Local field potential beta activity in the subthalamic nucleus of patients with Parkinson's disease is associated with improvements 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: 4.62). 06/2008; 213(1):108-13.
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Parkinson's disease (PD) is characterized by widespread neural interactions in cortico-basal-ganglia networks primarily in beta oscillations (approx. 10–30 Hz), as suggested by previous findings of levodopa-modulated interhemispheric coherence between the bilateral subthalamic nuclei (STN) in local field potential recordings (LFPs). However, due to confounding effects of volume conduction the existence of ‘genuine’ interhemispheric subcortical coherence remains an open question. To address this issue we utilized the imaginary part of coherency (iCOH) which, in contrast to the standard coherence, is not susceptible to volume conduction. LFPs were recorded from eight patients with PD during wakeful rest before and after levodopa administration. We demonstrated genuine coherence between the bilateral STN in both 10–20 and 21–30 Hz oscillations, as revealed by a non-zero iCOH. Crucially, increased iCOH in 10–20 Hz oscillations positively correlated with the worsening of motor symptoms in the OFF medication condition across patients, which was not the case for standard coherence. Furthermore, across patients iCOH was increased after levodopa administration in 21–30 Hz oscillations. These results suggest a functional distinction between low and high beta oscillations in STN-LFP in line with previous studies. Furthermore, the observed functional coupling between the bilateral STN might contribute to the understanding of bilateral effects of unilateral deep brain stimulation. In conclusion, the present results imply a significant contribution of time-delayed neural interactions to interhemispheric coherence, and the clinical relevance of long-distance neural interactions between bilateral STN for motor symptoms in PD.
    European Journal of Neuroscience 09/2014; · 3.67 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In recent years the authors have developed what appears to be a very successful phenomenological model for analyzing the role of deep brain stimulation (DBS) in alleviating the symptoms of Parkinson's disease. In this paper, we extend the scope of the model by using it to predict the generation of new frequencies from networks tuned to a specific frequency, or indeed not self-oscillatory at all.We have discussed two principal cases: firstly where the constituent systems are coupled in an excitatory-excitatory fashion, which we designate by “+/+”; and secondly where the constituent systems are coupled in an excitatory-inhibitory fashion, which we designate “+/-”. The model predicts that from a basic system tuned to tremor frequency we can generate an unlimited range of frequencies. We illustrate in particular, starting from systems which are initially non-oscillatory, that when the coupling coefficient exceeds a certain value, the system begins to oscillate at an amplitude which increases with the coupling strength. Another very interesting feature, which has been shown by colleagues of ours to arise through the coupling of complicated networks based on the physiology of the basal ganglia, can be illustrated by the root locus method which shows that increasing and decreasing frequencies of oscillation, existing simultaneously, have the property that their geometric mean remains substantially constant as the coupling strength is varied. We feel that with the present approach, we have provided another tool for understanding the existence and interaction of pathological oscillations which underlie, not only Parkinson's disease, but other conditions such as Tourette's syndrome, depression and epilepsy.
    2014 ELEKTRO; 05/2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Excessive beta oscillations (15-25Hz) in the basal ganglia have been linked to the akineto-rigid symptoms of Parkinson's disease (PD) although it remains unclear whether the underlying mechanism is causative or associative. While a number of studies have reported beta activity in the subthalamic nucleus and globus pallidus internus, relatively little is known about the beta rhythm of the motor thalamus and its relation to movement disorders. To test whether thalamic beta oscillations are related to parkinsonian symptoms, we examined the spectral properties of neuronal activity in the ventral thalamic nuclei of five Parkinson's disease patients (two female, age range 50-72 years) and compared them to five essential tremor (three female, aged 41-75) and four central pain patients (one female, aged 38-60). Spike and local field potential recordings were obtained during microelectrode-guided localization of thalamic nuclei prior to the implantation of deep brain stimulating electrodes. A total of 118 movement-related neurons in the region of the ventral intermediate nucleus (Vim) were analyzed across all patients groups. Eighty of these neurons (68%) displayed significant oscillatory firing in the beta range with the limbs at rest. In contrast, only 5.7% of the ventral oral posterior (Vop) (χ(2) test, p<0.05) and only 7.2 % of the ventral caudal (Vc) neurons fired rhythmically at beta frequency (χ(2) test, p<0.05). Beta power was significantly decreased during limb movements (ANOVA, p<0.05) and was inversely related to tremor-frequency power during tremor epochs in ET and PD (r(2)=0.44). Comparison between patient groups showed that Vim beta power was significantly higher in ET patients versus pain and PD groups (ANOVA, p<0.05). The findings suggest that beta oscillations are found predominantly in Vim and are involved in movement but are not enhanced in tremor-dominant Parkinson's patients.
    Experimental Neurology 09/2014; · 4.62 Impact Factor