Experimental Brain Research最新文献

Neuropathic pain is a chronic pain condition that is primarily caused by underlying neurological damage and dysfunction. Recent studies have identified microRNAs (miRNAs) as a key factor in the treatment of neuropathic pain. To explore the effects of miR-133a-3p on neuroinflammation and neuropathic pain via GTP cyclohydrolase (GCH1), and its underlying mechanisms. In vitro models were constructed using BV-2 cells that had been treated with lipopolysaccharide, followed by treatment with either miR-133a-3p mimic or GCH1 viral knockdown/overexpression. The expression of miR-133a-3p and GCH1 in BV-2 cells was quantified by RT-qPCR. The degree of neuroinflammation was quantified using an enzyme-linked immunosorbent assay (ELISA). The targeting relationship between miR-133a-3p and GCH1 was confirmed by western blot and dual luciferase reporter assay. A chronic constriction injury model was employed to induce neuropathic pain in rats, and the mechanical withdrawal threshold (MWT) was quantified. Immunofluorescence was used to demonstrate alterations in microglial cells. The expression of miR-133a-3p was found to be decreased in lipopolysaccharide-induced BV-2 cells. The overexpression of miR-133a-3p was observed to inhibit the expression of IL-1β, IL-6, TNF-α and iNOS, which was attributed to a reduction in GCH1.Nevertheless, OE-GCH1 could partially reverse the downregulation by miR-133a-3p of the expression of inflammatory factors. In animal experiments, intrathecal injection of AVV-miR-133a-3p was observed to alleviate mechanical nociceptive abnormalities induced by activated microglia. Furthermore, miR-133a-3p ameliorated neuroinflammation in the spinal cord of chronic constriction injury rats. In summary, miR-133a-3p improves neuroinflammation and neuropathic pain by binding to GCH1. The binding of miR-133a-3p to GCH1 has been demonstrated to improve neuroinflammation and neuropathic pain.This insight will facilitate the development of new methods to effectively treat neuropathic pain.

Spinal evoked motor responses (SEMR) are utilized in longitudinal pre-clinical and human studies to reflect the in-vivo physiological changes in neural networks secondary to a spinal cord injury (SCI) or neuro-rehabilitative treatments utilizing epidural stimulation (ES). However, it remains unknown whether the repeated ES exposure during SEMR testing itself modulates spinal cord physiology and accompanying SEMR characteristics. To answer this, ES was delivered to the cervical spinal cord using standard stimulation paradigms during multiple SEMR data acquisition sessions (~ 17 h spanning across 100 days) in ten healthy adult rats. Cervical SEMR at rest and forelimb muscle activity during reaching and grasping task were collected before and after 100 days. We noted a persistent increase in SEMR activity relative to baseline, with prominent changes in the mono and poly-synaptic components of SEMR. The findings indicate increased spinal cord excitability. Increased spinal cord excitability translated into increased forelimb muscle activation during the reaching and grasping task. For the majority of SEMR and muscle activity increase, effect size was large or very large. Cervical SEMR are amenable to modulation by routine ES testing protocols, with prominent changes in the mono and poly-synaptic components of SEMR. Since repeated stimulation during multiple testing alone increases cord excitability, we recommend (1) SEMR may be used with caution to infer the physiological status of the spinal circuitry (2) utilizing appropriate control groups and motor behavioral correlates for meaningful functional interpretation in longitudinal neuromodulation studies involving multiple SEMR testing sessions following a SCI.

The purpose of this study was to determine whether the intermittent adaptation to pelvis perturbation load enhances retention of improved weight transfer and generalization of motor skills from treadmill to overground walking, compared with effects of the continuous adaptation. Fifteen individuals with incomplete SCI participated in two experimental sessions. Each session consisted of (1) perturbed treadmill walking with either intermittent (i.e., interspersed 3 intervals of no perturbation) or continuous (no interval) adaptation to novel walking patterns induced by external pelvis perturbation and (2) instrumented treadmill walking and overground walking before, immediately, and 10-min post perturbed treadmill walking. The external pulling force was applied to the pelvis towards the lateral side while the leg touched the treadmill belt. Participants showed a retention of improved mediolateral weight transfer (P = 0.002) and of enhanced activation of hip abductor (P = 0.016) and calf muscles (P < 0.05) in the intermittent condition, whereas the continuous condition did not (P ≥ 0.05). After the perturbed treadmill walking practice, participants exhibited increased mediolateral weight transfer during overground walking (P = 0.04) and enhanced propulsion (P = 0.047) during the instrumented treadmill walking for the intermittent condition, whereas the continuous condition did not show significant changes (P ≥ 0.13). Further, the intermittent condition induced a greater increase in overground walking speed than the continuous condition did (P = 0.002). In conclusion, intermittent adaptation to the pelvis perturbation load during treadmill walking can promote retention and generalization of motor learning for improving walking and balance in people with incomplete SCI.

