Adaptive HD-sEMG decomposition: towards robust real-time decoding of neural drive.

Objective. Neural interfacing via decomposition of high-density surface electromyography (HD-sEMG) should be robust to signal non-stationarities incurred by changes in joint pose and contraction intensity.Approach. We present an adaptive real-time motor unit decoding algorithm and test it on HD-sEMG collected from the extensor carpi radialis brevis during isometric contractions over a range of wrist angles and contraction intensities. The performance of the algorithm was verified using high-confidence benchmark decompositions derived from concurrently recorded intramuscular electromyography.Main results. In trials where contraction conditions between the initialization and testing data differed, the adaptive decoding algorithm maintained significantly higher decoding accuracies when compared to static decoding methods.Significance. Using "gold standard" verification techniques, we demonstrate the limitations of filter re-use decoding methods and show the necessity of parameter adaptation to achieve robust neural decoding.

Semi-Automated Identification of Motor Units Concurrently Recorded in High-Density Surface and Intramuscular Electromyography.

An increasing focus on extending automated surface electromyography (EMG) decomposition algorithms to operate under non-stationary conditions requires rigorous and robust validation. However, relevant benchmarks derived manually from iEMG are laborsome to obtain and this is further exacerbated by the need to consider multiple contraction conditions. This work demonstrates a semi-automatic technique for extracting motor units (MUs) whose activities are present in concurrently recorded high-density surface EMG (HD-sEMG) and intramuscular EMG (iEMG) during isometric contractions. We leverage existing automatic surface decomposition algorithms for initial identification of active MUs. Resulting spike times are then used to identify (trigger) the sources that are concurrently detectable in iEMG. We demonstrate this technique on recordings targeting the extensor carpi radialis brevis in five human subjects. This dataset consists of 117 trials across different force levels and wrist angles, from which the presented method yielded a set of 367 high-confidence decompositions. Thus, our approach effectively alleviates the overhead of manual decomposition as it efficiently produces reliable benchmarks under different conditions.Clinical Relevance- We present an efficient method for obtaining high-quality in-vivo decomposition particularly useful in the verification of new surface decomposition approaches.

Optimal Motor Unit Subset Selection for Accurate Motor Intention Decoding: Towards Dexterous Real-Time Interfacing.

OBJECTIVE: Motor unit (MU) discharge timings encode human motor intentions to the finest degree. Whilst tapping into such information can bring significant gains to a range of applications, current approaches to MU decoding from surface signals do not scale well with the demands of dexterous human-machine interfacing (HMI). To optimize the forward estimation accuracy and time-efficiency of such systems, we propose the inclusion of task-wise initialization and MU subset selection. METHODS: Offline analyses were conducted on data recorded from 11 non-disabled subjects. Task-wise decomposition was applied to identify MUs from high-density surface electromyography (HD-sEMG) pertaining to 18 wrist/forearm motor tasks. The activities of a selected subset of MUs were extracted from test data and used for forward estimation of intended motor tasks and joint kinematics. To that end, various combinations of subset selection and estimation algorithms (both regression and classification-based) were tested for a range of subset sizes. RESULTS: The mutual information-based minimum Redundancy Maximum Relevance (mRMR-MI) criterion retained MUs with the highest predicative power. When the portion of tracked MUs was reduced down to 25%, the regression performance decreased only by 3% (R2=0.79) while classification accuracy dropped by 2.7% (accuracy = 74%) when kernel-based estimators were considered. CONCLUSION AND SIGNIFICANCE: Careful selection of tracked MUs can optimize the efficiency of MU-driven interfacing. In particular, prioritization of MUs exhibiting strong nonlinear relationships with target motions is best leveraged by kernel-based estimators. Hence, this frees resources for more robust and adaptive MU decoding techniques to be implemented in future.

Muscle Synergy-driven Motor Unit Clustering for Human-Machine Interfacing.

