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1.
J Neuroeng Rehabil ; 21(1): 169, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39304930

ABSTRACT

BACKGROUND: Delivering HD-tDCS on individual motor hotspot with optimal electric fields could overcome challenges of stroke heterogeneity, potentially facilitating neural activation and improving motor function for stroke survivors. However, the intervention effect of this personalized HD-tDCS has not been explored on post-stroke motor recovery. In this study, we aim to evaluate whether targeting individual motor hotspot with HD-tDCS followed by EMG-driven robotic hand training could further facilitate the upper extremity motor function for chronic stroke survivors. METHODS: In this pilot randomized controlled trial, eighteen chronic stroke survivors were randomly allocated into two groups. The HDtDCS-group (n = 8) received personalized HD-tDCS using task-based fMRI to guide the stimulation on individual motor hotspot. The Sham-group (n = 10) received only sham stimulation. Both groups underwent 20 sessions of training, each session began with 20 min of HD-tDCS and was then followed by 60 min of robotic hand training. Clinical scales (Fugl-meyer Upper Extremity scale, FMAUE; Modified Ashworth Scale, MAS), and neuroimaging modalities (fMRI and EEG-EMG) were conducted before, after intervention, and at 6-month follow-up. Two-way repeated measures analysis of variance was used to compare the training effect between HDtDCS- and Sham-group. RESULTS: HDtDCS-group demonstrated significantly better motor improvement than the Sham-group in terms of greater changes of FMAUE scores (F = 6.5, P = 0.004) and MASf (F = 3.6, P = 0.038) immediately and 6 months after the 20-session intervention. The task-based fMRI activation significantly shifted to the ipsilesional motor area in the HDtDCS-group, and this activation pattern increasingly concentrated on the motor hotspot being stimulated 6 months after training within the HDtDCS-group, whereas the increased activation is not sustainable in the Sham-group. The neuroimaging results indicate that neural plastic changes of the HDtDCS-group were guided specifically and sustained as an add-on effect of the stimulation. CONCLUSIONS: Stimulating the individual motor hotspot before robotic hand training could further enhance brain activation in motor-related regions that promote better motor recovery for chronic stroke. TRIAL REGISTRATION: This study was retrospectively registered in ClinicalTrials.gov (ID NCT05638464).


Subject(s)
Electromyography , Hand , Robotics , Stroke Rehabilitation , Transcranial Direct Current Stimulation , Upper Extremity , Humans , Male , Pilot Projects , Female , Middle Aged , Stroke Rehabilitation/methods , Robotics/methods , Transcranial Direct Current Stimulation/methods , Magnetic Resonance Imaging , Aged , Recovery of Function/physiology , Motor Cortex/diagnostic imaging , Motor Cortex/physiology , Stroke/physiopathology , Adult
2.
Article in English | MEDLINE | ID: mdl-39218244

ABSTRACT

OBJECTIVE: To derive and validate a prediction model for minimal clinically important differences (MCID) in upper extremity (UE) motor function after intention-driven robotic-hand training using residual voluntary EMG signals from affected UE. DESIGN: A prospective longitudinal multicenter cohort study. We collected pre-intervention candidate predictors: demographics, clinical characteristics, Fugl-Meyer assessment of UE (FMAUE), Action Research Arm Test scores, and motor-intention of flexor digitorum and extensor digitorum (ED) measured by EMG during maximal voluntary contraction (MVC). For EMG measures, recognizing challenges for stroke survivors to move paralyzed hand, peak signals were extracted from eight time-windows during MVC-EMG (0.1s-5s) to identify subjects' motor-intention. Classification And Regression Tree algorithm was employed to predict survivors with MCID of FMAUE. Relationship between predictors and motor-improvements was further investigated. SETTING: Nine rehabilitation centers. PARTICIPANTS: Chronic stroke survivors (N=131), including 87 for Derivation-sample, and 44 for Validation-sample. INTERVENTIONS: All participants underwent 20-session robotic-hand training (40min/session, 3-5sessions/week). MAIN OUTCOME MEASURES: Prediction efficacies of models were assessed by area under the receiver operating characteristic curve (AUC). The best effective model was final model and validated using AUC and overall accuracy. RESULTS: The best model comprised FMAUE (cut-off score: 46) and peak activity of ED from one-second MVC-EMG (MVC-EMG 4.604 times higher than resting-EMG), which demonstrated significantly higher prediction accuracy (AUC: 0.807) than other time-windows or solely using clinical-scores (AUC: 0.595). In external validation, this model displayed robust prediction (AUC: 0.916). Significant quadratic relationship was observed between ED-EMG and FMAUE increases. CONCLUSIONS: This study presents a prediction model for intention-driven robotic-hand training in chronic stroke survivors. It highlights significance of capturing motor-intention through 1-second EMG-window as a predictor for MCID improvement in UE motor-function after 20-session robotic-training. Survivors in two conditions showed high percentage of clinical motor-improvement: moderate-to-high motor-intention and low-to-moderate function; as well as high-intention and high-function.

