Basal ganglia activity patterns in parkinsonism and computational modeling of their downstream effects

• Type of Material: Article
• Authors: Jonathan E. Rubin, University of Pittsburgh; Cameron C. McIntyre, Cleveland Clinic; Robert S Turner, University of Pittsburgh; Thomas Wichmann, Emory University
• Language: English
• Date: 2012-07-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1111/j.1460-9568.2012.08108.x
• Title of Journal or Parent Work: European Journal of Neuroscience
• ISSN: 0953-816X
• Volume: 36
• Issue: 2
• Start Page: 2213
• End Page: 2228
• Grant/Funding Information: The writing of this review was supported by the following grants: NIH R01 NS070865 (JR, RT), NSF DMS1021701 (JR), NIH R01 NS047388 (CM), NIH P50 NS071669 (TW), NIH R01 NS062876 (TW), NIH R01 NS054976 (TW), NIH P51 RR-000165 (Yerkes National Primate Research Center).
• Keywords: LOCAL-FIELD POTENTIALS; oscillation; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE PRIMATE MODEL; Life Sciences & Biomedicine; NIGRA PARS RETICULATA; synchrony; THALAMIC NEURONAL-ACTIVITY; deep brain stimulation; HUMAN SUBTHALAMIC NUCLEUS; HIGH-FREQUENCY STIMULATION; Neurosciences & Neurology; Neurosciences; Science & Technology; basal ganglia; EVENT-RELATED DESYNCHRONIZATION/SYNCHRONIZATION; parkinsonism; DOPAMINE REPLACEMENT THERAPY; DEEP-BRAIN-STIMULATION; GLOBUS-PALLIDUS INTERNUS; burst
• Research Categories: Engineering, Biomedical; Mathematics; Biology, Neuroscience

Abstract

The availability of suitable animal models and the opportunity to record electrophysiologic data in movement disorder patients undergoing neurosurgical procedures has allowed researchers to investigate parkinsonism-related changes in neuronal firing patterns in the basal ganglia and associated areas of the thalamus and cortex. These studies have shown that parkinsonism is associated with increased activity in the basal ganglia output nuclei, along with increases in burst discharges, oscillatory firing and synchronous firing patterns throughout the basal ganglia. Computational approaches have the potential to play an important role in the interpretation of these data. Such efforts can provide a formalized view of neuronal interactions in the network of connections between the basal ganglia, thalamus, and cortex, allow for the exploration of possible contributions of particular network components to parkinsonism, and potentially result in new conceptual frameworks and hypotheses that can be subjected to biological testing. It has proven very difficult, however, to integrate the wealth of the experimental findings into coherent models of the disease. In this review, we provide an overview of the abnormalities in neuronal activity that have been associated with parkinsonism. Subsequently, we discuss some particular efforts to model the pathophysiologic mechanisms that may link abnormal basal ganglia activity to the cardinal parkinsonian motor signs and may help to explain the mechanisms underlying the therapeutic efficacy of deep brain stimulation for Parkinson's disease. We emphasize the logical structure of these computational studies, making clear the assumptions from which they proceed and the consequences and predictions that follow from these assumptions. Parkinsonism has been linked with changes in neuronal firing patterns in the basal ganglia (BG) and associated areas of the thalamus and cortex. We provide an overview of these findings and discuss some efforts to use computational models to understand these relationships as well as the therapeutic effects of deep brain stimulation (DBS). In particular, several modeling studies that we consider focus on the idea that DBS works by regularizing BG outputs. For example, models show how parkinsonian basal ganglia outputs may compromise thalamocortical relay of excitatory inputs (curly brackets), while DBS- induced regularization may restore relay fidelity, and these ideas lead to predictions about the importance of particular BG outputs in the emergence of parkinsonian signs and of particular DBS properties in alleviating these signs.