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Stochastic Modeling of Mouse Motor Activity under Deep Brain Stimulation: The Extraction of Arousal Information

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  • Daniel M Keenan
  • Amy W Quinkert
  • Donald W Pfaff

Abstract

In the present paper, we quantify, with a rigorous approach, the nature of motor activity in response to Deep Brain Stimulation (DBS), in the mouse. DBS is currently being used in the treatment of a broad range of diseases, but its underlying principles are still unclear. Because mouse movement involves rapidly repeated starting and stopping, one must statistically verify that the movement at a given stimulation time was not just coincidental, endogenously-driven movement. Moreover, the amount of activity changes significantly over the circadian rhythm, and hence the means, variances and autocorrelations are all time varying. A new methodology is presented. For example, to discern what is and what is not impacted by stimulation, velocity is classified (in a time-evolving manner) as being zero-, one- and two-dimensional movement. The most important conclusions of the paper are: (1) (DBS) stimulation is proven to be truly effective; (2) it is two-dimensional (2-D) movement that strongly differs between light and dark and responds to stimulation; and, (3) stimulation in the light initiates a manner of movement, 2-D movement, that is more commonly seen in the (non-stimulated) dark. Based upon these conclusions, it is conjectured that the above patterns of 2-D movement could be a straightforward, easy to calculate correlate of arousal. The above conclusions will aid in the systematic evaluation and understanding of how DBS in CNS arousal pathways leads to the activation of behavior.Author Summary: Brainstem and thalamic regulation of arousal has been studied experimentally since the mid 20-th century. Today, Deep Brain Stimulation (DBS) is used in the treatment of movement disorders, chronic pain, clinical depression, amongst others. At present, the proper choice of DBS parameters (frequency and strength of the electric stimulation), and how those parameters should be modified as conditions change, are not well understood. In this work, using motor activity as the observed response, a statistical framework is developed for such study, and a quantitative relationship between parameter values and response is established. Within this framework, a possible correlate of arousal, the rapid onset of spatial (two-dimensional) movement, is uncovered and also studied. One long-term hope for techniques such as DBS are that they could assist in the treatment of disorders of consciousness, by supplementing or replacing (e.g., in Traumatic Brain Injury) what should ordinarily be the appropriate endogenous stimulation.

Suggested Citation

  • Daniel M Keenan & Amy W Quinkert & Donald W Pfaff, 2015. "Stochastic Modeling of Mouse Motor Activity under Deep Brain Stimulation: The Extraction of Arousal Information," PLOS Computational Biology, Public Library of Science, vol. 11(2), pages 1-24, February.
    • Handle: RePEc:plo:pcbi00:1003883
    DOI: 10.1371/journal.pcbi.1003883
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