Safety and immunogenicity of the SARS-CoV-2 LYB001 RBD-based VLP vaccine (CHO cell) phase 1 in Chinese adults: a randomized, double-blind, positive-parallel-controlled study.

BACKGROUND: Vaccination remains the cornerstone of defense against COVID-19 globally. This study aims to assess the safety and immunogenicity profile of innovative vaccines LYB001. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, parallel-controlled trial, in 100 healthy Chinese adults (21 to 72 years old). Three doses of 30 or 60 µg of SARS-CoV-2 RBD-based VLP vaccine (LYB001), or the SARS-CoV-2 RBD-based protein subunit vaccine (ZF2001, control group) were administered with a 28-day interval. Differences in the incidence of adverse events (AEs) and indicators of humoral and cellular immunity among the different groups were measured. RESULTS: No severe adverse events were confirmed to be vaccine-related, and there was no significant difference in the rate of adverse events between the LYB001 and control group or the age subgroups (p > 0.05). The LYB001 groups had significantly higher or comparable levels of seroconversion rates, neutralization antibody, S protein-binding antibody, and cellular immunity after whole vaccination than the control group. CONCLUSIONS: Our findings support that LYB001 developed on the VLP platform is safe and well tolerated with favorable immunogenicity for fundamental vaccination in healthy adults. Therefore, further larger-scale clinical studies are warranted. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT05552573).

Use, satisfaction, and preference of online health services among older adults with multimorbidity in Hong Kong primary care during COVID-19.

BACKGROUND: The use of online and mobile internet and social media has been increasing in healthcare service delivery. However, there is limited literature on the acceptance and use of online health services for older adults with multimorbidity who require more medical care and assistance. This study aims to explore the use of social media in older adults with multimorbidity in Hong Kong primary care and to assess the feasibility and usage of online health services in this population, including satisfaction, preference, and problems encountered. METHODS: This is a cross-sectional study among older adults with multimorbidity conducted between November 2020 and March 2021 in a Hong Kong primary care programme. Online and face-to-face services were offered based on the needs of the participants. Demographic characteristics and health conditions were assessed at baseline. Participants using online services were invited to complete a feedback questionnaire. RESULTS: The study included 752 participants, of which 66.1% use social media every day. Participants who declined to use online services were found to be significantly older, live alone, have lower income, have social security assistance, have greater cognitive decline, and be less depressed (p < 0.05). Non-responders to the online questionnaire had fewer years of education and greater cognitive decline (p < 0.05). The median satisfaction with the online services was 8 (interquartile range: 7, 9), and 14.6% of the participants preferred online more than face-to-face services. Lower education levels, fewer internet connection issues, and more self-efficacy on mobile apps were associated with a higher level of online satisfaction after adjustment (p < 0.05). Fewer internet connection issues and more self-efficacy on mobile apps were associated with participants' preference for online services (p < 0.05). CONCLUSIONS: More than half of Hong Kong older adults with multimorbidity in primary care use social media daily. Internet connection issues can be a significant barrier to the usage of online services in this population. Prior use and training can be beneficial to enhance use and satisfaction in older adults.

Association of positive and adverse childhood experiences with risky behaviours and mental health indicators among Chinese university students in Hong Kong: an exploratory study.

Background: Different childhood experiences may affect adult health differently. Objective: To explore the association of different types of positive childhood experiences(PCEs) and adverse childhood experiences (ACEs) with risky behaviours and mental health indicators, andhow PCEs and ACEs are associated with health outcomes in the context of each other. Method: This was an exploratory cross-sectional online survey including 332 university students in Hong Kong. ACEs (abuse and household challenges), PCEs (perceived safety, positive quality of life, and interpersonal support), risky behaviours (smoking, binge drinking, and sexual initiation), and mental health indicators(depression, anxiety, loneliness, self-rated health, multimorbidity, meaning in life, and life satisfaction)were measured. Results: The multivariable logistic regression analysis indicated cumulative effects of PCEs in lowered risks of depression, anxiety, loneliness, as well as better self-rated health, life satisfaction, and meaning in life (p < .05), after adjusting for ACEs. Results also indicated that ACEs had an increasing relationship with poorer mental health indicators, such as anxiety, loneliness, and life satisfaction (p < .05), after adjusting for PCEs. There was also an adverse association between having ≥4 ACEs with smoking and binge drinking. In addition, each type of PCE and ACE was significantly associated with one or more risky behaviours and mental health indicators. Stratified results showed that PCEs had stronger associations with mental health indicators in participants with fewer ACEs. Furthermore, ACEs had stronger associations with mental health indicators in participants with more PCEs than in those with fewer PCEs. Conclusions: In this study, PCE was proven to be an independent protective factor against poor mental health after accounting for ACE. ACE was also proven to be an independent risk factor for poor mental health and risky behaviours. These findings suggest a crucial need for the active promotion of PCEs and the prevention of child maltreatment. The results of subtypes and stratifications can be taken into consideration when developing targeted interventions in the future. HIGHLIGHTS: PCE is an independent protective factor against poor mental health after accounting for ACE. ACE is an independent risk factor for poor mental health and risky behaviours.PCEs and ACEs have different associations with health outcomes in the context of one another.

