Abstract
Exaggerated local field potential bursts of activity at frequencies in the low beta band are a well-established phenomenon in the subthalamic nucleus of patients with Parkinson’s disease. However, such activity is only moderately correlated with motor impairment. Here we test the hypothesis that beta bursts are just one of several dynamic states in the subthalamic nucleus local field potential in Parkinson’s disease, and that together these different states predict motor impairment with high fidelity.Local field potentials were recorded in 32 patients (64 hemispheres) undergoing deep brain stimulation surgery targeting the subthalamic nucleus. Recordings were performed following overnight withdrawal of anti-parkinsonian medication, and after administration of levodopa. Local field potentials were analysed using hidden Markov modelling to identify transient spectral states with frequencies under 40 Hz.Findings in the low beta frequency band were similar to those previously reported; levodopa reduced occurrence rate and duration of low beta states, and the greater the reductions, the greater the improvement in motor impairment. However, additional local field potential states were distinguished in the theta, alpha and high beta bands, and these behaved in an opposite manner. They were increased in occurrence rate and duration by levodopa, and the greater the increases, the greater the improvement in motor impairment. In addition, levodopa favoured the transition of low beta states to other spectral states. When all local field potential states and corresponding features were considered in a multivariate model it was possible to predict 50% of the variance in patients’ hemibody impairment OFF medication, and in the change in hemibody impairment following levodopa. This only improved slightly if signal amplitude or gamma band features were also included in the multivariate model. In addition, it compares with a prediction of only 16% of the variance when using beta bursts alone.We conclude that multiple spectral states in the subthalamic nucleus local field potential have a bearing on motor impairment, and that levodopa-induced shifts in the balance between these states can predict clinical change with high fidelity. This is important in suggesting that some states might be upregulated to improve parkinsonism and in suggesting how local field potential feedback can be made more informative in closed-loop deep brain stimulation systems.
Highlights
Parkinson’s disease (PD) is a neurodegenerative condition involving degeneration of dopaminergic neurons in the substantia nigra of the midbrain and characterised by the cardinal symptoms of bradykinesia, rigidity and tremor
Medication-induced changes in subthalamic nucleus (STN) local field potential (LFP) states Time delay embedded Hidden Markov Modelling (HMM) (TDE-HMM) was run on the STN LFP data to identify a temporal sequence of states in each STN LFP channel, where each state can be interpreted as a transient spectral event of a certain type, including, but not limited to, beta bursts.[28]
We have demonstrated that multiple spectral states in the STN LFP have a bearing on motor impairment in PD patients, and that levodopa modulates these states and shifts the balance between them in a way that predicts clinical change with high fidelity
Summary
Parkinson’s disease (PD) is a neurodegenerative condition involving degeneration of dopaminergic neurons in the substantia nigra of the midbrain and characterised by the cardinal symptoms of bradykinesia, rigidity and tremor. Symptomatology is partially reversed by the dopamine prodrug, levodopa, but more advanced disease may necessitate deep brain stimulation (DBS). This therapy involves the chronic electrical stimulation of key targets in the basal ganglia, like the subthalamic nucleus (STN), that have been functionally compromised by the effects of dopaminergic denervation.[1] The effectiveness of DBS has increased interest in the nature of activity in the neural circuits modulated by stimulation. The reduction in mean beta power in the local field potential (LFP) recorded in the STN after administration of levodopa or during DBS is positively correlated with the attendant improvement of motor impairment.[3,4,5,6,7,8,9,10,11]
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