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Many individuals with movement disorders are unable to make efficient use of graphical computer interfaces commonly employed in personal computers. In this study, performance limitations in target tracking with a computer mouse were studied for eight young subjects aged 19 to 29 (M=23, SD=3), four old subjects aged 70 to 73 (M=72, SD=1), and five motor-disabled subjects aged 37 to 74 (M=65, SD=16). Subjects tracked simple one- and two-dimensional motions at various frequencies. Performance was measured using an accuracy index derived from root-mean-square error, and a linearity index based on coherence estimation. A maximum bandwidth of 2 Hz for accuracy of mouse use was found, which often decreased due to advanced age or motor disability. Tracking linearity of all groups decreased as frequency increased. A significant degree of nonlinearity existed in all results (p<0.05), with disabled subjects nearing complete nonlinearity in two-dimensional tracking. The data show that with advanced age and disability, mouse use becomes increasingly inaccurate and nonlinear. Assistive computer interfacing techniques, such as signal filtering, may improve mouse use. [ABSTRACT FROM AUTHOR]

Seventy or so defibrillation trials were typically attempted to determine the relationship between defibrillation success rate and energy (DSRE). Clinically, it may be desirable to estimate the DSRE relationship with fewer trials. We used the statistical resampling technique called the 'bootstrap' to determine the number of defibrillation trials necessary for an accurate estimation of the DSRE relationship. The bootstrap technique assumes that the observed database is the maximum likelihood sample of the estimated population. The observed database is repeatedly resampled to produce a large bootstrap database and the bootstrap best estimate of a statistic is determined. DSRE data were obtained from ten dogs (20.5 ± 1.5 kg). We bootstrapped our experimental DSRE data by two methods: (1) randomly choosing with replacement a specified number of defibrillation trials per energy; and (2) randomly choosing with replacement a specified number of defibrillation trials per bootstrap replication. For both bootstrap techniques, 100 replications were made. We performed a linear regression analysis on the bootstrap success rates and the observed success rates determined from 71.0 ± 6.8 defibrillation attempts from each of the ten dogs. We concluded that 28 defibrillation trials are necessary to estimate the observed DSRE relationship with a correlation coefficient of 0.95. [ABSTRACT FROM AUTHOR]

Aim: We tested the hypothesis that early recovery of cortical SEP would be associated with milder hypoxic-ischemic injury and better outcome after resuscitation from CA.Methods: Sixteen adult male Wistar rats were subjected to asphyxial cardiac arrest. Half underwent 7min of asphyxia (Group CA7) and half underwent 9min (Group CA9). Continuous SEPs from median nerve stimulation were recorded from these rats for 4h immediately following CA, and at 24, 48, and 72h. Clinical recovery was evaluated using the Neurologic Deficit Scale.Results: All rats in group CA7 survived to 72h, while only 50% of rats in group CA9 survived to that time. Mean NDS values in the CA7 group at 24, 48, and 72h after CA were significantly higher than those of CA9. The N10 (first negative potential at 10ms) amplitude was significantly lower within 1h after CA in rats that suffered longer CA durations. SEPs were also analyzed by separating the rats into good (NDS>or=50) vs. bad (NDS<50) outcomes at 72h, again showing significant difference in N10 and peak-to-peak amplitudes between the two groups. In addition, a smaller N7 potential was consistently observed to recover earlier in all rats.Conclusions: The diminished recovery of N10 is associated with longer CA times in rats. Higher N10 and peak-to-peak amplitudes during early recovery are associated with better neurologic outcomes. N7, which may represent thalamic activity, recovers much earlier than cortical responses (N10), suggesting failure of thalamocortical conduction during early recovery. [ABSTRACT FROM AUTHOR]

Electroencephalographic reactivity (EEG-R) is a promising early predictor of arousal in comatose patients after cardiac arrest. Despite recent guidelines advocating for the integration of EEG-R into the multimodal prognostication model, EEG-R testing methods remain heterogeneous across studies. While efforts towards standardization have been made to reduce interrater variability by the development of quantitative approaches and machine learning models, future validation studies are needed to increase clinical applicability. Furthermore, the specific neurophysiological mechanisms and neuroanatomical correlates underlying EEG-R are not fully understood. In this narrative review, we explore the value and possible mechanisms of EEG-R, focusing on post-cardiac arrest comatose patients. We aim to discuss the current standard of knowledge and future directions, as well as elucidate possible implications for patient care and research., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Geocadin and Dr. Thakor are supported in part by cardiac arrest related grants from the National Institutes of Health (NIH) (UH3HL145269-04; RO1HL071568; RO1NS119825; RO1 NS 127959). Dr. Cho is funded by the NIH (K23HL157610). Dr. Habela is supported by the Doris Duke Foundation and the NIH Clinical Scientist Award (K08NS102526). Dr. Kaplan has been an expert witness on qEEG, a member of the ExCo of IFCN and receives royalties from publication from Wiley-Blackwell and Demos. Dr. Geocadin is a member of the Editorial Board of Resuscitation., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In the field of sensory neuroprostheses, one ultimate goal is for individuals to perceive artificial somatosensory information and use the prosthesis with high complexity that resembles an intact system. To this end, research has shown that stimulation-elicited somatosensory information improves prosthesis perception and task performance. While studies strive to achieve sensory integration, a crucial phenomenon that entails naturalistic interaction with the environment, this topic has not been commensurately reviewed. Therefore, here we present a perspective for understanding sensory integration in neuroprostheses. First, we review the engineering aspects and functional outcomes in sensory neuroprosthesis studies. In this context, we summarize studies that have suggested sensory integration. We focus on how they have used stimulation-elicited percepts to maximize and improve the reliability of somatosensory information. Next, we review studies that have suggested multisensory integration. These works have demonstrated that congruent and simultaneous multisensory inputs provided cognitive benefits such that an individual experiences a greater sense of authority over prosthesis movements (i.e., agency) and perceives the prosthesis as part of their own (i.e., ownership). Thereafter, we present the theoretical and neuroscience framework of sensory integration. We investigate how behavioral models and neural recordings have been applied in the context of sensory integration. Sensory integration models developed from intact-limb individuals have led the way to sensory neuroprosthesis studies to demonstrate multisensory integration. Neural recordings have been used to show how multisensory inputs are processed across cortical areas. Lastly, we discuss some ongoing research and challenges in achieving and understanding sensory integration in sensory neuroprostheses. Resolving these challenges would help to develop future strategies to improve the sensory feedback of a neuroprosthetic system., (© 2024. International Federation for Medical and Biological Engineering.)