Antecedentes: Las diferentes experiencias de la infancia pueden afectar la salud de los adultos de manera diferente.Objetivo: Explorar la asociación de diferentes tipos de experiencias infantiles positivas (EIP) y experiencias infantiles adversas (EIA) con conductas de riesgo e indicadores de salud mental, y cómo las EIP y las EIA se asocian con resultados de salud en el contexto de cada uno.Método: Esta fue una encuesta transversal exploratoria en línea que incluyó a 332 estudiantes universitarios en Hong Kong. EIA (abuso y desafíos domésticos), EIP (seguridad percibida, calidad de vida positiva y apoyo interpersonal), comportamientos de riesgo (fumar, beber en exceso e iniciación sexual) e indicadores de salud mental (depresión, ansiedad, soledad, salud autoevaluada, multimorbilidad, sentido de la vida y satisfacción con la vida) fueron medidos.Resultados: El análisis de regresión logística multivariable indicó efectos acumulativos de EIP en disminuir el riesgo de depresión, ansiedad, soledad, así como mejor autoevaluación de la salud, satisfacción con la vida y sentido de la vida (p < 0,05), después de ajustar por EIA. Los resultados también indicaron que EIA tuvo una relación de incremento con indicadores de salud mental más deficientes, como ansiedad, soledad y satisfacción con la vida (p < 0,05), después de ajustar por EIP. También hubo una asociación adversa entre tener ≥4 EIA con fumar y beber en exceso. Además, cada tipo de EIP y EIA se asoció significativamente con uno o más comportamientos de riesgo e indicadores de salud mental. Los resultados estratificados mostraron que EIP tuvo asociaciones más fuertes con indicadores de salud mental en participantes con menos EIA. Además, EIA tuvo asociaciones más fuertes con indicadores de salud mental en participantes con más EIA que en aquellos con menos EIP.Conclusiones: En este estudio, se demostró que EIP es un factor protector independiente contra una pobre salud mental después de tomar en cuenta EIA. También se demostró que EIA es un factor de riesgo independiente para una pobre salud mental y comportamientos de riesgo. Estos hallazgos sugieren una necesidad crucial para la promoción activa de EIPs y la prevención del maltrato infantil. Los resultados de los subtipos y estratificaciones se pueden tener en cuenta al desarrollar intervenciones focalizadas en el futuro.

Recombinant Human Thymosin ß4 (rhTß4) Modulates the Anti-Inflammatory Responses to Alleviate Benzalkonium Chloride (BAC)-Induced Dry Eye Disease.

Dry eye disease (DED) is a multifactorial ocular disorder that interferes with daily living and reduces quality of life. However, there is no most ideal therapeutic treatment to address all the deleterious defects of DED. The purpose of this study was to investigate the ability of recombinant human thymosin ß4 (rhTß4) to promote healing in a benzalkonium chloride (BAC)-induced mice DED model and the anti-inflammatory effects involved in that process. Eye drops consisting of 0.05% and 0.1% rhTß4 were used for treatment of DED. Tear volume and corneal staining scores were measured after 7 days. Periodic acid-Schiff staining for gobleT cells in conjunctiva, immunohistochemical staining for CD4+ T cells, TUNEL assay for apoptotic positive cells in cornea and conjunctiva, qRT-PCR and ELISA assays for multiple cytokines were performed. All clinical parameters showed improvement in both the 0.05% and 0.1% rhTß4 groups. Specifically, topical application of rhTß4 significantly increased conjunctival gobleT cells and reduced apoptotic cells in conjunctiva. Mechanically, the rhTß4 groups showed significantly reduced inflammatory cytokine levels and CD4+ T cells in conjunctiva by blocking NF-κB (nuclear factor kappa B) activation, suggesting that 0.05-0.1% rhTß4 eye drops may be used as a potential therapeutic treatment for DED.

