Experimental Brain Research最新文献

The controlled release of grasping forces underlies skilled dexterous interactions with objects. While declines in force generation and maintenance are well documented in people with Parkinson's disease (PwPD), limited data exist related to how PD impacts the motor control of grasping force release. The aim of this project was to determine how PD impacts grip force release relative to the generation and maintenance of force. It was hypothesized that PwPD would exhibit global deficits in force control relative to controls but would perform disproportionately worse during the controlled release of grip force. Ten PwPD and 10 age-matched controls completed a force-tracking paradigm requiring grip force generation, maintenance, and release. Compared to controls, PwPD were less accurate (i.e. less time within target range), had greater error (i.e. greater relative root mean squared error), and had more trial-to-trial variability in error during grip force release. Ongoing studies are examining the potential neural mechanism(s) underlying of force release impairments in PD, and the relationships between PD severity, manual dexterity, and force release declines.

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.

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.

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.

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.

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.

This study investigates how the combination of robot-mediated haptic interaction and cerebellar neuromodulation can improve task performance and promote motor skill development in healthy individuals using a robotic exoskeleton worn on the index finger. The authors propose a leader-follower type of mirror game where participants can follow a leader in a two-dimensional virtual reality environment while the exoskeleton tracks the index finger motion using an admittance filter. The game requires two primary learning phases: the initial phase focuses on mastering the pinching interface, while the second phase centers on predicting the leader's movements. Cerebral transcranial direct current stimulation (tDCS) with anodal polarity is applied to the subjects during the game. It is shown that the subjects' performance improves as they play the game. The combination of tDCS with finger exoskeleton significantly enhances task performance. Our research indicates that modulation of the cerebellum during the mirror game improves the motor skills of healthy individuals. The results also indicate potential uses for motor neurorehabilitation in hemiplegia patients.

Suffering an acute asymmetry in vestibular function (i.e., vestibular neuritis) causes increased sway. Non-causal studies report associations between lateral semicircular canal function and balance ability, but direct links remain controversial. We investigate the immediate effect on body sway after unilateral vestibulo-ocular reflex (VOR) gain down adaptation simulating acute peripheral vestibular hypofunction. Eighteen healthy adults, mean age 27.4 (± 12.4), stood wearing an inertial measurement device with their eyes closed on foam before and after incremental VOR gain down adaptation to simulate mild unilateral vestibular neuritis. Active head impulse VOR gain was measured before and after the adaptation to ensure VOR gain adaptation. Percentage change for VOR gain was determined. Sway area was compared before and after VOR adaptation. VOR gain decreased unilaterally exceeding meaningful change values. Sway area was significantly greater immediately after VOR gain down adaptation, but quickly returned to baseline. In a subset of subjects VOR gain was re-assessed and found to remain adapted despite sway normalization. These results indicate that oculomotor adaptation targeting the lateral semicircular canal VOR pathway has an immediate, albeit transient increase in body sway. Rapid return of body sway to baseline levels suggests dynamic sensory reweighting between vestibular and somatosensory inputs to resolve the undesirable increased body sway.

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.

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.