3.
J Neurosci ; 44(37)2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39147592

ABSTRACT

The act of recalling memories can paradoxically lead to the forgetting of other associated memories, a phenomenon known as retrieval-induced forgetting (RIF). Inhibitory control mechanisms, primarily mediated by the prefrontal cortex, are thought to contribute to RIF. In this study, we examined whether stimulating the medial prefrontal cortex (mPFC) with transcranial direct current stimulation modulates RIF and investigated the associated electrophysiological correlates. In a randomized study, 50 participants (27 males and 23 females) received either real or sham stimulation before performing retrieval practice on target memories. After retrieval practice, a final memory test to assess RIF was administered. We found that stimulation selectively increased the retrieval accuracy of competing memories, thereby decreasing RIF, while the retrieval accuracy of target memories remained unchanged. The reduction in RIF was associated with a more pronounced beta desynchronization within the left dorsolateral prefrontal cortex (left-DLPFC), in an early time window (<500 ms) after cue onset during retrieval practice. This led to a stronger beta desynchronization within the parietal cortex in a later time window, an established marker for successful memory retrieval. Together, our results establish the causal involvement of the mPFC in actively suppressing competing memories and demonstrate that while forgetting arises as a consequence of retrieving specific memories, these two processes are functionally independent. Our findings suggest that stimulation potentially disrupted inhibitory control processes, as evidenced by reduced RIF and stronger beta desynchronization in fronto-parietal brain regions during memory retrieval, although further research is needed to elucidate the specific mechanisms underlying this effect.


Subject(s)
Mental Recall , Parietal Lobe , Prefrontal Cortex , Transcranial Direct Current Stimulation , Humans , Male , Female , Mental Recall/physiology , Prefrontal Cortex/physiology , Parietal Lobe/physiology , Transcranial Direct Current Stimulation/methods , Young Adult , Adult , Beta Rhythm/physiology , Cortical Synchronization/physiology
4.
Sci Transl Med ; 16(760): eadi2245, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39141703

ABSTRACT

Antisense oligonucleotides (ASOs) are promising therapeutics for treating various neurological disorders. However, ASOs are unable to readily cross the mammalian blood-brain barrier (BBB) and therefore need to be delivered intrathecally to the central nervous system (CNS). Here, we engineered a human transferrin receptor 1 (TfR1) binding molecule, the oligonucleotide transport vehicle (OTV), to transport a tool ASO across the BBB in human TfR knockin (TfRmu/hu KI) mice and nonhuman primates. Intravenous injection and systemic delivery of OTV to TfRmu/hu KI mice resulted in sustained knockdown of the ASO target RNA, Malat1, across multiple mouse CNS regions and cell types, including endothelial cells, neurons, astrocytes, microglia, and oligodendrocytes. In addition, systemic delivery of OTV enabled Malat1 RNA knockdown in mouse quadriceps and cardiac muscles, which are difficult to target with oligonucleotides alone. Systemically delivered OTV enabled a more uniform ASO biodistribution profile in the CNS of TfRmu/hu KI mice and greater knockdown of Malat1 RNA compared with a bivalent, high-affinity TfR antibody. In cynomolgus macaques, an OTV directed against MALAT1 displayed robust ASO delivery to the primate CNS and enabled more uniform biodistribution and RNA target knockdown compared with intrathecal dosing of the same unconjugated ASO. Our data support systemically delivered OTV as a potential platform for delivering therapeutic ASOs across the BBB.


