Local field potential beta activity in the subthalamic nucleus of patients with Parkinson’s disease is associated with mprovements in bradykinesia after dopamine and deep brain stimulation

Department of Anatomy, Physiology and Genetics, University of Oxford, Parks Road, OX1 3PT, USA.
Experimental Neurology (Impact Factor: 4.7). 06/2008; 213(1):108-13. DOI: 10.1016/j.expneurol.2008.05.008
Source: PubMed


Parkinson's disease is treated pharmacologically with dopamine replacement medication and, more recently, by stimulating basal-ganglia nuclei such as the subthalamic nucleus (STN). Depth recordings after this procedure have revealed excessive activity at frequencies between 8 and 35 Hz (Brown et al., 2001; Kuhn et al., 2004; Priori et al., 2004) that are reduced by dopamine therapy in tandem with improvements in bradykinesia/rigidity, but not tremor (Kuhn et al., 2006). It has also been shown that improvements in motor symptoms after dopamine correlate with single unit activity in the beta range (Weinberger et al., 2006). We recorded local field potentials (LFPs) from the subthalamic nucleus of patients with Parkinson's disease (PD) after surgery to implant deep brain stimulating electrodes while they were on and off dopaminergic medication. As well as replicating Kuhn et al., using the same patients we were able to extend Weinberger et al. to show that LFP beta oscillatory activity correlated with the degree of improvement in bradykinesia/rigidity, but not tremor, after dopamine medication. We also found that the power of beta oscillatory activity uniquely predicted improvements in bradykinesia/rigidity, but again not tremor, after stimulation of the STN in a regression analysis. However improvements after STN stimulation related inversely to beta power, possibly reflecting the accuracy of the electrode placement and/or the limits of STN stimulation in patients with the greatest levels of beta oscillatory activity.

