Distinct Features of Interictal Activity Predict Seizure Localization and Burden in a Mouse Model of Childhood Epilepsy.

The epileptic brain is distinguished by spontaneous seizures and interictal epileptiform discharges (IEDs). Basic patterns of mesoscale brain activity outside of seizures and IEDs are also frequently disrupted in the epileptic brain and likely influence disease symptoms, but are poorly understood. We aimed to quantify how interictal brain activity differs from that in healthy individuals, and identify what features of interictal activity influence seizure occurrence in a genetic mouse model of childhood epilepsy. Neural activity across the majority of the dorsal cortex was monitored with widefield Ca2+ imaging in mice of both sexes expressing a human Kcnt1 variant (Kcnt1m/m ) and wild-type controls (WT). Ca2+ signals during seizures and interictal periods were classified according to their spatiotemporal features. We identified 52 spontaneous seizures, which emerged and propagated within a consistent set of susceptible cortical areas, and were predicted by a concentration of total cortical activity within the emergence zone. Outside of seizures and IEDs, similar events were detected in Kcnt1m/m and WT mice, suggesting that the spatial structure of interictal activity is similar. However, the rate of events whose spatial profile overlapped with where seizures and IEDs emerged was increased, and the characteristic global intensity of cortical activity in individual Kcnt1m/m mice predicted their epileptic activity burden. This suggests that cortical areas with excessive interictal activity are vulnerable to seizures, but epilepsy is not an inevitable outcome. Global scaling of the intensity of cortical activity below levels found in the healthy brain may provide a natural mechanism of seizure protection.SIGNIFICANCE STATEMENT Defining the scope and structure of an epilepsy-causing gene variant's effects on mesoscale brain activity constitutes a major contribution to our understanding of how epileptic brains differ from healthy brains, and informs the development of precision epilepsy therapies. We provide a clear roadmap for measuring how severely brain activity deviates from normal, not only in pathologically active areas, but across large portions of the brain and outside of epileptic activity. This will indicate where and how activity needs to be modulated to holistically restore normal function. It also has the potential to reveal unintended off-target treatment effects and facilitate therapy optimization to deliver maximal benefit with minimal side-effect potential.

mTORC2 Inhibition Improves Morphological Effects of PTEN Loss, But Does Not Correct Synaptic Dysfunction or Prevent Seizures.

Hyperactivation of PI3K/PTEN-mTOR signaling during neural development is associated with focal cortical dysplasia (FCD), autism, and epilepsy. mTOR can signal through two major hubs, mTORC1 and mTORC2, both of which are hyperactive following PTEN loss of function (LOF). Here, we tested the hypothesis that genetic inactivation of the mTORC2 complex via deletion of Rictor is sufficient to rescue morphologic and electrophysiological abnormalities in the dentate gyrus caused by PTEN loss, as well as generalized seizures. An established, early postnatal mouse model of PTEN loss in male and female mice showed spontaneous seizures that were not prevented by mTORC2 inactivation. This lack of rescue occurred despite the normalization or amelioration of many morphologic and electrophysiological phenotypes. However, increased excitatory connectivity proximal to dentate gyrus granule neuron somas was not normalized by mTORC2 inactivation. Further studies demonstrated that, although mTORC2 inactivation largely rescued the dendritic arbor overgrowth caused by PTEN LOF, it increased synaptic strength and caused additional impairments of presynaptic function. These results suggest that a constrained increase in excitatory connectivity and co-occurring synaptic dysfunction is sufficient to generate seizures downstream of PTEN LOF, even in the absence of characteristic changes in morphologic properties.SIGNIFICANCE STATEMENT Homozygous deletion of the Pten gene in neuronal subpopulations in the mouse serves as a valuable model of epilepsy caused by mTOR hyperactivation. To better understand the physiological mechanisms downstream of Pten loss that cause epilepsy, as well as the therapeutic potential of targeted gene therapies, we tested whether genetic inactivation of the mTORC2 complex could improve the cellular, synaptic, and in vivo effects of Pten loss in the dentate gyrus. We found that mTORC2 inhibition improved or rescued all morphologic effects of Pten loss in the dentate gyrus, but synaptic changes and seizures persisted. These data suggest that synaptic dysfunction can drive epilepsy caused by hyperactivation of PI3K/PTEN-mTOR, and that future therapies should focus on this mechanistic link.

