Noninvasive closed-loop acoustic brain-computer interface for seizure control.

Rationale: The brain-computer interface (BCI) is core tasks in comprehensively understanding the brain, and is one of the most significant challenges in neuroscience. The development of novel non-invasive neuromodulation technique will drive major innovations and breakthroughs in the field of BCI. Methods: We develop a new noninvasive closed-loop acoustic brain-computer interface (aBCI) for decoding the seizure onset based on the electroencephalography and triggering ultrasound stimulation of the vagus nerve to terminate seizures. Firstly, we create the aBCI system and decode the onset of seizure via a multi-level threshold model based on the analysis of wireless-collected electroencephalogram (EEG) signals recorded from above the hippocampus. Then, the different acoustic parameters induced acoustic radiation force were used to stimulate the vagus nerve in a rat model of epilepsy-induced by pentylenetetrazole. Finally, the results of epileptic EEG signal triggering ultrasound stimulation of the vagus nerve to control seizures. In addition, the mechanism of aBCI control seizures were investigated by real-time quantitative polymerase chain reaction (RT-qPCR). Results: In a rat model of epilepsy, the aBCI system selectively actives mechanosensitive neurons in the nodose ganglion while suppressing neuronal excitability in the hippocampus and amygdala, and stops seizures rapidly upon ultrasound stimulation of the vagus nerve. Physical transection or chemical blockade of the vagus nerve pathway abolish the antiepileptic effects of aBCI. In addition, aBCI shows significant antiepileptic effects compared to conventional vagus nerve electrical stimulation in an acute experiment. Conclusions: Closed-loop aBCI provides a novel, safe and effective tool for on-demand stimulation to treat abnormal neuronal discharges, opening the door to next generation non-invasive BCI.

Wormlike Micellar Glycerol Solutions Formed from a Double-Tailed Surfactant with Two Quaternary Ammonium Head Groups.

Herein, a quaternary ammonium surfactant with dual heads and tails, N1,N1,N1,N3,N3-pentamethyl-N3-(3-(2-tetradecylhexadecanamido)propyl)propane-1,3-diaminium dibromide, abbreviated as Di-C14-N2, was synthesized. For the first time, clear observation of aggregate structures formed by surfactants in pure glycerol systems was achieved using cryogenic transmission electron microscopy (cryo-TEM). The system's rheological properties were analyzed using both steady-state shear and oscillatory rheological measurements. The lubricating efficiency of the Di-C14-N2 glycerol solution was assessed for its tribological properties using a tribological wear tester, white light interferometer, and scanning electron microscope. In glycerol, Di-C14-N2 formed long wormlike micelles, which resulted in a glycerol solution with the zero-shear viscosity of 1013 Pa·s at 90 mM, which is the most viscous glycerol system up to now. The system displayed distinct rheological properties from the aqueous system, as evidenced by two intersections in the loss and storage moduli. The formed wormlike micelles in glycerol lead to a significant alteration in the viscoelasticity of the system, thus endowing the Di-C14-N2 glycerol solution with potential as an eco-friendly lubricant. The friction coefficient of the system was found to be 23% lower and the wear rate was 83% lower than that of pure glycerol after the addition of Di-C14-N2. This demonstrates that the addition of Di-C14-N2 greatly improves the frictional properties of pure glycerol. This study offers the possibility of directly observing the aggregate structures formed by surfactants in pure glycerol systems. It contributes to the exploration of the self-assembly behavior of surfactants in nonaqueous polar media, thereby aiding in a deeper understanding of the correlation between molecular structure, mesoscale structure, and macroscopic properties.

Effects of Lactobacillus plantarum on Broiler Health: Integrated Microbial and Metabolomics Analysis.

