| Summary: |
Obsessive-Compulsive Disorder (OCD) is a prevalent neuropsychiatric disorder characterized by recurrent intrusive thoughts (obsessions) that lead to repetitive behaviors (compulsions), causing significant disruption of daily life activities as well as high anxiety and stress. Consequently, OCD has a high personal, societal, and economic burden, interfering with social adjustments and socioeconomic conditions of those afflicted. The etiology and pathophysiology of OCD are poorly understood, and available treatments are limited to targeting secondary symptoms. This leads to high rates of treatment-resistance (40-60%) and relapse. Therefore, there is a critical need for the development of next-generation therapies for treatmentresistant OCD.
Deep brain stimulation (DBS), which includes implanting electrodes inside the brain that can deliver electric pulses to modulate brain activity, is an emerging therapy for refractory OCD patients. Recent clinical trials have demonstrated that DBS of the regions related to the cortico-striatalthalamic-cortical (CSTC) brain circuit can markedly reduce obsessive-compulsive and anxiety symptoms in patients with OCD. However, the mechanisms and the electrophysiological correlates of DBS effectiveness in OCD remain largely unknown, which has hindered clinicians' ability to better understand how OCD disrupts brain activity and to derive patient-specific stimulation parameters that maximize therapeutic effects. Because no therapeutic biomarkers exist for OCD, the current implementation of DBS in clinical practice relies on continuous and invariable stimulation parameters which are adjusted by subjective trial-and-error processes in routine consultations, limiting its therapeutic efficacy and increasing the risk of side effects.
Adaptive DBS (aDBS) is a novel strategy for brain stimulation, whereby stimulation parameters are controlled in a closed-loop manner in response to brain activity acquired from DBS electrodes in new-g  |
Summary
Obsessive-Compulsive Disorder (OCD) is a prevalent neuropsychiatric disorder characterized by recurrent intrusive thoughts (obsessions) that lead to repetitive behaviors (compulsions), causing significant disruption of daily life activities as well as high anxiety and stress. Consequently, OCD has a high personal, societal, and economic burden, interfering with social adjustments and socioeconomic conditions of those afflicted. The etiology and pathophysiology of OCD are poorly understood, and available treatments are limited to targeting secondary symptoms. This leads to high rates of treatment-resistance (40-60%) and relapse. Therefore, there is a critical need for the development of next-generation therapies for treatmentresistant OCD.
Deep brain stimulation (DBS), which includes implanting electrodes inside the brain that can deliver electric pulses to modulate brain activity, is an emerging therapy for refractory OCD patients. Recent clinical trials have demonstrated that DBS of the regions related to the cortico-striatalthalamic-cortical (CSTC) brain circuit can markedly reduce obsessive-compulsive and anxiety symptoms in patients with OCD. However, the mechanisms and the electrophysiological correlates of DBS effectiveness in OCD remain largely unknown, which has hindered clinicians' ability to better understand how OCD disrupts brain activity and to derive patient-specific stimulation parameters that maximize therapeutic effects. Because no therapeutic biomarkers exist for OCD, the current implementation of DBS in clinical practice relies on continuous and invariable stimulation parameters which are adjusted by subjective trial-and-error processes in routine consultations, limiting its therapeutic efficacy and increasing the risk of side effects.
Adaptive DBS (aDBS) is a novel strategy for brain stimulation, whereby stimulation parameters are controlled in a closed-loop manner in response to brain activity acquired from DBS electrodes in new-generation DBS systems. This enables autonomous adjustment of stimulation parameters on an individual basis, in accordance with the patient's needs and the fluctuations of brain circuits, thus enhancing the clinical efficacy of DBS while minimizing the incidence of adverse effects and the consumption of battery power. aDBS has very recently (January 2025) been approved in the EU
for Parkinson's Disease, with the expectation that this approval will extend to other brain disorders benefiting from DBS in the coming years.
Thus, this project aims to position our research at the forefront for adoption of aDBS for OCD by identifying and validating neurophysiological biomarkers predictive of obsessive-compulsive behaviors that can guide the choice of stimulation parameters that maximize the therapeutic effect for each patient. To bridge this critical gap in neurostimulation for OCD, we will leverage intracranial electrophysiological recordings from OCD patients implanted with new generation DBS systems (only approved for use in the EU in 2020), that permit simultaneous recording and stimulation of deep brain activity, and signal processing and machine learning approaches.
The ultimate goal is to develop a framework for adaptive neurostimulation protocols, where the identified biomarkers can guide the choice of optimal stimulation parameters for personalized treatment in OCD. To reach this goal we will: 1) collect electrophysiological recordings from OCD patients in response to obsessive and compulsive behavioral events; 2) design an open source application to process and analyze data from new generation DBS systems to search for relevant electrophysiological biomarkers that correlate with obsessive and compulsive behaviors and other clinical parameters; 3) program and validate in silico a microcontroller with machine learning capabilities to extract relevant features from electrophysiological signals in real-time and automatically adjust stimulation parameters.
This project relies on a highly multidisciplinary team with experience and a track record in brain interface tools development and functional assessment of brain dynamics in neuropsychiatric disorders, as well as clinical outcome evaluation and physical therapies in OCD. The successful completion of this project will establish the groundwork for aDBS in OCD and contribute to next-generation precision medicine to improve the life of those affected by brain disorders. |