Recruitment order of motor neurons promoted by epidural stimulation in individuals with spinal cord injury.

Spinal cord epidural stimulation (scES) combined with activity-based training can promote motor function recovery in individuals with motor complete spinal cord injury (SCI). The characteristics of motor neuron recruitment, which influence different aspects of motor control, are still unknown when motor function is promoted by scES. Here, we enrolled five individuals with chronic motor complete SCI implanted with an scES unit to study the recruitment order of motor neurons during standing enabled by scES. We recorded high-density electromyography (HD-EMG) signals on the vastus lateralis muscle and inferred the order of recruitment of motor neurons from the relation between amplitude and conduction velocity of the scES-evoked EMG responses along the muscle fibers. Conduction velocity of scES-evoked responses was modulated over time, whereas stimulation parameters and standing condition remained constant, with average values ranging between 3.0 ± 0.1 and 4.4 ± 0.3 m/s. We found that the human spinal circuitry receiving epidural stimulation can promote both orderly (according to motor neuron size) and inverse trends of motor neuron recruitment, and that the engagement of spinal networks promoting rhythmic activity may favor orderly recruitment trends. Conversely, the different recruitment trends did not appear to be related with time since injury or scES implant, nor to the ability to achieve independent knees extension, nor to the conduction velocity values. The proposed approach can be implemented to investigate the effects of stimulation parameters and training-induced neural plasticity on the characteristics of motor neuron recruitment order, contributing to improve mechanistic understanding and effectiveness of epidural stimulation-promoted motor recovery after SCI.NEW & NOTEWORTHY After motor complete spinal cord injury, the human spinal cord receiving epidural stimulation can promote both orderly and inverse trends of motor neuron recruitment. The engagement of spinal networks involved in the generation of rhythmic activity seems to favor orderly recruitment trends

Neurophysiological markers predicting recovery of standing in humans with chronic motor complete spinal cord injury

The appropriate selection of individual-specific spinal cord epidural stimulation (scES) parameters is crucial to re-enable independent standing with self-assistance for balance in individuals with chronic, motor complete spinal cord injury, which is a key achievement toward the recovery of functional mobility. To date, there are no available algorithms that contribute to the selection of scES parameters for facilitating standing in this population. Here, we introduce a novel framework for EMG data processing that implements spectral analysis by continuous wavelet transform and machine learning methods for characterizing epidural stimulation-promoted EMG activity resulting in independent standing. Analysis of standing data collected from eleven motor complete research participants revealed that independent standing was promoted by EMG activity characterized by lower median frequency, lower variability of median frequency, lower variability of activation pattern, lower variability of instantaneous maximum power, and higher total power. Additionally, the high classification accuracy of assisted and independent standing allowed the development of a prediction algorithm that can provide feedback on the effectiveness of muscle-specific activation for standing promoted by the tested scES parameters. This framework can support researchers and clinicians during the process of selection of epidural stimulation parameters for standing motor rehabilitation

Oral Treatment with Iododiflunisal Delays Hippocampal Amyloid-β Formation in a Transgenic Mouse Model of Alzheimer's Disease: A Longitudinal in vivo Molecular Imaging Study

Transthyretin (TTR) is a tetrameric, amyloid-β (Aβ)-binding protein, which reduces Aβ toxicity. The TTR/Aβ interaction can be enhanced by a series of small molecules that stabilize its tetrameric form. Hence, TTR stabilizers might act as disease-modifying drugs in Alzheimer's disease. Objective: We monitored the therapeutic efficacy of two TTR stabilizers, iododiflunisal (IDIF), which acts as small-molecule chaperone of the TTR/Aβ interaction, and tolcapone, which does not behave as a small-molecule chaperone, in an animal model of Alzheimer's disease using positron emission tomography (PET). Methods: Female mice (AβPPswe/PS1A246E/TTR+/-) were divided into 3 groups (n=7 per group): IDIF-treated, tolcapone-treated, and non-treated. The oral treatment (100mg/Kg/day) was started at 5 months of age. Treatment efficacy assessment was based on changes in longitudinal deposition of Aβ in the hippocampus (HIP) and the cortex (CTX) and determined using PET-[18F]florbetaben. Immunohistochemical analysis was performed at age=14 months. Results: Standard uptake values relative to the cerebellum (SUVr) of [18F]florbetaben in CTX and HIP of non-treated animals progressively increased from age=5 to 11 months and stabilized afterwards. In contrast, [18F]florbetaben uptake in HIP of IDIF-treated animals remained constant between ages=5 and 11 months and significantly increased at 14 months. In the tolcapone-treated group, SUVr progressively increased with time, but at lower rate than in the non-treated group. No significant treatment effect was observed in CTX. Results from immunohistochemistry matched the in vivo data at age=14 months. Conclusion: Our work provides encouraging preliminary results on the ability of small-molecule chaperones to ameliorate Aβ deposition in certain brain regions

