This paradigm yielded a marked reduction in akinesia in all four limbs, but most notably in the contralateral arm to the stimulation site, as measured by accelerometers. Importantly, this adaptive closed-loop DBS successfully triggered a reduction of pallidal firing rate and a decrease of oscillatory activity in GPi (Rosin et al., 2011). The use of closed-loop DBS with motor cortex as the reference structure for triggering pallidal stimulation led to a reduction of stimulation frequency and also to an increase in the variability of the interstimulus interval when compared with standard

high frequency stimulation. Could the improvements observed simply reflect the fact that the stimulation pattern was of lower frequency and more irregular? Lapatinib research buy In order to demonstrate that the observed effects were due to the adaptive closed-loop nature of the stimulation, the authors performed two experiments. In one they applied an open-loop stimulation at low frequency (10 Hz versus standard DBS at 130 Hz). In another, they applied a stimulation pattern

based on previous recordings from M1, with the same variability as the online adaptive stimulation pattern, but unrelated to the ongoing activity at the moment of the stimulation. In both cases no relevant improvements in behavior or neuronal modulation were observed, strengthening the conclusion that it was HTS assay not the statistics of the stimulation pattern that promoted the behavioral improvements in closed-loop DBS, but rather the fact that the stimulation pattern reflected ongoing activity. This study offers important insights into how DBS works. Previous studies suggested that there is increased neural activity in the STN of MPTP-treated primates (Crossman et al., 1985). of Accordingly, lesioning the STN in the MPTP primate model reverted the Parkinson-like symptoms (Bergman et al., 1990). Since both electrical stimulation of STN and STN lesions produced amelioration of PD symptoms,

it was hypothesized that DBS leads to decreased activity in STN or decreased transmission from STN to GPi, therefore leading to reduced activity in GPi. Another suggestion has been that both STN lesions and DBS would disrupt the pathological oscillations observed in PD, leading to an improvement in motor symptoms; this view is supported by recent studies which suggest that DBS does not work by inhibiting STN neurons (Bar-Gad et al., 2004, Carlson et al., 2010 and Gradinaru et al., 2009). Interestingly, Rosin and colleagues uncovered that the application of a closed-loop protocol in which GPi activity triggered GPi stimulation resulted in a reduction in pallidal discharge rate with no change in GPi oscillatory activity, and even in an increase in oscillatory activity in motor cortex (Rosin et al., 2011).