Subject(s)
Blood-Brain Barrier , Oligonucleotides, Antisense , RNA, Long Noncoding , Receptors, Transferrin , Animals , Humans , Mice , Biological Transport , Blood-Brain Barrier/metabolism , Gene Knockdown Techniques , Macaca fascicularis , Oligonucleotides, Antisense/pharmacokinetics , Oligonucleotides, Antisense/administration & dosage , Receptors, Transferrin/metabolism , RNA, Long Noncoding/metabolism , RNA, Long Noncoding/genetics , Tissue Distribution
5.
Entropy (Basel) ; 26(7)2024 Jun 23.
Article in English | MEDLINE | ID: mdl-39056901

ABSTRACT

This study examines pedaling asymmetry using the electromyogram (EMG) complexity of six bilateral lower limb muscles for chronic stroke survivors. Fifteen unilateral chronic stroke and twelve healthy participants joined passive and volitional recumbent pedaling tasks using a self-modified stationary bike with a constant speed of 25 revolutions per minute. The fuzzy approximate entropy (fApEn) was adopted in EMG complexity estimation. EMG complexity values of stroke participants during pedaling were smaller than those of healthy participants (p = 0.002). For chronic stroke participants, the complexity of paretic limbs was smaller than that of non-paretic limbs during the passive pedaling task (p = 0.005). Additionally, there was a significant correlation between clinical scores and the paretic EMG complexity during passive pedaling (p = 0.022, p = 0.028), indicating that the paretic EMG complexity during passive movement might serve as an indicator of stroke motor function status. This study suggests that EMG complexity is an appropriate quantitative tool for measuring neuromuscular characteristics in lower limb dynamic movement tasks for chronic stroke survivors.

6.
Neurorehabil Neural Repair ; 38(8): 595-606, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38812378

ABSTRACT

BACKGROUND: Intensive task-oriented training has shown promise in enhancing distal motor function among patients with chronic stroke. A personalized electromyography (EMG)-driven soft robotic hand was developed to assist task-oriented object-manipulation training effectively. Objective. To compare the effectiveness of task-oriented training using the EMG-driven soft robotic hand. METHODS: A single-blinded, randomized controlled trial was conducted with 34 chronic stroke survivors. The subjects were randomly assigned to the Hand Task (HT) group (n = 17) or the control (CON) group (n = 17). The HT group received 45 minutes of task-oriented training by manipulating small objects with the robotic hand for 20 sessions, while the CON group received 45 minutes of hand-functional exercises without objects using the same robot. Fugl-Meyer assessment (FMA-UE), Action Research Arm Test (ARAT), Modified Ashworth Score (MAS), Box and Block test (BBT), Maximum Grip Strength, and active range of motion (AROM) of fingers were assessed at baseline, after intervention, and 3 months follow-up. The muscle co-contraction index (CI) was analyzed to evaluate the session-by-session variation of upper limb EMG patterns. RESULTS: The HT group showed more significant improvement in FMA-UE (wrist/hand, shoulder/elbow) compared to the CON group (P < .05). At 3-month follow-up, the HT group demonstrated significant improvements in FMA-UE, ARAT, BBT, MAS (finger), and AROMs (P < .05). The HT group exhibited a more significant decrease in muscle co-contractions compared to the CON group (P < .05). CONCLUSIONS: EMG-driven task-oriented training with the personalized soft robotic hand was a practical approach to improving motor function and muscle coordination. CLINICAL TRIAL REGISTRY NAME: Soft Robotic Hand System for Stroke Rehabilitation. CLINICAL TRIAL REGISTRATION-URL: https://clinicaltrials.gov/. UNIQUE IDENTIFIER: NCT03286309.


Subject(s)
Electromyography , Hand , Robotics , Stroke Rehabilitation , Humans , Stroke Rehabilitation/methods , Stroke Rehabilitation/instrumentation , Male , Female , Middle Aged , Single-Blind Method , Aged , Hand/physiopathology , Stroke/physiopathology , Stroke/complications , Exercise Therapy/methods , Chronic Disease , Adult , Outcome Assessment, Health Care , Hand Strength/physiology , Range of Motion, Articular/physiology
7.
Front Rehabil Sci ; 5: 1405549, 2024.
Article in English | MEDLINE | ID: mdl-38751819
8.
J Dent ; 146: 105018, 2024 07.
Article in English | MEDLINE | ID: mdl-38679133

