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This Article Full Text Full Text (PDF) All Versions of this Article: 99/3/1477    most recent 01080.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Guo, Y. Articles by Terman, D. PubMed PubMed Citation Articles by Guo, Y. Articles by Terman, D.

Thalamocortical Relay Fidelity Varies Across Subthalamic Nucleus Deep Brain Stimulation Protocols in a Data-Driven Computational Model

¹Department of Mathematics, Drexel University, Philadelphia, Pennsylvania; ²Department of Mathematics, University of Pittsburgh, Pittsburgh, Pennsylvania; ³Departments of Biomedical Engineering and ⁴Neuroscience, Cleveland Clinic, Cleveland; and ⁵Department of Mathematics, The Ohio State University, Columbus, Ohio

Submitted 27 September 2007; accepted in final form 29 December 2007

The therapeutic effectiveness of deep brain stimulation (DBS) of the subthalamic nucleus (STN) may arise through its effects on inhibitory basal ganglia outputs, including those from the internal segment of the globus pallidus (GPi). Changes in GPi activity will impact its thalamic targets, representing a possible pathway for STN-DBS to modulate basal ganglia-thalamocortical processing. To study the effect of STN-DBS on thalamic activity, we examined thalamocortical (TC) relay cell responses to an excitatory input train under a variety of inhibitory signals, using a computational model. The inhibitory signals were obtained from single-unit GPi recordings from normal monkeys and from monkeys rendered parkinsonian through arterial 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injection. The parkinsonian GPi data were collected in the absence of STN-DBS, under sub-therapeutic STN-DBS, and under therapeutic STN-DBS. Our simulations show that inhibition from parkinsonian GPi activity recorded without DBS-compromised TC relay of excitatory inputs compared with the normal case, whereas TC relay fidelity improved significantly under inhibition from therapeutic, but not sub-therapeutic, STN-DBS GPi activity. In a heterogeneous model TC cell population, response failures to the same input occurred across multiple TC cells significantly more often without DBS than in the therapeutic DBS case and in the normal case. Inhibitory signals preceding successful TC relay were relatively constant, whereas those before failures changed more rapidly. Computationally generated inhibitory inputs yielded similar effects on TC relay. These results support the hypothesis that STN-DBS alters parkinsonian GPi activity in a way that may improve TC relay fidelity.