From Gut Microbiota to Brain Waves: The Potential of the Microbiome and EEG as Biomarkers for Cognitive Impairment.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder and a leading cause of dementia. Aging is a significant risk factor for AD, emphasizing the importance of early detection since symptoms cannot be reversed once the advanced stage is reached. Currently, there is no established method for early AD diagnosis. However, emerging evidence suggests that the microbiome has an impact on cognitive function. The gut microbiome and the brain communicate bidirectionally through the gut-brain axis, with systemic inflammation identified as a key connection that may contribute to AD. Gut dysbiosis is more prevalent in individuals with AD compared to their cognitively healthy counterparts, leading to increased gut permeability and subsequent systemic inflammation, potentially causing neuroinflammation. Detecting brain activity traditionally involves invasive and expensive methods, but electroencephalography (EEG) poses as a non-invasive alternative. EEG measures brain activity and multiple studies indicate distinct patterns in individuals with AD. Furthermore, EEG patterns in individuals with mild cognitive impairment differ from those in the advanced stage of AD, suggesting its potential as a method for early indication of AD. This review aims to consolidate existing knowledge on the microbiome and EEG as potential biomarkers for early-stage AD, highlighting the current state of research and suggesting avenues for further investigation.

Amelioration of Anxiety Associated with Opioid Withdrawal by Activation of Spinal Mechanoreceptors Via Novel Heterodyned Whole Body Vibration.

Objectives: Opioid use disorder (OUD)-associated overdose deaths have reached epidemic proportions worldwide. An important driving force for relapse is anxiety associated with opioid withdrawal. We hypothesized that our new technology, termed heterodyned whole-body vibration (HWBV) would ameliorate anxiety associated with OUD. Methods: Using a randomized, placebo (sham)-controlled, double-blind study design in an NIH-sponsored Phase 1 trial, we evaluated 60 male and 26 female participants diagnosed with OUD and undergoing treatment at pain and rehabilitation clinics. We utilized the Hamilton Anxiety Scale (HAM-A) and a daily visual analog scale anxiety rating (1-10) to evaluate anxiety. Subjects were treated for 10 min 5X/week for 4 weeks with either sham vibration (no interferential beat or harmonics) or HWBV (beats and harmonics). The participants also completed a neuropsychological test battery at intake and discharge. Results: In OUD subjects with moderate anxiety, there was a significant improvement in daily anxiety scores in the HWBV group compared to the sham treatment group (p=3.41 × 10-7). HAM-A scores in OUD participants at intake showed moderate levels of anxiety in OUD participants (HWBV group: 15.9 ± 1.6; Sham group: 17.8 ± 1.6) and progressively improved in both groups at discharge, but improvement was greater in the HWBV group (p=1.37 × 10-3). Furthermore, three indices of neuropsychological testing (mental rotations, spatial planning, and response inhibition) were significantly improved by HWBV treatment. Conclusions: These findings support HWBV as a novel, non-invasive, non-pharmacological treatment for anxiety associated with OUD.

Interoceptive posture awareness and accuracy: a novel photographic strategy towards making posture actionable.

Interoception, sometimes referred to as the 'hidden sense,' communicates the state of internal conditions for autonomic energy regulation and is important for human motor control as well as self-awareness. The insula, the cortex of interoception, integrates internal senses such as hunger, thirst and emotions. With input from the cerebellum and proprioceptive inputs, it creates a vast sensorimotor network essential for static posture and dynamic movement. With humans being bipedal to allow for improved mobility and energy utilization, greater neuromotor control is required to effectively stabilize and control the four postural zones of mass (i.e., head, torso, pelvis, and lower extremities) over the base of support. In a dynamic state, this neuromotor control that maintains verticality is critical, challenging energy management for somatic motor control as well as visceral and autonomic functions. In this perspective article, the authors promote a simple series of posture photographs to allow one to integrate more accurate alignment of their postural zones of mass with respect to the gravity line by correlating cortical interoception with cognitive feedback. Doing this focuses one on their body perception in space compared to the objective images. Strengthening interoceptive postural awareness can shift the net result of each zone of postural mass during day-to-day movement towards stronger posture biomechanics and can serve as an individualized strategy to optimize function, longevity, and rehabilitation.

