Attempts have been made to modulate motor sequence learning (MSL) through repetitive transcranial magnetic stimulation, targeting different sites within the sensorimotor network. However, the target with the optimum modulatory effect on neural plasticity associated with MSL remains unclarified. This study was therefore designed to compare the role of the left primary motor cortex and the left supplementary motor area proper (SMAp) in modulating MSL across different complexity levels and for both hands, as well as the associated neuroplasticity by applying intermittent theta burst stimulation together with the electroencephalogram and concurrent transcranial magnetic stimulation. Our data demonstrated the role of SMAp stimulation in modulating neural communication to support MSL, which is achieved by facilitating regional activation and orchestrating neural coupling across distributed brain regions, particularly in interhemispheric connections. These findings may have important clinical implications, particularly for motor rehabilitation in populations such as post-stroke patients.
Humans ; Transcranial Magnetic Stimulation ; Motor Cortex/physiology* ; Male ; Electroencephalography ; Neuronal Plasticity/physiology* ; Female ; Adult ; Evoked Potentials, Motor/physiology* ; Young Adult ; Learning/physiology*

Reach-to-grasp movements require integrating information on both object location and grip type, but how these elements are planned and to what extent they interact remains unclear. We designed a new experimental paradigm in which monkeys sequentially received reach and grasp cues with delays, requiring them to retain and integrate both cues to grasp the goal object with appropriate hand gestures. Neural activity in the dorsal premotor cortex (PMd) revealed that reach and grasp were similarly represented yet not independent. Upon receiving the second cue, the PMd continued encoding the first, but over half of the neurons displayed incongruent modulations: enhanced, attenuated, or even reversed. Population-level analysis showed significant changes in encoding structure, forming distinct neural patterns. Leveraging canonical correlation analysis, we identified a shared subspace preserving the initial cue's encoding, contributed by both congruent and incongruent neurons. Together, these findings reveal a novel perspective on the interactive planning of reach and grasp within the PMd, providing insights into potential applications for brain-machine interfaces.
Animals ; Motor Cortex/physiology* ; Hand Strength/physiology* ; Macaca mulatta ; Psychomotor Performance/physiology* ; Neurons/physiology* ; Male ; Cues ; Movement/physiology* ; Gestures

The organization of the brain follows a topological hierarchy that changes dynamically during development. However, it remains unknown whether and how cognitive training administered over multiple years during development can modify this hierarchical topology. By measuring the brain and behavior of school children who had carried out abacus-based mental calculation (AMC) training for five years (starting from 7 years to 12 years old) in pre-training and post-training, we revealed the reshaping effect of long-term AMC intervention during development on the brain hierarchical topology. We observed the development-induced emergence of the default network, AMC training-promoted shifting, and regional changes in cortical gradients. Moreover, the training-induced gradient changes were located in visual and somatomotor areas in association with the visuospatial/motor-imagery strategy. We found that gradient-based features can predict the math ability within groups. Our findings provide novel insights into the dynamic nature of network recruitment impacted by long-term cognitive training during development.
Child ; Humans ; Cognitive Training ; Magnetic Resonance Imaging ; Brain ; Brain Mapping ; Motor Cortex

Neuromuscular electrical stimulation (NMES) has been proven to promote human balance, but research on its impact on motor ability mainly focuses on external physical analysis, with little analysis on the intrinsic neural regulatory mechanisms. This study, for the first time, investigated the effects of NMES on cortical activity and cortico-muscular functional coupling (CMFC) during standing balance. Twelve healthy subjects were recruited in bilateral NMES training, with each session consisting of 60 electrically induced isometric contractions. Electroencephalogram (EEG) signals, electromyogram (EMG) signals, and center of pressure (COP) signals of the foot sole were collected before stimulation, two weeks after stimulation, and four weeks after stimulation while the subjects maintained standing balance. The results showed that NMES training improved subjects' postural stability during standing balance. Additionally, based on the EMG power spectral density (PSD), the κ frequency band was defined, and EEG-EMG time-frequency maximal information coefficients (TFMIC) were calculated. It was found that NMES enhanced functional connectivity between the cortex and lower limb muscles, with varying degrees of increase in β-κ and γ-κ frequency band CMFC after stimulation. Furthermore, sample entropy (SE) of EEG signals also increased after training. The results of this study confirm that NMES training can enhance CMFC and brain activation during standing balance. This study, from the perspective of physiological electrical signals, validates the effectiveness of NMES for balance training and provides objective assessment metrics for the training effects of NMES.
Humans ; Postural Balance/physiology* ; Electromyography ; Electroencephalography ; Muscle, Skeletal/physiology* ; Electric Stimulation ; Motor Cortex/physiology* ; Male ; Standing Position ; Adult ; Female