Primary School Students' Online Learning During Coronavirus Disease 2019: Factors Associated With Satisfaction, Perceived Effectiveness, and Preference.

Emergency online education has been adopted worldwide due to coronavirus disease 2019 (COVID-19) pandemic. Prior research regarding online learning predominantly focused on the perception of parents, teachers, and students in tertiary education, while younger children's perspectives have rarely been examined. This study investigated how family, school, and individual factors would be associated with primary school students' satisfaction, perceived effectiveness, and preference in online learning during COVID-19. A convenient sample of 781 Hong Kong students completed an anonymous online survey from June to October 2020. Logistic regression was conducted for 13 potential factors. Results indicated that only 57% of students were satisfied with their schools' online learning arrangement and 49.6% regarded the online learning as an effective learning mode. Only 12.8% of students preferred online learning, while 67.2% of students preferred in-person schooling. Multiple analyses suggested that teacher-student interaction during online classes was positively associated with students' satisfaction, perceived effectiveness, and preferences in online learning. Compared to grades 1-2 students, grades 3-6 students perceived more effectiveness and would prefer online learning. Happier schools were more likely to deliver satisfying and effective online education. Students who reported less happiness at school would prefer online learning, and students who reported less happiness at home would be less satisfied with online learning and reflected lower effectiveness. Teachers are encouraged to deliver more meaningful interactions to students and offer extra support to younger children during online classes. Primary schools and parents are encouraged to create a healthy and pleasant learning environment for children. The government may consider building up happy schools in the long run. The study findings are instrumental for policymakers, institutions, educators, and researchers in designing online education mechanisms.

Does It Matter Who You Live with during COVID-19 Lockdown? Association of Living Arrangements with Psychosocial Health, Life Satisfaction, and Quality of Life: A Pilot Study.

BACKGROUND: Living arrangements might greatly impact psychosocial health and quality of life, particularly during the COVID-19 lockdown. This pilot study aimed to examine the association of different common living arrangements with psychosocial health, life satisfaction, and quality of life among Chinese adults during the COVID-19 lockdown. METHODS: An anonymous online survey was conducted using convenience sampling through the WeChat application in February 2020. Mental health (Patient Health Questionnaire-2, Generalized Anxiety Disorder-2, post-traumatic stress disorder symptoms, Patient Health Questionnaire-15, and meaning in life), social health (UCLA-3), quality of life (EQ5D and EQ-VAS), and life satisfaction were measured. Linear regression models were used. RESULT: The study included 1245 adults (mean age: 34.14 ± 10.71) in China. Compared to other living arrangements, participants who "live with partner and children" or "live with partner, children and parents" were more likely to have better outcomes of mental health, social health, quality of life, and life satisfaction. Participants who "live with parents or grandparents" or "live with partner" were more likely to have better health outcomes compared with those who "live with children" or "live alone". CONCLUSION: Living with a partner, children, and/or parents could be a protective factor against poor psychosocial health during lockdown and quarantine.

Fenofibrate suppresses corneal neovascularization by regulating lipid metabolism through PPARα signaling pathway.