Background: Somatosensory evoked potentials (SEPs) are highly specific predictors of poor prognosis in hypoxic-ischemic coma when cortical responses (N20s) are absent. However, bilateral N20 presence is nonspecific for good outcomes. High-frequency oscillations (HFOs) in the SEP waveform predict neurologic recovery in animals, but clinical applications are poorly understood. We sought to develop a clinical measure of HFOs to potentially improve detection of good outcomes in coma., Materials and Methods: We collected SEP waveform data from all comatose inpatients (GCS<=8) who underwent neurologic prognostication from 2020 to 2022 at Johns Hopkins Hospital. We developed a novel measure - HFO evoked to spontaneous ratios (HFO-ESRs) - and applied this to those patients with bilaterally present N20s using both standard univariate classification and cubic kernal vector machine (SVM) models to predict the last documented in-hospital Glasgow Coma Scale (GCS) prior to discharge or death., Results: Of 58 total patients, 34 (58.6%) had bilaterally present N20s. Of these, 14 had final GCS>=9, and 20 had final GCS<=8. Mean age was 52 (+/- 17) years, 20.1% female. Etiologies of coma were primarily global hypoxic-ischemic brain injury (79.4%), intracranial hemorrhage (11.8%), and traumatic brain injury (2.9%). In univariate classification, the addition of averaged HFO-ESRs to bilaterally present N20s predicted final GCS>=9 with 68% specificity. The SVM model further improved specificity to 85%., Conclusions: In this pilot investigation, we developed a novel clinical measure of SEP HFOs. Incorporation of this measure may improve the specificity of the SEP to predict in-hospital GCS outcomes in coma, but requires further validation in specific neurologic injuries and with longitudinal outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The study of autonomic responses to cardiac arrest (CA) resuscitation deserves attention due to the impact of autonomic function on survival and arousal. Orexins are known to modulate autonomic function, but the role of endogenous orexin in hyperacute recovery of autonomic function post-resuscitation is not well understood. We hypothesized that endogenous orexin facilitates hyperacute cardiovascular sympathetic activity post-resuscitation, and this response could be attenuated by suvorexant, a dual orexin receptor antagonist., Methods: A well-established 7-min asphyxial CA rat model was studied. Heart rate (HR) and blood pressure were monitored from baseline to 90-min post-resuscitation. Autonomic function was evaluated by spectral analysis of HR variability, whereby the ratio of low- and high-frequency components (LF/HF ratio) represents the balance between sympathetic/parasympathetic activities. Plasma orexin-A levels and orexin receptors immunoreactivity in the rostral ventrolateral medulla (RVLM), the key central region for regulating sympathetic output, were measured post-resuscitation. Neurological outcome was assessed via neurologic-deficit score at 4-h post-resuscitation., Key Results: A significant increase in HR was found over 25-40 min post-resuscitation ( p < 0.01 vs. baseline), which was attenuated by suvorexant significantly ( p < 0.05). Increased HR (from 15-to 25-min post-resuscitation) was correlated with better neurological outcomes ( rs = 0.827, p = 0.005). There was no evident increase in mean arterial pressure over 25-40 min post-resuscitation, while systolic pressure was reduced greatly by suvorexant ( p < 0.05). The LF/HF ratio was higher in animals with favorable outcomes than in animals injected with suvorexant over 30-40 min post-resuscitation ( p < 0.05). Plasma orexin-A levels elevated at 15-min and peaked at 30-min post-resuscitation ( p < 0.01 vs. baseline). Activated orexin receptors-immunoreactive neurons were found co-stained with tyrosine hydroxylase-immunopositive cells in the RVLM at 2-h post-resuscitation., Conclusion: Together, increased HR and elevated LF/HF ratio indicative of sympathetic arousal during a critical window (25-40 min) post-resuscitation are observed in animals with favorable outcomes. The orexin system appears to facilitate this hyperacute autonomic response post- CA., Competing Interests: The authors declared that this study was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Guo, Gharibani, Agarwal, Modi, Cho, Thakor and Geocadin.)

Introduction: Muscle reinnervation (MR) surgery offers rehabilitative benefits to amputees by taking severely damaged nerves and providing them with new denervated muscle targets (DMTs). However, the influence of physical changes to muscle tissue during MR surgery on long-term functional outcomes remains understudied. Methods: Our rat hindlimb model of MR surgery utilizes vascularized, directly neurotized DMTs made from the lateral gastrocnemius (LG), which we employed to assess the impact of muscle tissue size on reinnervation outcomes, specifically pairing the DMT with the transected peroneal nerve. We conducted MR surgery with both DMTs at full volume and DMTs with partial volume loss of 500 mg at the time of surgery ( n = 6 per group) and measured functional outcomes after 100 days of reinnervation. Compound motor action potentials (CMAPs) and isometric tetanic force production was recorded from reinnervated DMTs and compared to contralateral naïve LG muscles as positive controls. Results: Reinnervated DMTs consistently exhibited lower mass than positive controls, while DMTs with partial volume loss showed no significant mass reduction compared to full volume DMTs ( p = 0.872). CMAP amplitudes were lower on average in reinnervated DMTs, but a broad linear correlation also exists between muscle mass and maximum CMAP amplitude irrespective of surgical group (R 2 = 0.495). Surprisingly, neither MR group, with or without volume loss, demonstrated decreased force compared to positive controls. The average force output of reinnervated DMTs, as a fraction of the contralateral LG's force output, approached 100% for both MR groups, a notable deviation from the 9.6% (±6.3%) force output observed in our negative control group at 7 days post-surgery. Tissue histology analysis revealed few significant differences except for a marked decrease in average muscle fiber area of reinnervated DMTs with volume loss compared to positive controls ( p = 0.001). Discussion: The results from our rat model of MR suggests that tissue electrophysiology (CMAPs) and kinesiology (force production) may recover on different time scales, with volumetric muscle loss at the time of MR surgery not significantly reducing functional outcome measurements for the DMTs after 100 days of reinnervation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lowe, Rivera Santana, Bopp, Quinn, Johnson, Ward, Chung, Tuffaha and Thakor.)

