Need for multiple biomarkers to adjust parameters of closed-loop deep brain stimulation for Parkinson’s disease

Closed-loop deep brain stimulation (DBS): DBS has been established as a surgical therapy for movement disorders and select neuropsychiatric disorders. Various efforts to improve the clinical outcomes of the procedure have been previously made. Several factors affect the DBS clinical outcomes such as lead position, programming technique, and surgical complications (Morishita et al., 2010). Currently, there are two approaches for improving DBS: directional DBS lead (Contarino et al., 2014) and closed-loop DBS (Rosin et al., 2011). The directional DBS is a straightforward approach that delivers the electrical stimulation accurately to the treated target area. Despite the more complicated programming paradigm in comparison with conventional programming, directional DBS offers an easier stereotactic procedure in terms of lead positioning. On the other hand, the notion of the basic closed-loop DBS system involves automatically adjustable DBS programming parameters including on/off switching based on the physiological condition of the patient. Typically, this programming procedure requires three to six months until achieving the optimal setting for existing open-loop DBS system, even for an expert DBS practitioner. Moreover, the parameters need to be adjusted to address the clinical symptoms at various stages of Parkinson’s disease (PD) (Bronstein et al., 2011). An ideal closed-loop DBS system has been considered to address this issue. In a recent animal study, Rosin et al. (2011) proposed a delayed feedback closed-loop DBS paradigm as an effective system. However, the clinical efficacy of the closed-loop DBS has not been tested yet. Even though the concept of closed-loop DBS system seems intriguing and promising, a powerful biomarker indicating the clinical conditions of PD has yet to be identified. Currently, the most investigated potential biomarker is beta-band oscillation. Recent studies have demonstrated an abnormal synchronization of the beta-band oscillation activities between the basal ganglia and the motor cortex (de Hemptinne et al., 2015). Therapeutic DBS is reportedly considered to disconnect the abnormal coupling; thus, most closed-loop DBS concepts are designed to modulate the electrical stimulation parameters by beta-band oscillation. A recent study using a computational model indicated that delayed feedback may not suppress the abnormal synchronization (Dovzhenok et al., 2013). In an animal study, closed-loop DBS that delivered electrical stimulation only when beta activity was elevated in the subthalamic nucleus was not as effective as continuous DBS (Johnson et al., 2016).