Purpose: The purpose of this study was to explore the potential underlying mechanism of anti-vascular effects of peroxisome proliferator-activated receptor α (PPARα) agonist fenofibrate against corneal neovascularization (CNV) through the changes of lipid metabolism during CNV. Methods: A suture-induced CNV model was established and the clinical indications were evaluated from day 1 to day 7. Treatments of vehicle and fenofibrate were performed for 5 days after suture and the CNV areas were compared among the groups. The eyeballs were collected for histological analysis, malondialdehyde (MDA) measurement, terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) staining, western blot, quantitative real-time PCR (qRT-PCR) assays and immunohistochemical (IHC) staining to elucidate pathological changes and the underlying mechanism. Results: Lipi-Green staining and MDA measurement showed that lipid deposition and peroxidation were increased in the CNV cornea while the expression of long-chain acyl-coenzyme A synthetase 1 (ACSL1), carnitine palmitoyltransterase 1A(CPT1A) and medium-chain acyl-coenzyme A dehydrogenase (ACADM), which are key enzymes of fatty acid ß-oxidation (FAO) and targeted genes of peroxisome proliferator-activated receptor alpha (PPARα) pathway, were decreased in CNV cornea. Fenofibrate suppressed lipid accumulation and peroxidation damage in the CNV cornea. Fenofibrate upregulated the expression levels of PPARα, ACSL1, CPT1A, and ACADM compared with vehicle group. IHC staining indicated that fenofibrate also decreased the expression of VEGFa, VEGFc, TNFα, IL1ß and CD68. Conclusion: Disorder of lipid metabolism may be involved in the formation of suture-induced CNV and fenofibrate played anti-neovascularization and anti-inflammatory roles on cornea by regulating the key enzymes of lipid metabolism and ameliorating lipid peroxidation damage of cornea through PPARα signaling pathway.

Autophagosomal Membrane Origin and Formation.

Autophagosome formation is a regulated membrane remodeling process, which involves the generation of autophagosomal membrane precursors (vesicles), the assembly of the autophagosomal membrane precursors to form the phagophore, and phagophore elongation to complete the autophagosome. The sources of the autophagosomal membrane precursors are endomembrane compartments, such as the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment (ERGIC), ER-exit sites (ERES), and endosomes. In response to stress, these structures are remodeled, to generate the early autophagosomal membrane precursors. The phagophore assembly site (PAS), which mainly localizes on the ER, harbors the site for autophagosomal membrane assembly, elongation, and completion. ATG proteins, membrane remodeling factors, and autophagic membranes follow a precise choreography to complete the overall process. In this chapter, we briefly discuss our current knowledge on the membrane origins of the autophagosome, as well as autophagosomal precursor generation, assembly, and expansion.

Comparison of Treatment Effect and Tolerance of the Topical Application of Mizoribine and Cyclosporine A in a Mouse Dry Eye Model.

Purpose: To compare the treatment effects and tolerability of a topical application of mizoribine (MZR) and cyclosporine A (CsA) eye drops (Restasis; Allergan, Inc., Irvine, CA, USA) in a mouse dry eye model. Methods: C57BL/6 mice subjected to desiccating stress (DS) were treated with 0.05% MZR in phosphate-buffered saline (PBS) or Restasis eye drops four times a day for 5 days. Untreated mice served as control. Tear secretion, Oregon green dextran staining, and the conjunctival goblet cell quantity were evaluated. The apoptosis and matrix metalloproteinase 9 (MMP-9) in the ocular surface, conjunctival CD4, and T helper-related cytokines were verified. The ocular tolerance of these two drugs was evaluated by observing the mice's behavioral changes. Results: Topical administrations of MZR or Restasis both increased tear production, maintained goblet cell density, and improved corneal barrier function. Both MZR and Restasis suppressed the expression of MMP-9 and apoptosis in the ocular surface. Meanwhile, both MZR and Restasis decreased the infiltration of CD4+ T cells, reversed the production of interferon-γ, interleukin (IL)-17A, and IL-13 in conjunctiva under DS. The abovementioned efficacies between these two eye drops were not statistically significant. However, the number of scratching and wiping behaviors in the MZR-treated group was significantly less than in the Restasis-treated group. Conclusions: MZR (0.05% in PBS) could be a good competitive product for Restasis because of the comparable treatment effect in dry eye diseases and better ocular tolerability in ocular itch and pain. Translational Relevance: This study provided an immunosuppressive agent comparable to Restasis for the treatment of dry eye disease.

Selenoprotein F knockout leads to glucose and lipid metabolism disorders in mice.

