Movement-related ERS and connectivity in the gamma frequency decrease with practice.

Previous work showed that movements are accompanied by modulation of electroencephalographic (EEG) activity in both beta (13-30 Hz) and gamma (>30 Hz) ranges. The amplitude of beta event-related synchronization (ERS) is not linked to movement characteristics, but progressively increases with motor practice, returning to baseline after a period of rest. Conversely, movement-related gamma ERS amplitude is proportional to movement distance and velocity. Here, high-density EEG was recorded in 51 healthy subjects to investigate whether i) three-hour practice in two learning tasks, one with a motor component and one without, affects gamma ERS amplitude and connectivity during a motor reaching test, and ii) 90-minutes of either sleep or quiet rest have an effect on gamma oscillatory activity. We found that, while gamma ERS was appropriately scaled to the target extent at all testing points, its amplitude decreased after practice, independently of the type of interposed learning, and after both quiet wake and nap, with partial correlations with subjective fatigue scores. During movement execution, connectivity patterns within fronto-parieto-occipital electrodes, over areas associated with attentional networks, decreased after both practice and after 90-minute rest. While confirming the prokinetic nature of movement-related gamma ERS, these findings demonstrated the preservation of gamma ERS scaling to movement velocity with practice, despite constant amplitude reduction. We thus speculate that such decreases, differently from the practice-related increases of beta ERS, are related to reduced attention or working memory mechanisms due to fatigue or a switch of strategy toward automatization of movement execution and do not specifically reflect plasticity phenomena.

Aging Does Not Affect Beta Modulation during Reaching Movements.

During movement, modulation of beta power occurs over the sensorimotor areas, with a decrease just before its start (event-related desynchronization, ERD) and a rebound after its end (event-related synchronization, ERS). We have recently found that the depth of ERD-to-ERS modulation increases during practice in a reaching task and the following day decreases to baseline levels. Importantly, the magnitude of the beta modulation increase during practice is highly correlated with the retention of motor skill tested the following day. Together with other evidence, this suggests that the increase of practice-related modulation depth may be the expression of sensorimotor cortex's plasticity. Here, we determine whether the practice-related increase of beta modulation depth is equally present in a group of younger and a group of older subjects during the performance of a 30-minute block of reaching movements. We focused our analyses on two regions of interest (ROIs): the left sensorimotor and the frontal region. Performance indices were significantly different in the two groups, with the movements of older subjects being slower and less accurate. Importantly, both groups presented a similar increase of the practice-related beta modulation depth in both ROIs in the course of the task. Peak latency analysis revealed a progressive delay of the ERS peak that correlated with the total movement time. Altogether, these findings support the notion that the depth of beta modulation in a reaching movement task does not depend on age and confirm previous findings that only ERS peak latency but not ERS magnitude is related to performance indices.

Tracking neural correlates of successful learning over repeated sequence observations.

The neural correlates of memory formation in humans have long been investigated by exposing subjects to diverse material and comparing responses to items later remembered to those forgotten. Tasks requiring memorization of sensory sequences afford unique possibilities for linking neural memorization processes to behavior, because, rather than comparing across different items of varying content, each individual item can be examined across the successive learning states of being initially unknown, newly learned, and eventually, fully known. Sequence learning paradigms have not yet been exploited in this way, however. Here, we analyze the event-related potentials of subjects attempting to memorize sequences of visual locations over several blocks of repeated observation, with respect to pre- and post-block recall tests. Over centro-parietal regions, we observed a rapid P300 component superimposed on a broader positivity, which exhibited distinct modulations across learning states that were replicated in two separate experiments. Consistent with its well-known encoding of surprise, the P300 deflection monotonically decreased over blocks as locations became better learned and hence more expected. In contrast, the broader positivity was especially elevated at the point when a given item was newly learned, i.e., started being successfully recalled. These results implicate the Broad Positivity in endogenously-driven, intentional memory formation, whereas the P300, in processing the current stimulus to the degree that it was previously uncertain, indexes the cumulative knowledge thereby gained. The decreasing surprise/P300 effect significantly predicted learning success both across blocks and across subjects. This presents a new, neural-based means to evaluate learning capabilities independent of verbal reports, which could have considerable value in distinguishing genuine learning disabilities from difficulties to communicate the outcomes of learning, or perceptual impairments, in a range of clinical brain disorders.

Sleep reverts changes in human gray and white matter caused by wake-dependent training.

