Biology subjects

Huang, H. J.

Publications and source records attributed to Huang, H. J..

11 recordsLinked to original sources

bioRxiv2026

Consistency Analyses of Open-source Software for Motor Unit Decomposition Using High-density Electromyography Signal

Motor unit (MU) decomposition using high-density surface electromyography (HD-sEMG) has been widely used to characterize MU behavior in neurophysiology and to build neural-machine interfaces for wearable robots. Recently, many open-source software tools for MU decomposition have been made available on GitHub, which could reduce the effort of researchers in the field. However, the consistency among these open-source tools has never been studied, making researchers hesitate to use them. In this study, we collected 7 open-source software tools on GitHub and applied them to decompose MUs from an open-source HD-sEMG dataset (including 11 isometric contraction trials) to investigate the consistency among these tools. To create a comprehensive MU pool for reference, we combined all unique MUs identified by seven tools, visually inspected and removed bad MUs, and manually edited all remaining MU spike trains. Across 7 tools for 11 trials, the number of identified MUs ranges from 167 to 736. The number of valid MUs after expert inspection ranges from 29 to 210, which is 10% to 72% of the reference pool. The rate of agreement between the raw MUSTs and the manually edited MUSTs ranges from 0.86 to 0.94, and the averaged number of edits per MU to correct misalignments ranges from 14 to 39. The results show inconsistency in the implementation and procedures of each tool, which results in an inconsistent number of identified MUs and valid MUs (29 vs 210). In general, a substantial amount of effort is required to process the raw MUSTs from each tool to conduct further research analysis. This study provided a guideline for using open-source software tools for MU decomposition and indicated that it would be beneficial to develop tools to automatically edit the MUSTs.

bioengineering↗

bioRxiv2026

Impact of Kernel Dimensionality on the Generalizability and Efficiency of Convolutional Neural Networks to Decode Neural Drive from High-density Electromyography Signal

Convolutional neural networks (CNNs) have been widely used to estimate neural drive from high-density surface electromyography (HD-sEMG) signals in neural machine interfaces owing to their real-time capability. Depending on kernel dimensionality (1D, 2D, or 3D), CNNs can extract temporal, spatial, or spatiotemporal features. Given that motor unit action potentials propagate across both space and time, architectures that exploit spatial features may offer advantages for neural drive estimation. Despite the potential importance of kernel dimensionality, its influence on neural drive estimation remains poorly understood. Existing studies have mainly evaluated CNN generalizability across participants, contraction intensities, or muscles within the same HD-sEMG dataset, while computational efficiency has seldom been considered. As a result, it remains unclear whether different kernel dimensionalities affect cross-dataset generalizability and computational efficiency. In this study, we implemented three CNN architectures--differing only in kernel dimensionality-- to investigate whether exploiting the spatial and spatiotemporal features of motor unit action potentials improves the generalizability and computational efficiency of neural drive estimation from HD-sEMG recorded during lower-limb isometric contractions. We trained the CNNs on one HD-sEMG dataset and evaluated them, without retraining, on two independent, unseen datasets recorded from different participants, sessions, and protocols--one spanning three contraction intensities and the other three muscles. All three architectures are generalized to both unseen datasets. The 2D and 3D CNNs marginally outperformed the 1D CNN with a 0.2% increase in R, while the 3D CNN showed no advantage over the 2D CNN. Computational efficiency depended on kernel dimensionality in a platform-dependent manner. On the CPU, the 3D CNN showed the slowest inference time, which was 2x slower than the 2D and 1D CNN, owing to the higher arithmetic cost of its spatiotemporal convolutions. On the GPU, all three architectures achieved similar inference times of about 1.36 ms/sample. These findings indicate that increased architectural complexity of CNN does not improve generalizability for neural drive estimation, and that a 2D CNN offers the best balance of accuracy and efficiency for a reliable, deployable CNN-based neural drive estimator--particularly on CPU-only or resource-constrained platforms.

