Neural Mechanism Underlying Task-Specific Enhancement of Motor Learning by Concurrent Transcranial Direct Current Stimulation

The optimal protocol for neuromodulation by transcranial direct current stimulation(tDCS)remains unclear.Using the rotarod paradigm,we found that mouse motor learning was enhanced by anodal tDCS(3.2 mA/cm^(2))during but not before or after the performance of a task.Dual-task experiments showed that motor learning enhancement was specific to the task accompanied by anodal tDCS.Studies using a mouse model of stroke induced by middle cerebral artery occlusion showed that concurrent anodal tDCS restored motor learning capability in a task-specific manner.Transcranial in vivo Ca^(2+)imaging further showed that anodal tDCS elevated and cathodal tDCS suppressed neuronal activity in the primary motor cortex(M1).Anodal tDCS specifically promoted the activity of task-related M1 neurons during task performance,suggesting that elevated Hebbian synaptic potentiation in task-activated circuits accounts for the motor learning enhancement.Thus,application of tDCS concurrent with the targeted behavioral dysfunction could be an effective approach to treating brain disorders.

Artificial intelligence and machine learning in motor recovery: A rehabilitation medicine perspective

Artificial intelligence(AI)and machine learning(ML)are powerful technologies with the potential to revolutionize motor recovery in rehabilitation medicine.This perspective explores how AI and ML are harnessed to assess,diagnose,and design personalized treatment plans for patients with motor impairments.The integration of wearable sensors,virtual reality,augmented reality,and robotic devices allows for precise movement analysis and adaptive neurorehabilitation approaches.Moreover,AI-driven telerehabilitation enables remote monitoring and consultation.Although these applications show promise,healthcare professionals must interpret AI-generated insights and ensure patient safety.While AI and ML are in their early stages,ongoing research will determine their effectiveness in rehabilitation medicine.

Bimanual motor skill learning and robotic assistance for chronic hemiparetic stroke: a randomized controlled trial

Using robotic devices might improve recovery post-stroke, but the optimal way to apply robotic assistance has yet to be determined. The current study aimed to investigate whether training under the robotic active-assisted mode improves bimanual motor skill learning(biMSkL) more than training under the active mode in stroke patients. Twenty-six healthy individuals(HI) and 23 chronic hemiparetic stroke patients with a detectable lesion on MRI or CT scan, who demonstrated motor deficits in the upper limb, were randomly allocated to two parallel groups. The protocol included a two-day training on a new bimanual cooperative task, LIFT-THE-TRAY, under either the active or activeassisted modes(where assistance decreased in a pre-determined stepwise fashion) with the bimanual version of the REAplan? robotic device. The hypothesis was that the active-assisted mode would result in greater biMSkL than the active mode. The biMSkL was quantified by a speed-accuracy trade-off(SAT) before(T1) and immediately after(T2) training on days 1 and 2(T3 and T4). The change in SAT after 2 days of training(T4/T1) indicated that both HI and stroke patients learned and retained the bimanual cooperative task. After 2 days of training, the active-assisted mode did not improve biMSkL more than the active mode(T4/T1) in HI nor stroke patients. Whereas HI generalized the learned bimanual skill to different execution speeds in both the active and active-assisted subgroups, the stroke patients generalized the learned skill only in the active subgroup. Taken together, the active-assisted mode, applied in a pre-determined stepwise decreasing fashion, did not improve biMSkL more than the active mode in HI and stroke subjects. Stroke subjects might benefit more from robotic assistance when applied "as-needed." This study was approved by the local ethical committee(Comité d'éthique médicale, CHU UCL Namur, MontGodinne, Yvoir, Belgium;Internal number: 54/2010, Eudra CT number: NUB B039201317382) on July 14, 2016 and was registered with ClinicalTrials.gov(Identifier: NCT03974750) on June 5, 2019.