Executive function (EF) is improved following a single bout of exercise and impaired when an individual experiences mental fatigue (MF). These performance outcomes have been linked to a bi-directional change in cerebral blood flow (CBF). Here, we sought to determine whether MF-induced by a sustained vigilance task (i.e., psychomotor vigilance task: PVT) is mitigated when preceded by a single bout of exercise. Participants completed 20-min single bouts of active exercise (cycle ergometry involving volitional muscle activation), passive exercise (cycle ergometry involving a mechanical flywheel) and a non-exercise control intervention. EF was assessed pre- and post-intervention via the antisaccade task. Following each intervention, a 20-min PVT was completed to induce and assess MF, and transcranial Doppler ultrasound of middle cerebral artery velocity (MCAv) was used to estimate intervention- and PVT-based changes in CBF. Active and passive exercise provided a post-intervention reduction in antisaccade reaction times; that is, exercise benefitted EF. Notably, however, frequentist and Bayesian statistics indicated the EF benefit did not mitigate MF during the PVT. As well, although exercise (active and passive) and the PVT respectively increased and decreased CBF, these changes were not correlated with behavioral measures of EF or MF. Accordingly, a postexercise EF benefit does not mitigate MF during a sustained vigilance task and a bi-directional change in CBF does not serve as a primary mechanism associated with EF and MF changes. Such results provide a framework for future work to explore how different exercise types, intensities and durations may impact MF.

Gentamicin is a bactericidal aminoglycoside antibiotic that broadly targets Gram-negative microbes. Both human and animal studies have shown that administration of gentamicin is ototoxic by several routes of administration and results in sensorineural hearing loss due to damaged hair cell at the base of the cochlea. However, gentamicin is also administered intranasally to treat sinusitis in humans, but no animal studies have examined ototoxicity of gentamicin administered via this route. We hypothesized that intranasal irrigation of gentamicin will result in ototoxicity and impaired auditory function similar to systemic delivery. We investigated this hypothesis in Sprague-Dawley rats that received intranasal irrigations of gentamicin or saline from postnatal day (P) 21-31. We examined auditory function by assessing brainstem auditory evoked potentials in response to both broadband clicks and pure tone-pips (4, 8, 16, 24 and 32 kHz) on P41. We found significant changes in auditory function in gentamicin-exposed animals. Specifically, gentamicin-exposed animals had significantly higher thresholds in response to both clicks and tone-pips. In response to broadband clicks, there were no changes in latency for waves I through IV. However, we found significantly longer wave and interwave latencies for all waves in response to the 24 kHz tone-pip. Together, these findings suggest that intranasal administration of gentamicin results in impaired auditory function consistent with other routes of delivery.

The ability to seamlessly switch between different visuomotor mappings is critical for effective interactions in a dynamic environment. This experiment aimed to establish the contributions of implicit (unconscious) processes to the concurrent adaptation of one's reaches to two opposing, randomly switching, novel visuomotor mappings (i.e., dual visuomotor adaptation). 59 right-handed participants were divided into two groups, a Dual adaptation group and a Single adaptation group, and trained to reach when small visuomotor distortions were introduced. The Dual group trained to reach when cursor feedback was rotated (i) 20° clockwise (CW) relative to hand motion when a target was displayed in the left visual workspace and (ii) 20° counterclockwise (CCW) relative to hand motion when a target was displayed in the right visual workspace. The Single group trained to reach with just one 20° cursor rotation (CW or CCW) in both visual workspaces. Results revealed that all participants adapted their reaches to the distorted cursor feedback. For all groups, visuomotor adaptation arose implicitly, in the absence of explicit (conscious strategy) contributions. However, the Dual group demonstrated significantly less implicit adaptation than participants who trained with a Single CW distortion, even after additional reach training trials. Together, these results indicate a role for implicit processes in simultaneously updating one's reaches to two small visuomotor mappings.

