Characterizing Effects of Subthalamic Nucleus Deep Brain Stimulation on Methamphetamine-Induced Circling Behavior in Hemi-Parkinsonian Rats

So, Rosa; McConnell, George C.; August, Auriel; Grill, Warren M.

doi:10.1109/tnsre.2012.2197761

Cited by 28 publications

(41 citation statements)

References 36 publications

(62 reference statements)

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“…Rats with unilateral SNc lesions rotate ipsilaterally toward the lesion, and the rate of turning is increased following injection with methamphetamine (Ungersted and Arbuthnott 1970). Reversal of this pathological turning during DBS depends on stimulation frequency in a manner that parallels the clinical effects of DBS (McConnell et al 2012;So et al 2012b). In each experiment the rat was administered pie charts showing the percentage of the total time spent during IPIs of 3 different durations: Ͻ10 ms (i.e., short pauses), between 10 and 50 ms (i.e., medium pauses), and Ͼ50 ms (i.e., long pauses).…”

Section: Methodsmentioning

confidence: 99%

“…Epochs of 1 min of DBS were separated by 2 min of no stimulation to minimize carry-over effects. Each rat was subjected to at least two circling tests, one to test various stimulation frequencies and one to test various stimulation patterns, because some rats were used in previous studies (McConnell et al 2012: use of 11 of 12 rats overlapped with the present study; So et al 2012b: use of 7 of 16 rats overlapped with the present study). Consecutive tests were performed at least 2 days apart.…”

Section: Methodsmentioning

confidence: 99%

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Failure to suppress low-frequency neuronal oscillatory activity underlies the reduced effectiveness of random patterns of deep brain stimulation

McConnell

Grill

2016

Journal of Neurophysiology

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McConnell GC, So RQ, Grill WM. Failure to suppress lowfrequency neuronal oscillatory activity underlies the reduced effectiveness of random patterns of deep brain stimulation. J Neurophysiol 115: 2791-2802, 2016. First published March 9, 2012 doi:10.1152/jn.00822.2015.-Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established treatment for the motor symptoms of Parkinson's disease (PD). However, the mechanisms of action of DBS are unknown. Random temporal patterns of DBS are less effective than regular DBS, but the neuronal basis for this dependence on temporal pattern of stimulation is unclear. Using a rat model of PD, we quantified the changes in behavior and single-unit activity in globus pallidus externa and substantia nigra pars reticulata during high-frequency STN DBS with different degrees of irregularity. Although all stimulus trains had the same average rate, 130-Hz regular DBS more effectively reversed motor symptoms, including circling and akinesia, than 130-Hz irregular DBS. A mixture of excitatory and inhibitory neuronal responses was present during all stimulation patterns, and mean firing rate did not change during DBS. Low-frequency (7-10 Hz) oscillations of single-unit firing times present in hemiparkinsonian rats were suppressed by regular DBS, and neuronal firing patterns were entrained to 130 Hz. Irregular patterns of DBS less effectively suppressed 7-to 10-Hz oscillations and did not regularize firing patterns. Random DBS resulted in a larger proportion of neuron pairs with increased coherence at 7-10 Hz compared with regular 130-Hz DBS, which suggested that long pauses (interpulse interval Ͼ50 ms) during random DBS facilitated abnormal low-frequency oscillations in the basal ganglia. These results suggest that the efficacy of high-frequency DBS stems from its ability to regularize patterns of neuronal firing and thereby suppress abnormal oscillatory neural activity within the basal ganglia. These observations led to the hypothesis that DBS disrupts pathological patterns of neuronal activity Garcia et al. 2005;Hashimoto et al. 2003) and that the resulting regularization of neuronal activity is critical to the mechanism of DBS McCairn and Turner 2009).The importance of the temporal pattern of neuronal activity was reinforced in clinical studies comparing the effects of irregular and regular patterns of DBS on motor symptoms (Gross and McDougal 2013;Hess et al. 2013). Stimulation that was periodically cycled on and off was less effective than continuous DBS (Montgomery 2005), and random patterns of stimulation, even when delivered at a high frequency, were less effective than regular stimulation at reducing tremor (Birdno et al. 2008(Birdno et al. , 2012 and bradykinesia (Dorval et al. 2010). However, these studies did not reveal why irregular high-frequency stimulation was not sufficient to treat symptoms.In the present study, we quantified behavior and single-unit neuronal activity in the globus pallidus externa (GPe) and substantia nigra pars reticulata (SNr) during differen...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Failure to suppress low-frequency neuronal oscillatory activity underlies the reduced effectiveness of random patterns of deep brain stimulation

