Study protocol for the ACTIVE SCHOOL study investigating two different strategies of physical activity to improve academic performance in Schoolchildren.

BACKGROUND: Previous research has suggested that school-based physical activity (PA) interventions may have a positive impact on academic performance. However, existing literature on school-based interventions encompasses various forms of PA, spanning from vigorous intensity PA outside the academic classes to light intensity PA and movement integrated into academic learning tasks, and results on academic performance are inconclusive. ACTIVE SCHOOL will implement two different PA interventions for one school year and assess the effects on the pupils' academic performance, with math performance as the primary outcome. METHODS/DESIGN: The ACTIVE SCHOOL project consists of two phases: 1) Development phase and 2) Randomized Controlled Trial (RCT). In phase one, two interventions were developed in collaboration with school staff. The two interventions were tested in an 8-weeks feasibility study. In phase two, a RCT-study with three arms will be conducted in 9-10-year-old children for one school year. The RCT-study will be carried out in two intervention rounds during the school years 2023/2024 and 2024/2025. Schools will be randomized to one of two interventions or control;1) Run, Jump & Fun intervention (4 × 30 min/week of moderate-to-vigorous physical activity; 2) Move & Learn intervention (4 × 30 min/week focusing on embodied learning in math and Danish lessons); or 3) a control condition, consisting of normal teaching practices. Outcome measures include academic performance, PA level, cognitive functions, cardiorespiratory fitness, anthropometry, well-being and school motivation (collected before, during and after the intervention period). A process evaluation will be conducted to assess implementation. DISCUSSION: The ACTIVE SCHOOL study will expand knowledge regarding the impact of PA on academic performance. The study will have the potential to significantly contribute to future research, as well as the scientific and educational debate on the best way to implement PA to support education and learning. TRIAL REGISTRATION: The study was registered on the 25th of October 2022 in ClinicalTrials.gov, NCT05602948.

Motor-enriched learning for improving pre-reading and word recognition skills in preschool children aged 5-6 years - study protocol for the PLAYMORE randomized controlled trial.

BACKGROUND: Results from previous studies suggest that bodily movements, spanning from gestures to whole-body movements, integrated into academic lessons may benefit academic learning. However, only few studies have investigated the effects of movement integrated into reading practice. The PLAYMORE study aims to investigate the effects of two interventions focusing on a close and meaningful coupling between bodily movement and academic content on early pre-reading and word recognition skills in children. Further, the study aims to compare two interventions involving either hand movements (i.e. using arms and hands) or whole-body movements (i.e. using the whole body). Potential mediating factors underlying the link between bodily movement on early pre-reading and word recognition skills will be explored. METHODS/DESIGN: The PLAYMORE study will be conducted as a three-armed randomized controlled trial including children aged five to six years recruited from four schools in the Copenhagen area, Denmark. Stratified by class, children will be randomly allocated to one of three 8-week intervention/control periods: 1) teaching involving whole-body movements, 2) teaching involving hand movements (i.e. arms and hands) or 3) teaching involving minimal motor movements (i.e. seated on a chair using paper and pencil). Outcome measurements, including pre-reading and word recognition skills, will be collected before and after the intervention period to assess the intervention effects. This study protocol follows the SPIRIT guidelines. DISCUSSION: The PLAYMORE study will add to the current knowledge concerning the link between bodily movement and academic performance with important details about pre-reading and word recognition skills in preschool children. If effective, evaluation of the implementation of the PLAYMORE program should be conducted in order to investigate whether the effects can be transferred into standard school settings. The PLAYMORE study will lay the foundation for future research that have the potential to inform the political and scientific debate and importantly, to provide teachers with detailed information of how to implement movements effectively during teaching in order to support and motivate children in the process of learning to read. TRIAL REGISTRATION: The study was retrospectively registered in ClinicalTrials.gov ( NCT04618822 ) the 5th of November 2020.

Immobilization leads to reduced stretch reflexes but increased central reflex gain in the rat.

