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Motor imagery (MI) is one of the popular control paradigms in the non-invasive brain-computer interface (BCI) field. MI-BCI generally requires users to conduct the imagination of movement (e.g., left or right hand) to collect training data for generating a classification model during the calibration phase. However, this calibration phase is generally time-consuming and tedious, as users conduct the imagination of hand movement several times without being given feedback for an extended period. This obstacle makes MI-BCI non user-friendly and hinders its use. On the other hand, motor execution (ME) and motor observation (MO) are relatively easier tasks, yield lower fatigue than MI, and share similar neural mechanisms to MI. However, few studies have integrated these three tasks into BCIs. In this study, we propose a new task-to-task transfer learning approach of 3-motor tasks (ME, MO, and MI) for building a better user-friendly MI-BCI. For this study, 28 subjects participated in 3-motor tasks experiment, and electroencephalography (EEG) was acquired. User opinions regarding the 3-motor tasks were also collected through questionnaire survey. The 3-motor tasks showed a power decrease in the alpha rhythm, known as event-related desynchronization, but with slight differences in the temporal patterns. In the classification analysis, the cross-validated accuracy (within-task) was 67.05 % for ME, 65.93 % for MI, and 73.16 % for MO on average. Consistently with the results, the subjects scored MI (3.16) as the most difficult task compared with MO (1.42) and ME (1.41), with p < 0.05. In the analysis of task-to-task transfer learning, where training and testing are performed using different task datasets, the ME-trained model yielded an accuracy of 65.93 % (MI test), which is statistically similar to the within-task accuracy (p > 0.05). The MO-trained model achieved an accuracy of 60.82 % (MI test). On the other hand, combining two datasets yielded interesting results. ME and 50 % of the MI-trained model (50-shot) classified MI with a 69.21 % accuracy, which outperformed the within-task accuracy (p < 0.05), and MO and 50 % of the MI-trained model showed an accuracy of 66.75 %. Of the low performers with a within-task accuracy of 70 % or less, 90 % (n = 21) of the subjects improved in training with ME, and 76.2 % (n = 16) improved in training with MO on the MI test at 50-shot. These results demonstrate that task-to-task transfer learning is possible and could be a promising approach to building a user-friendly training protocol in MI-BCI., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Neural circuits produce reliable activity patterns despite disturbances in the environment. For this to occur, neurons elicit synaptic plasticity during perturbations. However, recent work suggests that plasticity not only regulates circuit activity during disturbances, but these modifications may also linger to stabilize circuits during future perturbations. The implementation of such a regulation scheme for real-life environmental challenges of animals remains unclear. Amphibians provide insight into this problem in a rather extreme way, as circuits that generate breathing are inactive for several months during underwater hibernation and use compensatory plasticity to promote ventilation upon emergence., Results: Using ex vivo brainstem preparations and electrophysiology, we find that hibernation in American bullfrogs reduces GABA A receptor (GABA A R) inhibition in respiratory rhythm generating circuits and motor neurons, consistent with a compensatory response to chronic inactivity. Although GABA A Rs are normally critical for breathing, baseline network output at warm temperatures was not affected. However, when assessed across a range of temperatures, hibernators with reduced GABA A R signaling had greater activity at cooler temperatures, enhancing respiratory motor output under conditions that otherwise strongly depress breathing., Conclusions: Hibernation reduces GABA A R signaling to promote robust respiratory output only at cooler temperatures. Although frogs do not ventilate lungs during underwater hibernation, we suggest this would be beneficial for stabilizing breathing when the animal passes through a large temperature range during emergence in the spring. More broadly, these results demonstrate that compensatory synaptic plasticity can increase the operating range of circuits in harsh environments, thereby promoting adaptive behavior in conditions that suppress activity., (© 2024. The Author(s).)

Perceptual decision-making involves multiple cognitive processes, including accumulation of sensory evidence, planning, and executing a motor action. How these processes are intertwined is unclear; some models assume that decision-related processes precede motor execution, whereas others propose that movements reflecting ongoing decision processes occur before commitment to a choice. Here we combine two complementary methods to study the relationship between decision processes and the movements leading up to a choice. The first is a free-response pulse-based evidence accumulation task, in which stimuli continue until choice is reported, and the second is a motion-based drift diffusion model (mDDM), in which movement variables from video pose estimation constrain decision parameters on a trial-by-trial basis. We find that the mDDM provides a better fit to rats' decisions in the free-response accumulation task than traditional drift diffusion models. Interestingly, on each trial we observed a period, before choice, that was characterized by head immobility. The length of this period was positively correlated with the rats' decision bounds, and stimuli presented during this period had the greatest impact on choice. Together these results support a model in which internal decision dynamics are reflected in movements and demonstrate that inclusion of movement parameters improves the performance of diffusion-to-bound decision models. NEW & NOTEWORTHY In this study we combine a novel pulse-based evidence accumulation task with a newly developed motion-based drift diffusion model (mDDM). In this model, we incorporate movement parameters derived from high-resolution video data to estimate parameters of the model on a trial-by-trial basis. We find that this new model is an improved description of animal choice behavior.

Background: This study aimed to investigate the effects of Video-Based Action Observation Training and Live Action Observation Training on motor function, activity participation, and secondary outcome measures in children with spastic diparetic cerebral palsy (CP)., Materials and Methods: Thirty-nine children with spastic diparetic cerebral palsy, aged 5-14 years, with Gross Motor Function Classification System I-III, were distributed in equal numbers to any of the Video-Based Action Observation Training (conventional physiotherapy + Video-Based Action Observation Training), Live Action Observation Training (conventional physiotherapy + Live Action Observation Training), and control (conventional physiotherapy) groups through stratified randomization. For 8 weeks, action observation training groups received 20 minutes of conventional physiotherapy followed by 20 minutes of action observation training, and the control group received 40 minutes of conventional physiotherapy. Primary outcome measures were Gross Motor Function Measurement and Child and Adolescent Scale of Participation, secondary outcome measures were Pediatric Berg Balance Scale, timed-up-and-go test, five times sit-to-stand test (FTSST), Gillette Functional Assessment Questionnaire (GFAQ), and 1-minute walk test (1MWT)., Results: Improvements were observed in all other evaluation parameters of the groups except Gross Motor Function Measurement-lying and rolling ( P  = .066) in the Live Action Observation Training Group, and lying and rolling ( P  = .317) and crawling and kneeling ( P  = .063) motor subtests and Gillette Functional Assessment Questionnaire-walking scale ( P  = .513) in the control group. Comparisons of the increases in all other measurements between the groups, except for the dimensions of Gross Motor Function Measurement-lying and rolling ( P  = .172), were statistically significant ( P  < .05) and this difference was in favor of action observation training., Conclusion: It was found that 2 different AOTs applied in addition to conventional physiotherapy in children with spastic diparetic cerebral palsy were more effective on all outcomes than was conventional physiotherapy alone., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Conventional treatments are ineffective in reversing disease progression. Recently, the therapeutic and rehabilitation potential of vagus nerve stimulation (VNS) in PD has been explored. However, the underlying mechanisms remain largely unknown. In this study, we investigated the neuroprotective effects of VNS in a lateral lesioned mice model of PD. Excluding controls, experimental mice received cuff electrode implantation on the left vagus nerve and 6-hydroxydopamine administration into the bilateral striatum. After ten days, electrical stimulation was delivered for 11 consecutive days onto PD animals. Behavioral tests were performed after stimulation. The expression of TH, Iba-1, GFAP, adrenergic receptors and cytokines in the SN and striatum was detected by immunofluorescence or western blotting. The activity of noradrenergic neurons in the locus coeruleus (LC) was also measured. Our results suggest that VNS improved behavioral performance in rod rotation, open field tests and pole-climbing tests in PD mice, accompanied by a decrease in the loss of dopaminergic neurons in the SN and increased TH expression in the striatum. Neuroinflammation-related factors, such as GFAP, Iba-1, TNF-α and IL-1β were also suppressed in PD mice after VNS compared to those without treatment. Furthermore, the proportion of c-Fos-positive noradrenergic neurons in the LC increased when animals received VNS. Additionally, the expression of the adrenergic receptor of α1BR was also upregulated after VNS compared to PD mice. In conclusion, VNS has potential as a novel PD therapy for neuroprotective effects, and indicate that activation of norepinephric neurons in LC may plays an important role in VNS treatment for PD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Many recent studies indicate that control of decisions and actions is integrated during interactive behavior. Among these, several carried out in humans and monkeys conclude that there is a coregulation of choices and movements. Another perspective, based on human data only, proposes a decoupled control of decision duration and movement speed, allowing, for instance, trading decision duration for movement duration when time pressure increases. Crucially, it is not currently known whether this ability to flexibly dissociate decision duration from movement speed is specific to humans, whether it can vary depending on the context in which a task is performed, and whether it is stable over time. These are important questions to address, especially to rely on monkey electrophysiology to infer the neural mechanisms of decision-action coordination in humans. To do so, we trained two macaque monkeys in a perceptual decision-making task and analyzed data collected over multiple behavioral sessions. Our findings reveal a strong and complex relationship between decision duration and movement vigor. Decision duration and action duration can covary but also "compensate" each other. Such integrated but decoupled control of decisions and actions aligns with recent studies in humans, validating the monkey model in electrophysiology as a means of inferring neural mechanisms in humans. Crucially, we demonstrate for the first time that this control can evolve with experience, in an adapted manner. Together, the present findings contribute to deepening our understanding of the integrated control of decisions and actions during interactive behavior. NEW & NOTEWORTHY The mechanism by which the integrated control of decisions and actions occurs, coupled or interactive but decoupled, is debated. In the present study, we show in monkeys that decisions and actions influence each other in a decoupled way. For the first time, we also demonstrate that this control can evolve depending the subject's experience, allowing the trade of movement time for decision time and limiting the temporal discounting of reward value.

