Improving consolidation by applying anodal transcranial direct current stimulation at primary motor cortex during repetitive practice

Abstract

Engagement of primary motor cortex (M1) is important for successful consolidation of motor skills. Recruitment of M1 has been reported to be more extensive during interleaved compared to repetitive practice and this differential recruitment has been proposed to contribute to the long-term retention benefit associated with interleaved practice. The present study administered anodal direct current stimulation (tDCS) during repetitive practice in an attempt to increase M1 activity throughout repetitive practice with the goal to improve the retention performance of individuals exposed to this training format. Fifty-four participants were assigned to one of three experimental groups that included: interleaved-sham, repetitive-sham, and repetitive-anodal tDCS. Real or sham stimulation at M1 was administered during practice of three motor sequences for approximately 20-min. Performance in the absence of any stimulation was evaluated prior to practice, immediately after practice as well as at 6-hr, and 24-h after practice was complete. As expected, for the sham conditions, interleaved as opposed repetitive practice resulted in superior offline gain. This was manifest as more rapid stabilization of performance after 6-h as well as an enhancement in performance with a period of overnight sleep. Administration of anodal stimulation at M1 during repetitive practice improved offline gains assessed at both 6-h and 24-h tests compared to the repetitive practice sham group. These data are consistent with the claims that reduced activation at M1 during repetitive practice impedes offline gain relative to interleaved practice and that M1 plays an important role in early consolidation of novel motor skills even in the context of the simultaneous acquisition of multiple new skills. Moreover, these findings highlight a possible role for M1 during sleep-related consolidation, possibly as part of a network including the dorsal premotor region, which supports delayed performance enhancement.

Introduction

Competent motor behavior resulting from skill acquisition is the foundation of most human daily activity. Acquisition of motor skills and the associated neuroplastic changes that occur are dependent on exposure to extensive practice. Practice however should be organized to optimize its effectiveness (Wright et al., 2014). In this regard, interleaved practice has been reported to foster superior long-term retention compared to repetitive practice when multiple novel motor skill are being acquired simultaneously (Shea and Morgan, 1979, Lage et al., 2015, Wright et al., 2016). Interleaved practice is characterized by a frequent change in task demands for the learner across practice trials by being required to execute a different motor skill on each trial. Conversely, repetitive practice involves the repeated execution of the same motor task for a pre-determined number of trials before facing practice of other to-be-learned motor tasks. The retention benefit from interleaved practice is manifest as stable performance during the initial wake hours after practice with further improvement overnight. In contrast, following repetitive practice, significant forgetting occurs immediately after practice is complete with no gain in performance overnight (Wright et al., 2016, Kim and Wright, 2020). These data suggest that interleaved practice fosters effective post-practice consolidation, a process that has been described as critical to the establishment of a robust motor memory (McGaugh, 2000).

Muellbacher et al. (2002) proposed that M1 plays a crucial role in consolidation of motor skills based on the finding that performance improvement of a relatively simple pinch-force task is attenuated by administering 1-Hz repetitive transcranial magnetic stimulation (rTMS) at M1 for 15-min immediately after practice, but not when applied to occipital or dorsolateral prefrontal regions. The interference from rTMS is eliminated if applied approximately 6-hr after practice suggesting early consolidation of new learning is impacted. Modulation of post-practice consolidation can also be mediated via the administration of transcranial direct current stimulation (tDCS) (Buch et al., 2017, Stagg et al., 2018). Importantly, for the present work, application of anodal tDCS at M1 during practice has been shown to facilitate human motor learning by influencing consolidation. Specifically, Reis et al. (2009) had individuals practice a sequential force-pinch skill over the course of five days in the presence of either anodal or sham tDCS at M1. A significant benefit from stimulation during practice was manifest offline. That is, performance enhancement from the application of anodal tDCS at M1 emerged during the intervals between practice sessions and remained for some time after training was over. These data were further elaborated by Reis et al. (2015) noting that similar offline gain is observed following the passage of sufficient time in the absence of sleep (~15-min to 3-h following stimulation).

Since the efficacy of post-practice consolidation has been linked to the long-term retention benefits of interleaved practice, it is possible that the relative greater recruitment of M1 during interleaved practice accounts, at least in part, for the effectiveness of this practice format compared to repetitive practice. Indeed, data are available revealing differential involvement of M1 during interleaved and repetitive practice. Specifically, (a) activity at M1 during response preparation is greater during interleaved practice and correlates with off-line learning for individuals exposed to this schedule of practice (Cross et al., 2007, Wymbs and Grafton, 2009), (b) M1 excitability at the time of retention is greater following interleaved practice and the additional excitability is related to the performance differences between repetitive & interleaved practice at the time of test (Lin et al., 2011), (c) applying supra-threshold single pulse TMS at M1 after interleaved practice trials attenuates the offline gain commonly observed following this type of practice (Lin et al., 2008, Lin et al., 2010), and (d) stronger task-related functional connectivity later in training between the right dorsal premotor area and M1 during interleaved practice is associated with the subsequent retention advantage exhibited by interleaved practice participants (Lin et al., 2013). On the basis of these data, the present study was designed to examine if modifying activity at M1 during repetitive practice, via the application anodal tDCS, can change online and offline performance for individuals that encounter this type of training.

To accomplish this goal, participants were assigned to one of three experimental groups that included two control conditions (Interleaved-Sham, Repetitive-Sham) that performed in the absence of real stimulation and a novel third group that involved the administration of anodal stimulation at M1 throughout repetitive practice (Repetitive-Anodal). In all conditions, motor sequence performance was evaluated during practice (i.e., online) as well as during delayed tests (i.e., offline) using total response time (TT) as the primary dependent variable (Kim et al., 2018). Individuals in the sham conditions were expected to mimic the outcomes commonly observed in previous studies addressing the influence of interleaved and repetitive practice for learning. Specifically, the repetitive practice participants were expected to reveal significant forgetting following the conclusion of practice. In contrast, interleaved practice was expected to support initial stable performance immediately after practice and further performance enhancement following overnight sleep (Shea and Morgan, 1979, Lage et al., 2015, Wright et al., 2016). Motor performance, following practice that was combined with anodal tDCS, was anticipated to improve offline gain resulting in the individuals assigned to Repetitive-Anodal outperforming their Repetitive-Sham counterparts during delayed test. The inclusion of tests administered 6-h as well as 24-h after practice offered the opportunity to assess if any offline benefits from anodal stimulation during repetitive practice are restricted to either early time-dependent and/or sleep-related improvements.