Given China's prohibition on the utilization of antibiotics as feed additives in 2020, we aim to investigate nutrition additives that are both efficient and safe. Lactobacillus, a well-recognized beneficial probiotic, has explicitly been investigated for its effects on health status of the host and overall impact on food industry. To evaluate effects of Lactobacillus plantarum (LW) supplementation on broiler chicken, we conducted comprehensive multi-omics analysis, growth performance evaluation, RT-qPCR analysis, and immunofluorescence. The findings revealed that LW supplementation resulted in a substantial progress in growth performance (approximately 205 g increase in final body weight in comparison to the control group (p < 0.01)). Additionally, LW exhibited promising potential for enhancing antioxidant properties of serum and promoting gut integrity and growth as evidenced by improved antioxidant indices (p < 0.01), intestinal villus morphology (p < 0.01), and enhanced gut barrier function (p < 0.01). Meanwhile, the multi-omics analysis, including 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry, revealed an enrichment of beneficial microbes in the gut of broilers that were supplemented with LW, while simultaneously depleting harmful microorganisms. Moreover, a noteworthy modification was observed in gut metabolic profiling subsequent to the execution of the probiotic strategy. Specifically, variations were noticed in the levels of metabolites and metabolic pathways such as parathyroid hormone synthesis, inflammatory mediator regulation of TRP channels, oxidative phosphorylation, and mineral absorption. Taken together, our findings validate that LW administration produces valuable effects on the health and growth performance of broilers owing to its capability to boost the gut microbiota homeostasis and intestinal metabolism. Present findings signify the potential of LW as a dietary additive to promote growth and development in broiler chickens.

Pediococcus pentosaceus PP34 Ameliorates 5-Fluorouracil-Induced Intestinal Mucositis via Inhibiting Oxidative Stress and Restoring the Gut Microbiota.

Chemotherapy-induced intestinal mucositis based on 5-fluorouracil (5-FU) slows down the progress of cancer treatment and causes significant suffering to patients. Pediococcus pentosaceus (P. pentosaceus), as a type of LAB, has a range of probiotic properties, including antioxidant, immune benefits, and cholesterol-lowering effects, which are attracting increasing attention. However, studies on the protective effect of P. pentosaceus against chemotherapeutic-induced intestinal mucositis caused by 5-FU remain unclear. Therefore, this study aimed to investigate the potential relieving effects of P. pentosaceus PP34 on 5-FU-induced intestinal mucositis and its mechanism. In the present study, a P. pentosaceus PP34 solution (2 × 109 CFU/mL) was administered daily by gavage followed by intraperitoneal injection of 5-FU to model intestinal mucositis. The body weight, serum biochemical indices, jejunal pathological organization, and expression levels of inflammatory cytokines in the jejunum were examined. The results indicated that the mice induced with 5-FU developed typical intestinal mucositis symptoms and histopathological changes with intense inflammatory and oxidative responses. Moreover, the gut microbiota was disturbed, while PP34 effectively decreased the oxidative reactions and the expression levels of inflammatory mediators and regulated the gut microbiota in 5-FU-exposed mice. Taken together, the study indicated that P. pentosaceus PP34 ameliorates 5-Fluorouracil-induced intestinal mucositis via inhibiting oxidative stress and restoring the gut microbiota.

Spatiotemporal Distributions of Acoustic Propagation in Skull During Ultrasound Neuromodulation.

There is widespread interest and concern about the evidence and hypothesis that the auditory system is involved in ultrasound neuromodulation. We have addressed this problem by performing acoustic shear wave simulations in mouse skull and behavioral experiments in deaf mice. The simulation results showed that shear waves propagating along the skull did not reach sufficient acoustic pressure in the auditory cortex to modulate neurons. Behavioral experiments were subsequently performed to awaken anesthetized mice with ultrasound targeting the motor cortex or ventral tegmental area (VTA). The experimental results showed that ultrasound stimulation (US) of the target areas significantly increased arousal scores even in deaf mice, whereas the loss of ultrasound gel abolished the effect. Immunofluorescence staining also showed that ultrasound can modulate neurons in the target area, whereas neurons in the auditory cortex required the involvement of the normal auditory system for activation. In summary, the shear waves propagating along the skull cannot reach the auditory cortex and induce neuronal activation. Ultrasound neuromodulation-induced arousal behavior needs direct action on functionally relevant stimulation targets in the absence of auditory system participation.

Wormlike micellar solutions formed by an anionic surfactant and a cationic surfactant with two head groups.