Shear wave elastography demonstrates different material properties between the medial collateral ligament and anterolateral ligament.

BACKGROUND: Anterolateral ligament and medial collateral ligament injuries could happen concomitantly with anterior cruciate ligament ruptures. The anterolateral ligament is injured more often than the medial collateral ligament during concomitant anterior cruciate ligament ruptures although it offers less restraint to knee movement. Comparing the material properties of the medial collateral ligament and anterolateral ligament helps improve our understanding of their structure-function relationship and injury risk before the onset of injury. METHODS: Eight cadaveric lower extremity specimens were prepared and mechanically tested to failure in a laboratory setting using a hydraulic platform. Measurements of surface strains of superficial surface of each medial collateral ligament and anterolateral ligament specimen were found using three-dimensional digital image correlation. Ligament stiffness was found using ultrasound shear-wave elastography. t-tests were used to assess for significant differences in strain, stress, Young's modulus, and stiffness in the two ligaments. FINDINGS: The medial collateral ligament exhibited greater ultimate failure strain along its longitudinal axis (p = 0.03) and Young's modulus (p < 0.0018) than the anterolateral ligament. Conversely, the anterolateral ligament exhibited greater ultimate failure stress than the medial collateral ligament (p < 0.0001). Medial collateral ligament failure occurred mostly in the proximal aspect of the ligament, while most anterolateral ligament failure occurred in the distal or midsubstance aspect (P = 0.04). INTERPRETATION: Despite both being ligamentous structures, the medial collateral ligament and anterolateral ligament exhibited separate material properties during ultimate failure testing. The weaker material properties of the anterolateral ligament likely contribute to higher rates of concomitant injury with anterior cruciate ligament ruptures.

Acute effects of an isometric neck warm-up programme on neck performance characteristics and ultrasound-based morphology.

OBJECTIVE: Athletic performance can be enhanced immediately after an isometric warm-up, a phenomenon termed post-activation performance enhancement (PAPE). While isometric warm-ups can improve lower extremity sprint and jump performance, neck-specific isometric warm-ups need development and validation for mild traumatic brain disorders and neck pain. This study examined acute effects of isometric warm-ups on neck performance and morphology. METHODS: Arm 1: Twenty-six adults (13 M:13F) completed neck performance testing before and after a 10-minute neck isometric warm-up or stationary bike (sham) between two visits. Testing included visual-motor reaction time, peak force, rate of force development, force steadiness, and force replication/proprioception measured by a 6-axis load cell. An inclinometer assessed range-of-motion. Paired t-tests and two-way ANOVA examined effects of neck/bike warm-up and interaction effects, respectively. Arm 2: 24 adults (11 M:13F) completed ultrasound scans of cervical muscles: before 20-minute rest (sham), and before/after a 5-min neck isometric warm-up. Longus colli cross-sectional area and sternocleidomastoid/upper trapezius thickness and stiffness, and cervical extensors thickness was assessed. One-way ANOVA compared morphological values at sham, before, and after warm-up. Significance was set at p < 0.05. RESULTS: Isometric neck warm-up increased rate of force development in flexion (p = 0.022), extension (p = 0.001-0.003), right lateral flexion (p = 0.004-0.032), left lateral flexion (p = 0.005-0.014), while peak force improved only in left lateral flexion (p = 0.032). Lateral flexion range-of-motion increased after neck warm-up (p = 0.003-0.026). Similarly, longus colli cross-sectional area (p = 0.016) and sternocleidomastoid thickness (p = 0.004) increased. CONCLUSIONS: Increased neck performance characteristics and morphology are likely due to PAPE effects of isometric neck warm-up. For coaches and athletes, simple isometric contractions could be added to existing warm-ups to reduce prevalence, incidence, and severity of mild traumatic brain injuries and neck pain.