Memory intrusion is a characteristic of posttraumatic stress disorder manifesting as involuntary flashbacks of negative events. Interference of memory reconsolidation using cognitive tasks has been employed as a noninvasive therapy to prevent subsequent intrusive retrieval. The present study aims to test whether physical activity, with its cognitive demands and unique physiological effects, may provide a novel practice to reduce later involuntary retrieval via the reconsolidation mechanism. In addition, the study investigates the EEG representation of neural function in interpreting the interplay of intrusion and recognition. Eighty-seven participants were tested on successive sessions comprised encoding (Day 0), reconsolidation (24-hr) and priming retrieval (Day 7) in a between-subject design with random assignment to 3 different groups: whole-body exercise, sensorimotor engagement and sitting groups. Of the key results, when involuntary retrieval was subsequently triggered by relevant stimuli, reduced subjective recognition was observed, and working memory maintenance was shortened, indicated by shorter Negative Slow Wave duration. The study implicates the potential neurophysiological mechanism of cognitive and behavioral interventions, specifically those aimed at reducing intrusion frequency through the reconsolidation mechanism; these are proposed to facilitate accelerated recovery from involuntary memories.

Many motor tasks are comprised of sequentially linked action phases, as when reaching for, lifting, transporting, and replacing a cup of coffee. During such tasks, discrete visual, auditory and/or haptic feedback are typically associated with mechanical events at the completion of each action phase, as when breaking and subsequently making contact between the cup and the table. An emerging concept is that important sensorimotor control operations, that affect subsequent action phases, are centred on these discrete multisensory events. By predicting sensory feedback at the completion of action phases, and comparing with the actual feedback that arises, task performance can be continuously monitored. If errors are detected, the sensorimotor system can quickly respond with task-protective corrective actions. The aim of this study was to investigate how discrete multisensory feedback at the completion of action phases are used in these control operations. To investigate this question, 42 healthy human participants (both male and female) performed a visually guided sequential reaching task where auxiliary discrete visual, auditory and/or haptic feedback was associated with the completion of action phases. Occasionally however, this feedback was removed in one or two modalities. The results show that although the task was visually guided, its control was critically influenced by discrete auditory and haptic feedback. Multisensory integration effects occurred, that enhanced the corrective actions, when auditory feedback was unexpectedly removed along with haptic or visual feedback. This multisensory enhancement may facilitate the ability to detect errors during sequential actions and amplify task-protective corrective actions.

Subclinical neck pain (SCNP) is a subset of the recurrent neck pain population for which individuals have not received treatment. Individuals with SCNP have been shown to have altered cerebellar processing. The cerebellum integrates sensorimotor information to refine and update internal models necessary for reaching movements. The impact of SCNP on sensorimotor integration and motor behavior has not been fully elucidated in the context of goal-directed reaching movements. Therefore, our study investigated the role of SCNP on these processes by comparing upper limb reaching movements to controls with the dominant and non-dominant hands using light and heavy styli in the vertical plane. The results show that those with SCNP have quicker reaction times and end their primary movement closer to the target compared to controls. This is likely to allow for greater central visual processing, thus illustrating the tendency for those with SCNP to rely more on visual feedback in order to compensate for an altered body schema.

Although flexible and portable virtual reality technologies have simplified measuring participants' perception of acoustic space, their clinical adoption remains limited, often lacking ecological fidelity. In clinical practice, participants are typically instructed to remain still when testing sound localization, whereas head movements are crucial in daily life. Additionally, assessing spatial hearing extends beyond measuring accuracy to include meta-cognitive evaluations like perceived effort and confidence, which are rarely adopted. Our study hypothesized that allowing head movement during sound localization, compared to a static head condition, would reduce perceived listening effort and enhance confidence in normal hearing participants. Conducted across three audiology and otology hospital services in Northern Italy, the study involved personnel inexperienced with our VR equipment. This also tested the feasibility and usability of our VR approach in clinical settings. Results showed that head movements reduced subjective effort but did not significantly affect perceived confidence. However, during the active condition, participants reporting higher confidence exhibited less head movement and explored the space less. Similarly, those with less head movement reported lower listening effort. These findings underscore the importance of allowing natural posture to capture the full extent of spatial hearing capabilities and the value of including metacognitive evaluations in assessing performance. Our use of affordable, off-the-shelf VR equipment effectively measured spatial hearing in clinical settings, providing a flexible alternative to current static systems. This approach highlights the potential for more dynamic and comprehensive assessments in clinical audiology.