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Motor skills are acquired and refined across alternating phases of practice (online) and subsequent consolidation in the absence of further skill execution (offline). Both stages of learning are sustained by dynamic interactions within a widespread motor learning network including the premotor and primary motor cortices. Here, we aimed to investigate the role of the dorsal premotor cortex (dPMC) and its interaction with the primary motor cortex (M1) during motor memory consolidation. Forty-eight healthy human participants (age 22.1 ± 3.1 years) were assigned to three different groups corresponding to either low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of left dPMC, rTMS of left M1, or sham rTMS. rTMS was applied immediately after explicit motor sequence training with the right hand. Motor evoked potentials were recorded before training and after rTMS to assess potential stimulation-induced changes in corticospinal excitability (CSE). Participants were retested on motor sequence performance after eight hours to assess consolidation. While rTMS of dPMC significantly increased CSE and rTMS of M1 significantly decreased CSE, no CSE modulation was induced by sham rTMS. However, all groups demonstrated similar significant offline learning indicating that consolidation was not modulated by the post-training low-frequency rTMS intervention despite evidence of an interaction of dPMC and M1 at the level of CSE. Motor memory consolidation ensuing explicit motor sequence training seems to be a rather robust process that is not affected by low-frequency rTMS-induced perturbations of dPMC or M1. Findings further indicate that consolidation of explicitly acquired motor skills is neither mediated nor reflected by post-training CSE. [ABSTRACT FROM AUTHOR]

Previous studies have shown that persons with Parkinson's disease (pwPD) share specific deficits in learning new sequential movements, but the neural substrates of this impairment remain unclear. In addition, the degree to which striatal dopaminergic denervation in PD affects the cortico-striato-thalamo-cerebellar motor learning network remains unknown. We aimed to answer these questions using fMRI in 16 pwPD and 16 healthy age-matched control subjects while they performed an implicit motor sequence learning task. While learning was absent in both pwPD and controls assessed with reaction time differences between sequential and random trials, larger error-rates during the latter suggest that at least some of the complex sequence was encoded. Moreover, we found that while healthy controls could improve general task performance indexed by decreased reaction times across both sequence and random blocks, pwPD could not, suggesting disease-specific deficits in learning of stimulus-response associations. Using fMRI, we found that this effect in pwPD was correlated with decreased activity in the hippocampus over time. Importantly, activity in the substantia nigra (SN) and adjacent bilateral midbrain was specifically increased during sequence learning in pwPD compared to healthy controls, and significantly correlated with sequence-specific learning deficits. As increased SN activity was also associated (on trend) with higher doses of dopaminergic medication as well as disease duration, the results suggest that learning deficits in PD are associated with disease progression, indexing an increased drive to recruit dopaminergic neurons in the SN, however, unsuccessfully. Finally, there were no differences between pwPD and controls in task modulation of the cortico-striato-thalamo-cerebellar network. However, a restricted nigral-striatal model showed that negative modulation of SN to putamen connection was larger in pwPD compared to controls during random trials, while no differences between the groups were found during sequence learning. We speculate that learning-specific SN recruitment leads to a relative increase in SN- > putamen connectivity, which returns to a pathological reduced state when no learning takes place. [ABSTRACT FROM AUTHOR]

Compared to relapsing-remitting multiple sclerosis (MS), progressive MS is characterized by a lack of spontaneous recovery and a poor response to pharmaceutical immunomodulatory treatment. These patients may, therefore, particularly benefit from interventions that augment training-induced plasticity of the central nervous system. In this cross-sectional double-blind cross-over pilot study, effects of transcranial direct current stimulation (tDCS) on motor sequence learning were examined across four sessions on days 1, 3, 5, and 8 in 16 patients with progressive MS. Active or sham anodal tDCS of the primary motor cortex was applied immediately after each training session. Participants took part in two experiments separated by at least four weeks, which differed with respect to the type of posttraining tDCS (active or sham). While task performance across blocks of training and across sessions improved significantly in both the active and sham tDCS experiment, neither online nor offline motor learning was modulated by the type of tDCS. Accordingly, the primary endpoint (task performance on day 8) did not differ between stimulation conditions. In sum, patients with progressive MS are able to improve performance in an ecologically valid motor sequence learning task through training. However, even multisession posttraining tDCS fails to promote motor learning in progressive MS. [ABSTRACT FROM AUTHOR]