Effects of neuromuscular and proprioceptive training on self-reported wellness and health scores and knee sensorimotor characteristics in active seniors.

INTRODUCTION: Athletes regularly engage in comprehensive neuromuscular and proprioceptive training (NPT) to prevent musculoskeletal (MSK) injuries. NPT exercises such as movement technique, agility, balance, and posture as well as yoga-based stretching and slow/deep breathing have shown added benefits in psychological and other well-being. This study aimed to examine the effects of NPT on knee sensorimotor characteristics and multi-domain wellness and health scores in active seniors. METHODS: Twenty seniors participated in the NPT intervention (15-20min session twice a week for 10 weeks) while the control group did not receive any intervention. All participants completed surveys (general health, frailty, anxiety, stress, mindfulness, optimism, and sleep quality) and laboratory testing before and after intervention. Laboratory testing included frailty tests (grip strength, 4-m walk speed, and calcaneal ultrasound-based bone density) and knee sensorimotor characteristics (peak force, visual-motor reaction time, and force steadiness). RESULTS: There was significant increase in general mental health (Short Form 36 Mental Health; p = 0.005) and decrease in stress (Perceived Stress Scale; p = 0.010) and sleep disturbances (Pittsburgh Sleep Quality Index; p = 0.019) post-intervention while no significant changes were observed in the control group (p = 0.310-0.654). Peak knee forces in all directions and some visual-motor reaction time and force steadiness were significantly improved post-intervention only in the experimental group (p = 0.001-0.038). CONCLUSION: A simple, yet, comprehensive NPT has potential to improve MSK health as well as various domains of well-being among active seniors.

The effectiveness of clinic versus home-based, artificial intelligence-guided therapy in patients with low back pain: Non-randomized clinical trial.

BACKGROUND: Low back pain is a common cause of disability in the US with increasing financial burden on healthcare. A variety of treatment options exist to combat LBP. Home-based therapy is a low-cost option, but there is a lack of data on how it compares to therapy in clinical settings. It was hypothesized that when using artificial intelligence-guided therapy, supervised in-clinic interventions would have a greater influence on patient-reported outcomes and strength than unsupervised, home interventions. METHODS: This is a non-randomized controlled trial of 51 patients (28 female, 23 male). The investigation compared an 8-week, core-focused exercise intervention in a Clinic (supervised) versus Home (unsupervised) setting. Outcome variables included measures of strength, performance, and patient-reported outcomes related to function. Generalized linear regression (p < 0.05) was used to evaluate outcomes were evaluated with respect to sex, intervention setting, and time. FINDINGS: Male subjects exhibited greater strength (p ≤ 0.02) but not greater patient-reported outcomes (p ≥ 0.30) than females. The Clinic group exhibited slightly greater lateral pull-down strength (p = 0.002), greater eccentric phase range of motion during overhead press (p < 0.01), and shorter concentric phase duration during bench press (p < 0.01) than the Home group. Significance between groups was not observed in any other strength, performance, or patient-reported outcome (p ≥ 0.11). INTERPRETATION: A lack of consistent significance indicated that the hypothesis was not supported. AI-guided, telehealth exercise produced comparable outcomes in both home and clinical settings. Telehealth options may offer a lower-cost alternative to clinic-based exercise therapy for patients with nonspecific lower back pain.

Differences in psychological readiness for return to sport after anterior cruciate ligament injury is evident in thigh musculature motor unit characteristics.

