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Stimulating at the right time to recover network states in a model of the cortico-basal ganglia-thalamic circuit

West, Timothy O; Magill, Peter J; Sharott, Andrew; Litvak, Vladimir; Farmer, Simon F; Cagnan, Hayriye; (2022) Stimulating at the right time to recover network states in a model of the cortico-basal ganglia-thalamic circuit. PLoS Computational Biology , 18 (3) , Article e1009887. 10.1371/journal.pcbi.1009887. Green open access

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Abstract

Synchronization of neural oscillations is thought to facilitate communication in the brain. Neurodegenerative pathologies such as Parkinson's disease (PD) can result in synaptic reorganization of the motor circuit, leading to altered neuronal dynamics and impaired neural communication. Treatments for PD aim to restore network function via pharmacological means such as dopamine replacement, or by suppressing pathological oscillations with deep brain stimulation. We tested the hypothesis that brain stimulation can operate beyond a simple "reversible lesion" effect to augment network communication. Specifically, we examined the modulation of beta band (14-30 Hz) activity, a known biomarker of motor deficits and potential control signal for stimulation in Parkinson's. To do this we setup a neural mass model of population activity within the cortico-basal ganglia-thalamic (CBGT) circuit with parameters that were constrained to yield spectral features comparable to those in experimental Parkinsonism. We modulated the connectivity of two major pathways known to be disrupted in PD and constructed statistical summaries of the spectra and functional connectivity of the resulting spontaneous activity. These were then used to assess the network-wide outcomes of closed-loop stimulation delivered to motor cortex and phase locked to subthalamic beta activity. Our results demonstrate that the spatial pattern of beta synchrony is dependent upon the strength of inputs to the STN. Precisely timed stimulation has the capacity to recover network states, with stimulation phase inducing activity with distinct spectral and spatial properties. These results provide a theoretical basis for the design of the next-generation brain stimulators that aim to restore neural communication in disease.

Type: Article
Title: Stimulating at the right time to recover network states in a model of the cortico-basal ganglia-thalamic circuit
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pcbi.1009887
Publisher version: https://doi.org/10.1371/journal.pcbi.1009887
Language: English
Additional information: © 2022 West et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience
URI: https://discovery.ucl.ac.uk/id/eprint/10144885
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