Back to 'normal'? BMI, physical fitness and health-related quality of life of children from North East England before, during and after the COVID-19 lockdowns.

We assessed whether changes in children's body mass index (BMI), physical fitness and health-related quality of life observed post-2020 United Kingdom COVID-19 lockdown remained 12 and 18 months later. Twenty-metre shuttle run test (20mSRT), handgrip strength, standing broad jump, sit-and-reach, height, body mass, and health-related quality of life (Kidscreen27 questionnaire) were measured in 90 children (8-9 years) during October 2019 ("T0"), November 2020 ("T1"), November 2021 ("T2") and June 2022 ("T3"). Mixed-effects models showed age- and sex-normalised BMI increased from T0 (mean: 0.71) to T1 (0.97), remaining elevated at T2 (0.95) and T3 (0.89). Decreases in 20mSRT performance were observed from T0 (22.0) to T1 (19.3), then increased at T2 (23.5) and T3 (28.3). Standing broad jump and handgrip strength increased over time. The proportion of children with overweight/obesity increased from T0 (32%) to T3 (48%). Health-related quality of life decreased for "Physical Wellbeing" yet increased for "Autonomy & Parents". Our findings highlight that lockdowns may have had lasting implications for children's health, and the urgent need to reduce overweight and obesity in North East England. Improving health and fitness behaviours to maximise long-term health outcomes and build resilience to future emergencies and disruptions to health behaviours is also paramount.

Reliability of Measures of Lower-Body Strength and Speed in Academy Male Adolescent Soccer Players.

ABSTRACT: Ferguson, J, Gibson, NV, Weston, M, and McCunn, R. Reliability of measures of lower body strength and speed in academy male adolescent soccer players. J Strength Cond Res 38(3): e96-e103, 2024-The Nordbord and ForceFrame represent a practical and time efficient means of assessing eccentric hamstring and isometric adductor strength in the large number of squads and players associated with youth soccer academies, yet measurement reliability in this population is unexamined. Therefore, over a period of 4 days, with no less than 24 hours and no more than 48 hours between trials, 37 players (age: 14.7 ± 0.8 years, stature: 168.7 ± 7.8 cm, mass: 57.7 ± 9.1 kg, and maturity offset: 0.8 ± 0.9 years) were assessed for eccentric hamstring strength (force, torque), isometric adductor strength (long and short lever positions), and 30-m sprint (5, 10, and 20-m splits), using the Nordbord, ForceFrame, and electronic timing gates, respectively, on 3 separate occasions. Relative reliability (intraclass correlation coefficient) was rated as good for all Nordbord (range: 0.86-0.89) and ForceFrame (0.78-0.85) measures and ranged from moderate (0.53) to excellent (0.93) for the speed measures, improving with increased distance. Absolute reliability (standard error of the measurement [%SEM]) ranged from 7 to 8% (Nordbord), 3 to 11% (ForceFrame), and 1 to 4% (sprints). Our data provide the first Nordbord and ForceFrame reliability estimates in adolescent soccer academy players. To interpret test sensitivity, practitioners are encouraged to interpret our estimates of absolute reliability against meaningful change values derived from personal experience and evidence-based knowledge and not against absolute or standardized thresholds.

Atom-Specific Probing of Electron Dynamics in an Atomic Adsorbate by Time-Resolved X-Ray Spectroscopy.

The electronic excitation occurring on adsorbates at ultrafast timescales from optical lasers that initiate surface chemical reactions is still an open question. Here, we report the ultrafast temporal evolution of x-ray absorption spectroscopy (XAS) and x-ray emission spectroscopy (XES) of a simple well-known adsorbate prototype system, namely carbon (C) atoms adsorbed on a nickel [Ni(100)] surface, following intense laser optical pumping at 400 nm. We observe ultrafast (∼100 fs) changes in both XAS and XES showing clear signatures of the formation of a hot electron-hole pair distribution on the adsorbate. This is followed by slower changes on a few picoseconds timescale, shown to be consistent with thermalization of the complete C/Ni system. Density functional theory spectrum simulations support this interpretation.

Symmetry-resolved CO desorption and oxidation dynamics on O/Ru(0001) probed at the C K-edge by ultrafast x-ray spectroscopy.

