The ocular vestibular evoked myogenic potential (oVEMP) is a measure of otolith function. The initial n10 peak follows a contralateral pathway from ipsilateral utricle to contralateral inferior oblique muscle. Following the n10, a series of positive and negative waves are elicited in the inferior oblique, but their characteristics and generators are unknown. This paper therefore investigated the latency, amplitude, and laterality of these late peaks in patients with hearing or vestibular loss compared to healthy volunteers. oVEMPs were elicited to bone-conducted (BC) square wave pulses and air-conducted (AC) clicks in 63 healthy volunteers, 15 patients with profound hearing loss (HL), 45 patients with unilateral vestibular loss (uVL), and 10 patients with bilateral vestibular loss (bVL). In healthy volunteers, up to 5 peaks and troughs were elicited to BC bilaterally. The first two peaks were largest, and amplitude decreased linearly thereafter. In healthy volunteers stimulated with AC clicks and patients with uVL stimulated with either stimulus, the first 2-3 oVEMP waves were significantly larger on the side opposite the healthy/stimulated ear, while the later waves were smaller and had similar amplitude bilaterally. All peaks were absent stimulating ears with no measurable vestibular function. Late peaks were elicited in patients with intact vestibular function regardless of hearing status, demonstrating the vestibular origin of all peaks. Like the clinical n10-p15 waves, the second waves followed a dominant contralateral pathway, while waves 3 onwards appear to have a separate origin and may represent bilateral projections to the extra-ocular muscles.

Motor imagery and execution often indicate a similar trend in the temporal characteristics of movements. This finding supports the notion of functional equivalence, whereby imagery and execution use a common neural representation. However, there is comparatively limited evidence related to the spatial characteristics of movements; no doubt owing to the absence of an actual spatial trajectory during imagery. Therefore, we adapted the trajectory priming paradigm involving an obstacle, where the trajectory adopted in a trial (n) is directly contaminated by a previous trial (n-1). If imagery accurately represents the spatial characteristics, then we would predict a similar priming effect as execution. Participants completed a series of trial blocks under different imagery/execution protocols, where the test trial (n) comprised execution alone, while the previous trial (n-1) involved imagery or execution. Each block comprised pairs of trials with alternate or consistent presentations of a virtual obstacle (O) or no obstacle (N): N-N, N-O, O-N, O-O. For trial n-1 (imagery/execution), there was a more prolonged reaction and movement time for imagery compared execution. Most importantly for trial n (execution), there was an increase in early angular and peak deviation following an obstacle compared to no obstacle in trial n-1, but only when it was execution and not imagery. These findings suggest imagery holds a limited representation of the spatial characteristics, while functional equivalence may be limited to the temporal characteristics.

Myelination is a crucial process in the nervous system. This study aimed to evaluate the progression of myelin sheath development in different brain regions of neonatal rats at distinct developmental stages using Chemical Exchange Saturation Transfer (CEST) 7-T MRI. Male SD rats of different ages (3 days, 1 week, 2 weeks, 3 weeks, 1 month, 2 months) were selected for the study. Advanced in vivo MRI experiments were conducted using a 7-T MRI scanner. Custom MatLab scripts were employed to generate MR images and process the data. Myelin staining was used to assess myelin distribution in various brain regions. Statistical analysis was performed using repeated measures multivariate analysis of variance (MANOVA) and Spearman's rank correlation. The progression of myelination was significantly different in different brain regions (F(5, 30) = 3.34, P < 0.05), with the corpus callosum showing an accelerated rate of myelination. Within the first month alone, there was an increase of 46.1% in myelination (t(35) = 2.29, P < 0.05). The hypothalamus and internal capsule exhibited a more gradual yet consistent increase in myelination over the two-month period, with increases of 47.1% (t(35) = 2.27, P < 0.05) and 39.8% (t(35) = 2.59, P < 0.05), respectively. A substantial positive correlation was found between the MRI-based and histological measurements of myelination (r = 0.31, P < 0.05). This study demonstrates the potential of CEST 7-T MRI as a non-invasive tool for assessing myelination progression and provides insights into the differential myelination rates across various brain regions during early development.

