Motor learning interference is proportional to occlusion of LTP-like plasticity

Abstract

Learning interference occurs when learning something new causes forgetting of an older memory (retrograde interference) or when learning a new task disrupts learning of a second subsequent task (anterograde interference). This phenomenon, described in cognitive, sensory, and motor domains, limits our ability to learn multiple tasks in close succession. It has been suggested that the source of interference is competition of neural resources, although the neuronal mechanisms are unknown. Learning induces long-term potentiation (LTP), which can ultimately limit the ability to induce further LTP, a phenomenon known as occlusion. In humans we quantified the magnitude of occlusion of anodal transcranial direct current stimulation-induced increased excitability after learning a skill task as an index of the amount of LTP-like plasticity used. We found that retention of a newly acquired skill, as reflected by performance in the second day of practice, is proportional to the magnitude of occlusion. Moreover, the degree of behavioral interference was correlated with the magnitude of occlusion. Individuals with larger occlusion after learning the first skill were (1) more resilient to retrograde interference and (2) experienced larger anterograde interference when training a second task, as expressed by decreased performance of the learned skill in the second day of practice. This effect was not observed if sufficient time elapsed between training the two skills and LTP-like occlusion was not present. These findings suggest competition of LTP-like plasticity is a factor that limits the ability to remember multiple tasks trained in close succession.

Figures

Figure 1.

Experimental protocol for all groups. Group AA (n = 11) trained Skill A, and then returned the following day for a retention test of Skill A. Group ABA (n = 10) trained Skill A, then immediately trained Skill B, then returned the following day for a retention test. Group BAA (n = 10) trained Skill B first then Skill A, and returned the following day for a retention test. Group R (n = 10) trained a randomized version of the skill task. Training involved practice of each of the skill tasks in four epochs of 30 trials. Group ABA-6HRS (n = 8) trained Skill A and B identical to Group ABA except that a 6 h delay was introduced on the first day between training of Skill A and B. In these groups, MEP amplitudes (black arrows) were measured before and after application of A-tDCS (gray ray). This was assessed on separate days, D0 when there was no training and on D1 after training. To control for the effects of A-tDCS in between training blocks Group Sham-ABA (n = 8) trained on Skills A and B, as done in Group ABA, but with sham tDCS (light gray ray) applied in between training.

Figure 2.

Performance of Skill A. Black circles are the average performances of Skill A in the AA group, light gray diamonds represent Skill A in the ABA group, dark gray triangles are the Skill A performance average in the BAA group, and white circles are the skill performance average for the R group. Vertical dotted line denotes the separation between D1 and D2 of training. A, The y-axis represents the skill measure of A and the x-axis depicts epochs of training. Note that subjects who trained in the Group AA outperformed both interference groups (Group ABA and Group BAA) on D2 of training, whereas no significant differences in performance between groups were seen for D1. Group R showed no accumulation of learning. B, The bar graph shows group averages of Skill A measure on D2 relative to D1. Group AA was significantly better than ABA and BAA for D2–D1. Data are means ± SEM. *p ≤ 0.05.

Figure 3.

Behavioral results for the ABA-6HRS and sham stimulation control groups. A, Performance of Skill A for the ABA-6HRS group. The y-axis represents the skill measure of A and the x-axis depicts epochs of training. Black circles are the average performances of Skill A in the AA group; light gray squares represent Skill A in the ABA-6HRS group. Vertical dotted line denotes the separation between D1 and D2 of training. Subjects in the ABA-6HRS group showed similar performance of Skill A on both D1 and D2 of training compared with subjects who trained in Group AA. B, Performance of Skill A for the Sham-ABA group. The y-axis represents the skill measure of A and the x-axis depicts epochs of training. Black circles are the average performances of Skill A in the ABA group and light gray diamonds represent Skill A in the Sham-ABA group. Vertical dotted line denotes the separation between D1 and D2 of training. Note that subjects who trained in the Group ABA with real stimulation showed similar performance and interference compared with subjects in Group ABA with sham stimulation. Data are means ± SEM.

Figure 4.

Error versus movement time. Black circles are the average performances of Skill A in the AA group, light gray diamonds represent Skill A in the ABA group, dark gray triangles are the Skill A performance average in the BAA group. Vertical dotted line denotes the separation between D1 and D2 of training. A, The y-axis represents the error rate of Skill A and the x-axis shows epochs of training. Subjects who trained in the BAA paradigm had significantly more errors in Skill A on D1 compared with both Group AA and ABA. B, The y-axis represents the movement time of A and the x-axis depicts subsequent epochs of training. Subjects who trained in the BAA paradigm were faster on Skill A D1 compared with Groups AA and ABA. Data are means ± SEM. *p ≤ 0.05.

Figure 5.

MEP amplitude ratios for pre- and post-A-tDCS. The y-axis represents the average MEP amplitude standardized to the pre-tDCS MEP amplitude and the x-axis represents successive TMS measurements taken before application of A-tDCS (Pre), immediately after A-tDCS (Post 1; P1) and repeated every 5 min up to 25 min post-A-tDCS (P2…P6). Black circles are the mean MEP amplitude for all subjects on D0 (Baseline Day). Gray diamonds are the mean MEP amplitude for all subjects on D1 (Training Day). Bar graphs depict average MEP amplitude for P1–P6 for Baseline Session (B) and for Training Session (T). Far left graph is MEP amplitudes for AA subjects after training Skill A. Second from left graph is MEP amplitudes for ABA subjects after training Skill A. Second from right graph is MEP amplitudes after training Skill B. Far right graph is the mean MEP amplitude for subjects in Group R (no learning). After training either Skill A or Skill B, subjects had a significant reduction of potentiation aftereffects following application of A-tDCS (occlusion) compared with following a period of rest. Subjects who trained on the randomized task showed similar amounts of LTP-like plasticity either at rest or following training demonstrating no occlusion when accumulation of learning does not occur. Data are means ± SEM. *p ≤ 0.05.

Figure 6.

MEP amplitude ratios for pre- and post-A-tDCS of the ABA-6HRS control group. The y-axis represents the average MEP amplitude standardized to the pre-tDCS MEP amplitude and the x-axis represents successive TMS measurements taken before application of A-tDCS (Pre), immediately after A-tDCS (Post 1, P1), and repeated every 5 min up to 25 min post-A-tDCS (P2…P6). Black circles are the mean MEP amplitude for all subjects on D0 (Baseline Day). Gray diamonds are the mean MEP amplitude for all subjects on D1 (Training Day). Bar graph depicts average MEP amplitude for P1–P6 for Baseline Session (B) and for Training Session (T). Note that MEP measurements were assessed 6 h following training of Skill A. Data are means ± SEM.

Figure 7.

Correlation between occlusion of LTP-like plasticity and behavior. The y-axis represents average skill measure of A on D2 minus D1 and x-axis represents the OI. Black circles represent individual subjects of Group AA, light gray diamonds correspond to ABA subjects, and dark gray triangles represent BAA subjects. Note that subjects in the AA group who had the largest OI following training of Skill A had the highest retention and performance of Skill A on D2 relative to D1. Subjects in the ABA group who had the largest OI following training of Skill A had the best performance of Skill A on D2 relative to D1. Finally, subjects in the BAA group with the largest OI after training of Skill B had the poorest performance of Skill A on D2 relative to D1.