After an amputation, advanced prosthetic limbs can be used to interface with the nervous system and restore motor function. Despite numerous breakthroughs in the field, many of the recent research advancements have not been widely integrated into clinical practice. This review highlights recent innovations in neuromuscular implants-specifically those that interface with skeletal muscle-which could improve the clinical translation of prosthetic technologies. Skeletal muscle provides a physiologic gateway to harness and amplify signals from the nervous system. Recent surgical advancements in muscle reinnervation surgeries leverage the "bio-amplification" capabilities of muscle, enabling more intuitive control over a greater number of degrees of freedom in prosthetic limbs than previously achieved. We anticipate that state-of-the-art implantable neuromuscular interfaces that integrate well with skeletal muscle and novel surgical interventions will provide a long-term solution for controlling advanced prostheses. Flexible electrodes are expected to play a crucial role in reducing foreign body responses and improving the longevity of the interface. Additionally, innovations in device miniaturization and ongoing exploration of shape memory polymers could simplify surgical procedures for implanting such interfaces. Once implanted, wireless strategies for powering and transferring data from the interface can eliminate bulky external wires, reduce infection risk, and enhance day-to-day usability. By outlining the current limitations of neuromuscular interfaces along with potential future directions, this review aims to guide continued research efforts and future collaborations between engineers and specialists in the field of neuromuscular and musculoskeletal medicine., (© 2023 Wiley Periodicals LLC.)

Background: Tremors are involuntary rhythmic movements commonly present in neurological diseases such as Parkinson's disease, essential tremor, and multiple sclerosis. Intention tremor is a subtype associated with lesions in the cerebellum and its connected pathways, and it is a common symptom in diseases associated with cerebellar pathology. While clinicians traditionally use tests to identify tremor type and severity, recent advancements in wearable technology have provided quantifiable ways to measure movement and tremor using motion capture systems, app-based tasks and tools, and physiology-based measurements. However, quantifying intention tremor remains challenging due to its changing nature., Methodology & Results: This review examines the current state of upper limb tremor assessment technology and discusses potential directions to further develop new and existing algorithms and sensors to better quantify tremor, specifically intention tremor. A comprehensive search using PubMed and Scopus was performed using keywords related to technologies for tremor assessment. Afterward, screened results were filtered for relevance and eligibility and further classified into technology type. A total of 243 publications were selected for this review and classified according to their type: body function level: movement-based, activity level: task and tool-based, and physiology-based. Furthermore, each publication's methods, purpose, and technology are summarized in the appendix table., Conclusions: Our survey suggests a need for more targeted tasks to evaluate intention tremors, including digitized tasks related to intentional movements, neurological and physiological measurements targeting the cerebellum and its pathways, and signal processing techniques that differentiate voluntary from involuntary movement in motion capture systems., (© 2024. The Author(s).)

Ultrasound technology can provide high-resolution imaging of blood flow following spinal cord injury (SCI). Blood flow imaging may improve critical care management of SCI, yet its duration is limited clinically by the amount of contrast agent injection required for high-resolution, continuous monitoring. In this study, we aim to establish non-contrast ultrasound as a clinically translatable imaging technique for spinal cord blood flow via comparison to contrast-based methods and by measuring the spatial distribution of blood flow after SCI. A rodent model of contusion SCI at the T12 spinal level was carried out using three different impact forces. We compared images of spinal cord blood flow taken using both non-contrast and contrast-enhanced ultrasound. Subsequently, we processed the images as a function of distance from injury, yielding the distribution of blood flow through space after SCI, and found the following. (1) Both non-contrast and contrast-enhanced imaging methods resulted in similar blood flow distributions (Spearman's ρ = 0.55, p < 0.0001). (2) We found an area of decreased flow at the injury epicenter, or umbra (p < 0.0001). Unexpectedly, we found increased flow at the periphery, or penumbra (rostral, p < 0.05; caudal, p < 0.01), following SCI. However, distal flow remained unchanged, in what is presumably unaffected tissue. (3) Finally, tracking blood flow in the injury zones over time revealed interesting dynamic changes. After an initial decrease, blood flow in the penumbra increased during the first 10 min after injury, while blood flow in the umbra and distal tissue remained constant over time. These results demonstrate the viability of non-contrast ultrasound as a clinical monitoring tool. Furthermore, our surprising observations of increased flow in the injury periphery pose interesting new questions about how the spinal cord vasculature reacts to SCI, with potentially increased significance of the penumbra., (© 2024. The Author(s).)

Background: Tension in the spinal cord is a trademark of tethered cord syndrome. Unfortunately, existing tests cannot quantify tension across the bulk of the cord, making the diagnostic evaluation of stretch ambiguous. A potential non-destructive metric for spinal cord tension is ultrasound-derived shear wave velocity (SWV). The velocity is sensitive to tissue elasticity and boundary conditions including strain. We use the term Ultrasound Tensography to describe the acoustic evaluation of tension with SWV., Methods: Our solution Tethered cord Assessment with Ultrasound Tensography (TAUT) was utilized in three sub-studies: finite element simulations, a cadaveric benchtop validation, and a neurosurgical case series. The simulation computed SWV for given tensile forces. The cadaveric model with induced tension validated the SWV-tension relationship. Lastly, SWV was measured intraoperatively in patients diagnosed with tethered cords who underwent treatment (spinal column shortening). The surgery alleviates tension by decreasing the vertebral column length., Results: Here we observe a strong linear relationship between tension and squared SWV across the preclinical sub-studies. Higher tension induces faster shear waves in the simulation (R 2  = 0.984) and cadaveric (R 2  = 0.951) models. The SWV decreases in all neurosurgical procedures (p < 0.001). Moreover, TAUT has a c-statistic of 0.962 (0.92-1.00), detecting all tethered cords., Conclusions: This study presents a physical, clinical metric of spinal cord tension. Strong agreement among computational, cadaveric, and clinical studies demonstrates the utility of ultrasound-induced SWV for quantitative intraoperative feedback. This technology is positioned to enhance tethered cord diagnosis, treatment, and postoperative monitoring as it differentiates stretched from healthy cords., (© 2024. The Author(s).)

