Neuromuscular Coupling Research Articles

Advanced waveform analysis of diaphragm surface EMG allows for continuous non-invasive assessment of respiratory effort in critically ill patients at different PEEP levels

BackgroundRespiratory effort should be closely monitored in mechanically ventilated ICU patients to avoid both overassistance and underassistance. Surface electromyography of the diaphragm (sEMGdi) offers a continuous and non-invasive modality to assess respiratory effort based on neuromuscular coupling (NMCdi). The sEMGdi derived electrical activity of the diaphragm (sEAdi) is prone to distortion by crosstalk from other muscles including the heart, hindering its widespread use in clinical practice. We developed an advanced analysis as well as quality criteria for sEAdi waveforms and investigated the effects of clinically relevant levels of PEEP on non-invasive NMCdi.MethodsNMCdi was derived by dividing end-expiratory occlusion pressure (Pocc) by sEAdi, based on three consecutive Pocc manoeuvres at four incremental (+ 2 cmH2O/step) PEEP levels in stable ICU patients on pressure support ventilation. Pocc and sEAdi quality was assessed by applying a novel, automated advanced signal analysis, based on tolerant and strict cut-off criteria, and excluding inadequate waveforms. The coefficient of variations (CoV) of NMCdi after basic manual and automated advanced quality assessment were evaluated, as well as the effect of an incremental PEEP trial on NMCdi.Results593 manoeuvres were obtained from 42 PEEP trials in 17 ICU patients. Waveform exclusion was primarily based on low sEAdi signal-to-noise ratio (Ntolerant = 155, 37%, Nstrict = 241, 51% waveforms excluded), irregular or abrupt cessation of Pocc (Ntolerant = 145, 35%, Nstrict = 145, 31%), and high sEAdi area under the baseline (Ntolerant = 94, 23%, Nstrict = 79, 17%). Strict automated assessment allowed to reduce CoV of NMCdi to 15% from 37% for basic quality assessment. As PEEP was increased, NMCdi decreased significantly by 4.9 percentage point per cmH2O.ConclusionAdvanced signal analysis of both Pocc and sEAdi greatly facilitates automated and well-defined identification of high-quality waveforms. In the critically ill, this approach allowed to demonstrate a dynamic NMCdi (Pocc/sEAdi) decrease upon PEEP increments, emphasising that sEAdi-based assessment of respiratory effort should be related to PEEP dependent diaphragm function. This novel, non-invasive methodology forms an important methodological foundation for more robust, continuous, and comprehensive assessment of respiratory effort at the bedside.

Neuro-Muscular Responses Adaptation to Dynamic Changes in Grip Strength.

Precise control of strength is of significant importance in upper limb functional rehabilitation. Understanding the neuro-muscular response in strength regulation can help optimize the rehabilitation prescriptions and facilitate the relative training process for recovery control. This study aimed to investigate the inherent characteristics of neural-muscular activity during dynamic hand strength adjustment. Four dynamic grip force tracking modes were set by manipulating different magnitude and speed of force variations, and thirteen healthy young individuals took participation in the experiment. Electroencephalography were recorded in the contralateral sensorimotor cortex area, as well as the electromyography from the first dorsal interosseous muscle were collected synchronously. The metrics of the Event-related desynchronization, the electromyography stability index, and the force variation, were used to represent the corresponding cortical neural responses, muscle contraction activities, and the level of strength regulation, respectively; and further neuro-muscular coupling between the sensorimotor cortex and the first dorsal interosseous muscle was investigated by transfer entropy analysis. The results indicated a strong relationship that the increase of force regulation demand would result in a force variation increase as well as a stability reduction in muscle motor unit output. Meanwhile, the intensity of neural response increased in both the α and β frequency bands. As the force regulation demand increased, the strength of bidirectional transfer entropy showed a clear shift from β to the γ frequency band, which facilitate rapid integration of dynamic strength compensation to adapt to motor task changes.