Selenoprotein F (Selenof), an endoplasmic reticulum (ER)-resident protein, is considered to be involved in glycoprotein folding and quality control in the ER. However, its function has not yet been thoroughly addressed. In this study, proteomics analysis revealed that Selenof deficiency in mice led to the differential expression of hepatic proteins associated with glucose and lipid metabolism. The phenotype analysis revealed that Selenof knockout mice showed glucose intolerance and insulin reduction, even with a normal diet. Additionally, Selenof knockout exacerbated high-fat diet-induced obesity, hyperglycemia, glucose intolerance, and hepatic steatosis. Furthermore, lipoprotein lipase and carboxylesterase 1D, two glycoproteins involved in lipid metabolism, were significantly decreased in the liver of Selenof knockout mice with a normal or high-fat diet. Collectively, these findings suggested that Selenof deficiency might cause the perturbation of glycoprotein quality control and thus contribute to glucose and lipid metabolism disorders, implying a novel biological function of Selenof.

Binless Kernel Machine: Modeling Spike Train Transformation for Cognitive Neural Prostheses.

Modeling spike train transformation among brain regions helps in designing a cognitive neural prosthesis that restores lost cognitive functions. Various methods analyze the nonlinear dynamic spike train transformation between two cortical areas with low computational eficiency. The application of a real-time neural prosthesis requires computational eficiency, performance stability, and better interpretation of the neural firing patterns that modulate target spike generation. We propose the binless kernel machine in the point-process framework to describe nonlinear dynamic spike train transformations. Our approach embeds the binless kernel to eficiently capture the feedforward dynamics of spike trains and maps the input spike timings into reproducing kernel Hilbert space (RKHS). An inhomogeneous Bernoulli process is designed to combine with a kernel logistic regression that operates on the binless kernel to generate an output spike train as a point process. Weights of the proposed model are estimated by maximizing the log likelihood of output spike trains in RKHS, which allows a global-optimal solution. To reduce computational complexity, we design a streaming-based clustering algorithm to extract typical and important spike train features. The cluster centers and their weights enable the visualization of the important input spike train patterns that motivate or inhibit output neuron firing. We test the proposed model on both synthetic data and real spike train data recorded from the dorsal premotor cortex and the primary motor cortex of a monkey performing a center-out task. Performances are evaluated by discrete-time rescaling Kolmogorov-Smirnov tests. Our model outperforms the existing methods with higher stability regardless of weight initialization and demonstrates higher eficiency in analyzing neural patterns from spike timing with less historical input (50%). Meanwhile, the typical spike train patterns selected according to weights are validated to encode output spike from the spike train of single-input neuron and the interaction of two input neurons.

Hepatic proteomic analysis of selenoprotein F knockout mice by iTRAQ: An implication for the roles of selenoprotein F in metabolism and diseases.

Selenoprotein F (Selenof) is an endoplasmic reticulum (ER)-resident protein. It may be functionally linked to glycoprotein folding in the ER but the detail function is not fully understood. To study the function of Selenof, we used CRISPR/Cas9 to generate Selenof knockout mice and performed proteomic analysis of hepatic proteins by iTRAQ. Collectively, 83 differently expressed proteins (DEPs) were identified in the liver of Selenof knockout mice. The changes of mRNA and protein levels of 6 selected DEPs, Fatty acid synthase, ATP-citrate synthase, Glutathione S-transferase P 1, Transformer-2 protein homolog beta, Pyruvate kinase, Metallothionein-2, were further verified by quantitative real-time PCR or Western blot. The roles of 83 DEPs are mainly related to metabolism and cancer. Consistently, the levels of NADPH and ATP, two molecules closely related to energy metabolism, are significantly changed in the livers of Selenof knockout mice. SIGNIFICANCE: Our study identified potential biological pathways and proteins related to Selenof deletion. These findings will provide possible proteins/pathways related to Selenof and help to understand the function of Selenof as well as the relationship between Selenof and certain diseases.

Invasive Brain Machine Interface System.

Because of high spatial-temporal resolution of neural signals obtained by invasive recording, the invasive brain-machine interfaces (BMI) have achieved great progress in the past two decades. With success in animal research, BMI technology is transferring to clinical trials for helping paralyzed people to restore their lost motor functions. This chapter gives a brief review of BMI development from animal experiments to human clinical studies in the following aspects: (1) BMIs based on rodent animals; (2) BMI based on non-human primates; and (3) pilot BMIs studies in clinical trials. In the end, the chapter concludes with a summary of potential opportunities and future challenges in BMI technology.

Brain-Machine Interface-Based Rat-Robot Behavior Control.