Previous research in young adults has demonstrated that both motor learning and transcranial direct current stimulation (tDCS) trigger decreases in the levels of gamma‐aminobutyric acid (GABA) in the sensorimotor cortex, and these decreases are linked to greater learning. Less is known about the role of GABA in motor learning in healthy older adults, a knowledge gap that is surprising given the established aging‐related reductions in sensorimotor GABA. Here, we examined the effects of motor learning and subsequent tDCS on sensorimotor GABA levels and resting‐state functional connectivity in the brains of healthy older participants. Thirty‐six older men and women completed a motor sequence learning task before receiving anodal or sham tDCS to the sensorimotor cortex. GABA‐edited magnetic resonance spectroscopy of the sensorimotor cortex and resting‐state (RS) functional magnetic resonance imaging data were acquired before and after learning/stimulation. At the group level, neither learning nor anodal tDCS significantly modulated GABA levels or RS connectivity among task‐relevant regions. However, changes in GABA levels from the baseline to post‐learning session were significantly related to motor learning magnitude, age, and baseline GABA. Moreover, the change in functional connectivity between task‐relevant regions, including bilateral motor cortices, was correlated with baseline GABA levels. These data collectively indicate that motor learning‐related decreases in sensorimotor GABA levels and increases in functional connectivity are limited to those older adults with higher baseline GABA levels and who learn the most. Post‐learning tDCS exerted no influence on GABA levels, functional connectivity or the relationships among these variables in older adults. [ABSTRACT FROM AUTHOR]

The retention of a new sequential motor skill relies on repeated practice and subsequent consolidation in the absence of active skill practice. While the early phase of skill acquisition remains relatively unaffected in older adults, posttraining consolidation appears to be selectively impaired by advancing age. Motor learning is associated with posttraining changes of oscillatory alpha and beta neuronal activities in the motor cortex. However, whether or not these oscillatory dynamics relate to posttraining consolidation and how they relate to the age-specific impairment of motor consolidation in older adults remains elusive. Transcranial alternating current stimulation (tACS) is a noninvasive brain stimulation technique capable of modulating such neuronal oscillations. Here, we examined whether tACS targeting M1 immediately following explicit motor sequence training is capable of modulating motor skill consolidation in older adults. In two sets of double-blind, sham-controlled experiments, tACS targeting left M1 was applied at either 10 Hz (alpha-tACS) or 20 Hz (beta-tACS) immediately after termination of a motor sequence training with the right (dominant) hand. Task performance was retested after an interval of 6 hours to assess consolidation of the training-acquired skill. EEG was recorded over left M1 to be able to detect local after-effects on oscillatory activity induced by tACS. Relative to the sham intervention, consolidation was selectively disrupted by posttraining alpha-tACS of M1, while posttraining beta-tACS of M1 had no effect on delayed retest performance compared to the sham intervention. No significant postinterventional changes of oscillatory activity in M1 were detected following alpha-tACS or beta-tACS. Our findings point to a frequency-specific interaction of tACS with posttraining motor memory processing and may suggest an inhibitory role of immediate posttraining alpha oscillations in M1 with respect to motor consolidation in healthy older adults. [ABSTRACT FROM AUTHOR]