Efficient responses in dynamic environments rely on a combination of readiness and flexibility, regulated by anticipatory and online response control mechanisms. The latter are required when a motor response needs to be reprogrammed or when flanker stimuli induce response conflict and they are crucially modulated by anticipatory signals such as response and conflict expectations. The mutual influence and interplay of these control processes remain to be elucidated. Our behavioral study employed a novel combined response cueing/conflict task designed to test for interactive effects of response reprogramming and conflict resolution and their modulation by expectations. To this end, valid and invalid response cues were combined with congruent and incongruent target flankers. Expectations were modulated by systematically manipulating the proportions of valid versus invalid cues and congruent versus incongruent flanker stimuli in different task blocks. Reaction time and accuracy were assessed in thirty-one healthy volunteers. The results revealed response reprogramming and conflict resolution interactions for both behavioral measures, modulated by response and conflict expectations. Accuracy decreased disproportionally when invalidly cued targets with incongruent flankers were least expected. These findings support coordinated and partially overlapping anticipatory and online response control mechanisms within motor-cognitive networks., (© 2024. The Author(s).)

Introduction: Alpha-synuclein (αSyn) is believed to play a central role in the pathogenesis of Parkinson's disease (PD). Cerebrospinal fluid (CSF) total αSyn were significantly lower in PD patients, whereas the aggregates were higher, and this phenomenon was further exacerbated with longer disease duration. However, whether CSF αSyn can be the cause and/or a consequence in PD is not fully elucidated., Method: We administered 2 ng or 200 ng αSyn preformed fibrils (PFFs) by intracerebroventricular injection for consecutive 7 days in C57BL/6 mice. The olfactory function was assessed by the olfactory discrimination test and buried food-seeking test. The locomotor function was assessed by the rotarod test, pole test, open field test and CatWalk gait analysis. Phosphorylated αSyn at serine 129 was detected by the immunohistochemistry staining. Iron levels was determined by Perl's-diaminobenzidine iron staining and synchrotron-based X-ray fluorescence., Results: The mice did not exhibit any diffuse synucleinopathy in the brain for up to 30 weeks, although αSyn PFFs induced aggregation in SH-SY5Y cells and in the substantia nigra and striatum of mice with stereotactic injection. No impairment of motor behaviors or olfactory functions were observed, although there was a temporary motor enhancement at 1 week. We then demonstrated iron levels were comparable in certain brain regions, suggesting there was no iron deposition/redistribution occurred., Conclusion: The intraventricular injection of αSyn PFFs does not induce synucleinopathy or behavioral symptoms. These findings have implications that CSF αSyn aggregates may not necessarily contribute to the onset or progression in PD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Peripersonal space (PPS), as opposed to extrapersonal space (EPS), refers to the area surrounding the body within which individuals interact with objects or conspecifics. However, objects in PPS can belong to oneself or to others, which was found to influence how these objects are encoded. We analyzed the performances of motor responses in a reachability judgment task concerning self-owned and other-owned objects (cups) presented in PPS or EPS. EMG activities were recorded on the thumbs (flexor pollicis brevis) to detect correct and erroneous motor activations. Behavioral data showed that motor responses were shorter and longer for self-owned cups compared to other-owned cups in PPS and EPS, respectively. Ten percent of trials showed initial response errors, which were higher in the EPS for self-owned cups and in the PPS for other-owned cups. Eighty-two percent of these errors were corrected online, with corrections being more efficient for self-owned cups in the PPS. Overall, the data revealed that reachability judgments were faster and more accurate in the PPS, with more efficient inhibition processes in the presence of motor errors. Motor selection and correction are thus modulated by the social context of object ownership, highlighting the specific role of the PPS in encoding self-relevant objects for action., (© 2024 Society for Psychophysiological Research.)

The positional preference of an animal can be very informative regarding the choices it makes about how to interact with its environment. The fruit fly Drosophila melanogaster has been used as a robust system for examining neurobiological mechanisms underlying behavior. Fruit fly positional preference can be gathered from TriKinetics Drosophila activity monitors (DAMs), which contain four infrared beams, allowing for tracking the position of individual flies along the length of a tube. Here, we describe a method for using DAM5Ms to examine food preference. Specifically, we show an example in which circadian changes in food preference are compared between different Drosophila species. More information about the evolution of behavior can be gathered by measuring feeding preference relative to time of day. Noni, fruit from Morinda citrifolia , contains octanoic acid, a chemical toxic to many species of Drosophila D. melanogaster and D. simulans , both food generalists, show high sensitivity to octanoic acid, whereas D. sechellia , a specialist, can tolerate high concentrations. When two different food substrates are provided at each end of a tube, food preference can be inferred at various times of the day, using the sleep and circadian analysis MATLAB program (SCAMP) to extract and analyze positional data from DAM5Ms. Data gathered from these analyses can be used to compare avoidance or attraction to nutrients, tastants, or odors between species and genotypes or after specific different treatments. Additionally, such data can be examined as a function of time of day., (© 2024 Cold Spring Harbor Laboratory Press.)

This primer describes research on the development of motor behavior. We focus on infancy when basic action systems are acquired-posture, locomotion, manual actions, and facial actions-and we adopt a developmental systems perspective to understand the causes and consequences of developmental change. Experience facilitates improvements in motor behavior and infants accumulate immense amounts of varied everyday experience with all the basic action systems. At every point in development, perception guides behavior by providing feedback about the results of just prior movements and information about what to do next. Across development, new motor behaviors provide new inputs for perception. Thus, motor development opens up new opportunities for acquiring knowledge and acting on the world, instigating cascades of developmental changes in perceptual, cognitive, and social domains. This article is categorized under: Cognitive Biology > Cognitive Development Psychology > Motor Skill and Performance Neuroscience > Development., (© 2024 Wiley Periodicals LLC.)

Sleep is a fundamental feature of life for virtually all multicellular animals, but many questions remain about how sleep is regulated and what biological functions it plays. Substantial headway has been made in the study of both circadian rhythms and sleep in the fruit fly Drosophila melanogaster , much of it through studies of individual fly activity using beam break counts from Drosophila activity monitors (DAMs). The number of laboratories worldwide studying sleep in Drosophila has grown from only a few 20 years ago to hundreds today. The utility of these studies is limited by the quality of the metrics that can be extracted from the data. Many software options exist to help analyze DAM data; however, these are often expensive or have significant limitations. Therefore, we describe here a method for analyzing DAM-based data using the sleep and circadian analysis MATLAB program (SCAMP). This user-friendly software has an advantage of combining several analyses of both sleep and circadian rhythms in one package and produces graphical outputs as well as spreadsheets of the outputs for further statistical analysis. The version of SCAMP described here is also the first published software package that can analyze data from multibeam DAM5Ms, enabling determination of positional preference over time., (© 2024 Cold Spring Harbor Laboratory Press.)