ABSTRACT

OBJECTIVES: This study aimed to identify the oral microbiota factors contributing to low birth weight (LBW) in Chinese pregnant women and develop a prediction model using machine learning. METHODS: A nested case-control study was conducted in a prospective cohort of 580 Chinese pregnant women, with 23 LBW cases and 23 healthy delivery controls matched for age and smoking habit. Saliva samples were collected at early and late pregnancy, and microbiome profiles were analyzed through 16S rRNA gene sequencing. RESULTS: The relative abundance of Streptococcus was over-represented (median 0.259 vs. 0.116) and Saccharibacteria_TM7 was under-represented (median 0.033 vs. 0.068) in the LBW case group than in controls (p < 0.001, p = 0.015 respectively). Ten species were identified as microbiome biomarkers of LBW by LEfSe analysis, which included 7 species within the genus of Streptococcus or as part of 'nutritionally variant streptococci' (NVS), 2 species of opportunistic pathogen Leptotrichia buccalis and Gemella sanguinis (all LDA score>3.5) as risk biomarkers, and one species of Saccharibacteria TM7 as a beneficial biomarker (LDA= -4.5). The machine-learning model based on these 10 distinguished oral microbiota species could predict LBW, with an accuracy of 82 %, sensitivity of 91 %, and specificity of 73 % (AUC-ROC score 0.89, 95 % CI: 0.75-1.0). Results of α-diversity showed that mothers who delivered LBW infants had less stable salivary microbiota construction throughout pregnancy than the control group (measured by Shannon, p = 0.048; and Pielou's, p = 0.021), however the microbiome diversity did not improve the prediction accuracy of LBW. CONCLUSIONS: A machine-learning oral microbiome model shows promise in predicting low-birth-weight delivery. Even in cases where oral health is not significantly compromised, opportunistic pathogens or rarer taxa associated with adverse pregnancy outcomes can still be identified in the oral cavity. CLINICAL SIGNIFICANCE: This study highlights the potential complexity of the relationship between oral microbiome and pregnancy outcomes, indicating that mechanisms underlying the association between oral microbiota and adverse pregnancy outcomes may involve complex interactions between host factors, microbiota, and systemic conditions. Using machine learning to develop a predictive model based on specific oral microbiota biomarkers provides a potential for personalized medicine approaches. Future prediction models should incorporate clinical metadata to be clinically useful for improving maternal and child health.


Subject(s)
Infant, Low Birth Weight , Machine Learning , Microbiota , Mouth , RNA, Ribosomal, 16S , Saliva , Streptococcus , Humans , Female , Pregnancy , Case-Control Studies , Infant, Newborn , Adult , Saliva/microbiology , Mouth/microbiology , Prospective Studies , RNA, Ribosomal, 16S/analysis , Streptococcus/isolation & purification , Biomarkers/analysis , China , Leptotrichia , Risk Factors
9.
Med Image Anal ; 93: 103095, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38310678

ABSTRACT

Segmenting prostate from magnetic resonance imaging (MRI) is a critical procedure in prostate cancer staging and treatment planning. Considering the nature of labeled data scarcity for medical images, semi-supervised learning (SSL) becomes an appealing solution since it can simultaneously exploit limited labeled data and a large amount of unlabeled data. However, SSL relies on the assumption that the unlabeled images are abundant, which may not be satisfied when the local institute has limited image collection capabilities. An intuitive solution is to seek support from other centers to enrich the unlabeled image pool. However, this further introduces data heterogeneity, which can impede SSL that works under identical data distribution with certain model assumptions. Aiming at this under-explored yet valuable scenario, in this work, we propose a separated collaborative learning (SCL) framework for semi-supervised prostate segmentation with multi-site unlabeled MRI data. Specifically, on top of the teacher-student framework, SCL exploits multi-site unlabeled data by: (i) Local learning, which advocates local distribution fitting, including the pseudo label learning that reinforces confirmation of low-entropy easy regions and the cyclic propagated real label learning that leverages class prototypes to regularize the distribution of intra-class features; (ii) External multi-site learning, which aims to robustly mine informative clues from external data, mainly including the local-support category mutual dependence learning, which takes the spirit that mutual information can effectively measure the amount of information shared by two variables even from different domains, and the stability learning under strong adversarial perturbations to enhance robustness to heterogeneity. Extensive experiments on prostate MRI data from six different clinical centers show that our method can effectively generalize SSL on multi-site unlabeled data and significantly outperform other semi-supervised segmentation methods. Besides, we validate the extensibility of our method on the multi-class cardiac MRI segmentation task with data from four different clinical centers.