Electromyographic signals (EMGs) can provide information on the overall activity of the innervating motor neuros in any given muscle but also globally reflect the underlying neuromechanics of human movement (e.g., muscle synergies). motor unit(MU) decomposition is a technique based on the deconvolution of high-density EMGs (HD-EMG) in order to derive the activities of the corresponding motor neurons. This powerful yet very sensitive tool has seen some traction in human-machine interfacing (HMI) for rehabilitation. Here, we propose combining the synergy-inspired channel clustering in order to isolate the most prominent regions of EMG activation in each targeted degree of freedom (DoF) and thus cater to decomposition's sensitivity demands. Our assumption is that this will lead to a higher number of extracted MUs and consequently better motion estimation in HMIs. Indeed, in four subjects, we have shown a 69% average increase in the number of MUs when decomposition was done using muscle-synergy channel clustering. Consequently, all three of our kinematic estimators benefited from an increased pool of units, with the linear regressor showing the greatest improvement once compared to, the artificial neural network and the gated recurrent unit, which had the overall best performance. Clinical Relevance- The results demonstrated in this work provide a new perspective on the online EMG-driven HMI systems that can be greatly beneficial in the rehabilitation of motor disorders.

Co-Adaptive Control of Bionic Limbs via Unsupervised Adaptation of Muscle Synergies.

OBJECTIVE: In this work, we present a myoelectric interface that extracts natural motor synergies from multi-muscle signals and adapts in real-time with new user inputs. With this unsupervised adaptive myocontrol (UAM) system, optimal synergies for control are continuously co-adapted with changes in user motor control, or as a function of perturbed conditions via online non-negative matrix factorization guided by physiologically informed sparseness constraints in lieu of explicit data labelling. METHODS: UAM was tested in a set of virtual target reaching tasks completed by able-bodied and amputee subjects. Tests were conducted under normative and electrode perturbed conditions to gauge control robustness with comparisons to non-adaptive and supervised adaptive myocontrol schemes. Furthermore, UAM was used to interface an amputee with a multi-functional powered hand prosthesis during standardized Clothespin Relocation Tests, also conducted in normative and perturbed conditions. RESULTS: In virtual tests, UAM effectively mitigated performance degradation caused by electrode displacement, affording greater resilience over an existing supervised adaptive system for amputee subjects. Induced electrode shifts also had negligible effect on the real world control performance of UAM with consistent completion times (23.91 ±1.33 s) achieved across Clothespin Relocation Tests in the normative and electrode perturbed conditions. CONCLUSION: UAM affords comparable robustness improvements to existing supervised adaptive myocontrol interfaces whilst providing additional practical advantages for clinical deployment. SIGNIFICANCE: The proposed system uniquely incorporates neuromuscular control principles with unsupervised online learning methods and presents a working example of a freely co-adaptive bionic interface.

Can Multi-DoF Training Improve Robustness of Muscle Synergy Inspired Myocontrollers?

Non-negative Matrix Factorization (NMF) has been effective in extracting commands from surface electromyography (EMG) for the control of upper-limb prostheses. This approach enables Simultaneous and Proportional Control (SPC) over multiple degrees-of-freedom (DoFs) in a minimally supervised way. Here, like with other myoelectric approaches, robustness remains essential for clinical adoption, with device donning/doffing being a known cause for performance degradation. Previous research has demonstrated that NMF-based myocontrollers, trained on just single-DoF activations, permit a certain degree of user adaptation to a range of disturbances. In this study, we compare this traditional NMF controller with its sparsity constrained variation that allows initialization using both single and combined-DoF activations (NMF-C). The evaluation was done on 12 able bodied participants through a set of online target-reaching tests. Subjects were fitted with an 8-channel bipolar EMG setup, which was shifted by 1cm in both transversal directions throughout the experiments without system retraining. In the baseline condition NMF performed somewhat better than NMFC, but it did suffer more following the electrode repositioning, making the two perform on par. With no significant difference present across the conditions, results suggest that there is no immediate advantage from the naïve inclusion of more comprehensive training sets to the classic synergy-inspired implementation of SPC.

Directional Forgetting for Stable Co-Adaptation in Myoelectric Control.

Conventional myoelectric controllers provide a mapping between electromyographic signals and prosthetic functions. However, due to a number of instabilities continuously challenging this process, an initial mapping may require an extended calibration phase with long periods of user-training in order to ensure satisfactory performance. Recently, studies on co-adaptation have highlighted the benefits of concurrent user learning and machine adaptation where systems can cope with deficiencies in the initial model by learning from newly acquired data. However, the success remains highly dependent on careful weighting of these new data. In this study, we proposed a function driven directional forgetting approach to the recursive least-squares algorithm as opposed to the classic exponential forgetting scheme. By only discounting past information in the same direction of the new data, local corrections to the mapping would induce less distortion to other regions. To validate the approach, subjects performed a set of real-time myoelectric tasks over a range of forgetting factors. Results show that directional forgetting with a forgetting factor of 0.995 outperformed exponential forgetting as well as unassisted user learning. Moreover, myoelectric control remained stable after adaptation with directional forgetting over a range of forgetting factors. These results indicate that a directional approach to discounting past training data can improve performance and alleviate sensitivities to parameter selection in recursive adaptation algorithms.