Objective: There is a complex interaction between nervous and cardiovascular systems, but sparse data exist on brain-heart electrophysiological responses to cardiac arrest resuscitation. Our aim was to investigate dynamic changes in autonomic and cortical function during hyperacute stage post-resuscitation., Methods: Ten rats were resuscitated from 7-min cardiac arrest, as indicators of autonomic response, heart rate (HR), and its variability (HRV) were measured. HR was monitored through continuous electrocardiography, while HRV was assessed via spectral analysis, whereby the ratio of low-/high-frequency (LF/HF) power indicates the balance between sympathetic/parasympathetic activities. Cortical response was evaluated by continuous electroencephalography and quantitative analysis. Parameters were quantified at 5-min intervals over the first-hour post-resuscitation. Neurological outcome was assessed by Neurological Deficit Score (NDS, range 0-80, higher = better outcomes) at 4-h post-resuscitation., Results: A significant increase in HR was noted over 15-30 min post-resuscitation (p < 0.01 vs.15-min, respectively) and correlated with higher NDS (rs = 0.56, p < 0.01). LF/HF ratio over 15-20 min was positively correlated with NDS (rs = 0.75, p < 0.05). Gamma band power surged over 15-30 min post-resuscitation (p < 0.05 vs. 0-15 min, respectively), and gamma band fraction during this period was associated with NDS (rs ≥0.70, p < 0.05, respectively). Significant correlations were identified between increased HR and gamma band power during 15-30 min (rs ≥0.83, p < 0.01, respectively) and between gamma band fraction and LF/HF ratio over 15-20 min post-resuscitation (rs = 0.85, p < 0.01)., Interpretations: Hyperacute recovery of autonomic and cortical function is associated with favorable functional outcomes. While this observation needs further validation, it presents a translational opportunity for better autonomic and neurologic monitoring during early periods post-resuscitation to develop novel interventions., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Tissue elasticity remains an essential biomarker of health and is indicative of irregularities such as tumors or infection. The timely detection of such abnormalities is crucial for the prevention of disease progression and complications that arise from late-stage illnesses. However, at both the bedside and the operating table, there is a distinct lack of tactile feedback for deep-seated tissue. As surgical techniques advance toward remote or minimally invasive options to reduce infection risk and hasten healing time, surgeons lose the ability to manually palpate tissue. Furthermore, palpation of deep structures results in decreased accuracy, with the additional barrier of needing years of experience for adequate confidence of diagnoses. This review delves into the current modalities used to fulfill the clinical need of quantifying physical touch. It covers research efforts involving tactile sensing for remote or minimally invasive surgeries, as well as the potential of ultrasound elastography to further this field with non-invasive real-time imaging of the organ's biomechanical properties. Elastography monitors tissue response to acoustic or mechanical energy and reconstructs an image representative of the elastic profile in the region of interest. This intuitive visualization of tissue elasticity surpasses the tactile information provided by sensors currently used to augment or supplement manual palpation. Focusing on common ultrasound elastography modalities, we evaluate various sensing mechanisms used for measuring tactile information and describe their emerging use in clinical settings where palpation is insufficient or restricted. With the ongoing advancements in ultrasound technology, particularly the emergence of micromachined ultrasound transducers, these devices hold great potential in facilitating early detection of tissue abnormalities and providing an objective measure of patient health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Kumar, Kempski Leadingham, Kerensky, Sankar, Thakor and Manbachi.)

Objective: Our study defines a novel electrode placement method called Functionally Adaptive Myosite Selection (FAMS), as a tool for rapid and effective electrode placement during prosthesis fitting. We demonstrate a method for determining electrode placement that is adaptable towards individual patient anatomy and desired functional outcomes, agnostic to the type of classification model used, and provides insight into expected classifier performance without training multiple models., Methods: FAMS relies on a separability metric to rapidly predict classifier performance during prosthesis fitting., Results: The results show a predictable relationship between the FAMS metric and classifier accuracy (3.45%SE), allowing estimation of control performance with any given set of electrodes. Electrode configurations selected using the FAMS metric show improved control performance ( ) for target electrode counts compared to established methods when using an ANN classifier, and equivalent performance ( R 2 ≥ .96) to previous top-performing methods on an LDA classifier, with faster convergence ( ). We used the FAMS method to determine electrode placement for two amputee subjects by using the heuristic to search through possible sets, and checking for saturation in performance vs electrode count. The resulting configurations that averaged 95.8% of the highest possible classification performance using a mean 25 number of electrodes (19.5% of the available sites)., Significance: FAMS can be used to rapidly approximate the tradeoffs between increased electrode count and classifier performance, a useful tool during prosthesis fitting.

Cerebral vascular autoregulation is impaired following resuscitation from cardiac arrest (CA), and its quantification may allow assessing CA-induced brain injury. However, hyperemia occurring immediately post-resuscitation limits the application of most metrics that quantify autoregulation. Therefore, to characterize autoregulation during this critical period, we developed three novel metrics based on how the cerebrovascular resistance (CVR) covaries with changes in cerebral perfusion pressure (CPP): (i) θ CVR , which quantifies the CVR vs CPP gradient, (ii) a CVR-based transfer function analysis, and (iii) CVRx, the correlation coefficient between CPP and CVR. We tested these metrics in a model of asphyxia induced CA and resuscitation using seven adult male Wistar rats. Mean arterial pressure (MAP) and cortical blood flow recorded for 30 min post-resuscitation via arterial cannulation and laser speckle contrast imaging, were used as surrogates of CPP and cerebral blood flow (CBF), while CVR was computed as the CPP/CBF ratio. Using our metrics, we found that the status of cerebral vascular autoregulation altered substantially during hyperemia, with changes spread throughout the 0-0.05 Hz frequency band. Our metrics push the boundary of how soon autoregulation can be assessed, and if validated against outcome markers, may help develop a reliable metric of brain injury post-resuscitation., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background: Virtual and augmented reality (AR) have become popular modalities for training myoelectric prosthesis control with upper-limb amputees. While some systems have shown moderate success, it is unclear how well the complex motor skills learned in an AR simulation transfer to completing the same tasks in physical reality. Limb loading is a possible dimension of motor skill execution that is absent in current AR solutions that may help to increase skill transfer between the virtual and physical domains., Methods: We implemented an immersive AR environment where individuals could operate a myoelectric virtual prosthesis to accomplish a variety of object relocation manipulations. Intact limb participants were separated into three groups, the load control (CG LD ; [Formula: see text]), the AR control (CG AR ; [Formula: see text]), and the experimental group (EG; [Formula: see text]). Both the CG AR and EG completed a 5-session prosthesis training protocol in AR while the CG LD performed simple muscle training. The EG attempted manipulations in AR while undergoing limb loading. The CG AR attempted the same manipulations without loading. All participants performed the same manipulations in physical reality while operating a real prosthesis pre- and post-training. The main outcome measure was the change in the number of manipulations completed during the physical reality assessments (i.e. completion rate). Secondary outcomes included movement kinematics and visuomotor behavior., Results: The EG experienced a greater increase in completion rate post-training than both the CG AR and CG LD . This performance increase was accompanied by a shorter motor learning phase, the EG's performance saturating in less sessions of AR training than the CG AR ., Conclusion: The results demonstrated that limb loading plays an important role in transferring complex motor skills learned in virtual spaces to their physical reality analogs. While participants who did not receive limb loading were able to receive some functional benefit from AR training, participants who received the loading experienced a greater positive change in motor performance with their performance saturating in fewer training sessions., (© 2023. The Author(s).)