To investigate differences in proprioception using four proprioceptive tests in children with and without hypermobility. Additionally, it was tested if the results on one proprioceptive test predict the results on the other tests. Of the children (8-11years), 100 were classified as normal mobile (Beighton score 0-4) and 50 as hypermobile (Beighton score 5-9). To test proprioception, in the upper extremity the unilateral and bilateral joint position reproduction tasks were used and for the lower extremity the loaded and unloaded wedges task. No differences were found in any of the proprioception tests between the two groups. Estimating the height of the wedges was easier in the loaded position (mean penalty in standing and sitting position, 4.78 and 6.19, respectively). Recalling the elbow position in the same arm resulted in smaller errors compared to tasks reproducing the position with the contralateral arm. Of the four angles used (110°, 90°, 70°, 50°), the position recall in the 90° angle had the smallest position error (1.8°). Correlations between the proprioception tests were weak (Loaded and Unloaded (r 0. 28); Uni and Bilateral (r 0.39), Upper and Lower extremity not significant). No indication of poorer proprioception was found in children with hypermobile joints compared to their normal mobile peers. Loading gives extra information that leads to fewer errors in the wedges task performed while standing, but this effect is independent of joint mobility. Proprioception test outcomes are dependent on the test used; upper extremity results do not predict lower extremity outcomes or vice versa.

The N-methyl-D-aspartate (NMDA) receptors are related to the various functioning of the nervous system. It has been shown that the NR2B subunit plays an important role in neurological hypoxic/ischemic diseases by regulating NMDA receptor function. NR2B tyrosine phosphorylation is also an important regulatory mechanism for NMDA receptor function. However, the mechanism of NR2B tyrosine phosphorylation in hypoxic/ischemic injury is still unclear. Therefore, in the present study, we aimed to further clarify the changes in NR2B tyrosine phosphorylation in hypoxic/ischemic damage in the brain and its relationship with neuronal survival under hypoxic/ischemic conditions. Four types of NR2B tyrosine site mutants (Tyr → Phe at 1252, 1336, and 1472, and all three mutations together, named Y1252F, Y1336F, Y1472F, and Triple) and wild-type plasmids were transfected into HT22 cells. The cells were then exposed to oxygen-glucose deprivation and reoxygenation (OGD/R). NR2B, cell apoptosis-related molecules, and neuronal survival factor CREB-related signaling proteins (CaMKII, ERK, Akt) were measured. Cell viability was assessed using the CCK-8 assay. Cell apoptosis and cell cycle were evaluated using flow cytometry. The death ratio of HT22 cells under OGD conditions was further tested using a live cell analysis platform. The viability of HT22 cells in the Y1252F, Y1336F, Y1472F, Triple mutants, and wild-type groups was elevated. Compared to the wild-type, western blotting and real-time PCR showed that Y1252F, Y1336F, Y1472F, and Triple mutants downregulated the expression of apoptosis factors and upregulated anti-apoptosis factors in the OGD/R model. Flow cytometry and cell cycle analysis demonstrated that Y1252F, Y1336F, Y1472F, and Triple mutants reduced the apoptosis rate. The percentage of cells in the S phase decreased significantly. Live cell analysis illustrated that the Y1252F, Y1336F, Y1472F, and Triple mutants contributed to HT22 cell survival under OGD conditions. Additionally, the Y1252F, Y1336F, Y1472F, and Triple mutants activated the survival signaling pathway. Furthermore, compared to the control group (without plasmid), only the Y1336F, Y1472F, and Triple mutants groups showed significant differences in the above tests. The tyrosine phosphorylation of NR2B at Y1336 and Y1472 plays key roles in hypoxic/ischemic injury. These phosphorylation sites may be potential targets for hypoxic/ischemic neural protection.

A vexing characteristic of motor disability after stroke is that many individuals fail to use their affected arm effectively despite having the capacity to do so, a phenomenon termed arm nonuse. Based on the hypothesis that nonuse is influenced by the competing cognitive demands of many daily activities, we examined the effects of cognitive load on arm choice and motor performance in individuals with stroke using a novel virtual reality paradigm that mimics the demands of real-life visual search, object selection, and reaching to targets. Twenty individuals with single left or right hemispheric chronic stroke (11 left cerebrovascular accident; 9 right cerebrovascular accident) and 10 age-matched neurotypical participants completed the Virtual Reality Arm Choice task, in which they reached for target objects in an array under varied cognitive demand. To manipulate cognitive demand, we varied the semantic similarity of objects in the reaching space and the presence or absence of a secondary task. The results showed reduced use of the paretic arm under increased demand. Under cognitive load, participants with stroke also showed slower reach initiation, slower movements, increased reach curvature, and increased performance differences between the paretic and non-paretic arms. The arm choice of neurotypical individuals was also modulated under cognitive load. These data indicate that cognitive factors influence arm choice and motor performance in naturalistic reaching tasks in individuals with chronic stroke. Performance decrements under cognitive load may in turn influence reduced paretic arm use during daily activities.