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    • "This ectopic oscillatory activity is recorded yet again on local field potential recordings from the subthalamic nucleus, specifically in the gamma frequency range, among PD patients who present with tremor (Weinberger et al., 2009). Data obtained from depth recordings on patients undergoing Deep Brain Stimulation also showed the presence of excessive synchronization in the form of 'pathological' beta oscillations in the subthalamic nucleus; a phenomenon that was correlated with the degree to which patient's respond to dopaminergic medication (Weinberger et al., 2006;Ray et al., 2008;Kühn et al., 2009). Animal models of Parkinson's Disease have also provided robust evidence of impaired neuronal network synchronization. "
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    ABSTRACT: Increasingly in the realm of neurological disorders, particularly those involving neurodegeneration, mitochondrial dysfunction is emerging at the core of their pathogenic processes. Most of these diseases still lack effective treatment and are hampered by a shortfall in the development of novel medicines. Clearly new targets that translate well to the clinic are required. Physiological parameters in the form of neuronal network activity are increasingly being used as a therapeutic screening approach in drug development and disorders with mitochondrial dysfunction generally display neuronal network activity disturbance. However research directly linking the disturbances in neuronal network activity with mitochondrial dysfunction is only just starting to emerge. This review will summarize the breadth of knowledge linking neuronal network activity to mitochondrial dysfunction in neurodegenerative diseases and suggest potential avenues for exploration in respect to future drug development.
    Full-text · Article · Oct 2015 · Neuropharmacology
    • "Studies in animal models of Parkinson's disease also support the hypothesis that altered connectivity in the cortico-basal ganglia-thalamocortical circuit plays a key role in the pathology of the disease [13], [14]. Bradykinesia and rigidity, hallmark motor symptoms of Parkinson's disease, have been shown to correlate with synchronous beta-band oscillatory activity in the basal ganglia [15], [16]. A correlative relationship between limb tremor in patients and oscillatory activity in the theta (or tremor) frequency range has also been established [17]. "
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    ABSTRACT: Parkinson's disease is a progressive, neurodegenerative disorder, characterized by hallmark motor symptoms. It is associated with pathological, oscillatory neural activity in the basal ganglia. Deep brain stimulation (DBS) is often successfully used to treat medically refractive Parkinson's disease. However, the selection of stimulation parameters is based on qualitative assessment of the patient which can result in a lengthy tuning period and a suboptimal choice of parameters. This study explores fourth-order, control theory-based models of oscillatory activity in the basal ganglia. Describing function analysis is applied to examine possible mechanisms for the generation of oscillations in interacting nuclei and to investigate the suppression of oscillations with high frequency stimulation. The theoretical results for the suppression of the oscillatory activity obtained using both the fourth-order model, and a previously described second-order model, are optimized to fit clinically recorded local field potential data obtained from Parkinsonian patients with implanted DBS. Close agreement between the power of oscillations recorded for a range of stimulation amplitudes is observed (R2 = 0:68-0:97). The results suggest that the behavior of the system and the suppression of pathological neural oscillations with DBS is well described by the macroscopic models presented. The results also demonstrate that in this instance, a second-order model is sufficient to model the clinical data, without the need for added complexity. Describing the system behavior with computationally efficient models could aid in the identification of optimal stimulation parameters for patients in a clinical environment.
    No preview · Article · Aug 2015 · IEEE transactions on bio-medical engineering
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    • "The role of beta oscillatory activity in the cortico-basal ganglia circuit is comparatively much more studied, and beta network alterations have been reported in a variety of studies (Pfurtscheller and Aranibar, 1977; Pfurtscheller and Lopes da Silva, 1999; Kü hn et al., 2004, 2008a, b; Lalo et al., 2007; Ray et al., 2008; Hirschmann et al., 2011; Litvak et al., 2011a; Brü cke et al., 2012; Alegre et al., 2013). A suppression of beta band activity has frequently been reported during motor tasks in the motor cortex (Pfurtscheller and Aranibar, 1977; Pfurtscheller and Lopes da Silva, 1999; Lalo et al., 2007), GPi (Brü cke et al., 2008, 2012; Singh et al., 2011a, b; Herrojo Ruiz et al., 2014), the subthalamic nucleus (Kü hn et al., 2004; Litvak et al., 2012; Alegre et al., 2013) and the motor thalamus (Paradiso et al, 2004; Kempf et al., 2009; Brü cke et al., 2013). "
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    ABSTRACT: Primary dystonia has been associated with an underlying dysfunction of a wide network of brain regions including the motor cortex, basal ganglia, cerebellum, brainstem and spinal cord. Dystonia can be effectively treated by pallidal deep brain stimulation although the mechanism of this effect is not well understood. Here, we sought to characterize cortico-basal ganglia functional connectivity using a frequency-specific measure of connectivity-coherence. We recorded direct local field potentials from the human pallidum simultaneously with whole head magnetoencephalography to characterize functional connectivity in the cortico-pallidal oscillatory network in nine patients with idiopathic dystonia. Three-dimensional cortico-pallidal coherence images were compared to surrogate images of phase shuffled data across patients to reveal clusters of significant coherence (family-wise error P < 0.01, voxel extent 1000). Three frequency-specific, spatially-distinct cortico-pallidal networks have been identified: a pallido-temporal source of theta band (4-8 Hz) coherence, a pallido-cerebellar source of alpha band (7-13 Hz) coherence and a cortico-pallidal source of beta band (13-30 Hz) coherence over sensorimotor areas. Granger-based directionality analysis revealed directional coupling with the pallidal local field potentials leading in the theta and alpha band and the magnetoencephalographic cortical source leading in the beta band. The degree of pallido-cerebellar coupling showed an inverse correlation with dystonic symptom severity. Our data extend previous findings in patients with Parkinson's disease describing motor cortex-basal ganglia oscillatory connectivity in the beta band to patients with dystonia. Source coherence analysis revealed two additional frequency-specific networks involving the temporal cortex and the cerebellum. Pallido-cerebellar oscillatory connectivity and its association with dystonic symptoms provides further confirmation of cerebellar involvement in dystonia that has been recently reported using functional magnetic resonance imaging and fibre tracking.
    Full-text · Article · May 2015 · Brain
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