Description:For many facing depression, therapy and medication offer a way forward. But what happens when nothing seems to work?In this episode of Off Label: Data, Diagnostics, and the Future of Mental Health, Dr. Steve Rondeau explores how dysfunction in the brain’s Default Mode Network (DMN) may be a key driver behind Treatment-Resistant Depression (TRD). The DMN—often active during introspection and self-reflection—can become overactive, misaligned, or rigid in TRD, reinforcing rumination, hopelessness, and cognitive inflexibility.We examine the neuroscience of the DMN, how its connectivity patterns shift in chronic depression, and why standard treatments often fail to reach the root of the problem. You'll also hear how emerging interventions—from neuroimaging-guided therapy to neurofeedback and targeted cognitive approaches—aim to regulate DMN activity and restore mental flexibility.Whether you're a clinician, neuroscientist, or someone navigating the complex terrain of TRD, this episode offers a brain-based lens into the mechanisms behind “stuck” depression—and what it might take to break free.

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