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

Journal article

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 (Non-Parametric Directionality, NPD). We also used a 'conditioned' version of the NPD analysis which reveals the dependence of correlation between two signals upon a third reference signal. We find evidence of 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 "hyper-direct" 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. Further, 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 when compared to low beta. These results further inform our understanding of the substrates for pathological rhythms in salient brain networks in Parkinsonism.

Authors: West, TO; Berthouze, L; Halliday, DM; Litvak, V; Sharott, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Physiological Society
• Journal: Journal of Neurophysiology
• Volume: 119
• Issue: 5
• Pages: 1608-1628
• Publication date: 2018-01-10
• Acceptance date: 2018-01-03
• DOI: 10.1152/jn.00629.2017
• ISSN: 1522-1598 and 0022-3077
• Pmid: 29357448
• Language: English
• Keywords: Parkinson's Disease; synchronization; local field potential; basal ganglia; connectivity