Learning leads to rapid microstructural changes in gray (GM) and white (WM) matter. Do these changes continue to accumulate if task training continues, and can they be reverted by sleep? We addressed these questions by combining structural and diffusion weighted MRI and high-density EEG in 16 subjects studied during the physiological sleep/wake cycle, after 12 h and 24 h of intense practice in two different tasks, and after post-training sleep. Compared to baseline wake, 12 h of training led to a decline in cortical mean diffusivity. The decrease became even more significant after 24 h of task practice combined with sleep deprivation. Prolonged practice also resulted in decreased ventricular volume and increased GM and WM subcortical volumes. All changes reverted after recovery sleep. Moreover, these structural alterations predicted cognitive performance at the individual level, suggesting that sleep's ability to counteract performance deficits is linked to its effects on the brain microstructure. The cellular mechanisms that account for the structural effects of sleep are unknown, but they may be linked to its role in promoting the production of cerebrospinal fluid and the decrease in synapse size and strength, as well as to its recently discovered ability to enhance the extracellular space and the clearance of brain metabolites.

Repetitive transcranial magnetic stimulation enhances BDNF-TrkB signaling in both brain and lymphocyte.

Repetitive transcranial magnetic stimulation (rTMS) induces neuronal long-term potentiation or depression. Although brain-derived neurotrophic factor (BDNF) and its cognate tyrosine receptor kinase B (TrkB) contribute to the effects of rTMS, their precise role and underlying mechanism remain poorly understood. Here we show that daily 5 Hz rTMS for 5 d improves BDNF-TrkB signaling in rats by increasing the affinity of BDNF for TrkB, which results in higher tyrosine-phosphorylated TrkB, increased recruitment of PLC-γ1 and shc/N-shc to TrkB, and heightened downstream ERK2 and PI-3K activities in prefrontal cortex and in lymphocytes. The elevated BDNF-TrkB signaling is accompanied by an increased association between the activated TrkB and NMDA receptor (NMDAR). In normal human subjects, 5 d rTMS to motor cortex decreased resting motor threshold, which correlates with heightened BDNF-TrkB signaling and intensified TrkB-NMDAR association in lymphocytes. These findings suggest that rTMS to cortex facilitates BDNF-TrkB-NMDAR functioning in both cortex and lymphocytes.

Dopaminergic striatal innervation predicts interlimb transfer of a visuomotor skill.

We investigated whether dopamine influences the rate of adaptation to a visuomotor distortion and the transfer of this learning from the right to the left limb in human subjects. We thus studied patients with Parkinson disease as a putative in vivo model of dopaminergic denervation. Despite normal adaptation rates, patients showed a reduced transfer compared with age-matched healthy controls. The magnitude of the transfer, but not of the adaptation rate, was positively predicted by the values of dopamine-transporter binding of the right caudate and putamen. We conclude that striatal dopaminergic activity plays an important role in the transfer of visuomotor skills.

Modulation of gamma and theta spectral amplitude and phase synchronization is associated with the development of visuo-motor learning.

The formation of new motor memories, which is fundamental for efficient performance during adaptation to a visuo-motor rotation, occurs when accurate planning is achieved mostly with feedforward mechanisms. The dynamics of brain activity underlying the switch from feedback to feedforward control is still matter of debate. Based on the results of studies in declarative learning, it is likely that phase synchronization of low and high frequencies as well as their temporal modulation in power amplitude underlie the formation of new motor memories during visuo-motor adaptation. High-density EEG (256 electrodes) was recorded in 17 normal human subjects during adaptation to a visuo-motor rotation of 60° in four incremental steps of 15°. We found that initial learning is associated with enhancement of gamma power in a right parietal region during movement execution as well as gamma/theta phase coherence during movement planning. Late stages of learning are instead accompanied by an increase of theta power over that same right parietal region during movement planning, which is correlated with the degree of learning and retention. Altogether, these results suggest that the formation of new motor memories and, thus, the switch from feedback to feedforward control is associated with the modulation of gamma and theta spectral activities, with respect to their amplitude and phase, during movement planning and execution. Specifically, we propose that gamma/theta phase coupling plays a pivotal role in the integration of a new representation into motor memories.

Movement-related beta ERD and ERS abnormalities in neuropsychiatric disorders.