Innovation in the molecular structure of surfactants is important for the preparation of soft materials with novel properties. In this study, we synthesized a cationic surfactant, N1,N1,N1,N1,N3,N3,N3-pentamethyl-N3-(3-stearamidopropyl)propane-1,3-diammonium bromide, hereafter referred to as C18-DQA. Unlike conventional cationic surfactants, C18-DQA contains two quaternary ammonium head groups and a long-saturated alkyl chain equal to a chain length of 21 carbon atoms. C18-DQA exhibits a low Krafft point of ∼0 °C and a water solubility >1000 mM at 25 °C. The critical micelle concentration (cmc) of C18-DQA was determined to be 0.59 mM using the Nile red method. C18-DQA was mixed with sodium laurate (SL) at different molar ratios to produce transparent solutions with excellent viscoelasticity over a wide concentration range. The 1 : 1.5 molar ratio C18-DQA/SL mixed solutions exhibited gel-like behavior for a total surfactant concentration of 2.88 wt% (75 mM). The solution with a total surfactant concentration of 300 mM (120 mM C18-DQA and 180 mM SL) achieved a maximum zero-shear viscosity (η0) of 4224 Pa s. Cryogenic transmission electron microscopy analysis revealed the formation of extremely long wormlike micelles, with a cross-sectional diameter of 5 nm and contour length >3 µm, in the mixed solutions. C18-DQA and SL molecules were drawn close by electrostatic attractions, leading to a suitable molecular geometry for the extensive growth of wormlike micelles. This work will act as an important reference for the future preparation of highly viscoelastic solutions by mixing cationic and anionic surfactants. The proposed system is also expected to have potential applications in cosmetic formulations, home care products, and oilfield fracturing fluids.

Toroidal micelles formed in viscoelastic aqueous solutions of a double-tailed surfactant with two quaternary ammonium head groups.

Innovation in surfactant structures is an effective way to prepare new soft materials with novel applications. In this study, we synthesized a double-tailed surfactant containing two quaternary ammonium head groups (Di-C12-N2). The Di-C12-N2 solution behavior was investigated by surface tension, fluorescence, rheology, and cryo-TEM methods. Although Di-C12-N2 contained a large double-tailed hydrophobic group, the solubility of Di-C12-N2 was ∼90 mmol L-1 at 25 °C with a Krafft temperature of ∼1 °C. The increase in Di-C12-N2 concentration in the solutions led to the formation of various aggregates, including spherical micelles, worm-like micelles, multi-layered vesicles, and a rare type of small toroidal micelles. The two quaternary ammonium head groups in Di-C12-N2 led to strong electrostatic interactions between molecules, which was critical for the formation of toroidal micelles. Moreover, with an added NaCl concentration of 40 mmol L-1, the viscosity of the 5 mmol L-1Di-C12-N2 solution increased by ∼1000 times compared to the pure 5 mmol L-1Di-C12-N2 solution, revealing the high sensitivity of the unique head groups to ionic strength. This study enriches the research on the self-assembly principles of surfactants and brings new potential applications for new soft materials.

Ultrasound Deep Brain Stimulation Regulates Food Intake and Body Weight in Mice.

Given the widespread occurrence of obesity, new strategies are urgently needed to prevent, halt and reverse this condition. We proposed a noninvasive neurostimulation tool, ultrasound deep brain stimulation (UDBS), which can specifically modulate the hypothalamus and effectively regulate food intake and body weight in mice. Fifteen-min UDBS of hypothalamus decreased 41.4% food intake within 2 hours. Prolonged 1-hour UDBS significantly decreased daily food intake lasting 4 days. UDBS also effectively restrained body weight gain in leptin-receptor knockout mice (Sham: 96.19%, UDBS: 58.61%). High-fat diet (HFD) mice treated with 4-week UDBS (15 min / 2 days) reduced 28.70% of the body weight compared to the Sham group. Meanwhile, UDBS significantly modulated glucose-lipid metabolism and decreased the body fat. The potential mechanism is that ultrasound actives pro-opiomelanocortin (POMC) neurons in the hypothalamus for reduction of food intake and body weight. These results provide a noninvasive tool for controlling food intake, enabling systematic treatment of obesity.

Transthoracic Ultrasound Improves Cardiac Function in Mice.

