Optimization of Prefrontal Theta-Burst Stimulation to Treat Depression: A Bench to First-in-Human Study
- Tarek Rajji, Centre for Addiction and Mental Health
- Graham Collingridge, Mount Sinai
- Evelyn Lambe, University of Toronto
- Sanjeev Sockalingam, Centre for Addiction and Mental Health
- Branka Agic, Centre for Addiction and Mental Health
- Daniel Blumberger, Centre for Addiction and Mental Health
- John Georgiou, Mount Sinai Hospital
- Clement Ma, Centre for Addiction and Mental Health
- Benoit Mulsant, CAMH, University of Toronto
- Reza Zomorrodi, Centre for Addiction and Mental Health
- Bell/Bell Let's Talk
Major depression is among the most common and most burdensome human diseases worldwide. While there are several existing treatments, overall current treatments are modest in their efficacy. Over the past few decades, there has been significant development in the field of Transcranial Magnetic Stimulation (TMS) to treat depression. TMS protocols are usually well tolerated and as effective as medications. Among the more recent forms of TMS treatments is a protocol called Theta-Burst Stimulation (TBS). TBS has been shown to be effective to treat depression but its efficacy is modest, similar to other forms of depression treatments.
TBS was developed based on a stimulation protocol that was developed originally in rodents (rats and mice) to enhance brain plasticity, i.e. the ability of the brain to change itself in response to experience. In rodents, TBS was initially developed and later optimized in a brain region called the hippocampus, which is a deep structure in the brain. However, in humans, TBS is delivered to a frontal region of the brain, which is at the surface of the brain and called the prefrontal cortex.
Thus, this project has three major goals: (1) to optimize the ability of TBS to enhance brain plasticity in the prefrontal cortex of mice; (2) to test this optimized TBS protocol in patients with depression and test whether it is better than the currently used TBS in improving brain plasticity in the prefrontal cortex of patients with depression; (3) translate the knowledge gained from animal and human studies to different stakeholders including trainees, patients and families, clinicians, and other researchers.
Our project is unique in focusing on translating new discoveries from animal to human studies. If successful, it could lead to a more effective treatment for depression, a condition that continues to cause tremendous personal and societal burden.