Acoustic stimulation increases implicit adaptation in sensorimotor adaptation.

Previous studies have shown that performing a motor action toward a target decreases the perceptual asynchrony observed in a temporal order judgment (TOJ) of a change in the target's visual attributes. We examined the temporal limit of this effect and whether this temporal limit can be extended through sensorimotor adaptation. Participants performed a TOJ task related to changes of the position and color of a visual stimulus in a perceptual and a motor task. A fixed change (color or position) occurred 250 or 500ms following an auditory cue (perceptual task) or the end of a manual reaching action (motor task), whereas the variable change (position or color) occurred randomly within a time window of ±200ms locked to the fixed change. The points of subjective simultaneity (PSSs) revealed that performing a voluntary action decreased the temporal asynchrony observed in the perceptual task, but only in the 250-ms delay condition. In Experiment 2, the fixed change occurred 1s after either an auditory cue or the end of a manual reaching action, and the variable change occurred either simultaneously (new sensorimotor contingencies, 60% of trials) or within a time window of ±200ms (40% of trials). The PSSs revealed that temporal asynchrony decreased in the motor task, but only after adaptation to the 1-s delay. Taken together, these data show that voluntary motor action affects the temporal binding of visual attributes for a period of less than 500ms after the end of the action. Sensorimotor adaptation can nevertheless extend this time interval, at least up to 1s.

The purpose of this study was to evaluate the influence of high-definition transcranial direct current stimulation (HD-tDCS) on finger motor skill acquisition. Thirty-one healthy adult males were randomly assigned to one of three groups: online HD-tDCS (administered during motor skill learning), offline HD-tDCS (delivered before motor skill learning), and a sham group. Participants engaged in a visual isometric pinch task for three consecutive days. Overall motor skill learning and speed-accuracy tradeoff function were used to evaluate the efficacy of tDCS. Electroencephalography was recorded and power spectral density was calculated. Both online and offline HD-tDCS total motor skill acquisition was significantly higher than the sham group (P < 0.001 and P < 0.05, respectively). Motor skill acquisition in the online group was higher than offline (P = 0.132, Cohen's d =1.46). Speed-accuracy tradeoff function in the online group was higher than both offline and sham groups in the post-test. The online group exhibited significantly lower electroencephalography activity in the frontal, fronto-central, and centro-parietal alpha band regions compared to the sham (P < 0.05). The findings suggest that HD-tDCS application can boost finger motor skill acquisition, with online HD-tDCS displaying superior facilitation. Furthermore, online HD-tDCS reduces the power of alpha rhythms during motor skill execution, enhancing information processing and skill learning efficiency.

We compared intraindividual and interindividual variability in the plasma levels of fibrinogen, tissue-type plasminogen activator (TPA) antigen, plasminogen activator inhibitor (PAI) activity, and C-reactive protein (CRP) in 20 healthy, young individuals and 26 patients with stable angina pectoris (AP) who were at higher risk for cardiovascular disease. For each of the four parameters, the contribution of the intraindividual variation to the total variance (13% and 9% for fibrinogen, 3% and 5% for TPA antigen, 4% and 20% for In[PAI activity], and 14% and 9% for In[CRP] for the healthy volunteers and AP patients, respectively) was smaller than the contribution from the interindividual variation. These results indicate that single sampling is sufficient to assess an individual level for TPA antigen and PAI activity, whereas duplicate sampling for fibrinogen and triplicate sampling for CRP are recommended. In an epidemiological study the sample sizes, based on the variances found in the transverse part of the study, needed to detect a 15% difference between the two groups (with alpha = 0.01 and a statistical power = .90) are 31 and 40 for fibrinogen, 568 and 146 for TPA antigen, 603 and 119 for PAI activity, and 1490 and 2263 for CRP in healthy volunteers and patients with AP, respectively. Additionally, we studied the contribution of genetic polymorphisms of the B beta-fibrinogen (Bcl I and G-->A-455) and PAI activity (HindIII and CA-repeat) genes to intraindividual and interindividual variation. Fibrinogen genotypes were associated with plasma fibrinogen levels in the volunteers but not in the AP patients. No effects of fibrinogen or PAI polymorphisms on intraindividual variation were observed in either healthy individuals or AP patients. In this study intraindividual variation in plasma levels of the cardiovascular risk indicators fibrinogen, TPA antigen, PAI activity, and CRP was small when compared with the interindividual variation in healthy, young volunteers and patients with stable AP.