Cardiac dysfunction is a severe complication that is associated with an increased risk of mortality in multiple diseases. Cardioprotection solution that has been researched is the electrical stimulation of the vagus nerve to exert cardio protection. This method has been shown to reduce the systemic inflammatory response and maintain the immune homeostasis of the heart. However, the invasive procedure of electrode implantation poses a risk of nerve or fiber damage. Here, we propose transthoracic ultrasound stimulation (US) of the vagus nerve to alleviate cardiac dysfunction caused by lipopolysaccharide (LPS). We developed a noninvasive transthoracic US system and exposed anesthetized mice to ultrasound protocol or sham stimulation 24 h after LPS treatment. Results showed that daily heart targeting US for 4 days significantly increased left ventricular systolic function ( p = 0.01) and improved ejection fraction ( p = 0.03) and shortening fraction ( p = 0.04). Furthermore, US significantly reduced inflammation cytokines, including IL-6 ( p = 0.03) and IL- 1ß ( p = 0.04). In addition, cervical vagotomy abrogated the effect of US, suggesting the involvement of the vagus nerve's anti-inflammatory effect. Finally, the same ultrasound treatment but for a longer period (14 days) also significantly increased cardiac function in naturally aged mice. Collectively, these findings suggest the potential of transthoracic US as a possible novel noninvasive approach in the context of cardiac dysfunction with reduced systolic function and provide new targets for rehabilitation of peripheral organ function.

The Effect of Lactobacillus sakei on Growth Performance and Intestinal Health in Dogs: Gut Microbiota and Metabolism Study.

The gut microbiota is the largest and most complex ecosystem consisting of trillions of microorganisms, which influenced by various external factors. As an important probiotic species, Lactobacillus helps to improve gut microbial diversity and composition, underlying potential efficacy in growth performance and disease prevention. However, limited studies have been investigated the relationship between Lactobacillus sakei and intestinal health in dogs. In this study, dogs in the two groups were fed a standard diet (group C, n = 8) and Lactobacillus sakei diet (group P, n = 8), respectively. The growth performance, serum biochemical indices, antioxidant capacity, gut microbiota, and metabolism of dogs in both groups were studied. Results from growth trials showed that L. sakei can significantly improve the growth performance of dogs, including increased weight gain (p < 0.05), serum biochemical indices, i.e., ALP, TP, and ALB (p < 0.05), and better antioxidant capacity, i.e., SOD and GSH-Px (p < 0.05). Significant changes in the gut microbial composition were detected in dogs fed Lactobacillus sakei, as evidenced by an increase in the level of Firmicutes, Spirochaetota, and Patescibacteria, all of them play an important role in maintaining intestinal health. Moreover, a decrease in the level of microorganisms that threaten health, such as Mucispirillum and Clostridium_sensu_stricto_13. The metabolic analysis showed that the Lactobacillus sakei enhanced metabolic pathways such as vitamin B6 metabolism, glutathione metabolism, retinol metabolism, and fatty acid degradation. Our findings suggested that Lactobacillus sakei supplementation had beneficial effects on the growth performance and health status of dogs by improving gut microbiota balance and promoting metabolism. There are an estimated 200 million dogs in China, and the population is continuing to grow at a rapid pace. It is essential to explore an effective way to promote health in dogs. Intestinal diseases, particularly colitis and diarrhea, are common clinical conditions in dogs and are associated with gut microbiota. Lactobacillus sakei, as an important species of probiotics, the relationship between L. sakei and intestinal health in dogs remains unclear. Our study suggests that L. sakei significantly promotes growth performance and health states involving weight gain, regulation of gut microbiota, and metabolism. Overall, our findings shed light on the potential role of L. sakei as an alternative in promoting health in dogs.

Effects of lactic acid bacteria isolated from Tibetan chickens on the growth performance and gut microbiota of broiler.