Sleep is a fundamental feature of life for virtually all multicellular animals, but many questions remain about how sleep is regulated by circadian rhythms, homeostatic sleep drive that builds up with wakefulness, and modifying factors such as hunger or social interactions, as well as about the biological functions of sleep. Substantial headway has been made in the study of both circadian rhythms and sleep in the fruit fly Drosophila melanogaster , much of it through studies of individual fly activity using Drosophila activity monitors (DAMs). Here, we describe approaches for the activation of specific neurons of interest using optogenetics (involving genetic modifications that allow for light-based neuronal activation) and thermogenetics (involving genetic modifications that allow for temperature-based neuronal activation) so that researchers can evaluate the roles of those neurons in controlling rest and activity behavior. In this protocol, we describe how to set up a rig for simultaneous optogenetic or thermogenetic stimulation and activity monitoring for analysis of sleep and circadian rhythms in Drosophila , how to raise appropriate flies, and how to perform the experiment. This protocol will allow researchers to assess the causative role in the regulation of sleep and activity rhythms of any genetically tractable subset of cells., (© 2024 Cold Spring Harbor Laboratory Press.)

Habitual physical activity has been shown to improve memory performance, yet investigations into its effects concerning memory interference remain limited. Additionally, minimal research has evaluated the association between habitual physical activity behaviors occurring in different contexts (e.g., walking, basketball, swimming) and memory. Based on these gaps in the literature, the present set of six experiments evaluated the association between contextually-different physical activity behaviors (e.g., individual physical activities, physical activities performed in social settings) and memory interference among young adult samples from America and Germany. Across six experiments, we reliably demonstrated that Germans exhibited greater memory performance than Americans. We also reliably demonstrated that contextually-different physical activities are not associated with memory performance or attenuated memory interference., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study examined the clinimetrics of the Brazilian-Portuguese translation of the Grade-4/5 Motor Activity Log (MAL 4/5), which assesses everyday use of the more affected upper-limb (UL) in stroke survivors with moderate/severe or severe motor impairment., Materials and Methods: The translated MAL 4/5 was administered to 47 stroke survivors with moderate/severe or severe UL motor impairment. Accelerometers were worn on participants' wrists for five days on average prior to the first assessment. Test-retest and inter-rater reliabilities were assessed using the intraclass correlation coefficient (ICC), internal consistency using Cronbach's α, and construct validity was tested with correlations with the accelerometry. The measurement error (SEM) and the minimal detectable change (MDC) were calculated., Results: MAL4/5-Brazil's test-retest reliability (AOU: ICC = 0.84; QOU: ICC = 0.90), inter-rater reliability (AOU: ICC = 0.83; QOU: ICC = 0.91), internal consistency (Cronbach's α = 0.91 and 0.95 for AOU and QOU scales, respectively), the SEM and MDC were 0.3 and 0.8 points for the AOU subscale and 0.2 and 0.5 points for the QOU subscale, respectively. The construct validity (AOU scale: r  = 0.67; QOU scale: r  = 0.76) was high., Conclusion: Grade-4/5 Motor Activity Log-Brazil is a reliable and valid instrument for assessing the more-affected UL use of stroke patients with moderate/severe or severe UL motor impairments.

Rationale: The phenylalkylamine hallucinogen (-)-2,5-dimethoxy-4-methylamphetamine (DOM) exhibits an inverted U-shaped dose-response curve for both head twitch response (HTR) and locomotor activity in mice. Accumulated studies suggest that HTR and locomotor hyperactivity induced by DOM are mainly caused by the activation of serotonin 5-hydroxytryptamine 2 A receptor (5-HT 2A receptor). However, the mechanisms underlying the biphasic dose response of HTR and locomotor activity induced by DOM, particularly at high doses, remain unclear., Objectives: The primary objective of this study is to investigate the modulation of 5-HT 2A/2C/1A receptors in HTR and locomotor activity, while also exploring the potential receptor mechanisms underlying the biphasic dose response of DOM., Methods: In this study, we employed pharmacological methods to identify the specific 5-HT receptor subtypes responsible for mediating the biphasic dose-response effects of DOM on HTR and locomotor activity in C57BL/6J mice., Results: The 5-HT 2A receptor selective antagonist (R)-[2,3-di(methoxy)phenyl]-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]methanol (M100907) (500 µg/kg, i.p.) fully blocked the HTR at every dose of DOM (0.615-10 mg/kg, i.p.) in C57BL/6J mice. M100907 (50 µg/kg, i.p.) decreased the locomotor hyperactivity induced by a low dose of DOM (0.625, 1.25 mg/kg, i.p.), but had no effect on the locomotor hypoactivity induced by a high dose of DOM (10 mg/kg) in C57BL/6J mice. The 5-HT 2C antagonist 6-chloro-5-methyl-1-[(2-[2-methylpyrid-3yloxy]pyrid-5yl)carbamoyl]indoline (SB242084) (0.3, 1 mg/kg, i.p.) reduced the HTR induced by a dose of 2.5 mg/kg DOM, but did not affect the response to other doses. SB242084 (1 mg/kg, i.p.) significantly increased the locomotor activity induced by DOM (0.615-10 mg/kg, i.p.) in mice. The 5-HT 1A antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]N-(2-pyridinyl) cyclohexane carboxamide maleate (WAY100635) (1 mg/kg, i.p.) increased both HTR and locomotor activity induced by DOM in mice. The 5-HT 1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1 mg/kg, i.p.) significantly reduced both the HTR and locomotor activity induced by DOM in mice. Additionally, pretreatment with the Gα i/o inhibitor PTX (0.25 µg/mouse, i.c.v.) enhanced the HTR induced by DOM and attenuated the effect of DOM on locomotor activity in mice., Conclusions: Receptor subtypes 5-HT 2C and 5-HT 1A are implicated in the inverted U-shaped dose-response curves of HTR and locomotor activity induced by DOM in mice. The biphasic dose-response function of HTR and locomotor activity induced by DOM has different mechanisms in mice., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The integration of numerical information with motor processes has emerged as a fascinating area of investigation in both animal and human cognition. The interest in a sensorimotor number system has recently generated neurophysiological and psychophysical evidence which combine to highlight the importance of motor functions in the encoding of numerical information. Nevertheless, several key questions remain, such as the influence of non-numerical motor parameters over numerical perception. Here we tested the role of physical effort, a parameter positively correlated with the number of actions, in modulating the link between hand-actions and visual numerosity perception. Effort was manipulated during sensorimotor adaptation as well as during a new actions-estimation paradigm. The results of Experiment 1 shows that physical effort in the absence of actions (passive effort) is not sufficient to activate the sensorimotor number system, indicating that self-produced actions are instead necessary. Further experiments demonstrated that effort is marginally integrated during motor adaptation (Experiment 2) but discarded when estimating the number of self-produced hand actions (Experiment 3). Overall, the results indicate that the sensorimotor number system is largely fed by the number of discrete actions rather than the amount of effort but also indicates that effort (under specific circumstances) might be integrated. These findings provide novel insights into the sensorimotor numerical integration, paving the way for future investigations, such as on its functional role., (© 2024. The Author(s).)

