Resting oscillatory cortico-subthalamic connectivity in patients with Parkinson's disease

Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London, UK.
Brain (Impact Factor: 9.2). 02/2011; 134(Pt 2):359-74. DOI: 10.1093/brain/awq332
Source: PubMed


Both phenotype and treatment response vary in patients with Parkinson's disease. Anatomical and functional imaging studies suggest that individual symptoms may represent malfunction of different segregated networks running in parallel through the basal ganglia. In this study, we use a newly described, electrophysiological method to describe cortico-subthalamic networks in humans. We performed combined magnetoencephalographic and subthalamic local field potential recordings in thirteen patients with Parkinson's disease at rest. Two spatially and spectrally separated networks were identified. A temporoparietal-brainstem network was coherent with the subthalamic nucleus in the alpha (7-13 Hz) band, whilst a predominantly frontal network was coherent in the beta (15-35 Hz) band. Dopaminergic medication modulated the resting beta network, by increasing beta coherence between the subthalamic region and prefrontal cortex. Subthalamic activity was predominantly led by activity in the cortex in both frequency bands. The cortical topography and frequencies involved in the alpha and beta networks suggest that these networks may be involved in attentional and executive, particularly motor planning, processes, respectively.

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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.
    Brain 05/2015; DOI:10.1093/brain/awv109 · 9.20 Impact Factor
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    • "To this end we explore a model system in which synchronization can be readily shifted between pathological exaggeration and more physiological levels. The model system consists of the basal ganglia in patients with Parkinson's disease, a condition that, in the untreated state, is dominated by exaggerated synchronization and coherence in the basal gangliacortical circuit (Brown et al., 2001; Williams et al., 2002; Weinberger et al., 2006; Pogosyan et al., 2010; Hirschmann et al., 2011; Litvak et al., 2011). Such synchronization is diminished by dopaminergic therapy, in tandem with amelioration of motor deficit (Kü hn et al., 2006, 2009; Weinberger et al., 2006; Ray et al., 2008). "
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    ABSTRACT: Optimal phase alignment between oscillatory neural circuits is hypothesized to optimize information flow and enhance system performance. This theory is known as communication-through-coherence. The basal ganglia motor circuit exhibits exaggerated oscillatory and coherent activity patterns in Parkinson's disease. Such activity patterns are linked to compromised motor system performance as evinced by bradykinesia, rigidity and tremor, suggesting that network function might actually deteriorate once a certain level of net synchrony is exceeded in the motor circuit. Here, we characterize the processes underscoring excessive synchronization and its termination. To this end, we analysed local field potential recordings from the subthalamic nucleus and globus pallidus of five patients with Parkinson's disease (four male and one female, aged 37-64 years). We observed that certain phase alignments between subthalamic nucleus and globus pallidus amplified local neural synchrony in the beta frequency band while others either suppressed it or did not induce any significant change with respect to surrogates. The increase in local beta synchrony directly correlated with how long the two nuclei locked to beta-amplifying phase alignments. Crucially, administration of the dopamine prodrug, levodopa, reduced the frequency and duration of periods during which subthalamic and pallidal populations were phase-locked to beta-amplifying alignments. Conversely ON dopamine, the total duration over which subthalamic and pallidal populations were aligned to phases that left beta-amplitude unchanged with respect to surrogates increased. Thus dopaminergic input shifted circuit dynamics from persistent periods of locking to amplifying phase alignments, associated with compromised motoric function, to more dynamic phase alignment and improved motoric function. This effect of dopamine on local circuit resonance suggests means by which novel electrical interventions might prevent resonance-related pathological circuit interactions. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.
    Brain 04/2015; 138(6). DOI:10.1093/brain/awv093 · 9.20 Impact Factor
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    • "Oscillatory activities are synchronized not only locally within the STN, but also between the STN and the ipsilateral cerebral cortex (Marsden et al., 2001; Lalo et al., 2008). This coupling of neuronal activities has been demonstrated in terms of coherence between subcortical STN LFPs and cortical EEG in PD patients at rest (Williams et al., 2002; Fogelson et al., 2006; Hirschmann et al., 2011; Litvak et al., 2011). This coherence suggests that there are several functional subloops between the STN and the motor cortex (MCx), which are generally distinguished by their frequencies: the sub-beta frequency band (sub-beta band) in the 3–13 Hz range and the beta frequency band (beta band) in the 14–35 Hz range (Lalo et al., 2008). "
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    ABSTRACT: It has been suggested that abnormal synchronization and oscillation of neuronal activity in the subthalamic nucleus (STN) is associated with sensorimotor dysfunction in Parkinson's disease (PD). We investigated the bilateral subcortico-cortical functional coupling in PD patients. We simultaneously recorded local field potentials from the bilateral STN using electrodes inserted for deep brain stimulation and electroencephalograms from the bilateral motor cortices (MCx) in 11 patients at rest, and analyzed their coherences and causalities. Significant coherence in the sub-beta and beta frequency bands was simultaneously observed between the STN and contralateral STN (STN-cSTN), the STN and ipsilateral MCx (STN-iMCx), and the STN and contralateral MCx (STN-cMCx). In each patient, the frequency of the peak STN-cSTN coherence was similar to that of the peak STN-iMCx and STN-cMCx coherence. The causality between the STN and MCx was strongest in the one-way direction from the MCx to the ipsilateral STN. Abnormal oscillations in the STN in the sub-beta and beta bands were functionally coupled among bilateral STN and MCx at the eigen-frequency in individual patients with PD. Synchronized activity through cortico-subcortical transmission may have an important role in the pathophysiology of PD. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 12/2014; 53. DOI:10.1016/j.clinph.2014.12.007 · 3.10 Impact Factor
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