Projects / Programmes
Influence of real-time individualization of stimulation frequency on therapeutic efficacy of transcranial magnetic stimulation in depression
| Code |
Science |
Field |
Subfield |
| 3.09.00 |
Medical sciences |
Psychiatry |
|
| Code |
Science |
Field |
| B650 |
Biomedical sciences |
Psychiatry, clinical psychology, psychosomatics |
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
depression, treatment, transcranial magnetic stimulation, electrophysiology, individualisation of stimulation
Researchers (12)
Organisations (2)
Abstract
Transcranial magnetic stimulation (TMS) has become a viable and recognized therapeutic option for treatment resistant depression. Despite the high response and remission rates, it is currently unknown why some patients respond while others do not. In fact, the mechanisms by which TMS produces its therapeutic benefit are poorly understood. Since TMS was approved as a safe and viable treatment, researchers have been trying to deepen our understanding of the neurobiological mechanisms of depression, in order to improve TMS treatment protocols. As a result of this research drive, it is now known that depression involves widespread functional connectivity imbalances that are mediated by rhythmic oscillatory activity, particularly at the alpha and theta frequencies. Another recent line of research has found that stimulation delivered in a manner timed with and informed by the ongoing brain oscillatory activity produces much less variable neuroplastic effects on healthy subjects. In this project, we aim at combining the findings from these two state of the art research directions with a novel recently approved highly efficient stimulation protocol, intermittent theta burst stimulation (iTBS). Our goal is to develop a more effective TMS treatment method for depression, by individualizing the frequency of stimulation in real time, that is, in a brain-state informed closed-loop paradigm.
While attempts at individualization have so far been focused on the alpha frequency band, we argue that theta might be a more logical target, since it is known to be involved in overall brain connectivity. Moreover, studies of the hippocampus activity in animals and humans have revealed that theta plays an important role in plasticity mechanisms.
The research project that we propose here will be accomplished in 4 distinct phases. First, we will re-analyze multimodal data we collected in a previous ARRS project on patients with depression, with the specific aim of better characterizing the abnormalities in the theta frequency band and how they change after TMS treatment. Second, a highly optimized algorithm will be developed in order to enable fast and reliable estimation of the individual’s peak theta frequency in near real-time, so that stimulation frequency can be adjusted online in real-time. Third, the newly developed algorithm will be piloted on healthy subjects while oscillatory activity is recorded, in order to further optimize it and, at the same time, quantify the amount of disruption produced by each stimulation train on oscillatory activity. In a fourth and final phase, the newly developed individualized stimulation protocol will be tested against the standard iTBS protocol in the patient population in a double blinded randomized controlled trial, in order to determine whether the individualized protocol represents a more effective treatment. Clinical, molecular, genetic and imaging multimodal data that will be collected will be used to define neurobiological subtypes of depression, with goal of predicting selective treatment response to TBS stimulation.
Significance for science
Depression is one of the most important medical disorders regarding the disease burden caused to society. Because treatment response rates to antidepressants are still relatively low, it is of utmost importance to search for new types of treatment, which are at the same time safer and more acceptable for patients due to their better side effects profiles. One of the overall goals of our project is to improve the response rates to treatment of depression, by adapting and changing the relatively new method of biological stimulation for treatment of depression, which is still not understood very well in scientific and professional communities.
Potential results of our project will also help further the neuroscientific understanding of mechanisms of brain function in health and disease, and help improve the technology available for medical treatments.
Significance for the country
Depression is one of the most important medical disorders regarding the disease burden caused to society. Because treatment response rates to antidepressants are still relatively low, it is of utmost importance to search for new types of treatment, which are at the same time safer and more acceptable for patients due to their better side effects profiles. One of the overall goals of our project is to improve the response rates to treatment of depression, by adapting and changing the relatively new method of biological stimulation for treatment of depression, which is still not understood very well in scientific and professional communities.
Potential results of our project will also help further the neuroscientific understanding of mechanisms of brain function in health and disease, and help improve the technology available for medical treatments.
Most important scientific results
Interim report
Most important socioeconomically and culturally relevant results
