Detecting a Cortical Fingerprint of Parkinson's Disease for Closed-Loop Neuromodulation

Recent evidence suggests that deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) mediates its clinical effects by modulating cortical oscillatory activity, presumably via a direct cortico-subthalamic connection. This observation might pave the way for novel closed-loop approaches comprising a cortical sensor. Enhanced beta oscillations (13-35 Hz) have been linked to the pathophysiology of PD and may serve as such a candidate marker to localize a cortical area reliably modulated by DBS. However, beta-oscillations are widely distributed over the cortical surface, necessitating an additional signal source for spotting the cortical area linked to the pathologically synchronized cortico-subcortical motor network. In this context, both cortico-subthalamic coherence and cortico-muscular coherence (CMC) have been studied in PD patients. Whereas, the former requires invasive recordings, the latter allows for non-invasive detection, but displays a rather distributed cortical synchronization pattern in motor tasks. This distributed cortical representation may conflict with the goal of detecting a cortical localization with robust biomarker properties which is detectable on a single subject basis. We propose that this limitation could be overcome when recording CMC at rest. We hypothesized that—unlike healthy subjects—PD would show CMC at rest owing to the enhanced beta oscillations observed in PD. By performing source space analysis of beta CMC recorded during resting-state magnetoencephalography, we provide preliminary evidence in one patient for a cortical hot spot that is modulated most strongly by subthalamic DBS. Such a spot would provide a prominent target region either for direct neuromodulation or for placing a potential sensor in closed-loop DBS approaches, a proposal that requires investigation in a larger cohort of PD patients.