Motor skill learning and performance are improved when successful actions are paired with extrinsic rewards, such as money. Positive feedback indicating successful task performance is thought to induce intrinsic reward associated with goal attainment, evidenced by increases in positive affect that correlate with neural reward signaling. However, it is not clear whether the subjective, internal reward processes elicited by positive feedback promote motor learning and performance.Here, we tested the hypothesis that intrinsic reward elicited by positive feedback promotes motor learning and performance. Participants practiced a visuomotor interception task using a joystick, and received feedback during practice indicating success or failure depending on their accuracy. During practice, the accuracy demands were adapted to control and vary the frequency of positive feedback across randomly ordered blocks of practice at either 50%, 70%, or 90%. Performance was measured for each condition as the average accuracy during practice. Learning was estimated by measuring the accuracy pre and post practice in the absence of feedback. We queried participants periodically on their enjoyment of the task to index affective responses to performance feedback.The intrinsic reward elicited by positive feedback, operationalized by the increase in enjoyment immediately following positive versus negative feedback, was positively correlated with learning from pre to post practice. However, increasing the overall amount of positive feedback by lower accuracy demands did not improve performance. These results suggest that experiencing intrinsic reward due to positive feedback benefits motor learning only when it is contingent on good performance.

This study aims to assess fixational eye movements (FEMs) obtained under binocular and monocular viewing in normal individuals across different age groups. We recruited 68 healthy participants divided into Group 1 (children, 3-9 years, n = 20), Group 2 (adolescents, 10-19 years, n = 26), and Group 3 (adults, 20-73 years, n = 22). FEMs were collected using a high-resolution video-based tracker under 3 viewing conditions: binocular viewing (BV), monocular viewing right eye (MV_RE), and monocular viewing left eye (MV_LE). We quantified fixation stability, the frequency, amplitude, and disconjugacy of fixational saccades, and inter-saccadic drift velocity in BV, MV_RE, and MV_LE. We also computed inter-ocular fixation stability under binocular viewing and monocular viewing in the 3 groups. Fixation instability (FI) and fixational saccade amplitudes were higher in Group 1 than in Group 3 whereas inter-saccadic drifts were increased in Group 3. Vergence stability was greater in binocular viewing than in monocular viewing likely due to binocular summation in all groups. However, the fixational saccade amplitude and drift velocity of the right and left eye did not significantly differ across different viewing conditions within each group. Interestingly, the inter-ocular fixation stability ratio and vergence stability showed no significant differences between the groups. In conclusion, FEMs differ across age groups but inter-ocular FEMs are immune to the effects of age and can be a valuable parameter while evaluating FEM abnormalities in diseases like amblyopia.

In psychophysiological research, the use of Virtual Reality (VR) for stimulus presentation allows for the investigation of how perceptual processing adapts to varying degrees of realism. Previous time-domain studies have shown that perceptual processing involves modality-specific neural mechanisms, as evidenced by distinct stimulus-locked components. Analyzing induced oscillations across different frequency bands can provide further insights into neural processes that are not strictly phase-locked to stimulus onset. This study uses a simple perceptual paradigm presenting images of faces and cars on both a standard 2D monitor and in an immersive VR environment. To investigate potential modality-dependent differences in attention, cognitive load, and task-related post-movement processing, the induced alpha, theta and beta band responses are compared between the two modalities. No evidence was found for differences in stimulus-dependent attention or task-related post-movement processing between the 2D conditions and the realistic virtual conditions in electrode space, as posterior alpha suppression and re-synchronization of centro-parietal beta did not differ between conditions. However, source analysis revealed differences in the attention networks engaged during 2D and 3D perception. Midfrontal theta was significantly stronger in laboratory conditions, indicating higher cognitive load than in the VR environment. Exploratory analysis of posterior theta showed stronger responses in VR, possibly reflecting the processing of depth information provided only by the 3D material. In addition, the theta response seems to be generated by distinct neuronal sources under realistic virtual conditions indicating enhanced involvement of semantic information processing and social cognition.

