Responders to Wide-Pulse, High-Frequency Neuromuscular Electrical Stimulation Show Reduced Metabolic Demand: A 31P-MRS Study in Humans.

Conventional (CONV) neuromuscular electrical stimulation (NMES) (i.e., short pulse duration, low frequencies) induces a higher energetic response as compared to voluntary contractions (VOL). In contrast, wide-pulse, high-frequency (WPHF) NMES might elicit-at least in some subjects (i.e., responders)-a different motor unit recruitment compared to CONV that resembles the physiological muscle activation pattern of VOL. We therefore hypothesized that for these responder subjects, the metabolic demand of WPHF would be lower than CONV and comparable to VOL. 18 healthy subjects performed isometric plantar flexions at 10% of their maximal voluntary contraction force for CONV (25 Hz, 0.05 ms), WPHF (100 Hz, 1 ms) and VOL protocols. For each protocol, force time integral (FTI) was quantified and subjects were classified as responders and non-responders to WPHF based on k-means clustering analysis. Furthermore, a fatigue index based on FTI loss at the end of each protocol compared with the beginning of the protocol was calculated. Phosphocreatine depletion (ΔPCr) was assessed using 31P magnetic resonance spectroscopy. Responders developed four times higher FTI's during WPHF (99 ± 37 ×103 N.s) than non-responders (26 ± 12 ×103 N.s). For both responders and non-responders, CONV was metabolically more demanding than VOL when ΔPCr was expressed relative to the FTI. Only for the responder group, the ∆PCr/FTI ratio of WPHF (0.74 ± 0.19 M/N.s) was significantly lower compared to CONV (1.48 ± 0.46 M/N.s) but similar to VOL (0.65 ± 0.21 M/N.s). Moreover, the fatigue index was not different between WPHF (-16%) and CONV (-25%) for the responders. WPHF could therefore be considered as the less demanding NMES modality-at least in this subgroup of subjects-by possibly exhibiting a muscle activation pattern similar to VOL contractions

Modulation of spinal excitability following neuromuscular electrical stimulation superimposed to voluntary contraction

Purpose. Neuromuscular electrical stimulation (NMES) superimposed on voluntary muscle contraction has been recently shown as an innovative training modality within sport and rehabilitation, but its effects on the neuromuscular system are still unclear. The aim of this study was to investigate acute responses in spinal excitability, as measured by the Hoffmann (H) reflex, and in maximal voluntary contraction (MVIC) following NMES superimposed to voluntary isometric contractions (NMES+ISO) compared to passive NMES only and to voluntary isometric contractions only (ISO). Method. Fifteen young adults were required to maintain an ankle plantar-flexor torque of 20% MVC for 20 repetitions during each experimental condition (NMES+ISO, NMES and ISO). Surface electromyography was used to record peak-to-peak Hreflex and motor waves following percutaneous stimulation of the posterior tibial nerve in the dominant limb. An isokinetic dynamometer was used to assess maximal voluntary contraction output of the ankle plantar flexor muscles. Results. H-reflex amplitude was increased by 4.5% after the NMES+ISO condition (p < 0.05), while passive NMES and ISO conditions showed a decrease by 7.8% (p < 0.05) and no change in reflex responses, respectively. There was no change in amplitude of maximal motor wave and in MVIC torque during each experimental condition. Conclusion. The reported facilitation of spinal excitability following NMES+ISO could be due to a combination of greater motor neuronal and corticospinal excitability, thus suggesting that NMES superimposed onto isometric voluntary contractions may provide a more effective neuromuscular stimulus and, hence, training modality compared to NMES alone

Specific brain activation patterns associated with two neuromuscular electrical stimulation protocols.