Movement-related oscillations in the beta range (from 13 to 30 Hz) have been observed over sensorimotor areas with power decrease (i.e., event-related desynchronization, ERD) during motor planning and execution followed by an increase (i.e., event-related synchronization, ERS) after the movement's end. These phenomena occur during active, passive, imaged, and observed movements. Several electrophysiology studies have used beta ERD and ERS as functional indices of sensorimotor integrity, primarily in diseases affecting the motor system. Recent literature also highlights other characteristics of beta ERD and ERS, implying their role in processes not strictly related to motor function. Here we review studies about movement-related ERD and ERS in diseases characterized by motor dysfunction, including Parkinson's disease, dystonia, stroke, amyotrophic lateral sclerosis, cerebral palsy, and multiple sclerosis. We also review changes of beta ERD and ERS reported in physiological aging, Alzheimer's disease, and schizophrenia, three conditions without overt motor symptoms. The review of these works shows that ERD and ERS abnormalities are present across the spectrum of the examined pathologies as well as development and aging. They further suggest that cognition and movement are tightly related processes that may share common mechanisms regulated by beta modulation. Future studies with a multimodal approach are warranted to understand not only the specific topographical dynamics of movement-related beta modulation but also the general meaning of beta frequency changes occurring in relation to movement and cognitive processes at large. Such an approach will provide the foundation to devise and implement novel therapeutic approaches to neuropsychiatric disorders.

Temporal evolution of oscillatory activity predicts performance in a choice-reaction time reaching task.

In this study, we characterized the patterns and timing of cortical activation of visually guided movements in a task with critical temporal demands. In particular, we investigated the neural correlates of motor planning and on-line adjustments of reaching movements in a choice-reaction time task. High-density electroencephalography (EEG, 256 electrodes) was recorded in 13 subjects performing reaching movements. The topography of the movement-related spectral perturbation was established across five 250-ms temporal windows (from prestimulus to postmovement) and five frequency bands (from theta to beta). Nine regions of interest were then identified on the scalp, and their activity was correlated with specific behavioral outcomes reflecting motor planning and on-line adjustments. Phase coherence analysis was performed between selected sites. We found that motor planning and on-line adjustments share similar topography in a fronto-parietal network, involving mostly low frequency bands. In addition, activities in the high and low frequency ranges have differential function in the modulation of attention with the former reflecting the prestimulus, top-down processes needed to promote timely responses, and the latter the planning and control of sensory-motor processes.

Increased sensorimotor network activity in DYT1 dystonia: a functional imaging study.

Neurophysiological studies have provided evidence of primary motor cortex hyperexcitability in primary dystonia, but several functional imaging studies suggest otherwise. To address this issue, we measured sensorimotor activation at both the regional and network levels in carriers of the DYT1 dystonia mutation and in control subjects. We used (15)Oxygen-labelled water and positron emission tomography to scan nine manifesting DYT1 carriers, 10 non-manifesting DYT1 carriers and 12 age-matched controls while they performed a kinematically controlled motor task; they were also scanned in a non-motor audio-visual control condition. Within- and between-group contrasts were analysed with statistical parametric mapping. For network analysis, we first identified a normal motor-related activation pattern in a set of 39 motor and audio-visual scans acquired in an independent cohort of 18 healthy volunteer subjects. The expression of this pattern was prospectively quantified in the motor and control scans acquired in each of the gene carriers and controls. Network values for the three groups were compared with ANOVA and post hoc contrasts. Voxel-wise comparison of DYT1 carriers and controls revealed abnormally increased motor activation responses in the former group (P < 0.05, corrected; statistical parametric mapping), localized to the sensorimotor cortex, dorsal premotor cortex, supplementary motor area and the inferior parietal cortex. Network analysis of the normative derivation cohort revealed a significant normal motor-related activation pattern topography (P < 0.0001) characterized by covarying neural activity in the sensorimotor cortex, dorsal premotor cortex, supplementary motor area and cerebellum. In the study cohort, normal motor-related activation pattern expression measured during movement was abnormally elevated in the manifesting gene carriers (P < 0.001) but not in their non-manifesting counterparts. In contrast, in the non-motor control condition, abnormal increases in network activity were present in both groups of gene carriers (P < 0.001). In this condition, normal motor-related activation pattern expression in non-manifesting carriers was greater than in controls, but lower than in affected carriers. In the latter group, measures of normal motor-related activation pattern expression in the audio-visual condition correlated with independent dystonia clinical ratings (r = 0.70, P = 0.04). These findings confirm that overexcitability of the sensorimotor system is a robust feature of dystonia. The presence of elevated normal motor-related activation pattern expression in the non-motor condition suggests that abnormal integration of audio-visual input with sensorimotor network activity is an important trait feature of this disorder. Lastly, quantification of normal motor-related activation pattern expression in individual cases may have utility as an objective descriptor of therapeutic response in trials of new treatments for dystonia and related disorders.