Gait adaptability is crucial for meeting environmental demands, and impaired gait adaptation increases fall risk, particularly in older adults. While prior research exists on older adults' gait adaptation, particularly in perturbation studies, the specific contributions of temporal and spatial adaptation strategies to step length asymmetry (SLA) during split-belt treadmill walking require further examination. This study fills this gap by evaluating how distinct adaptation strategies contribute to SLA in healthy young and older adults. 19 healthy young adults (20.4 ± 1.1 years) and 19 healthy older adults (68.3 ± 8.1 years) walked on a split-belt treadmill requiring their non-dominant leg to move twice as fast as their dominant leg. Repeated measures ANOVA investigated (1) spatial and temporal contributions to SLA, (2) SLA across gait adaptation epochs, and (3) rates of adaptation and deadaptation. Older adults displayed reduced temporal contributions to SLA compared to younger adults (F = 6.42, p = .02, ŋ = .15), but no group differences were observed in spatial contributions to SLA (F = 3.23, p = .08, ŋ = .082). SLA during adaptation and deadaptation did not differ by age group, nor did the rate of adaptation (F = 0.594, p = .45) or deadaptation F = 2.886, p = .09). These findings suggest that while older adults rely less on temporal strategies for gait adaptation, but maintain overall adaptability comparable to younger adults. Findings enhance our understanding of age-related changes in gait adaptation mechanisms and may inform targeted interventions to improve gait adaptability in older populations.

The goal of this study was to determine the effects of applying random vs. constant constraint force to the non-paretic leg during walking on enhanced use of the paretic leg in individuals post-stroke, and examine the underlying brain mechanisms. Twelve individuals with chronic stroke were tested under two conditions while walking on a treadmill: random vs. constant magnitude of constraint force applied to the non-paretic leg during swing phase of gait using a custom designed robotic system. Leg kinematics, muscle activity of the paretic leg, and electroencephalography (EEG) were recorded during treadmill walking. Paretic step length and muscle activity of the paretic ankle plantarflexors significantly increased after walking with random and constant constraint forces. Cortico-cortical connectivity between motor cortices and cortico-muscular connectivity from the lesioned motor cortex to the paretic ankle plantarflexors significantly increased for the random force condition but not for the constant force condition. In addition, individuals post-stroke with greater baseline gait variability showed greater improvements in the paretic step length after walking with random force condition but not with the constant force condition. In conclusion, application of random constraint force to the non-paretic leg may enhance the use of the paretic leg during walking by facilitating cortical drive from the lesioned motor cortex to the paretic ankle plantarflexors. Results from this study may be used for the development of constraint induced locomotor intervention approaches aimed at improving locomotor function in individuals after stroke.

Many athletes with recurrent ankle sprains complain of neurophysiological deficits related to chronic ankle instability (CAI). However, it remains unclear how changes in the corticospinal pathway affect the potential risk of subsequent ankle sprains. The purpose of this study was to investigate whether the corticospinal excitability (input-output properties) and silent period (SP) could be related to the risk of subsequent ankle sprains among athletes. Forty-three male collegiate basketball athletes were enrolled, and 82 ankles were finally sorted into four ankle groups based on symptoms (CAI, sub-CAI, copers, and normal). The neurophysiological data was recorded in both ankles using transcranial magnetic stimulation (TMS) as baseline assessments. Subsequently, we prospectively followed the occurrence of subsequent ankle sprain injuries for 24 months (SG, subsequent ankle sprain group; NSG, non-sprain group). In the baseline assessment, we confirmed that the threshold of the input-output properties in the CAI group was higher than those in the normal group. After the follow-up, 22 ankles sustained subsequent ankle sprains (SGs). We also found that SGs exhibited a significantly longer SP at the middle and high stimulus intensities of TMS compared to NSGs (60 ankles) (middle: p = 0.012, Cohen's d = 0.644, and high: p = 0.020, Cohen's d = 0.590). These findings suggest that a prolonged SP could be a crucial factor affecting subsequent ankle sprains in athletes. To prevent further recurrent sports injuries, neurophysiologic probes, particularly a longer SP, might be a potential assessment tool to return to the field.