Advances in neuroimaging over the past 20 years have provided insight into the dynamic neural processes underlying human motor skill acquisition, focusing primarily on brain networks that are engaged during early versus late stages of learning. What has been challenging for the field is to tightly link these shifting neural processes with what is known about measureable behavioral changes and strategic processes that occur during learning. The complex nature of behavior and strategy in motor learning often result in a trade-off between experimental control and external validity. Researchers in different disciplines have employed varying approaches to understand motor learning but with relatively little crosstalk. Here, we bring together a set of papers which investigate skill learning spanning multiple domains. There are several striking and unique features about the papers assembled for this special issue. One is the broad range of investigative techniques brought to bear on the problem of understanding skill acquisition, including cutting edge analytical approaches (Abe and Sternad, 2013; Sami and Miall, 2013), metrics of brain structure and function (Kam et al., 2012; Steele et al., 2012; Bernard and Seidler, 2013; Gentili et al., 2013; Wadden et al., 2013), behavioral experiments with carefully crafted conditions (Armstrong et al., 2013; Kitago et al., 2013; Leow et al., 2013; Nemeth et al., 2013; Taylor and Ivry, 2013), and comprehensive reviews which put forth new theories and novel viewpoints for interpretation (Abrahamse et al., 2013; Bock, 2013; Heuer and Sulzenbruck, 2013; King et al., 2013; Ruddy and Carson, 2013; Vadakkan, 2013). We expect that motor scientists will find inspiring new ideas, techniques, approaches, and theories in this collection of articles. Another important aspect of these papers is that they report on differing types of skill acquisition including practice of a new skill, adaptation to visuomotor distortions, and acquiring new action sequences. For example, Heuer and Sulzenbruck review their findings evaluating how subjects learn the transformation of a sliding first-order level. This has highly practical implications as this tool type is used in minimal access surgery. The sliding first-order level is a type of tool often used in laproscopic surgery; a fulcrum effect at the skin insertion site results in forward hand movements producing backward tool movements. Moreover, linear hand motions result in curved tool tip paths. Taylor and Ivry leverage comparisons of subjects adapting to visuomotor rotations and to visual translational shifts, and report an interaction between the type of perturbation applied and whether targets are presented in a circular or rectilinear arrangement. Interestingly, they observed that generalization of adaptation across the workspace was linked more to the environmental context than to the perturbation type. Steele and colleagues report findings from a multimodal neuroimaging study using their well-characterized temporal motor sequence task, which requires participants to learn both spatial response locations and a temporal rhythm, similar to playing a musical instrument. They report complementary structural and functional changes with learning; the rate of learning was positively correlated with gray matter volume in cerebellar lobules HV and VI. These same regions exhibit decreases in functional activation with training. Finally, Kitago et al. focus on unlearning in an effort to determine whether it represents forgetting of acquired representations or just reverting back to habitual performance. Their findings support that unlearning is not just forgetting, but is rather an active process. This has important implications for individuals who need to learn new ways of performing everyday skills after suffering from injury or neurological insult. Several of the papers in this special issue also highlight the differing contributions of neurocognitive mechanisms across learning, consolidation and retention. For example, Nemeth et al. assessed skill learning in healthy adults and those with mild cognitive impairment to investigate the role of the hippocampus and medial temporal lobe (MTL) structures in skilled learning. Using the alternating serial response task (ASRT) they report that individuals with MCI, and likely compromised hippocampal/MTL structures, demonstrate a reduced ability to reactivate/recall learned sequences in subsequent blocks of practice. Interestingly, they report that differences in learning disappeared during the second half of a practice block suggesting a differential role for hippocampus/MTL structures across practice even within a block. In a second paper,Wadden et al. evaluated individual variability in the neural networks underlying motor sequence learning in middle aged adults. Comparing initial task performance to that at a delayed retention test following 5 days of continuous tracking practice they report variability in overall measures of implicit sequence specific learning. However, when learning was decomposed into temporal and spatial elements to account for individual variation, improvement in temporal elements were associated with a network of cortical, sub-cortical and

Transcranial laser stimulation: Mitochondrial and cerebrovascular effects in younger and older healthy adults

Mild cognitive impairment (MCI) is a transitional phase between normal cognitive aging and dementia. As the world population is aging rapidly, more MCI patients will be identified, posing significant problems to society. Normal aging is associated with cognitive and motor decline, and MCI brings additional impairments. Compared to healthy older adults, MCI patients show poorer motor control in a variety of tasks. Efficient motor control and skill learning are essential for occupational and leisure purposes; degradation of motor behaviors in MCI patients often adversely affects their health and quality of life. In this article, we first define MCI and describe its pathology and neural correlates. After this, we review cognitive changes and motor control and skill learning in normal aging. This section is followed by a discussion of MCI-related degradation of motor behaviors. Finally, we propose that multicomponent interventions targeting both cognitive and motor domains can improve MCI patients' motor functions. Future research directions are also raised.