As pollinators, bees are key to maintaining the biodiversity of angiosperm plants, and for agriculture they provide a billion-dollar ecosystem service. But they also compete for resources (primarily nectar and pollen), especially the highly social bees that live in perennial colonies. So, how do they organize their daily temporal activities? Here, we present a versatile, low-cost device for the continuous, automatic recording and data analysis of the locomotor activity in the colony-entrance tube of highly eusocial bees. Consisting of an in-house built block containing an infrared detector, the passage of bees in the colony entrance tunnel is registered and automatically recorded in an Arduino environment, together with concomitant recordings of temperature and relative humidity. With a focus on the highly diverse Neotropical stingless bees (Meliponini), we obtained 10-day consecutive recordings for two colonies each of the species Melipona quadrifasciata and Frieseomelitta varia, and also for the honey bee. The Lomb-Scargle periodogram analysis identified a predominant circadian rhythmicity for all three species, but also indications of ultradian rhythms. For M. quadrifasciata, which is comparable in size to the honey bee, we found evidence for a possibly anticipatory activity already before sunrise. As all three species also presented activity at night in the colony entrance tube, this also raises questions about sleep organization in social insects. The cost and versatility of the device and the open-source options for data analysis make this an attractive system for conducting studies on circadian rhythms in social bees under natural conditions, complementing studies on flower visits by these important pollinators., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Despite the connections and clear importance of the cerebellum in motor function, research utilizing cerebellar neuromodulation for treatment of movement disorders is still underdeveloped. Here we conduct a systematic review to investigate non-invasive neurostimulation of the cerebellum and its potential impact on motor systems and its function. Our aim is to give a general review of each neurostimulation study focusing on the cerebellum as a treatment target in the past five years at time of search, in order to update the field on current findings and inspire similar cerebellar neurostimulation research without unnecessary repetition., Methods: Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, our search included articles over the past five years that evaluated neurostimulation of the cerebellum (e.g., transcranial magnetic stimulation, transcranial direct current stimulation, and transcranial alternating current stimulation, etc.). Inclusion criteria included: (1) neurostimulation (repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS)) of the cerebellum; (2) only original articles, and (3) outcomes focused on motor functions. Exclusion criteria included: (1) neurostimulation with the goal of targeting any brain structure other than the cerebellum and (2) reviews and conference abstracts., Results: The search revealed 82 distinct articles relevant to the research question. Included are 17 articles concerning rTMS, 56 articles concerning tDCS, and 9 articles concerning tACS. The majority of the studies are controlled trials of varying types, with 79, with two case studies and one pilot study., Conclusions: Many studies showed significant effects on motor function and circuitry via non-invasive neurostimulation of the cerebellum. Common targets of cerebellar neurostimulation include visuomotor control, stroke rehabilitation for improvements in balance and coordination, and motor skill acquisition. The field is still exploring ideal parameters of neurostimulation for each disorder or function of interest. Future research areas should include the inclusion of individual anatomy, including functional connectivity, and improving stimulation selectivity., (© 2024 The Author(s). Published by IMR Press.)

Objective . Motor-related neural activity is more widespread than previously thought, as pervasive brain-wide neural correlates of motor behavior have been reported in various animal species. Brain-wide movement-related neural activity have been observed in individual brain areas in humans as well, but it is unknown to what extent global patterns exist. Approach. Here, we use a decoding approach to capture and characterize brain-wide neural correlates of movement. We recorded invasive electrophysiological data from stereotactic electroencephalographic electrodes implanted in eight epilepsy patients who performed both an executed and imagined grasping task. Combined, these electrodes cover the whole brain, including deeper structures such as the hippocampus, insula and basal ganglia. We extract a low-dimensional representation and classify movement from rest trials using a Riemannian decoder. Main results . We reveal global neural dynamics that are predictive across tasks and participants. Using an ablation analysis, we demonstrate that these dynamics remain remarkably stable under loss of information. Similarly, the dynamics remain stable across participants, as we were able to predict movement across participants using transfer learning. Significance . Our results show that decodable global motor-related neural dynamics exist within a low-dimensional space. The dynamics are predictive of movement, nearly brain-wide and present in all our participants. The results broaden the scope to brain-wide investigations, and may allow combining datasets of multiple participants with varying electrode locations or calibrationless neural decoder., (Creative Commons Attribution license.)

Background: Evidence suggests that aging contributes to decreased cerebral blood flow and brain oxyhemoglobin (HbO 2 ) in the association cortices during rest. However, the influence of aging on functional brain activation is still controversial. The objective of this study was to investigate the age-related dependence of HbO 2 across distinct motor control conditions in both primary and association cortices., Methods: Using functional near-infrared spectroscopy (fNIRS), this study assessed HbO 2 level changes within the primary somatosensory cortex (PSC), primary motor cortex (PMC), supplementary motor cortex (SMC), prefrontal cortex (PFC) and dorsolateral prefrontal cortex (DLPFC) under various motor control conditions. Analysis examined changes in the concentration of HbO 2 measured by fNIRS during rest, motor execution (ME), motor passivity (MP) and motor imagery (MI) with elbow flexion in 30 younger (21.5 ± 1.17 years old) and 30 older (60.9 ± 0.79 years old) adults., Results: During motor execution HbO 2 was higher in younger adults than older adults in bilateral PMC, bilateral PFC, left PSC, left SMC and left DLPFC ( p < 0.05). During motor passivity, HbO 2 was higher in younger adults than older adults in bilateral PMC, left PSC and left SMC ( p < 0.05). During motor imagery, HbO 2 was higher in younger adults than older adults in bilateral PFC and bilateral DLPFC ( p < 0.05)., Conclusion: This study provided evidence that HbO 2 levels are different in the primary and association cortices during different motor control conditions in young and old adults and that HbO 2 levels in different brain regions under different motor control conditions can be influenced by age., (© 2024 The Author(s). Published by IMR Press.)

Study Design: Experimental study utilizing with a standardized model (MASCIS Impactor) of Spinal Cord Injury (SCI) in Balb C mouse model with implantation of mononuclear stem cells derived from the human umbilical cord and placenta blood in the early chronic phase of SCI., Objectives: The aim of this study was to evaluate the nerve regeneration and motor functional recovery in Balb C mice with surgically induced paraplegia in response to the use of mononuclear stem cells, in early chronic phase (> 2 weeks and < 6 months), because there is yet potential of neuronal and functional recovery as the neuronal scar is not still completely established., Methods: Forty-eight mice were randomly assigned to 6 groups of 8 animals. Group 1 received the stem cells 3 weeks after the trauma, and Group 2 received them six weeks later. In Group 3, saline solution was injected at the site of the lesion 3 weeks after the trauma, and in Group 4, 6 weeks later. Group 5 underwent only spinal cord injury and Group 6 underwent laminectomy only. The scales used for motor assessment were BMS and MFS for 12 weeks., Results: The intervention groups showed statistically significant motor improvement. In the histopathological analysis, the intervention groups had a lower degree of injury (p < 0.05). Regarding axonal budding, the intervention groups showed increasing in axonal budding in the caudal portion (p < 0.05)., Conclusions: The use of stem cells in mice in the chronic phase after 3 and 6 weeks of SCI brings functional and histopathological benefits to them., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Competing Interests: The authors declare no competing financial interests.