Neuromuscular coupling of obligatory respiratory muscles to inspiratory pressure is reduced in dystrophic (mdx) mice

Neuromuscular coupling (NMC) is a recognised clinical index of inspiratory muscle function which reflects the efficiency of conversion of neural activation to inspiratory pressure. Duchenne muscular dystrophy (DMD) is characterised by respiratory insufficiency culminating in respiratory failure. We investigated inspiratory pressure generating capacity and electrical activation of obligatory inspiratory muscles in X-linked muscular dystrophy ( mdx) mice, to evaluate NMC of diaphragm, external intercostal and parasternal intercostal to inspiratory pressure across a range of behaviours in early established to late progressive disease.In urethane anaesthetised mice (1.7 g/kg i.p.), inspiratory pressure was recorded via a pressure transducer positioned in the thoracic oesophagus. Diaphragm EMG activity was recorded using needle electrodes. Studies were performed in male wildtype (WT) and mdx mice at 4, 8, 12 and 16 months old. Recordings were made at baseline and during sustained tracheal occlusion to task failure, defined as an inability to sustain peak pressure. Peak pressure was determined from the average of five successive peak efforts at the maximum response. The corresponding peak inspiratory EMG activities were determined. Two factor (age x genotype) analysis of variance was performed.Obligatory muscle EMG activities were significantly lower in mdx mice from 4 months of age. Peak inspiratory pressure was significantly greater in mdx at 4 months of age. At 8 months, peak inspiratory pressure was equivalent between WT and mdx followed by a significant decrease in peak inspiratory pressure in 12- and 16-month-old mdx. NMC was lower in mdx mice across the ventilatory and non-ventilatory range, emerging early in dystrophic disease.Reduced NMC of obligatory muscles to inspiratory pressure in mdx mice reveals a greater reliance on accessory muscles to support respiratory performance in dystrophic disease. Remarkably, this burden is adequately accommodated in early disease with a preserved capacity to generate peak inspiratory pressure. We reason that the loss of compensation afforded by accessory muscles to peak inspiratory pressure generation underpins the emergence of respiratory compromise in advanced disease. Our results may have implications for the understanding and treatment of DMD. Funded by Science Foundation Ireland SFI/19/6628 INSPIRE DMD. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A 3D cell culture system for bioengineering human neuromuscular junctions to model ALS.

The signals that coordinate and control movement in vertebrates are transmitted from motoneurons (MNs) to their target muscle cells at neuromuscular junctions (NMJs). Human NMJs display unique structural and physiological features, which make them vulnerable to pathological processes. NMJs are an early target in the pathology of motoneuron diseases (MND). Synaptic dysfunction and synapse elimination precede MN loss suggesting that the NMJ is the starting point of the pathophysiological cascade leading to MN death. Therefore, the study of human MNs in health and disease requires cell culture systems that enable the connection to their target muscle cells for NMJ formation. Here, we present a human neuromuscular co-culture system consisting of induced pluripotent stem cell (iPSC)-derived MNs and 3D skeletal muscle tissue derived from myoblasts. We used self-microfabricated silicone dishes combined with Velcro hooks to support the formation of 3D muscle tissue in a defined extracellular matrix, which enhances NMJ function and maturity. Using a combination of immunohistochemistry, calcium imaging, and pharmacological stimulations, we characterized and confirmed the function of the 3D muscle tissue and the 3D neuromuscular co-cultures. Finally, we applied this system as an in vitro model to study the pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and found a decrease in neuromuscular coupling and muscle contraction in co-cultures with MNs harboring ALS-linked SOD1 mutation. In summary, the human 3D neuromuscular cell culture system presented here recapitulates aspects of human physiology in a controlled in vitro setting and is suitable for modeling of MND.

Adaptation of the Corticomuscular and Biomechanical Systems of Pianists.