Lactic acid bacteria (LAB) are organic supplements that have several advantages for the health of the host. Tibetan chickens are an ancient breed, which evolve unique gut microbiota due to their adaptation to the hypoxic environment of high altitude. However, knowledge of LAB isolated from Tibetan chickens is very limited. Thus, the purpose of this study was to assess the probiotic properties of Lactobacillus Plantarum (LP1), Weissella criteria (WT1), and Pediococcus pentosaceus (PT2) isolated from Tibetan chickens and investigate their effects on growth performance, immunoregulation and intestinal microbiome in broiler chickens. Growth performance, serum biochemical analysis, real-time PCR, and 16S rRNA sequencing were performed to study the probiotic effects of LP1, WT1, and PT2 in broiler chickens. Results showed that LP1, WT1 and PT2 were excellent inhibitors against Escherichia coli (E. coli ATCC25922), meanwhile, LP1, WT1, and PT2 significantly increased weekly weight gain, villus height, antioxidant ability and gut microbiota diversity indexes in broilers. In addition, LP1 and PT2 increased the relative abundance of Lactobacillus and decreased Desulfovibrio in comparison with T1 (control group). Additionally, oral LAB can reduce cholesterol and regulate the expression of tight junction genes in broiler chickens, suggesting that LAB can improve the integrity of the cecal barrier and immune response. In conclusion, LAB improved the growth performance, gut barrier health, intestinal flora balance and immune protection of broiler chickens. Our findings revealed the uniqueness of LAB isolated from Tibetan chickens and its potential as a probiotic additive in poultry field.

Fast identification and quantification of c-Fos protein using you-only-look-once-v5.

In neuroscience, protein activity characterizes neuronal excitability in response to a diverse array of external stimuli and represents the cell state throughout the development of brain diseases. Importantly, it is necessary to characterize the proteins involved in disease progression, nuclear function determination, stimulation method effect, and other aspects. Therefore, the quantification of protein activity is indispensable in neuroscience. Currently, ImageJ software and manual counting are two of the most commonly used methods to quantify proteins. To improve the efficiency of quantitative protein statistics, the you-only-look-once-v5 (YOLOv5) model was proposed. In this study, c-Fos immunofluorescence images data set as an example to verify the efficacy of the system using protein quantitative statistics. The results indicate that YOLOv5 was less time-consuming or obtained higher accuracy than other methods (time: ImageJ software: 80.12 ± 1.67 s, manual counting: 3.41 ± 0.25 s, YOLOv5: 0.0251 ± 0.0003 s, p < 0.0001, n = 83; simple linear regression equation: ImageJ software: Y = 1.013 × X + 0.776, R 2 = 0.837; manual counting: Y = 1.0*X + 0, R 2 = 1; YOLOv5: Y = 0.9730*X + 0.3821, R 2 = 0.933, n = 130). The findings suggest that the YOLOv5 algorithm provides feasible methods for quantitative statistical analysis of proteins and has good potential for application in detecting target proteins in neuroscience.

Ultrasound Deep Brain Stimulation Modulates Body Temperature in Mice.

Body temperature plays a critical role in rehabilitation, and numerous studies proved that the regulation of body temperature contributes to the sensorimotor recovery of patients with brain diseases such as stroke. The hypothalamus plays a key role in thermoregulation. Ultrasound deep brain stimulation (UDBS) can noninvasively modulate deep brain nuclei and have potential applications in the treatment of Parkinson's disease, Alzheimer's disease, and depression, among others. The purpose of this study was to investigate whether ultrasound stimulation of the hypothalamus could regulate body temperature in free-moving mice. Results showed that thermoregulation was related to ultrasonic parameters (pulse repetition frequency (PRF), duty cycle, total time, and acoustic pressure). UDBS of the preoptic area of the anterior hypothalamus at 500 Hz PRF could significantly reduce body temperature ( [Formula: see text] at t = 5 min, [Formula: see text] at t = 10 min, [Formula: see text] at t = 15 min). Meanwhile, UDBS of the dorsomedial hypothalamus at 10 Hz PRF triggered a significant increase in body temperature ( [Formula: see text] at t = 5 min, [Formula: see text] at t = 10 min). These results suggest that UDBS, as a noninvasive neuromodulation tool, may play a key role in the future clinical treatment of malignant hyperthermia and hypothermia.

Ultrasound Stimulation of Prefrontal Cortex Improves Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice.