The 5-lipoxygenase/leukotriene system has been implicated in both physiological and pathological states within the central nervous system. Understanding how this system interacts with the dopaminergic system could provide valuable insights into dopamine-related pathologies. This study focused on examining both motor and non-motor dopamine-related responses in 5-lipoxygenase/leukotriene-deficient mice. We used pharmacological agents such as amphetamine, apomorphine, and reserpine to challenge the dopaminergic system, evaluating their effects on prepulse inhibition reaction (PPI), general motor activity, and oral involuntary movements. Additionally, we analyzed striatal glial marker expression (GFAP and Iba-1) in reserpine-treated mice. The 5-lipoxygenase/leukotriene-deficient mice exhibited increased spontaneous locomotor activity, including both horizontal and vertical exploration, along with stereotyped behavior compared to wild-type mice. This hyperactivity was reduced by acute apomorphine treatment. Although basal PPI responses were unchanged, 5-lipoxygenase/leukotriene-deficient mice displayed a significant reduction in susceptibility to amphetamine-induced PPI disruption. Conversely, these mice were more vulnerable to reserpine-induced involuntary movements. There were no significant differences in the basal expression of striatal GFAP and Iba-1 positive cells between 5-lipoxygenase/leukotriene-deficient and wild-type mice. However, reserpine treatment significantly increased GFAP immunoreactivity in wild-type mice, an effect not observed in 5-lipoxygenase-deficient mice. Additionally, the percentage of activated microglia was significantly higher in reserpine-treated wild-type mice, an effect absents in 5-lipoxygenase/leukotriene-deficient mice. Our findings suggest that 5-lipoxygenase/leukotriene deficiency leads to a distinctive dopaminergic phenotype, indicating that leukotrienes may influence the modulation of dopamine-mediated responses., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Dopamine's role as the principal neurotransmitter in motor functions has long been accepted. We broaden this conventional perspective by demonstrating the involvement of non-dopaminergic mechanisms. In mouse models of Parkinson's disease, we observed that L-DOPA elicited a substantial motor response even when its conversion to dopamine was blocked by inhibiting the enzyme aromatic amino acid decarboxylase (AADC). Remarkably, the motor activity response to L-DOPA in the presence of an AADC inhibitor (NSD1015) showed a delayed onset, yet greater intensity and longer duration, peaking at 7 h, compared to when L-DOPA was administered alone. This suggests an alternative pathway or mechanism, independent of dopamine signalling, mediating the motor functions. We sought to determine the metabolites associated with the pronounced hyperactivity observed, using comprehensive metabolomics analysis. Our results revealed that the peak in motor activity induced by NSD1015/L-DOPA in Parkinson's disease mice is associated with a surge (20-fold) in brain levels of the tripeptide ophthalmic acid (also known as ophthalmate in its anionic form). Interestingly, we found that administering ophthalmate directly to the brain rescued motor deficits in Parkinson's disease mice in a dose-dependent manner. We investigated the molecular mechanisms underlying ophthalmate's action and discovered, through radioligand binding and cAMP-luminescence assays, that ophthalmate binds to and activates the calcium-sensing receptor (CaSR). Additionally, our findings demonstrated that a CaSR antagonist inhibits the motor-enhancing effects of ophthalmate, further solidifying the evidence that ophthalmate modulates motor functions through the activation of the CaSR. The discovery of ophthalmate as a novel regulator of motor function presents significant potential to transform our understanding of brain mechanisms of movement control and the therapeutic management of related disorders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Mu rhythm (∼8-12 Hz) in the somatosensory cortex has traditionally been linked with doing and seeing motor activities. Here, we aimed to learn how the medium (physical or screened) in which motor actions are seen could impact on that specific brain rhythm. To do so, we presented to 40 participants the very same narrative content both in a one-shot movie with no cuts and in a real theatrical performance. We recorded subjects' brain activities with electroencephalographic (EEG) procedures, and analyzed Mu rhythm present in left (C3) and right (C4) somatosensory areas in relation to the 24 motor activities included in each visual stimulus (screen vs. reality) (24 motor and grasping actions x 40 participants x 2 conditions = 1920 trials). We found lower Mu spectral power in the somatosensory area after the onset of the motor actions in real performance than on-screened content, more pronounced in the left hemisphere. In our results, the sensorimotor Mu-ERD (event-related desynchronization) was stronger during the real-world observation compared to screen observation. This could be relevant in research areas where the somatosensory cortex is important, such as online learning, virtual reality, or brain-computer interfaces., (© 2024. The Author(s).)

Many animals adapt their activity patterns to the best environmental conditions using daily rhythms. African mole-rats are among the mammals that have become models for studying how these rhythms can be entrained by light or temperature in experimental laboratory studies. However, it is unclear whether they exhibit similar circadian rhythms in their natural lightless, subterranean environment. In this study, we used biologging to investigate the activity rhythms of wild, highveld mole-rats. We show that their activity cycle exhibited an ultradian rhythm with a length between 4 and 8 h. On an individual level, mole-rats displayed about five activity bouts per day, occurring at various times during the day and night. On a population level, activity peaked in the afternoon, coinciding with the peak in ambient temperature. Our research suggests that wild subterranean mammals, which experience reduced environmental variation, are unlikely to show clear circadian rhythmicity in activity patterns. Instead, activity periods are distributed over several bouts throughout the day and night, and activity coincides with the peak in daily temperature. We propose that ultradian rhythms in activity may be more common than previously thought and discuss how physiological processes may generate differences in periodicity between laboratory and wild populations.

The gene FOXP2 is well established for a role in human speech and language; far less is known about FOXP1. However, this related gene has also been implicated in human language development as well as disorders associated with features of autism spectrum disorder (ASD). FOXP1 protein expression has also recently been identified in the cerebellum-a neural structure previously shown to express FOXP2 protein. The current study sought to elucidate the behavioral implications of a conditional knock-out of Foxp1 using an En1-Cre driver, which is active in the entirety of the cerebellum and a subset of neurons in the midbrain and spinal cord, in mice using a test battery including motor tasks associated with cerebellar dysfunction, as well as communicative and autistic-relevant behaviors. Male and female mice with a conditional knock-out (cKO, n = 31) and wildtype littermate controls (WT, n = 34) were assessed for gross and orofacial motor control, motor-coordination learning, locomotion, social behavior, anxiety, auditory processing and expressive vocalizations. Overall results suggest Foxp1 plays a specific role in the development of communicative systems, and phenotypic expression of disruptions may interact with sex. Robust motor deficits associated with Foxp1 protein loss may particularly affect vocalizations based on significant orofacial motor deficits in cKO subjects could also contribute to vocalization anomalies. In summary, the current study provides key insights into the role of Foxp1 in cerebellar function and associated behaviors in mice, with implications for an improved understanding of communicative and motor-based neurodevelopmental disabilities in humans., (© 2024 The Author(s). Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)