Acquisition and retention of motor sequences: the effects of time of the day and sleep.

STUDY OBJECTIVES: We used a sequence-learning task to assess whether: 1. The time interval between awakening and training equally affects the rate of acquisition of sequence order, a declarative component, and the kinematic optimization process, an implicit component; 2. Sleep enhances the retention of both these aspects of sequence learning. DESIGN: For aim 1, we compare the acquisition rate of a new motor sequence in a group trained in the morning and another in the evening. For aim 2., we tested retention of the same motor sequence twelve hours later, either without sleep (normal day activity or a night of sleep deprivation) or with interposed sleep (afternoon napping or regular full night sleep). SETTING: Training and Testing were performed in a controlled laboratory setting. PARTICIPANTS: Thirty-six right-handed normal subjects (age range 18-24 years; 16 women). RESULTS: During the training, acquisition rate of the sequence order was significantly higher in the AM-trained than in the PM-trained group, without differences in the kinematic optimization processes. Both declarative and implicit learning indices were significantly higher in the subjects tested after sleep compared to those tested without interposed sleep. CONCLUSION: The best time for fast and efficient acquisition of new declarative material is the morning, while the kinematic aspects of skill acquisition are not sensitive to the time of day. However, better retention of both declarative material and motor skills requires two conditions: a period of post-training sleep and the achievement of performance saturation during training.

Extended Visual Sequence Learning Leaves a Local Trace in the Spontaneous EEG.

We have previously demonstrated that, in rested subjects, extensive practice in a motor learning task increased both electroencephalographic (EEG) theta power in the areas involved in learning and improved the error rate in a motor test that shared similarities with the task. A nap normalized both EEG and performance changes. We now ascertain whether extensive visual declarative learning produces results similar to motor learning. Thus, during the morning, we recorded high-density EEG in well rested young healthy subjects that learned the order of different visual sequence task (VSEQ) for three one-hour blocks. Afterward, a group of subjects took a nap and another rested quietly. Between each VSEQ block, we recorded spontaneous EEG (sEEG) at rest and assessed performance in a motor test and a visual working memory test that shares similarities with VSEQ. We found that after the third block, VSEQ induced local theta power increases in the sEEG over a right temporo-parietal area that was engaged during the task. This local theta increase was preceded by increases in alpha and beta power over the same area and was paralleled by performance decline in the visual working memory test. Only after the nap, VSEQ learning rate improved and performance in the visual working memory test was restored, together with partial normalization of the local sEEG changes. These results suggest that intensive learning, like motor learning, produces local theta power increases, possibly reflecting local neuronal fatigue. Sleep may be necessary to resolve neuronal fatigue and its effects on learning and performance.

Neural fatigue due to intensive learning is reversed by a nap but not by quiet waking.

Do brain circuits become fatigued due to intensive neural activity or plasticity? Is sleep necessary for recovery? Well-rested subjects trained extensively in a visuo-motor rotation learning task (ROT) or a visuo-motor task without rotation learning (MOT), followed by sleep or quiet wake. High-density electroencephalography showed that ROT training led to broad increases in EEG power over a frontal cluster of electrodes, with peaks in the theta (mean ± SE: 24% ± 6%, p = 0.0013) and beta ranges (10% ± 3%, p = 0.01). These traces persisted in the spontaneous EEG (sEEG) between sessions (theta: 42% ± 8%, p = 0.0001; beta: 35% ± 7%, p = 0.002) and were accompanied by increased errors in a motor test with kinematic characteristics and neural substrates similar to ROT (81.8% ± 0.8% vs. 68.2% ± 2.3%; two-tailed paired t-test: p = 0.00001; Cohen's d = 1.58), as well as by score increases of subjective task-specific fatigue (4.00 ± 0.39 vs. 5.36 ± 0.39; p = 0.0007; Cohen's d = 0.60). Intensive practice with MOT did not affect theta sEEG or the motor test. A nap, but not quiet wake, induced a local sEEG decrease of theta power by 33% (SE: 8%, p = 0.02), renormalized test performance (70.9% ± 2.9% vs 79.1% ± 2.7%, p = 0.018, Cohen's d = 0.85), and improved learning ability in ROT (adaptation rate: 71.2 ± 1.2 vs. 73.4 ± 0.9, p = 0.024; Cohen's d = 0.60). Thus, sleep is necessary to restore plasticity-induced fatigue and performance.

