title: Detecting a Cortical Fingerprint of Parkinson's Disease for Closed-Loop Neuromodulation.
abstract: 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.
authors.affiliation: Division of Functional and Restorative Neurosurgery and Centre for Integrative Neuroscience, Eberhard Karls University Tuebingen Tuebingen, Germany.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kern
authors.affiliation: Division of Functional and Restorative Neurosurgery and Centre for Integrative Neuroscience, Eberhard Karls University Tuebingen Tuebingen, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Naros
authors.affiliation: Magnetoencephalography Center, Eberhard Karls University TuebingenTuebingen, Germany; Center for Mind/Brain Sciences (CIMeC), University of TrentoItaly.
authors.forename: Christoph
authors.initials: C
authors.lastname: Braun
authors.affiliation: Department for Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research and German Centre of Neurodegenerative Diseases (DZNE), Eberhard Karls University Tuebingen Tuebingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weiss
authors.affiliation: Division of Functional and Restorative Neurosurgery and Centre for Integrative Neuroscience, Eberhard Karls University Tuebingen Tuebingen, Germany.
authors.forename: Alireza
authors.initials: A
authors.lastname: Gharabaghi
keywords: Parkinson's disease; beta cortico-muscular coherence; closed-loop stimulation; cortical targeting; deep brain stimulation; neurophysiological biomarker; source space