Background: Following anterior cruciate ligament (ACL) injury, many athletes that undergo surgery and 6-9 months of rehabilitation struggle to return to sport. Evidence suggests that psychological factors contribute to this failure to return-to-sport. Objective: Determine the motor control relationship between thigh musculature motor unit characteristics and psychological readiness to return to sport between ACL-injured and healthy controls. Study design: A longitudinal cohort study. Methods: Athletes longitudinally completed the ACL Return to Sport after Injury (ACL-RSI) survey and isometric strength measures with a measurement of electromyography (EMG) of the vastus lateralis, vastus medialis, biceps femoris, and semitendinosus. A score cut-off of 61 on the ACL-RSI was used to divide ACL-injured groups. EMG was decomposed to provide each identified motor unit's characteristics (amplitude, average firing rate, etc). Results: Data demonstrated increased average firing rate for hamstrings (p<0.001), decreased average firing rate for vastus lateralis (p<0.001) and decreased motor unit size for both the quadriceps and hamstrings at return-to-sport post-ACL reconstruction compared with sex-matched and age-matched healthy controls (p<0.001). Furthermore, there were marked differences in disparate ACL-RSI scores between ACL-injured athletes. Conclusions: At return to sport, ACL-injured athletes have major alterations of thigh musculature motor control, with smaller motor units used by those with low ACL-RSI scores. This study uniquely demonstrates objective thigh muscle motor unit characteristics that coincide with subjective reports of psychological readiness. This information will be important to address psychomotor complexes of injury for future rehabilitation protocols.

Arthrogenic muscle inhibition after anterior cruciate ligament injury: Injured and uninjured limb recovery over time.

Introduction: It is well documented that marked weakness of the quadriceps is present after knee joint injury. This joint trauma induces a presynaptic reflex inhibition of musculature surrounding the joint, termed arthrogenic muscle inhibition (AMI). The extent to which anterior cruciate ligament (ACL) injury affects thigh musculature motor unit activity, which may affect restoration of thigh muscle strength after injury, is undetermined. Methods: A randomized protocol of knee flexion and extension isometric contractions (10%-50% maximal voluntary isometric contraction) were performed for each leg on 54 subjects with electromyography array electrodes placed on the vastus medialis, vastus lateralis, semitendinosus, and biceps femoris. Longitudinal assessments for motor unit recruitment and average firing rate were acquired at 6-month intervals for 1 year post ACL injury. Results: The ACL-injured population demonstrated smaller quadriceps and hamstrings motor unit size (assessed via motor unit action potential peak-to-peak amplitude) and altered firing rate activity in both injured and uninjured limbs compared to healthy controls. Motor unit activity remained altered compared to healthy controls at 12 months post ACL reconstruction (ACLR). Discussion: Motor unit activity was altered after ACLR up to 12 months post-surgery. Further research is warranted to optimize rehabilitation interventions that adequately address altered motor unit activity and improve safety and success with return to sport after ACLR. In the interim, evidence based clinical reasoning with a focus on development of muscular strength and power capacity should be the impetus behind rehabilitation programming to address motor control deficits.

Neck strength and force in reaction time task of adolescent athletes with and without concussion history: A pilot study.

OBJECTIVES: Assess the impact of concussion by comparing reaction time, peak force recruitment, and rate of force development of adolescent athletes returning from concussion against age- and sex-matched controls in visual-elicited neck movement. DESIGN: Athletes sat secured in a custom-built isometric device with their heads secured in a helmet and attached to a 6-axis load cell. They performed neck flexion, extension, and lateral flexion in response to a visual cue. Three trials in each direction were used for statistical analyses; peak force and rate of force development were normalized against athlete mass. SETTING: Laboratory. PARTICIPANTS: 26 adolescent/young adult athletes (8F/18M), either recently concussed (and cleared for return to sport) or an age- and sex-matched healthy control. MAIN OUTCOME MEASURES: Reaction time, angle, standard deviation of angle, deviation from target angle, peak force, and RFD over 50, 100, 150,and 200 ms of movement were measured for each trial. RESULTS: Concussed athletes had decreased normalized peak force (P = 0.008) and rate of force development (P < 0.001-0.007). In neck extension, concussed athletes also had decreased movement precision (P = 0.012). CONCLUSIONS: Concussion is associated with alterations of neck biomechanics that decrease overall neck strength.

