Remote limb ischemic conditioning enhances motor learning in healthy humans

Significance Statement

This study investigated the potential of ischemic conditioning, delivered via blood pressure cuff inflation and deflation to the arm, to facilitate learning. Our data show, for the first time in humans or animals, that ischemic conditioning can enhance motor learning and that the enhancement is retained over time. These results open up the possibility that ischemic conditioning might be harnessed as a neurorecovery agent for people suffering from stroke and other neurological conditions. A major advantage of ischemic conditioning over other potential agents is its simple technology, low cost, and clinical feasibility. While our first translational target is stroke, the potential benefits of ischemic conditioning extend far beyond stroke to other neuro-, geriatric (e.g. balance and falls), and pediatric rehabilitation populations.

Figure legend

Motor learning was enhanced in every participant who received ischemic conditioning (green lines) compared to those who received sham conditioning (black lines). The enhancement was maintained 2 and 4 weeks later, without an additional conditioning or training. X-Axis: time, with training delivered for 5 consecutive days between the pretest and post-test assessments. Y-Axis: performance on a standing balance board, quantified by the number of seconds participants were able to hold the board level (± 3 degrees). A larger number of seconds indicates better performance.

Journal Reference

J Neurophysiol. 2015 Jun 1;113(10):3708-19.

Cherry-Allen KM¹, Gidday JM², Lee JM³, Hershey ^T4, Lang CE⁵.

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Program in Physical Therapy, Washington University School of Medicine, St. Louis, Missouri;
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri; Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri;
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri;
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri; Department of Radiology, Washington University School of Medicine, St. Louis, Missouri; and.
Program in Physical Therapy, Washington University School of Medicine, St. Louis, Missouri; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri; Program in Occupational Therapy, Washington University School of Medicine, St. Louis, Missouri [email protected].

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Abstract

Brief bouts of sublethal ischemia have been shown to protect exposed tissue (ischemic conditioning) and tissues at remote sites (remote ischemic conditioning) against subsequent ischemic challenges. Given that the mechanisms of this protective phenomenon are multifactorial and epigenetic, we postulated that remote limb ischemic conditioning (RLIC) might enhance mechanisms responsible for neural plasticity, and thereby facilitate learning. Specifically, we hypothesized that conditioning of the nervous system with remote limb ischemic conditioning, achieved through brief repetitive limb ischemia prior to training, would facilitate the neurophysiological processes of learning, thus making training more effective and more long-lasting. Eighteen healthy adults participated in this study; nine were randomly allocated to remote limb ischemic conditioning and nine to sham conditioning. All subjects underwent seven consecutive weekday sessions and 2-wk and 4-wk follow-up sessions. We found that remote limb ischemic conditioning resulted in significantly greater motor learning and longer retention of motor performance gains in healthy adults. Changes in motor performance do not appear to be due to a generalized increase in muscle activation or muscle strength and were not associated with changes in serum brain-derived neurotrophic factor (BDNF) concentration. Of note, remote limb ischemic conditioning did not enhance cognitive learning on a hippocampus-dependent task. While future research is needed to establish optimal conditioning and training parameters, this inexpensive, clinically feasible paradigm might ultimately be implemented to enhance motor learning in individuals undergoing neuromuscular rehabilitation for brain injury and other pathological conditions.

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