We report on carbon monoxide desorption and oxidation induced by 400 nm femtosecond laser excitation on the O/Ru(0001) surface probed by time-resolved x-ray absorption spectroscopy (TR-XAS) at the carbon K-edge. The experiments were performed under constant background pressures of CO (6 × 10-8 Torr) and O2 (3 × 10-8 Torr). Under these conditions, we detect two transient CO species with narrow 2π* peaks, suggesting little 2π* interaction with the surface. Based on polarization measurements, we find that these two species have opposing orientations: (1) CO favoring a more perpendicular orientation and (2) CO favoring a more parallel orientation with respect to the surface. We also directly detect gas-phase CO2 using a mass spectrometer and observe weak signatures of bent adsorbed CO2 at slightly higher x-ray energies than the 2π* region. These results are compared to previously reported TR-XAS results at the O K-edge, where the CO background pressure was three times lower (2 × 10-8 Torr) while maintaining the same O2 pressure. At the lower CO pressure, in the CO 2π* region, we observed adsorbed CO and a distribution of OC-O bond lengths close to the CO oxidation transition state, with little indication of gas-like CO. The shift toward "gas-like" CO species may be explained by the higher CO exposure, which blocks O adsorption, decreasing O coverage and increasing CO coverage. These effects decrease the CO desorption barrier through dipole-dipole interaction while simultaneously increasing the CO oxidation barrier.

To Measure Peak Velocity in Soccer, Let the Players Sprint.

ABSTRACT: Kyprianou, E, Di Salvo, V, Lolli, L, Al Haddad, H, Villanueva, AM, Gregson, W, and Weston, M. To measure peak velocity in soccer, let the players sprint. J Strength Cond Res 36(1): 273-276, 2022-Expressing externals loads relative to a player's individual capacities has potential to enhance understanding of dose-response. Peak velocity is an important metric for the individualization process and is usually measured during a sprint test. Recently, however, peak velocity was reported to be faster during soccer matches when compared with a 40-m sprint test. With the aim of developing the practice of individualized training prescription and match evaluation, we examined whether the aforementioned finding replicates in a group of elite youth soccer players across a broader range of soccer activities. To do this, we compared the peak velocities of 12 full-time male youth soccer players (age 16.3 ± 0.8 years) recorded during a 40-m sprint test with peak velocity recorded during their routine activities (matches, sprints, and skill-based conditioning drills: small-sided games [SSG], medium-sided games [MSG], large-sided games [LSG]). All activities were monitored with 10-Hz global positioning systems (Catapult Optimeye S5, version 7.32) with the highest speed attained during each activity retained as the instantaneous peak velocity. Interpretation of clear between-activity differences in peak velocity was based on nonoverlap of the 95% confidence intervals for the mean difference between activities with sprint testing. Peak velocity was clearly faster for the sprint test (8.76 ± 0.39 m·s-1) when compared with matches (7.94 ± 0.49 m·s-1), LSG (6.94 ± 0.65 m·s-1), MSG (6.40 ± 0.75 m·s-1), and SSG (5.25 ± 0.92 m·s-1), but not sprints (8.50 ± 0.36 m·s-1). Our data show the necessity for 40-m sprint testing to determine peak velocity.

Initial fitness, maturity status, and total training explain small and inconsistent proportions of the variance in physical development of adolescent footballers across one season.

To investigate how initial fitness, maturity status, and training time explain changes in physical performance across one season. Eighty-eight adolescent male footballers, representing four age categories (Under 15 [n = 12], Under 14 [n = 21], Under 13 [n = 25], Under 12 [n = 30]), were tested using physical performance tests (20 m sprint, change of direction, squat jump and yo-yo intermittent recovery test level 1 [YYIRTL1]) and maturity offset at the season start (Test 1) and end (Test 2). Multiple regression determined the proportion of variance in test score changes, explained by three predictor variables: initial fitness (i.e., Test 1), maturity offset change, and training time. With combined categories, predictor variables explained 0.051 to 0.297 of the variance in physical performance score changes. Analysing age categories separately, predictor variables explained 0.047 to 0.407 (20 m sprint), 0.202 to 0.626 (change of direction), 0.336 to 0.502 (squat jump), and 0.196 to 0.777 (YYIRTL1) of variance in test score changes. Of the limited differences in relative predictor contribution, Test 1 was the strongest predictor of test score change. Initial fitness, maturity status change, and training time explain small and inconsistent proportions of variance in adolescent footballers' physical development across one season.