Subject(s)
Interdisciplinary Placement , Prostatic Neoplasms , Male , Humans , Prostate/diagnostic imaging , Prostatic Neoplasms/diagnostic imaging , Entropy , Magnetic Resonance Imaging
10.
Article in English | MEDLINE | ID: mdl-38051622

ABSTRACT

EMG-driven robot hand training can facilitate motor recovery in chronic stroke patients by restoring the interhemispheric balance between motor networks. However, the underlying mechanisms of reorganization between interhemispheric regions remain unclear. This study investigated the effective connectivity (EC) between the ventral premotor cortex (PMv), supplementary motor area (SMA), and primary motor cortex (M1) using Dynamic Causal Modeling (DCM) during motor tasks with the paretic hand. Nineteen chronic stroke subjects underwent 20 sessions of EMG-driven robot hand training, and their Action Reach Arm Test (ARAT) showed significant improvement ( ß =3.56, [Formula: see text]). The improvement was correlated with the reduction of inhibitory coupling from the contralesional M1 to the ipsilesional M1 (r=0.58, p=0.014). An increase in the laterality index was only observed in homotopic M1, but not in the premotor area. Additionally, we identified an increase in resting-state functional connectivity (FC) between bilateral M1 ( ß =0.11, p=0.01). Inter-M1 FC demonstrated marginal positive relationships with ARAT scores (r=0.402, p=0.110), but its changes did not correlate with ARAT improvements. These findings suggest that the improvement of hand functions brought about by EMG-driven robot hand training was driven explicitly by task-specific reorganization of motor networks. Particularly, the restoration of interhemispheric balance was induced by a reduction in interhemispheric inhibition from the contralesional M1 during motor tasks of the paretic hand. This finding sheds light on the mechanistic understanding of interhemispheric balance and functional recovery induced by EMG-driven robot training.


Subject(s)
Motor Cortex , Robotics , Stroke , Humans , Magnetic Resonance Imaging , Motor Cortex/physiology , Hand
11.
Article in English | MEDLINE | ID: mdl-38083192

ABSTRACT

Recent semi-supervised learning approaches appealingly advance medical image segmentation for their effectiveness in alleviating the need for a large amount of expert-demanding annotations. However, most of them have two limitations: (i) neglect of the intra-class variation caused by different patients and scanning protocols, which makes the pixel-level label propagation difficult; (ii) non-selective stability learning (a.k.a., consistency regularization), resulting in distraction by the redundant easy regions. To address these, in this work, we propose a novel synergistic label-stability learning (SLSL) framework for semi-supervised medical image segmentation. Specifically, our method is built upon the teacher-student framework. Then, the label learning process includes the typical pseudo label learning that reinforces confirmation of well-classified easy regions and the cyclic real label learning that takes advantage of real labels and class prototypes to regularize the distribution of intra-class features from unlabeled data to facilitate label propagation. In addition, the difficulty-selective stability learning aims to regularize the perturbed stability only at the high-entropy (can be regarded as difficult) regions, rather than being distracted by the less-informative easy regions. Extensive experiments on left atrium segmentation from MRI show that our method can effectively exploit the unlabeled data and outperform other semi-supervised medical image segmentation methods.Clinical relevance- The proposed method can help develop a high-performance automatic left atrium segmentation model for treating atrial fibrillation under limited expert-demanding annotation budgets.


Subject(s)
Atrial Fibrillation , Heart Atria , Humans , Heart Atria/diagnostic imaging , Entropy , Supervised Machine Learning
12.
Cerebrovasc Dis ; 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38118431