Cardiac arrest (CA) remains the leading cause of coma, and early arousal recovery indicators are needed to allocate critical care resources properly. High-frequency oscillations (HFOs) of somatosensory evoked potentials (SSEPs) have been shown to indicate responsive wakefulness days following CA. Nonetheless, their potential in the acute recovery phase, where the injury is reversible, has not been tested. We hypothesize that time-frequency (TF) analysis of HFOs can determine arousal recovery in the acute recovery phase. To test our hypothesis, eleven adult male Wistar rats were subjected to asphyxial CA (five with 3-min mild and six with 7-min moderate to severe CA) and SSEPs were recorded for 60 min post-resuscitation. Arousal level was quantified by the neurological deficit scale (NDS) at 4 h. Our results demonstrated that continuous wavelet transform (CWT) of SSEPs localizes HFOs in the TF domain under baseline conditions. The energy dispersed immediately after injury and gradually recovered. We proposed a novel TF-domain measure of HFO: the total power in the normal time-frequency space (NTFS) of HFO. We found that the NTFS power significantly separated the favorable and unfavorable outcome groups. We conclude that the NTFS power of HFOs provides earlier and objective determination of arousal recovery after CA.

Touch-like phantom limb sensations can be elicited through targeted transcutaneous electrical nerve stimulation (tTENS) in individuals with upper limb amputation. The corresponding impact of sensory stimulation on cortical activity remains an open question. Brain network research shows that sensorimotor cortical activity is supported by dynamic changes in functional connections between relevant brain regions. These groups of interconnected regions are functional modules whose architecture enables specialized function and related neural processing supporting individual task needs. Using electroencephalographic (EEG) signals to analyze modular functional connectivity, we investigated changes in the modular architecture of cortical large-scale systems when participants with upper limb amputations performed phantom hand movements before, during, and after they received tTENS. We discovered that tTENS substantially decreased the flexibility of the default mode network (DMN). Furthermore, we found increased interconnectivity (measured by a graph theoretic integration metric) between the DMN, the somatomotor network (SMN) and the visual network (VN) in the individual with extensive tTENS experience. While for individuals with less tTENS experience, we found increased integration between DMN and the attention network. Our results provide insights into how sensory stimulation promotes cortical processing of combined somatosensory and visual inputs and help develop future tools to evaluate sensory combination for individuals with amputations., (© 2022. The Author(s).)

The poor translation of nanomedicines from bench to bedside can be attributed to (i) lack of a delivery system with precise drug compositions with no batch-to-batch variations, (ii) off-target or undesirable release of payload, and (iii) lack of a method to monitor the fate of the specific drug of interest, which often has to be modified with a fluorescent tag or replaced with a model drug which can be tracked. To overcome these translation hurdles, we developed dual responsive organelle targeted nanoreactors (DRONEs) with precise drug composition, site specific payload release and which enable accurate in-vivo monitoring. DRONEs consist of a polyprodrug inner core composed of a dual responsive backbone containing a photosensitizer (Protoporphyrin IX) grafted with functionalized polyethylene glycol (PEG) outer shell to prolong blood circulation and a tumour homing pro-apoptotic peptide (CGKRK D [KLAKLAK] 2 ) (THP). DRONEs can significantly reduce the tumour burden in an orthotopic glioblastoma model due to its BBB penetrating and tumour homing capabilities. DRONEs exhibit good safety profile and biocompatibility along with a reliable route of elimination. DRONEs showed great potential as an in-situ vaccine which can not only eliminate the tumour but also trigger an adaptive immune response which would provide long-term anti-tumoural immunity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Olfactory hedonic evaluation is the primary dimension of olfactory perception and thus central to our sense of smell. It involves complex interactions between brain regions associated with sensory, affective and reward processing. Despite a recent increase in interest, several aspects of olfactory hedonic evaluation remain ambiguous: uncertainty surrounds the communication between, and interaction among, brain areas during hedonic evaluation of olfactory stimuli with different levels of pleasantness, as well as the corresponding supporting oscillatory mechanisms. In our study we investigated changes in functional interactions among brain areas in response to odor stimuli using electroencephalography (EEG). To this goal, functional connectivity networks were estimated based on phase synchronization between EEG signals using the weighted phase lag index (wPLI). Graph theoretic metrics were subsequently used to quantify the resulting changes in functional connectivity of relevant brain regions involved in olfactory hedonic evaluation. Our results indicate that odor stimuli of different hedonic values evoke significantly different interaction patterns among brain regions within the olfactory cortex, as well as in the anterior cingulate and orbitofrontal cortices. Furthermore, significant hemispheric laterality effects have been observed in the prefrontal and anterior cingulate cortices, specifically in the beta ((13-30) Hz) and gamma ((30-40) Hz) frequency bands.