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/cm²) 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 Ca²⁺ 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.
Transcranial Direct Current Stimulation/methods* ; Motor Cortex/physiology* ; Neurons ; Transcranial Magnetic Stimulation

OBJECTIVE: To observe the effects of electroacupuncture (EA) on cardiac function and local field potential (LFP) in sensory and motor cortices in mice with stress cardiomyopathy (SC), and to explore the possible mechanism of EA in improving SC. METHODS: Twenty-seven female C57BL/6 mice were randomized into a blank group, a model group and an EA group, 9 mice in each group. In the model group and the EA group, SC model was established by continuous intraperitoneal injection of isoproterenol (ISO) for 14 days. At the same time of modeling, EA was applied at "Neiguan" (PC 6) and "Shenmen" (HT 7) in the EA group, with disperse-dense wave, in frequency of 2 Hz/15 Hz, 15 min each time, once a day for 14 days. After intervention, the total movement distance, the number of crossing grid and the number of crossing central grid of open field test within 5 minutes were observed; the left ventricular function indexes (left ventricular diameter of end-diastole [LVIDd], left ventricular diameter of end-systole [LVIDs], left ventricular volume of end-diastole [LVEDV], left ventricular volume of end-systole [LVESV], ejection fraction [EF] and fraction shortening [FS]) were detected by echocardiography; the changes in ST-segment amplitude and PR interval of electrocardiogram were observed; the morphology of myocardial tissue was observed by HE staining; the serum levels of cortisol (CORT), cardiac troponin T (cTnT) and brain natriuretic peptide (BNP) were detected by ELISA; the changes of LFP in sensory and motor cortices were recorded by Plexon multi-channel acquisition system. RESULTS: Compared with the blank group, in the model group, the total movement distance, the number of crossing grid and the number of crossing central grid of open field test were decreased (P<0.05); LVIDd, LVIDs, LVEDV and LVESV were increased (P<0.05), EF and FS were decreased (P<0.05); ST-segment amplitude was increased (P<0.05) and PR interval was prolonged (P<0.05); irregular myocardial fiber arrangement, interstitial edema and inflammatory cell infiltration were observed; the serum levels of CORT, cTnT and BNP were increased (P<0.05); in the sensory cortex, the ratios of delta, theta, alpha and beta frequency bands were increased (P<0.05), the maximum energy spectrum of theta and beta frequency bands was increased (P<0.05), the power spectral density (PSD) of delta, theta, alpha, beta and gamma frequency bands was increased (P<0.05); in the motor cortex, the ratios of delta, theta, alpha and beta frequency bands were increased (P<0.05), the maximum energy spectrum as well as PSD of delta, theta, alpha, beta and gamma frequency bands were increased (P<0.05). Compared with model group, in the EA group, the total movement distance, the number of crossing grid and the number of crossing central grid of open field test were increased (P<0.05); LVIDd, LVIDs, LVEDV and LVESV were decreased (P<0.05), EF and FS were increased (P<0.05); ST-segment amplitude was decreased (P<0.05), and the PR interval was shortened (P<0.05); myocardial fiber injury and inflammatory cell infiltration were reduced; the serum levels of CORT, cTnT and BNP were decreased (P<0.05); in the sensory cortex, the ratios of theta, alpha and beta frequency bands were decreased (P<0.05), the ratio of gamma frequency band was increased (P<0.05), the maximum energy spectrum of theta frequency band as well as the PSD of theta, alpha, beta and gamma frequency bands were decreased (P<0.05); in the motor cortex, the ratios of theta, alpha and beta frequency bands were decreased (P<0.05) and the ratio of gamma frequency band was increased (P<0.05), the maximum energy spectrum of delta frequency band was increased (P<0.05), the maximum energy spectrum of theta frequency band as well as the PSD of theta and gamma frequency bands were decreased (P<0.05). CONCLUSION EA can improve cardiac function in mice with stress cardiomyopathy, and its mechanism may be related to the regulation of local field potentials in sensory and motor cortices.
Female ; Mice ; Animals ; Electroacupuncture ; Takotsubo Cardiomyopathy ; Motor Cortex ; Mice, Inbred C57BL ; Myocardium