O-GlcNAcylation in Ventral Tegmental Area Dopaminergic Neurons Regulates Motor Learning and the Response to Natural Reward

Protein O-GlcNAcylation is a post-translational modification that links environmental stimuli with changes in intracellular signal pathways,and its disturbance has been found in neurodegenerative diseases and metabolic disorders.However,its role in the mesolimbic dopamine(DA)system,especially in the ventral tegmental area(VTA),needs to be elucidated.Here,we found that injection of Thiamet G,an O-GlcNAcase(OGA)inhibitor,in the VTA and nucleus accumbens(NAc)of mice,facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod test.Mice with DAergic neuron-specific knockout of O-GlcNAc transferase(OGT)displayed severe metabolic abnormalities and died within 4–8 weeks after birth.Furthermore,mice specifically overexpressing OGT in DAergic neurons in the VTA had learning defects in the operant response to sucrose,and impaired motor learning in the rotarod test.Instead,overexpression of OGT in GABAergic neurons in the VTA had no effect on these behaviors.These results suggest that protein O-GlcNAcylation of DAergic neurons in the VTA plays an important role in regulating the response to natural reward and motor learning in mice.

Effects of Different Feedback Conditions on Sensorimotor Adaptation Revealed in a Mirror Reversal Paradigm

Humans are able to overcome sensory perturbations imposed on their movements through motor learning. One of the key mechanisms to accomplish this is sensorimotor adaptation, an implicit, error-driven learning mechanism. Past work on sensorimotor adaptation focused mainly on adaptation to rotated visual feedback—A paradigm known as visuomotor rotation. Recent studies have shown that sensorimotor adaptation can also occur under mirror-reversed visual feedback. In visuomotor rotation, sensorimotor adaptation can be driven by both endpoint and online feedback [1] [2]. However, it’s not been clear whether both kinds of feedback can similarly drive adaptation under a mirror reversed perturbation. We performed a study to establish what kinds of feedback can drive adaptation under mirror reversal. In the first two conditions, the participants were asked to ignore visual feedback. In the first condition, we provided mirror reversed online feedback and endpoint feedback. We reproduced previous findings showing that online feedback elicited adaptation under mirror reversal. In a second condition, we provided mirror reversed endpoint feedback. However, in the second condition, we found that endpoint feedback alone failed to elicit adaptation. In a third condition, we provided both types of feedback at the same time, but in a conflicting way: endpoint feedback was non-reversed while online feedback was mirror reversed. The participants were asked to ignore online visual feedback and try to hit the target with help from veridical endpoint feedback. In the third condition, in which veridical endpoint feedback and mirror reversed online feedback were provided, adaptation still occurred. Our results showed that endpoint feedback did not elicit adaptation under mirror reversal but online feedback did. This dissociation between effects of endpoint feedback and online feedback on adaptation under mirror reversal suggests that adaptation under these different kinds of feedback might in fact operate via distinct mechanisms.

Improvement of learning and memory abilities and motor function in rats with cerebral infarction by intracerebral transplantation of neuron-like cells derived from bone marrow stromal cells