Art therapy for Parkinson's disease.

OBJECTIVE: To explore the potential rehabilitative effect of art therapy and its underlying mechanisms in Parkinson's disease (PD). METHODS: Observational study of eighteen patients with PD, followed in a prospective, open-label, exploratory trial. Before and after twenty sessions of art therapy, PD patients were assessed with the UPDRS, Pegboard Test, Timed Up and Go Test (TUG), Beck Depression Inventory (BDI), Modified Fatigue Impact Scale and PROMIS-Self-Efficacy, Montreal Cognitive Assessment, Rey-Osterrieth Complex Figure Test (RCFT), Benton Visual Recognition Test (BVRT), Navon Test, Visual Search, and Stop Signal Task. Eye movements were recorded during the BVRT. Resting-state functional MRI (rs-fMRI) was also performed to assess functional connectivity (FC) changes within the dorsal attention (DAN), executive control (ECN), fronto-occipital (FOC), salience (SAL), primary and secondary visual (V1, V2) brain networks. We also tested fourteen age-matched healthy controls at baseline. RESULTS: At baseline, PD patients showed abnormal visual-cognitive functions and eye movements. Analyses of rs-fMRI showed increased functional connectivity within DAN and ECN in patients compared to controls. Following art therapy, performance improved on Navon test, eye tracking, and UPDRS scores. Rs-fMRI analysis revealed significantly increased FC levels in brain regions within V1 and V2 networks. INTERPRETATION: Art therapy improves overall visual-cognitive skills and visual exploration strategies as well as general motor function in patients with PD. The changes in brain connectivity highlight a functional reorganization of visual networks.

Early Parkinson's disease: longitudinal changes in brain activity during sequence learning.

Impairment of sequence learning is common in Parkinson's disease (PD), but the time course of this cognitive abnormality is not known. We assessed longitudinal changes in sequence learning performance and associated task-related cerebral blood flow in 13 early stage PD patients who underwent H(2)(15)O PET at baseline and again 2 years later. Ten healthy volunteer subjects served as controls. A trend toward decline in learning performance (p=0.08) was evident over the 2 years of follow-up. During this interval, significant declines in learning-related activation were detected in parietal and temporo-occipital association areas and in the right dorsolateral prefrontal cortex. Learning-related activation in these regions was normal at baseline, but declined to subnormal levels (p<0.01) at 2 years. Significant hippocampal activation (p<0.005) was present in the subjects with high learning performance over time. The findings are consistent with a decline in learning-related neural activity in cortical areas with prominent Lewy body formation.

Local sleep and learning.

Human sleep is a global state whose functions remain unclear. During much of sleep, cortical neurons undergo slow oscillations in membrane potential, which appear in electroencephalograms as slow wave activity (SWA) of <4 Hz. The amount of SWA is homeostatically regulated, increasing after wakefulness and returning to baseline during sleep. It has been suggested that SWA homeostasis may reflect synaptic changes underlying a cellular need for sleep. If this were so, inducing local synaptic changes should induce local SWA changes, and these should benefit neural function. Here we show that sleep homeostasis indeed has a local component, which can be triggered by a learning task involving specific brain regions. Furthermore, we show that the local increase in SWA after learning correlates with improved performance of the task after sleep. Thus, sleep homeostasis can be induced on a local level and can benefit performance.

Arm immobilization causes cortical plastic changes and locally decreases sleep slow wave activity.

Sleep slow wave activity (SWA) is thought to reflect sleep need, increasing after wakefulness and decreasing after sleep. We showed recently that a learning task involving a circumscribed brain region produces a local increase in sleep SWA. We hypothesized that increases in cortical SWA reflect synaptic potentiation triggered by learning. To further investigate the link between synaptic plasticity and sleep, we asked whether a procedure leading to synaptic depression would cause instead a decrease in sleep SWA. We show here that if a subject's arm is immobilized during the day, motor performance deteriorates and both somatosensory and motor evoked potentials decrease over contralateral sensorimotor cortex, indicative of local synaptic depression. Notably, during subsequent sleep, SWA over the same cortical area is markedly reduced. Thus, cortical plasticity is linked to local sleep regulation without learning in the classical sense. Moreover, when synaptic strength is reduced, local sleep need is also reduced.