neuroscience↗

bioRxiv2025

Atg16l1 promotes lung transplant tolerance by regulating glycolysis in macrophages

Lung transplant survival is limited by the development of chronic lung allograft dysfunction (CLAD), a type of graft rejection that lacks effective treatments. Autophagy plays a crucial role in maintaining cellular homeostasis. In a single-nucleotide polymorphism screen, we found that lung recipients with two copies of a common hypofunctional genetic variant of autophagy-related 16-like 1 rs2241880 (ATG16L1T300A/T300A), known to deplete this protein from macrophages, were more likely to develop early CLAD. To understand this, we used a mouse orthotopic lung transplant model. Recipients encoding myeloid cell-specific deletion of Atg16l1 (Atg16l1{Delta}/{Delta}) or who harbor an engineered orthologous mutation (Atg16l1T316A/T316A) showed similar susceptibility to CLAD. Transcript profiling and mitochondrial tracking studies indicated that increased mitochondrial damage and decreased autophagic removal of mitochondria in Atg16l1-deficient macrophages were associated with heightened activation of the hypoxia-inducible factor 1 (Hif1) pathway and accumulation of glycolytic transcripts. Metabolic analysis revealed reduced oxidative phosphorylation, increased glycolytic activity, and higher IL-1{beta} expression in Atg16l1-deficient macrophages. Notably, the development of CLAD in Atg16l1{Delta}/{Delta} lung recipients could be significantly prevented by additionally deleting Hif1 in myeloid cells or by treating with the glycolysis inhibitor 2-deoxyglucose. Our results show how a common autophagy-related genetic variant disrupts macrophage metabolism and impairs lung transplant tolerance, pointing toward potential therapeutic strategies to combat CLAD.

immunology↗

bioRxiv2025

Age-related Reorganization of Corticomuscular Connectivity During Locomotor Perturbations

Locomotor perturbations elicit cortical and muscular responses that help minimize motor errors through neural processes involving multiple brain regions. The anterior cingulate cortex monitors motor errors, the supplementary motor areas integrate sensory and executive control, and the posterior parietal cortices process sensorimotor predictions, while muscles show increased activation and co-contraction patterns. With aging, these neural control strategies shift; older adults demonstrate less flexible cortical and muscular responses, using compensatory overactivation and simpler muscle synergies to maintain performance comparable to young adults. We investigated corticomuscular connectivity patterns during perturbed recumbent stepping in seventeen young adults (age 25{+/-}4.9 years) and eleven older adults (age 68{+/-}3.6 years) using high-density EEG (128 electrodes) and EMG from six bilateral muscles. Brief mechanical perturbations (200ms of increased resistance) were applied at left or right leg extension-onset or mid-extension during continuous stepping at 60 steps per minute. We applied independent component analysis, source localization, and direct directed transfer function to quantify bidirectional information flow between cortical clusters and muscles in theta (3-8 Hz), alpha (8-13 Hz), and beta (13-35 Hz) bands. Young adults demonstrated concentrated electrocortical sources in anterior cingulate cortex, bilateral supplementary motor areas, and bilateral posterior parietal cortices, with strong theta-band synchronization following perturbations. In contrast, older adults showed fewer differentiated cortical sources, particularly lacking distinct anterior cingulate activity, and exhibited only minimal synchronization changes. Baseline corticomuscular connectivity was significantly stronger in older adults compared to young adults (p=0.012), suggesting fundamental differences in resting motor control states. During perturbations, young adults employed flexible, task-specific connectivity modulation involving error-processing networks, with the anterior cingulate showing selective bidirectional connectivity changes with specific muscles. Older adults relied on more diffuse (i.e., not focused to specific brain area) connectivity patterns dominated by motor and posterior parietal cortices, with strong connections to multiple upper and lower limb muscles simultaneously. These findings reveal an age-related strategic reorganization from dynamic, error-driven neural control to a more constrained, stability-focused approach that may reflect compensation for sensorimotor changes. The distinct connectivity signatures establish perturbed recumbent stepping as a valuable tool for assessing corticomuscular communication and provide normative benchmarks for developing targeted rehabilitation interventions to restore efficient motor control in aging and neurological populations.

neuroscience↗

bioRxiv2024

Impaired complement regulation drives chronic lung allograft dysfunction after lung transplantation.