Ultrafast Adsorbate Excitation Probed with Subpicosecond-Resolution X-Ray Absorption Spectroscopy.

We use a pump-probe scheme to measure the time evolution of the C K-edge x-ray absorption spectrum from CO/Ru(0001) after excitation by an ultrashort high-intensity optical laser pulse. Because of the short duration of the x-ray probe pulse and precise control of the pulse delay, the excitation-induced dynamics during the first picosecond after the pump can be resolved with unprecedented time resolution. By comparing with density functional theory spectrum calculations, we find high excitation of the internal stretch and frustrated rotation modes occurring within 200 fs of laser excitation, as well as thermalization of the system in the picosecond regime. The ∼100 fs initial excitation of these CO vibrational modes is not readily rationalized by traditional theories of nonadiabatic coupling of adsorbates to metal surfaces, e.g., electronic frictions based on first order electron-phonon coupling or transient population of adsorbate resonances. We suggest that coupling of the adsorbate to nonthermalized electron-hole pairs is responsible for the ultrafast initial excitation of the modes.

Distribution of External Load During Acquisition Training Sessions and Match Play of a Professional Soccer Team.

ABSTRACT: Castillo, D, Raya-González, J, Weston, M, and Yanci, J. Distribution of external load during acquisition training sessions and match play of a professional soccer team. J Strength Cond Res 35(12): 3453-3458, 2021-The aim of this study was to use global position systems to analyze the external loads of the 3 different acquisition training sessions (ATS) with competitive matches in professional soccer players over a 6-week period. Sixteen professional soccer players participated in the study, which analyzed the distribution of external load during the training microcycle of a professional soccer team. The 3 types of ATS undertaken by the players were as follows: ATS1 (strength), ATS2 (endurance), and ATS3 (speed). The total distance covered, the distance covered at above 14 km·h-1, the distance covered >21 km·h-1, the number of high accelerations (>3 m·s-2), and player load were recorded. The results showed that external loads were consistently higher during matches when compared with all training sessions (range of effect sizes: 1.06-3.38). Between training session comparisons revealed higher external loads during ATS1 and ATS2, when compared with ATS3 (range of effect sizes: 0.60-2.41). The only external load variable that differed between ATS1 and ATS2 was the distance covered >21 km·h-1, which was higher for ATS1. Our findings suggest that technical staff should consider the physical demands of weekly periodization to understand the training process regarding optimizing player physical performance.

Altered excitatory transmission onto hippocampal interneurons in the IQSEC2 mouse model of X-linked neurodevelopmental disease.

Mutations in the X-linked gene IQSEC2 are associated with multiple cases of epilepsy, epileptic encephalopathy, intellectual disability and autism spectrum disorder, the mechanistic understanding and successful treatment of which remain a significant challenge in IQSEC2 and related neurodevelopmental genetic diseases. To investigate disease etiology, we studied behaviors and synaptic function in IQSEC2 deficient mice. Hemizygous Iqsec2 null males exhibit growth deficits, hyperambulation and hyperanxiety phenotypes. Adult hemizygotes experience lethal spontaneous seizures, but paradoxically have a significantly increased threshold to electrically induced limbic seizures and relative resistance to chemically induced seizures. Although there are no gross defects in brain morphology, hemizygotes exhibit stark hippocampal reactive astrogliosis. Electrophysiological recordings of hippocampal neurons reveal increased excitatory drive specifically onto interneurons, and significant alterations in intrinsic electrical properties specific to the interneuron population. As they age, hemizygotes also develop an increased abundance of parvalbumin-positive interneurons in the hippocampus, neurons in which IQSEC2 is expressed in addition to the excitatory neurons. These findings point to a novel role of IQSEC2 in hippocampal interneuron synaptic function and development with implications for a class of intractable neurodevelopmental diseases.

Time-resolved observation of transient precursor state of CO on Ru(0001) using carbon K-edge spectroscopy.