Brain-machine interface (BMI) provides a bidirectional pathway between the brain and external facilities. The machine-to-brain pathway makes it possible to send artificial information back into the biological brain, interfering neural activities and generating sensations. The idea of the BMI-assisted bio-robotic animal system is accomplished by stimulations on specific sites of the nervous system. With the technology of BMI, animals' locomotion behavior can be precisely controlled as robots, which made the animal turning into bio-robot. In this chapter, we reviewed our lab works focused on rat-robot navigation. The principles of rat-robot system have been briefly described first, including the target brain sites chosen for locomotion control and the design of remote control system. Some methodological advances made by optogenetic technologies for better modulation control have then been introduced. Besides, we also introduced our implementation of "mind-controlled" rat navigation system. Moreover, we have presented our efforts made on combining biological intelligence with artificial intelligence, with developments of automatic control and training system assisted with images or voices inputs. We concluded this chapter by discussing further developments to acquire environmental information as well as promising applications with write-in BMIs.

Design and Use of an Apparatus for Presenting Graspable Objects in 3D Workspace.

Reaching and grasping are highly-coupled movements, and their underlying neural dynamics have been widely studied in the last decade. To distinguish reaching and grasping encodings, it is essential to present different object identities independent of their positions. Presented here is the design of an automatic apparatus that is assembled with a turning table and three-dimensional (3D) translational device to achieve this goal. The turning table switches different objects corresponding to different grip types while the 3D translational device transports the turning table in 3D space. Both are driven independently by motors so that the target position and object are combined arbitrarily. Meanwhile, wrist trajectory and grip types are recorded via the motion capture system and touch sensors, respectively. Furthermore, representative results that demonstrate successfully trained monkey using this system are described. It is expected that this apparatus will facilitate researchers to study kinematics, neural principles, and brain-machine interfaces related to upper limb function.

Human Mind Control of Rat Cyborg's Continuous Locomotion with Wireless Brain-to-Brain Interface.

Brain-machine interfaces (BMIs) provide a promising information channel between the biological brain and external devices and are applied in building brain-to-device control. Prior studies have explored the feasibility of establishing a brain-brain interface (BBI) across various brains via the combination of BMIs. However, using BBI to realize the efficient multidegree control of a living creature, such as a rat, to complete a navigation task in a complex environment has yet to be shown. In this study, we developed a BBI from the human brain to a rat implanted with microelectrodes (i.e., rat cyborg), which integrated electroencephalogram-based motor imagery and brain stimulation to realize human mind control of the rat's continuous locomotion. Control instructions were transferred from continuous motor imagery decoding results with the proposed control models and were wirelessly sent to the rat cyborg through brain micro-electrical stimulation. The results showed that rat cyborgs could be smoothly and successfully navigated by the human mind to complete a navigation task in a complex maze. Our experiments indicated that the cooperation through transmitting multidimensional information between two brains by computer-assisted BBI is promising.

Longitudinal in vivo intrinsic optical imaging of cortical blood perfusion and tissue damage in focal photothrombosis stroke model.

A thorough understanding of the spatiotemporal dynamics of blood supply and tissue viability is of great importance in stroke researches. In the current study, vascular and cellular responses to focal ischemia were monitored with optical coherence tomography on chronic rat photothrombotic stroke model. The 3D mapping of blood perfusion and cellular scattering were achieved by analyzing the temporal dynamics and depth attenuation of intrinsic backscattered light respectively. Optical coherence tomography revealed that vessels of different types presented various spatial and temporal dynamics during the photothrombotic occlusion and the later recovery period. The large distal middle cerebral arteries presented a spontaneous recanalization and the small pial microvessels presented a reperfusion along with newly appeared vessels from the peripheral into the core area. The cortical capillary perfusion presented a weak recovery. Compared to the male group, the female rats showed a faster vascular recovery after photothrombotic. Moreover, the dynamic changes of the cellular scattering signal showed a high spatial and temporal correlation with the cortical capillary perfusion. Combined with well-designed photothrombotic stroke model and chronic optical window, optical coherence tomography imaging offers a unique approach to improve the understanding of stroke procedure and evaluate the treatment outcomes.

An automated behavioral apparatus to combine parameterized reaching and grasping movements in 3D space.