Independent control of movements between the fingers plays a role in hand dexterity characterizing skilled individuals. However, it remains unknown whether and in what manner neuromuscular and biomechanical constraints on the movement independence of the fingers depend on motor expertise. Here, we compared motor dexterity, corticospinal excitability of multiple muscles, muscular activation, and anatomical features of the fingers between the pianists and nonpianists. When the ring finger was passively moved by a robot, passive motions produced at the adjacent fingers were smaller for the pianists than the nonpianists, indicating reduced biomechanical constraint of fingers in the pianists. In contrast, when the ring finger moved actively, we found no group difference in passive motions produced at the adjacent fingers; however, reduced inhibition of corticospinal excitability of the adjacent fingers in the pianists compared with the nonpianists. This suggests strengthened neuromuscular coupling between the fingers of the pianists, enhancing the production of coordinated finger movements. These group differences were not evident during the index and little finger movements. Together, pianists show expertise-dependent biomechanical and neurophysiological adaptations, specifically at the finger with innately low movement independence. Such contrasting adaptations of pianists may subserve dexterous control of both the individuated and coordinated finger movements.

A Case Report of Functional Acupuncture in the Treatment of Senile Left Persistent Facial Paralysis

Introduction: Idiopathic facial palsy, also known as Bell's palsy (BP) or facial neuritis, is an acute onset of peripheral facial neuropathy. The onset of this disease is rapid, and there is a history of cold, mostly on one side of the face. Objective: to introduce and analyze the method and curative effect of functional acupuncture on one case of senile left persistent facial paralysis. Methods: focus on the functional parts of the affected area that need to be improved, select the acupuncture areas with improved trigger function, and select the stimulation dose of electroacupuncture. In other words, functional acupuncture is the main acupuncture method in the treatment process, that is, to take a functional position before acupuncture on the paralyzed side of the cheek, that is, to lift the patient's left corner of the mouth outward to above the functional position with a surgical small retractor (the largest lifting mouth angle is tilted to the left side), to determine the left cheek muscle functional area (needle entry area), and to make corresponding adjustment on the left cheek Acupoints selected in functional areas: Xiaguan, zygomatic Luo, buccal Che, Yingxiang, Renzhong, Taiyang, sizhukong, Chengzhi, yangbai. The needle of 0.35 mm × 40 mm was selected, and 0.3-1 inch flat needling was used with electroacupuncture. The waveform was density wave. Five times a week, 10 times for a course of treatment. Results: after two courses of functional acupuncture treatment, the patient's left eyelid was basically closed, and the air leakage during the left cheek bulging was significantly improved. After eating, the food left in the left cheek disappeared, the left nasolabial groove appeared, the left frontal lines appeared, and the symptoms of the left mouth angle slanting to the right were significantly improved (see the figure below). Conclusion: the essence of functional acupuncture improvement is to re form a strong neuromuscular effect in muscles, destroy the paralysis and weakness of target muscles, and reconstruct the normal neuromuscular coupling mode. The aim of this balance mechanism is to destroy the reflex pattern of abnormal muscle paralysis and muscle weakness and reconstruct an orderly and normal neuromuscular reflex.

Intra-gastrointestinal amyloid-β1-42 oligomers perturb enteric function and induce Alzheimer's disease pathology.

Key points Alzheimer's disease (AD) patients and transgenic mice have beta‐amyloid (Aβ) aggregation in the gastrointestinal (GI) tract.It is possible that Aβ from the periphery contributes to the load of Aβ in the brain, as Aβ has prion‐like properties.The present investigations demonstrate that Aβ injected into the GI tract of ICR mice is internalised into enteric cholinergic neurons; at 1 month, administration of Aβ into the body of the stomach and the proximal colon was observed to partly redistribute to the fundus and jejunum; at 1 year, vagal and cerebral β‐amyloidosis was present, and mice exhibited GI dysfunction and cognitive deficits.These data reveal a previously undiscovered mechanism that potentially contributes to the development of AD. Alzheimer's disease (AD) is the most common age‐related cause of dementia, characterised by extracellular beta‐amyloid (Aβ) plaques and intracellular phosphorylated tau tangles in the brain. Aβ deposits have also been observed in the gastrointestinal (GI) tract of AD patients and transgenic mice, with overexpression of amyloid precursor protein. In the present studies, we investigate whether intra‐GI administration of Aβ can potentially induce amyloidosis in the central nervous system (CNS) and AD‐related pathology such as dementia. We micro‐injected Aβ1–42 oligomers (4 μg per site, five sites) or vehicle (saline, 5 μl) into the gastric wall of ICR mice under general anaesthesia. Immunofluorescence staining and in vivo imaging showed that HiLyte Fluor 555‐labelled Aβ1–42 had migrated within 3 h via the submucosa to nearby areas and was internalised into cholinergic neurons. At 1 month, HiLyte Fluor 555‐labelled Aβ1–42 in the body of the stomach and proximal colon had partly re‐distributed to the fundus and jejunum. At 1 year, the jejunum showed functional alterations in neuromuscular coupling (P < 0.001), and Aβ deposits were present in the vagus and brain, with animals exhibiting cognitive impairments in the Y‐maze spontaneous alteration test (P < 0.001) and the novel object recognition test (P < 0.001). We found that enteric Aβ oligomers induce an alteration in gastric function, amyloidosis in the CNS, and AD‐like dementia via vagal mechanisms. Our results suggest that Aβ load is likely to occur initially in the GI tract and may translocate to the brain, opening the possibility of new strategies for the early diagnosis and prevention of AD.

