Effects of a novel regimen of repetitive transcranial magnetic stimulation (rTMS) on neural remodeling and motor function in adult male mice with ischemic stroke.

Neuroinflammation caused by excessive microglial activation plays a key role in the pathogenesis of ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulatory technique that has recently been reported to regulate microglial functions and exert anti-inflammatory effects. The intermittent burst stimulation (iTBS) regimen in rTMS improves neuronal excitability. However, whether iTBS exerts its anti-inflammatory effects by stimulating neurons and thereby modulating microglial polarization remains unclear. Motor function was assessed after 1 week of rTMS (iTBS regimen) treatment in adult male mice with occlusion/reperfusion of the middle cerebral artery (MCAO/r) injury. We also investigated the molecular biological alterations associated with microglial polarization using a cell proliferation assay, multiplex cytokine bioassays, and immunofluorescence staining. iTBS regimen can improve balance and motor coordination function, increase spontaneous movement, and improve walking function in mice with early cerebral ischemia injury. Expression levels of IL-1ß, TNF-α, and IL-10 increased significantly in mice with MCAO injury. Especially, rTMS significantly increased the number of proliferating cells in the infarcted cortex. The fluorescence intensity of MAP2 in the peri-infarct area of MCAO injured mice was low, but the signal was broader. Compared with MCAO group, the fluorescence intensity of MAP2 in rTMS group was significantly increased. rTMS inhibited pro-inflammatory M1 activation (Iba1+/CD86+) and improved anti-inflammatory M2 activation (Iba1+/CD206+) in the peri-infarct zone, thus significantly changing the phenotypic ratio M1/M2. rTMS improves motor dysfunction and neuroinflammation after cerebral I/R injury in mice by regulating microglial polarization.

Adolescent chemogenetic activation of dopaminergic neurons leads to reversible decreases in amphetamine-induced stereotypic behavior.

Chronic perturbations of neuronal activity can evoke homeostatic and new setpoints for neurotransmission. Using chemogenetics to probe the relationship between neuronal cell types and behavior, we recently found reversible decreases in dopamine (DA) transmission, basal behavior, and amphetamine (AMPH) response following repeated stimulation of DA neurons in adult mice. It is unclear, however, whether altering DA neuronal activity via chemogenetics early in development leads to behavioral phenotypes that are reversible, as alterations of neuronal activity during developmentally sensitive periods might be expected to induce persistent effects on behavior. To examine the impact of developmental perturbation of DA neuron activity on basal and AMPH behavior, we expressed excitatory hM3D(Gq) in postnatal DA neurons in TH-Cre and WT mice. Basal and CNO- or AMPH-induced locomotion and stereotypy was evaluated in a longitudinal design, with clozapine N-oxide (CNO, 1.0 mg/kg) administered across adolescence (postnatal days 15-47). Repeated CNO administration did not impact basal behavior and only minimally reduced AMPH-induced hyperlocomotor response in adolescent TH-CrehM3Dq mice relative to WThM3Dq littermate controls. Following repeated CNO administration, however, AMPH-induced stereotypic behavior robustly decreased in adolescent TH-CrehM3Dq mice relative to controls. A two-month CNO washout period rescued the diminished AMPH-induced stereotypic behavior. Our findings indicate that the homeostatic compensations that take place in response to chronic hM3D(Gq) stimulation during adolescence are temporary and are dependent on ongoing chemogenetic stimulation.

The association between physical activity and neck circumference with cardiovascular disease risk in older wheelchair users.

OBJECTIVE: To examine the association between physical activity, neck circumference, and cardiovascular disease risk in older wheelchair users. DESIGN: A cross-sectional study. SUBJECTS/PATIENTS: Sixty-one Korean wheelchair users aged 50 years and older. METHODS: Physical activity was assessed using a self-administered questionnaire. Neck circumference was measured with a tape ruler. Cardiovascular disease risk was evaluated by calculating the Framingham risk score (FRS) for estimating 10-year cardiovascular disease risk, which was classified as low-moderate (19% or less) or high risk (20% or more). RESULTS: The FRS for 10-year cardiovascular disease risk was inversely related to physical activity (beta [SE] = -0.213 (0.103), p = 0.043) and positively related to neck circumference (beta [SE] = 1.331 ± 0.419, p = 0.003). Binary logistic regression showed that those with low physical activity (odds ratio [95% confidence interval] = 4.256 (1.188~15.243), p = 0.026) or a large neck circumference (odds ratio [95% confidence interval] = 3.645 (1.172~11.338), p = 0.025) had a higher risk for high cardiovascular disease risk compared with those with high physical activity or normal neck circumference. CONCLUSION: The current study findings suggest that an intervention targeting physical inactivity and upper-body obesity should be implemented to reduce cardiovascular disease risk in older wheelchair users.