Objective: Necrotizing enterocolitis (NEC) is the most prevalent gastrointestinal emergency in premature infants and is characterized by a dysfunctional gut microcirculation. Therefore, there is a dire need for in vivo methods to characterize NEC-induced changes in the structure and function of the gut microcirculation, that is, its vascular phenotype. Since in vivo gut imaging methods are often slow and employ a single-contrast mechanism, we developed a rapid multicontrast imaging technique and a novel analyses pipeline for phenotyping the gut microcirculation., Methods: Using an experimental NEC model, we acquired in vivo images of the gut microvasculature and blood flow over a 5000 × 7000 μm 2 field of view at 5 μm resolution via the following two endogenous contrast mechanisms: intrinsic optical signals and laser speckles. Next, we transformed intestinal images into rectilinear "flat maps," and delineated 1A/V gut microvessels and their perfusion territories as "intestinal vascular units" (IVUs). Employing IVUs, we quantified and visualized NEC-induced changes to the gut vascular phenotype., Results: In vivo imaging required 60-100 s per animal. Relative to the healthy gut, NEC intestines showed a significant overall decrease (i.e. 64-72%) in perfusion, accompanied by vasoconstriction (i.e. 9-12%) and a reduction in perfusion entropy (19%)within sections of the vascular bed., Conclusions: Multicontrast imaging coupled with IVU-based in vivo vascular phenotyping is a powerful new tool for elucidating NEC pathogenesis., (© 2022 The Authors. Microcirculation published by John Wiley & Sons Ltd.)

Imaging of spinal cord microvasculature holds great potential in directing critical care management of spinal cord injury (SCI). Traditionally, contrast agents are preferred for imaging of the spinal cord vasculature, which is disadvantageous for long-term monitoring of injury. Here, we present FlowMorph, an algorithm that uses mathematical morphology techniques to segment non-contrast Doppler-based videos of rat spinal cord. Using the segmentation, it measures single-vessel parameters such as flow velocity, rate, and radius, with visible cardiac cycles in individual vessels showcasing the spatiotemporal resolution. The segmentation outlines vessels well with little extraneous labeling, and outlines are smooth through time. Radius measurements of perforating vessels are similar to what is seen in the literature through other methods. Verification of the algorithm through comparison to manual measurement and in vitro microphantom standards highlights points of future improvement. This method will be vital for future work studying the vascular effects of SCI and can be adopted to other species as well.

Background: Cerebral blood flow (CBF) plays an important role in neurological recovery after cardiac arrest (CA) resuscitation. However, the variations of CBF recovery in distinct brain regions and its correlation with neurologic recovery after return of spontaneous circulation (ROSC) have not been characterized. This study aimed to investigate the characteristics of regional cerebral reperfusion following resuscitation in predicting neurological recovery., Methods: Twelve adult male Wistar rats were studied, ten resuscitated from 7-min asphyxial CA and two uninjured rats, which were designated as healthy controls (HCs). Dynamic changes in CBF in the cerebral cortex, hippocampus, thalamus, brainstem, and cerebellum were assessed by pseudocontinuous arterial spin labeling magnetic resonance imaging, starting at 60 min after ROSC to 156 min (or time to spontaneous arousal). Neurologic outcomes were evaluated by the neurologic deficit scale at 24 h post-ROSC in a blinded manner. Correlations between regional CBF (rCBF) and neurological recovery were undertaken., Results: All post-CA animals were found to be nonresponsive during the 60-156 min post ROSC, with reductions in rCBF by 24-42% compared with HC. Analyses of rCBF during the post-ROSC time window from 60 to 156 min showed the rCBF recovery of hippocampus and thalamus were positively associated with better neurological outcomes (rs = 0.82, p = 0.004 and rs = 0.73, p < 0.001, respectively). During 96 min before arousal, thalamic and cortical rCBF exhibited positive correlations with neurological recovery (rs = 0.80, p < 0.001 and rs = 0.65, p < 0.001, respectively); for predicting a favorable neurological outcome, the thalamic rCBF threshold was above 50.84 ml/100 g/min (34% of HC) (area under the curve of 0.96), whereas the cortical rCBF threshold was above 60.43 ml/100 g/min (38% of HC) (area under the curve of 0.88)., Conclusions: Early magnetic resonance imaging analyses showed early rCBF recovery in thalamus, hippocampus, and cortex post ROSC was positively correlated with neurological outcomes at 24 h. Our findings suggest new translational insights into the regional reperfusion and the time window that may be critical in neurological recovery and warrant further validation., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Olfactory perception is shaped by dynamic in-teractions among networks of widely distributed brain regions involved in several neurocognitive processes. However, the neural mechanisms that enable effective coordination and integrative processing across these brain regions, which have different functions and operating characteristics, are not yet fully understood. In this study we use electroencephalography (EEG) signals and a multilayer network formalism to model cross-frequency coupling across the brain and identify brain regions that operate as connecting hubs, thus facilitating inte-grative function. To this goal, we investigate α-γ coupling and θ-γ coupling during exposure to olfactory stimuli of different pleasantness levels. We found that a wider distributed network of hubs emerges in the higher pleasantness condition and that significant differences in the hub connectivity are located in the middle frontal and central regions. Our results indicate the consistent functional role that γ band activity plays in information integration in olfactory perception.

With the advent of autonomous driving, the issue of human intervention during safety-critical events is an urgent topic of research. Supervisory monitoring, taking over vehicle control during automation failures and then bringing the vehicle to safety under time pressure are cognitively demanding tasks that pose varying difficulties across the driving population. This underpins a need to investigate individual differences (i.e., how people differ in their dispositional traits) in driver responses to automation system limits, so that autonomous vehicle design can be tailored to meet the safety-critical needs of higher-risk drivers. However, few studies thus far have examined individual differences, with self-report measures showing limited ability to predict driver takeover performance. To address this gap, the present study explored the utility of an established brain activity-based objective index of trait attentional control (frontal theta/beta ratio; TBR) in predicting driver interactions with conditional automation. Frontal TBR predicted drivers' average takeover reaction time, as well as the likelihood of accident after takeover. Moving towards practical applications, this study also demonstrated the utility of streamlined estimates of frontal TBR measured from the forehead electrodes and from a single crown electrode, with the latter showing better fidelity and predictive value. Overall, TBR is behaviourally relevant, measurable with minimal sensors and easily computable, rendering it a promising candidate for practical and objective assessment of drivers' neurocognitive traits that contribute to their AV driving readiness., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Peripheral neural interface (PNI) with a stable integration of synthetic elements with neural tissue is key for successfulneuro-prosthetic applications. An inevitable phenomenon of reactive fibrosis is a primary hurdle for long term functionality of PNIs. This proof-of-concept study aimed to fabricate and test a novel, stable PNI that harnesses fibro-axonal outgrowth at the nerve end and includes fibrosis in the design., Methods: Two non-human primates were implanted with Substrate-guided, Tissue-Electrode Encapsulation and Integration (STEER) PNIs. The implant included a 3D printed guide that strove to steer the regrowing nerve towards encapsulation of the electrodes into a fibro-axonal tissue. After four months from implantation, we performed electrophysiological measurements to test STEER's functionality and examined the macro and micro- morphology of the outgrowth tissue., Results: We observed a highly structured fibro-axonal composite within the STEER PNI. A conduction of intracranially generated action potentials was successfully recorded across the neural interface. Immunohistology demonstrated uniquely configured laminae of myelinated axons encasing the implant., Conclusion: STEER PNI reconfigured the structure of the fibro-axonal tissue and facilitated long-term functionality and stability of the neural interface., Significance: The results point to the feasibility of our concept for creating a stable PNI with long-term electrophysiologic functionality by using simple design and materials.