Gamma frequency band shift of contralateral corticomuscular synchronous oscillations with force strength for hand movement tasks.

Bilateral voluntary contractions involve functional changes in both primary motor cortices. However how the unilateral voluntary contraction of hand muscles influences the contralateral corticomuscular synchronous oscillations mechanisms remains unclear. In the bimanual tasks, nine healthy subjects were instructed to generate force by abducting their left-hand index finger against a force sensor and simultaneously the right-hand precise pinch task with visual feedback. They were divided into four conditions according to the two contraction force levels of the left-hand muscles 5% and 50% maximal isometric voluntary contraction (MVC) and with/without visual feedback for the right hand. Corticomuscular synchronization of the right hand in the beta band was revealed when the subjects performed the bimanual exercise with 5% MVC of left-hand muscles, which is consistent with previous studies. As the contraction strength of the left-hand muscle increased to 50% MVC, the corticomuscular coherence (CMC) frequency of the right hand shifted to gamma band, and the CMC in beta band decreased significantly (P < 0.05) in the electroencephalography→electromyography direction. This phenomenon suggests that the corticomuscular synchronous oscillation will shift from beta band to higher frequencies (principally gamma) as the contraction force of the contralateral hand increases, which may be due to the changes in the subject's attention and more frequent synchronization of neuromuscular motor neurons oscillations. These findings will be helpful to explore the hand motion control and feedback mechanisms, and further provide a basis for the application of neuromuscular coupling in clinical rehabilitation evaluation.Video abstract: http://links.lww.com/WNR/A571.

A Case Report of Functional Acupuncture for Treatment of Elderly Type 2 Diabetic Oculomotor Nerve Palsy

Objective: To introduce and analyze the method and effect of functional acupuncture in treating one case of elderly type 2 diabetic oculomotor nerve palsy. Methods: The main emphasis is on taking the functional position of the affected area, selecting the functional acupuncture area, and choosing the electroacupuncture stimulation dose. That is, the functional acupuncture method is the main acupuncture method during treatment, that is, the functional position is taken before the upper eyelid acupuncture, and the patient’s left upper eyelid Lift to above the functional position (maximum lifting position-eye open state), determine the muscle functional area around the eye (needle entry area) of the raised eyelid, and select acupoints in the corresponding functional area around the eye: Cuanzhu, Yuyao, Sizhu For Kong, Shenting, Tou Linqi and Ashi points, choose a needle with a model of 0.35 mm×40 mm, take a 0.3 to 1 inch flat puncture, and use an electroacupuncture to form a dense wave. Results: After 20 days of functional acupuncture, the symptoms of ptosis of the left eye of the patient improved significantly, and the limitation of movement of the left eye was significantly improved. Follow-up six months later, there was no recurrence, and the clinical effect was satisfactory. Conclusion: The essence of functional acupuncture improvement is to re-form a powerful neuromuscular effect in the muscles, destroy the paralysis and weakness of the targeted muscle groups, and rebuild the normal neuromuscular coupling mode. The goal of this balancing mechanism is to destroy abnormal muscle paralysis and The reflex pattern of muscle weakness reconstructs an orderly and normal neuromuscular reflex.