Consolidation, by which performance increments after a training intervention are secured and sometimes generated, is reduced in elderly humans. The present study addressed the question whether transcranial direct current stimulation (tDCS) applied after motor training improves consolidation of explicit motor sequence learning in healthy older humans. In the first experiment, anodal or cathodal tDCS to the left primary motor cortex, anodal tDCS to premotor cortex, or sham tDCS was applied immediately after completion of a finger sequence learning task. Performance was retested at 8 and 22 hours after the initial training session. Whereas all groups achieved similar performance at the end of training, off-line improvements differed between groups at later retesting, depending on the type of intervention. Relative to the other 3 interventions, anodal tDCS to primary motor cortex (M1) led to performance improvements already at retesting 8 hours after initial learning and were maintained on the next day. In the second experiment, effects of the timing of post-training anodal tDCS to M1 with respect to the end of training were studied. Participants received anodal tDCS of M1 immediately or 60 or 120 minutes after training and were retested on sequence performance 8 hours post training. Only application of tDCS immediately after the end of training, but not after 1 or 2 hours, enhanced off-line consolidation. These findings suggest that anodal tDCS applied off-line immediately post training to M1 interacts specifically with early processes promoting consolidation of motor sequence learning in healthy older individuals. [ABSTRACT FROM AUTHOR]

• Effect of anodal tDCS on motor memory consolidation in older adults is lateralized. • Post-learning tDCS to right M1 disrupted motor memory consolidation. • Post-learning tDCS to left M1 did not affect motor memory consolidation. • Sustained recruitment of early learning brain areas paralleled impaired consolidation. • tDCS-based neuro-rehabilitative approaches should consider lateralized effects. Previous research has consistently demonstrated that older adults have difficulties transforming recently learned movements into robust, long-lasting memories (i.e., motor memory consolidation). One potential avenue to enhance consolidation in older individuals is the administration of transcranial direct current stimulation (tDCS) to task-relevant brain regions after initial learning. Although this approach has shown promise, the underlying cerebral correlates have yet to be revealed. Moreover, it is unknown whether the effects of tDCS are lateralized, an open question with implications for rehabilitative approaches following predominantly unilateral neurological injuries. In this research, healthy older adults completed a sequential motor task before and 6 h after receiving anodal or sham stimulation to right or left primary motor cortex (M1) while functional magnetic resonance images were acquired. Unexpectedly, anodal stimulation to right M1 following left-hand sequence learning significantly hindered consolidation as compared to a sham control, whereas no differences were observed with left M1 stimulation following right-hand learning. Impaired performance following right M1 stimulation was paralleled by sustained engagement of regions known to be critical for early learning stages, including the caudate nucleus and the premotor and parietal cortices. Thus, post-learning tDCS in older adults not only exerts heterogenous effects across the two hemispheres but can also disrupt ongoing memory processing. [ABSTRACT FROM AUTHOR]

Recent studies show that limb apraxia is a quite frequent, yet often underdiagnosed, higher motor impairment following stroke. Because it adversely affects every-day life and personal independence, successful rehabilitation of apraxia is essential for personal well-being. Nevertheless, evidence of long-term efficacy of training schemes and generalization to untrained actions is still scarce. One possible reason for the tendency of this neurological disorder to persist may be a deficit in planning, conceptualisation and storage of complex motor acts. This pilot study aims at investigating explicit motor learning in apractic stroke patients. In particular, we addressed the ability of apractic patients to learn and to retain new explicit sequential finger movements across 10 training sessions over a 3-week interval. Nine stroke patients with ideomotor apraxia in its chronic stage participated in a multi-session training regimen and were included in data analyses. Patients performed an explicit finger sequence learning task (MSLT – motor sequence learning task), which is a well-established paradigm to investigate motor learning and memory processes. Patients improved task performance in terms of speed and accuracy across sessions. Specifically, they showed a noticeable reduction in the mean time needed to perform a correct sequence and the number of erroneous sequences. We found also a trend for improved performance at the Goldenberg apraxia test protocol: "imitation of meaningless hand and finger gestures" relative to when assessed before the MSLT training. Patients with ideomotor apraxia demonstrated the ability to acquire and maintain a novel sequence of movements; and, this training was associated with hints towards improvement of apraxia symptoms. • Apraxia patients with deficits of imitation and pantomime can learn new explicit motor sequences in a multi-session training. • A trend was observed for the improvement of apraxia symptoms following motor sequence learning task (MSLT) training. • Intensive motor training promisses to be effective in Apraxia. [ABSTRACT FROM AUTHOR]