Serum zinc-alpha2-glycoprotein correlates with adiposity, triglycerides, and the key components of the metabolic syndrome in Chinese subjects.

CONTEXT: Zinc-alpha2-glycoprotein (ZAG) is a 40-kDa circulating glycoprotein secreted from the liver and adipose tissues. Animal studies have demonstrated the role of ZAG as a lipid-mobilizing factor involved in regulating lipid metabolism and adiposity. However, the clinical relevance of these findings remains to be established. OBJECTIVE: This study aimed to address the relationship of serum ZAG levels with adiposity and cardiometabolic risk factors in humans. DESIGN AND SETTING: A total of 258 Chinese subjects [aged 55.1 +/- 12.5 yr; 120 males, 138 females; body mass index (BMI), 25.4 +/- 4.1 kg/m(2)] were randomly selected from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study, based on their BMI. Serum ZAG levels were determined with ELISA. The relationship between serum ZAG levels and cardiometabolic parameters was assessed. RESULTS: Serum ZAG levels were higher in men (P < 0.001 vs. women). Serum ZAG correlated positively with age, parameters of adiposity (waist circumference and BMI), fasting insulin, insulin resistance indices, serum triglycerides, adipocyte-fatty acid-binding protein, and C-reactive protein, and diastolic blood pressure (all P < 0.005, age- and sex-adjusted), and inversely with high-density lipoprotein-cholesterol levels (P = 0.008, age- and sex-adjusted). It was also elevated progressively with an increasing number of components of the metabolic syndrome (P for trend < 0.001). On multivariate analysis, serum ZAG was independently associated with male sex, the metabolic syndrome (or type 2 diabetes and serum triglycerides), and C-reactive protein (all P

Circulating levels of adipocyte and epidermal fatty acid-binding proteins in relation to nephropathy staging and macrovascular complications in type 2 diabetic patients.

OBJECTIVE: To investigate the relationships of serum adipocyte fatty acid-binding protein (A-FABP) and epidermal fatty acid-binding protein (E-FABP) with renal dysfunction and macrovascular complications in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: The associations of serum A-FABP and E-FABP with markers of renal function, nephropathy staging, and macrovascular complications were examined in 237 type 2 diabetic patients. RESULTS: Serum A-FABP and E-FABP correlated significantly with serum creatinine, mean albumin excretion rate, and glomerular filtration rate (all P < 0.001) and were independently associated with diabetic nephropathy staging (P = 0.001 and P < 0.05, respectively). Circulating levels of both types of FABP were increased (P < 0.01) in subjects with macrovascular complications. Serum A-FABP was independently associated with macrovascular complications (odds ratio 2.92 [95% CI 1.42-6.01]; P = 0.004). CONCLUSIONS: Serum A-FABP and E-FABP might be novel serum biomarkers for evaluating the progression of nephropathy and its cardiovascular risk in type 2 diabetic patients.

Epidermal fatty-acid-binding protein: a new circulating biomarker associated with cardio-metabolic risk factors and carotid atherosclerosis.

AIMS: Epidermal fatty-acid-binding protein (E-FABP) is highly homologous to adipocyte FABP (A-FABP), which mediates obesity-related metabolic syndrome (MetS), diabetes and atherosclerosis in animals. Combined deficiency of E-FABP and A-FABP protects against the MetS and atherosclerosis in mice. This study investigated the association of serum E-FABP with cardio-metabolic risk factors and carotid atherosclerosis in humans. METHODS AND RESULTS: The presence of E-FABP in human plasma was detected by tandem mass spectrometry. Serum E-FABP levels, determined by an enzyme-linked immunosorbent assay in 479 Chinese subjects (age: 55.4 ± 13.5 years; M/F: 232/247), correlated positively (P < 0.05 to <0.001, age-adjusted) with parameters of adiposity, adverse lipid profiles, serum insulin, A-FABP, and C-reactive protein levels and were higher in subjects with the MetS (P < 0.001 vs. no MetS). The association of E-FABP with the MetS was independent of A-FABP. Furthermore, serum E-FABP correlated with carotid intima-media thickness (IMT; P < 0.001) and was independently associated with carotid IMT in men (adjusted P = 0.03). CONCLUSION: E-FABP is a new circulating biomarker associated with increased cardio-metabolic risk. It may contribute to the development of the MetS and carotid atherosclerosis in humans, independent of the effect of A-FABP.