ABSTRACT

INTRODUCTION: After a stroke, individuals commonly experience visual problems and impaired cognitive function, which can significantly impact their daily life. In addition to visual neglect and hemianopia, stroke survivors often have difficulties with visual search tasks. Researchers are increasingly interested in using eye tracking technology to study cognitive processing and determine whether eye tracking metrics can be used to screen and assess cognitive impairment in patients with neurological disorders. As such, assessing these areas and understanding their relationship is crucial for effective stroke rehabilitation. METHODS: We enrolled 60 stroke patients in this study and evaluated their eye tracking performance and cognitive function through a series of tests. Subsequently, we divided the subjects into two groups based on their scores on the HK-MoCA test, with scores below 21 out of 30 indicating cognitive impairment. We then compared the eye tracking metrics between the two groups and identified any significant differences that existed. Spearman correlation analysis was conducted to explore the relationship between clinical test scores and eye tracking metrics. Moreover, we employed a Mann-Whitney U test to compare eye tracking metrics between groups with and without cognitive impairment. RESULTS: Our results revealed significant correlations between various eye tracking metrics and cognitive tests (p=<.001-.041). Furthermore, the group without cognitive impairment demonstrated higher saccade velocity, gaze path velocity, and shorter time to target than the group with cognitive impairment (p=<.001-.040). ROC curve analyses were performed, and the optimal cut-off values for gaze path velocity and saccade velocity were 329.665 (px/s) (sensitivity= 0.80, specificity = 0.533) and 2.150 (px/s) (sensitivity= 0.733, specificity= 0.633), respectively. CONCLUSIONS: Our findings indicate a significant correlation between eye tracking metrics and cognitive test scores. Furthermore, the group with cognitive impairment exhibited a significant difference in these metrics, and a cut-off value was identified to predict whether a client was experiencing cognitive impairment.

13.
Front Neurosci ; 17: 1241772, 2023.
Article in English | MEDLINE | ID: mdl-38146541

ABSTRACT

Hand rehabilitation in chronic stroke remains challenging, and finding markers that could reflect motor function would help to understand and evaluate the therapy and recovery. The present study explored whether brain oscillations in different electroencephalogram (EEG) bands could indicate the motor status and recovery induced by action observation-driven brain-computer interface (AO-BCI) robotic therapy in chronic stroke. The neurophysiological data of 16 chronic stroke patients who received 20-session BCI hand training is the basis of the study presented here. Resting-state EEG was recorded during the observation of non-biological movements, while task-stage EEG was recorded during the observation of biological movements in training. The motor performance was evaluated using the Action Research Arm Test (ARAT) and upper extremity Fugl-Meyer Assessment (FMA), and significant improvements (p < 0.05) on both scales were found in patients after the intervention. Averaged EEG band power in the affected hemisphere presented negative correlations with scales pre-training; however, no significant correlations (p > 0.01) were found both in the pre-training and post-training stages. After comparing the variation of oscillations over training, we found patients with good and poor recovery presented different trends in delta, low-beta, and high-beta variations, and only patients with good recovery presented significant changes in EEG band power after training (delta band, p < 0.01). Importantly, motor improvements in ARAT correlate significantly with task EEG power changes (low-beta, c.c = 0.71, p = 0.005; high-beta, c.c = 0.71, p = 0.004) and task/rest EEG power ratio changes (delta, c.c = -0.738, p = 0.003; low-beta, c.c = 0.67, p = 0.009; high-beta, c.c = 0.839, p = 0.000). These results suggest that, in chronic stroke, EEG band power may not be a good indicator of motor status. However, ipsilesional oscillation changes in the delta and beta bands provide potential biomarkers related to the therapeutic-induced improvement of motor function in effective BCI intervention, which may be useful in understanding the brain plasticity changes and contribute to evaluating therapy and recovery in chronic-stage motor rehabilitation.