Increasing evidence indicates that inflammatory responses may influence brain neurochemical pathways, inducing depressive-like behaviors. Ultrasound stimulation (US) is a promising non-invasive treatment for neuropsychiatric diseases. We investigated whether US can suppress inflammation and improve depressive-like behaviors. Mice were intraperitoneally injected with lipopolysaccharide to induce depressive-like behaviors. Ultrasound wave was delivered into the prefrontal cortex (PFC) for 30 min. Depressive- and anxiety-like behaviors were evaluated through the forced swimming test (FST), tail suspension test (TST), and elevated plus maze (EPM). Biochemical analyses were performed to assess the expression of inflammatory cytokines in the PFC and serum. The results indicated that US of the PFC significantly improved depressive-like behaviors in the TST (p < 0.05) and FST (p < 0.05). Anxiety-like behaviors also improved in the EPM (p < 0.05). Furthermore, the lipopolysaccharide-mediated upregulation of IL-6, IL-1ß, and TNF-α in the PFC was significantly reduced (p < 0.05) by US. In addition, no tissue damage was observed. Overall, US of PFC can effectively improve lipopolysaccharide-induced depressive-like behaviors, possibly through the downregulation of inflammatory cytokines in the PFC. US may be a safe and promising tool for improvement of depression.

Muscular injury was identified the risk factor of post-operative stenosis after large area but non-circumferential esophageal endoscopic submucosal dissection.

BACKGROUND: The incidence of post-operative stenosis after esophageal Endoscopic Submucosal Dissection (ESD) ranks high. This study aimed to investigate the association between the degree of muscular injury and the incidence of post-operative stenosis. RESEARCH DESIGN: This was a retrospective study of 133 patients with superficial esophageal lesions treated by non-circumferential ESD enrolled between January 2016 and May 2021 at two endoscopy centers. Demographic and clinical parameters were analyzed. A novel muscular injury classification system was proposed. Stenosis risk factors were identified using multivariate logistic regression. The association between the different degrees of muscular injury and the incidence of post-operative stenosis was investigated further by propensity score matching (PSM). RESULTS: There were 133 cases evaluated in this study, 33 of which developed stenosis. Multivariate analysis suggested lesions located in the upper 1/3 of the esophagus, resections >5/6 of the circumference, and muscular injury (Grade 3 or 4 according to our proposed classification) were risk factors for stenosis. Correlation analysis suggested a positive association between the degree of muscular injury and the incidence of post-operative stenosis (r = 0.408, p < .05). For PSM, 29 stenosis cases were matched and univariate analysis further corroborated that muscular injuries of grade 3 (OR = 6.429, 95%CI = 1.318-31.367, p = .021) or 4 (OR = 7, 95%CI = 1.068-45.901, p = .043) were risk factors for stenosis. CONCLUSION: Grade 3-4 muscular injury was identified as a risk factor of post-operative stenosis.

Complete genome analysis of Bacillus subtilis derived from yaks and its probiotic characteristics.

Probiotics have attracted attention due to their multiple health benefits to the host. Yaks inhabiting the Tibetan plateau exhibit excellent disease resistance and tolerance, which may be associated with their inner probiotics. Currently, research on probiotics mainly focuses on their positive effects on the host, but information regarding their genome remains unclear. To reveal the potential functional genes of Bacillus subtilis isolated from yaks, we sequenced its whole genome. Results indicated that the genomic length of Bacillus subtilis was 866,044,638 bp, with 4,429 coding genes. The genome of this bacteria was composed of one chromosome and one plasmid with lengths of 4,214,774 and 54,527 bp, respectively. Moreover, Bacillus subtilis contained 86 tRNAs, 27 rRNAs (9 16S_rRNA, 9 23S_rRNA, and 9 5S_rRNA), and 114 other ncRNA. KEGG annotation indicated that most genes in Bacillus subtilis were associated with biosynthesis of amino acids, carbon metabolism, purine metabolism, pyrimidine metabolism, and ABC transporters. GO annotation demonstrated that most genes in Bacillus subtilis were related to nucleic acid binding transcription factor activity, transporter activity, antioxidant activity, and biological adhesion. EggNOG uncovered that most genes in Bacillus subtilis were related to energy production and conversion, amino acid transport and metabolism, carbohydrate transport and metabolism. CAZy annotation found glycoside hydrolases (33.65%), glycosyl transferases (22.11%), polysaccharide lyases (3.84%), carbohydrate esterases (14.42%), auxiliary activities (3.36%), and carbohydrate-binding modules (22.59%). In conclusion, this study investigated the genome and genetic properties of Bacillus subtilis derived from yaks, which contributed to understanding the potential prebiotic mechanism of probiotics from the genetic perspective.