The influence of neuromuscular electrical stimulation (NMES) parameters on brain activation has been scarcely investigated. We aimed at comparing two frequently used NMES protocols - designed to vary in the extent of sensory input. Whole-brain functional magnetic resonance imaging was performed in sixteen healthy subjects during wide-pulse high-frequency (WPHF, 100 Hz-1 ms) and conventional (CONV, 25 Hz-0.05 ms) NMES applied over the triceps surae. Each protocol included 20 isometric contractions performed at 10% of maximal force. Voluntary plantar flexions (VOL) were performed as control trial. Mean force was not different among the three protocols, however, total current charge was higher for WPHF than for CONV. All protocols elicited significant activations of the sensorimotor network, cerebellum and thalamus. WPHF resulted in lower deactivation in the secondary somatosensory cortex and precuneus. Bilateral thalami and caudate nuclei were hyperactivated for CONV. The modulation of the NMES parameters resulted in differently activated/deactivated regions related to total current charge of the stimulation but not to mean force. By targeting different cerebral brain regions, the two NMES protocols might allow for individually-designed rehabilitation training in patients who can no longer execute voluntary movements

Identifying motor functional neurological disorder using resting-state functional connectivity

BACKGROUND Motor functional neurological disorder (mFND) is a clinical diagnosis with reliable features; however, patients are reluctant to accept the diagnosis and physicians themselves bear doubts on potential misdiagnoses. The identification of a positive biomarker could help limiting unnecessary costs of multiple referrals and investigations, thus promoting early diagnosis and allowing early engagement in appropriate therapy. OBJECTIVES To test whether resting-state (RS) functional magnetic resonance imaging could discriminate patients suffering from mFND from healthy controls. METHODS We classified 23 mFND patients and 25 age- and gender-matched healthy controls based on whole-brain RS functional connectivity (FC) data, using a support vector machine classifier and the standard Automated Anatomic Labeling (AAL) atlas, as well as two additional atlases for validation. RESULTS Accuracy, specificity and sensitivity were over 68% (p = 0.004) to discriminate between mFND patients and controls, with consistent findings between the three tested atlases. The most discriminative connections comprised the right caudate, amygdala, prefrontal and sensorimotor regions. Post-hoc seed connectivity analyses showed that these regions were hyperconnected in patients compared to controls. CONCLUSIONS The good accuracy to discriminate patients from controls suggests that RS FC could be used as a biomarker with high diagnostic value in future clinical practice to identify mFND patients at the individual level

Wide-pulse-high-frequency neuromuscular electrical stimulation in cerebral palsy.

The present study assesses whether wide-pulse-high-frequency (WPHF) neuromuscular electrical stimulation (NMES) could result in extra-force production in cerebral palsy (CP) patients as previously observed in healthy individuals. Ten CP and 10 age- and sex-matched control participants underwent plantar flexors NMES. Two to three 10-s WPHF (frequency: 100 Hz, pulse duration: 1 ms) and conventional (CONV, frequency 25 Hz, pulse duration: 50 μs) trains as well as two to three burst-like stimulation trains (2s at 25 Hz, 2s at 100 Hz, 2s at 25 Hz; pulse duration: 1 ms) were evoked. Resting soleus and gastrocnemii maximal H-reflex amplitude (Hmax) was normalized by maximal M-wave amplitude (Mmax) to quantify α-motoneuron modulation. Similar Hmax/Mmax ratio was found in CP and control participants. Extra-force generation was observed both in CP (+18 ± 74%) and control individuals (+94 ± 124%) during WPHF (p&lt;0.05). Similar extra-forces were found during burst-like stimulations in both groups (+108 ± 110% in CP and +65 ± 85% in controls, p&gt;0.05). Although the mechanisms underlying extra-force production may differ between WPHF and burst-like NMES, similar increases were observed in patients with CP and healthy controls. Development of extra-forces in response to WPHF NMES evoked at low stimulation intensity might open new possibilities in neuromuscular rehabilitation

Are Clinical Impairments Related to Kinematic Gait Variability in Children and Young Adults With Cerebral Palsy?