The transient dynamics of carbon monoxide (CO) molecules on a Ru(0001) surface following femtosecond optical laser pump excitation has been studied by monitoring changes in the unoccupied electronic structure using an ultrafast X-ray free-electron laser (FEL) probe. The particular symmetry of perpendicularly chemisorbed CO on the surface is exploited to investigate how the molecular orientation changes with time by varying the polarization of the FEL pulses. The time evolution of spectral features corresponding to the desorption precursor state was well distinguished due to the narrow line-width of the C K-edge in the X-ray absorption (XA) spectrum, illustrating that CO molecules in the precursor state rotated freely and resided on the surface for several picoseconds. Most of the CO molecules trapped in the precursor state ultimately cooled back down to the chemisorbed state, while we estimate that ∼14.5 ± 4.9% of the molecules in the precursor state desorbed into the gas phase. It was also observed that chemisorbed CO molecules diffused over the metal surface from on-top sites toward highly coordinated sites. In addition, a new "vibrationally hot precursor" state was identified in the polarization-dependent XA spectra.

No association between perceived exertion and session duration with hamstring injury occurrence in professional football.

Training and competition loads have emerged as modifiable composite risk factors of non-contact injury. Hamstring strains are the most common injuries in football with substantial burden on the individual player and club. Nevertheless, robust evidence of a consistent load-hamstring injury relationship in professional football is lacking. Using available data from the Qatar Stars League over three competitive seasons, this study investigated the separate and combined effects of perceived exertion and session duration on hamstring injury occurrence in a sample of 30 outfield football players. Load variables were calculated into 7-day, 14-day, 21-day, 28-day periods of data, and week-to-week changes for average ratings of perceived exertion (RPE; au) score and session-RPE (s-RPE; session-duration  ×  score), plus the cumulative training and match minutes and s-RPE, respectively. Conditional logistic regression models estimated load-injury relationships per 2-within-subject standard deviation increments in each candidate variable. Associations were declared practically important based on the location of the confidence interval in relation to thresholds of 0.90 and 1.11 defining small beneficial and harmful effects, respectively. The uncertainty for the corrected odds ratios show that typically high within-subject increments in each candidate variable were not practically important for training- and match-related hamstring injury (95% confidence intervals range: 0.85 to 1.16). We found limited exploratory evidence regarding the value of perceived exertion and session duration as etiological factors of hamstring injury in Middle-East professional football. Monitoring remains valuable to inform player load management strategies, but our exploratory findings suggest its role for type-specific injury risk determination appears empirically unsupported.

High-intensity endurance capacity assessment as a tool for talent identification in elite youth female soccer.

Talent identification and development programmes have received broad attention in the last decades, yet evidence regarding the predictive utility of physical performance in female soccer players is limited. Using a retrospective design, we appraised the predictive value of performance-related measures in a sample of 228 youth female soccer players previously involved in residential Elite Performance Camps (age range: 12.7-15.3 years). With 10-m sprinting, 30-m sprinting, counter-movement jump height, and Yo-Yo Intermittent Recovery Test Level 1 (IR1) distance as primary predictor variables, the Akaike Information Criterion (AIC) assessed the relative quality of four penalised logistic regression models for determining future competitive international squads U17-U20 level selection. The model including Yo-Yo IR1 was the best for predicting career outcome. Predicted probabilities of future selection to the international squad increased with higher Yo-Yo IR1 distances, from 4.5% (95% confidence interval, 0.8 to 8.2%) for a distance lower than 440 m to 64.7% (95% confidence interval, 47.3 to 82.1%) for a score of 2040 m. The present study highlights the predictive utility of high-intensity endurance capacity for informing career progression in elite youth female soccer and provides reference values for staff involved in the talent development of elite youth female soccer players.

A survey of talent identification and development processes in the youth academies of professional soccer clubs from around the world.

Talent identification (TID) and development (TDE) are large fields in professional soccer and in science. However,  TID and TDE processes in youth academies have not been assessed in detail. As such, our aim was to survey professional clubs from around the world about their youth academy TID and TDE processes, with 29 clubs responding to the survey. TID and TDE processes changed as a function of player age. TID processes involved finding the best players locally and regionally, but for older players the search widened to nationally and internationally for the needs of the first team. Clubs used a multidisciplinary approach to TID, but more so with older players. Median number of academy players was 80, 100, and 66 players at 8-11 years, 12-16 years, and 17-21 years, respectively. Annual player turnover in the most recent season (selections/de-selections) was 29% across all age groups, with competition from other clubs cited as a limitation to TID. TDE processes involved weekly matches and 3-5 training sessions per week led by experienced, well-qualified coaches, with most clubs providing players with academic education, residency and transportation services. Our findings extend previous research assessing professional soccer youth academy TID and TDE processes by quantifying worldwide practices.

