When it comes to finding a lasting treatment for depression, a team of researchers in Toronto say it may come down to finding the perfect rhythm.
The approach, being developed by scientists at Sinai Health, the Center for Addiction and Mental Health (CAMH) and the University of Toronto, has nothing to do with music and everything to do with editing of an existing form of brain stimulation therapy.
To improve the technology and test it in patients, four researchers were awarded grants today by Bell Let’s Talk and Brain Canada.
“This is a very exciting collaboration that combines laboratory and bedside research in the same project,” said Tarek Rajjiprincipal investigator and clinical manager of the project.
Rajji is the Executive Director of the Toronto Dementia Research Alliance (TDRA) and Chief of the Division of Adult Neurodevelopment and Geriatric Psychiatry at the Center for Addiction and Mental Health (CAMH), as well as a Clinician Scientist at the Campbell Family Mental Health Research Institute in CAMH. He is also an Associate Professor in the Department of Psychiatry at Temerty Medical School.
The research is centered on transcranial magnetic stimulation, or TMS, a form of brain stimulation therapy that has shown tremendous promise in helping patients with treatment-resistant depression. The approach uses a device to deliver pulses of magnetic stimulation to the prefrontal cortex, a part of the brain associated with mood regulation.
The core science component of the project involves brain stimulation to determine whether altering the spacing or timing of impulses to the brain could ultimately provide lasting relief from symptoms of depression.
“The stimulation pattern is vital,” said Graham Collingridge, principal investigator at Sinai Health’s Lunenfeld-Tanenbaum Research Institute (LTRI) and professor of physiology and director of the Tanz Center for Research in Neurodegenerative Diseases at Temerty Medicine. “We recently discovered that instead of applying rhythm in a short period of time, [if] you pause for a few minutes and then repeat the stimulation, the effect on the synapses in the brain is stronger and longer lasting.
Collingridge studies a process called long-term potentiation, in which a brief period of intense neuronal activity leads to a lasting increase in the strength of the connections between nerve cells.
To find the perfect pattern, Rajji and Collingridge collaborate with Evelyne LambeAssociate Professor of Physiology at Temerty Medicine, who is leading work to optimize stimulation parameters in the prefrontal cortex, the region targeted by TMS in patients, as part of the Bell Let’s Brain Canada research grant.
“The goal is to optimize the treatment to rebuild the connections between neurons essential for mood regulation,” Lambe said.
His lab’s work on the impact of social isolation on the brain has become increasingly relevant to mental health during the COVID19 pandemic. “Social isolation and other stressors wear us down by impairing brain function at the cellular level,” Lambe notes.
Rajji, meanwhile, will adapt the optimized stimulation parameters to humans using TMS and electroencephalography. His team will investigate which stimulation pattern leads to better brain plasticity in the frontal lobes of adults with acute depression.
All along the project, Sanjeev Sockalingam, clinician-scientist and vice president of education at CAMH, and professor of psychiatry at Temerty Medicine, will lead the knowledge translation component of the work. This will involve mental health clinicians, people with lived/living experience and families working with researchers from the start of the project.
“The integrated approach involving clinicians and service users will help us co-create knowledge that gets to the people who can use it faster and more effectively,” Sockalingam said.
With files from Sinai Health, Center for Addiction and Mental Health, and Department of Physiology at the University of Toronto.