Effects of a short-term high-nitrate diet on exercise performance

It has been reported that nitrate supplementation can improve exercise performance. Most of the studies have used either beetroot juice or sodium nitrate as a supplement; there is lack of data on the potential ergogenic benefits of an increased dietary nitrate intake from a diet based on fruits and vegetables. Our aim was to assess whether a high-nitrate diet increases nitric oxide bioavailability and to evaluate the effects of this nutritional intervention on exercise performance. Seven healthy male subjects participated in a randomized cross-over study. They were tested before and after 6 days of a high (HND) or control (CD) nitrate diet (~8.2 mmol 19day(-1) or ~2.9 mmol 19day(-1), respectively). Plasma nitrate and nitrite concentrations were significantly higher in HND (127 \ub1 64 \ub5M and 350 \ub1 120 nM, respectively) compared to CD (23 \ub1 10 \ub5M and 240 \ub1 100 nM, respectively). In HND (vs. CD) were observed: (a) a significant reduction of oxygen consumption during moderate-intensity constant work-rate cycling exercise (1.178 \ub1 0.141 vs. 1.269 \ub1 0.136 L\ub7min(-1)); (b) a significantly higher total muscle work during fatiguing, intermittent sub-maximal isometric knee extension (357.3 \ub1 176.1 vs. 253.6 \ub1 149.0 Nm\ub7s\ub7kg(-1)); (c) an improved performance in Repeated Sprint Ability test. These findings suggest that a high-nitrate diet could be a feasible and effective strategy to improve exercise performance

Effects of NMES-elicited versus voluntary low-level conditioning contractions on explosive knee extensions

Objectives: Electrically-induced or voluntary conditioning-contractions (CC) can be used to affect contractile properties of a subsequent explosive contraction (EC). Here, we aimed at comparing the effect of neuromuscular-electrical-stimulation (NMES) vs voluntary CC performed prior to explosive contractions of the knee extensors. Methods: A 10 sec NMES CC (100Hz, 1000µs, 10% MVC), or a voluntary contraction (VOL CC) mimicking the NMES CC, preceded an isometric EC of the knee extensors. Explosive contraction was performed with the goal to reach the target (70% MVC) as quickly as possible. Results: All the parameters related with the explosive contractions’ muscle-output were similar between protocols (difference ranging from 0.23%, Mean Torque; to 5.8%, Time to Target), except for the Time to Peak Torque, which was lower when preceded by NMES (11.1%, p=0.019). Interestingly, the RTD 0–50 ms_EC was 37.3% higher after the NMES compared with the VOL CC protocol. Conclusion: Explosive contraction was potentiated by an NMES CC as compared with a voluntary CC. This may be due to a reduction in descending drive following VOL CC, which has been shown to occur even with low-level voluntary efforts. These findings could be used to improve rehabilitation or training protocols that include conditioning contractions

Effects of gravitational versus iso-inertial resistance training on leg muscle force and metabolic cost of walking in healthy older adults

BACKGROUND: The purpose was to compare the effects of 8-week resistance training programs (flywheel iso-inertial [FW] versus traditional gravity-dependent resistance training [GD]) performed twice a week at the same rate of perceived exertion (RPE), on muscle force and power capacities and physical performance in healthy older participants. METHODS: Twenty-four participants were randomly assigned to either FW (male/female ratio: 7/5, age: 67.1±3.8 years) or GD (male/female ratio: 6/6, age 68.3±3.0 years) group. Knee extension maximal isometric voluntary contractions (MVC), lower limb maximal explosive power (MEP), Six-Minute Walking Test (6MWT), Timed Up-and-Go Test (TUG), metabolic cost of walking (CW) and agonist-antagonist co-contraction time (CCT) during walking were evaluated before and after training. RESULTS: absolute MEP and MEP normalized for body mass increased only in FW than GD group (+10.8% vs. +0.31%, P=0.056, respectively; +14.8% vs. +13.9%, P<0.001, respectively). Both training modalities improved MVC to a similar extent (+11.1% in FW vs. +13.4% in GD, P<0.001). Analogously, 6MWT distance increased in FW and GD (+5.2 and +5.5%, P<0.041, respectively). No effects of time and training modality were observed on the other parameters. CONCLUSIONS: The results of this study suggest that when FW and GD are administered at the same RPE with FW performed at higher movement speed in the concentric phase, both the trainings generate similar improvements in muscle strength but only the former can promote greater muscle power enhancements than GDin healthy older adults