How does ECT Work?
This is a question I face in clinical practice all the time. It is a very important one, and while there has been a lot of research on it and there are some clues about it, we still have work to do. Therefore, it should be no surprise that I was extremely excited to start a collaboration with Dr.Timothy Murphy to use optogenetics technology to address this question. Here is some preliminary work on this that will be presented at the 2nd International Brainstimulation conference in two weeks.
Title: Mesoscale cortical mapping reveals region-specific and frequency-dependent changes in a mouse model of electroconvulsive therapy.
Authors: Blair Jovellar; Jeffrey LeDue; Fidel Vila-Rodriguez; Timothy H. Murphy.
Depression is a leading cause of disability worldwide. As a treatment for depression, electroconvulsive therapy (ECT) remains the most effective. In spite of such unparalleled efficacy, our understanding of the therapeutic mechanisms of ECT remains lacking. Using Electroconvulsive stimulation (ECS)—an animal model of ECT—we determine how ECT alters the mesoscale spatiotemporal activity of different brain regions.
Wide-field fluorescent imaging of resting-state activity was performed in awake head-fixed mice expressing GCaMP6 (a genetically-encoded calcium indicator). This allowed longitudinal imaging of intracellular calcium which reflect changes in spiking activity at a cellular level. ECS was done once daily, every other day, for a total of 10 treatments. Imaging was done daily ~10min and 24h after ECS.
Quantification of GCaMP6 fluorescence revealed increased standard deviation of spontaneous activity in the anterior cingulate. An even greater increase in standard deviation of resting-state activity was observed in the restrosplenial cortex. Further analyses demonstrated increased power of the retrosplenial cortex at the delta frequency band (1-4 Hz).
These findings suggest that ECS effects are brain-region specific and are frequency-dependent. To our knowledge, this is the first animal model that incorporates longitudinal imaging of spiking activity after ECS and provides opportunities to further dissect the therapeutic mechanism of ECT.