Basic information

Investigator: doc. MUDr.Monika Klírová, Ph.D.
Main recipient: National Institute of Mental Health (NIMH)
Co-recipient: n/a
Research period:  1/5/2025 - 31/12/2028
Total budget: 12,960,000.00 CZK
NIMH budget: 12,960,000.00 CZK
Supported by: Czech Health Research Council (AZV ČR)

 

 

 

 

Annotation

There is a significant lack of effective treatment strategies for treatment-resistant (TR) obsessive-compulsive disorder (OCD), and alternatives are needed to expand this limited range of treatment options. Recently, deep transcranial magnetic stimulation (dTMS) of the medial prefrontal cortex (mPFC) has been suggested as a first-choice intervention for TR-OCD, specifically for serotonin reuptake inhibitor-resistant OCD. However, it is still unclear which patients may benefit from this treatment. The purpose of the proposed study is to determine how the efficacy of FDA-approved mPFC-dTMS in OCD patients is affected by electrophysiological and imaging findings prior to treatment, with the ultimate goal of providing clinicians with more information about the indications for mPFC-dTMS in the treatment of these patients. Successful demonstration of this information would mean that clinicians could indicate mPFC-dTMS in patients with expected dTMS efficacy. In order to allow physicians to make informed decisions about treatment choices based on the literature and secondary analysis of the results of this study, a goal of this study would be to preliminarily determine whether an a priori neuroimaging or electrophysiological differential predictor for mPFC-dTMS can identify appropriate patients for this treatment. The double-blind, randomized, and placebocontrolled study will map behavioral (Y-BOCS), structural (MRI), and functional brain changes (EEG, fMRI) after treatment and in relation to treatment response in areas related to the pathophysiology of OCD. We plan to enroll 75 patients diagnosed with OCD (60 active dTMS; 15 shams). The project builds on our previous work and pilot data examining neurobiological changes in OCD (OCDEM) and a pilot study examining the effect of mPFC-dTMS in treating OCD. The ultimate goal is to contribute to the optimization of OCD treatment and to contribute to introducing mPFC-dTMS into clinical practice.

The main aim of the project is to elucidate the effect of deep repetitive transcranial magnetic stimulation (dTMS) of the medial prefrontal cortex (mPFC-dTMS) in patients with obsessive-compulsive disorder (OCD) and to identify neurophysiological factors that are causally related to refractoriness to mPFC-dTMS in these patients. Our project is based on the assumption of structural and functional changes that have been found in a number of studies in patients with OCD. Smaller volume of medial frontal cortex structures and functional changes involving the medial frontal cortex have been described in patients compared to healthy subjects, including altered functional connectivity between the ventromedial prefrontal region and the striatum and a different amplitude of the ERN (error-related negativity) electrical potential in response to error output. We hypothesize that reduced thickness of selected subregions of the medial frontal cortex, e.g., the ACC (anterior cingulate cortex), will be present in nonresponders to rTMS treatment prior to treatment, and nonresponders, unlike responders, will not show the plastic changes in cortical structure and ERN amplitude changes after 6- week treatment that will be present in responders. We also predict that the decrease in OCD symptoms in responders will be related to amplitude decreases in the ERN, percentage increases in gray matter in selected regions of the medial frontal cortex, and changes in functional connectivity.