NEW & NOTEWORTHY We have previously reported that visuospatial working memory performance and magnitude of activation in the right dorsolateral prefrontal cortex predict the rate of manual visuomotor adaptation. Sensorimotor savings, or faster adaptation to a previously experienced perturbation, has been recently linked to cognitive processes. We show that facilitating the right prefrontal cortex with anodal transcranial direct current stimulation enhances sensorimotor savings compared with sham stimulation.

We have previously reported that visuospatial working memory performance and magnitude of activation in the right dorsolateral prefrontal cortex predict the rate of visuomotor adaptation. Recent behavioral studies suggest that sensorimotor savings, or faster relearning on second exposure to a task, are due to recall of these early, strategic components of adaptation. In the present study we applied anodal transcranial direct current stimulation to right or left prefrontal cortex or left motor cortex. We found that all groups adapted dart throwing movements while wearing prism lenses at the same rate as subjects receiving sham stimulation on day 1 . On test day 2 , which was conducted a few days later, the right prefrontal and left motor cortex groups adapted faster than the sham group. Moreover, only the right prefrontal group exhibited greater savings, expressed as a greater difference between day 1 and day 2 errors, compared with sham stimulation. These findings support the hypothesis that the right prefrontal cortex contributes to sensorimotor adaptation and savings.

to navigate the world, we often need to adapt our movements in response to changes in the external environment or in the fidelity of sensory inputs. Sensorimotor adaptation is frequently investigated as a model process for such modifications. Although often considered an implicit, obligatory process, several studies support a role for spatial cognitive processes, mediated by right prefrontal cortex, in sensorimotor adaptation. For example, adaptation occurs when participants are explicitly instructed about the visual distortions (Benson et al. 2011), although movement preparation time increases dramatically. Higher spatial working memory scores (Anguera et al. 2010) and greater activation levels in the right dorsolateral prefrontal cortex (Anguera et al. 2011) are associated with faster adaption early in practice, and patients with prefrontal (Taylor and Ivry 2014) or parietal lesions (Mutha et al. 2014) are specifically impaired in the early stages of adaptation, suggesting contributions of frontoparietal networks to adaptation.

Prefrontal cognitive contributions also may be involved in savings, or the faster adaptation that is seen when individuals adapt to a perturbation they have previously experienced. Morehead et al. (2015) recently reported that savings only occur when participants adapt to large perturbations, which are more likely to be explicitly detected (Werner et al. 2015). Moreover, when explicit and implicit components of adaptation were dissociated, savings were only observed in the former. Huberdeau et al. (2015) found that savings occur when as few as five adaptation trials are performed on the first day, and Haith et al. (2015) demonstrated that savings expression requires longer movement preparation time. These findings suggest that savings reflect recall of the initially successful strategy (Morehead et al. 2015), raising the possibility that right dorsolateral prefrontal cortex (DLPFC) may also contribute to savings. A critical role of the right DLPFC is to link working memory representations with upcoming actions. For example, Pochon et al. (2001) reported right DLPFC activation during delay and response periods when individuals held a visuospatial pattern in working memory and used it to prepare a sequence of actions. When participants had to maintain the visuospatial pattern but were not required to make the sequence of actions, right DLPFC was not active.

In the present study we probed the contribution of the right DLPFC to sensorimotor adaptation and savings by applying anodal transcranial direct current stimulation (tDCS; Soterix Medical) while participants threw darts with and without Fresnel prism lenses (The Fresnel Prism and Lens Co.) over 2 days of practice. Additional subject groups received anodal tDCS to the left DLFPC, the left M1, or sham stimulation for comparison. Anodal stimulation is thought to depolarize resting membrane potential, increasing the likelihood of an action potential and enhancing neuroplasticity. Cathodal stimulation, in contrast, is thought to decrease the likelihood of neuronal firing via hyperpolarization (Nitsche and Paulus 2000). Additionally, it is thought that anodal stimulation modulates synaptic activity in a long-term potentiation-type fashion, with cathodal stimulation having effects akin to those of long-term depression (Stagg and Nitsche 2011). We hypothesized that right DLPFC anodal stimulation would accelerate adaptation, particularly for the early, steep portion of the learning curve, and would be associated with greater savings on readaptation on day 2. We further investigated whether this potential effect would be mediated by improvements in spatial working memory, because our previous work demonstrated a link between spatial working memory and rate of early adaptation, mediated by right DLPFC functional magnetic resonance imaging (fMRI) activation levels (Anguera et al. 2010, 2011). Moreover, studies have demonstrated that anodal tDCS applied to the right PFC results in enhanced spatial working memory performance (Jeon and Han 2012; Giglia et al. 2014).