Analysis of multichannel intermuscular coupling characteristics during rehabilitation after stroke

To better analyze the problem of abnormal neuromuscular coupling related to motor dysfunction for stroke patients, the functional coupling of the multichannel electromyography (EMG) were studied and the difference between stroke patients and healthy subjects were further analyzed to explore the pathological mechanism of motor dysfunction after stroke. Firstly, the cross-frequency coherence (CFC) analysis and non-negative matrix factorization (NMF) were combined to construct a CFC-NMF model to study the linear coupling relationship in bands and the nonlinear coupling characteristics in different frequency ratios during elbow flexion and extension movement. Furthermore, the significant coherent area and sum of cross-frequency coherence were respectively calculated to quantitatively describe the intermuscular linear and nonlinear coupling characteristics. The results showed that the linear coupling relationship between multichannel muscles was different in frequency bands and the overall coupling was stronger in low frequency band. The linear coupling strength of the stroke patients was lower than that of the healthy subjects in different frequency bands especially in beta and gamma bands. For the nonlinear coupling, the intermuscular coupling strength of stroke patients in different frequency ratios was significantly lower than that of the healthy subjects, and the coupling strength in the frequency ratio 1∶2 was higher than that in the frequency ratio 1∶3. This method can provide a theoretical basis for exploring the intermuscular coupling mechanism of patients with motor dysfunction.

Activation of Hedgehog Signaling Promotes Development of Mouse and Human Enteric Neural Crest Cells, Based on Single-Cell Transcriptome Analyses

It has been a challenge to develop fully functioning cells from human pluripotent stem cells (hPSCs). We investigated how activation of hedgehog signaling regulates derivation of enteric neural crest (NC) cells from hPSCs. We analyzed transcriptomes of mouse and hPSC-derived enteric NCs using single-cell RNA sequencing (scRNA-seq) to identify the changes in expression associated with lineage differentiation. Intestine tissues were collected from Tg(GBS-GFP), Sufuf/f; Wnt1-cre, Ptch1+/-, and Gli3Δ699/Δ699 mice and analyzed by flow cytometry and immunofluorescence for levels of messenger RNAs encoding factors in the hedgehog signaling pathway during differentiation of enteric NCs. Human NC cells (HNK-1+p75NTR+) were derived from IMR90 and UE02302 hPSC lines. hPSCs were incubated with a hedgehog agonist (smoothened agonist [SAG]) and antagonists (cyclopamine) and analyzed for differentiation. hPSC-based innervated colonic organoids were derived from these hPSC lines and analyzed by immunofluorescence and neuromuscular coupling assay for expression of neuronal subtype markers and assessment of the functional maturity of the hPSC-derived neurons, respectively. Single-cell RNA sequencing analysis showed that neural fate acquisition by human and mouse enteric NC cells requires reduced expression of NC- and cell cycle-specific genes and up-regulation of neuronal or glial lineage-specific genes. Activation of the hedgehog pathway was associated with progression of mouse enteric NCs to the more mature state along the neuronal and glial lineage differentiation trajectories. Activation of the hedgehog pathway promoted development of cultured hPSCs into NCs of greater neurogenic potential by activating expression of genes in the neurogenic lineage. The hedgehog agonist increased differentiation of hPSCs into cells of the neuronal lineage by up-regulating expression of GLI2 target genes, including INSM1, NHLH1, and various bHLH family members. The hedgehog agonist increased expression of late neuronal markers and neuronal activities in hPSC-derived neurons. In enteric NCs from humans and mice, activation of hedgehog signaling promotes differentiation into neurons by promoting cell-state transition, expression of genes in the neurogenic lineage, and functional maturity of enteric neurons.

Involuntary Neuromuscular Coupling between the Thumb and Finger of Stroke Survivors during Dynamic Movement.