Closed-loop wearable ultrasound deep brain stimulation system based on EEG in mice.

Objective. Epilepsy is one of the most common severe brain disorders. Ultrasound deep brain stimulation (UDBS) has shown a potential capability to suppress seizures. However, because seizures occur sporadically, it is necessary to develop a closed-loop system to suppress them. Therefore, we developed a closed-loop wearable UDBS system that delivers ultrasound to the hippocampus to suppress epileptic seizures.Approach.Mice were intraperitoneally injected with 10 mg kg-1kainic acid and divided into sham and UDBS groups. Epileptic seizures were detected by applying both long short-term memory (LSTM) and bidirectional LSTM (BILSTM) networks according to EEG signal characteristics. When epileptic seizures were detected, the closed-loop UDBS system automatically activated a trigger switch to stimulate the hippocampus for 10 min and continuously record EEG signals until 20 min after ultrasonic stimulation. EEG signals were analyzed using the MATLAB software. After EEG recording, we observed the survival rate of the experimental mice for 72 h.Main results.The BiLSTM network was found to have preferable classification performance over the LSTM network. The closed-loop UDBS system with BiLSTM could automatically detect epileptic seizures using EEG signals and effectively reduce epileptic EEG power spectral density and seizure duration by 10.73%, eventually improving the survival rate of early epileptic mice from 67.57% in the sham group to 88.89% in the UDBS group.Significance.The closed-loop UDBS system developed in this study could be an effective clinical tool for the control of epilepsy.

Noninvasive Ultrasound Stimulation of Ventral Tegmental Area Induces Reanimation from General Anaesthesia in Mice.

Evidence in animals suggests that deep brain stimulation or optogenetics can be used for recovery from disorders of consciousness (DOC). However, these treatments require invasive procedures. This report presents a noninvasive strategy to stimulate central nervous system neurons selectively for recovery from DOC in mice. Through the delivery of ultrasound energy to the ventral tegmental area, mice were aroused from an unconscious, anaesthetized state in this study, and this process was controlled by adjusting the ultrasound parameters. The mice in the sham group under isoflurane-induced, continuous, steady-state general anaesthesia did not regain their righting reflex. On insonation, the emergence time from inhaled isoflurane anaesthesia decreased (sham: 13.63 ± 0.53 min, ultrasound: 1.5 ± 0.19 min, p < 0.001). Further, the induction time (sham: 12.0 ± 0.6 min, ultrasound: 17.88 ± 0.64 min, p < 0.001) and the concentration for 50% of the maximal effect (EC50) of isoflurane (sham: 0.6%, ultrasound: 0.7%) increased. In addition, ultrasound stimulation reduced the recovery time in mice with traumatic brain injury (sham: 30.38 ± 1.9 min, ultrasound: 7.38 ± 1.02 min, p < 0.01). This noninvasive strategy could be used on demand to promote emergence from DOC and may be a potential treatment for such disorders.

Neuroprotective Effect of Ultrasound Neuromodulation on Kainic Acid- Induced Epilepsy in Mice.

Preliminary evidence suggests that low-intensity pulsed ultrasound (LIPUS) has neuroprotective effects on ischemic stroke, depression, and other conditions leading to neuronal cell death (e.g., Parkinson's disease). The purpose of this study was to investigate the neuroprotective effects of LIPUS in epileptic mice. Mice were made epileptic through kainic acid (KA) administration and then stimulated with LIPUS. The neuroprotective effect of ultrasound was evaluated by observing the latency, anxiety-like behavior, and levels of proteins related to inflammation, apoptosis, or signaling pathways. The safety of LIPUS was assessed by hematoxylin and eosin (H&E) and Nissl stainings. LIPUS prolonged the latency (Sham: 6.00 ± 0.26 days; 1-kHz pulse repetition frequency (PRF): 7.00 ± 0.31 days), improved the anxiety-like behavior, and inhibited the expression of inflammatory factors and apoptosis-related proteins. In addition, H&E and Nissl staining results confirmed that LIPUS did not damage the brain. These findings suggest that LIPUS has neuroprotective effects in mice with KA-induced epilepsy. LIPUS may offer a new therapeutic approach to epilepsy.