Plastic adaptations are known to take place in muscles, tendons, joints, and the nervous system in response to changes in muscle activity. However, few studies have addressed how these plastic adaptations are related. Thus this study focuses on changes in the mechanical properties of the ankle plantarflexor muscle-tendon unit, stretch reflex activity, and spinal neuronal pathways in relation to cast immobilization. The left rat hindlimb from toes to hip was immobilized with a plaster cast for 1, 2, 4, or 8 wk followed by acute electrophysiological recordings to investigate muscle stiffness and stretch reflex torque. Moreover, additional acute experiments were performed after 4 wk of immobilization to investigate changes in the central gain of the stretch reflex. Monosynaptic reflexes (MSR) were recorded from the L4 and L5 ventral roots following stimulation of the corresponding dorsal roots. Rats developed reduced range of movement in the ankle joint 2 wk after immobilization. This was accompanied by significant increases in the stiffness of the muscle-tendon complex as well as an arthrosis at the ankle joint at 4 and 8 wk following immobilization. Stretch reflexes were significantly reduced at 4-8 wk following immobilization. This was associated with increased central gain of the stretch reflex. These data show that numerous interrelated plastic changes occur in muscles, connective tissue, and the central nervous system in response to changes in muscle use. The findings provide an understanding of coordinated adaptations in multiple tissues and have important implications for prevention and treatment of the negative consequences of immobilization following injuries of the nervous and musculoskeletal systems.NEW & NOTEWORTHY Immobilization leads to multiple simultaneous adaptive changes in muscle, connective tissue, and central nervous system.

The Subprimary Range of Firing Is Present in Both Cat and Mouse Spinal Motoneurons and Its Relationship to Force Development Is Similar for the Two Species.

In the motor system, force gradation is achieved by recruitment of motoneurons and rate modulation of their firing frequency. Classical experiments investigating the relationship between injected current to the soma during intracellular recording and the firing frequency (the I-f relation) in cat spinal motoneurons identified two clear ranges: a primary range and a secondary range. Recent work in mice, however, has identified an additional range proposed to be exclusive to rodents, the subprimary range (SPR), due to the presence of mixed mode oscillations of the membrane potential. Surprisingly, fully summated tetanic contractions occurred in mice during SPR frequencies. With the mouse now one of the most popular models to investigate motor control, it is crucial that such discrepancies between observations in mice and basic principles that have been widely accepted in larger animals are resolved. To do this, we have reinvestigated the I-f relation using ramp current injections in spinal motoneurons in both barbiturate-anesthetized and decerebrate (nonanesthetized) cats and mice. We demonstrate the presence of the SPR and mixed mode oscillations in both species and show that the SPR is enhanced by barbiturate anesthetics. Our measurements of the I-f relation in both cats and mice support the classical opinion that firing frequencies in the higher end of the primary range are necessary to obtain a full summation. By systematically varying the leg oil pool temperature (from 37°C to room temperature), we found that only at lower temperatures can maximal summation occur at SPR frequencies due to prolongation of individual muscle twitches.SIGNIFICANCE STATEMENT This work investigates recent revelations that mouse motoneurons behave in a fundamentally different way from motoneurons of larger animals with respect to the importance of rate modulation of motoneuron firing for force gradation. The current study systematically addresses the proposed discrepancies between mice and larger species (cats) and demonstrates that mouse motoneurons, in fact, use rate modulation as a mechanism of force modulation in a similar manner to the classical descriptions in larger animals.

Muscle disuse caused by botulinum toxin injection leads to increased central gain of the stretch reflex in the rat.

Botulinum toxin (Btx) is used in children with cerebral palsy and in other neurological patients to diminish spasticity and reduce the risk of development of contractures. We investigated changes in the central gain of the stretch reflex circuitry in response to Btx injection in the triceps surae muscle in rats. Experiments were performed in 21 rats. Eight rats were a control group, and 13 rats were injected with 6 IU of Btx in the left triceps surae muscle. Two weeks after Btx injection, larger monosynaptic reflexes (MSR) were recorded from the left (injected) than the right (noninjected) L4 + L5 ventral roots following stimulation of the corresponding dorsal roots. A similar increase on the left side was observed in response to stimulation of descending motor tracts, suggesting that increased excitability of spinal motor neurons may at least partly explain the increased reflexes. However, significant changes were also observed in postactivation depression of the MSR, suggesting that plastic changes in transmission from Ia afferent to the motor neurons also may be involved. The data demonstrate that muscle paralysis induced by Btx injection is accompanied by plastic adaptations in the central stretch reflex circuitry, which counteract the antispastic effect of Btx.NEW & NOTEWORTHY Injection of botulinum toxin into ankle muscles causes increased gain of stretch reflex. This is caused by adaptive changes in regulation of transmitter release from Ia afferents and increased excitability of spinal motor neurons.

Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat.

Botulinum toxin is used with the intention of diminishing spasticity and reducing the risk of development of contractures. Here, we investigated changes in muscle stiffness caused by reflex activity or elastic muscle properties following botulinum toxin injection in the triceps surae muscle in rats. Forty-four rats received injection of botulinum toxin in the left triceps surae muscle. Control measurements were performed on the noninjected contralateral side in all rats. Acute experiments were performed, 1, 2, 4, and 8 wk following injection. The triceps surae muscle was dissected free, and the Achilles tendon was cut and attached to a muscle puller. The resistance of the muscle to stretches of different amplitudes and velocities was systematically investigated. Reflex-mediated torque was normalized to the maximal muscle force evoked by supramaximal stimulation of the tibial nerve. Botulinum toxin injection caused severe atrophy of the triceps surae muscle at all time points. The force generated by stretch reflex activity was also strongly diminished but not to the same extent as the maximal muscle force at 2 and 4 wk, signifying a relative reflex hyperexcitability. Passive muscle stiffness was unaltered at 1 wk but increased at 2, 4, and 8 wk (P < 0.01). These data demonstrate that botulinum toxin causes a relative increase in reflex stiffness, which is likely caused by compensatory neuroplastic changes. The stiffness of elastic elements in the muscles also increased. The data are not consistent with the ideas that botulinum toxin is an efficient antispastic medication or that it may prevent development of contractures.

Functional interaction between Lypd6 and nicotinic acetylcholine receptors.

Nicotinic acetylcholine receptors (nAChRs) affect multiple physiological functions in the brain and their functions are modulated by regulatory proteins of the Lynx family. Here, we report for the first time a direct interaction of the Lynx protein LY6/PLAUR domain-containing 6 (Lypd6) with nAChRs in human brain extracts, identifying Lypd6 as a novel regulator of nAChR function. Using protein cross-linking and affinity purification from human temporal cortical extracts, we demonstrate that Lypd6 is a synaptically enriched membrane-bound protein that binds to multiple nAChR subtypes in the human brain. Additionally, soluble recombinant Lypd6 protein attenuates nicotine-induced hippocampal inward currents in rat brain slices and decreases nicotine-induced extracellular signal-regulated kinase phosphorylation in PC12 cells, suggesting that binding of Lypd6 is sufficient to inhibit nAChR-mediated intracellular signaling. We further show that perinatal nicotine exposure in rats (4 mg/kg/day through minipumps to dams from embryonic day 7 to post-natal day 21) significantly increases Lypd6 protein levels in the hippocampus in adulthood, which did not occur after exposure to nicotine in adulthood only. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain, and that Lypd6 is dysregulated by nicotine exposure during early development. Regulatory proteins of the Lynx family modulate the function of nicotinic receptors (nAChRs). We report for the first time that the Lynx protein Lypd6 binds to nAChRs in human brain extracts, and that recombinant Lypd6 decreases nicotine-induced ERK phosphorylation and attenuates nicotine-induced hippocampal inward currents. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain.

Spinal cord injury enables aromatic L-amino acid decarboxylase cells to synthesize monoamines.