Assessment of EN-RAGE, sRAGE, and its isoforms: cRAGE, esRAGE in obese patients treated by moderate caloric restriction combined with physical activity conducted in hospital condition.

BACKGROUND: AGEs, their receptor (RAGE), and the extracellular newly identified receptor for AGEs product-binding protein (EN-RAGE) are implicated in the pathogenesis of inflammation. AIM: We analyzed serum EN-RAGE, soluble RAGE (sRAGE), and their isoforms: endogenous secretory - esRAGE and cleaved - cRAGE concentrations in lean controls (n = 74) and in patients with obesity (n = 71) treated for three weeks with moderate calorie restriction (CR) combined with physical activity in a hospital condition. METHODS: Using the ELISA method, serum sRAGE, esRAGE, and EN-RAGE were measured before and after CR. RESULTS: The serum level of sRAGE and esRAGE in patients with obesity was lower than that in non-obese individuals, contrary to cRAGE. EN-RAGE concentration was about three times higher in obese patients. Gradually, a rise in BMI resulted in sRAGE, esRAGE reduction, and EN-RAGE increase. The sRAGE concentration was sex-dependent, indicating a higher value in lean men. A moderate negative correlation was observed between BMI and all RAGE isoforms, whereas EN-RAGE displays a positive correlation. CR resulted in an expected decrease in anthropometric, metabolic, and proinflammatory parameters and EN-RAGE, but no RAGE isoforms. The ratio EN-RAGE/sRAGE was higher in obese humans than in control and was not modified by CR. CONCLUSION: Obesity decreases sRAGE and esRAGE and increases EN-RAGE concentration. Moderate CR and physical activity by decreasing inflammation reduces EN-RAGE but is insufficient to increase sRAGE and esRAGE to the extent observed in lean patients. EN-RAGE instead of sRAGE could be helpful to indicate a better outcome of moderate dietary intervention in obese subjects.

Changes in motor behavior and lumbar motoneuron morphology following repeated chlorpyrifos exposure in rats.

Chlorpyrifos is an organophosphate pesticide associated with numerous health effects including motor performance decrements. While many studies have focused on the health effects following acute chlorpyrifos poisonings, almost no studies have examined the effects on motoneurons following occupational-like exposures. The main objective of this study was to examine the broad effects of repeated occupational-like chlorpyrifos exposures on spinal motoneuron soma size relative to motor activity. To execute our objective, adult rats were exposed to chlorpyrifos via oral gavage once a day, five days a week for two weeks. Chlorpyrifos exposure effects were assessed either three days or two months following the last exposure. Three days following the last repeated chlorpyrifos exposure, there were transient effects in open-field motor activity and plasma cholinesterase activity levels. Two months following the chlorpyrifos exposures, there were delayed effects in sensorimotor gating, pro-inflammatory cytokines and spinal lumbar motoneuron soma morphology. Overall, these results offer support that subacute repeated occupational-like chlorpyrifos exposures have both short-term and longer-term effects in motor activity, inflammation, and central nervous system mechanisms.

Social setting interacts with hyper dopamine to boost the stimulant effect of ethanol.