Recurrence quantification analysis of isokinetic strength tests: A comparison of the anterior cruciate ligament reconstructed and the uninjured limb.

BACKGROUND: Despite widespread use of return to sport testing following anterior cruciate ligament reconstruction, studies suggest inadequacy in current testing criteria, such as limb symmetry index calculations, to determine athletes' readiness to return to play. Recurrence quantification analysis, an emerging non-linear data analysis tool, may reveal subtle neuromuscular differences between the injured and uninjured limb that are not captured by traditional testing. We hypothesized that isokinetic torque curve data of the injured limb would demonstrate lower determinism and entropy as compared to the uninjured limb. METHODS: 102 patients (44 M, 58F, 10 ± 1 months post-anterior cruciate ligament reconstruction) underwent isokinetic quadriceps strength testing using a HumacNorm dynamometer. Patients completed maximum effort knee extension and flexion at 60°/sec. Data were post-processed with a MATLAB CRQA Graphical User Interface and determinism and entropy values were extracted. Paired-sample t-tests (α = 0.05) were used to compare data from the injured and uninjured limb. FINDINGS: Determinism and entropy values in the torque curves were lower in the injured limb than the uninjured limb (p < 0.001). Our findings indicate there is less predictability and complexity present in the torque signals of injured limbs. INTERPRETATION: Recurrence quantification analysis can be used to assess neuromuscular differences between limbs in patients who have undergone anterior cruciate ligament reconstruction. Our findings offer further evidence that there are changes to the neuromuscular system which persist following reconstruction. Further investigation is needed to establish thresholds of determinism and entropy values needed for safe return to sport and to evaluate the utility of recurrence quantification analysis as a return to sport criterion.

Physical clinical care and artificial-intelligence-guided core resistance training improve endurance and patient-reported outcomes in subjects with lower back pain.

BACKGROUND: Low back pain is an extremely prevalent issue with an extensive impact, ranging from decreased quality of life to lost years of productivity. Many interventions have been developed to alleviate chronic lower back pain, yet it remains a widespread problem. The objective of this study was to examine the role of artificial intelligence guided resistance training relative to clinical variables in subjects experiencing lower back pain. METHODS: 69 out of 108 enrolled and 92 accrued subjects completed the 8-week intervention. Subjects were randomized into four groups (Control, Training, Clinical, or Combined). The Training cohort received supervised artificial-intelligence-guided core-focused resistance training while the Clinical group received clinical care. The Combined group received both clinical care and artificial-intelligence-guided training and the Control group received no treatment. Participants were evaluated using functional testing and patient-reported outcomes at baseline, 4 weeks, and 8 weeks. FINDINGS: In the clinical tests, the Clinical and Combined cohorts showed increased total time for isometric extensor endurance and the Clinical cohort increased total distance traveled in the 6-min walk test at 8 weeks. The Training, Clinical, and Combined groups showed improvements in Patient-reported outcomes after 8 weeks. Most of the significant improvements were only seen at the 8-week evaluation for both the clinical evaluations and Patient-reported outcomes. The Control group did not show significant improvements in any outcome measures. INTERPRETATION: The present data indicate that core-focused interventions, including artificial-intelligence-guided moderate-resistance exercise, can increase objective functional outcomes and patient satisfaction using Patient-reported outcomes in individuals with lower back pain.

Arthrogenic muscle inhibition manifests in thigh musculature motor unit characteristics after anterior cruciate ligament injury.