Paradoxically visual dependence is reported to increase with age, contributing to falls risk, whereas visual function typically declines. This study assesses the relationship between age, objective and subjective measures of visual function and visual dependence, in healthy young and older adults. Forty-four healthy Young (YA; n = 32; 18 males, aged 26.2 ± 5.3 yrs.) and Older (OA; n = 12; 3 males, aged 62.4 ± 6.7 yrs.) adults were assessed for objective (visual acuity, contrast sensitivity, depth perception, and lower peripheral vision), and subjective visual function (VFQ-25) along with motion sickness susceptibility. Subjective Visual Vertical (SVV) and induced nausea and vection were assessed using the Rod and Disc Test (RDT). Groups were compared using Mann-Whitney U, whilst determinants of SVV variability were evaluated using Multiple regression modelling. Visual acuity (p < 0.01) and contrast sensitivity (p = 0.04) were lower in OA. Visual dependence (SVV tilt errors) was not associated with ageing (p = 0.46). YA experienced greater RDT-induced vection (p = 0.03). Visual acuity and contrast sensitivity accounted for modest proportions of variance in SVV tilt errors (VA; R = 0.14, F(1,42) = 8.00, p < 0.01; β = 6.37) and (CS; R = 0.06, F(1,42) = 3.93, p = 0.05; β = -4.97), respectively. Our findings suggest that subclinical differences in visual acuity and contrast sensitivity contribute to SVV tilt error variability, among both healthy young and older adults. Further studies are needed to define the inter-relationship between age-related visual function, non-visual factors (including vestibular and somatosensory fidelity, activity levels, fear of falling and cognitive function) and visual dependence.

Paraxanthine (PXN) is the main metabolite of caffeine (CAF). PXN supplementation has been shown to increase measures of cognition, memory, reasoning, response time, and sustained attention; however, no preclinical study has compared the effects of PXN with those of CAF. The aim of this study was to compare the effects of PXN and CAF on memory and related biomarkers in rats. The effects of two different doses of PXN (PXN LOW, PXN HIGH), CAF (CAF HIGH), and a control group on cognition (escape latency in the Morris water maze test), neurotransmitters (acetylcholine, dopamine, and gamma-aminobutyric acid), and neurochemicals (BDNF, catalase, glutathione, and cyclic GMP) were analyzed from whole brain samples in young (8 weeks old) and aged (16 months old) rats. Compared to the control group, escape latency improved in PXN LOW, PXN HIGH, and CAF HIGH (all P < 0.05) in young animals, and in PXN HIGH and CAF HIGH in older animals (P < 0.001). PXN HIGH improved escape latency compared to CAF HIGH in both young (P < 0.001) and old animals (P = 0.003). BDNF levels increased in PXN LOW, PXN HIGH, and CAF HIGH (all P < 0.001), with PXN HIGH increasing BDNF to a greater extent compared to CAF HIGH (P = 0.03). PXN HIGH also significantly increased BDNF levels compared to PXN LOW (P < 0.001). All other neurotransmitters and neurochemicals significantly increased in the PXN HIGH and CAF HIGH groups compared to the control. In conclusion, PXN showed greater improvements in cognition and BDNF levels compared to CAF, further substantiating PXN as a nootropic with greater benefits compared to CAF.

The aim of this study is to investigate the effect of induced excitation of the bottom-up pathways at the lateral elbow muscles on local muscle fatigue in the neck region in healthy participants. Eligible participants (n:55) were randomly allocated to an intervention group (n:28) or a control group (n:27). The fatigue of bilateral neck flexor(sternocleidomastoid) and extensor (upper trapezius) muscles was evaluated using surface electromyography, at baseline and immediately post-intervention during a neck flexor and extensor endurance test respectively. Excitation of the bottom-up pathways was performed at multiple lateral elbow muscles in the intervention group by using a temporal summation protocol of mechanical pain, and the pressure pain threshold was determined once in each of the multiple lateral elbow muscles in the control group. Linear mixed model analyses were performed for each outcome measure to evaluate changes over time and within- and between-group differences. No significant "group X time" interaction effects were detected for any of the outcome measures. Significant main effects for time was found for "amplitude over time" of the left upper trapezius (p:0.003) and right sternocleidomastoid muscle (p: 0.013), and for "amplitude changes" of the left upper trapezius muscle (p:0.021). Significant within-group changes were identified in some outcomes in the control group: increased "amplitude over time" of the right sternocleidomastoid muscle (p:0.024) and decreased "amplitude changes" of the left upper trapezius muscle (p:0.024), decreased "normalized median frequency slope over time" of the left UT (p: 0.013). There were no significant within-group changes in the intervention group. No significant between-group differences for any of the outcome measures were found. This study shows no effect of the induction of excitation of the bottom-up pathways at the lateral elbow muscles on the neck muscles' fatigue characteristics compared to a control intervention. Clinical Trial Number: NCT05146960. Date of Registration: December 7, 2021.