Decreased junctional adhesion molecule-A expression during blood-brain barrier breakdown.

Tight junctions between brain endothelial cells are one of the specialized structural components of the blood-brain barrier (BBB) to proteins. Research in the last decade has demonstrated that the integral membrane proteins of cerebral endothelial tight junctions are claudin, occludin, and junctional adhesion molecule (JAM). Altered expression of these tight junction proteins could cause BBB breakdown following brain injury leading to edema. In this study, expression of JAM-A, was analyzed by immunostaining and immunoblotting in the rat cortical cold injury model, a well-characterized in vivo model of BBB breakdown. Temporal and spatial expression of JAM-A was examined at 12 hours, days 2, 4, and 6 post-lesion in cold-injured and control rats. Control rats showed punctate JAM-A immunoreactivity at intervals along the circumference of the endothelial layer at tight junctions where JAM-A colocalized with occludin. A significant decrease in JAM-A expression was noted at the lesion site by immunoblotting at 12 h only. At this time period, lesion vessels showed loss of endothelial JAM-A immunostaining while day 2 onwards, there was recovery of endothelial JAM-A immunoreactivity. Dual labelling for JAM-A and fibronectin showed that only lesion vessels with BBB breakdown to fibronectin at 12 h also showed lack of endothelial JAM-A immunoreactivity supporting the evidence that JAM-A contributes to tight junction integrity.

Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans.

OBJECTIVE: Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple beneficial effects on glucose homeostasis and insulin sensitivity in animal models. This study aimed to investigate the relationship between its serum levels and various cardiometabolic parameters in humans. RESEARCH DESIGN AND METHODS: A newly developed immunoassay was used to measure serum FGF21 levels in 232 Chinese subjects recruited from our previous cross-sectional studies. The mRNA expression levels of FGF21 in the liver and adipose tissues were quantified by real-time PCR. RESULTS: Serum FGF21 levels in overweight/obese subjects were significantly higher than in lean individuals. Serum FGF21 correlated positively with adiposity, fasting insulin, and triglycerides but negatively with HDL cholesterol, after adjusting for age and BMI. Logistic regression analysis demonstrated an independent association between serum FGF21 and the metabolic syndrome. Furthermore, the increased risk of the metabolic syndrome associated with high serum FGF21 was over and above the effects of individual components of the metabolic syndrome. Our in vitro study detected a differentiation-dependent expression of FGF21 in 3T3-L1 adipocytes and human adipocytes. In db/db obese mice, FGF21 mRNA expression was markedly increased in both the liver and adipose tissue compared with that in their lean littermates. Furthermore, FGF21 expression in subcutaneous fat correlated well with its circulating concentrations in humans. CONCLUSIONS: FGF21 is a novel adipokine associated with obesity-related metabolic complications in humans. The paradoxical increase of serum FGF21 in obese individuals, which may be explained by a compensatory response or resistance to FGF21, warrants further investigation.

Inflammatory biomarkers associated with obesity and insulin resistance: a focus on lipocalin-2 and adipocyte fatty acid-binding protein.

Obesity is an important risk factor for a cluster of metabolic and cardiovascular diseases, including insulin resistance, Type 2 diabetes, nonalcoholic fatty liver disease and atherosclerosis. Systemic low-grade inflammation, characterized by elevated circulating concentrations of proinflammatory factors, has recently been proposed to be a key mediator that links obesity with its medical complications. Adipose tissue is now recognized as the major contributor to systemic inflammation associated with obesity. As obesity develops, adipose tissue is infiltrated with activated macrophages. The 'inflamed' adipose tissue secretes a large number of proinflammatory adipokines and/or cytokines, which can act either in an autocrine manner to perpetuate local inflammation or in an endocrine manner to induce insulin resistance and endothelial dysfunction. In this review, we summarize recent advances in several newly identified adipose tissue-derived inflammatory factors, with the focus on lipocalin-2 and adipocyte fatty acid-binding protein (A-FABP). Both lipocalin-2 and A-FABP possess lipid-binding properties and are important integrators of metabolic and inflammatory pathways. A growing body of evidence from experimental, epidemiological and genetic studies suggests that both lipocalin-2 and A-FABP represent a novel class of serum biomarkers for risk prediction and therapeutic intervention of obesity-related medical complications.

Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study.

BACKGROUND: Adipocyte-fatty acid binding protein (A-FABP), a major cytoplasmic protein in adipocytes, plays a central role in the development of diabetes and atherosclerotic cardiovascular disease in experimental animals. We have previously shown that A-FABP is present in the bloodstream and that its circulating levels correlate with metabolic risk factors in a cross-sectional study. In the present study, we further evaluated the prospective association of A-FABP with the metabolic syndrome (MetS) as defined by the updated National Cholesterol Education Program criteria. METHODS AND RESULTS: In the present study, 495 nondiabetic adults from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study were prospectively followed up for 5 years. The relationship of serum A-FABP with the MetS and its components was investigated. At baseline, high A-FABP levels were associated with the MetS (odds ratio, 4.0; 95% CI, 1.5 to 10.4; highest versus lowest sex-specific tertile, adjusted for age, body mass index, the homeostasis model assessment index for insulin resistance, C-reactive protein, and adiponectin, P=0.005). On long-term follow-up, subjects with higher baseline A-FABP levels had progressively worse cardiometabolic risk profile and increasing risk of the MetS. Among 376 subjects without the MetS at baseline, 50 had developed it at 5 years. Apart from the homeostasis model assessment index for insulin resistance (P=0.001), baseline A-FABP was the only independent predictor of the development of the MetS during the 5-year follow-up (odds ratio, 4.7; 95% CI, 1.8 to 11.9; highest versus lowest sex-specific tertile, P=0.001, adjusted for the homeostasis model assessment index for insulin resistance and body mass index). A-FABP was predictive of the MetS even after adjustment for each of its individual components. CONCLUSIONS: Circulating A-FABP predicts the development of the MetS independently of adiposity and insulin resistance.

Puerarin, an isoflavonoid derived from Radix puerariae, potentiates endothelium-independent relaxation via the cyclic AMP pathway in porcine coronary artery.

Puerarin, an isoflavonoid derived from the Chinese medicinal herb Radix puerariae, has been suggested to be useful in the management of various cardiovascular disorders. The present study examined the effect of acute exposure (30 min) to puerarin on vascular relaxation. Rings from porcine coronary artery of either sex were used. The highest concentration of puerarin (100 microM) produced a small but statistically significant relaxation of U46619-contracted rings. Vascular relaxations were also studied in the presence of lower concentrations of puerarin (0.1, 1 and 10 microM) which had no direct relaxation effect. Puerarin enhanced vasorelaxation to endothelium-independent relaxing agents, sodium nitroprusside and cromakalim. However, puerarin had no effect on vasorelaxation induced by endothelium-dependent relaxing agents, bradykinin and calcium ionophore A23187. The potentiating action of puerarin (10 microM) on sodium nitroprusside-mediated relaxation was not affected by the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME; 300 microM), or by the disruption of the endothelium with Triton X-100. The effect of puerarin was reversible following a washout period. The potentiating effects were comparable with the 3'-5'-cyclic adenosine monophosphate (cyclic AMP) analogues, 8-bromoadenosine-3'-5'-cyclic monophosphate (8-Br-cyclic AMP; 10 muM) and Sp-isomer [S nomenclature refers to phosphorus] of adenosine-3', 5'-cyclic monophosphorothioate (Sp-cyclic AMPS; 3 microM), but not the 3'-5'-cyclic guanosine monophosphate (cyclic GMP) analogue, 8-bromoguanosine-3'-5'-cyclic monophosphate (8-Br-cyclic GMP; 3 microM). The cyclic AMP antagonist, Rp-isomer [R nomenclature refers to phosphorus] of 8-bromoadenosine-3', 5'-cyclic monophosphorothioate (Rp-8-Br-cyclic AMPS; 10 microM), but not cyclic GMP antagonist, Rp-isomer of 8-bromoguanosine-3', 5'-cyclic monophosphorothioate (Rp-8-Br-cyclic GMPS; 10 microM), reversed the effects of puerarin (10 microM) on the enhancement of vasorelaxation to sodium nitroprusside. Our results demonstrated that puerarin enhanced sodium nitroprusside-induced relaxation, possibly via the cyclic AMP-dependent pathway.