The effect of 12 weeks of combined upper- and lower-body high-intensity interval training on muscular and cardiorespiratory fitness in older adults.

BACKGROUND: High-intensity interval training (HIT) can impact cardiorespiratory and muscular fitness simultaneously, yet protocols typically focus on lower-body exercise. For older adults however, performing activities of daily living requires upper- and lower-body fitness. AIMS: To assess the effects of combined upper- and lower-body HIT on fitness in adults aged > 50 years. METHODS: Thirty-six adults (50-81 years; 21 male) were assigned via minimisation to either HIT (n = 18) or a no-exercise control group (CON, n = 18) following baseline assessment of leg extensor muscle power, handgrip strength, cardiorespiratory fitness (predicted VO2max) and health-related quality of life (HRQoL). The HIT group completed two training sessions per week for 12-weeks, performing a combination of upper-, lower- and full-body exercises using a novel hydraulic resistance ergometer. Data were analysed via ANCOVA with probabilistic inferences made about the clinical relevance of observed effects. RESULTS: All participants completed the intervention with mean (82 ± 6%HRmax) and peak (89 ± 6%HRmax) exercise heart rates confirming a high-intensity training stimulus. Compared with CON, HIT showed possibly small beneficial effects for dominant leg power (10.5%; 90% confidence interval 2.4-19.4%), non-dominant leg power (9.4%; 3.3-16.0%) and non-dominant handgrip strength (6.3%; 1.2-11.5%) while the intervention effect was likely trivial (5.9%; 0.5-11.5%) for dominant handgrip strength. There was a likely small beneficial effect for predicted VO2max (8.4%; 1.8-15.4%) and small-moderate improvements across several domains of HRQoL. CONCLUSION: Combined upper- and lower-body HIT has small clinically relevant beneficial effects on muscular and cardiorespiratory fitness in older adults.

The effects of same-session combined exercise training on cardiorespiratory and functional fitness in older adults: a systematic review and meta-analysis.

Endurance and strength training are effective strategies for counteracting age-associated reductions in physical performance in older adults, with a combination of both exercise modes recommended to maximise potential fitness benefits. This meta-analysis sought to quantify the effects of same-session combined endurance and strength training on fitness in adults aged over 50 years. Five electronic databases were searched with studies required to include one of the following outcome measures: VO2peak, 6-min walk test (6MWT), 8-ft timed up-and-go (TUG), and 30-s chair stand. Separate random-effects meta-analyses compared combined training with (1) no-exercise control, (2) endurance training, and (3) strength training with probabilistic magnitude-based inferences subsequently applied. Twenty-seven studies involving 1346 subjects with a mean age of 68.8 years (range 54-85 years) were included in the analysis. The meta-analysed effect on VO2peak was a moderately beneficial effect for the combined training compared to no-exercise controls (3.6 mL kg-1 min-1; ± 95% confidence limits 0.8 mL kg-1 min-1) with additional increases for studies with greater proportions of female participants and shorter training interventions. Combined training also had small-to-moderately beneficial effects on VO2peak when compared to endurance training (0.8 mL kg-1 min-1; ± 1.0 mL kg-1 min-1), 30-s chair stand when compared with strength training (1.1 repetitions; ± 0.5 repetitions) and on TUG (0.8 s; ± 0.7 s), 30-s chair stand (2.8 repetitions; ± 1.7 repetitions), and 6MWT (31.5 m; ± 22.4 m) when compared to no-exercise controls. All other comparisons were unclear. Same-session combined training can induce clinically relevant fitness improvements in older adults.

Using differential ratings of perceived exertion to assess agreement between coach and player perceptions of soccer training intensity: An exploratory investigation.

