UNASSIGNED: Transcutaneous auricular vagus nerve stimulation (taVNS) has garnered attention for stroke rehabilitation, with studies demonstrating its benefits when combined with motor rehabilitative training or delivered before motor training. The necessity of concurrently applying taVNS with motor training for post-stroke motor rehabilitation remains unclear. We aimed to investigate the necessity and advantages of applying the taVNS concurrently with motor training by an electromyography (EMG)-triggered closed-loop system for post-stroke rehabilitation.
UNASSIGNED: We propose a double-blinded, randomized clinical trial involving 150 stroke patients assigned to one of three groups: concurrent taVNS, sequential taVNS, or sham control condition. In the concurrent group, taVNS bursts will synchronize with upper extremity motor movements with EMG-triggered closed-loop system during the rehabilitative training, while in the sequential group, a taVNS session will precede the motor rehabilitative training. TaVNS intensity will be set below the pain threshold for both concurrent and sequential conditions and at zero for the control condition. The primary outcome measure is the Fugl-Meyer Assessment of Upper Extremity (FMA-UE). Secondary measures include standard upper limb function assessments, as well as EMG and electrocardiogram (ECG) features.
UNASSIGNED: Ethical approval has been granted by the Medical Ethics Committee, affiliated with Zhujiang Hospital of Southern Medical University for Clinical Studies (2023-QX-012-01). This study has been registered on ClinicalTrials (NCT05943431). Signed informed consent will be obtained from all included participants. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings.
UNASSIGNED: This study represents a pioneering effort in directly comparing the impact of concurrent taVNS with motor training to that of sequential taVNS with motor training on stroke rehabilitation. Secondly, the incorporation of an EMG-triggered closed-loop taVNS system has enabled the automation and individualization of both taVNS and diverse motor training tasks-a novel approach not explored in previous research. This technological advancement holds promise for delivering more precise and tailored training interventions for stroke patients. However, it is essential to acknowledge a limitation of this study, as it does not delve into examining the neural mechanisms underlying taVNS in the context of post-stroke rehabilitation.

Implantable neuromodulation devices have significantly advanced treatments for neurological disorders such as Parkinson\'s disease, epilepsy, and depression. Traditional open-loop devices like deep brain stimulation (DBS) and spinal cord stimulators (SCS) often lead to overstimulation and lack adaptive precision, raising safety and side-effect concerns. Next-generation closed-loop systems offer real-time monitoring and on-device diagnostics for responsive stimulation, presenting a significant advancement for treating a range of brain diseases. However, the high false alarm rates of current closed-loop technologies limit their efficacy and increase energy consumption due to unnecessary stimulations. In this study, we introduce an artificial intelligence-integrated circuit co-design that targets these issues and using an online demonstration system for closed-loop seizure prediction to showcase its effectiveness. Firstly, two neural network models are obtained with neural-network search and quantization strategies. A binary neural network is optimized for minimal computation with high sensitivity and a convolutional neural network with a false alarm rate as low as 0.1/h for false alarm rejection. Then, a dedicated low-power processor is fabricated in 55 nm technology to implement the two models. With reconfigurable design and event-driven processing feature the resulting application-specific integrated circuit (ASIC) occupies only 5mm2 silicon area and the average power consumption is 142 μW. The proposed solution achieves a significant reduction in both false alarm rates and power consumption when benchmarked against state-of-the-art counterparts.

In order to improve the living standards of diabetes patients and reduce the negative health effects of this disease, the medical community has been actively searching for more effective treatments. In recent years, an artificial pancreas has emerged as an important approach to managing diabetes. Despite these recent advances, meeting the requirements for miniaturized size, accurate sensing and large-volume pumping capability remains a great challenge. Here, we present a novel miniaturized artificial pancreas based on a long microtube sensor integrated with an ultrasonic pump. Our device meets the requirements of achieving both accurate sensing and high pumping capacity. The artificial pancreas is constructed based on a long microtube that is low cost, painless and simple to operate, where the exterior of the microtube is fabricated as a glucose sensor for detecting diabetes and the interior of the microtube is used as a channel for delivering insulin through an ultrasonic pump. This work successfully achieved closed-loop control of blood glucose and treatment of diabetes in rats. It is expected that this work can open up new methodologies for the development of microsystems, and advance the management approach for diabetes patients.