The possible cognitive effect of sense of agency (SoA) has attracted increasing attention. Previous findings suggest that SoA has an effect on action control, time perception, and memory. Here we investigated whether SoA can also influence decision-making. We conducted two experiments, in which we induced high or low predictability by manipulating the contingency between keypresses (action) and ball movements (effect), before assessing SoA and risk-taking (in Experiment 1); and induced both predictability and short or long time delay of action-effect, before assessing SoA, risk-taking, and intertemporal decision-making (in Experiment 2). Higher predictability increased SoA and promoted risk-taking, but did not impact intertemporal decision-making; Shorter delay increased SoA and promoted Larger-Later options, but did not impact risk-taking decision-making. While our findings suggest that some decision-making processes are affected by the same factors as SoA is, we did not find any evidence for any direct impact of SoA on decision-making.

The purpose of our study was to evaluate the accuracy with which classification algorithms could distinguish among standing postures based on center-of-pressure (CoP) trajectories. We performed a secondary analysis of published data from three studies: Study A) assessment of balance control on firm or foam surfaces with eyes-open or closed, Study B) quantification of postural sway in forward-backward and side-to-side directions during four standing-balance tasks that differed in difficulty, and Study C) an evaluation of the impact of two modes of transcutaneous electrical nerve stimulation on balance control in older adults. Three classification algorithms (decision tree, random forest, and k-nearest neighbor) were used to classify standing postures based on the extracted features from CoP trajectories in both the time and time-frequency domains. Such classifications enable the identification of differences and similarities in control strategy. Our results, especially those involving time-frequency features, demonstrated that distinct CoP trajectories could be identified from the extracted features in all conditions and postures in each study. Although the overall classification accuracy was similar using time-frequency features (~ 86%) for the three studies, there were substantial differences in accuracy across conditions and postures in Studies A and B but not in Study C. Nonetheless, the models were far superior to the published results with conventional metrics in distinguishing between the conditions and postures. Moreover, a Shapley Additive exPlanation analysis was able to identify the most important features that contributed to the classification performance of the models.

Recent studies highlight a persistent increase in subsequent injury risk following a sport-related concussion (SRC) despite clinical recovery. However, markers of persistent alterations in sensorimotor integration have yet to be identified. One possibility is that compensatory adaptation following SRC may only be unmasked during transient periods of high task complexity in specific sensorimotor circuits. The current study used short-latency afferent inhibition (SAI) to investigate the long-term sequelae of sport-related concussion (SRC) in different short-latency sensorimotor circuits converging in the motor cortex. Specific sensorimotor circuits sensitive to posterior-anterior current with a positive phase lasting 120µs (PA) and anterior-posterior current with a positive phase lasting 30µs (AP) were assessed using controllable pulse parameter transcranial magnetic stimulation (cTMS) while young adults with and without a history of SRC were at rest or responded to valid and invalid sensorimotor cues. SAI was quantified as the ratio of the motor-evoked potential (MEP) elicited by peripherally conditioned cTMS stimuli to the unconditioned MEP for each cTMS configuration. Individuals with a SRC history demonstrated persistent adaptation in AP SAI, but only in response to invalid cues. Persistent adaptation in AP SAI was not apparent at rest or during simple sensorimotor transformations in response to valid cues. PA SAI demonstrated similar responses at rest and in response to both valid and invalid cues, regardless of SRC history. AP-sensitive sensorimotor circuits may mark the long-term SRC sequelae and the increased susceptibility to momentary breakdowns in sensorimotor integration during periods of high cognitive-motor demands.