Serotonin (5-HT), an important modulator of both sensory and motor functions in the mammalian spinal cord, originates mainly in the raphe nuclei of the brainstem. However, following complete transection of the spinal cord, small amounts of 5-HT remain detectable below the lesion. It has been suggested, but not proven, that this residual 5-HT is produced by intraspinal 5-HT neurons. Here, we show by immunohistochemical techniques that cells containing the enzyme aromatic l-amino acid decarboxylase (AADC) occur not only near the central canal, as reported by others, but also in the intermediate zone and dorsal horn of the spinal gray matter. We show that, following complete transection of the rat spinal cord at S2 level, AADC cells distal to the lesion acquire the ability to produce 5-HT from its immediate precursor, 5-hydroxytryptophan. Our results indicate that this phenotypic change in spinal AADC cells is initiated by the loss of descending 5-HT projections due to spinal cord injury (SCI). By in vivo and in vitro electrophysiology, we show that 5-HT produced by AADC cells increases the excitability of spinal motoneurons. The phenotypic change in AADC cells appears to result from a loss of inhibition by descending 5-HT neurons and to be mediated by 5-HT1B receptors expressed by AADC cells. These findings indicate that AADC cells are a potential source of 5-HT at spinal levels below an SCI. The production of 5-HT by AADC cells, together with an upregulation of 5-HT2 receptors, offers a partial explanation of hyperreflexia below a chronic SCI.

Spinal Cord Hemisection Facilitates Aromatic L-Amino Acid Decarboxylase Cells to Produce Serotonin in the Subchronic but Not the Chronic Phase.

Neuromodulators, such as serotonin (5-hydroxytryptamine, 5-HT) and noradrenalin, play an essential role in regulating the motor and sensory functions in the spinal cord. We have previously shown that in the rat spinal cord the activity of aromatic L-amino acid decarboxylase (AADC) cells to produce 5-HT from its precursor (5-hydroxytryptophan, 5-HTP) is dramatically increased following complete spinal cord transection. In this study, we investigated whether a partial loss of 5-HT innervation could similarly increase AADC activity. Adult rats with spinal cord hemisected at thoracic level (T11/T12) were used with a postoperation interval at 5 days or 60 days. Using immunohistochemistry, first, we observed a significant reduction in the density of 5-HT-immunoreactive fibers in the spinal cord below the lesion on the injured side for both groups. Second, we found that the AADC cells were similarly expressed on both injured and uninjured sides in both groups. Third, increased production of 5-HT in AADC cells following 5-HTP was seen in 5-day but not in 60-day postinjury group. These results suggest that plastic changes of the 5-HT system might happen primarily in the subchronic phase and for longer period its function could be compensated by plastic changes of other intrinsic and/or supraspinal modulation systems.

Decrease in reaction time for volleyball athletes during saccadic eye movement task: A preliminary study with evoked potentials.

AIM: This preliminary study investigated the differences in event-related potential and reaction time under two groups (athletes vs. non-athletes). MATERIAL AND METHODS: The P300 was analyzed for Fz, Cz, and Pz electrodes in thirty-one healthy volunteers divided into two groups (volleyball athletes and non-athletes). In addition, the participants performed a saccadic eye movement task to measure reaction time. RESULTS: The EEG analysis showed that the athletes, in comparison to the no-athletes, have differences in the P300 in the frontal area (p = 0.021). In relation to reaction time, the results show lower reaction time for athletes (p = 0.001). CONCLUSIONS: The volleyball athletes may present a greater allocation of attention during the execution of the inhibition task, since they have a lower reaction time for responses when compared to non-athletes.

Transient activation of mTOR following forced treadmill exercise in rats.

The beneficial effect of exercise on hippocampal plasticity is possibly mediated by increased angiogenesis and neurogenesis. In angiogenesis, insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor 1, alpha subunit (HIF1α) are important factors, while the induction of neurogenesis requires signaling through the VEGF receptor, Flk-1 (VEGFR-2). VEGF expression is believed to be regulated by two distinct mTOR (mammalian target of Rapamycin)-containing multiprotein complexes mTORC1 and mTORC2, respectively. This study was initiated to investigate the effect of exercise on the expression of VEGF, cognate receptors, HIF1α, mTORC1, and mTORC2 in hippocampus and frontal cortex. To this end, we measured messenger RNA (mRNA) levels in rat brain using quantitative real-time polymerase chain reaction (real-time qPCR) after forced treadmill exercise for 1 day, 2 weeks, and 8 weeks. Rats were euthanized either immediately (0 h) or 24 h after last exercise session. Here, we show that exercise affected mRNA levels of VEGF, VEGFR2, and the coreceptor neuropilin 2 (NRP2) when the rats were euthanized immediately, whereas at 24 h only the expression of mTOR was regulated after a single bout of exercise. In conclusion, the effect of treadmill exercise on the VEGF system is acute rather than chronic and there is a transient activation of mTOR. More studies are needed to understand whether this could be beneficial in the treatment of neuropsychiatric disorders.