The secondary motor cortex (M2) encodes choice-related information and plays an important role in cue-guided actions. M2 neurons innervate the dorsal striatum (DS), which also contributes to decision-making behavior, yet how M2 modulates signals in the DS to influence perceptual decision-making is unclear. Using mice performing a visual Go/No-Go task, we showed that inactivating M2 projections to the DS impaired performance by increasing the false alarm (FA) rate to the reward-irrelevant No-Go stimulus. The choice signal of M2 neurons correlated with behavioral performance, and the inactivation of M2 neurons projecting to the DS reduced the choice signal in the DS. By measuring and manipulating the responses of direct or indirect pathway striatal neurons defined by M2 inputs, we found that the indirect pathway neurons exhibited a shorter response latency to the No-Go stimulus, and inactivating their early responses increased the FA rate. These results demonstrate that the M2-to-DS pathway is crucial for suppressing inappropriate responses in perceptual decision behavior.
Mice ; Animals ; Motor Cortex ; Corpus Striatum/physiology* ; Neostriatum ; Neurons/physiology* ; Reaction Time

Gyrus Cinguli ; Claustrum ; Cerebral Cortex ; Basal Ganglia ; Motor Activity ; Neural Pathways

OBJECTIVES: To compare the effects of electroacupuncture (EA) with different time intervals on corticospinal excitability of the primary motor cortex (M1) and the upper limb motor function in healthy subjects and observe the after-effect rule of acupuncture. METHODS: Self-comparison before and after intervention design was adopted. Fifteen healthy subjects were included and all of them received three stages of trial observation, namely EA₀ group (received one session of EA), EA_6h group (received two sessions of EA within 1 day, with an interval of 6 h) and EA_48h group (received two sessions of EA within 3 days, with an interval of 48 h). The washout period among stages was 1 week. In each group, the needles were inserted perpendicularly at Hegu (LI 4) on the left side, 23 mm in depth and at a non-acupoint, 0.5 cm nearby to the left side of Hegu (LI 4), separately. Han's acupoint nerve stimulator (HANS-200A) was attached to these two needles, with continuous wave and the frequency of 2 Hz. The stimulation intensity was exerted higher than the exercise threshold (local muscle twitching was visible, and pain was tolerable by healthy subjects, 1-2 mA ). The needles were retained for 30 min. Using the single pulse mode of transcranial magnetic stimulation (TMS) technique, before the first session of EA (T0) and at the moment (T1), in 2 h (T2) and 24 h (T3) after the end of the last session of EA, on the left first dorsal interosseous muscle, the amplitude, latency (LAT), resting motor threshold (rMT) of motor evoked potentials (MEPs) and the completion time of grooved pegboard test (GPT) were detected. Besides, in the EA_6h group, TMS was adopted to detect the excitability of M1 (amplitude, LAT and rMT of MEPs) before the last session of EA (T0*). RESULTS: The amplitude of MEPs at T1 and T2 in the EA₀ group, at T0* in the EA_6h group and at T1, T2 and T3 in the EA_48h group was higher when compared with the value at T0 in each group separately (P<0.001). At T1, the amplitude of MEPs in the EA₀ group and the EA_48h group was higher than that in the EA_6h group (P<0.001, P<0.01); at T2, it was higher in the EA₀ group when compared with that in the EA_6h group (P<0.01); at T3, the amplitude in the EA₀ group and the EA_6h group was lower than that of the EA_48h group (P<0.001). The LAT at T1 was shorter than that at T0 in the three groups (P<0.05), and the changes were not obvious at the rest time points compared with that at T0 (P > 0.05). The GPT completion time of healthy subjects in the EA₀ group and the EA_48h group at T1, T2 and T3 was reduced in comparison with that at T0 (P<0.001). The completion time at T3 was shorter than that at T0 in the EA_6h group (P<0.05); at T2, it was reduced in the EA_48h group when compared with that of the EA_6h group (P<0.05). There were no significant differences in rMT among the three groups and within each group (P>0.05). CONCLUSIONS Under physiological conditions, EA has obvious after-effect on corticospinal excitability and upper limb motor function. The short-term interval protocol (6 h) blocks the after-effect of EA to a certain extent, while the long-term interval protocol (48 h) prolongs the after-effect of EA.
Humans ; Electroacupuncture ; Motor Cortex/physiology* ; Transcranial Magnetic Stimulation/methods* ; Upper Extremity ; Exercise ; Muscle, Skeletal/physiology*

Humans ; Depressive Disorder, Major ; Motor Cortex ; Magnetic Resonance Imaging