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

Abstract

Much of the motor impairment associated with Parkinson’s disease is thought to arise from pathological activity in the networks formed by the basal ganglia (BG) and motor cortex. To evaluate several hypotheses proposed to explain the emergence of pathological oscillations in parkinsonism, we investigated changes to the directed connectivity in BG networks following dopamine depletion. We recorded local field potentials (LFPs) in the cortex and basal ganglia of rats rendered parkinsonian by injection of 6-hydroxydopamine (6-OHDA) and in dopamine-intact controls. We performed systematic analyses of the networks using a novel tool for estimation of directed interactions (nonparametric directionality, NPD). We used a “conditioned” version of the NPD analysis that reveals the dependence of the correlation between two signals on a third reference signal. We find evidence of the dopamine dependency of both low-beta (14–20 Hz) and high-beta/low-gamma (20–40 Hz) directed network interactions. Notably, 6-OHDA lesions were associated with enhancement of the cortical “hyperdirect” connection to the subthalamic nucleus (STN) and its feedback to the cortex and striatum. We find that pathological beta synchronization resulting from 6-OHDA lesioning is widely distributed across the network and cannot be located to any individual structure. Furthermore, we provide evidence that high-beta/gamma oscillations propagate through the striatum in a pathway that is independent of STN. Rhythms at high beta/gamma show susceptibility to conditioning that indicates a hierarchical organization compared with those at low beta. These results further inform our understanding of the substrates for pathological rhythms in salient brain networks in parkinsonism.NEW & NOTEWORTHY We present a novel analysis of electrophysiological recordings in the cortico-basal ganglia network with the aim of evaluating several hypotheses concerning the origins of abnormal brain rhythms associated with Parkinson’s disease. We present evidence for changes in the directed connections within the network following chronic dopamine depletion in rodents. These findings speak to the plausibility of a “short-circuiting” of the network that gives rise to the conditions from which pathological synchronization may arise.

Aberrant striatal oscillations after dopamine loss in parkinsonian non-human primates

“…Previous studies have addressed the current questions by comparing and contrasting the oscillations, but specifically in the 13-30 Hz in PD patients, MPTP-treated NHP models of PD, and 6-OHDA-lesioned rat (Sharott et al, 2005;Hammond et al, 2007;Stein and Bar-Gad, 2013). Similar to our study, a recent rodent study shows the evidence of the dopamine dependency of low-beta (14-20 Hz) directed interactions within the basal ganglia and corticobasal ganglia networks (West et al, 2018). The pharmacotherapy of PD is primarily based on two classes of drugs: dopamine precursors, (levodopa) and dopamine receptor agonists (apomorphine) and both therapies reduces the beta-band activity.…”

Electrocorticographic dissociation of alpha and beta rhythmic activity in the human sensorimotor system

“…High-density laminar recordings of alpha and beta rhythmic activity might be able to test whether those rhythms propagate through different cortical layers (van Kerkoerle et al, 2014). Another possibility is that different corticothalamo-cortical and cortico-striatal-thalamo-cortical circuits lead to different alpha and beta travelling waves across the sensorimotor cortex (Bastos et al, 2014;Schreckenberger et al, 2004;West et al, 2018). The latter possibility could accommodate the observation that sources/sinks of the traveling waves were independent from electrodes sampling rhythms with larger amplitudes, and that there were no obvious phase-shifts between neighboring electrodes spanning a cortical fold.…”

“…Neuronal local field potentials in the sensorimotor cortex are organized in two prominent spectral clusters, alpha-and beta-band rhythms, known to be relevant for movement selection and to differ across several features. For instance, there are differences in the cortico-subcortical loops supporting alpha-and beta-band rhythms (Bastos et al, 2014;Leventhal et al, 2012;Schreckenberger et al, 2004;West et al, 2018), and only the latter rhythm has clear modulatory effects on corticospinal neurons (Baker et al, 1997;Madsen et al, 2019;Mima and Hallett, 1999;van Elswijk et al, 2010). Yet, the neurophysiological characteristics of alpha-and beta-band rhythms have often been studied by aggregating these two rhythms into the same (mu-) rhythm category (Cuevas et al, 2014;Hari, 2006;Miller et al, 2010), an approach often justified by the partial overlap in their spatial and spectral distributions (Bressler and Richter, 2015;Haegens et al, 2014;Salmelin and Hari, 1994;Szurhaj et al, 2003) and by the temporal correlation of their power envelopes (Carlqvist et al, 2005;de Lange et al, 2008;Tiihonen et al, 1989).…”

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

“…and neurological disorders [1,2,[19][20][21][22][23][24][25][26][27]. However, the mechanisms of these oscillations, 10 and their role in motor behavior and its dysfunctions, remain poorly understood.…”

“…Disorders 4 of the DA and motor systems, such as Parkinson's, Huntington's, Tourette's, and many 5 others, result in abnormal network activity within striatum [1-9]. Rhythmic activity is 6 observed in both striatal spiking and local field potential, and oscillations in the 7 striatum are correlated with voluntary movement, reward, and decision-making in 8 March 8, 2020 2/50 healthy individuals [10-18], while disruptions of these rhythms are biomarkers of mental 9and neurological disorders [1,2,[19][20][21][22][23][24][25][26][27]. However, the mechanisms of these oscillations, 10 and their role in motor behavior and its dysfunctions, remain poorly understood.…”