The Electrocorticogram Signal Can Be Modulated With Deep Brain Stimulation of the Subthalamic Nucleus in the Hemiparkinsonian Rat

Abstract

Electrocorticogram (ECoG) recordings of the 6-hydroxydopamine (6-OHDA)-lesioned parkinsonian rat have shown an increase in the power of cortical beta-band (15-30 Hz) oscillations ipsilateral to the lesion. The power of these oscillations is decreased with dopamine agonist administration. Here, we demonstrate that stimulation of an electrode implanted in the subthalamic nucleus alters the power of cortical beta and gamma oscillations in 6-OHDA-lesioned animals. These alterations are dependent on stimulation frequency, charge, and amplitude/pulse width. Oscillations were significantly reduced during 200- and 350-Hz stimulation. A minimum charge of 4 nC was required to elicit a reduction in oscillation power. A number of amplitude and pulse width combinations that reached 4 nC were tested; it was found that only the combinations of 33 microA/120 micros and 65 microA/60 micros significantly reduced cortical oscillations. The reduction in beta/gamma oscillation power due to deep brain stimulation (DBS) was consistent with a significant reduction in the animals' rotational behavior, a typical symptom of parkinsonism in the rat. A significant shift from high beta to low gamma was observed in the peak frequencies of ECoG recordings while animals were at rest versus walking on a treadmill. However, DBS exhibited no differential effect on oscillations between these two states. EEG recordings from rodent models of DBS may provide surrogate information about the neural signatures of Parkinson's disease relative to the efficacy of DBS.

Effects of subthalamic deep brain stimulation on blink abnormalities of 6-OHDA lesioned rats

“…2) could result from changes in the substantia nigra input that reduce the collicular response to trigeminal input from the condition stimulus. Our demonstration that 16-Hz STN DBS creates R2 trigeminal reflex blink hyperexcitability in normal rats (Kaminer et al 2014) supports the hypothesis that hypersynchronized beta oscillations associated with PD (Brown and Eusebio 2008;Gatev et al 2006;Jenkinson and Brown 2011) and the 6-OHDA rat model (Lehmkuhle et al 2009;Li et al 2007;Mallet et al 2008;McConnell et al 2012;Sharott et al 2005) can reduce the responsiveness of collicular neurons to trigeminal inputs in PD. The suppression of beta oscillations by 130-Hz STN DBS (Dorval et al 2010;McConnell et al 2012;Ray et al 2008;Wingeier et al 2006) and its restoration of normal blink reflex excitability (Fig.…”

“…3 and 4). Given the apparent importance of hypersynchronized beta oscillations in impairing blink plasticity (Kaminer et al 2014), 130-Hz STN DBS may restore plasticity by suppressing exaggerated beta oscillations in 6-OHDA lesioned rats (Lehmkuhle et al 2009;Li et al 2007;McConnell et al 2012). Our experiment showing that delivering 130-Hz STN DBS only during the HFS-B treatment (130-D) restores blink reflex plasticity (Fig.…”

“…It is likely that the disruption of normal basal ganglia-cerebellar interactions (Bostan et al 2010;Bostan and Strick 2010;Hoshi et al 2005; Jinnah and Hess 2006) by PD's pathological basal ganglia activity impairs blink reflex plasticity. Given that 16-Hz STN DBS impairs blink reflex plasticity in normal rats (Kaminer et al 2014), the hypersynchronized beta oscillations found in PD (Brown et al 2001;Kuhn et al 2005) and 6-OHDA lesioned rats (Lehmkuhle et al 2009;Li et al 2007;Mallet et al 2008;McConnell et al 2012;Sharott et al 2005) are probably responsible for impairing blink plasticity in PD. The frequency of hypersynchronized basal ganglia oscillatory activity may be critical in how basal ganglia disorders affect plasticity.…”

“…One effect of 130-Hz STN DBS is disruption of the basal ganglia's characteristic hypersynchronized beta band activity seen in both PD patients (Dorval et al 2010;Ray et al 2008;Wingeier et al 2006) and in the 6-OHDA rat model of PD (Lehmkuhle et al 2009;Li et al 2007;McConnell et al 2012). The therapeutic effectiveness of high-frequency STN DBS may be a result of reducing this 10-to 30-Hz beta-oscillation.…”

Optogenetics and Deep Brain Stimulation Neurotechnologies

“…Much evidence has suggested the presence of exaggerated oscillations in the cortical-basal ganglion circuit at beta frequencies (oscillations around 20Hz). Exaggerated beta oscillations closely parallel the key PD motor deficits, bradykinesia, rigidty, akinesia, and tremor (Levy, Hutchison et al 2000;Brown, Oliviero et al 2001;Levy, Hutchison et al 2002;Boraud, Brown et al 2005;, and are largely suppressed by effective dopamine replacement treatment (Brown, Oliviero et al 2001;Levy, Ashby et al 2002;Williams, Tijssen et al 2002;Priori, Foffani et al 2004;Silberstein, Pogosyan et al 2005) and DBS (Wingeier, Tcheng et al 2006;Kuhn, Kempf et al 2008;Kuhn, Tsui et al 2009;Lehmkuhle, Bhangoo et al 2009). It has thus been suggested that DBS therapeutic effect is through reducing beta oscillations.…”