Theta Burst Stimulation in Young Adults With Depression

Not Applicable

Completed

Conditions: Depression

Interventions: Device: Intermittent Theta Burst Stimulation
Device: Continuous Theta Burst Stimulation
Device: Sham Theta Burst Stimulation

Registration Number: NCT03737032

Lead Sponsor: Erika Forbes

Brief Summary: For the proposed 2-year study, the investigators will conduct a within-subject, counterbalanced investigation using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to examine the acute effects of theta-burst stimulation (TBS) on function in dorsomedial prefrontal cortex (dmPFC) in 35 young adults with depression (18-25 years, 50% female).

Detailed Description: Each participant will undergo 3 sessions of TMS, one each of continuous and intermittent TBS--with the goal of decreasing or increasing dmPFC responding, respectively--and one of sham TBS. Session order will be counterbalanced, with a double-blind approach to condition. Brain function, behavior, and mood will be assessed before and after each TBS session. Broadly, the investigators predict that inhibitory TBS to the dmPFC will enhance neural, behavioral, and subjective aspects of reward function by reducing dmPFC function and dmPFC connectivity with the ventral striatum (VS).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 29

Inclusion Criteria

• DSM-5 Diagnosis of Major Depressive Disorder, Persistent Depressive Disorder (Dysthymia), Other Specified Depressive Disorder, or Other Unspecified Depressive Disorder

Exclusion Criteria

Bipolar disorder, substance dependence, or lifetime history of psychosis
Neurological disorder (e.g., seizure disorder)
Pregnant
MRI contradictions: claustrophobia, permanent orthodontic devices, metal implants or other forms of metal in the body that cannot be removed

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Intermittent, Continuous, Sham Order	Continuous Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Intermittent theta burst stimulation, 2) Continuous theta burst stimulation, 3) Sham theta burst stimulation.
Continuous, Sham, Intermittent Order	Sham Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Continuous theta burst stimulation, 2) Sham theta burst stimulation, 3) Intermittent theta burst stimulation.
Sham, Intermittent, Continuous Order	Intermittent Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Sham theta burst stimulation, 2) Intermittent theta burst stimulation, 3) Continuous theta burst stimulation.
Intermittent, Continuous, Sham Order	Sham Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Intermittent theta burst stimulation, 2) Continuous theta burst stimulation, 3) Sham theta burst stimulation.
Intermittent, Sham, Continuous Order	Continuous Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Intermittent theta burst stimulation, 2) Sham theta burst stimulation, 3) Continuous theta burst stimulation.
Continuous, Sham, Intermittent Order	Intermittent Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Continuous theta burst stimulation, 2) Sham theta burst stimulation, 3) Intermittent theta burst stimulation.
Intermittent, Continuous, Sham Order	Intermittent Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Intermittent theta burst stimulation, 2) Continuous theta burst stimulation, 3) Sham theta burst stimulation.
Intermittent, Sham, Continuous Order	Intermittent Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Intermittent theta burst stimulation, 2) Sham theta burst stimulation, 3) Continuous theta burst stimulation.
Intermittent, Sham, Continuous Order	Sham Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Intermittent theta burst stimulation, 2) Sham theta burst stimulation, 3) Continuous theta burst stimulation.
Continuous, Intermittent, Sham Order	Intermittent Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Continuous theta burst stimulation, 2) Intermittent theta burst stimulation, 3) Sham theta burst stimulation.
Continuous, Intermittent, Sham Order	Continuous Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Continuous theta burst stimulation, 2) Intermittent theta burst stimulation, 3) Sham theta burst stimulation.
Continuous, Intermittent, Sham Order	Sham Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Continuous theta burst stimulation, 2) Intermittent theta burst stimulation, 3) Sham theta burst stimulation.
Sham, Intermittent, Continuous Order	Sham Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Sham theta burst stimulation, 2) Intermittent theta burst stimulation, 3) Continuous theta burst stimulation.
Sham, Intermittent, Continuous Order	Continuous Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Sham theta burst stimulation, 2) Intermittent theta burst stimulation, 3) Continuous theta burst stimulation.
Sham, Continuous, Intermittent Order	Intermittent Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Sham theta burst stimulation, 2) Continuous theta burst stimulation, 3) Intermittent theta burst stimulation.
Continuous, Sham, Intermittent Order	Continuous Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Continuous theta burst stimulation, 2) Sham theta burst stimulation, 3) Intermittent theta burst stimulation.
Sham, Continuous, Intermittent Order	Continuous Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Sham theta burst stimulation, 2) Continuous theta burst stimulation, 3) Intermittent theta burst stimulation.
Sham, Continuous, Intermittent Order	Sham Theta Burst Stimulation	3 sessions of theta burst stimulation administered in the following order: 1) Sham theta burst stimulation, 2) Continuous theta burst stimulation, 3) Intermittent theta burst stimulation.

Primary Outcome Measures

Name	Time	Method
Dorsomedial Prefrontal Cortex Activation	Task fMRI is conducted after each of 3 TBS sessions (intermittent, continuous, sham; in randomized, counterbalanced order) at approx 3, 5, and 7 weeks after study entry.	This measure captures brain function in the dorsomedial prefrontal cortex (dmPFC) based on blood oxygen level dependent (BOLD) response measured using functional magnetic resonance imaging (fMRI) during a reward task. Data are analyzed using Statistical Parametric Mapping. Magnitude of dmPFC response is in arbitrary units, with higher values reflecting higher activation. Theoretical minimum and maximum scores do not exist. Study hypotheses predict that dmPFC will decrease (based on statistical significance) with continuous TBS.

Secondary Outcome Measures

Name	Time	Method
VS-dmPFC Functional Connectivity	Task fMRI is conducted after each of 3 TBS sessions (intermittent, continuous, sham; in randomized, counterbalanced order). Sessions occur at approx 3, 5, and 7 weeks after study entry.	Outcome measure is assessed with functional magnetic resonance imaging (fMRI), in which brain function is recorded during a reward task. Functional connectivity between 2 regions of neural reward circuitry, the ventral striatum (VS) and the dorsomedial prefrontal cortex (dmPFC), is computed using general psychophysiologic interaction for this pair of regions in Statistical Parametric Mapping software. FC data are in arbitrary units, with higher values reflecting higher degree of coordination between the regions. Theoretical minimum and maximum scores do not exist. Higher scores do not represent "better" or "worse" outcomes or change in health. Based on study hypotheses, FC is predicted to decrease with continuous TBS, based on significance of statistical tests.
Positive Affect	pre and post each of 3 TBS administrations, with TBS lasting up to 190 seconds. cTBS, iTBS, and sham TBS each occurred in a single day.	Self-reported pleasant mood was measured with the Positive Affect (PA) scale of the Positive and Negative Affect Schedule (PANAS). This scale consists of a number of words that describe different feelings and emotions, participants are instructed to read each item and then mark to which extent they have felt like this in the past few hours. The PA scale contains 10 items, with each item rated on a 5-point scale of 1 (very slightly or not at all), 2 (a little), 3 (moderately), 4 (quite a bit), or 5 (extremely). Higher scores indicate greater PA. The total PA score is calculated by finding the sum of the 10 positive items. Scores range from 10-50. A higher score indicates higher intensity of positive affect. The PANAS PA data analyzed were from administrations pre- and post-TBS at visits #3-5 (approximately 30 minutes before and 1 hour after TBS administration).