14.
Front Bioeng Biotechnol ; 11: 1227327, 2023.
Article in English | MEDLINE | ID: mdl-37929198

ABSTRACT

The limited portability of pneumatic pumps presents a challenge for ankle-foot orthosis actuated by pneumatic actuators. The high-pressure requirements and time delay responses of pneumatic actuators necessitate a powerful and large pump, which renders the entire device heavy and inconvenient to carry. In this paper, we propose and validate a concept that enhances portability by employing a slack cable tendon mechanism. By managing slack tension properly, the time delay response problem of pneumatic actuators is eliminated through early triggering, and the system can be effectively controlled to generate the desired force for dorsiflexion assistance. The current portable integration of the system weighs approximately 1.6 kg, with distribution of 0.5 kg actuation part on the shank and 1.1 kg power system on the waist, excluding the battery. A mathematical model is developed to determine the proper triggering time and volumetric flow rate requirements for pump selection. To evaluate the performance of this actuation system and mathematical model, the artificial muscle's response time and real volumetric flow rate were preliminarily tested with different portable pumps on a healthy participant during treadmill walking at various speeds ranging from 0.5 m/s to 1.75 m/s. Two small pumps, specifically VN-C1 (5.36 L/min, 300 g) and VN-C4 (9.71L/min, 550 g), meet our design criteria, and then tested on three healthy subjects walking at normal speeds of 1 m/s and 1.5 m/s. The kinematic and electromyographic results demonstrate that the device can facilitate ankle dorsiflexion with a portable pump (300-500 g), generating sufficient force to lift up the foot segment, and reducing muscle activity responsible for ankle dorsiflexion during the swing phase by 8% and 10% at normal speeds of 1 m/s and 1.5 m/s respectively. This portable ankle robot, equipped with a compact pump weighing approximately 1.6 kg, holds significant potential for assisting individuals with lower limb weakness in walking, both within their homes and in clinical settings.

16.
Nat Commun ; 14(1): 5053, 2023 08 19.
Article in English | MEDLINE | ID: mdl-37598178

ABSTRACT

Brain exposure of systemically administered biotherapeutics is highly restricted by the blood-brain barrier (BBB). Here, we report the engineering and characterization of a BBB transport vehicle targeting the CD98 heavy chain (CD98hc or SLC3A2) of heterodimeric amino acid transporters (TVCD98hc). The pharmacokinetic and biodistribution properties of a CD98hc antibody transport vehicle (ATVCD98hc) are assessed in humanized CD98hc knock-in mice and cynomolgus monkeys. Compared to most existing BBB platforms targeting the transferrin receptor, peripherally administered ATVCD98hc demonstrates differentiated brain delivery with markedly slower and more prolonged kinetic properties. Specific biodistribution profiles within the brain parenchyma can be modulated by introducing Fc mutations on ATVCD98hc that impact FcγR engagement, changing the valency of CD98hc binding, and by altering the extent of target engagement with Fabs. Our study establishes TVCD98hc as a modular brain delivery platform with favorable kinetic, biodistribution, and safety properties distinct from previously reported BBB platforms.


Subject(s)
Blood-Brain Barrier , Brain , Animals , Mice , Tissue Distribution , Antibodies , Engineering , Macaca fascicularis
17.
Sensors (Basel) ; 23(13)2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37448037

ABSTRACT

This paper proposes a method for accurate 3D posture sensing of the soft actuators, which could be applied to the closed-loop control of soft robots. To achieve this, the method employs an array of miniaturized sponge resistive materials along the soft actuator, which uses long short-term memory (LSTM) neural networks to solve the end-to-end 3D posture for the soft actuators. The method takes into account the hysteresis of the soft robot and non-linear sensing signals from the flexible bending sensors. The proposed approach uses a flexible bending sensor made from a thin layer of conductive sponge material designed for posture sensing. The LSTM network is used to model the posture of the soft actuator. The effectiveness of the method has been demonstrated on a finger-size 3 degree of freedom (DOF) pneumatic bellow-shaped actuator, with nine flexible sponge resistive sensors placed on the soft actuator's outer surface. The sensor-characterizing results show that the maximum bending torque of the sensor installed on the actuator is 4.7 Nm, which has an insignificant impact on the actuator motion based on the working space test of the actuator. Moreover, the sensors exhibit a relatively low error rate in predicting the actuator tip position, with error percentages of 0.37%, 2.38%, and 1.58% along the x-, y-, and z-axes, respectively. This work is expected to contribute to the advancement of soft robot dynamic posture perception by using thin sponge sensors and LSTM or other machine learning methods for control.