BACKGROUND： Transplantation of fetal cell suspension or blocks of fetal tissue can ameliorate the nerve function after the injury or disease in the central nervous system, and it has been used to treat neurodegenerative disorders induced by Parkinson disease. OBJECTIVE： To observe the effects of the transplantation of neuron-like cells derived from bone marrow stromal cells （rMSCs） into the brain in restoring the dysfunctions of muscle strength and balance as well as learning and memory in rat models of cerebral infarction. DESIGN ： A randomized controlled experiment.SETTING ： Department of Pathophysiology, Zhongshan Medical College of Sun Yat-sen University.MATERIALS ： Twenty-four male SD rats （3-4 weeks of age, weighing 200-220 g） were used in this study （Certification number：2001A027）. METHODS： The experiments were carried out in Zhongshan Medical College of Sun Yat-sen University between December 2003 and December 2004. ① Twenty-four male SD rats randomized into three groups with 8 rats in each： experimental group, control group and sham-operated group. Rats in the experiment al group and control group were induced into models of middle cerebral artery occlusion （MCAO）. After in vitro cultured, purified and identified with digestion, the Fischer344 rMSCs were induced to differentiate by tanshinone IIA, which was locally injected into the striate cortex （18 area） of rats in the experimental group, and the rats in the control group were injected by L-DMEM basic culture media （without serum） of the same volume to the corresponding brain area. In the sham-operated group, only muscle and vessel of neck were separated. ② At 2 and 8 weeks after the transplantation, the rats were given the screen test, prehensile-traction test, balance beam test and Morris water-maze test. ③ The survival and distribution of the induced cells in corresponding brain area were observed with Nissl stained with toluidine blue and hematoxylin and eosin （HE） staining in the groups.MAIN OUTCOME MEASURES ： ① Results of the behavioral tests （time of the Morris water-maze test screen test, prehensile-traction test, balance beam test）; ② Survival and distribution of the induced cells.RESULTS： All the 24 rats were involved in the analysis of results. ① Two weeks after transplantation, rats with neuron-like cells grafts in the experimental group had significant improvement on their general muscle strength than those in the control group [screen test： （9.4±1.7）, （4.7±1.0） s, P 〈 0.01]; forelimb muscle strength [prehensile-traction test： （7.6±1.4）, （5.2±1.2） s, P 〈 0.01], ability to keep balance [balance beam test： （7.9±0.74）, （6.1±0.91） s, P 〈 0.01] and abilities of learning and memory [latency to find the platform： （35.8±5.9）, （117.5±11.6） s, P 〈 0.01; distance： （623.1±43.4）, （1 902.3±98.6） cm, P 〈 0.01] as compared with those in the control group. The functional performances in the experimental group at 8 weeks were better than those at two weeks, which were still obviously different from those in the sham-operated group （P 〈 0.05）. ② The HE and Nissl stained brain tissue section showed that there was nerve cell proliferation at the infarcted cortex in the experiment group, the density was higher than that in the control group, plenty of aggregative or scattered cells could be observed at the site where needle was inserted for transplantation, the cells migrated directively towards the area around them, the cerebral vascular walls were wrapped by plenty of cells; In the control group, most of the cortices were destroyed, karyopyknosis and necrosis of neurons were observed, normal nervous tissue structure disappeared induced by edema, only some nerve fibers and glial cells remained.CONCLUSION： The rMSCs transplantation can obviously enhance the motor function and the abilities of learning and memory in rat models of cerebral infarction.

Is effect of transcranial direct current stimulation on visuomotor coordination dependent on task difficulty?

Transcranial direct current stimulation （tDCS）, an emerging technique for non-invasive brain stimulation, is increasingly used to induce changes in cortical excitability and modulate motor behavior, especially for upper limbs. The purpose of this study was to investigate the effects of tDCS of the primary motor cortex on visuomotor coordination based on three levels of task difficulty in healthy subjects. Thirty-eight healthy participants underwent real tDCS or sham tDCS. Using a single-blind, sham-controlled crossover design, tDCS was applied to the primary motor cortex. For real tDCS conditions, tDCS intensity was 1 mA while stimulation was applied for 15 minutes. For the sham tDCS, electrodes were placed in the same position, but the stimu- lator was turned off after 5 seconds. Visuomotor tracking task, consisting of three levels （levels 1, 2, 3） of difficulty with higher level indicating greater difficulty, was performed before and after tDCS application. At level 2, real tDCS of the primary motor cortex improved the accurate index compared to the sham tDCS. However, at levels 1 and 3, the accurate index was not significantly increased after real tDCS compared to the sham tDCS. These findings suggest that tasks of mod- erate difficulty may improve visuomotor coordination in healthy subjects when tDCS is applied compared with easier or more difficult tasks.

Is transcranial direct current stimulation a potential method for improving response inhibition?

Inhibitory control of movement in motor learning requires the ability to suppress an inappropriate action, a skill needed to stop a planned or ongoing motor response in response to changes in a variety of environments. This study used a stop-signal task to determine whether transcranial direct-current stimulation over the pre-supplementary motor area alters the reaction time in motor inhibition. Forty healthy subjects were recruited for this study and were randomly assigned to either the transcranial direct-current stimulation condition or a sham-transcranial direct-current stimulation condition. All subjects consecutively performed the stop-signal task before, during, and after the delivery of anodal transcranial direct-current stimulation over the pre-supplementary motor area （pre-transcranial direct-current stimulation phase, transcranial direct-current stimulation phase, and post-transcranial direct-current stimulation phase）. Compared to the sham condition, there were significant reductions in the stop-signal processing times during and after transcranial direct-current stimulation, and change times were significantly greater in the transcranial direct-current stimulation condition. There was no significant change in go processing-times during or after transcranial direct-current stimulation in either condition. Anodal transcranial direct-current stimulation was feasibly coupled to an interactive improvement in inhibitory control. This coupling led to a decrease in the stop-signal process time required for the appropriate responses between motor execution and inhibition. However, there was no transcranial direct-current stimulation effect on the no-signal reaction time during the stop-signal task. Transcranial direct-current stimulation can adjust certain behaviors, and it could be a useful clinical intervention for patients who have difficulties with response inhibition.