Chronic wounds arising from accidents, surgeries, or diseases impose a significant clinical and economic burden, underscoring the need for effective solutions to prevent severe complications. Recent advancements in materials science and electrochemical technology have facilitated the development of conformable electrochemical platforms for detection and management, incorporating monitoring, diagnosis, and treatment. Nevertheless, current wound detection and therapy systems face challenges related to the stability and specificity of sensor monitoring, as well as the need for on-site and comprehensive evaluation criteria to offer timely treatment guidance and follow-up care. This review provides a comprehensive overview of the closed-loop management system, emphasizing wound biomarker detection, wound assessment, and on-demand treatment, ultimately culminating in an integrated wound management approach by conformable electrochemical devices. Additionally, we explore the challenges, opportunities, and future prospects of soft and stretchable electrochemical biosensors, with the aim of enhancing the efficiency and timeliness of wound management.

More recently, soft actuators have evoked great interest in the next generation of soft robots. Despite significant progress, the majority of current soft actuators suffer from the lack of real-time sensory feedback and self-control functions, prohibiting their effective sensing and multitasking functions. Therefore, in this work, a near-infrared-driven bimorph membrane, with self-sensing and feedback loop control functions, is produced by layer by layer (LBL) assembling MXene/PDDA (PM) onto liquid crystal elastomer (LCE) film. The versatile integration strategy successfully prevents the separation issues that arise from moduli mismatch between the sensing and the actuating layers, ultimately resulting in a stable and tightly bonded interface adhesion. As a result, the resultant membrane exhibited excellent mechanical toughness (tensile strengths equal to 16.3 MPa (||)), strong actuation properties (actuation stress equal to 1.56 MPa), and stable self-sensing (gauge factor equal to 4.72) capabilities. When applying the near-infrared (NIR) laser control, the system can perform grasping, traction, and crawling movements. Furthermore, the wing actuation and the closed-loop controlled motion are demonstrated in combination with the insect microcontroller unit (MCU) models. The remote precision control and the self-sensing capabilities of the soft actuator pave a way for complex and precise task modulation in the future.

The present study aimed to investigate the effectiveness of closed-loop transcranial ultrasound stimulation (closed-loop TUS) as a non-invasive, high temporal-spatial resolution method for modulating brain function to enhance memory. For this purpose, we applied closed-loop TUS to the CA1 region of the rat hippocampus for 7 consecutive days at different phases of theta cycles. Following the intervention, we evaluated memory performance through behavioral testing and recorded the neural activity. Our results indicated that closed-loop TUS applied at the peak phase of theta cycles significantly improves the memory performance in rats, as evidenced by behavioral testing. Furthermore, we observed that closed-loop TUS modifies the power and cross-frequency coupling strength of local field potentials (LFPs) during memory task, as well as modulates neuronal activity patterns and synaptic transmission, depending on phase of stimulation relative to theta rhythm. We demonstrated that closed-loop TUS can modulate neural activity and memory performance in a phase-dependent manner. Specifically, we observed that effectiveness of closed-loop TUS in regulating neural activity and memory is dependent on the timing of stimulation in relation to different theta phase. The findings implied that closed-loop TUS may have the capability to alter neural activity and memory performance in a phase-sensitive manner, and suggested that the efficacy of closed-loop TUS in modifying neural activity and memory was contingent on timing of stimulation with respect to the theta rhythm. Moreover, the improvement in memory performance after closed-loop TUS was found to be persistent.

