Dose of remote limb ischemic conditioning for enhancing learning in healthy young adults

Abstract

Remote limb ischemic conditioning (RLIC) is a technique in which tissues distant from the target organ are exposed to brief, sub-lethal bouts of ischemia. The effects of remotely applied ischemic conditioning are systemically transferred to the target organ, and typically manifested as protection from subsequent ischemic injury. Previous studies in our lab have found and confirmed that RLIC enhances learning and retention during motor training on a balance task. The current study tested the effect of RLIC dose (number of cycles) on learning enhancement in young, healthy adults. Forty healthy participants age 18-40 years were randomized to receive 5 cycles of sham conditioning (n = 9), 3 cycles of RLIC (n = 11), 4 cycles of RLIC (n = 10), or 5 cycles of RLIC (n = 10) using a blood pressure cuff around the upper arm once a day for 7 consecutive weekdays (Days 1-7). Participants concurrently trained on a balance task, bimanual cup stacking task, and a discrete sequence production task on Days 3-7. Change in performance on each of the three tasks was compared across groups. Participants in all four groups improved their performance on each of the three tasks over time. However, RLIC at any dose did not enhance learning on any of the three tasks. While RLIC is safe, inexpensive, and clinically feasible, reproducibility may be challenged by unidentified factors, raising critical challenges to the straightforward translation of RLIC for improving rehabilitation outcomes in individuals recovering from neurological injury.

Keywords: Ischemic conditioning; Motor learning; Psychomotor performance.

Conflict of interest statement

Conflict of Interest: The authors declare that they have no conflict of interest.

Figures

Fig 1. CONSORT flow diagram

149 individuals were assessed for eligibility. Of those, 109 individuals were excluded for not meeting inclusion/exclusion criteria, declining to participate/uninterested, or inability to meet time commitment. 40 individuals were allocated to 1 of 4 groups. No participants were lost to follow up or discontinued the study. Nine individuals in the Sham group, 11 in the RLIC-3 group, 10 in the RLIC-4 group, and 10 in the RLIC-5 group had complete data sets, which were used for analysis. Microsoft Publisher was used to create this figure

Fig 2. Experimental design and tasks

(a)Study timeline, (b) Bimanual cup stacking patterns. Participants must stack and unstack cups beginning with sequence 1 (top) and ending with sequence 3 (bottom). (c) Discrete Sequence Production task computer view. Left panel depicts a sequence identity cue, displayed before the first stimulus (middle panel). When the correct and corresponding key is pushed, the next stimulus would immediately appear (right panel). Microsoft Publisher was used to create this figure

Fig 3. Balance and bimanual cup stacking

(a) Average number of seconds in balance during 30-second trials for each group. Data points represent the average of 5 trials (Pre-Test and Post-Test) or 15 trials (D3-D7). Error bars represent SEM. (b) Average Movement Time in seconds for each group. Data points represent the average of 3 trials (Pre-Test) or 5 trials (D3-D6 and Post-Test). Error bars represent SEM. GraphPad Prism was used to create this figure

Fig 4. Discrete Sequence Production

Average Movement Time in seconds per exposure level for each group. (a) Extensive (EXT) sequences, (b) Moderate (MOD) sequences, (c) Minimum (MIN) sequences. Data points represent the average of 5 trials (Pre-test and Post-test) or pre-determined number of exposures for each training level described above (D3-D7). Error bars represent SEM. GraphPad Prism was used to create this figure