Alcohol consumption occurring in a social or solitary setting often yields different behavioural responses in human subjects. For example, social drinking is associated with positive effects while solitary drinking is linked to negative effects. However, the neurobiological mechanism by which the social environment during alcohol intake impacts on behavioural responses remains poorly understood. We investigated whether distinct social environments affect behavioural responses to ethanol and the role of the dopamine system in this phenomenon in the fruit fly Drosophila melanogaster. The wild-type Canton-S (CS) flies showed higher locomotor response when exposed to ethanol in a group setting than a solitary setting, and there was no difference in females and males. Dopamine signalling is crucial for the locomotor stimulating effect of ethanol. When subjected to ethanol exposure alone, the dopamine transport mutant flies fumin (fmn) with hyper dopamine displayed the locomotor response similar to CS. When subjected to ethanol in a group setting, however, the fmn's response to the locomotor stimulating effect was substantially augmented compared with CS, indicating synergistic interaction of dopamine signalling and social setting. To identify the dopamine signalling pathway important for the social effect, we examined the flies defective in individual dopamine receptors and found that the D1 receptor dDA1/Dop1R1 is the major receptor mediating the social effect. Taken together, this study underscores the influence of social context on the neural and behavioural responses to ethanol.

Making precise movements increases confidence in perceptual decisions.

Perceptual decision-making often lacks explicit feedback, making confidence in our choices pivotal for guiding subsequent actions. Recent studies have highlighted the role of motor responses in modulating decision confidence. Two competing mechanisms have been proposed to elucidate this phenomenon. The "fluency hypothesis" posits that the ease and smoothness of executing a motor response can serve as a cue to enhance retrospective confidence. Conversely, the "monitoring hypothesis" suggests that the extent of action monitoring during response selection may boost retrospective confidence, with heightened monitoring potentially offsetting response fluency. We conducted a pre-registered experiment to directly test these hypotheses. Participants engaged in a perceptual task involving the discrimination of Gabor patch orientation. Perceptual responses required high or low motor precision, manipulated by the size of target circles that participants had to reach with the computer mouse to provide a response. Contrary to the "fluency hypothesis", our results showed that, in trials requiring higher precision (utilizing small circles), participants reported higher confidence levels compared to trials with less demanding responses (involving larger circles). Importantly, this increase in confidence did not coincide with any change in perceptual accuracy. These findings align with the "monitoring hypothesis," suggesting that the degree of action monitoring during response execution can indeed influence retrospective decision confidence.

The effects of MEPaL on oxidative stress and motor function in the rats affected by prenatal hypoxia.

BACKGROUND AND OBJECTIVES: Maternal hypoxia disrupts neural development and subsequently leads to cerebral palsy and epilepsy in newborns. Hypoxia plays a role in neurodegeneration by increasing oxidative stress. Pistacia atlantica is known as an important antioxidant, and its anti-inflammatory and antioxidant effects have been shown in various studies. This study aims to investigate the effects of methanolic extract of P. atlantica leaves (MEPaLs) on the oxidative parameters in the serum of rats affected by maternal hypoxia. MATERIAL AND METHODS: In this study, eight pregnant rats were used. The newborns were divided into four groups, including the control and the hypoxia groups, which are affected by maternal hypoxia, hypoxia + MEPaL 100 mg/kg, and hypoxia + MEPaL 150 mg/kg. MEPaL was injected (i.p) for 21 days into the neonatal rats after the lactation period. Hypoxia was induced by keeping pregnant rats in a hypoxic chamber with 7% oxygen and 93% nitrogen intensity for 3 h on the 20th day of pregnancy. Behavioral changes were measured using open-field and rotarod tests. Finally, biomarkers of oxidative stress, nitric oxide (NO), glutathione (GSH), GSSG, TAS, TOS, and oxidative stress index (OSI) were measured in the experimental groups. RESULTS: Behavioral results showed that the anxiety behavior in the hypoxia group increased, but the motor activity (moved distance and movement speed) decreased. Moreover, the amount of time spent maintaining balance on the rotarod rod was significantly decreased in the hypoxia group. The concentration of NO in the group of hypoxia + MEPaL 100 mg/kg showed a significant decrease, and MEPaL 100, and 150 mg/kg + hypoxia also increased the concentration of GSH and decreased GSSG. In addition, MEPaL100 and 150 mg/kg caused a significant increase in the ratio of GSH to GSSG and decreased OSI and total oxidant capacity. CONCLUSIONS: Oxidative stress increased in the rats affected by maternal hypoxia and may be the main mechanism for motor activity impairment and balance disturbance, whereas MELaL improved motor performance by decreasing oxidative stress.