Subject(s)
Robotics , Porosity , Equipment Design , Motion , Robotics/methods , Perception
18.
Med Image Anal ; 88: 102880, 2023 08.
Article in English | MEDLINE | ID: mdl-37413792

ABSTRACT

Semi-supervised learning has greatly advanced medical image segmentation since it effectively alleviates the need of acquiring abundant annotations from experts, wherein the mean-teacher model, known as a milestone of perturbed consistency learning, commonly serves as a standard and simple baseline. Inherently, learning from consistency can be regarded as learning from stability under perturbations. Recent improvement leans toward more complex consistency learning frameworks, yet, little attention is paid to the consistency target selection. Considering that the ambiguous regions from unlabeled data contain more informative complementary clues, in this paper, we improve the mean-teacher model to a novel ambiguity-consensus mean-teacher (AC-MT) model. Particularly, we comprehensively introduce and benchmark a family of plug-and-play strategies for ambiguous target selection from the perspectives of entropy, model uncertainty and label noise self-identification, respectively. Then, the estimated ambiguity map is incorporated into the consistency loss to encourage consensus between the two models' predictions in these informative regions. In essence, our AC-MT aims to find out the most worthwhile voxel-wise targets from the unlabeled data, and the model especially learns from the perturbed stability of these informative regions. The proposed methods are extensively evaluated on left atrium segmentation and brain tumor segmentation. Encouragingly, our strategies bring substantial improvement over recent state-of-the-art methods. The ablation study further demonstrates our hypothesis and shows impressive results under various extreme annotation conditions.


Subject(s)
Benchmarking , Brain Neoplasms , Humans , Brain Neoplasms/diagnostic imaging , Consensus , Entropy , Heart Atria , Supervised Machine Learning , Image Processing, Computer-Assisted
19.
Cereb Cortex ; 33(17): 9867-9876, 2023 08 23.
Article in English | MEDLINE | ID: mdl-37415071

ABSTRACT

Menstrually-related migraine (MM) is a primary migraine in women of reproductive age. The underlying neural mechanism of MM was still unclear. In this study, we aimed to reveal the case-control differences in network integration and segregation for the morphometric similarity network of MM. Thirty-six patients with MM and 29 healthy females were recruited and underwent MRI scanning. The morphometric features were extracted in each region to construct the single-subject interareal cortical connection using morphometric similarity. The network topology characteristics, in terms of integration and segregation, were analyzed. Our results revealed that, in the absence of morphology differences, disrupted cortical network integration was found in MM patients compared to controls. The patients with MM showed a decreased global efficiency and increased characteristic path length compared to healthy controls. Regional efficiency analysis revealed the decreased efficiency in the left precentral gyrus and bilateral superior temporal gyrus contributed to the decreased network integration. The increased nodal degree centrality in the right pars triangularis was positively associated with the attack frequency in MM. Our results suggested MM would reorganize the morphology in the pain-related brain regions and reduce the parallel information processing capacity of the brain.


Subject(s)
Brain , Migraine Disorders , Humans , Female , Brain/diagnostic imaging , Migraine Disorders/diagnostic imaging , Magnetic Resonance Imaging/methods , Prefrontal Cortex , Pain
20.
Brain Struct Funct ; 228(7): 1643-1655, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37436503

ABSTRACT

Transcranial alternating current stimulation (tACS) offers a unique method to temporarily manipulate the activity of the stimulated brain region in a frequency-dependent manner. However, it is not clear if repetitive modulation of ongoing oscillatory activity with tACS over multiple days can induce changes in grey matter resting-state functional connectivity and white matter structural integrity. The current study addresses this question by applying multiple-session theta band stimulation on the left dorsolateral prefrontal cortex (L-DLPFC) during arithmetic training. Fifty healthy participants (25 males and 25 females) were randomly assigned to the experimental and sham groups, half of the participants received individually adjusted theta band tACS, and half received sham stimulation. Resting-state functional magnetic resonance (rs-fMRI) and diffusion-weighted imaging (DWI) data were collected before and after 3 days of tACS-supported procedural learning training. Resting-state network analysis showed a significant increase in connectivity for the frontoparietal network (FPN) with the precuneus cortex. Seed-based analysis with a seed defined at the primary stimulation site showed an increase in connectivity with the precuneus cortex, posterior cingulate cortex (PCC), and lateral occipital cortex. There were no effects on the structural integrity of white matter tracts as measured by fractional anisotropy, and on behavioral measures. In conclusion, the study suggests that multi-session task-associated tACS can produce significant changes in resting-state functional connectivity; however, changes in functional connectivity do not necessarily translate to changes in white matter structure or behavioral performance.


Subject(s)
Transcranial Direct Current Stimulation , Male , Female , Humans , Dorsolateral Prefrontal Cortex , Transcranial Magnetic Stimulation/methods , Prefrontal Cortex/physiology , Brain , Magnetic Resonance Imaging/methods
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