Training Intensity Affects Motor Rehabilitation Efficacy Following Unilateral Ischemic Insult of the Sensorimotor Cortex in C57BL/6 Mice

Abstract

Background: Motor rehabilitative training improves behavioral functionality and promotes beneficial neural reorganization following stroke but is often insufficient to normalize function. Rodent studies have relied on skilled reaching tasks to model motor rehabilitation and explore factors contributing to its efficacy. It has been found that greater training intensity (sessions/day) and duration (training days) facilitates motor skill learning in intact animals. Whether rehabilitative training efficacy varies with intensity following stroke is unclear.

Methods: Mice were trained preoperatively on a skilled reaching task. Following focal ischemic lesions, mice received rehabilitative training either twice daily (high intensity [HI]), once daily (low intensity [LI]), or not at all (control) to determine the effects of rehabilitative training intensity on skilled motor performance.

Results: Within 7 days, the HI-trained mice achieved preischemic levels of performance. Mice receiving LI training eventually reached similar performance levels but required a greater quantity of training. Training intensity did not consistently affect the maintenance of performance gains, which were partially lost over time in both groups.

Discussion: These data indicate that increased training intensity increases the rate of functional improvements per time and per training session following ischemic insult. Thus, training intensity is an important variable to consider in efforts to optimize rehabilitation efficacy.

Keywords: learning; motor cortex; motor skills; recovery of function; stroke.

Figure 1

Lesion verification and analysis for Experiment 1 (A and B) and 2 (C and D). There were no significant differences between groups in lesion size for Experiment 1 (A) or 2 (B). Individual lesions are represented by open circles. Lesions were also consistent in placement, centered around the sensorimotor cortex (Experiment 1 B; Experiment 2 C). Error bars represent SEM.

Figure 2

Experiment 1: High intensity training results in improved behavioral outcome compared with low intensity training. High intensity training resulted in significantly better performance beginning on PO 9 through the termination of motor skill training. * indicates p < 0.05 between high and low intensity, ** indicates p < 0.05 from both low intensity and control. Error bars represent SEM.

Figure 3

Experiment 2: High intensity training results in faster functional improvement but not better skilled motor performance. When the number of training sessions were accounted for, training regimens resulted in similar behavioral outcome (B). However, a session by session analysis revealed that high intensity training resulted in quicker gains of function, with low intensity trained mice requiring the full motor skill training regimen to reach a similar performance level (B). * indicates p < 0.05. Error bars represent SEM.

Figure 4

Experiment 2: Performance maintenance over time. Both high and low intensity trained mice exhibited a decrease in performance levels following the cessation of rehabilitative motor skill training. There were no differences between groups in the maintenance of performance improvements over time. Error bars represent SEM.