A greater understanding of chronic lung allograft dysfunction (CLAD) pathobiology, the primary cause of mortality after lung transplantation, is needed to improve outcomes. The complement system links innate to adaptive immune responses and is activated early post-lung transplantation to form the C3 convertase, a critical enzyme that cleaves the central complement component C3. We hypothesized that LTx recipients with a genetic predisposition to enhanced complement activation have worse CLAD-free survival mediated through increased adaptive alloimmunity. We interrogated a known functional C3 polymorphism (C3R102G) that increases complement activation through impaired C3 convertase inactivation in two independent LTx recipient cohorts. C3R102G, identified in at least one out of three LTx recipients, was associated with worse CLAD-free survival, particularly in the subset of recipients who developed donor-specific antibodies (DSA). In a mouse orthotopic lung transplantation model, impaired recipient complement regulation resulted in more severe obstructive airway lesions when compared to wildtype controls, despite only moderate differences in graft-infiltrating effector T cells. Impaired complement regulation promoted the intragraft accumulation of memory B cells and antibody-secreting cells, resulting in increased DSA levels. In summary, genetic predisposition to complement activation is associated with B cell activation and worse CLAD-free survival. BRIEF SUMMARYLung transplant recipients genetically predisposed to impaired complement regulation demonstrate worse chronic rejection-free survival. This phenotype is associated with intragraft B cell-activation and donor-specific antibodies.

immunology↗

bioRxiv2023

HNF4α mediated QPRT expression in the kidney facilitates resilience against acute kidney injury

Nicotinamide adenine dinucleotide (NAD+) levels decline in experimental models of acute kidney injury (AKI). Attenuated enzymatic conversion of tryptophan to NAD+ in tubular epithelium may contribute to adverse cellular and physiological outcomes. Mechanisms underlying defense of tryptophan-dependent NAD+ production are incompletely understood. Here we show that regulation of a bottleneck enzyme in this pathway, quinolinate phosphoribosyltransferase (QPRT) may contribute to kidney resilience. Expression of QPRT declined in two unrelated models of AKI. Haploinsufficient mice developed worse outcomes compared to littermate controls whereas novel, conditional gain-of-function mice were protected from injury. Applying these findings, we then identified hepatocyte nuclear factor 4 alpha (HNF4) as a candidate transcription factor regulating QPRT expression downstream of the mitochondrial biogenesis regulator and NAD+ biosynthesis inducer PPARgamma coactivator-1-alpha (PGC1). This was verified by chromatin immunoprecipitation. A PGC1a-HNF4 -QPRT axis controlled NAD+ levels across cellular compartments and modulated cellular ATP. These results propose that tryptophan-dependent NAD+ biosynthesis via QPRT and induced by HNF4 may be a critical determinant of kidney resilience to noxious stressors.

physiology↗

bioRxiv2022

Reprogramming Alveolar Macrophage Responses to TGF-β Reveals CCR2+ Monocyte Activity that Promotes Bronchiolitis Obliterans Syndrome