Zygotic Exposure to Venlafaxine Disrupts the Circadian Locomotor Activity Behaviour in Zebrafish Larvae.

The antidepressant venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is commonly prescribed to treat major depressive disorder and is found at high concentrations in the aquatic environment. Concerns have been raised related to the health of aquatic organisms in response to this nontargeted pharmaceutical exposure. For instance, we previously demonstrated that exposure to venlafaxine perturbs neurodevelopment, leading to behavioural alterations in zebrafish (Danio rerio). We also observed disruption in serotonin expression in the pineal and raphe, regions critical in regulating circadian rhythms, leading us to hypothesize that zygotic exposure to venlafaxine disrupts the circadian locomotor rhythm in larval zebrafish. To test this, we microinjected zebrafish embryos with venlafaxine (1 or 10 ng) and recorded the locomotor activity in 5-day-old larvae over a 24-h period. Venlafaxine deposition reduced larval locomotor activity during the light phase, but not during the dark phase of the diurnal cycle. The melatonin levels were higher in the dark compared to during the light photoperiod and this was not affected by embryonic venlafaxine deposition. Venlafaxine exposure also did not affect the transcript abundance of clock genes, including clock1a, bmal2, cry1a and per2, which showed a clear day/night rhythmicity. A notable finding was that exposure to luzindole, a melatonin receptor antagonist, decreased the locomotor activity in the control group in light, whereas the activity was higher in larvae raised from the venlafaxine-deposited embryos. Overall, zygotic exposure to venlafaxine disrupts the locomotor activity of larval zebrafish fish during the day, demonstrating the capacity of antidepressants to disrupt the circadian rhythms in behaviour. Our results suggest that disruption in melatonin signalling may be playing a role in the venlafaxine impact on circadian behaviour, but further investigation is required to elucidate the possible mechanisms in larval zebrafish.

Assessing motor development and function in mouse models of neurodevelopmental disorders.

Alterations in motor development often accompany neurodevelopmental disorders (NDD) and can have an impact on social interaction and communication. Studying motor development and function in mouse models of NDDs can offer a window to identify underlying biological mechanisms and establish preclinical outcome measures for testing therapeutics. This chapter describes tests to measure motor developmental milestones early postnatally and adult motor functions in mouse models of NDDs.

The association between the child's age and mothers' physical activity: results from the population-based German National Cohort study.

BACKGROUND: Since physical activity is an important determinant of physical and mental health, lower levels of physical activity among mothers reported in previous research are concerning. The aim of this study was to examine whether physical activity levels differ among mothers depending on the age of the youngest child. METHODS: Cross-sectional data from the German National Cohort study, comprising 3959 mothers aged 22-72 years with offspring aged 0-54 years (grouped into 0-5, 6-11, 12-17, 18-29 and > 30 years) was used. The Global Physical Activity Questionnaire (GPAQ) was used to assess physical activity among mothers in leisure time, transport and (occupational and non-occupational) work settings, quantified as MET-minutes per week. Means (with 95% confidence interval) of mothers' weekly MET-minutes were visualized in graphs, stratified by mothers' and the youngest child's age. Linear regression analyses assessed the association between the child's age and self-reported time and intensity of mothers' physical activity within each activity domain and for the total physical activity. RESULTS: Adjusted results suggested that the MET-minutes in work settings were lower among mothers with younger children. This association was clearest in mothers whose youngest child was under 12 years old, among whom lower self-reported physical activity at work compared to mothers with children at age 30 and older was found. No association was observed between the age of the youngest child and mothers' MET-minutes in leisure nor in transport settings. The self-reported physical activity of mothers whose youngest child was in the same child age group was found to be lower with increased maternal age. As expected, the work related activity dominated the self-reported physical activity. CONCLUSIONS: The results show differences in mothers' self-reported physical activity by the age of the youngest child. The strongest difference was related to physical activity in work settings, indicating the need for supportive actions.

Measures of fragmentation of rest activity patterns: mathematical properties and interpretability based on accelerometer real life data.

