The Parkinsonian Subthalamic Network: Measures of Power, Linear, and Non-linear Synchronization and their Relationship to L-DOPA Treatment and OFF State Motor Severity

Abstract

In this paper we investigated the dopaminergic modulation of neuronal interactions occurring in the subthalamic nucleus (STN) during Parkinson's disease (PD). We utilized linear measures of local and long range synchrony such as power and coherence, as well as Detrended Fluctuation Analysis for Phase Synchrony (DFA-PS)- a recently developed non-linear method that computes the extent of long tailed autocorrelations present in the phase interactions between two coupled signals. Through analysis of local field potentials (LFPs) taken from the STN we seek to determine changes in the neurodynamics that may underpin the pathophysiology of PD in a group of 12 patients who had undergone surgery for deep brain stimulation. We demonstrate up modulation of alpha-theta (5–12 Hz) band power in response to L-DOPA treatment, whilst low beta band power (15–20 Hz) band-power is suppressed. We also find evidence for significant local connectivity within the region surrounding STN although there was evidence for its modulation via administration of L-DOPA. Further to this we present evidence for a positive correlation between the phase ordering of bilateral STN interactions and the severity of bradykinetic and rigidity symptoms in PD. Although, the ability of non-linear measures to predict clinical state did not exceed standard measures such as beta power, these measures may help identify the connections which play a role in pathological dynamics.

A biophysical model of striatal microcircuits suggests gamma and beta oscillations interleaved at delta/theta frequencies mediate periodicity in motor control

“…Supporting this hypothesis, the β frequency generated by D2 SPNs in our model is substantially lower than that generated by the D1 SPN subnetwork in the high DA condition (Fig 6). Experimental work suggests that parkinsonian β is specifically a low (<20 Hz) β, and that treatment by L-DOPA or deep brain stimulation specifically reduces power in the low β band without affecting high β power [93,109,110]. Our model suggests that this distinction in β frequency bands is at least in part due to differences in excitatory drive between subtypes of SPNs expressing different DA receptors.…”

Propagation of beta/gamma rhythms in the cortico-basal ganglia circuits of the parkinsonian rat

“…Excessive beta oscillations (14–30 Hz) in the BG associated with dopamine depletion have been observed reliably in untreated patients with PD ( Brown et al 2001 ; Hammond et al 2007 ; Levy et al 2000 ; Weinberger et al 2006 ). Beta rhythms are attenuated by treatments such as dopamine replacement therapy ( Beudel et al 2017 ; Kühn et al 2006 ; Levy et al 2002 ; Weinberger et al 2006 ; West et al 2016 ) and deep brain stimulation (DBS) ( Eusebio et al 2011 ; Ray et al 2008 ; Whitmer et al 2012 ) in a way that correlates with the degree of improvement of akinetic/rigid motor symptoms. This has strengthened the argument that the pathological beta rhythms are directly related to the functional impairment seen in patients ( Brittain and Brown 2014 ; Hanslmayr et al 2012 ).…”

A biophysical model of striatal microcircuits suggests delta/theta-rhythmically interleaved gamma and beta oscillations mediate periodicity in motor control

“…6). Experimental work suggests that parkinsonian β is specifically a 409 low (<20 Hz) β, and that treatment by L-DOPA or deep brain stimulation specifically 410 reduces power in the low β band without affecting high β power [93,109,110]. Our 411 model suggests that this distinction in β frequency bands is at least in part due to 412 differences in excitatory drive between subtypes of SPNs expressing different DA 413 receptors.…”