Visuomotor skill learning in young adults with Down syndrome.

BACKGROUND: Individuals with Down syndrome (DS) have impaired general motor skills compared to typically developed (TD) individuals. AIMS: To gain knowledge on how young adults with DS learn and retain new motor skills. METHODS AND PROCEDURES: A DS-group (mean age = 23.9 ± 3 years, N = 11), and an age-matched TD-group (mean age 22.8 ± 1.8, N = 14) were recruited. The participants practiced a visuomotor accuracy tracking task (VATT) in seven blocks (10.6 min). Online and offline effects of practice were assessed based on tests of motor performance at baseline immediate and 7-day retention. OUTCOMES AND RESULTS: The TD-group performed better than the DS-group on all blocks (all P < 0.001). Both groups improved VATT-performance online from baseline to immediate retention, (all P < 0.001) with no difference in online effect between groups. A significant between-group difference was observed in the offline effect (∆TD - ∆DS, P = 0.04), as the DS-group's performance at 7-day retention was equal to their performance at immediate retention (∆DS, P > 0.05), whereas an offline decrease in performance was found in the TD-group (∆TD, P < 0.001). CONCLUSIONS AND IMPLICATIONS: Visuomotor pinch force accuracy is lower for adults with DS compared to TD. However, adults with DS display significant online improvements in performance with motor practice similar to changes observed for TD. Additionally, adults with DS demonstrate offline consolidation following motor learning leading to significant retention effects.

The Health Effects of 14 Weeks of Physical Activity in a Real-Life Setting for Adults with Intellectual Disabilities.

Background: The life expectancy of individuals with intellectual disabilities (ID) is reduced compared to the general population, and one of the main contributors to earlier death is inactivity. Aim: To investigate how 14 weeks of physical activity (PA) in a real-life setting affects cardiovascular fitness, body composition and bone health of adults with ID. Methods: Adults with ID were recruited into a PA-group (N = 52) or a control group (CON, N = 14). The PA-group participated in 14 weeks of PA, and body composition, cardiovascular fitness and bone health were assessed before and after the intervention. Outcomes and Results. Cardiovascular fitness and body composition improved from pre to post within the PA-group: Heart rates (HR) during the last 30 seconds of two increments of a treadmill test, were reduced (3.2 km/h: -4.4 bpm, p < 0.05; 4.8 km/h: -7.5 bpm, p < 0.001) and fat mass was reduced (-1.02 kg, p < 0.05). A between-group difference in favour of the PA-group, were observed in whole body bone mineral density (BMD) (0.024 g/cm2, p < 0.05). Conclusions and Implications. Fourteen weeks of PA performed in a real-life setting increased cardiovascular fitness, reduced fat mass and improved BMD in the weight-bearing skeleton in the PA-group. Increased and regular PA seems to be a promising tool to promote physical health in adults with ID.

Effects of 8 Weeks with Embodied Learning on 5-6-Year-Old Danish Children's Pre-reading Skills and Word Reading Skills: the PLAYMORE Project, DK.

The aim of this study was to investigate the effects of embodied learning on children's pre-reading and word reading skills. We conducted a three-armed randomized controlled trial including two intervention groups and one control group. One hundred forty-nine children from grade 0 (5-6 years old) who had just started school were recruited from 10 different classes from four elementary schools. Within each class, children were randomly assigned to receive teaching of letter-sound couplings and word decoding either with whole-body movements (WM), hand movements (HM), or no movements (CON) over an 8-week period. Children were evaluated on pre-reading, word reading, and motor skills before (T1), immediately after (T2), and after 17-22 weeks of retention period (T3) following the intervention. Between-group analysis showed a significant improvement in children's ability to name letter-sounds correctly from T1 to T2 (p < 0.001) and from T1 to T3 (p < 0.05) for WM compared to CON. HM and WM improved significantly in naming conditional letter-sounds from T1 to T2 (p < 0.01, p < 0.01) compared to CON and from T1 to T3 for the HM group compared to CON (p < 0.05). We did not find an effect on word reading or a correlation between motor skill performance and reading. Results from the present study suggest that there are beneficial effects of using whole-body movements for children. Hand motor movements indeed also had a performance effect on letter-sound knowledge; however, the whole-body movements had longer-lasting effects. We do not see an effect on whole word reading.