McConnell

Grill

2016

Journal of Neurophysiology

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“…The block of eleven epochs was two hours in duration and this design was dictated by the limited time of action of the drugs. The task was performed four times per animal for each drug, in line with other rodent studies [18], [30]. Video data in 3D was captured using a Microsoft Kinect (Microsoft, Washington, USA) and was processed in Matlab to determine the angular movement of the rat over time.…”

Section: E Behavioral Measuresmentioning

confidence: 99%

Characterizing Motor and Cognitive Effects Associated With Deep Brain Stimulation in the GPi of Hemi-Parkinsonian Rats

Summerson

Aazhang

Kemere

2014

IEEE Trans. Neural Syst. Rehabil. Eng.

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The globus pallidus internus (GPi) is the main output nucleus of the basal ganglia, which is associated with a variety of functions including motor performance and cognition. The GPi is one of the primary targets of deep brain stimulation (DBS) in patients with movement disorders. However, the therapeutic mechanism of GPi-DBS is poorly understood and rodent models have not been characterized. Cognitive side effects, such as impulsivity and depression, of DBS treatment for Parkinson's disease are known, but their relationship to the efficacy of the treatment is not well explained. The goal of this study is to illuminate the effects of GPi-DBS on both motor and cognitive function in a hemi-Parkinsonian rat model. In this work, we study the motor performance of the rodents in multiple behaviors, as well as of impulsivity and depression, and consider the relationship between these behavioral variables and the stimulation frequency of the DBS signal. For the first time, the connection is directly established between stimulating the GPi, motor performance and cognition is directly established in the hemi-Parkinsonian rodent model.

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“…Our experiments for up to six weeks demonstrated greater beneficial effects for unipolar compared with bipolar DBS [22]. Unipolar stimulation has also been suggested for the hemiparkinsonian rat model by [17].…”

Section: Discussionmentioning

confidence: 58%

“…In these experiments, external stimulators are often used, and the behavioral outcomes are not examined [10][11][12][13][14][15]. In another approach, implanted DBS electrodes are connected to stationary stimulators via cables, which enable the movement of the animals in a confined area during behavioral testing [16][17][18]. DBS stimulators fixed to the heads of rats enabled the animals to move freely in experiments conducted for up to five weeks [19,20].…”

Section: Introductionmentioning

confidence: 99%

Impedance detection of the electrical resistivity of the wound tissue around deep brain stimulation electrodes permits registration of the encapsulation process in a rat model

Badstuebner

Stubbe

Kroeger

et al. 2017

Journal of Electrical Bioimpedance

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An animal model of deep brain stimulation (DBS) was used in in vivo studies of the encapsulation process of custom-made platinum/iridium microelectrodes in the subthalamic nucleus of hemiparkinsonian rats via electrical impedance spectroscopy. Two electrode types with 100-µm bared tips were used: i) a unipolar electrode with a 200-µm diameter and a subcutaneous gold wire counter electrode and ii) a bipolar electrode with two parallelshifted 125-µm wires. Miniaturized current-controlled pulse generators (130 Hz, 200 µA, 60 µs) enabled chronic DBS of the freely moving animals. A phenomenological electrical model enabled recalculation of the resistivity of the wound tissue around the electrodes from daily in vivo recordings of the electrode impedance over two weeks. In contrast to the commonly used 1 kHz impedance, the resistivity is independent of frequency, electrode properties, and current density. It represents the ionic DC properties of the tissue. Significant resistivity changes were detected with a characteristic decrease at approximately the 2nd day after implantation. The maximum resistivity was reached before electrical stimulation was initiated on the 8th day, which resulted in a decrease in resistivity. Compared with the unipolar electrodes, the bipolar electrodes exhibited an increased sensitivity for the tissue resistivity.

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Characterizing Effects of Subthalamic Nucleus Deep Brain Stimulation on Methamphetamine-Induced Circling Behavior in Hemi-Parkinsonian Rats

Cited by 28 publications

References 36 publications

Failure to suppress low-frequency neuronal oscillatory activity underlies the reduced effectiveness of random patterns of deep brain stimulation

Failure to suppress low-frequency neuronal oscillatory activity underlies the reduced effectiveness of random patterns of deep brain stimulation

Characterizing Motor and Cognitive Effects Associated With Deep Brain Stimulation in the GPi of Hemi-Parkinsonian Rats

Impedance detection of the electrical resistivity of the wound tissue around deep brain stimulation electrodes permits registration of the encapsulation process in a rat model

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