Finger–thumb coordination is crucial to manual dexterity but remains incompletely understood, particularly following neurological injury such as stroke. While being controlled independently, the index finger and thumb especially must work in concert to perform a variety of tasks requiring lateral or palmar pinch. The impact of stroke on this functionally critical sensorimotor control during dynamic tasks has been largely unexplored. In this study, we explored finger–thumb coupling during close–open pinching motions in stroke survivors with chronic hemiparesis. Two types of perturbations were applied randomly to the index with a novel Cable-Actuated Finger Exoskeleton: a sudden joint acceleration stretching muscle groups of the index finger and a sudden increase in impedance in selected index finger joint(s). Electromyographic signals for specific thumb and index finger muscles, thumb tip trajectory, and index finger joint angles were recorded during each trial. Joint angle perturbations invoked reflex responses in the flexor digitorum superficialis (FDS), first dorsal interossei (FDI), and extensor digitorum communis muscles of the index finger and heteronymous reflex responses in flexor pollicis brevis of the thumb (p < 0.017). Phase of movement played a role as a faster peak reflex response was observed in FDI during opening than during closing (p < 0.002) and direction of perturbations resulted in shorter reflex times for FDS and FDI (p < 0.012) for extension perturbations. Surprisingly, when index finger joint impedance was suddenly increased, thumb tip movement was substantially increased, from 2 to 10 cm (p < 0.001). A greater effect was seen during the opening phase (p < 0.044). Thus, involuntary finger–thumb coupling was present during dynamic movement, with perturbation of the index finger impacting thumb activity. The degree of coupling modulated with the phase of motion. These findings reveal a potential mechanism for direct intervention to improve poststroke hand mobility and provide insight on prospective neurologically oriented therapies.

Electroencephalogram-Electromyography Coupling Analysis in Stroke Based on Symbolic Transfer Entropy.

The coupling strength between electroencephalogram (EEG) and electromyography (EMG) signals during motion control reflects the interaction between the cerebral motor cortex and muscles. Therefore, neuromuscular coupling characterization is instructive in assessing motor function. In this study, to overcome the limitation of losing the characteristics of signals in conventional time series symbolization methods, a variable scale symbolic transfer entropy (VS-STE) analysis approach was proposed for corticomuscular coupling evaluation. Post-stroke patients (n = 5) and healthy volunteers (n = 7) were recruited and participated in various tasks (left and right hand gripping, elbow bending). The proposed VS-STE was employed to evaluate the corticomuscular coupling strength between the EEG signal measured from the motor cortex and EMG signal measured from the upper limb in both the time-domain and frequency-domain. Results showed a greater strength of the bi-directional (EEG-to-EMG and EMG-to-EEG) VS-STE in post-stroke patients compared to healthy controls. In addition, the strongest EEG–EMG coupling strength was observed in the beta frequency band (15–35 Hz) during the upper limb movement. The predefined coupling strength of EMG-to-EEG in the affected side of the patient was larger than that of EEG-to-EMG. In conclusion, the results suggested that the corticomuscular coupling is bi-directional, and the proposed VS-STE can be used to quantitatively characterize the non-linear synchronization characteristics and information interaction between the primary motor cortex and muscles.

Airflow limitation is accompanied by diaphragm dysfunction.

Chronic airflow limitation, caused by chronic obstructive pulmonary disease (COPD) or by asthma, is believed to change the shape and the position of the diaphragm due to an increase in lung volume. We have made a comparison of magnetic resonance imaging (MRI) of diaphragm in supine position with pulmonary functions, respiratory muscle function and exercise tolerance. We have studied the differences between patients with COPD, patients with asthma, and healthy subjects. Most interestingly we found the lung hyperinflation leads to the changes in diaphragmatic excursions during the breathing cycle, seen in the differences between the maximal expiratory diaphragm position (DPex) in patients with COPD and control group (p=0.0016). The magnitude of the diaphragmatic dysfunction was significantly related to the airflow limitation expressed by the ratio of forced expiratory volume in 1 s to slow vital capacity (FEV(1)/SVC), (%, p=0.0007); to the lung hyperinflation expressed as the ratio of the residual volume to total lung capacity (RV/TLC), (%, p=0.0018) and the extent of tidal volume constrain expressed as maximal tidal volume (V(Tmax)), ([l], p=0.0002); and the ratio of tidal volume to slow vital capacity (V(T)/SVC), (p=0.0038) during submaximal exercise. These results suggest that diaphragmatic movement fails to contribute sufficiently to the change in lung volume in emphysema. Tests of respiratory muscle function were related to the position of the diaphragm in deep expiration, e.g. neuromuscular coupling (P(0.1)/V(T)) (p=0.0232). The results have shown that the lung volumes determine the position of the diaphragm and function of the respiratory muscles. Chronic airflow limitation seems to change the position of the diaphragm, which thereafter influences inspiratory muscle function and exercise tolerance. There is an apparent relationship between the position of the diaphragm and the pulmonary functions and exercise tolerance.