Ultimately, the experience of pain derives from changes in brain excitability. Therefore, modulating the excitability of cortical areas involved in pain processing may become an attractive option in the context of multimodal analgesia during the postoperative period. Repetitive transcranial magnetic stimulation (rTMS) can reduce morphine consumption during the postoperative period after gastric bypass surgery. We tested the potential of another method of noninvasive brain stimulation, transcranial direct current stimulation (tDCS), to reduce morphine consumption or pain perception during the postoperative period. Fifty-nine ASA I to II patients undergoing lumbar spine surgery were randomized to receive anodal (n=20), cathodal (n=20), or sham (n=19) tDCS in the recovery room in a double-blind manner. Morphine consumption administrated through patient-controlled analgesia (PCA) was the primary outcome; pain perception as measured by visual analog scale was the secondary outcome. There were no statistically significant differences between the 3 groups of patients, either for PCA morphine consumption or for pain scores. Several factors may explain the observed lack of impact of tDCS on PCA morphine consumption and pain perception: the method of brain stimulation (tDCS/rTMS), potential interactions with anesthetic drugs, differences in patients population (gastric bypass surgery/lumbar spine surgery), and the previous experience of pain and chronic consumption of analgesic drugs. Further studies with tDCS should be performed before concluding that tDCS is inefficient for postoperative pain control, because noninvasive brain stimulation methods, such as rTMS and tDCS, may become attractive in the setting of multimodal analgesia.

The objective of the study was to evaluate safety and tolerability of tDCS treatment in schizophrenia patients. Our results confirm already established evidence that tDCS is a very safe and well tolerated method of non-invasive brain stimulation for patients with schizophrenia. Database of 219 tDCS sessions in patients with paranoid schizophrenia has been analyzed. During 219 tDCS sessions there were no serious adverse effects. All adverse effects were mild to moderate and transitory and the most frequent were: itching/tingling (81%), burning (53%) or heat sensation (48%) and skin reddening (35%). Itching/tingling and burning sensation were also frequently reported as at least moderately severe. All major adverse events (itching/tingling, burning/heat sensation) were more often localized by patients under the anodal pad. Men were more prone to experience some adverse events (itching/tingling, burning/heat sensation, skin reddening, metallic taste and tiredness). Most of the adverse events had their onset at the beginning of tDCS session, resolved by the end of tDCS session (with the exception of skin reddening, which recovered within 30 minutes after stimulation) and were associated with mild or moderate distress. Our results confirm already established evidence that tDCS is a very safe and well tolerated method of non-invasive brain stimulation for patients with schizophrenia.

ABSTRACTHuman motor skill acquisition is improved by performance feedback and coupling such feedback with extrinsic reward (such as money) can enhance skill learning. However, the neurophysiology underlying such behavioral effect is unclear. To bridge this gap, we assessed the effects of reward on multiple forms of motor plasticity during skill learning. Sixty-five healthy participants divided in three groups performed a pinch-grip skill task with sensory feedback only, sensory and reinforcement feedback or both feedback coupled with an extrinsic monetary reward during skill training. To probe motor plasticity, we applied transcranial magnetic stimulation on the left primary motor cortex at rest before, during and after training in the three groups. We evaluated the amplitude and variability of corticospinal output, GABA-ergic short-intracortical inhibition and use-dependent plasticity before training and at two time points during and after training. At the behavioral level, monetary reward accelerated skill learning. In parallel, corticospinal output became less variable early on during training in the presence of extrinsic reward. Interestingly, this effect was particularly pronounced for participants who were more sensitive to reward, as evaluated in an independent questionnaire. Other measures of motor excitability remained comparable across groups. These findings highlight that a mechanism underlying the benefit of reward on motor skill learning is the fine tuning of early-training resting-state corticospinal variability.SIGNIFICANCE STATEMENTSkill acquisition is enhanced in the presence of reward. Despite its potential clinical relevance for motor rehabilitation, the underlying neurophysiological mechanisms remain largely unexplored. Specifically, whether reward affects the plasticity of motor cortex in the context of skill learning is unclear. We show that reward reduces the variability of corticospinal output at an early stage during training and that this effect correlates with individual sensitivity to reward. Our results suggest that a key mechanism underlying the beneficial effect of reward on motor skill learning may be an increase in the stability of motor output in response to training during early stages of skill learning.

Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation method that, through its manipulation of endogenous oscillations, can affect cognition in healthy adults. Given the fact that both endogenous oscillations and cognition are impaired in various psychiatric diagnoses, tACS might represent a suitable intervention. We conducted a search of Pubmed and Web of Science databases and reviewed 27 studies where tACS is used in psychiatric diagnoses and cognition change is evaluated. TACS is a safe and well-tolerated intervention method, suitable for multiple-sessions protocols. It can be administered at home, individualized according to the patient'’s anatomical and functional characteristics, or used as a marker of disease progression. The results are varying across diagnoses and applied protocols, with some protocols showing a long-term effect. However, the overall number of studies is small with a great variety of diagnoses and tACS parameters, such as electrode montage or used frequency. Precise mechanisms of tACS interaction with pathophysiological processes are only partially described and need further research. Currently, tACS seems to be a feasible method to alleviate cognitive impairment in psychiatric patients; however, a more robust confirmation of efficacy of potential protocols is needed to introduce it into clinical practise.

Sleep spindles appear to play an important role in learning new motor skills. Motor skill learning engages several regions in the brain with two important areas being the motor cortex (M1) and the cerebellum. However, the neurophysiological processes in these areas during sleep, especially how spindle oscillations affect local and cross-region spiking, are not fully understood. We recorded activity from the M1 and cerebellar cortex in 8 rats during spontaneous activity to investigate how sleep spindles in these regions are related to local spiking as well as cross-region spiking. We found that M1 firing was significantly changed during both M1 and cerebellum spindles and this spiking occurred at a preferred phase of the spindle. On average, M1 and cerebellum neurons showed most spiking at the M1 or cerebellum spindle peaks. These neurons also developed a preferential phase-locking to local or cross-area spindles with the greatest phase-locking value at spindle peaks; however, this preferential phase-locking wasn't significant for cerebellar neurons when compared to cerebellum spindles. Additionally, we found the percentage of task-modulated cells in the M1 and cerebellum that fired with non-uniform spike-phase distribution during M1/ cerebellum spindle peaks were greater in the rats that learned a reach-to-grasp motor task robustly. Finally, we found that spindle-band LFP coherence (for M1 and cerebellum LFPs) showed a positive correlation with success rate in the motor task. These findings support the idea that sleep spindles in both the M1 and cerebellum recruit neurons that participate in the awake task to support motor memory consolidation.Significance Statement Neural processing during sleep spindles is linked to memory consolidation. However, little is known about sleep activity in the cerebellum and whether cerebellum spindles can affect spiking activity in local or distant areas. We report the effect of sleep spindles on neuron activity in the M1 and cerebellum-specifically their firing rate and phase-locking to spindle oscillations. Our results indicate that awake practice neuronal activity is tempered during local M1 and cerebellum spindles, and during cross-region spindles, which may support motor skill learning. We describe spiking dynamics in motor networks spindle oscillations that may aid in the learning of skills. Our results support the sleep reactivation hypothesis and suggest that awake M1 activity may be reactivated during cerebellum spindles.

Dopaminergic neurons in the ventral tegmental area, the major midbrain nucleus projecting to the motor cortex, play a key role in motor skill learning and motor cortex synaptic plasticity. Dopamine D1 and D2 receptor antagonists exert parallel effects in the motor system: they impair motor skill learning and reduce long-term potentiation. Traditionally, D1 and D2 receptor modulate adenylyl cyclase activity and cyclic adenosine monophosphate accumulation in opposite directions via different G-proteins and bidirectionally modulate protein kinase A (PKA), leading to distinct physiological and behavioral effects. Here we show that D1 and D2 receptor activity influences motor skill acquisition and long term synaptic potentiation via phospholipase C (PLC) activation in rat primary motor cortex. Learning a new forelimb reaching task is severely impaired in the presence of PLC, but not PKA-inhibitor. Similarly, long term potentiation in motor cortex, a mechanism involved in motor skill learning, is reduced when PLC is inhibited but remains unaffected by the PKA inhibitor. Skill learning deficits and reduced synaptic plasticity caused by dopamine antagonists are prevented by co-administration of a PLC agonist. These results provide evidence for a role of intracellular PLC signaling in motor skill learning and associated cortical synaptic plasticity, challenging the traditional view of bidirectional modulation of PKA by D1 and D2 receptors. These findings reveal a novel and important action of dopamine in motor cortex that might be a future target for selective therapeutic interventions to support learning and recovery of movement resulting from injury and disease.