Objectives: Neuroimaging studies of dyskinetic cerebral palsy (CP) are scarce and the neuropathological underpinnings are not fully understood. We delineated the corticospinal tract (CST) and cortico-striatal-thalamocortical (CSTC) pathways with probabilistic tractography to assess their (1) integrity and (2) association with motor functioning in people with dyskinetic CP., Methods: Diffusion weighted magnetic resonance images were obtained for 33 individuals with dyskinetic CP and 33 controls. Fractional anisotropy (FA) and mean diffusivity (MD) for the CST and the CSTC pathways were compared between groups. Correlation analyses were performed between tensor metric values and motor function scores of participants with dyskinetic CP as assessed by the Gross Motor Function Classification System (GMFCS), the Bimanual Fine Motor Function (BFMF), and the Manual Ability Classification System (MACS)., Results: White matter integrity in both the CST and the CSTC pathways was reduced in people with dyskinetic CP. The GMFCS, MACS and, less commonly, the BFMF were associated with FA and, particularly, MD in most portions of these pathways., Interpretation: The present study advances our understanding of the involvement of white matter microstructure in sensorimotor pathways and its relationship with motor impairment in people with dyskinetic CP. Our results are consistent with well-described relationships between upper limb function and white matter integrity in the CST and CSTC pathways in other forms of CP. This knowledge may ultimately help prognosis and therapeutic programmes., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Circadian clock properties vary between individuals and relate to variation in entrained timing in captivity. How this variation translates into behavioural differences in natural settings, however, is poorly understood. Here, we tested in great tits whether variation in the free-running period length (tau) under constant dim light (LL) was linked to the phase angle of the entrained rhythm ("chronotype") in captivity and in the wild, as recently indicated in our study species. We also assessed links between tau and the timing of first activity onset and offset under LL relative to the last experienced light-dark (LD) cycle. We kept 66 great tits, caught in two winters, in LL for 14 days and subsequently released them with a radio transmitter back to the wild, where their activity and body temperature rhythms were tracked for 1 to 22 days. For a subset of birds, chronotype was also recorded in the lab before release. Neither wild nor lab chronotypes were related to tau. We also found no correlation between lab and wild chronotypes. However, the first onset in LL had a positive relationship with tau, but only in males. Our results demonstrate that links between tau and phase of entrainment, postulated on theoretical grounds, may not consistently hold under natural conditions, possibly due to strong masking. This calls for more holistic research on how the many components of the circadian system interact with the environment to shape timing in the wild. Wild birds showed chronotypes in the field that were unlinked to their circadian period length tau measured in captivity. In males only, the first onset of activity after exposure to constant dim light did correlate with tau. Our study emphasises the need to investigate clocks in the real world, including a need to better understand masking., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Objective: To determine whether an accelerated protocol of 48 Hz cerebellar repetitive transcranial magnetic stimulation results in improved motor function in individuals with Parkinson's disease., Methods: In this double-blind randomized sham-controlled study, 35 individuals with Parkinson's disease and stable medical treatment were randomized to either sham or verum transcranial magnetic stimulation. The stimulation was applied bilaterally and medial over the cerebellum and comprised a novel accelerated protocol encompassing two sessions per day on 5 consecutive days. Patients were assessed at baseline, on day 5 after the last stimulation and 1 month post intervention. Measurements included dynamic posturography, UPDRS III, 8-Meter walk test, and Timed Up and Go test., Results: The accelerated protocol was safe and feasible in an outpatient setting. Patients in the verum group showed significant improvement (p < 0.001) of motor symptoms as measured in the UPDRS III. Improvement was mainly carried by the domains rigor, bradykinesia, and gait and persisted after 1 month (p = 0.009), whereas tremor remained unchanged., Interpretation: The effect of a high-dose transcranial magnetic stimulation in patients with Parkinson's disease is encouraging and comparable to other studies using much longer stimulation protocols. This short-term intervention of 5 days facilitates the future application in an outpatient setting. Reduction in hospitalization rates directly benefits patients with motor impairment., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Exposure to infectious or non-infectious immune activation during early development is a serious risk factor for long-term behavioural dysfunctions. Mouse models of maternal immune activation (MIA) have increasingly been used to address neuronal and behavioural dysfunctions in response to prenatal infections. One commonly employed MIA model involves administering poly(I:C) (polyriboinosinic-polyribocytdilic acid), a synthetic analogue of double-stranded RNA, during gestation, which robustly induces an acute viral-like inflammatory response. Using electroencephalography (EEG) and infrared (IR) activity recordings, we explored alterations in sleep/wake, circadian and locomotor activity patterns on the adult male offspring of poly(I:C)-treated mothers. Our findings demonstrate that these offspring displayed reduced home cage activity during the (subjective) night under both light/dark or constant darkness conditions. In line with this finding, these mice exhibited an increase in non-rapid eye movement (NREM) sleep duration as well as an increase in sleep spindles density. Following sleep deprivation, poly(I:C)-exposed offspring extended NREM sleep duration and prolonged NREM sleep bouts during the dark phase as compared with non-exposed mice. Additionally, these mice exhibited a significant alteration in NREM sleep EEG spectral power under heightened sleep pressure. Together, our study highlights the lasting effects of infection and/or immune activation during pregnancy on circadian activity and sleep/wake patterns in the offspring., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Rationale: Exercise attenuates addictive behavior; however, little is known about the contribution of exercise duration to this positive effect. The Renin Angiotensin System (RAS) has been implicated both in addictive responses and in the beneficial effects of exercise; though, its role in the advantageous effects of exercise on toluene-induced addictive responses has not been explored., Objectives: To evaluate the impact of different exercise regimens in mitigating the expression of toluene-induced locomotor sensitization and to analyze changes in RAS elements' expression at the mesocorticolimbic system after repeated toluene exposure and following voluntary wheel running in toluene-sensitized animals., Methods: Toluene-induced addictive-like response was evaluated with a locomotor sensitization model in mice. Toluene-sensitized animals had access to running wheels 1, 2, 4 or 24 h/day for 4 weeks; thereafter, locomotor sensitization expression was evaluated after a toluene challenge. RAS elements (ACE and ACE2 enzymes; AT1, AT2 and Mas receptors) expression was determined by Western blot in the VTA, NAc and PFCx of toluene-sensitized mice with and without exercise., Results: Individual differences in toluene-induced locomotor sensitization development were observed. Access to wheel running 1 and 2 h/day reduced but 4 and 24 h/day completely blocked locomotor sensitization expression. Repeated toluene exposure changed RAS elements' expression in the VTA, NAc and PFCx, while exercise mainly modified ACE and AT1 in air-exposed and toluene-sensitized mice., Conclusions: Inhalant-exposed animals show different sensitization phenotypes. Exercise duration determined its efficacy to attenuate the addictive-like response. Toluene exposure and exercise each modified RAS, the latter also modifying toluene-induced changes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Evidence from clinical and preclinical studies has shown that the cerebellum contributes to cognitive functions, including social behaviors. Now that the cerebellum's role in a wider range of behaviors has been confirmed, the question arises whether the cerebellum contributes to social behaviors via the same mechanisms with which it modulates movements. This review seeks to answer whether the cerebellum guides motor and social behaviors through identical pathways. It focuses on studies in which cerebellar cells, synapses, or genes are manipulated in a cell-type specific manner followed by testing of the effects on social and motor behaviors. These studies show that both anatomically restricted and cerebellar cortex-wide manipulations can lead to social impairments without abnormal motor control, and vice versa. These studies suggest that the cerebellum employs different cellular, synaptic, and molecular pathways for social and motor behaviors. Future studies warrant a focus on the diverging mechanisms by which the cerebellum contributes to a wide range of neural functions., (© 2024. The Author(s).)

The circadian system coordinates multiple behavioral outputs to ensure proper temporal organization. Timing information underlying circadian regulation of behavior depends on a molecular circadian clock that operates within clock neurons in the brain. In Drosophila and other organisms, clock neurons can be divided into several molecularly and functionally discrete subpopulations that form an interconnected central clock network. It is unknown how circadian signals are coherently generated by the clock network and transmitted across output circuits that connect clock cells to downstream neurons that regulate behavior. Here, we have exhaustively investigated the contribution of clock neuron subsets to the control of two prominent behavioral outputs in Drosophila : locomotor activity and feeding. We have used cell-specific manipulations to eliminate molecular clock function or induce electrical silencing either broadly throughout the clock network or in specific subpopulations. We find that clock cell manipulations produce similar changes in locomotor activity and feeding, suggesting that overlapping central clock circuitry regulates these distinct behavioral outputs. Interestingly, the magnitude and nature of the effects depend on the clock subset targeted. Lateral clock neuron manipulations profoundly degrade the rhythmicity of feeding and activity. In contrast, dorsal clock neuron manipulations only subtly affect rhythmicity but produce pronounced changes in the distribution of activity and feeding across the day. These experiments expand our knowledge of clock regulation of activity rhythms and offer the first extensive characterization of central clock control of feeding rhythms. Despite similar effects of central clock cell disruptions on activity and feeding, we find that manipulations that prevent functional signaling in an identified output circuit preferentially degrade locomotor activity rhythms, leaving feeding rhythms relatively intact. This demonstrates that activity and feeding are indeed dissociable behaviors, and furthermore suggests that differential circadian control of these behaviors diverges in output circuits downstream of the clock network., Competing Interests: Conflict of interest statementThe authors have no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Fluctuations in estradiol levels at each stage of life in women are considered one of the causes of mental diseases through their effects on the central nervous system. During menopause, a decrease in estradiol levels has been reported to affect the serotonin nervous system and induce depression-like and anxiety symptoms. However, the regulation of brain and behaviour during childhood and adolescence is poorly understood. Moreover, the role of oestrogen receptors α and β in the regulation of the serotonergic nervous system has been reported, but little is known about the involvement of G protein-coupled receptor 30. Therefore, in this study, we used an ovariectomized childhood mouse model to analyse behaviour and investigate the effects on the serotonin nervous system. We showed that ovariectomy surgery at 4 weeks of age, which is the weaning period, induced a decrease in spontaneous locomotor activity during the active period and a preference for novel mice over familiar mice in the three-chamber social test at 10 weeks of age. In addition, the administration of G-1, a protein-coupled receptor 30 agonist, to ovariectomized mice suppressed spontaneous locomotor activity and the preference for novel mice. Furthermore, we demonstrated that childhood ovariectomy induces increased tryptophan hydroxylase gene expression in the raphe nucleus and increased serotonin release in the amygdaloid nucleus, and administration of G-1 ameliorated these effects. Our study suggests that G protein-coupled receptor 30-mediated regulation of serotonin synthesis is involved in changes in activity and social-cognitive behaviour due to decreased estradiol levels during childhood., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Study Design: Experimental animal study., Objectives: To investigate the protective effect of remote limb ischemia preconditioning (RLPreC) on traumatic spinal cord injury (SCI) and explore the underlying biological mechanisms using RNA sequencing., Setting: China Rehabilitation Science Institute; Beijing; China., Methods: spinal cord injury was induced in mice using a force of 0.7 N. RLPreC treatment was administered. Motor function, pain behavior, and gene expression were assessed., Results: RLPreC treatment significantly improved motor function and reduced pain-like behavior in SCI mice. RNA-Seq analysis identified 5247 differentially expressed genes (DEGs). GO analysis revealed enrichment of immune response, inflammatory signaling, and synaptic transmission pathways among these DEGs. KEGG analysis indicated suppression of inflammation and promotion of synapse-related pathways., Conclusions: RLPreC is a promising therapeutic strategy for improving motor function and alleviating pain after traumatic SCI. RNA-Seq analysis provides insights into potential therapeutic targets and warrants further investigation., (© 2024. The Author(s), under exclusive licence to International Spinal Cord Society.)