Accelerometers, devices that measure body movements, have become valuable tools for studying the fragmentation of rest-activity patterns, a core circadian rhythm dimension, using metrics such as inter-daily stability (IS), intradaily variability (IV), transition probability (TP), and self-similarity parameter (named α ). However, their use remains mainly empirical. Therefore, we investigated the mathematical properties and interpretability of rest-activity fragmentation metrics by providing mathematical proofs for the ranges of IS and IV, proposing maximum likelihood and Bayesian estimators for TP, introducing the activity balance index (ABI) metric, a transformation of α , and describing distributions of these metrics in real-life setting. Analysis of accelerometer data from 2,859 individuals (age=60-83 years, 21.1% women) from the Whitehall II cohort (UK) shows modest correlations between the metrics, except for ABI and α . Sociodemographic (age, sex, education, employment status) and clinical (body mass index (BMI), and number of morbidities) factors were associated with these metrics, with differences observed according to metrics. For example, a difference of 5 units in BMI was associated with all metrics (differences ranging between -0.261 (95% CI -0.302, -0.220) to 0.228 (0.18, 0.268) for standardised TP rest to activity during the awake period and TP activity to rest during the awake period, respectively). These results reinforce the value of these rest-activity fragmentation metrics in epidemiological and clinical studies to examine their role for health. This paper expands on a set of methods that have previously demonstrated empirical value, improves the theoretical foundation for these methods, and evaluates their empirical use in a large dataset.

Barriers and enablers to promoting grandchildren's physical activity and reducing screen time: a qualitative study with Australian grandparents.

BACKGROUND: With an increasing number of grandparents providing care to their grandchildren, calls have been made for these caregivers to be considered important stakeholders in encouraging children's engagement in health-promoting behaviors, such as physical activity. Understanding the perspectives of grandparents who provide care is crucial to informing efforts that aim to increase children's physical activity, yet little is understood about their perceptions of specific barriers and enablers to promoting children's physical activity and reducing screen time. The present study sought to explore these perceptions. METHODS: Semi-structured focus groups and individual interviews were conducted with grandparents who reported providing care to a grandchild aged 3 to 14 years. A total of 20 grandparents were sampled (mean age = 67.8 years). Data were subjected to reflexive thematic analysis. RESULTS: Key reported barriers to physical activity included (i) the effort (physical and logistical) and financial cost associated with organizing physical activities, (ii) grandparents' age and mobility issues (e.g., due to injury or illness), (iii) caring for children of different ages (e.g., older children having different physical activity interests than younger children), and (iv) a local environment that is not conducive to physical activity (e.g., lack of appropriate facilities). Barriers to reducing screen time included (i) parents sending children to care with electronic devices and (ii) children's fear of missing out on social connection that occurs electronically. Strategies and enablers of physical activity included (i) integrating activity into caregiving routines (e.g., walking the dog), (ii) involving grandchildren in decision making (e.g., asking them in which physical activities they wish to engage), (iii) encouraging grandchildren to engage in activity with other children, and (iv) creating a physical and social environment that supports activity (e.g., owning play equipment). A common strategy for reducing screen time was the creation of a home environment that is not conducive to this activity (e.g., removing electronic devices from view). CONCLUSIONS: Findings suggest that grandparents may benefit from resources that assist them to identify activities that are inexpensive and require minimal effort to organize. Activities that account for grandparents' age and health status, as well as any environmental barriers, are likely to be well-received.

Revolutionizing motor dysfunction treatment: A novel closed-loop electrical stimulator guided by multiple motor tasks with predictive control.