Six Weeks of Basketball Combined With Mathematics in Physical Education Classes Can Improve Children's Motivation for Mathematics.

This study investigated whether 6 weeks of basketball combined with mathematics once a week in physical education lessons could improve children's motivation for mathematics. Seven hundred fifty-seven children (mean age = 10.4 years, age range: 7-12 years) were randomly selected to have either basketball combined with mathematics once a week (BM) or to have basketball sessions without mathematics (CON). Children in BM and CON motivation for classroom-based mathematics were measured using the Academic Self-Regulation Questionnaire (SRQ-A) before (T0) and after the intervention (T1). Among the BM, levels of intrinsic motivation, feelings of competence, and autonomy were measured using the Post-Experimental Intrinsic Motivation Inventory (IMI) questionnaire acutely after a basketball session combined with mathematics and immediately after a session of classroom-based mathematics. BM had significantly higher acute levels of perceived autonomy (+14.24%, p < 0.0001), competencies (+6.33%, p < 0.0001), and intrinsic motivation (+16.09%, p < 0.0001) during basketball sessions combined with mathematics compared to when having classroom-based mathematics. A significant decrease in the mean for intrinsic motivation was observed from T0 to T1 for CON (-9.38%, p < 0.001), but not for BM (-0.39%, p = 0.98). BM had a more positive development in intrinsic motivation compared to CON from T0 to T1 (p = 0.006), meaning that BM had a positive influence on children's intrinsic motivation for classroom-based mathematics. This study indicates that basketball combined with mathematics is an intrinsically motivating way to practice mathematics, which also has a positive influence on children's general intrinsic motivation for mathematics in the classroom.

Factors correlated with running economy among elite middle- and long-distance runners.

Running economy (RE) at a given submaximal running velocity is defined as oxygen consumption per minute per kg body mass. We investigated RE in a group of 12 male elite runners of national class. In addition to RE at 14 and 18 km h-1 we measured the maximal oxygen consumption (VO2max ) and anthropometric measures including the moment arm of the Achilles tendon (LAch ), shank and foot volumes, and muscular fascicle lengths. A 3-D biomechanical movement analysis of treadmill running was also conducted. RE was on average 47.8 and 62.3 ml O2  min-1  kg-1 at 14 and 18 km h-1 . Maximal difference between the individual athletes was 21% at 18 km h-1 . Mechanical work rate was significantly correlated with VO2 measured in L min-1 at both running velocities. However, RE and relative work rate were not significantly correlated. LAch was significantly correlated with RE at 18 km h-1 implying that a short moment arm is advantageous regarding RE. Neither foot volume nor shank volume were significantly correlated to RE. Relative muscle fascicle length of m. soleus was significantly correlated with RE at 18 km h-1 . Whole body stiffness and leg stiffness were significantly correlated with LAch indicating that a short moment arm coincided with high stiffness. It is concluded that a short LAch is correlated with RE. Probably, a short LAch allows for storage of a larger amount of elastic energy in the tendon and influences the force-velocity relation toward a lower contraction velocity.

Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury.

BACKGROUND: Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. RESULTS: Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. CONCLUSIONS: This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be used to alter the transcriptional response to prevent the motor neurons from entering a state of hyper-excitability.

Motor-Enriched Encoding Can Improve Children's Early Letter Recognition.

