The cortical footprint of deep brain stimulation in the superolateral medial forebrain bundle

• Applicant: Joana Pereira, Ph.D.
• Subject Area: Human Cognitive and Systems Neuroscience
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 510112977

Deep brain stimulation (DBS) is an established therapy for neurological disorders like Essential Tremor, Dystonia, or Parkinson’s Disease. More recently, deep brain stimulation has also been proposed as a treatment for severe disorders of psychiatric nature, among them major depressive disorder and obsessive-compulsive disorder. There is evidence that stimulation of the superolateral medial forebrain bundle (slMFB) has a quick and strong antidepressant effect in treatment-resistant major depressive disorder. However, the electrophysiological cortical effects of DBS in this particular pathway remain uncharacterized. Electroencephalography (EEG) is a non-invasive technique with sufficient spatial coverage and high temporal resolution which has been used to investigate the effects of deep brain stimulation at the cortical level, mostly in neurological disorders. A characterization of the effects of slMFB-DBS upon cortical regions and networks could contribute to the design of novel stimulation strategies that would be better tailored and individualized to the patients. Additionally, it would help shed light on the functional role of the slMFB in human emotion regulation and reward-oriented systems. The main objectives of this proposal are (1) describing the cortical effects of slMFB-DBS in a chronic setting, and (2) characterizing the sensitivity of patient-specific cortical markers to different DBS parameters. To accomplish these aims, the applicant of this proposal will investigate the presence of DBS-evoked EEG potentials as a result of low-frequent slMFB stimulation, and also study neural correlates in the EEG spectral domain (i.e., neural oscillations) of slMFB stimulation at the conventional high-frequency setting. The latter will be performed on a patient-specific level using multivariate approaches. Additionally, the so-called wash-out effects that might occur after cessation of stimulation will be described. Lastly, by slight variations of stimulation parameters (e.g., different amplitudes, temporal patterns or stimulation contacts), it will be investigated whether any of the neural correlates found (e.g., evoked cortical potentials or power in specific frequency bands) are sensitive to the stimulation parameters applied. This study will be performed in a population of patients diagnosed with major depressive disorder or with obsessive-compulsive disorder that have been treated with slMFB-DBS for more than one year.

• DFG Programme: WBP Position