Learning control in robot-assisted rehabilitation of motor skills-a

The key idea in iterative learning control is captured by the intuition of‘practice makes perfect’.The underlying learning is based on a gradient descent algorithm iteratively optimising an appropriate input–output measured criterion.How this paradigm is used to model quantitatively,at an input/output level,the learning that happens in the context of human motor skill learning is discussed in this note.Experimental studies of human motor learning,in robotically controlled environments,indicate that a model consisting of a classical(iterative)learning control augmented with an appropriate kinematic model of human motor motion fits the observed human learning behaviour well.In the context of the rehabilitation of motor skills,such models promise better human–machine interfaces that extend the capability and capacity of rehabilitation clinicians by creating effective robot–patient–clinician feedback loops.The economic promise of robot-assisted rehabilitation is to greatly extend the intervention capacity above what presently can be achieved by rehabilitation systems:addressing the needs of more people,over longer periods of time and at a distance in the comfort of their own personal environment.Moreover,the robot platforms provide for a more rigorous and quantitative evaluation of the patient’s motor skill across the entire personal rehabilitation trajectory,which opens up opportunities for improved,more individually tuned rehabilitation regimes.

Learning fuzzy controller and extended Kalman filter for sensorless induction motor robust against resistance variation

This paper presents a new sensorless vector controlled induction motor drive robust against rotor resistance variation. Indeed, the speed and rotor resistance are estimated using extended Kalman filter （EKF）. Then, we introduce a new fuzzy logic speed controller based on learning by minimizing cost function. This strategy is based on a topology control self-organized and an algorithm for modifying the knowledge base of fuzzy corrector. The learning mechanism addresses the con- sequences of corrector rules, which are modified according to the comparison between the current speed of machine and an output signal or a desired trajectory. Thus, fuzzy associative memory is constructed to meet the criteria imposed in problems either control or pursuit. The consequent algorithm updating consists of a regulator mechanism allowing a fast and robust learning without unnecessarily compromising the control signal and steady- state performance. The performance of this new strategy is satisfactory, even in the presence of noise or when there are variations in the parameters of induction motor drive.

Changes in brain activation patterns according to cross-training effect in serial reaction time task An functional MRI study

Cross-training is a phenomenon related to motor learning, where motor performance of the untrained limb shows improvement in strength and skill execution following unilateral training of the homologous contralateral limb. We used functional MRI to investigate whether motor performance of the untrained limb could be improved using a serial reaction time task according to motor sequential learning of the trained limb, and whether these skill acquisitions led to changes in brain activation patterns. We recruited 20 right-handed healthy subjects, who were randomly allocated into training and control groups. The training group was trained in performance of a serial reaction time task using their non-dominant left hand, 40 minutes per day, for 10 days, over a period of 2 weeks. The control group did not receive training. Measurements of response time and percentile of response accuracy were performed twice during pre- and post-training, while brain functional MRI was scanned during performance of the serial reaction time task using the untrained right hand. In the training group, prominent changes in response time and percentile of response accuracy were observed in both the untrained right hand and the trained left hand between pre- and post-training. The control group showed no significant changes in the untrained hand between pre- and post-training. In the training group, the activated volume of the cortical areas related to motor function （i.e., primary motor cortex, premotor area, posterior parietal cortex） showed a gradual decrease, and enhanced cerebellar activation of the vermis and the newly activated ipsilateral dentate nucleus were observed during performance of the serial reaction time task using the untrained right hand, accompanied by the cross-motor learning effect. However, no significant changes were observed in the control group. Our findings indicate that motor skills learned over the 2-week training using the trained limb were transferred to the opposite homologous limb, and motor skill acquisition of the untrained limb led to changes in brain activation patterns in the cerebral cortex and cerebellum.