BACKGROUND: This randomized and controlled prospective study tested the hypothesis that closed-loop Target-Controlled Infusion (TCI) of propofol would be associated with better system performance when compared with open-loop controlled delivery of propofol.
METHODS: Patients scheduled for elective breast surgery were randomly assigned to two groups: a closed-loop group, in which propofol infusion was performed by a closed-loop TCI system that used the Bispectral Index (BIS) as a feedback parameter to titrate the rate of propofol infusion, and an open-loop group, in which propofol infusion was performed manually and guided by the bispectral index.
RESULTS: A total of 156 patients were recruited for this study (closed-loop group n = 79; open-loop group n = 77). The Global Score (GS) of the closed-loop group was lower than that of the open-loop group (34.3 and 42.2) (p = 0.044). The proportions of time with a BIS value between 40 and 60 were almost identical in the closed-loop group and the open-loop group (68.7 ± 10.6% and 66.7 ± 13.3%) (p = 0.318). The individuals in the closed-loop group consumed more propofol compared with those in the open-loop group (7.20 ± 1.65 mg.kg-1.h-1 vs. 6.03 ± 1.31 mg.kg-1.h-1, p < 0.001). No intraoperative recall, somatic events or adverse events occurred. No significant difference in heart rate was observed between the two groups (p = 0.169).
CONCLUSIONS: The closed-loop protocol was associated with lower BIS variability and lower out-of-range BIS values, at the cost of a greater consumption of propofol when compared to the open loop group.
UNASSIGNED: ChiCTR-INR-17010399.

Parkinson\'s disease (PD) is a neurodegenerative disease with a heavy burden on patients, families, and society. Deep brain stimulation (DBS) can improve the symptoms of PD patients for whom medication is insufficient. However, current open-loop uninterrupted conventional DBS (cDBS) has inherent limitations, such as adverse effects, rapid battery consumption, and a need for frequent parameter adjustment. To overcome these shortcomings, adaptive DBS (aDBS) was proposed to provide responsive optimized stimulation for PD. This topic has attracted scientific interest, and a growing body of preclinical and clinical evidence has shown its benefits. However, both achievements and challenges have emerged in this novel field. To date, only limited reviews comprehensively analyzed the full framework and procedures for aDBS implementation. Herein, we review current preclinical and clinical data on aDBS for PD to discuss the full procedures for its achievement and to provide future perspectives on this treatment.

This paper presents an implementation scheme and experimental evaluation of a high-linearity closed-loop capacitive accelerometer based on ring-diode capacitance detection. By deducing the capacitance detection model of the ring-diode considering the influence of the diode, the existing theoretical model error of the ring-diode is corrected and a closed-loop scheme of reusing the detection electrode and the control electrode of the MEMS die is designed to apply this detection scheme to the parallel-plate accelerometer, which only has three independent electrodes. After analyzing the non-linear problems in the existing closed-loop control schemes, a theoretically absolute linear closed-loop control scheme is proposed, and an integrated closed-loop accelerometer is realized by combining the closed-loop diode detection. The experimental results of the ring-diode detection model are in agreement with the theoretical formula. The non-linearity of the accelerometer within ±1 g after the closed-loop is 130 ppm, compared with 1500 ppm when the open-loop is used.

Objective. Closed-loop transcranial ultrasound stimulation (TUS) can be applied at a specific time according to the state of neural activity to achieve timely and precise neuromodulation and improve the modulation effect. In a previous study, we found that closed-loop TUS at the peaks and troughs of the theta rhythm in the mouse hippocampus was able to increase the absolute power and decrease the relative power of the theta rhythm of local field potentials (LFPs) independent of the peaks and troughs of the stimulus. However, it remained unclear whether the modulation effect of this closed-loop TUS-induced mouse hippocampal neural oscillation depended on the peaks and troughs of the theta rhythm.Approach. In this study, we used ultrasound with different stimulation modes and durations to stimulate the peaks (peak stimulation) and troughs (trough stimulation) of the hippocampal theta rhythm. The LFPs in the area of ultrasound stimulation were recorded and the amplitudes and power spectra of the theta rhythm before and after ultrasound stimulation were analyzed.Main results. The results showed that (a) the relative change in amplitude of theta rhythm decreases as the number of stimulation trials under peak stimulation increases; (b) the relative change in the absolute power of the theta rhythm decreases as the number of stimulation trials under peak stimulation increases; (c) the relative change in amplitude of the theta rhythm increases nonlinearly with the stimulation duration (SD) under peak stimulation, and; (d) the relative change in absolute power exhibits a nonlinear increase with SD under peak stimulation.Significance. These results suggest that the modulation effect of closed-loop TUS on theta rhythm is dependent on the stimulation mode and duration under peak stimulation. TUS has the potential to precisely modulate theta rhythm-related neural activity.