Joint trauma induces a presynaptic reflex inhibition termed arthrogenic muscle inhibition (AMI) that prevents complete activation of muscles. Reduced motor unit (MU) output is a hypothesised mechanism for persistent strength deficits. The objective of this study was to determine MU characteristics of thigh musculature and determine how they change with anterior cruciate ligament (ACL) injury compared to healthy controls. A randomised protocol of knee flexion/extension isometric contractions (10-50% maximal voluntary isometric contraction) was performed for each leg with surface EMG 5-pin array electrodes placed on the vastus medialis, vastus lateralis, semitendinosus and biceps femoris. Longitudinal assessments for average rate coding, recruitment thresholds and MU action potentials were acquired at 6-month intervals. With exception of the vastus medialis, all thigh musculature of ACL-injured demonstrated smaller MU action potential peak-to-peak amplitude. For average rate coding, ACL-injured demonstrated lower coding rates than Controls for the quadriceps (p < .05) and higher rates than Controls for the hamstrings (p < .05). These MU characteristics were different from Controls after ACL reconstruction up to 12 months post-surgery, yet maximal strength increased during this time frame. As thigh MU characteristics are known across phases of ACL rehabilitation, future studies can assess these patterns of motor control and their potential to determine risk of re-injury. Further, future rehabilitation can target specific intervention programmes to restore motor control.HighlightsMotor unit strategies of arthrogenic muscle inhibition are characterised for the first time via decomposed EMG.Motor unit deficits of thigh musculature persist throughout all phases of ACL rehabilitation, even after return-to-sport.After ACL injury, motor unit sizes at similar recruitment thresholds were smaller than those of healthy controls.

Application of Shear-Wave Elastography in the Evaluation of Hamstring Stiffness in Young Basketball Athletes.

Background: Previous literature has postulated a relationship between greater hamstring stiffness and a higher risk of sustaining injury. Shear wave elastography (SWE) presents a relatively new means for non-invasive evaluation of soft tissue elasticity pre- and post- injury or intervention. Purpose: 1. To establish baseline hamstring stiffness measures for young competitive athletes and (2) determine effect of targeted neuromuscular training (TNMT) on shear wave stiffness of the hamstring. Study Design: Un-blinded, prospective, non-randomized, cohort study. Methods: Six-hundred forty-two lower extremities from 321 high school and collegiate basketball athletes (177 F: 139 M) were examined for hamstring stiffness prior to the start of their competitive basketball season. Teams were cluster assigned to either the control or intervention (TNMT) group. Subjects in the control group underwent regular season activities as directed, with no influence from the research team. For the TNMT group, the research team introduced a hamstring targeted dynamic warm-up program as an intervention focused on activating the hamstring musculature. Results: Collegiate status was significant to hamstring stiffness for both sexes (p ≤ 0.02), but hamstring stiffness did not correlate to age or sex (r2 ≤ 0.08). Intervention was a significant factor to hamstring stiffness when the hip was positioned in extension (p ≤ 0.01), but not in deeper flexion (p = 0.12). This effect was sex-specific as TNMT influenced hamstring stiffness in females (p = 0.03), but not in males (p ≥ 0.13). Control athletes suffered three HAM injuries; TNMT athletes suffered 0 hamstring injuries. Conclusion: Higher SWE measurements correlated with increased risk of injury, male sex, and collegiate athletics. TNMT intervention can lessen muscle stiffness which may reduce relate to injury incidence. Intervention effectiveness may be sex specific. Level of Evidence: II.

Altered neuromuscular control in the vastus medialis following anterior cruciate ligament injury: A recurrence quantification analysis of electromyogram recruitment.

BACKGROUND: Neuromuscular deficits exist following anterior cruciate ligament (ACL) injury. To observe these deficits, we examined nonlinear characteristics of vastus medialis electromyography (EMG) signals during submaximal isometric knee extensor contractions. Our purpose was to examine if determinism and entropy in EMG signals reflected neuromuscular control deficits in individuals with ACL-deficient limbs. METHODS: 24 participants (12 male, 12 female, mean age = 18.8 ± 3.1 years) with unilaterally injured ACLs and 25 age-similar healthy controls (11 male, 14 female, mean age = 18.8 ± 3.1 years) volunteered. Isometric knee extensions were tested at 10%, 25%, 35%, and 50% maximum voluntary contractions. Surface electrodes adhered over the vastus medialis captured EMG signals. EMG data were processed with recurrence quantification analyses. Specifically, determinism (an index of system predictability) and entropy (an index of system disorder) were calculated from recurrence plots. FINDINGS: Determinism and entropy in EMG signals were lower in the injured than uninjured limb, and lower than that from healthy controls (P < .05). INTERPRETATION: Vastus medialis EMG signals from the injured limb were less predictable and less complex than those from healthy limbs. The findings reflect impaired neuromuscular control in the injured limb's quadriceps and are consistent with a 'loss of complexity' hypothesis in physiologic signals emanating from pathologic states. Determinism and entropy in EMG signals may represent biomarkers of one's neuromuscular control system.

