Adaptive Deep Brain Stimulation in Advanced Parkinson's Disease: Bridging the Gap beetween Concept and Clinical Application

Parkinson’s disease (PD) is a common neurodegenerative disorder. Recent evidence points towards increased synchronous neuronal oscillations of the cortico-thalamic-basal ganglia circuits in the beta band (12–30 Hz) as the main pathophysiological abnormality associated with PD. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for improving PD motor symptoms. However, the current DBS systems have several limitations, mainly related to the fixed and continuous application of stimulation. Especially in the long-term, DBS can only partially control clinical fluctuations and can exacerbate undesirable adverse effects often reversible with a change of stimulation parameters. A new strategy called adaptive DBS (aDBS) allows for continuous adaptation of STN stimulation to the patient’s clinical state by directly harnessing the recordings of the STN pathological oscillatory activity or local field potentials (LFPs). With this project, we aimed to accelerate the clinical translational process by suggesting a pathway to the clinical practice. To do so, we developed an external portable LFPs-based aDBS device for clinical investigations in acute experimental sessions. We then conducted a proof of concept study investigating the functioning of the device and comparing aDBS and conventional DBS (cDBS) and how they interacted with the concurrent pharmacological treatment. Then, we monitored the clinical and neurophysiological fluctuations over a period of eight hours with and without aDBS. We thus investigated the preservation of LFPs-clinical state correlation and the aDBS management of motor fluctuations during daily activities. Because in the clinical practice the DBS therapy is provided by means of implantable pulse generators (IPGs), we evaluated whether the proposed aDBS approach, based on real-time LFPs processing, fits the power constraints of implantable devices. Finally, we contextualized our results and proposed an overview of the possible pathways toward the clinical practice.