We also predicted that left M1 stimulation would result in greater retention of adaptation (Galea et al. 2011). Recent work has demonstrated that left prefrontal cathodal stimulation suppresses verbal working memory and enhances golf putting performance (Zhu et al. 2015); thus we expected that left prefrontal anodal stimulation might slow the early phase of sensorimotor adaptation.

MATERIALS AND METHODS Participants. Sixty young adults (mean age 20.5 yr; 33 women) were recruited from the University of Michigan student community and were paid for their participation. All subjects were right-handed and used their dominant arm throughout the study. Before enrolling in the study, potential subjects completed a self-report questionnaire to exclude those with neurological or psychiatric disorders. Additional screening measures were administered in the laboratory to exclude subjects with any contraindications for tDCS. All subjects signed a consent form approved by the University of Michigan Institutional Review Board. tDCS setup. The experimental set up and protocol were identical on testing days 1 and 2 (Fig. 1), which were separated by 2 days for most participants. Three different tDCS electrode montages were selected for this study. Electrode placement was determined using the 10-20 EEG system (Jasper 1958). For right and left DLPFC, hereafter referred to as left and right prefrontal cortex (PFC), the anode was placed over scalp location F4/F3 and the cathode over Fp1/Fp2, respectively. For left M1, the anode was placed over location C3 and the cathode over Fp2. Current (2 mA) was administered for 20 min via two saline-soaked, 35-cm2 sponge electrodes (induced current density of 0.057 mA/cm2). A sham (control) group was also established in which the electrodes were set up using either the right PFC or M1 montage. For this group, the current was ramped up to 2.0 mA over 30 s and then ramped back down at the beginning and end of 20 min. Fig. 1.Overview of the experimental protocol. Participants first performed one version of the card rotations test (Card Rot) and 15 dart throws without prism lenses. tDCS was then turned on, and participants then performed a second version of the card rotations test, the proprioceptive alignment (PA) test, baseline, adaptation, and postadaptation dart throwing trials, and an additional PA test. The protocol was identical for testing days 1 and 2. Download figureDownload PowerPoint

Card rotations test. We assessed subjects' spatial working memory by having them complete the card rotations test (CRT; French et al. 1963) during two time points. This is the same test that we previously found to be associated with the rate of early adaptation (Anguera et al. 2010). Subjects had 3 min to work on each part of the test. One part was completed at baseline without stimulation, and the second part was completed as soon as the current reached 2 mA and the subject indicated that he/she was comfortable enough to begin the task; the two test parts were presented in a counterbalanced order across subjects and within subjects across days. The test is composed of 10 items. Each item has a template card to the left of a vertical line and eight cards to the right of the vertical line that have either been rotated in two-dimensional space from the template card or made into a mirror image and then rotated relative to the template. The subject's goal is to decide whether each item to the right of the vertical line is the same as or different from the template card to the left of the vertical line. A card is the same if it has been rotated in two-dimensional space, whereas a card is different if it is a mirror image. Scores are derived by totaling the number of correct items and subtracting the number of incorrect items. Alignment/realignment. We measured baseline proprioceptive alignment before the initial set of dart throws and immediately postadaptation to assess how this alignment changes following prism adaptation. Subjects were asked to stand with their toes against the edge of a black line on the floor and were instructed to “close your eyes and point your right arm at the location in space that you believe to be directly in front of your nose” (Redding and Wallace 1996). A Baseline goniometer was used to measure the angle between the subject's right shoulder and the outstretched arm. The difference between the baseline and postadaptation alignment angles was used to determine the degree of realignment that took place with adaptation to the prism goggles. Dart throwing task. Before beginning each set of dart throws, subjects were positioned so that they were standing behind a black line on the floor that was located 7 feet away from a standard dartboard. They were informed that their objective was to hit the red target in the center of the dartboard. They were also told that they should not attempt to aim by lining up their arm with the target before each throw. This rule was enforced by having participants leave their throwing arm relaxed at their side while looking up at the dartboard before each throw. Once the subject was ready, the researcher would give him/her a verbal cue, at which time the subject would raise his/her arm and throw the dart in one fluid, ballistic movement. Subjects completed two baseline blocks of dart throws (baseline 1 and baseline 2) consisting of 15 throws apiece, for a total of 30 baseline throws. tDCS current was turned on before baseline 2, allowing us to determine any tDCS effects on baseline performance. After each throw, the researchers manually measured and recorded the horizontal and vertical displacement (in cm) of the dart from the nearest edge of the target. Prism adaptation. For the adaptation blocks, subjects wore goggles with Fresnel 3M Press-on plastic lenses mounted in each eyepiece. The lenses were oriented so that the subjects' visual field was displaced to the left by 40 diopters (22.8°). Subjects were instructed to close their eyes while the researchers placed the goggles on their head over the electrodes and to then open them. Participants performed 30 throws with the lenses on. Postadaptation. After the final throw in the adaptation block, subjects were asked to again close their eyes while the researchers removed the goggles. They were then instructed to line their feet up against the black line in preparation for the second alignment measure. Participants then completed a final set of 30 postadaptation throws. After completing all experimental tasks on day 2, subjects filled out an exit survey asking whether they were explicitly aware of the visual perturbation introduced by the prism goggles and what conscious strategies, if any, they used to improve their throwing performance. Statistical analyses. Group × trial repeated-measures ANOVAs were conducted to evaluate whether stimulation group affected dart throwing performance on baseline, adaptation, and readaptation trials or savings. The Huynh-Feldt epsilon correction was used to examine whether sphericity was violated; in these cases, Greenhouse-Geisser adjusted degrees of freedom were used to interpret significance. Significant ANOVAs were followed up with direct contrasts comparing each stimulation group to sham across trials (i.e., group × trial analyses with 2 groups).

