using linear mixed effects models. For the response of Aim 1, we will possibly transform the responses to reduce levels of skewness. When conducting TEP measurements, the order in which participants receive stimulation will be randomly assigned such that 50% of participants receive stimulation to the DLPFC first and 50% receive stimulation to the TPJ first. For the behavioral responses of Aim 2 we will use Fisher's z-transform to symmetrize the distribution and stabilize the variance. The models will include two-level categorical factors for treatment and period; as the period and treatment factors are categorical, these models accommodate arbitrary treatment effects, and, for example, do not assume a linear trend across the treatments. We will include random intercepts for participant and will check whether additional covariance structure is required to account for within-participant correlations. We will also examine treatment by period interaction effects. If these effects are significant, we will report estimated effects and associated standard errors and p-values separately by period; if the interaction effects are non-significant, then we will report estimates of effect pooled over periods.
Interventions
DEVICETBS
aiTBS stimulation parameters. A MagVenture MagPro 100X stimulator with a B65 figure-8 coil will be used for the aiTBS sessions. A series of 20, 10 s trains will be presented over the course of the \~3.5 min session. Each train will consist of 2 s of stimulation with an 8 s ITI. During the 2 s of stimulation, 10, 50 Hz bursts will be repeated at intervals of 200 ms (5 Hz).
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Participants will undergo six study visits spaced over a 2-week period (Figure 1). Visit 1 will occur during week one and Visits 2-6 will occur during week two. Spacing between Visit 1 and Visit 2 may be adjusted to accommodate the schedule of the participant, study team, or to accommodate available resources, with the restriction that there will always be a minimum of two days between Visit 1 and Visit 2. On Visit 1, subjects will undergo the following procedures: 1) informed consent, 2) baseline assessment, 3) motor threshold assessment, and 4) a pre-stimulation MRI visit where they will complete the Sternberg WM Task, resting state fMRI, and all the other structural imaging needed to identify the optimal target and orientation of stimulation. Information from the targeting scan will be used to perform neuronavigation to ensure accurate target stimulation. The targeting scan may be skipped if existing data can be used for targeting. On visits 2 and 6, participants will complete the
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Able to give their consent * Right-handed or ambidextrous
Exclusion criteria
* Non-english speaking * Current or past non-anxiety-related psychiatric comorbidity. * Active or history of active suicidal ideation * Alcohol/drug problems in the past year or lifetime alcohol or drug dependence * Medications that act on the central nervous system * History of seizure * History of epilepsy * Increased risk of seizure for any reason * Pregnancy, or positive pregnancy test * Any medical (e.g., stroke, breathing problems, motion disorders) or neurological (e.g., a significant brain injury or brain infection history that increases seizure risk) condition that increases risk for fMRI or TMS (Protocol will follow recommendations from Rossi et al. 2021 doi:10.1016/j.clinph.2020.10.003) * Any metal in their body which would make having an MRI scan unsafe * Any sort of medical implants * Hearing loss * Claustrophobia * orthostatic hypotension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Spectral Dynamics | Participants will undergo six study visits spaced over a 2-week period. Outcome measures will be collected during study visits 2-6 during week 2. | All participants will undergo TEP measurements before and after aiTBS therapy (peri-therapeutic) at the left DLPFC and left TPJ to evaluate changes cortical excitability. We will average the results of repeated single pulse stimulation at an intensity of 120% RMT. Participants will also undergo scalp EEG recording during aiTBS sessions and while at rest. Peri-therapeutic oscillatory bands will be determined by averaging responses to across multiple baseline recording sessions using the MATLAB toolbox FieldTrip for detection of signal within the 4-8Hz spectral band. We hypothesize that theta power increases in participants after completing three days of aiTBS when compared against their respective baselines. Intra-therapeutic changes to theta oscillatory signal will also be collected as an additional primary outcome. Averages of theta oscillatory power within each day of aiTBS will be recorded and compared against baseline. |
| Task Performance | Participants will undergo six study visits spaced over a 2-week period. Outcome measures will be collected during study visits 2-6 during week 2. | Participants will complete both a working memory and affective interference task. The primary outcome measure will be task performance as measured by response time for each subject. Values collected after aiTBS will be compared against their pre-stimulation counterparts using a paired t-test for a given task. The change in these metrics will then be compared across the two tasks using an unpaired t-test. Change in performance metrics for each task will similarly be compared against changes in metrics of the participant group receiving stimulation to the alternate site. We hypothesize performance on network-congruent tasks increase after aiTBS. |
Contacts
CONTACTNicholas Balderston
PRINCIPAL_INVESTIGATORNicholas L Balderston, PhD
University of Pennsylvania
Outcome results
None listed