Intrinsic gait variability (GV), i.e., fluctuations in the regularity of gait patterns between repetitive cycles, is inherent to the sensorimotor system and influenced by factors such as age and pathology. Increased GV is associated with gait impairments in individuals with cerebral palsy (CP) and has been mainly studied based on spatiotemporal parameters. The present study aimed to describe kinematic GV in young people with CP and its associations with clinical impairments [i.e., passive range of motion (pROM), muscle weakness, reduced selective motor control (selectivity), and spasticity]. This retrospective study included 177 participants with CP (age range 5-25 years; Gross Motor Function Classification System I-III) representing 289 clinical gait analyses [n = 172 for unilateral CP (uCP) vs. 117 for bilateral CP (bCP)]. As variability metrics, Root Mean Square Deviation (RMSD) for nine lower-limb kinematic parameters and Gait Standard Deviation (GaitSD) - as composite score of the kinematic parameters - were computed for the affected (unilateral = uCP) and most affected side (bilateral = bCP), respectively, as defined by clinical scores. GaitSD was then computed for the non/less-affected side for between leg comparisons. Uni- and multivariate linear regressions were subsequently performed on GaitSD of the affected/most affected side with all clinical impairments (composite scores) as independent variables. Highest RMSD were found in the transverse plane (hip, pelvis), for distal joints in the sagittal plane (knee, ankle) and for foot progression. GaitSD was not different between uCP and bCP (affected/most affected side) but higher in the non-affected vs. affected side in uCP. GaitSD was associated with age (p &lt; 0.001), gait deviation index (GDI) (p &lt; 0.05), muscle weakness (p &lt; 0.001), selectivity (p &lt; 0.05), and pROM (p &lt; 0.001). After adjustment for age and GDI, GaitSD remained associated with muscle weakness (uCP: p = 0.003, bCP: p &lt; 0.001) and selectivity (bCP: p = 0.024). Kinematic GV can be expressed as global indicator of variability (GaitSD) in young people with CP given the strong correlation of RMSD for lower-limb kinematic parameters. In terms of asymmetry, increased variability of the non-affected vs. affected side may indicate contralateral compensation mechanisms in uCP. Notably muscle weakness (uCP, bCP) and selectivity (bCP) - but not spasticity - were associated with GaitSD. Further studies need to explore the clinical relevance of kinematic GV in CP to support the interpretation of clinical gait analyses and therapeutic decision-making

Synthesis and biological evaluation of 5-glycyl derivatives of uridine as inhibitors of 1,4-beta-galactosyltransferase

New 5'-glycyl derivatives of uridine containing fragments of varying lipophilicity were synthesized as analogues of natural peptidyl antibiotics. One of the studied compounds, 5'-O-(N-succinylglycyl)-2',3'-O-isopropylideneuridine (A4), showed moderate inhibition against 1,4-β-galactosyltransferase. However, additional studies showed that the observed inhibitory effect was due to binding to bovine serum albumin, which was used in assays as a stabilizer

Localized metabolic and t2 changes induced by voluntary and evoked contractions

International audiencePURPOSE: This study compared the metabolic and activation changes induced by electrically evoked (neuromuscular electrical stimulation (NMES)) and voluntary (VOL) contractions performed at the same submaximal intensity using P chemical shift imaging (CSI) and T2 mapping investigations. METHODS: Fifteen healthy subjects were asked to perform both NMES and VOL protocols with the knee extensors (i.e., 232 isometric contractions at 30% of maximal force) inside a 3-T scanner for two experimental sessions. During the first session, metabolic variations, i.e., phosphocreatine (PCr), inorganic phosphate (Pi), and pH, were recorded using localized P CSI. During a second session, T2 maps of the knee extensors were obtained at rest and immediately after each exercise. Voxels of interest were selected from the directly stimulated vastus lateralis and from the nondirectly stimulated rectus femoris/vastus intermedius muscles. RESULTS: PCr depletion recorded throughout the NMES session was significantly larger in the vastus lateralis as compared with the rectus femoris/vastus intermedius muscles for both conditions (VOL and NMES). A higher occurrence of Pi splitting and a greater acidosis was found during NMES as compared with VOL exercise, illustrating the heterogeneous activation of both slow and fast muscle fibers. T2 changes were greater after NMES as compared with VOL for both muscles but were not necessarily related to the localized metabolic demand. CONCLUSION: We provided direct evidence that the metabolic demand was strongly related to both the exercise modality and the site of stimulation. On the basis of the occurrence of Pi splitting, we suggested that NMES can activate fast muscle fibers even at low force levels