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.
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.
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ABSTRACT: Excessive synchronization of neuronal activity at around 20 Hz is a common finding in the basal ganglia of patients with untreated Parkinson's disease (PD). Correlative evidence suggests, but does not prove, that this spontaneous activity may contribute to slowness of movement in this condition. Here we investigate whether externally imposed synchronization through direct stimulation of the region of the subthalamic nucleus at 20 Hz can slow motor performance in a simple unimanual tapping task and whether this effect is frequency selective. Tapping rates were recorded on 42 sides in 22 patients with PD after overnight withdrawal of medication. Tapping was performed without stimulation and during bilateral stimulation at 20 Hz, 50 Hz and 130 Hz. We found that tapping rates were slowed by 8.2+/-3.2% (p=0.014) during 20-Hz stimulation in subjects with relatively preserved baseline function in the task. This effect was frequency selective. The current data provide proof of the principle that excessive beta synchrony within the basal ganglia-cortical loop may contribute to the slowing of movements in Parkinson's disease.Experimental Neurology 06/2007; 205(1):214-21. · 4.65 Impact Factor
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ABSTRACT: The subthalamic nucleus-globus pallidus network plays a central role in basal ganglia function and dysfunction. To determine whether the relationship between activity in this network and the principal afferent of the basal ganglia, the cortex, is altered in a model of Parkinson's disease, we recorded unit activity in the subthalamic nucleus-globus pallidus network together with cortical electroencephalogram in control and 6-hydroxydopamine-lesioned rats under urethane anaesthesia. Subthalamic nucleus neurones in control and 6-hydroxydopamine-lesioned animals exhibited low-frequency oscillatory activity, which was tightly correlated with cortical slow-wave activity (approximately 1 Hz). The principal effect of dopamine depletion was that subthalamic nucleus neurones discharged more intensely (233% of control) and globus pallidus neurones developed low-frequency oscillatory firing patterns, without changes in mean firing rate. Ipsilateral cortical ablation largely abolished low-frequency oscillatory activity in the subthalamic nucleus and globus pallidus. These data suggest that abnormal low-frequency oscillatory activity in the subthalamic nucleus-globus pallidus network in the dopamine-depleted state is generated by the inappropriate processing of rhythmic cortical input. A component (15-20%) of the network still oscillated following cortical ablation in 6-hydroxydopamine-lesioned animals, implying that intrinsic properties may also pattern activity when dopamine levels are reduced. The response of the network to global activation was altered by 6-hydroxydopamine lesions. Subthalamic nucleus neurones were excited to a greater extent than in control animals and the majority of globus pallidus neurones were inhibited, in contrast to the excitation elicited in control animals. Inhibitory responses of globus pallidus neurones were abolished by cortical ablation, suggesting that the indirect pathway is augmented abnormally during activation of the dopamine-depleted brain. Taken together, these results demonstrate that both the rate and pattern of activity of subthalamic nucleus and globus pallidus neurones are altered profoundly by chronic dopamine depletion. Furthermore, the relative contribution of rate and pattern to aberrant information coding is intimately related to the state of activation of the cerebral cortex.Neuroscience 02/2001; 106(2):313-30. · 3.12 Impact Factor
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ABSTRACT: Local field potentials (LFPs) recorded from the subthalamic nucleus (STN) of untreated patients implanted with stimulation electrodes for the treatment of Parkinson's disease (PD) demonstrate strong coherence with the cortical electroencephalogram over the beta-frequency range (15-30 Hz). However, studies in animal models of PD emphasize increased temporal coupling in cortico-basal ganglia circuits at substantially lower frequencies, undermining the potential usefulness of these models. Here we show that 6-hydroxydopamine (6-OHDA) lesions of midbrain dopamine neurons are associated with significant increases in the power and coherence of beta-frequency oscillatory activity present in LFPs recorded from frontal cortex and STN of awake rats, as compared with the healthy animal. Thus, the pattern of synchronization between population activity in the STN and cortex in the 6-OHDA-lesioned rodent model of PD closely parallels that seen in the parkinsonian human. The peak frequency of coherent activity in the beta-frequency range was increased in lesioned animals during periods of spontaneous and sustained movement. Furthermore, administration of the dopamine receptor agonist apomorphine to lesioned animals suppressed beta-frequency oscillations, and increased coherent activity at higher frequencies in the cortex and STN, before producing the rotational behaviour indicative of successful lesion. Taken together, these results support a crucial role for dopamine in the modulation of population activity in cortico-basal ganglia circuits, whereby dopaminergic mechanisms effectively filter out synchronized, rhythmic activity at beta-frequencies at the systems level, and shift temporal couplings in these circuits to higher frequencies. These changes may be important in regulating movement.European Journal of Neuroscience 04/2005; 21(5):1413-22. · 3.75 Impact Factor