Understanding the human brain's perception of different thermal sensations has sparked the interest of many neuroscientists. The identification of distinct brain patterns when processing thermal stimuli has several clinical applications, such as phantom-limb pain prediction, as well as increasing the sense of embodiment when interacting with neurorehabilitation devices. Notwithstanding the remarkable number of studies that have touched upon this research topic, understanding how the human brain processes different thermal stimuli has remained elusive. More importantly, very intense thermal stimuli perception dynamics, their related cortical activations, as well as their decoding using effective features are still not fully understood. In this study, using electroencephalography (EEG) recorded from three healthy human subjects, we identified spatial, temporal, and spectral patterns of brain responses to different thermal stimulations ranging from extremely cold and hot stimuli (very intense), moderately cold and hot stimuli (intense), to a warm stimulus (innocuous). Our results show that very intense thermal stimuli elicit a decrease in alpha power compared to intense and innocuous stimulations. Spatio-temporal analysis reveals that in the first 400 ms post-stimulus, brain activity increases in the prefrontal and central brain areas for very intense stimulations, whereas for intense stimulation, high activity of the parietal area was observed post-500 ms. Based on these identified EEG patterns, we successfully classified the different thermal stimulations with an average test accuracy of 84% across all subjects. En route to understanding the underlying cortical activity, we source localized the EEG signal for each of the five thermal stimuli conditions. Our findings reveal that very intense stimuli were anticipated and induced early activation (before 400 ms) of the anterior cingulate cortex (ACC). Moreover, activation of the pre-frontal cortex, somatosensory, central, and parietal areas, was observed in the first 400 ms post-stimulation for very intense conditions and starting 500 ms post-stimuli for intense conditions. Overall, despite the small sample size, this work presents novel findings and a first comprehensive approach to explore, analyze, and classify EEG-brain activity changes evoked by five different thermal stimuli, which could lead to a better understanding of thermal stimuli processing in the brain and could, therefore, pave the way for developing a real-time withdrawal reaction system when interacting with prosthetic limbs. We underpin this last point by benchmarking our EEG results with a demonstration of a real-time withdrawal reaction of a robotic prosthesis using a human-like artificial skin., (© 2022. The Author(s).)

Olfactory hedonic perception involves complex interplay among an ensemble of neurocognitive systems implicated in sensory, affective and reward processing. However, the mechanisms of these inter-system interactions have yet to be well-characterized. Here, we employ directed functional connectivity networks estimated from source-localized EEG to uncover how brain regions across the olfactory, emotion and reward systems integrate organically into cross-system communities. Using the integration coefficient, a graph theoretic measure, we quantified the effect of exposure to fragrance stimuli of different hedonic values (high vs low pleasantness levels) on inter-systems interactions. Our analysis focused on beta band activity (13-30 Hz), which is known to facilitate integration of cortical areas involved in sensory perception. Higher-pleasantness stimuli induced elevated integration for the reward system, but not for the emotion and olfactory systems. Furthermore, the nodes of reward system showed more outward connections to the emotion and olfactory systems than inward connections from the respective systems. These results suggest the centrality of the reward system-supported by beta oscillations-in actively coordinating multi-system interactivity to give rise to hedonic experiences during olfactory perception.

Consumer neuroscience is a rapidly emerging field, with the ability to detect consumer attitudes and states via real-time passive technologies being highly valuable. While many studies have attempted to classify consumer emotions and perceived pleasantness of olfactory products, no known machine learning approach has yet been developed to directly predict consumer reward-based decision-making, which has greater behavioral relevance. In this proof-of-concept study, participants indicated their decision to have fragrance products repeated after fixed exposures to them. Single-trial power spectral density (PSD) and approximate entropy (ApEn) features were extracted from EEG signals recorded using a wearable device during fragrance exposures, and served as subject-independent inputs for 4 supervised learning algorithms (kNN, Linear-SVM, RBF- SVM, XGBoost). Using a cross-validation procedure, kNN yielded the best classification accuracy (77.6%) using both PSD and ApEn features. Acknowledging the challenging prospects of single-trial classification of high-order cognitive states especially with wearable EEG devices, this study is the first to demonstrate the viability of using sensor-level features towards practical objective prediction of consumer reward experience.

Cardiac arrest (CA), the sudden cessation of effective cardiac pumping function, is still a major clinical problem with a high rate of early and long-term mortality. Post-cardiac arrest syndrome (PCAS) may be related to an early systemic inflammatory response leading to exaggerated and sustained neuroinflammation. Therefore, early intervention with targeted drug delivery to attenuate neuroinflammation may greatly improve therapeutic outcomes. Using a clinically relevant asphyxia CA model, we demonstrate that a single (i.p.) dose of dendrimer-N-acetylcysteine conjugate (D-NAC), can target "activated" microglial cells following CA, leading to an improvement in post-CA survival rate compared to saline (86% vs. 45%). D-NAC treatment also significantly improved gross neurological score within 4 h of treatment ( p  < 0.05) and continued to show improvement at 48 h ( p  < 0.05). Specifically, there was a substantial impairment in motor responses after CA, which was subsequently improved with D-NAC treatment ( p  < 0.05). D-NAC also mitigated hippocampal cell density loss seen post-CA in the CA1 and CA3 subregions ( p  < 0.001). These results demonstrate that early therapeutic intervention even with a single D-NAC bolus results in a robust sustainable improvement in long-term survival, short-term motor deficits, and neurological recovery. Our current work lays the groundwork for a clinically relevant therapeutic approach to treating post-CA syndrome., Competing Interests: Rangaramanujam M. Kannan, Sujatha Kannan, and Rishi Sharma have awarded and pending patents relating to the D‐NAC and dendrimer platform. Rangaramanujam M. Kannan and Sujatha Kannan are co‐founders and have financial interests in Ashvattha Therapeutics Inc., a startup involved with the translation of dendrimer drug delivery platforms., (© 2021 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

