Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson’s disease

Abstract

Local field potentials and pairs of neurones in the subthalamic nucleus (STN) of patients with Parkinson's disease show high-frequency oscillations (HFOs) at 15-30 Hz. This study explores how these HFOs are modulated by voluntary movements and by dopaminergic medication. We examined 15 patients undergoing implantation of bilateral deep brain stimulating electrodes using microelectrode recordings of pairs of STN neurones (eight patients) and macroelectrode recordings of local field potentials from the STN (14 patients). Synchronized HFOs between STN neurones were observed in 28 out of 37 pairs in five patients who had tremor in the operating room and none of 45 pairs in three patients who did not. In two of the three non-tremulous patients, HFOs in the frequency spectra of local field potentials were detected but were weaker than in those patients with tremor. Active movement suppressed synchronized HFOs in three out of five pairs of neurones, independent of changes in firing rate. HFOs observed in the local field potentials in nine out of 14 patients were reduced with voluntary movement in six of the eight patients tested. Dopaminergic medication decreased the incidence of synchronized HFOs in STN neurone pairs, reduced HFO synchrony in a pair of tremor cells concurrent with a reduction in firing rate and limb tremor, and decreased HFOs of local field potentials in the STN. These results demonstrate that HFO synchronization in the STN is reduced by voluntary movements and by exogenous dopaminergic medication. A mechanism for neuronal oscillatory synchronization in basal ganglia is proposed. It is suggested that the firing of STN neurones can be synchronized by 15-30 Hz cortical beta oscillatory activity, particularly when dopamine deficiency results in a higher background firing rate of STN neurones, and that this synchronization contributes to parkinsonian pathophysiology.

Mechanisms and Targets of Deep Brain Stimulation in Movement Disorders

“…86,87 Most notably in PD patients, synchronized bursting was present between the STN and the GPe, [88][89][90] in which oscillatory frequencies in the range of 15 Hz to 30 Hz (beta range) tended to predominate. 91 After dopaminergic treatment (e.g., levodopa), the power of these oscillations in the GP attenuated. 88 A similar effect in the GP was shown for clinically beneficial STN HFS parameter sets in humans.…”

Mechanisms of Deep Brain Stimulation in Movement Disorders as Revealed by Changes in Stimulus Frequency

“…41 There is an increase in the presence of bursts, low frequency oscillations, and synchronization in neurons in the basal ganglia and thalamus in movement disorders. 22,[42][43][44][45][46][47][48] Such changes in discharge patterns and synchronization play an important role in the pathophysiology of movement disorders. Motor symptoms including tremor, bradykinesia, and rigidity are associated with increased neuronal synchronization and low-frequency rhythmic oscillation, 49 -51 and bursts and oscillations parallel the appearance of motor symptoms in PD.…”

Mechanisms underlying cortical resonant states: implications for levodopa-induced dyskinesia

“…Several electrophysiological studies using animal models of PD have concluded that neuronal activity patterns in the parkinsonian state show an excessive synchronized oscillatory activity in practically all parts of the corticobasal ganglia circuits (Bergman et al, 1994;Nini et al, 1995;Sharott et al, 2005;Costa et al, 2006). Similar activity patterns have also been observed in PD patients where electrophysiological recordings have been obtained in conjunction with the implantation of deep brain stimulation (DBS) electrodes (Levy et al, 2000(Levy et al, , 2002. Specifically, synchronization of neuronal activity at lower frequencies, as measured by the power of local field potential (LFP) signals in the 8-to 35-Hz frequency band, has been suggested to directly correlate with the severity of motor symptoms in PD patients (K ü hn et al, 2006).…”