We aimed to assess the coach-player agreement of subjective soccer training loads via differential ratings of perceived exertion (dRPE). The coach initially underwent quantifiable familiarisation (blackness test) with the Borg CR100 scale. Data were collected from 16 semi-professional soccer players across seven consecutive training sessions. For the measurement of subjective training load, the coach and players provided dRPE (CR100) for legs (RPE-L), breathlessness (RPE-B) and technical exertion (RPE-T). Coach-prescribed dRPE were recorded prior to training, with coach observed and player reported dRPE collected post training. Statistical equivalence bounds for agreement between coach (prescribed and observed) and player reported dRPE scores were 4 arbitrary units on the CR100 and we used a probability outcome of likely (≥75%) to infer realistic equivalence. Following three familiarisation sessions, the coach improved their blackness test score from 39% to 83%. Coach observed and player reported RPE-T scores were likely equivalent, with all other comparisons not realistically equivalent. Since training prescription is coach-led, our data highlight the importance of accurate internal load measurement and feedback in soccer. The improved accuracy and precision of coach intensity estimation after three attempts at the blackness test suggests that this method could be worthwhile to researchers and practitioners employing dRPE.

Neuromuscular, physiological and perceptual responses to an elite netball tournament.

To examine responses to an International netball tournament, female athletes (n= 11) played three matches over consecutive days. External (accelerometry) and internal (heart rate; HR, session; sRPE, and differential; dRPE, rating of perceived exertion) load measures quantified match intensity. On match-day mornings, and three days after match 3, well-being (brief assessment of mood; BAM+), biochemical (creatine kinase concentration; CK), neuromuscular (jump height; JH, peak power output; PPO) and endocrine function (salivary cortisol; C, testosterone; T, concentrations) were assessed. External load was similar between matches whereas dRPE and sRPE were greatest for match 3. Following match 1, CK increased, whereas BAM+, JH, C and T decreased. Following two matches, BAM+, PPO, and T decreased with CK increasing versus baseline. Following consecutive matches, CK (likely moderate; 27.9% ± 19.5%) and C (possibly moderate; 43.3% ± 46.8%) increased, whilst BAM+ (possibly moderate; -20.6% ± 24.4%) decreased. Three days post-tournament BAM+, T, PPO, and JH decreased. Mid-court elicited higher mean HR (possibly moderate; 3.7% ± 3.8%), internal and external intensities (possibly very large; 85.7% ± 49.6%) compared with goal-based positions. Consecutive matches revealed a dose-response relationship for well-being and physiological function; a response evident three days post-tournament.

PTEN Loss Increases the Connectivity of Fast Synaptic Motifs and Functional Connectivity in a Developing Hippocampal Network.

Changes in synaptic strength and connectivity are thought to be a major mechanism through which many gene variants cause neurological disease. Hyperactivation of the PI3K-mTOR signaling network, via loss of function of repressors such as PTEN, causes epilepsy in humans and animal models, and altered mTOR signaling may contribute to a broad range of neurological diseases. Changes in synaptic transmission have been reported in animal models of PTEN loss; however, the full extent of these changes, and their effect on network function, is still unknown. To better understand the scope of these changes, we recorded from pairs of mouse hippocampal neurons cultured in a two-neuron microcircuit configuration that allowed us to characterize all four major connection types within the hippocampus. Loss of PTEN caused changes in excitatory and inhibitory connectivity, and these changes were postsynaptic, presynaptic, and transynaptic, suggesting that disruption of PTEN has the potential to affect most connection types in the hippocampal circuit. Given the complexity of the changes at the synaptic level, we measured changes in network behavior after deleting Pten from neurons in an organotypic hippocampal slice network. Slices containing Pten-deleted neurons showed increased recruitment of neurons into network bursts. Importantly, these changes were not confined to Pten-deleted neurons, but involved the entire network, suggesting that the extensive changes in synaptic connectivity rewire the entire network in such a way that promotes a widespread increase in functional connectivity.SIGNIFICANCE STATEMENT Homozygous deletion of the Pten gene in neuronal subpopulations in the mouse serves as a valuable model of epilepsy caused by mTOR hyperactivation. To better understand how gene deletions lead to altered neuronal activity, we investigated the synaptic and network effects that occur 1 week after Pten deletion. PTEN loss increased the connectivity of all four types of hippocampal synaptic connections, including two forms of increased inhibition of inhibition, and increased network functional connectivity. These data suggest that single gene mutations that cause neurological diseases such as epilepsy may affect a surprising range of connection types. Moreover, given the robustness of homeostatic plasticity, these diverse effects on connection types may be necessary to cause network phenotypes such as increased synchrony.