Trial Parameters
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Brief Summary
The goal of this clinical trial is to explore the effects of non-invasive brain stimulation protocols using intermittent theta-burst stimulation (iTBS) on brain plasticity and depression severity in depressed individuals aged 18 to 50 years old. Brain plasticity is the brain's ability to change through growth or reorganization. iTBS is a form of transcranial magnetic stimulation (TMS), where magnetic pulses are applied to the scalp using a coil. These pulses pass through the scalp, and can alter brain activity in the area underneath the coil. Based on previous research conducted in animals and humans, researchers believe that iTBS can strengthen the connections between cells in the brain, leading to improved brain plasticity. This trial will compare the effects of the compressed iTBS (iTBS-c) protocol, which is commonly used to treat depression, and the spaced iTBS (iTBS-s) protocol. Researchers want to find out which protocol is better able to produce changes in brain plasticity and improve symptoms of depression among individuals diagnosed with Major Depressive Disorder (MDD). In this trial, participants will be randomized to receive 3 sessions of iTBS-s or iTBS-c, undergo a washout period of at least 2 weeks, then complete 3 sessions of the opposite iTBS intervention. Participants will complete 5 study visits within the span of 2-3 months, including: * Screening assessments to determine eligibility \& 1 sham iTBS (iTBS-sh) session to assess tolerability of the brain stimulation (Visit 1); * 1 Magnetic Resonance Imaging (MRI) brain scan and randomization (Visit 2); * Safety and clinical assessments, iTBS-s or iTBS-c intervention, TMS evoked electroencephalography (TMS-EEG) measurements, and post-iTBS questionnaires (Visits 3-5) followed by a washout period of at least 2 weeks; * Safety and clinical assessments, the opposite iTBS-s or iTBS-c intervention originally randomized to, TMS-EEG measurements, and post-iTBS questionnaires (Visits 6-8).
Eligibility Criteria
Inclusion Criteria: * Aged 18-50 years old; * Must meet criteria for a current Major Depressive Episode (MDE) as ascertained using the Structured Clinical Interview for DSM 5 (SCID-5); * Hamilton Rating Scale for Depression (HRSD-17) score \> 7; * Must be on a stable antidepressant regimen for a minimum of 4 weeks prior to enrollment, if currently taking antidepressants; * Right handed or ambidextrous, assessed using the Edinburgh Handedness Inventory (EHI); * Sufficiently proficient in English to complete the required study assessments, as per investigator judgement; * Willingness and capacity to provide informed consent; * Willingness to comply with all study procedures. Exclusion Criteria: * Age 17 years or less, or greater than 51 years old, as brain plasticity is known to be affected by age; * Presence of any DSM-5 diagnosis (other than MDD), known to be associated with prefrontal cortical dysfunction, including lifetime diagnoses of bipolar disorder, intellectual disability, or a