Transcranial magnetic stimulation (TMS) is a method of noninvasive brain stimulation developed since the 1980s. Repetitive transcranial magnetic stimulation (rTMS) is one of the methods of noninvasive brain stimulation, which is increasingly used to treat psychiatric disorders. Recent years witnessed a dynamic growth in the number of sites offering therapy with rTMS and of the interest of patients in this method in Poland. This article presents the position statement of the working group of the Section of Biological Psychiatry of the Polish Psychiatric Association concerning the proper patients selection and safety of use of rTMS in the therapy of psychiatric conditions. Before starting to use rTMS, the involved personnel should undergo a period of training in one of the centers with relevant experience. Equipment dedicated to perform rTMS should be appropriately certified. The main therapeutic indication is depression, including drug-resistant patients. rTMS may also be used in obsessive-compulsive disorder, negative symptoms and auditory hallucinations in schizophrenia, nicotine addiction, cognitive and behavioral disturbances in Alzheimer's disease, and post-traumatic stress disorder. The strength of magnetic stimuli and the overall dosing of stimulation must be based on the recommendations of the International Federation of Clinical Neurophysiology. The main contraindications are the metal elements in the body, especially medical electronic devices near the stimulating coil, epilepsy, hearing loss, structural changes in the brain, which may be associated with epileptogenic foci, pharmacotherapy, which lowers the seizure threshold, and pregnancy. The main side effects are induction of epileptic seizure, syncope, pain and discomfort during stimulation, as well as induction of manic or hypomanic episodes. The respective management is described in the article.

Contrary to its well-established role in declarative learning, the impact of sleep on motor memory consolidation remains a subject of debate. Current literature suggests that while motor skill learning benefits from sleep, consolidation of sensorimotor adaptation (SMA) depends solely on the passage of time. This has led to the proposal that SMA may be an exception to other types of memories. Here, we addressed this ongoing controversy in humans through three comprehensive experiments using the visuomotor adaptation paradigm (N = 290, 150 females). In Experiment 1, we investigated the impact of sleep on memory retention when the temporal gap between training and sleep was not controlled. In line with the previous literature, we found that memory consolidates with the passage of time. In Experiment 2, we used an anterograde interference protocol to determine the time window during which SMA memory is most fragile and, thus, potentially most sensitive to sleep intervention. Our results show that memory is most vulnerable during the initial hour post-training. Building on this insight, in Experiment 3, we investigated the impact of sleep when it coincided with the critical first hour of memory consolidation. This manipulation unveiled a benefit of sleep (30% memory enhancement) alongside an increase in spindle density and spindle-SO coupling during NREM sleep, two well-established neural markers of sleep consolidation. Our findings reconcile seemingly conflicting perspectives on the active role of sleep in motor learning and point to common mechanisms at the basis of memory formation.

Motor skill acquisition inherently depends on the way one practices the motor task. The amount of motor task variability during practice has been shown to foster transfer of the learned skill to other similar motor tasks. In addition, variability in a learning schedule, in which a task and its variations are interweaved during practice, has been shown to help the transfer of learning in motor skill acquisition. However, there is little evidence on how motor task variations and variability schedules during practice act on the acquisition of complex motor skills such as music performance, in which a performer learns both the right movements (motor skill) and the right time to perform them (timing skill). This study investigated the impact of rate (tempo) variability and the schedule of tempo change during practice on timing and motor skill acquisition. Complete novices, with no musical training, practiced a simple musical sequence on a piano keyboard at different rates. Each novice was assigned to one of four learning conditions designed to manipulate the amount of tempo variability across trials (large or small tempo set) and the schedule of tempo change (randomized or non-randomized order) during practice. At test, the novices performed the same musical sequence at a familiar tempo and at novel tempi (testing tempo transfer), as well as two novel (but related) sequences at a familiar tempo (testing spatial transfer). We found that practice conditions had little effect on learning and transfer performance of timing skill. Interestingly, practice conditions influenced motor skill learning (reduction of movement variability): lower temporal variability during practice facilitated transfer to new tempi and new sequences; non-randomized learning schedule improved transfer to new tempi and new sequences. Tempo (rate) and the sequence difficulty (spatial manipulation) affected performance variability in both timing and movement. These findings suggest that there is a dissociable effect of practice variability on learning complex skills that involve both motor and timing constraints.