BACKGROUND: The neural principles underlying reaching and grasping movements have been studied extensively in primates for decades. However, few experimental apparatuses have been developed to enable a flexible combination of reaching and grasping in one task in three-dimensional (3D) space. NEW METHOD: By combining a custom turning table with a 3D translational device, we have developed a highly flexible apparatus that enables the subject to reach multiple positions in 3D space, and grasp differently shaped objects with multiple grip types in each position. Meanwhile, hand trajectory and grip types can be recorded via optical motion tracking cameras and touch sensors, respectively. RESULTS: We have used the apparatus to successfully train a macaque monkey to accomplish a visually-guided reach-to-grasp task, in which, six objects, fixed on the turning table, were grasped appropriately when they were transported to multiple positions in 3D space. A preliminary analysis of neural signals recorded in primary motor cortex, shows that plenty of neurons exhibit significant tuning to both target position and grip type. COMPARISON WITH EXISTING METHOD(S): Our apparatus realizes an arbitrary combination of parameterized reaching and grasping movements in a single task, which were usually separated or fixed in other systems. Meanwhile, the apparatus has high expansibility in terms of dynamic range, object shapes and applicable subjects. CONCLUSIONS: The apparatus provides a valuable platform to study upper limb functions in behavioral and neurophysiological studies, and may facilitate simultaneous reconstruction of reaching and grasping movements in brain-machine interfaces (BMIs).

Nonlinear Modeling of Neural Interaction for Spike Prediction Using the Staged Point-Process Model.

Neurons communicate nonlinearly through spike activities. Generalized linear models (GLMs) describe spike activities with a cascade of a linear combination across inputs, a static nonlinear function, and an inhomogeneous Bernoulli or Poisson process, or Cox process if a self-history term is considered. This structure considers the output nonlinearity in spike generation but excludes the nonlinear interaction among input neurons. Recent studies extend GLMs by modeling the interaction among input neurons with a quadratic function, which considers the interaction between every pair of input spikes. However, quadratic effects may not fully capture the nonlinear nature of input interaction. We therefore propose a staged point-process model to describe the nonlinear interaction among inputs using a few hidden units, which follows the idea of artificial neural networks. The output firing probability conditioned on inputs is formed as a cascade of two linear-nonlinear (a linear combination plus a static nonlinear function) stages and an inhomogeneous Bernoulli process. Parameters of this model are estimated by maximizing the log likelihood on output spike trains. Unlike the iterative reweighted least squares algorithm used in GLMs, where the performance is guaranteed by the concave condition, we propose a modified Levenberg-Marquardt (L-M) algorithm, which directly calculates the Hessian matrix of the log likelihood, for the nonlinear optimization in our model. The proposed model is tested on both synthetic data and real spike train data recorded from the dorsal premotor cortex and primary motor cortex of a monkey performing a center-out task. Performances are evaluated by discrete-time rescaled Kolmogorov-Smirnov tests, where our model statistically outperforms a GLM and its quadratic extension, with a higher goodness-of-fit in the prediction results. In addition, the staged point-process model describes nonlinear interaction among input neurons with fewer parameters than quadratic models, and the modified L-M algorithm also demonstrates fast convergence.

Rapid Decoding of Hand Gestures in Electrocorticography Using Recurrent Neural Networks.

Brain-computer interface (BCI) is a direct communication pathway between brain and external devices, and BCI-based prosthetic devices are promising to provide new rehabilitation options for people with motor disabilities. Electrocorticography (ECoG) signals contain rich information correlated with motor activities, and have great potential in hand gesture decoding. However, most existing decoders use long time windows, thus ignore the temporal dynamics within the period. In this study, we propose to use recurrent neural networks (RNNs) to exploit the temporal information in ECoG signals for robust hand gesture decoding. With RNN's high nonlinearity modeling ability, our method can effectively capture the temporal information in ECoG time series for robust gesture recognition. In the experiments, we decode three hand gestures using ECoG signals of two participants, and achieve an accuracy of 90%. Specially, we investigate the possibility of recognizing the gestures in a time interval as short as possible after motion onsets. Our method rapidly recognizes gestures within 0.5 s after motion onsets with an accuracy of about 80%. Experimental results also indicate that the temporal dynamics is especially informative for effective and rapid decoding of hand gestures.