Bronchiolitis obliterans syndrome (BOS) is a major impediment to lung transplant survival and is generally resistant to medical therapy. Extracorporeal photophoresis (ECP) is an immunomodulatory therapy that shows promise in stabilizing BOS patients but its mechanisms of action are unclear. In a mouse lung transplant model, we show that ECP blunts alloimmune responses and inhibits BOS through lowering airway TGF-{beta} bioavailability without altering its expression. Surprisingly, ECP-treated leukocytes are engulfed primarily by alveolar macrophages (AM), which become reprogrammed to become less responsive to TGF-{beta} and reduce TGF-{beta} bioavailability through secretion of the TGF-{beta} antagonist Decorin. In untreated recipients, high airway TGF-{beta} activity stimulates AM to express CCL2 leading to CCR2+ monocyte-driven BOS development. Moreover, we find TGF-{beta} receptor 2-dependent differentiation of CCR2+ monocytes is required for the generation of monocyte-derived AM, which in turn promote BOS by expanding tissue-resident memory CD8+ T cells that inflict airway injury through Blimp-1-mediated Granzyme B expression. Thus, through studying the effects of ECP, we have identified an AM functional plasticity that controls a TGF-{beta}-dependent network, which couples CCR2+ monocyte recruitment and differentiation to alloimmunity and BOS. Alveolar macrophage plasticity can be harnessed to prevent Bronchiolitis Obliterans Syndrome.

immunology↗

bioRxiv2021

Small Directional Treadmill Perturbations Induce Differential Gait Stability Adaptation

Introducing unexpected perturbations to challenge gait stability is an effective approach to investigate balance control strategies. Little is known about the extent to which people can respond to small perturbations during walking. This study aimed to determine how subjects adapted gait stability to multidirectional perturbations with small magnitudes applied on a stride-by-stride basis. Ten healthy young subjects walked on a treadmill that either briefly decelerated belt speed ("stick"), accelerated belt speed ("slip"), or shifted the platform medial-laterally at right leg mid-stance. We quantified gait stability adaptation in both anterior-posterior and medial-lateral directions using margin of stability and its components, base of support and extrapolated center of mass. Gait stability was disrupted upon initially experiencing the small perturbations as margin of stability decreased in the stick, slip, and medial shift perturbations and increased in the lateral shift perturbation. Gait stability metrics were generally disrupted more for perturbations in the coincident direction. Subjects employed both feedback and feedforward strategies in response to the small perturbations, but mostly use feedback strategies during adaptation. Subjects primarily used base of support (foot placement) control in the lateral shift perturbation and extrapolated center of mass control in the slip and medial shift perturbations. These findings provide new knowledge about the extent of gait stability adaptation to small magnitude perturbations applied on a stride-by-stride basis and reveal potential new approaches for balance training interventions to target foot placement and center of mass control. NEW & NOTEWORTHYLittle is known about if and how humans can adapt to small magnitude perturbations experienced on a stride-by-stride basis during walking. Here, we show that even small perturbations disrupted gait stability and that subjects could still adapt their reactive balance control. Depending on the perturbation direction, subjects might prefer adjusting their foot placement over their center of mass and vice versa. These findings could help potentially tune balance training to target specific aspects of balance.

bioengineering↗

bioRxiv2021

Speed-related but not detrended gait variability increases with more sensitive self-paced treadmill controllers at multiple slopes

Self-paced treadmills are being used more frequently to study humans walking with their self-selected gaits on a range of slopes. There are multiple options to purchase a treadmill with a built-in controller, or implement a custom written self-paced controller, which raises questions about how self-paced controller affect treadmill speed and gait biomechanics on multiple slopes. This study investigated how different self-paced treadmill controller sensitivities affected gait parameters and variability on decline, level, and incline slopes. We hypothesized that increasing self-paced controller sensitivity would increase gait variability on each slope. We also hypothesized that detrended variability could help mitigate differences in variability that arise from differences in speed fluctuations created by the self-paced controllers. Ten young adults walked on a self-paced treadmill using three controller sensitivities (low, medium, and high) and fixed speeds at three slopes (decline, -10{degrees}; level, 0{degrees}; incline, +10{degrees}). Within each slope, average walking speeds and spatiotemporal gait parameters were similar regardless of self-paced controller sensitivity. With higher controller sensitivities on each slope, speed fluctuations, speed variance, and step length variance increased whereas step frequency variance and step width variance were unaffected. Detrended variance was not affected by controller sensitivity suggesting that detrending variability helps mitigate differences associated with treadmill speed fluctuations. Speed-trend step length variances, however, increased with more sensitive controllers. Further, detrended step length variances were similar for self-paced and fixed speed walking, whereas self-paced walking included substantial speed-trend step length variance not present in fixed speed walking. In addition, regardless of the self-paced controller, subjects walked fastest on the level slope with the longest steps, narrowest steps, and least variance. Overall, our findings suggest that separating gait variability into speed-trend and detrended variability could be beneficial for interpreting gait variability among multiple self-paced treadmill studies and when comparing self-paced walking with fixed speed walking.