We conducted an fMRI study to investigate the neural basis of bimanual coordination, which is fundamental to upper extremity control. Considering bimanual movement as a combination of bimanual chord formation and sequence control, we hypothesized that the areas with the learning effect of both chord formation and sequence learning are critical in bimanual coordination. We adopted the serial reaction time task (SRTT) to test this hypothesis. Thirty-five healthy right-handed volunteers practiced visually cued bimanual SRTT, including the "mirror" and more complex "parallel" modes of random movements or repeating fixed sequences to separately depict the neural substrates of bimanual posture control for chord formation and those of sequence. Random movements' reaction time (RT) continuously declined, indicating learning of bimanual chord formation. The RT in the sequential condition declined more rapidly than in the random condition, confirming sequence learning. The parallel random conditions evoked a more prominent learning-related decrease of task-related activation in the left M1 and cerebellar vermis than the less difficult mirror random conditions. The left M1 showed learning-related enhancement of functional connectivity with the anterior cingulate cortex during the parallel random conditions compared with the mirror random conditions. Thus, the left M1, anterior cingulate cortex, and cerebellar vermis are related to learning bimanual chord formation. The left M1 and cerebellar vermis also showed sequence-specific learning-related activity increments more prominent in the parallel mode than in the mirror mode. Thus, the left M1 and cerebellar vermis are critical in the bimanual motor learning network.

Methamphetamine (METH) has well-documented long-term effects on the brain, including increased psychomotor activity and behavioral sensitization. However, its immediate effects on the brain's reward system following acute exposure, which may contribute to the development of addiction, are less understood. This study aimed to investigate the effects of acute METH on brain oscillations in the nucleus accumbens of C57BL/6 mice. Mice in the METH group received 5 mg/kg of METH for 5 days during the conditioning phase, followed by an 8-day abstinence period. Afterward, they underwent a 6-minute tail suspension test and were given a 1 mg/kg METH challenge. Local field potential (LFP) data were analyzed for percent total power, mean frequency indices, and phase-amplitude coupling (PAC) to assess the neural effects of METH exposure across these phases. A reduction in theta power was observed across the conditioning, abstinence, and challenge phases of METH exposure. The subsequent METH challenge enhanced gamma oscillations, and PAC analysis revealed a consistent theta-gamma coupling index during both the METH administration and challenge phases. It highlights the sensitivity of the reward system to intense, short-term drug exposure, providing new insights into how acute neural stimulation may contribute to the development of addictive behaviors, reinforcing the brain's vulnerability to drug-induced changes in neural circuitry.

Animal studies have shown that exposure of newborns to general anesthesia drugs can lead to neurodegenerative diseases and subsequent decline in learning and memory abilities. The neurotoxicity of general anesthesia drugs can also occur in the fetus. Therefore, in order to investigate the effect of the Long non-coding RNA(LncRNA)-LIN-microRNA(miRNA)-9-Dopamine receptor D2(DRD2) regulatory network on the development of the neuronal system after the inhalation of the anesthetic sevoflurane, RT-qPCR was used to detect the mRNA levels of LncRNA-LIN, miRNA-9, and DRD2. A dual-luciferase reporter system was used to detect the relationship between LncRNA-LIN and miRNA-9, and miRNA-9 and DRD2. Western blotting and immunofluorescence staining was employed to detect the protein levels of DRD2 and cleaved caspase-3. Flow cytometry was carried out to detect the number of apoptotic cells. The escape latency, swimming distance, and platform crossing times were analyzed using the Morris water maze. The results showed that, after treatment with sevoflurane, the mRNA levels of LncRNA-LIN and DRD2, the expression levels of the DRD2 protein, and the number of neuronal levels of DRD2 were significantly decreased, whereas the expression levels of miRNA-9 and the cleaved caspase-3 protein and neuronal apoptosis were significantly increased. miR-9 knockdown revealed that miRNA-9 regulated DRD2 expression and affected the function of mouse neuronal cells. In turn, LncRNA-LIN overexpression indicated that LncRNA-LIN regulated miR-9 and affected the function of mouse neuronal cells. The present results demonstrated that the LncRNA-LIN-miRNA-9-DRD2 regulatory network is involved in the effects of the inhalation anesthetic sevoflurane on neuronal system development.