Neuromotor control associates with muscle weakness observed with McArdle sign of multiple sclerosis.

OBJECTIVE: Multiple Sclerosis (MS) is often accompanied by myelopathy, which may be associated with progressive worsening. A specific finding of MS-associated myelopathy is McArdle sign, wherein neck flexion is associated with prominent increased limb weakness relative to that detected with neck extension. In this study, we characterized neuromotor control properties of finger extensors in association with the McArdle sign. METHODS: A custom-built device was utilized to monitor torque production of the wrist extensors with simultaneous recording of surface electromyography of the extensor digitorum. The electromyography was decomposed and analyzed via both linear and nominal regressions. RESULTS: Linear regressions demonstrated a strong difference between groups for MS from healthy controls and other myelopathies for motor unit action potential amplitude and average firing rate (p < 0.001). Further, linear regression demonstrated good correlations of neuromotor variables to mechanical torque output (0.24 ≤ R2 ≤ 0.76). Nominal regression distinguished MS from healthy controls with an AUC of 0.87, specificity of 0.97, and sensitivity of 0.64. Nominal regression of MS from other myelopathies demonstrated an AUC of 0.88, specificity of 0.85, and sensitivity of 0.79. INTERPRETATION: These data demonstrate the neuromotor control factors that largely determine muscle force production change with the observation of McArdle sign; these neuromotor control factors can differentiate MS from both healthy controls and other myelopathy conditions.

Modulation of dopamine release by ethanol is mediated by atypical GABAA receptors on cholinergic interneurons in the nucleus accumbens.

Previous studies indicate that moderate-to-high ethanol (EtOH) concentrations enhance dopamine (DA) neurotransmission in the mesolimbic DA system from the ventral tegmental area (VTA) and projecting to the nucleus accumbens core (NAc). However, voltammetry studies demonstrate that moderate-to-high EtOH concentrations decrease evoked DA release at NAc terminals. The involvement of γ-aminobutyric acid (GABA) receptors (GABAA Rs), glycine (GLY) receptors (GLYRs) and cholinergic interneurons (CINs) in mediating EtOH inhibition of evoked NAc DA release were examined. Fast scan cyclic voltammetry, electrophysiology, optogenetics and immunohistochemistry techniques were used to evaluate the effects of acute and chronic EtOH exposure on DA release and CIN activity in C57/BL6, CD-1, transgenic mice and δ-subunit knockout (KO) mice (δ-/-). Ethanol decreased DA release in mice with an IC50 of 80 mM ex vivo and 2.0 g/kg in vivo. GABA and GLY decreased evoked DA release at 1-10 mM. Typical GABAA R agonists inhibited DA release at high concentrations. Typical GABAA R antagonists had minimal effects on EtOH inhibition of evoked DA release. However, EtOH inhibition of DA release was blocked by the α4 ß3 δ GABAA R antagonist Ro15-4513, the GLYR antagonist strychnine and by the GABA ρ1 (Rho-1) antagonist TPMPA (10 µM) and reduced significantly in GABAA R δ-/- mice. Rho-1 expression was observed in CINs. Ethanol inhibited GABAergic synaptic input to CINs from the VTA and enhanced firing rate, both of which were blocked by TPMPA. Results herein suggest that EtOH inhibition of DA release in the NAc is modulated by GLYRs and atypical GABAA Rs on CINs containing δ- and Rho-subunits.

