Artificial manipulation of human motor memories Daichi Nozaki1, Atsushi Yokoi2, Takahiro Kimura3, Masaya Hirashima1,4, Jean-Jacques Orban de-Xivry5 ; 1Grad Edu, Univ Tokyo, 2Inst Cogn Neurosci, UCL ; 3Res Inst, Kochi Univ Tech; 4CiNet, Natl Inst Info 5

Comm Tech ; ICTEAM and IoNS, Univ catholique Louvain, Belgium

Appropriate context enables the formation and retrieval of distinct motor memories1 in situations where, in the absence of contextual information, interference prevents their formation2. Considering the significant role of primary motor cortex (M1) for creating motor memories3, we hypothesized that the effect of context on these memories was mediated by the influence of context on the states of M1. To examine this idea by a manipulative procedure, we had participants adapt reaching movements to conflicting dynamical environments when different states were artificially created in M1 via anodal and cathodal transcranial direct current stimulation (tDCS)4. We then tested whether artificially imposing one of these states could later lead to the recollection of the corresponding motor memory. Participants performed 12 blocks of 18 reaching movements (training period) during which their hand was perturbed by a velocity-dependent force-field. From one block to another, the force-field alternated between rightward and leftward directions (i.e., 6 blocks for each force-field). Critically, the tDCS polarity (±2mA, bi-hemispheric montage with electrodes on left and right M1) changed congruently with the force-field direction (Fig.1). That is, anodal tDCS of the left M1 was always associated with the rightward force-field, while cathodal tDCS was received during the leftward force-field perturbation. After the training period, participants performed 4 blocks of 22 error-clamp trials (test period) while receiving tDCS: T-TACAC group received anodal tDCS first and T-TCACA group received cathodal tDCS first (N = 8 for each subgroup). If tDCS did not have any influence on motor memory, then trial-dependent changes in the aftereffect (exerted force during error-clamp trials) should be identical between these two subgroups. However, the aftereffect exhibited a block-dependent change and the pattern of changes was completely opposite between the two subgroups (left panels of Fig.2). This reversal is highlighted when forces from the two groups are subtracted and centered on zero (Fig. 2B). Thus, the motor memories encoded during the training period were recollected during the test period. In contrast, when the tDCS was provided for the training period only (T-S group) or for the test period only (S-T group), such block-dependent changes in the aftereffect were not observed (right and middle panels of Fig.2). These results confirmed the idea that tDCS is able to tag motor memories by imposing a particular state to M1. Previous studies that deal with context-dependent declarative or fear memories5 suggest that reproducing the brain states at the time of learning might contribute to the recollection of the corresponding memory. The present results support this idea for motor memory in humans and bears similarities with the ability of optogenetics6 to induce context-specific formation and recollection of a fear memory. This use of the tDCS in order to tag motor memories fully depart from its conventional use, which is usually restricted to the modulation of motor performance, rehabilitation outcome, memory function etc7. Therefore, the present study opens up new avenues for the application of tDCS in neuroscience research. References : [1] Nozaki et al., Nat Neurosci 2006 ; [2] Caithness et al., JNS 2004; [3] Kadota et al., JNS 2014 ; [4] Orban de Xivry & Shadmehr, EBR (in press); [5] Maren et al., Nat Rev Neurosci 2013; [6] Liu et al., Nature 2012; [7] Fox, Nature 2012

Figure 1. Experimental procedure. In the training period, participants performed reaching movements under the presence of rightward or leftward velocity-dependent force-field (6 blocks of 18 trials for each force-field). Anodal tDCS to left M1 was associated with the rightward force-field training, cathodal tDCS with the leftward force-field training. In the following test period, the tDCS application continued, and error-clamp trials were used to examine how the aftereffect was modulated with the polarity of tDCS. We adopted three experimental groups: tDCS was applied both during training and test periods (T-T group), only during test period (S-T group), and only during training period (T-S group). Each group was further separated into subgroups according to the order of application of anodal and cathodal stimulation (N=8 for each subgroup).

Figure 2: Block-dependent changes in the aftereffect during test period. A. Trial dependent changes in the aftereffects (force at the peak velocity of the handle) were represented by dots. Each line indicates moving average data (4 trials). Shaded area indicates standard error (SE). B. The difference in the aftereffect between subgroups. C. The residuals after fitting the data by an exponential curve averaged for each block (error bar indicates SE). Block-dependent modulation of the aftereffect was observed only for T-T group that received tDCS both during training and test period (Effect of the polarity of tDCS tested by ANOVA: T-TACAC group: F(1,7)=19.35, p=0.003; T-TCACA group, F(1,7)=22.3; p=0.002). Note also that the pattern of the changes was completely opposite between both subgroups.