Background: In electroencephalographic (EEG) or electrocorticographic (ECoG) experiments, visual cues are commonly used for timing synchronization but may inadvertently induce neural activity and cognitive processing, posing challenges when decoding self-initiated tasks., New Method: To address this concern, we introduced four new visual cues (Fade, Rotation, Reference, and Star) and investigated their impact on brain signals. Our objective was to identify a cue that minimizes its influence on brain activity, facilitating cue-effect free classifier training for asynchronous applications, particularly aiding individuals with severe paralysis., Results: 22 able-bodied, right-handed participants aged 18-30 performed hand movements upon presentation of the visual cues. Analysis of time-variability between movement onset and cue-aligned data, grand average MRCP, and classification outcomes revealed significant differences among cues. Rotation and Reference cue exhibited favorable results in minimizing temporal variability, maintaining MRCP patterns, and achieving comparable accuracy to self-paced signals in classification., Comparison With Existing Methods: Our study contrasts with traditional cue-based paradigms by introducing novel visual cues designed to mitigate unintended neural activity. We demonstrate the effectiveness of Rotation and Reference cue in eliciting consistent and accurate MRCPs during motor tasks, surpassing previous methods in achieving precise timing and high discriminability for classifier training., Conclusions: Precision in cue timing is crucial for training classifiers, where both Rotation and Reference cue demonstrate minimal variability and high discriminability, highlighting their potential for accurate classifications in online scenarios. These findings offer promising avenues for refining brain-computer interface systems, particularly for individuals with motor impairments, by enabling more reliable and intuitive control mechanisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Kisspeptins are essential regulators of the reproductive axis, with capacity to potently activate gonadotropin-releasing hormone neurons, acting also as central conduits for the metabolic regulation of fertility. Recent evidence suggests that kisspeptins per se may also modulate several metabolic parameters, including body weight, food intake or energy expenditure, but their actual roles and site(s) of action remain unclear. We present herein a series of studies addressing the metabolic effects of central and peripheral administration of kisspeptin-10 (Kp-10; 1 nmol and 3 nmol daily, respectively) for 11 days in mice of both sexes. To assess direct metabolic actions of Kp-10 versus those derived indirectly from its capacity to modulate gonadal hormone secretion, kisspeptin effects were tested in adult male and female mice gonadectomized and supplemented with fixed, physiological doses of testosterone or 17β-estradiol, respectively. Central administration of Kp-10 decreased food intake in male mice, especially during the dark phase (~50%), which was accompanied by a reduction in total and nocturnal energy expenditure (~16%) and locomotor activity (~70%). In contrast, opposite patterns were detected in female mice, with an increase in total and nocturnal locomotor activity (>65%), despite no changes in food intake or energy expenditure. These changes were independent of body weight, as no differences were detected in mice of both sexes at the end of Kp-10 treatments. Peripheral administration of Kp-10 failed to alter any of the metabolic parameters analyzed, except for a decrease in locomotor activity in male mice and a subtle increase in 24 h food intake in female mice, denoting a predominant central role of kisspeptins in the control of energy metabolism. Finally, glucose tolerance and insulin sensitivity were not significantly affected by central or peripheral treatment with Kp-10. In conclusion, our data reveal a potential role of kisspeptins in the control of key metabolic parameters, including food intake, energy expenditure and locomotor activity, with a preferential action at central level, which is sex steroid-independent but sexually dimorphic., (© 2024 The Author(s). Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

The timing, rate, and quantity of gestational alcohol consumption, collectively referred to here as Maternal Drinking Patterns (MDPs), are of known importance to fetal developmental outcomes. However, few studies have directly evaluated the impact of MDPs on offspring behavior. To do so, we used specialized equipment to record the precise amount and timing of alcohol consumption in pregnant dams, and then characterized MDPs using Principle Component Analysis (PCA). We next tested offspring on behaviors we have previously identified as impacted by prenatal alcohol exposure, and evaluated them where possible in the context of MDPs. Male alcohol exposed mice exhibited longer latencies to fall on the rotarod compared to their controls, which we attribute to a delayed decrease in body weight-gain. This effect was mediated by MDPs within the first 15 min of alcohol access (i.e. alcohol frontloading), where the highest performing male offspring came from dams exhibiting the highest rate of alcohol frontloading. Female alcohol exposed mice displayed reduced locomotor activity in the open field compared to controls, which was mediated by MDPs encompassing the entire drinking session. Surprisingly, total gestational alcohol exposure alone was not associated with any behavioral outcomes. Finally, we observed allodynia in alcohol exposed mice that developed more quickly in males compared to females, and which was not observed in controls. To our knowledge, this report represents the highest resolution assessment of alcohol drinking throughout gestation in mice, and one of few to have identified relationships between specific alcohol MDPs and neurobehavioral outcomes in offspring., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to objectively assess signs of hyperactivity in adults suspected of having ADHD, addressing potential sex bias in diagnosis., Methods: About 13,179 (49% female) adults with an average age of 33 years with ADHD and 1,910 (41% female) adults with an average age of 36 years without ADHD were included. Motor activity was measured using the Quantified Behavioral Test, analyzing "provoked," and "basal" activity. Sex by group differences were analyzed using analysis of variance., Results: Results showed significant ADHD effects on the basal and provoked activity measures, while sex effects were only notable for provoked activity. Males, irrespective of diagnosis, exhibited higher provoked activity than females, while both sexes with ADHD displayed approximately twice the basal activity and about three times the provoked activity compared to their respective sex controls., Conclusion: These findings suggest that females with ADHD suffer equally from hyperactivity compared to males, challenging the notion of a sex-dependent presentation of hyperactivity. This may lead to more accurate and timely diagnoses, reducing ADHD-related burdens and comorbidities in females., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: One of the co-authors, K. Wettstein, is a shareholder in ADHDcentraal, which may be perceived as a potential conflict of interest related to this research. ADHDcentraal was not involved in the design, analysis, or reporting of this study. The remaining authors declare no conflicts of interest.

Objective: Advancements in neuroimaging technologies have significantly deepened our understanding of the neural physiopathology associated with stroke. Nevertheless, the majority of studies ignored the characteristics of dynamic changes in brain networks. The relationship between dynamic changes in brain networks and the severity of motor dysfunction after stroke needs further investigation. From the perspective of multilayer network module reconstruction, we aimed to explore the dynamic reorganization of the brain and its relationship with motor function in subcortical stroke patients., Methods: We recruited 35 healthy individuals and 50 stroke patients with unilateral limb motor dysfunction (further divided into mild-moderate group and severe group). Using dynamic multilayer network modularity analysis, we investigated changes in the dynamic modular reconfiguration of brain networks. Additionally, we assessed longitudinal clinical scale changes in stroke patients. Correlation and regression analyses were employed to explore the relationship between characteristic dynamic indicators and impairment and recovery of motor function, respectively., Results: We observed increased temporal flexibility in the Default Mode Network (DMN) and decreased recruitment of module reconfiguration in the Attention Network (AN), Sensorimotor Network (SMN), and DMN after stroke. We also observed reduced module loyalty following stroke. Additionally, correlation analysis showed that hyper-flexibility of the DMN was associated with better lower limb motor function performance in stroke patients with mild-to-moderate impairment. Regression analysis indicated that increased flexibility within the DMN and decreased recruitment coefficient within the AN may predict good lower limb function prognosis in patients with mild to moderate motor impairment., Conclusions: Our study revealed more frequent modular reconfiguration and hyperactive interaction of brain networks after stroke. Notably, dynamic modular remodeling was closely related to the impairment and recovery of motor function. Understanding the temporal module reconfiguration patterns in multilayer networks after stroke can provide valuable information for more targeted treatments., (© 2024 The Author(s). Published by IMR Press.)

