Abstract
Parkinson's disease (PD) is marked by excessive synchronous activity in the beta (8–35 Hz) band throughout the cortico-basal ganglia network. The optimal location of high frequency deep brain stimulation (HF DBS) within the subthalamic nucleus (STN) region and the location of maximal beta hypersynchrony are currently matters of debate. Additionally, the effect of STN HF DBS on neural synchrony in functionally connected regions of motor cortex is unknown and is of great interest. Scalp EEG studies demonstrated that stimulation of the STN can activate motor cortex antidromically, but the spatial specificity of this effect has not been examined. The present study examined the effect of STN HF DBS on neural synchrony within the cortico-basal ganglia network in patients with PD. We measured local field potentials dorsal to and within the STN of PD patients, and additionally in the motor cortex in a subset of these patients. We used diffusion tensor imaging (DTI) to guide the placement of subdural cortical surface electrodes over the DTI-identified origin of the hyperdirect pathway (HDP) between motor cortex and the STN. The results demonstrated that local beta power was attenuated during HF DBS both dorsal to and within the STN. The degree of attenuation was monotonic with increased DBS voltages in both locations, but this voltage-dependent effect was greater in the central STN than dorsal to the STN (p < 0.05). Cortical signals over the estimated origin of the HDP also demonstrated attenuation of beta hypersynchrony during DBS dorsal to or within STN, whereas signals from non-specific regions of motor cortex were not attenuated. The spatially-specific suppression of beta synchrony in the motor cortex support the hypothesis that DBS may treat Parkinsonism by reducing excessive synchrony in the functionally connected sensorimotor network.
Highlights
Parkinson’s disease (PD) is a progressive, debilitating neurological disease that is estimated to affect 6.3 million adults worldwide
We examined the effects of deep brain stimulation (DBS) on local field potentials (LFPs) in the subthalamic nucleus (STN) and ipsilateral motor cortex in patients with PD, asking several questions
Several studies have shown that beta power is attenuated transiently after periods of High frequency deep brain stimulation (HF DBS) (Wingeier et al, 2006; Kuhn et al, 2008; Bronte-Stewart et al, 2009), but until recently it was not feasible to measure LFPs in beta frequencies during DBS due to HF stimulation artifacts
Summary
Parkinson’s disease (PD) is a progressive, debilitating neurological disease that is estimated to affect 6.3 million adults worldwide. Beta hypersychrony in the STN is attenuated after administration of therapeutic doses of dopaminergic medication in parallel with motor improvement (Weinberger et al, 2006; Ray et al, 2008; Kuhn et al, 2009), and is attenuated after periods of DBS (Wingeier et al, 2006; Kuhn et al, 2008; Ray et al, 2008; Bronte-Stewart et al, 2009) It is currently a matter of debate whether beta hypersynchrony is attenuated during HF DBS (Rossi et al, 2008; Eusebio et al, 2010; Rosa et al, 2011), and to what extent. Localization of the sites in the STN area that exhibit maximal beta hypersynchrony, and the relationship between these sites and sites of clinical efficacy of DBS, are areas of active investigation (Kuhn et al, 2005; Chen et al, 2006; Fogelson et al, 2006; Magill et al, 2006; Weinberger et al, 2006; Trottenberg et al, 2007; Holdefer et al, 2010; Ince et al, 2010; Yoshida et al, 2010; Zaidel et al, 2010; de Solages et al, 2011)
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