Sleep-dependent improvement in visuomotor learning: a causal role for slow waves.

STUDY OBJECTIVES: Sleep after learning often benefits memory consolidation, but the underlying mechanisms remain unclear. In previous studies, we found that learning a visuomotor task is followed by an increase in sleep slow wave activity (SWA, the electroencephalographic [EEG] power density between 0.5 and 4.5 Hz during non-rapid eye movement sleep) over the right parietal cortex. The SWA increase correlates with the postsleep improvement in visuomotor performance, suggesting that SWA may be causally responsible for the consolidation of visuomotor learning. Here, we tested this hypothesis by studying the effects of slow wave deprivation (SWD). DESIGN: After learning the task, subjects went to sleep, and acoustic stimuli were timed either to suppress slow waves (SWD) or to interfere as little as possible with spontaneous slow waves (control acoustic stimulation, CAS). SETTING: Sound-attenuated research room. PARTICIPANTS: Healthy subjects (mean age 24.6 +/- 1.0 years; n = 9 for EEG analysis, n = 12 for behavior analysis; 3 women). MEASUREMENTS AND RESULTS: Sleep time and efficiency were not affected, whereas SWA and the number of slow waves decreased in SWD relative to CAS. Relative to the night before, visuomotor performance significantly improved in the CAS condition (+5.93% +/- 0.88%) but not in the SWD condition (-0.77% +/- 1.16%), and the direct CAS vs SWD comparison showed a significant difference (P = 0.0007, n = 12, paired t test). Changes in visuomotor performance after SWD were correlated with SWA changes over right parietal cortex but not with the number of arousals identified using clinically established criteria, nor with any sign of "EEG lightening" identified using a novel automatic method based on event-related spectral perturbation analysis. CONCLUSION: These results support a causal role for sleep slow waves in sleep-dependent improvement of visuomotor performance.

Cervical dystonia affects aimed movements of nondystonic segments.

Patients with focal dystonia exhibit proprioception abnormalities that can lead to kinematic deficits. Proprioceptive abnormalities are present in both symptomatic and asymptomatic body parts of dystonic patients. To ascertain whether in patients with idiopathic cervical dystonia (CD) movements performed with nondystonic segments display kinematic abnormalities, we studied trajectory formation of out and back arm reaching movements in 10 patients with CD (before and 3 weeks after treatment with Botulinum toxin) and in 10 age-matched controls. Before treatment, patients with CD showed significant trajectory abnormalities when compared with normal controls. Patients' trajectories were more curved with asymmetrical temporal velocity profiles as well as increased hand path areas, and had longer reversal lags between the out and back segments. Treatment with botulinum toxin improved all the kinematic parameters. These results suggest that in patients with CD, movements performed with nondystonic segments are abnormal. The kinematic abnormalities are likely to derive from long-standing defective integration of the proprioceptive input, which, in turn, causes general changes in the internal models of limb dynamics. It is plausible that treatment with botulinum toxin partially restores proprioceptive processing and thus, such internal models.

The serial reaction time task revisited: a study on motor sequence learning with an arm-reaching task.

With a series of novel arm-reaching tasks, we have shown that visuomotor sequence learning encompasses the acquisition of the order of sequence elements, and the ability to combine them in a single, skilled behavior. The first component, which is mostly declarative, is reflected by changes in movement onset time (OT); the second, which occurs without subject's awareness, is measured by changes in kinematic variables, including movement time (MT). Key-press-based serial reaction time tasks (SRTT) have been used to investigate sequence learning and results interpreted as indicative of the implicit acquisition of the sequence order. One limitation to SRT studies, however, is that only one measure is used, the response time, the sum of OT and MT: this makes interpretation of which component is learnt difficult and disambiguation of implicit and explicit processes problematic. Here, we used an arm-reaching version of SRTT to propose a novel interpretation of such results. The pattern of response time changes we obtained was similar to the key-press-based tasks. However, there were significant differences between OT and MT, suggesting that both partial learning of the sequence order and skill improvement took place. Further analyses indicated that the learning of the sequence order might not occur without subjects' awareness.