It is not known how effective specific types of motor-enriched activities are at improving academic learning and early reading skills in children. The aim of this study was to investigate whether fine or gross motor enrichment during a single session of recognizing letters "b"/"d" can improve within-session performance or delayed retention the following day in comparison to letter recognition practice without movement. Furthermore, the aim was to investigate children's motivation to perform the specific tasks. We used a randomized controlled intervention study-design to investigate the effect of 10-min motor-enriched "b"/"d" letter training on children's ability to recognize the letters "b" and "d" (n = 127, mean age = 7.61 ± SD = 0.44 years) acutely, and in a delayed retention test. Three groups were included: a fine motor-enriched group (FME), a gross motor-enriched group (GME), that received 10 min of "b" and "d" training with enriched gestures (fine or gross motor movements, respectively), and a control group (CON), which received non motor-enriched "b"/"d" training. The children's ability to recognize "b" and "d" were tested before (T0), immediately after (T1), and one day after the intervention (T2) using a "b"/"d" Recognition Test. Based on a generalized linear mixed model a significant group-time interaction was found for accuracy in the "b"/"d" Recognition Test. Specifically, FME improved their ability to recognize "b"/"d" at post intervention (T0→T1, p = 0.008) and one-day retention test (T0→T2, p < 0.001) more than CON. There was no significant difference in change between GME and CON. For reaction time there were no significant global interaction effects observed. However, planned post hoc comparisons revealed a significant difference between GME and CON immediately after the intervention (T0→T1, p = 0.03). The children's motivation-score was higher for FME and GME compared to CON (FME-CON: p = 0.01; GME-CON: p = 0.01). The study demonstrated that fine motor-enriched training improved children's letter recognition more than non motor activities. Both types of motor training were accompanied by higher intrinsic motivation for the children compared to the non motor training group. The study suggests a new method for motor-enriched letter learning and future research should investigate the underlying mechanisms.

Effects of Exercise on Cognitive Performance in Children and Adolescents with ADHD: Potential Mechanisms and Evidence-based Recommendations.

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with a complex symptomatology, and core symptoms as well as functional impairment often persist into adulthood. Recent investigations estimate the worldwide prevalence of ADHD in children and adolescents to be ~7%, which is a substantial increase compared to a decade ago. Conventional treatment most often includes pharmacotherapy with central nervous stimulants, but the number of non-responders and adverse effects call for treatment alternatives. Exercise has been suggested as a safe and low-cost adjunctive therapy for ADHD and is reported to be accompanied by positive effects on several aspects of cognitive functions in the general child population. Here we review existing evidence that exercise affects cognitive functions in children with and without ADHD and present likely neurophysiological mechanisms of action. We find well-described associations between physical activity and ADHD, as well as causal evidence in the form of small to moderate beneficial effects following acute aerobic exercise on executive functions in children with ADHD. Despite large heterogeneity, meta-analyses find small positive effects of exercise in population-based control (PBC) children, and our extracted effect sizes from long-term interventions suggest consistent positive effects in children and adolescents with ADHD. Paucity of studies probing the effect of different exercise parameters impedes finite conclusions in this regard. Large-scale clinical trials with appropriately timed exercise are needed. In summary, the existing preliminary evidence suggests that exercise can improve cognitive performance intimately linked to ADHD presentations in children with and without an ADHD diagnosis. Based on the findings from both PBC and ADHD children, we cautiously provide recommendations for parameters of exercise.

Chemical denervation using botulinum toxin increases Akt expression and reduces submaximal insulin-stimulated glucose transport in mouse muscle.

Botulinum toxin A (botox) is a toxin used for spasticity treatment and cosmetic purposes. Botox blocks the excitation of skeletal muscle fibers by preventing the release of acetylcholine from motor nerves, a process termed chemical denervation. Surgical denervation is associated with increased expression of the canonical insulin-activated kinase Akt, lower expression of glucose handling proteins GLUT4 and hexokinase II (HKII) and insulin resistant glucose uptake, but it is not known if botox has a similar effect. To test this, we performed a time-course study using supra-maximal insulin-stimulation in mouse soleus ex vivo. No effect was observed in the glucose transport responsiveness at day 1, 7 and 21 after intramuscular botox injection, despite lower expression of GLUT4, HKII and expression and phosphorylation of TBC1D4. Akt protein expression and phosphorylation of the upstream kinase Akt were increased by botox treatment at day 21. In a follow-up study, botox decreased submaximal insulin-stimulated glucose transport. The marked alterations of insulin signaling, GLUT4 and HKII and submaximal insulin-stimulated glucose transport are a potential concern with botox treatment which merit further investigation in human muscle. Furthermore, the botox-induced chemical denervation model may be a less invasive alternative to surgical denervation.