Background: The natural light environment is far more complex than that experienced by animals under laboratory conditions. As a burrowing species, wild mice are able to self-modulate their light exposure, a concept known as light environment sampling behaviour. By contrast, under laboratory conditions mice have little opportunity to exhibit this behaviour. To address this issue, here we introduce a simple nestbox paradigm to allow mice to self-modulate their light environment. Dark nestboxes fitted with passive infrared sensors were used to monitor locomotor activity, circadian entrainment, decision making and light environment sampling behaviour., Results: Under these conditions, mice significantly reduce their light exposure to an average of just 0.8 h across a 24 h period. In addition, mice show a distinct pattern of light environment sampling behaviour, with peaks at dawn and dusk under a ramped light dark cycle. Furthermore, we show that the timing of light environment sampling behaviour depends upon endogenous circadian rhythms and is abolished in mice lacking a circadian clock, indicating a feedback loop between light, the circadian clock and behaviour., Conclusions: Our results highlight the important role of behaviour in modifying the light signals available for circadian entrainment under natural conditions., (© 2024. The Author(s).)

Highveld mole-rats (Cryptomys hottentotus pretoriae) are social rodents that inhabit networks of subterranean tunnels. In their natural environment, they are rarely exposed to light, and consequently their visual systems have regressed over evolutionary time. However, in the laboratory they display nocturnal activity, suggesting that they are sensitive to changes in ambient illumination. We examined the robustness of the Highveld mole-rat circadian system by assessing its locomotor activity under decreasing light intensities. Mole-rats were subjected to seven consecutive light cycles commencing with a control cycle (overhead fluorescent lighting at 150 lx), followed by decreasing LED lighting (500, 300, 100, 10 and 1 lx) on a 12 h light:12 h dark (L:D) photoperiod and finally a constant darkness (DD) cycle. Mole-rats displayed nocturnal activity under the whole range of experimental lighting conditions, with a distinct spike in activity at the end of the dark phase in all cycles. The mole-rats were least active during the control cycle under fluorescent light, locomotor activity increased steadily with decreasing LED light intensities, and the highest activity was exhibited when the light was completely removed. In constant darkness, mole-rats displayed free-running rhythms with periods (τ) ranging from 23.77 to 24.38 h, but was overall very close to 24 h at 24.07 h. Our findings confirm that the Highveld mole-rat has a higher threshold for light compared with aboveground dwelling rodents, which is congruent with previous neurological findings, and has implications for behavioural rhythms., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Individual differences in drug use emerge soon after initial exposure, and only a fraction of individuals who initiate drug use go on to develop a substance use disorder. Variability in vulnerability to establishing drug self-administration behavior is also evident in preclinical rodent models. Latent characteristics that underlie this variability and the relationship between early drug use patterns and later use remain unclear. Here, we attempt to determine whether propensity to establish cocaine self-administration is related to subsequent cocaine self-administration behavior in male Sprague-Dawley rats (n = 14). Prior to initiating training, we evaluated basal locomotor and anxiety-like behavior in a novel open field test. We then trained rats to self-administer cocaine in daily 3 h cocaine (0.75 mg/kg/infusion) self-administration sessions until acquisition criteria (≥30 active lever presses with ≥70 % responding on the active lever in one session) was met and divided rats into Early and Late groups by median-split analysis based on their latency to meet acquisition criteria. After each rat met acquisition criteria, we gave them 10 additional daily cocaine self-administration sessions. We then conducted a progressive ratio, cocaine-induced locomotor sensitivity test, and non-reinforced cocaine seeking test after two weeks of forced abstinence. Early Learners exhibited significantly less locomotion after an acute injection of cocaine, but the groups did not differ in any other behavioral parameter examined. These results indicate that cocaine self-administration acquisition latency is not predictive of subsequent drug-taking behavior, but may be linked to physiological factors like drug sensitivity that can predispose rats to learn the operant task., Competing Interests: Conflict of Interest The authors declare no competing financial interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Muscle mass and phase angle (PhA) can be measured using multi-frequency bioelectrical impedance analysis (BIA). Osteoarthritis of the hip (OAhip) causes decreased muscle mass and PhA in the deformed lower limb. However, previous studies have not accounted for the influence of sex, and thus, the relationship between muscle mass, PhA, and motor function remains unclear. This study aimed to elucidate the relationship between PhA, an index of muscle mass and quality measured using BIA, and motor function during gait and standing in female patients with OAhip., Methods: Muscle mass and PhA of patients with OAhip were measured using BIA. Motor function was evaluated using the Timed Up and Go test, ground reaction/weight, rate of force development/weight, and load ratio between the osteoarthritic (OA) and contralateral sides when standing up. The difference between the OA side and the contralateral lower limb was tested to clarify the characteristics of the deformed lower limb. The relationship between each motor function was determined using a partial correlation coefficient with age as a control variable and multiple regression analysis with each motor function as the dependent variable and age, OA-side muscle mass/body weight ratio, and PhA as independent variables., Results: This study involved 60 patients with OAhip (age 65.6 ± 7.6 years, height 154.2 ± 6.0 cm, weight 56.8 ± 10.5 kg) scheduled for unilateral total hip arthroplasty. Muscle mass, PhA, and lower limb load ratio were significantly decreased in the lower limbs on the OA side. Furthermore, using a partial correlation coefficient with age as a control variable, PhA showed significant correlations with motor functions related to standing up and walking, and multiple regression analysis revealed that PhA was independently related to each motor function., Conclusions: Evaluation and interventions that consider muscle quality rather than muscle mass are important., (© 2024. The Author(s).)

The present study aimed to describe the cortical connectivity of a sector located in the ventral bank of the superior temporal sulcus in the macaque (intermediate area TEa and TEm [TEa/m]), which appears to represent the major source of output of the ventral visual stream outside the temporal lobe. The retrograde tracer wheat germ agglutinin was injected in the intermediate TEa/m in four macaque monkeys. The results showed that 58-78% of labeled cells were located within ventral visual stream areas other than the TE complex. Outside the ventral visual stream, there were connections with the memory-related medial temporal area 36 and the parahippocampal cortex, orbitofrontal areas involved in encoding subjective values of stimuli for action selection, and eye- or hand-movement related parietal (LIP, AIP, and SII), prefrontal (12r, 45A, and 45B) areas, and a hand-related dysgranular insula field. Altogether these data provide a solid substrate for the engagement of the ventral visual stream in large scale cortical networks for skeletomotor or oculomotor control. Accordingly, the role of the ventral visual stream could go beyond pure perceptual processes and could be also finalized to the neural mechanisms underlying the control of voluntary motor behavior., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Degeneration of dopaminergic neurons in the substantia nigra and their striatal axon terminals causes cardinal motor symptoms of Parkinson's disease. In idiopathic cases, high levels of mitochondrial DNA alterations, leading to mitochondrial dysfunction, are a central feature of these vulnerable neurons. Here we present a mouse model expressing the K320E variant of the mitochondrial helicase Twinkle in dopaminergic neurons, leading to accelerated mitochondrial DNA mutations. These K320E-TwinkleDaN mice showed normal motor function at 20 months of age, although ∼70% of nigral dopaminergic neurons had perished. Remaining neurons still preserved ∼75% of axon terminals in the dorsal striatum and enabled normal dopamine release. Transcriptome analysis and viral tracing confirmed compensatory axonal sprouting of the surviving neurons. We conclude that a small population of substantia nigra dopaminergic neurons is able to adapt to the accumulation of mitochondrial DNA mutations and maintain motor control., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)