Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Psilocybin has recently emerged as a high potential intervention for treatment-resistant depression (TRD), yet significant gaps remain in our understanding of its biological and therapeutic effects. While psilocybin's main mechanism is via the serotonin system, recent evidence shows other downstream mechanisms involving other neuronal pathways. One potential process, called neuroplasticity, appears to be implicated in multiple TRD treatments, including non-invasive brain stimulation, and can be measured by a type of imaging called transcranial magnetic stimulation-electroencephalography (TMS-EEG). Previous TMS-EEG investigations have shown abnormal neuroplasticity in TRD that improves with effective treatment. Here, the primary aim of this proposed project is to use TMS-EEG to measure brain processes before and after therapeutic psilocybin administration for TRD as part of a currently funded trial. We will also explore potential associations with symptom improvement. TMS-EEG recordings will occur both before psilocybin administration and 1 week post-administration. Markers reflecting neuroplasticity processes (specifically cortical inhibition and excitation) will be extracted from each participant's TMS-EEG data. Statistical comparisons will focus on treatment timepoint and depressive symptom improvement. The projected impact of the project will be to enhance our understanding of the mechanism of action of novel effective treatments for TRD, along with potentially identifying promising markers of response for future study. This will hopefully translate into improved treatment delivery and development in the near future.