RESULTS A total of eight subjects withdrew from the study due to discomfort with testing. It is difficult to determine whether this discomfort was related to wearing prism lenses, which has been shown to induce symptoms of motion sickness in many subjects, or to the tDCS stimulation. It is notable, however, that five of these eight subjects were in the right PFC stimulation group. One additional subject was omitted from analyses because he showed no reduction in aiming error with practice. Five additional subjects are only included in the day 1 analyses because they did not return for day 2 testing within a timely fashion. This resulted in the following total numbers of subjects for day 1: M1, 14; right PFC, 15; left PFC, 14; and sham, 10; and for day 2: M1, 12; right PFC, 12; left PFC, 12; and sham, 10. Savings were only evaluated for day 1 subjects who also participated in day 2 testing. Forty-two of the 46 subjects were scheduled for day 2 testing two days following day 1 testing. Scheduling difficulties resulted in four subjects being tested for day 2 three days following day 1; these four participants were distributed across groups. All participants reported awareness that there was some sort of visual perturbation induced by the lenses, although not all could describe the nature of the shift. Day 1 performance. When tDCS stimulation reached the 20-min mark, subjects were on average at adaptation in 26–29 of 30 throws across the groups. There was no effect of tDCS during the pretest period (group: F 1,3 = 1.49, P > 0.05; group × trial: F 1,3 = 0.95, P > 0.05). All participants adapted to the prism lenses with throwing practice, as evidenced by a significant reduction in errors across the adaptation period (trial effect: F 12.4,1421 = 82.4, P < 0.001), but the rate of adaptation did not vary by stimulation group (group: F 3,49 = 0.9, P > 0.05; group × trial: F 37.2,608 = 1.2, P > 0.05; Fig. 2). Likewise, all subjects exhibited a progressive recovery of accuracy after removing the prism goggles (trial effect: F 13.4,655 = 84.6, P < 0.001), but the rate did not differ by stimulation group (group: F 3,49 = 0.42, P > 0.05; group × trial: F 40,655 = 1.0, P > 0.05). Fig. 2.Horizontal dart throwing errors for day 1. The first 30 trials were baseline without prism lenses; tDCS stimulation was turned on halfway through this block. The subsequent 30 trials were adaptation, during which participants wore the prism lenses. The final 30 trials show re-adaptation after the prism lenses had been removed. There were no significant error differences by group on day 1. Download figureDownload PowerPoint

Participants showed an improvement in their CRT scores from the first to the second repetition on day 1 (effect of time: F 1,49 = 29.5, P < 0.0001), and this effect did not differ by group (group main effect: F 3,49 = 1.6, P = 0.19; group × time interaction: F 3,49 = 0.95, P = 0.42; Fig. 3). There was no correlation between CRT scores and slope of error change (linear functions provided a better fit to the data than exponential decay functions) during adaptation (P > 0.05). All participants experienced a shift in their perception of straight ahead as a function of prism adaptation (effect of time: F 1,49 = 48.8, P < 0.0001); this effect did not differ by stimulation group (group main effect: F 3,49 = 0.48, P = 0.69; group × time interaction: F 3,49 = 0.08, P = 0.97; Fig. 3). Fig. 3.Card rotations test (CRT) scores and proprioceptive realignment metrics for days 1 and 2. CRT scores (left) improved with multiple testing on day 1 and showed further improvements with consolidation from day 1 to day 2, with the exception of the left PFC group. Scores then remained constant across the 2 test occasions on day 2. Realignment of the perception of straight ahead direction (right) occurred with prism adaptation on both days 1 and 2 but decayed between the two days. There were no differences by group. Download figureDownload PowerPoint

