300-Hz subthalamic oscillations in Parkinson's disease

Abstract

Despite several studies and models, much remains unclear about how the human basal ganglia operate. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for complicated Parkinson's disease, but how DBS acts also remains unknown. The clinical benefit of DBS at frequencies >100 Hz suggests the possible importance of neural rhythms operating at frequencies higher than the range normally considered for basal ganglia processing (<100 Hz). The electrodes implanted for DBS also offer the opportunity to record neural activity from the human basal ganglia. This study aimed to assess whether oscillations at frequencies >100 Hz operate in the human STN. While recording local field potentials from the STN of nine patients with Parkinson's disease through DBS electrodes, we found a dopamine- and movement-dependent 300-Hz rhythm. At rest, and in the absence of dopaminergic medication, in most cases (eight out of 11 nuclei) the 100-1000 Hz band showed no consistent rhythm. Levodopa administration elicited (or markedly increased) a 300-Hz rhythm at rest [(mean +/- SD) central frequency: 319 +/- 33 Hz; bandwidth: 72 +/- 21 Hz; power increase (after medication - before medication)/before medication: 1.30 +/- 1.25; n = 11, P = 0.00098]. The 300-Hz rhythm was also increased by apomorphine, but not by orphenadrine. The 300-Hz rhythm was modulated by voluntary movement. Before levodopa administration, movement-related power increase in the 300-Hz rhythm was variably present in different subjects, whereas after levodopa it became a robust phenomenon [before 0.014 +/- 0.014 arbitrary units (AU), after 0.178 +/- 0.339 AU; n = 8, P = 0.0078]. The dopamine-dependent 300-Hz rhythm probably reflects a bistable compound nuclear activity and supports high-resolution information processing in the basal ganglia circuit. An absent 300-Hz subthalamic rhythm could be a pathophysiological clue in Parkinson's disease. The 300-Hz rhythm also provides the rationale for an excitatory--and not only inhibitory--interpretation of DBS mechanism of action in humans.

Mechanisms of physiological and epileptic HFO generation

“…In this overview we primarily consider cortical (including hippocampal) oscillations under normal and epileptic conditions, but we should note that subcortical HFOs exist, for instance in the basal ganglia where they are faster (~300 Hz) in Parkinson's Disease patients than in patients with other conditions (~200 Hz) (Danish et al, 2007;Foffani et al, 2003). We will first address general mechanisms of oscillations, at the level of cells and networks, and an account of experimental in vitro and in vivo models being used to investigate HFOs; this is followed by a section where the focus lies on the role of HFOs in experimental and clinical epilepsy and the underlying mechanisms; in the final part the contribution of computational modeling is reviewed.…”

Beta Reactivity, Prospective Facilitation of Executive Processing, and Its Dependence on Dopaminergic Therapy in Parkinson's Disease

“…Their tonic and phasic suppression by dopaminergic medication and salient cues correlates with changes in motor performance (Kühn et al, 2004(Kühn et al, , 2009Doyle et al, 2005;Williams et al, 2005;Kempf et al, 2007;Ray et al, 2008;Pogosyan et al, 2009;Ló pez-Azcárate et al, 2010;Zaidel et al, 2010). Such suppression is accompanied by a surge in dynamic interactions between basal ganglia neurons, involving increased neuronal discharge rates and synchronization at gamma, or higher, frequencies (Courtemanche et al, 2003;Foffani et al, 2003;Amirnovin et al, 2004;Alegre et al, 2005;Devos et al, 2006;Pogosyan et al, 2006;Kempf et al, 2007;Androulidakis et al, 2008;Kane et al, 2009;Ló pez-Azcárate et al, 2010;Ö zkurt et al, 2011). This raises two possibilities.…”

Pattern Identification of Subthalamic Local Field Potentials in Parkinson’s Disease

“…So as to we can classify the PD patients LFP before and after medication treatment, and accurately identify the brain functional state of PD patients. The brain functional state of PD patients identification model flow chart is shown in Figure 1: Figure 3,we can see that the power spectral density(PSD) amplitudes of LFP oscillations increase in theta bands (4)(5)(6)(7)(8),and high beta bands (20-30 Hz),and decrease in the range of low beta bangs(12-18 Hz).And only in the low beta bands Dopamine drugs can significantly suppress the STN oscillations of the band (P <0.05, t-test, Figure.3).We can also find that the balance of PSD between different frequency bands in LFP before and after the medication are also different. In this paper, the low frequency compoments of LFP signals were divided into four bands: theta (4-8 Hz), alpha (8-12 Hz), low beta (12-18 Hz) and high beta (20-30 Hz).Respectively calculated the power spectral ratio between each frequency band, used paired sample t-test analysis of STN LFP before and after medication to extract characteristics of different frequency bands energy ratio closely related to PD, for quantitying balance between different frequency bands.…”

“…The subthalamic nucleus (STN) is closely related to symptoms of PD patients [3].The local field potential (LFP) signals were recorded by implanted electrode into the patients STN which contains abundant information related to disease and symptoms [4,5].Therefore, this paper used the machine learning procedure to study the patients LFP before and after medication treatment, achieved the identification and judgment of brain function in PD patients.…”