Functional electrical stimulation (FES) has been demonstrated as a viable method for addressing motor dysfunction in individuals affected by stroke, spinal cord injury, and other etiologies. By eliciting muscle contractions to facilitate joint movements, FES plays a crucial role in fostering the restoration of motor function compromised nervous system. In response to the challenge of muscle fatigue associated with conventional FES protocols, a novel biofeedback electrical stimulator incorporating multi-motor tasks and predictive control algorithms has been developed to enable adaptive modulation of stimulation parameters. The study initially establishes a Hammerstein model for the stimulated muscle group, representing a time-varying relationship between the stimulation pulse width and the root mean square (RMS) of the surface electromyography (sEMG). An online parameter identification algorithm utilizing recursive least squares is employed to estimate the time-varying parameters of the Hammerstein model. Predictive control is then implemented through feedback corrections based on the comparison between predicted and actual outputs, guided by an optimization objective function. The integration of predictive control and roll optimization enables closed-loop control of muscle stimulation. The motor training tasks of elbow flexion and extension, wrist flexion and extension, and five-finger grasping were selected for experimental validation. The results indicate that the model parameters were accurately identified, with a RMS error of 3.83 % between actual and predicted values. Furthermore, the predictive control algorithm, based on the motor tasks, effectively adjusted the stimulus parameters to ensure that the stimulated muscle groups can achieve the desired sEMG characteristic trajectory. The biofeedback electrical stimulator that was developed has the potential to assist patients experiencing motor dysfunction in achieving the appropriate joint movements. This research provides a foundation for a novel intelligent electrical stimulation model.

A multimodal approach integrating cognitive and motor demands into physical activity for optimal mental health: Methodological issues and future directions.

Physical activity is known for its positive effects on cognition and affect, with existing literature suggesting that these mental health benefits may be optimally experienced by incorporating cognitive and motor demands during physical activity (PA). However, the existing body of literature lacks a comprehensive guideline for designing the qualitative characteristics of a PA program. Accordingly, this narrative review aimed to (1) provide a working two-dimension model that operationally defines the cognitive and motor demands involved in PA and the rationale for systematically studying these qualitative aspects of PA, (2) identify methods to assess the cognitive and motor demands of PA and address associated methodological issues, and (3) offer potential future directions for research on the cognitive and motor aspects of PA in support of the development of PA programs designed to maximize PA-induced cognitive and affective benefits. We anticipate this article to inform the need for future research and development on this topic, aiming to create clear, evidence-based guidelines for designing innovative and effective PA interventions.

"One size does not fit all" - Barriers to and facilitators of physical activity in adolescents with epilepsy.

OBJECTIVE: To explore the barriers to physical activity and to identify the support needed to facilitate physical activity in adolescents with epilepsy (AWE). METHODS: AWE (aged 11-16 years) and their caregivers completed survey-based open questions regarding perceived barriers to, and facilitators of physical activity in young people with epilepsy. The responses were analysed using Thematic Analysis. RESULTS: Themes concerning barriers to physical activity included concerns about seizure safety, general anxiety and anxiety related to seizures, stigma/negative attitudes associated with having epilepsy, tiredness, and perceived lack of physical competence. Themes regarding the support needed to facilitate physical activity included better education amongst staff/coaches about epilepsy (e.g., seizure management/prevention, associated fatigue/tiredness), improvements in societal attitudes towards epilepsy, flexibility/tailoring of activities to the child's needs (e.g., need for breaks), and peer support for young people with epilepsy to encourage engagement in physical activity. CONCLUSIONS: There is a perception among AWE and caregivers, that significant barriers exist with regard to engaging in physical activity for young people with epilepsy. Barriers are related to concerns about seizure management but also wider safety and social issues. A number of facilitators were identified to promote physical activity engagement in AWE, including education for staff and caregivers, peer support, and tailoring activities to the adolescent's needs. There is a need to develop interventions to reduce barriers to physical activity in young people with epilepsy.

A method to find temporal structure of neuronal coactivity patterns with across-trial correlations.

BACKGROUND: The across-trial correlation of neurons' coactivity patterns emerges to be important for information coding, but methods for finding their temporal structures remain largely unexplored. NEW METHOD: In the present study, we propose a method to find time clusters in which coactivity patterns of neurons are correlated across trials. We transform the multidimensional neural activity at each timing into a coactivity pattern of binary states, and predict the coactivity patterns at different timings. We devise a method suitable for these coactivity pattern predictions, call general event prediction. Cross-temporal prediction accuracy is then used to estimate across-trial correlations between coactivity patterns at two timings. We extract time clusters from the cross-temporal prediction accuracy by a modified k-means algorithm. RESULTS: The feasibility of the proposed method is verified through simulations based on ground truth. We apply the proposed method to a calcium imaging dataset recorded from the motor cortex of mice, and demonstrate time clusters of motor cortical coactivity patterns during a motor task. COMPARISON WITH EXISTING METHODS: While the existing cosine similarity method, which does not account for across-trial correlation, shows temporal structures only for contralateral neural responses, the proposed method reveals those for both contralateral and ipsilateral neural responses, demonstrating the effect of across-trial correlations. CONCLUSIONS: This study introduces a novel method for measuring the temporal structure of neuronal ensemble activity.