Effects of Sex and Age on Quadriceps and Hamstring Strength and Flexibility in High School Basketball Athletes.

BACKGROUND: Eccentric hamstring strength and hamstring/quadriceps strength ratios have been identified as modifiable risk factors of hamstring strains. Additionally, those strength and flexibility characteristics are commonly used as clinical tests to monitor progress of athletes with acute or chronic hamstring strains. Although hamstring strains are common among basketball athletes, normative values of knee strength and flexibility characteristics are scarce. Normative values for these athletes would be important in prevention and management of hamstring strains. PURPOSE: To establish quadriceps and hamstring isokinetic strength and flexibility values among high school basketball athletes and examine the effects of sex and age. STUDY DESIGN: Cross-sectional research. METHODS: Isokinetic knee muscular strength (concentric quadriceps [QuadC], concentric hamstring [HamC], eccentric hamstring [HamE], and strength ratios ([HamC/QuadC and HamE/Quad]), flexibility of hip flexors and quadriceps during a Modified Thomas test, and flexibility of hip extensors and hamstring during passive straight leg raise (SLR) and passive knee extension (PKE) tests were measured. Effects of sex and age were analyzed using t-tests and analysis of variance, respectively with Bonferroni corrected post hoc tests (p≤0.01). RESULTS: A total of 172 high school basketball athletes (64 males/108 females; mean age (range): 15.7 (14-18) years old) participated in the study. Male athletes were significantly stronger than female athletes (QuadC: p<0.001; HamC: p<0.001) while no differences were observed in strength ratio (HamC/QuadC: p=0.759-0.816; HamE/QuadC: p=0.022-0.061). Among male athletes, a significant effect of age on quadriceps and hamstring strength was observed: older male athletes were stronger than younger male athletes. Contrarily, there were no effects of age on strength among female athletes. There were significant sex differences in quadriceps flexibility, SLR, and PKE (female athletes were more flexible; p=0.001-0.005) while no sex differences were found in hip flexor flexibility (p=0.105-0.164). There were no effects of age for any flexibility variables within male and female athletes (p=0.151-0.984). CONCLUSION: The current results provide normative values for hamstring strength and flexibility in high school basketball athletes. These normative values may further assist sports medicine specialists to develop screening tests, interventions, and return-to-sport criteria in this population. LEVEL OF EVIDENCE: 3B.

Diminished neuromuscular system adaptability following anterior cruciate ligament injury: Examination of knee muscle force variability and complexity.

BACKGROUND: Anterior cruciate ligament (ACL) injuries impair knee extensor and flexor force generation and may alter force variability. Fractal scaling exponents quantify signal complexity and reflect neuromuscular system adaptability. The purpose of this study was to evaluate force variability magnitudes and fractal scaling exponents in persons with ACL injuries. METHODS: Twenty-four individuals with ACL injury (time from injury: 55 ± 66 days) and 25 uninjured controls completed 10-s isometric knee extension and flexion contractions on a dynamometer at 10%, 25%, 35%, and 50% of peak force. The middle 8-s of data were used to calculate coefficients of variation and fractal exponents. Injured and non-injured limbs as well as dominant and non-dominant limbs in the control group were compared with ANOVA (P < 0.05). FINDINGS: Peak knee extensor and flexor forces were 19% and 10% lower in the injured limb of ACL-deficient participants (P = 0.014 and P = 0.036, respectively). Fractal scaling exponents of knee extensor force signals at 25% and 35% peak force in injured limbs were higher than in non-injured limbs (P = 0.008 and P = 0.027, respectively). The fractal scaling exponent of knee extensor force signals was greater in injured limbs of ACL-deficient participants than in dominant limbs of the control group at 35% peak force (P = 0.046). The magnitude of variability did not differ between limbs in ACL-deficient participants or between the injured and control groups. INTERPRETATION: Altered fractal exponents in knee extensor force signals represent sensorimotor and neuromuscular system deficits in individuals with ACL injury. Overall, fractal analysis identified both between-limb and between-group differences.