Informational constraints on spontaneous visuomotor entrainment

Past research has revealed that an individual’s rhythmic limb movements become spontaneously entrained to an environmental rhythm if visual information about the rhythm is available and its frequency is near that of the individual’s movements. Research has also demonstrated that if the eyes track an environmental stimulus, the spontaneous entrainment to the rhythm is strengthened. One hypothesis explaining this enhancement of spontaneous entrainment is that the limb movements and eye movements are linked through a neuromuscular coupling or synergy. Another is that eye-tracking facilitates the pick up of important coordinating information. Experiment 1 investigated the first hypothesis by evaluating whether any rhythmic movement of the eyes would facilitate spontaneous entrainment. Experiments 2 and 3 (respectively) explored whether eye-tracking strengthens spontaneous entrainment by allowing the pickup of trajectory direction change information or allowing an increase in the amount of information to be picked-up. Results suggest that the eye-tracking enhancement of spontaneous entrainment is a consequence of increasing the amount of information available to be picked-up.

VALIDATION OF THE LEAST SQUARES FITTING METHOD (LSF) DURING NAVA AND PSV VENTILATION

The Least Squares Fitting (LSF) is a computerized method of analysis of respiratory system mechanics. It is based on applying a regression analysis for every sample points of the loop of pressure, flow and volume by fitting the equation Paw= Rrs× V' + VT/Crs+ PEEPtot during inspiration [1]. This technique has been already validated in Controlled Mechanical Ventilation (CMV) and at high level of Pressure Support Ventilation (PSV) [2]. However this method gives unreliable values of resistance (Rrs) and elastance (Ers) in presence of inspiratory muscle activity and in absence of an adequate neuromuscular coupling. We reasoned that NAVA (Neurally-Adjusted Ventilatory Assist) ventilation should assure a better neuromuscular coupling compared to PSV and hence the coefficient of determination (CD) of the above equation should be much higher during NAVA ventilation.

Electromyographic activity of the diaphragm during neostigmine or sugammadex-enhanced recovery after neuromuscular blockade with rocuronium: a randomised controlled study in healthy volunteers.

The use of neuromuscular blocking agents has been associated with severe postoperative respiratory morbidity. Complications can be attributed to inadequate reversal, and reversal agents may themselves have adverse effects. To compare the electromyographic activity of the diaphragm (EMGdi) during recovery from neuromuscular blockade using neostigmine and sugammadex. The hypothesis was that there would be better neuromuscular coupling of the diaphragm when sugammadex was used. A randomised, controlled, parallel-group, single-centre, double-blinded study. District general hospital in Belgium. Twelve healthy male volunteers. Individuals were anaesthetised with propofol and remifentanil. After rocuronium 0.6 mg kg, a transoesophageal electromyography (EMG) recorder was inserted. For reversal of neuromuscular blockade, volunteers received sugammadex 2 mg kg (n = 6) or neostigmine 70 μg kg (n = 6). EMGdi, airway pressure and flow were continuously measured during weaning from the ventilator until tracheal extubation. Arterial blood gas samples were obtained for PaO2 and PaCO2 analysis at the first spontaneous breathing attempt and after tracheal extubation. During weaning, 560 breaths were retained for analysis. The median (95% CI) peak EMGdi was 1.1 (0.9 to 1.5) μV in the neostigmine group and 1.6 (1.3 to 1.9) μV in the sugammadex group (P < 0.001). Individuals in the neostigmine group had 125 of 228 (55%) breaths with associated EMGdi at least 1 μV vs. 220 of 332 (66%) breaths in the sugammadex group (P = 0.008). The median (95% CI) tidal volume was 287 (256 to 335) ml after neostigmine and 359 (313 to 398) ml after sugammadex (P = 0.013). The median (95% CI) PaO2 immediately after extubation was 30.5 (22.8 to 37.1) kPa after sugammadex vs. 20.7 (12.9 to 27.5) kPa after neostigmine (P = 0.03). EMGdi, tidal volume and PaO2 following tracheal extubation were increased after sugammadex compared with neostigmine, reflecting diaphragm-driven inspiration after sugammadex administration. Sugammadex may free more diaphragmatic acetylcholine receptors than neostigmine, which has an indirect effect. EudraCT ref: 2013-002078-30.