bioengineering↗

bioRxiv2019

More Reliable EEG Electrode Digitizing Methods Can Reduce Source Estimation Uncertainty, But Current Methods Already Accurately Identify Brodmann Areas

Electroencephalography (EEG) and source estimation can be used to identify brain areas activated during a task, which could offer greater insight on cortical dynamics. Source estimation requires knowledge of the locations of the EEG electrodes. This could be provided with a template or obtained by digitizing the EEG electrode locations. Operator skill and inherent uncertainties of a digitizing system likely produce a range of digitization reliabilities, which could affect source estimation and the interpretation of the estimated source locations. Here, we compared the reliability of five digitizing methods (ultrasound, structured-light 3D scan, infrared 3D scan, motion capture probe, and motion capture) and determined the relationship between digitization reliability and source estimation uncertainty, assuming other contributors to source estimation uncertainty were constant. We digitized a mannequin head using each method five times and quantified the reliability and validity of each method. We created five hundred sets of electrode locations based on our reliability results and applied a dipole fitting algorithm (DIPFIT) to perform source estimation. The motion capture method, which recorded the locations of markers placed directly on the electrodes had the best reliability with an average electrode variability of 0.001cm. Then, in order of decreasing reliability were the method using a digitizing probe in the motion capture system, an infrared 3D scanner, a structured-light 3D scanner, and an ultrasound digitization system. Unsurprisingly, uncertainty of the estimated source locations increased with greater variability of EEG electrode locations and less reliable digitizing systems. If EEG electrode location variability was ~ 1 cm, a single source could shift by as much as 2 cm. To help translate these distances into practical terms, we quantified Brodmann area accuracy for each digitizing method and found that the average Brodmann area accuracy for all digitizing methods was > 80%. Using a template of electrode locations reduced the Brodmann area accuracy to ~ 50%. Overall, more reliable digitizing methods can reduce source estimation uncertainty, but the significance of the source estimation uncertainty depends on the desired spatial resolution. For accurate Brodmann area identification, any of the digitizing methods tested can be used confidently.

neuroscience↗

bioRxiv2019

Influence of Mismarking Fiducial Locations on EEG Source Estimation

Mismarking locations of the fiducials can have a significant influence on the digitized electrode locations and cortical source estimation using high-density EEG. Under-standing and quantifying how uncertainties in the fiducial locations affect the locations of cortical sources is important for interpreting EEG analyses. We systematically shifted fiducial locations to investigate the relationship between variations of fiducial locations and the corresponding estimations of the source locations. We quantified the uncertainty of the dipole locations using the enclosing volume of the dipole locations and the maximum width of the dipole cluster. Shifting fiducial locations 1.5 cm increased the uncertainty of the dipole locations to span a volume >1 cm3 and about 2.5 cm wide. Results suggest that the fiducials need to be digitized accurately within at least 0.5 cm of the absolute actual fiducial location to limit the uncertainty of a dipole location to <1 cm. Additionally, we used random fiducial shift combinations to estimate the effects of combinations of the fiducial shifts on dipole location estimation. This analysis showed that dipole locations were within the bounds of our dipole estimation uncertainty volumes. Based on the outcomes, we suggest marking fiducials carefully before placement of the cap and to use a digitization method with an accuracy of <0.5 cm.

neuroscience↗