Day 2 performance. All participants adapted on day 2, as well, and the rate varied by stimulation group (group × trial: F 87,1218 = 1.4, P < 0.01; Fig. 4). Both the right PFC and the M1 groups adapted faster than the sham group on day 2 (right PFC vs. sham group × trial: F 9.3,186 = 2.4, P = 0.01; M1 vs. sham group × trial: F 29,580 = 1.7, P = 0.01), whereas the left PFC and sham groups did not differ (F 9,179 = 1.5, P > 0.05). Similar to day 1, participants in the four groups recovered their accuracy at the same rate on day 2 on removal of the prism lenses (trial: F 11,461 = 50.9, P < 0.001; group × trial: F 33,461 = 1.0, P > 0.05; group: F 3,42 = 0.41, P > 0.05). Fig. 4.Horizontal dart throwing errors for day 2. The first 30 trials were baseline without prism lenses; tDCS stimulation was turned on halfway through this block. The subsequent 30 trials were adaptation, during which participants wore the prism lenses. The final 30 trials show re-adaptation after the prism lenses had been removed. The groups adapted at different rates on day 2, with right PFC and M1 groups improving faster than the sham group. Download figureDownload PowerPoint

CRT scores did not change across repetitions on day 2 (time: F 1,42 = 0.12, P = 0.74), and this did not vary by group (group: F 3,42 = 1.08, P = 0.37; group × time: F 3,42 = 0.12, P = 0.74). All participants again experienced a shift in their perceived straight ahead from pre- to post-prism adaptation (time: F 1,42 = 74.9, P < 0.0001), the magnitude of which did not vary by group (group: F 3,42 = 0.22, P = 0.88; group × time: F 3,42 = 2.06, P = 0.12). Savings from day 1 to day 2. Savings were calculated as the difference between prism trial errors on day 1 and day 2 on a trial-by-trial basis (Fig. 5). A group × trial repeated-measures ANOVA revealed that the groups exhibited differing savings effects (F 48,87 = 1.6, P < 0.05); specifically, the right PFC group exhibited greater savings than the sham group (right PFC and sham group × trial: F 29,580 = 1.7, P < 0.05), whereas the M1 (M1 and sham group × trial: F 29,580 = 0.8, P > 0.05) and left PFC (left PFC and sham group × trial: F 29,580 = 1.3, P > 0.05) groups did not differ from sham. Retention was calculated by comparing the first adaptation trial error on day 2 across the stimulation groups. The one-way ANOVA revealed no main effect of group (F 3,45 = 1.8, P > 0.10). Comparing just the right prefrontal error (−42.39 cm) with that of sham (−56.58 cm) resulted in a trend that was not significant after Bonferroni correction. The other tDCS groups were not significantly different relative to sham. This suggests that right PFC stimulation enhances savings but not retention. Fig. 5.Savings in performance from day 1 to day 2. The right PFC group showed more savings from day 1 to day 2 than the sham group. Download figureDownload PowerPoint

We tested for consolidation of CRT scores and realignment measures by comparing scores at the end of day 1 with those at the beginning of day 2. There was a main effect of time for the CRT scores, with improvements occurring offline between the 2 days of testing (F 1,42 = 30.9, P < 0.0001; see Fig. 3). There was a trend for a group × time effect (F 3,42 = 2.50, P = 0.07) with the left PFC group showing no consolidation, whereas all other groups did. All participants exhibited significant forgetting of the realignment shift between the two testing days (time: F 1,42 = 30.2, P < 0.0001); the magnitude of this forgetting did not differ by group (group: F 3,42 = 0.14, P = 0.94; group × time: F 3,42 = 0.25, P = 0.86).

GRANTS This work was supported by National Science Foundation Grant 1420042 (ORA Plus).

DISCLOSURES No conflicts of interest, financial or otherwise, are declared by the authors.

AUTHOR CONTRIBUTIONS R.D.S. and B.S.G. analyzed data; R.D.S., B.S.G., and B.G. interpreted results of experiments; R.D.S. and B.S.G. prepared figures; R.D.S., B.S.G., and B.G. drafted manuscript; R.D.S., B.S.G., and B.G. edited and revised manuscript; R.D.S., B.S.G., and B.G. approved final version of manuscript; B.S.G. performed experiments.