Early Brainwave Biomarkers for Personalized Neuromodulation in Treatment-resistant Depression

Early TMS-EEG Potentials as Biomarkers for Personalized Neuromodulation in Treatment-Resistant Depression (R61 Phase)

This study tests whether a brain stimulation treatment for depression called intermittent theta burst stimulation (iTBS) can be improved by tailoring it to each individual. A type of brain signal measured with electroencephalography (EEG) after a single pulse of brain stimulation, called an early local TMS-evoked potential (EL-TEP), is used to identify which stimulation settings work best for each participant. The investigators will compare individualized (personalized) iTBS settings to standard (non-personalized) settings and to inactive (sham) stimulation. Participants are adults with treatment-resistant depression.

Inclusion Criteria:

• Aged 18-65 years
• Clinical diagnosis of Major Depressive Disorder (MDD), confirmed by structured clinical interview
• Current moderate-to-severe depressive episode (MADRS score ≥ 20)
• Moderate-to-severe treatment resistance, assessed using the Maudsley Staging Method
• Able to comprehend English sufficiently to complete study procedures and assessments
• Able to maintain stable antidepressant regimen or remain medication-free for at least 4 weeks prior to and during the study

Exclusion Criteria:

• Primary psychiatric diagnosis other than MDD
• Contraindications to MRI (e.g., implanted metal)
• Conditions or medications that may increase risk associated with TMS
• Prior exposure to repetitive TMS (rTMS)
• Non-response to electroconvulsive therapy (ECT)
• History of psychosurgery for depression
• High suicidal risk as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)