EVER 2013 Lecture: Advances in OCT imaging

AbstractIn the brain there is a tight coupling between local neural activity and local blood flow and metabolism. This phenomenon called neurovascular coupling was proposed more than 100 years ago and since then confirmed by numerous experiments. A breakdown in functional hyperemia has been hypothesized to contribute to loss of neurons in diseases such as stroke, hypertension, spinal‐cord injury and Alzheimer’s disease. In the eye this phenomenon exists as well. During stimulation of the eye with flicker light there is a pronounced increase in retinal and optic nerve head blood flow. The mechanisms underlying neuromuscular coupling in the retina are complex and involve the interaction between neurons, astrocytes and blood vessels. In this process vasoactive arachidonic acid metabolites play a key role. In addition, the vascular endothelium is involved. The response of retinal vessels to flicker stimulation is also modified by nitric oxide and oxygen. Neurovascular coupling is altered in diseases such as glaucoma or diabetes and may contribute to neuronal loss in these diseases. A better understanding of these phenomena is required to achieve neuroprotection via the neuromuscular pathway.

Update on emerging drugs for sarcopenia – age-related muscle wasting

Sarcopenia – the progressive loss of muscle mass with advancing age is characterised by a deterioration of muscle quantity and quality leading to a gradual slowing of movement and a decline in strength and power. Sarcopenia is a highly significant public health problem. Frail elders often require assistance for accomplishing even basic tasks of independent living, and they are also at increased risk of serious injury from sudden falls and subsequent fractures. Since these age-related changes are largely attributed to the complex interaction of factors affecting neuromuscular transmission, muscle architecture, fibre composition, excitation-contraction coupling, and metabolism, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for novel drug discovery. Objective: This review provides an update on some of the emerging drugs for sarcopenia that have been in development during 2005 – 2008. Methods: This is a review of the current status of emerging therapies and novel approaches for sarcopenia. Results: Considerable research and development in academic and research institutions and in large and small pharma is being directed to sarcopenia and related health issues; specifically the development and evaluation of novel therapeutic strategies to attenuate, prevent, or ultimately reverse age-related muscle wasting and weakness. Conclusions: Few, if any, drugs have been developed for sarcopenia specifically, but there are many existing and emerging drugs that have potential application for tackling age-related muscle wasting, particularly drugs for neurodegenerative diseases.

Comparing the attractor strength of intra- and interpersonal interlimb coordination using cross-recurrence analysis

Previous research has demonstrated that intra- and interpersonal rhythmic interlimb coordination are both constrained by the self-organizing entrainment process of coupled oscillators. Despite intra- and interpersonal coordination exhibiting the same stable macroscopic movement patterns the variability of the coordination is typically found to be much greater for inter- compared to intrapersonal coordination. Researchers have assumed that this is due to the interpersonal visual-motor coupling producing a weaker attractor dynamic than the intrapersonal neuromuscular coupling. To determine whether this assumption is true, two experiments were conducted in which pairs of participants coordinated hand-held pendulums swung about the wrist, either intra- and interpersonally. Using the cross-recurrence statistics of percent recurrence and maxline to independently index the level of noise and the attractor strength of the coordination, respectively, the results confirmed that the attractor strength was significantly weaker for inter- compared to intrapersonal coordination and that a similar magnitude of noise underlies both.