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.

Spatio-temporal dynamics of cortical drive to human subthalamic nucleus neurons in Parkinson's disease

“…The sustained nature of this synchronisation could represent reverberation in the cortico-basal ganglia-thalmo cortical loop that would usually be prevented by the resistance of many basal ganglia neuron populations to being entrained by cortical oscillations ( Raz et al, 2000 , Magill et al, 2004 ). Recently, there has been much interest in the idea of closed-loop deep brain stimulation for the treatment of akinetic-rigid symptoms of PD ( Beuter et al, 2014 , Little and Brown, 2014 , Arlotti et al, 2016 , Kern et al, 2016 , Rossi et al, 2016 ). The utility of such an approach has been demonstrated in MPTP-treated primates ( Rosin et al, 2011 ), where stimulation of basal ganglia triggered with a fixed time delay by oscillating cortical spikes was substantially more effective than continuous stimulation.…”

Cortical stimulation in aphasia following ischemic stroke: toward model-guided electrical neuromodulation

“…These adjustments lead to a specific pattern of stimulation for each patient and period of time. Closed-loop stimulation is used in deep brain stimulation for Parkinson's disease (Herron et al 2017;Kern et al 2016;Little et al 2013;Meidahl et al 2017;Priori et al 2013;Rosin et al 2011;Swann et al 2018), for pain (Shirvalkar et al 2018) and for epilepsy (Edwards et al 2017). There are also promising results with episodic memory (Ezzyat et al 2018;Hanslmayr and Roux 2017).…”

Sensorimotor Mapping With MEG: An Update on the Current State of Clinical Research and Practice With Considerations for Clinical Practice Guidelines

“…Although tSSS is originally available for one type of MEG system (i.e., Elekta Oy, Helsinki, Finland), it has been adapted to another commonly available MEG system (i.e., CTF Inc, Vancouver, Canada). 48 Finally, other methods have been developed and tested to remove magnetic interferences from MEG signals such as, e.g., the blind source separation method, which has the advantage of being system independent. 49,50 Future progresses in this field of MEG signal processing will also increase the applicability of MEG for clinical indication.…”