, 2000 and Parush et al., 2011) of the BG activity. Therefore, these models predict inferior information processing of the BG network upon the emergence of synchronized activity that disrupts these decorrelations. Furthermore, large-scale synchronization of cortical activity could serve as the basis for akinesia (Brown, 2006). Since synchronization and oscillations tend to coincide, manipulations

affecting one can affect the other and therefore TGF-beta inhibitor the closed-loop stimulation in this study could disrupt synchrony as well. However, previous studies have demonstrated that oscillations and synchrony can exist independently (Heimer et al., 2006). Since theoretical studies have demonstrated the plausibility of closed-loop systems selleck inhibitor targeted at synchronization of activity (Popovych et al., 2005 and Tass, 2003), further experimental studies are needed. The closed-loop approach suggested in this study may not be limited to PD. Work done on animal models of several neurological

and psychiatric disorders indicate that recognizable pathological patterns emerge (Uhlhaas and Singer, 2006). Some bear marked resemblance to the patterns seen in PD; namely, synchrony and oscillatory activity are seen in schizophrenia, a highly prevalent and extremely debilitating psychiatric disorder (Uhlhaas and Singer, 2010). Attempts at using closed-loop approaches for the treatment of other brain disorders will first need to be made in animal models, where the study of the MPTP primate model substantially facilitates the investigation of PD (Langston et al., 1984 and Redmond et al., 1985). We did not carry out a comprehensive investigation to determine the optimal parameters for closing the DBS loop. The aggravation of akinesia during the closed-loop GPtrain|GP stimulus application (with 80 ms delay) may be due to the positive feedback to the ongoing oscillatory activity in the GPi, and further manipulation of the stimulus delay might identify the working regimens for a GPi based feedback paradigm. Using the same location for both reference and stimulation would no doubt reduce the surgical complexity (Rouse Linifanib (ABT-869) et al., 2011). Moreover, since the neuronal oscillatory activity demonstrated in PD patients includes

higher frequencies (beta band, approximately 15–35 Hz) than those observed in MPTP-treated primates, a delay that will best fit these frequencies should be chosen when attempting closed-loop stimulation in human PD patients (de Solages et al., 2010, Eusebio and Brown, 2009, Hammond et al., 2007, Kühn et al., 2009, Mallet et al., 2008, Weinberger et al., 2009 and Zaidel et al., 2009). Further studies should be performed to ensure the safety and maximal efficacy of different closed-loop parameters in experimental models of PD and human PD patients. These studies should examine the effects of changing the neural location used as the stimulation reference and the stimulated location (e.g., GPi versus STN; Follett et al., 2010 and Moro et al., 2010).