Altered Motor-Striatal Plasticity and Cortical Functioning in Patients with Schizophrenia

Patients with schizophrenia undergo changes in brain plasticity. In the present study, we characterized motor cortical-striatal plasticity in such patients. Compared with the potentiation following high-frequency repetitive transcranial magnetic stimulation in the control group, the patients demonstrated impaired plasticity of corticostriatal motor-evoked potentials recorded from hand muscles.Notably, the loss of cortical plasticity was correlated with impaired motor learning in a rotary pursuit task. Moreover,the loss of plasticity was correlated with the symptoms of schizophrenia. The results suggest that the progression of schizophrenia is accompanied by altered cortical plasticity and functioning.

Dscam mutation leads to hydrocephalus and decreased motor function

The nervous system is one of the most complicated organ systems in invertebrates and vertebrates.Down syndrome cell adhesion molecule(DSCAM)of the immunoglobulin(Ig)superfamily is expressed widely in the nervous system during embryonic development.Previous studies in Drosophila suggest that Dscam plays important roles in neural development including axon branching,dendritic tiling and cell spacing.However,the function of the mammalian DSCAM gene in the formation of the nervous system remains unclear.Here,we show that Dscam^(del17) mutant mice exhibit severe hydrocephalus,decreased motor function and impaired motor learning ability.Our data indicate that the mammalian DSCAM gene is critical for the formation of the central nervous system.

The Effect of Familiarization on the Reliability of Isokinetic Assessment in Breast Cancer Survivors

Purpose To determine the amount of familiarization sessions required by breast cancer survivors to achieve a reliable meas-urement of muscle function assessed using isokinetic dynamometry.Methods Twenty-six breast cancer survivors performed three isokinetic knee extension tests separated by,at least,48 h.The isokinetic testing protocol included one warm-up set of 10 submaximal knee extensions at 120°/s,followed by two sets of four maximal knee extensions at 60°/s,with 2-min rest interval between sets.Peak torque(PT),time to peak torque(TPT),angle of peak torque(APT),and average power(AP)of each trial was used for the assessment of testing reliability.Percentage change in the mean,typical error,coefficient of variation and intraclass correlation coefficients(ICC2.1)were calculated to determine test-retest reliability.Results For PT,change in mean was lower between trials 2 and 3 than between trials 1 and 2(4.18% and 13.18%,respec-tively),and ICC was greater between trials 2 and 3 than between trials 1 and 2(0.962 and 0.818,respectively).For TPT and APT,ICC was clinically acceptable only between trials 2 and 3(0.757 and 0.803,respectively).For AP,change in mean was clinically acceptable between trials 2 and 3(9.84%),while ICC met acceptable reliability between both,trials 1 and 2 and,trials 2 and 3(0.756 and 0.891,respectively).Conclusion At least one familiarization session is adequate to achieve reliable measurements of muscle function using isokinetic dynamometry,while avoiding the impact of learning effect of the measurements in breast cancer survivors.

Can We Capitalize on Central Nervous System Plasticity in Young Athletes to Inoculate Against Injury?

There are numerous physical,social,and psychological benefits of exercise,sport and play for youth athletes.However,dynamic activities come with a risk of injury that has yet to be abated,warranting novel therapeutics to promote injury-resistance and to keep an active lifestyle throughout the lifespan.The purpose of the present manuscript was to summarize the extant literature and potential connecting framework regarding youth brain development and neuroplasticity associated with musculoskeletal injury.This review provides the foundation for our proposed framework that utilizes the OPTIMAL(Optimizing Performance Through Intrinsic Motivation and Attention for Learning)theory of motor learning to elicit desir-able biomechanical adaptations to support injury prevention(injury risk reduction),rehabilitation strategies,and exercise performance for youth physical activity and play across all facets of sport(Prevention Rehabilitation Exercise Play;PREP).We conclude that both young male and females are ripe for OPTIMAL PREP strategies that promote desirable movement mechanics by leveraging a unique time window for which their heightened state of central nervous system plasticity is capable of enhanced adaptation through novel therapeutic interventions.