Ultraflexible electrodes for recording neural activity in the mouse spinal cord during motor behavior.

Implantable electrode arrays are powerful tools for directly interrogating neural circuitry in the brain, but implementing this technology in the spinal cord in behaving animals has been challenging due to the spinal cord's significant motion with respect to the vertebral column during behavior. Consequently, the individual and ensemble activity of spinal neurons processing motor commands remains poorly understood. Here, we demonstrate that custom ultraflexible 1-µm-thick polyimide nanoelectronic threads can conduct laminar recordings of many neuronal units within the lumbar spinal cord of unrestrained, freely moving mice. The extracellular action potentials have high signal-to-noise ratio, exhibit well-isolated feature clusters, and reveal diverse patterns of activity during locomotion. Furthermore, chronic recordings demonstrate the stable tracking of single units and their functional tuning over multiple days. This technology provides a path for elucidating how spinal circuits compute motor actions.

Crack cocaine inhalation increases seizure susceptibility by reducing acetylcholinesterase activity.

Crack cocaine is a highly addictive and potent stimulant drug. Animal studies have shown that the cholinergic system plays a role in neurotoxicity induced by cocaine or its active metabolites inhalation. Behavioral alterations associated with crack cocaine use include hyperactivity, depressed mood, and decreased seizure threshold. Here we evaluate the acetylcholinesterase (AChE) and reactive oxygen species (ROS) activity, behavioral profile, and the threshold for epileptic seizures in rats that received intrahippocampal pilocarpine (H-PILO) followed by exposure to crack cocaine (H-PILO + CRACK). Animals exposed to H-PILO + CRACK demonstrated increased severity and frequency of limbic seizures. The AChE activity was reduced in the groups exposed to crack cocaine alone (CRACK) and H-PILO + CRACK, whereas levels of ROS remained unchanged. In addition, crack cocaine exposure increased vertical locomotor activity, without changing water and sucrose intake. Short-term memory consolidation remained unchanged after H-PILO, H-PILO + CRACK, and CRACK administration. Overall, our data suggest that crack cocaine inhalation reduced the threshold for epileptic seizures in rats submitted to low doses of pilocarpine through the inhibition of AChE. Taken together, our findings can be useful in the development of effective strategies for preventing and treating the harmful effects of cocaine and crack cocaine on the central nervous system.

Classification of Motor Imagery Tasks Derived from Unilateral Upper Limb based on a Weight-optimized Learning Model.

BACKGROUND: The accuracy of decoding fine motor imagery (MI) tasks remains relatively low due to the dense distribution of active areas in the cerebral cortex. METHODS: To enhance the decoding of unilateral fine MI activity in the brain, a weight-optimized EEGNet model is introduced that recognizes six types of MI for the right upper limb, namely elbow flexion/extension, wrist pronation/supination and hand opening/grasping. The model is trained with augmented electroencephalography (EEG) data to learn deep features for MI classification. To address the sensitivity issue of the initial model weights to classification performance, a genetic algorithm (GA) is employed to determine the convolution kernel parameters for each layer of the EEGNet network, followed by optimization of the network weights through backpropagation. RESULTS: The algorithm's performance on the three joint classification is validated through experiment, achieving an average accuracy of 87.97%. The binary classification recognition rates for elbow joint, wrist joint, and hand joint are respectively 93.92%, 90.2%, and 94.64%. Thus, the product of the two-step accuracy value is obtained as the overall capability to distinguish the six types of MI, reaching an average accuracy of 81.74%. Compared to commonly used neural networks and traditional algorithms, the proposed method outperforms and significantly reduces the average error of different subjects. CONCLUSIONS: Overall, this algorithm effectively addresses the sensitivity of network parameters to initial weights, enhances algorithm robustness and improves the overall performance of MI task classification. Moreover, the method is applicable to other EEG classification tasks; for example, emotion and object recognition.