When nerves are damaged by trauma or disease, they are still capable of firing off electrical command signals that originate from the brain. Furthermore, those damaged nerves have an innate ability to partially regenerate, so they can heal from trauma and even reinnervate new muscle targets. For an amputee who has his/her damaged nerves surgically reconstructed, the electrical signals that are generated by the reinnervated muscle tissue can be sensed and interpreted with bioelectronics to control assistive devices or robotic prostheses. No two amputees will have identical physiologies because there are many surgical options for reconstructing residual limbs, which may in turn impact how well someone can interface with a robotic prosthesis later on. In this review, we aim to investigate what the literature has to say about different pathways for peripheral nerve regeneration and how each pathway can impact the neuromuscular tissue's final electrophysiology. This information is important because it can guide us in planning the development of future bioelectronic devices, such as prosthetic limbs or neurostimulators. Future devices will primarily have to interface with tissue that has undergone some natural regeneration process, and so we have explored and reported here what is known about the bioelectrical features of neuromuscular tissue regeneration.

Objectives: Prolonged cardiac arrest is known to cause global ischemic brain injury and functional impairment. Upon resuscitation, electroencephalographic recordings of brain activity begin to resume and can potentially be used to monitor neurologic recovery. We have previously shown that intrathecal orexin shows promise as a restorative drug and arousal agent in rodents. Our goal is to determine the electrophysiology effects of orexin in a rodent model of asphyxial cardiac arrest, focusing on the electroencephalographic activity in the gamma and super-gamma bands (indicative of return of higher brain function)., Design: Experimental animal study., Setting: University-based animal research laboratory., Subjects: Adult male Wistar rats., Interventions: In an established model of asphyxial cardiac arrest ( n = 24), we treated half of Wistar rats with orexin administered intranasally by atomizer 30 minutes post return of spontaneous circulation in one of two dose levels (10 and 50 µM); the rest were treated with saline as control. Continuous electroencephalographic recording was obtained and quantitatively analyzed for the gamma fraction. Gamma and high-frequency super-gamma band measures were compared against clinical recovery according to Neuro-Deficit Score., Measurements and Main Results: Compared with the control cohort, the high-dose orexin cohort showed significantly better Neuro-Deficit Score 4 hours after return of spontaneous circulation (55.17 vs 47.58; p < 0.02) and significantly higher mean gamma fraction (0.251 vs 0.177; p < 0.02) in cerebral regions surveyed by rostral electrodes for the first 170 minutes after administration of orexin., Conclusions: Our findings support early and continuous monitoring of electroencephalography-based gamma activity as a marker of better functional recovery after intranasal administration of orexin as measured by Neuro-Deficit Score in an established animal model of asphyxial cardiac arrest., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

To obtain deeper insights into the tactile processing pathway from a population-level point of view, we have modeled three stages of the tactile pathway from the periphery to the cortex in response to indentation and scanned edge stimuli at different orientations. Three stages in the tactile pathway are, (1) the first-order neurons which innervate the cutaneous mechanoreceptors, (2) the cuneate nucleus in the midbrain and (3) the cortical neurons of the somatosensory area. In the proposed network, the first layer mimics the spiking patterns generated by the primary afferents. These afferents have complex skin receptive fields. In the second layer, the role of lateral inhibition on projection neurons in the cuneate nucleus is investigated. The third layer acts as a biomimetic decoder consisting of pyramidal and cortical interneurons that correspond to heterogeneous receptive fields with excitatory and inhibitory sub-regions on the skin. In this way, the activity of pyramidal neurons is tuned to the specific edge orientations. By modifying afferent receptive field size, it is observed that the larger receptive fields convey more information about edge orientation in the first spikes of cortical neurons when edge orientation stimuli move across the patch of skin. In addition, the proposed spiking neural model can detect edge orientation at any location on the simulated mechanoreceptor grid with high accuracy. The results of this research advance our knowledge about tactile information processing and can be employed in prosthetic and bio-robotic applications.

One major challenge in upper limb prostheses is providing sensory feedback to amputees. Reproducing the spiking patterns of human primary tactile afferents can be considered as the first step for this challenging problem. In this study, a novel biomimetic circuit for SA-I and RA-I afferents is proposed to functionally replicate the spiking response of the biological tactile afferents to indentation stimuli. The circuit has been designed, laid out, and simulated in TSMC 180nm CMOS technology with a 1.8V supply voltage. A pair of SA-I and RA-I afferent circuits consume [Formula: see text] of power. The occupied silicon area is [Formula: see text] for 32 afferents. To provide the inputs for circuit testing, a patch of skin with a grid of mechanoreceptors is simulated and tested by an edge stimulus presented at different orientations. Experimental data are collected using indentation of 3D-printed edges at different orientations on a tactile sensor mounted on a robotic arm. Inspired by innervation patterns observed in biology, the artificial afferents are connected to several neighboring mechanoreceptors with different weights to form complex receptive fields which cover the entire mechanoreceptor grid. Machine learning algorithms are applied offline to classify the edge orientations based on the pattern of neural responses. Our results show that the complex receptive fields arising from the innervation pattern led to smaller circuit area and lower power consumption, while facilitating data encoding from high-resolution sensors. The proposed biomimetic circuit and tactile encoding example demonstrate potential applications in modern tactile sensing modules for developing novel bio-robotic and prosthetic technologies.

Brain injury following cardiac arrest (CA) is thought to be caused by a sudden loss of blood flow resulting in disruption in oxygen delivery, neural function and metabolism. However, temporal trajectories of the brain's physiology in the first few hours following CA have not been fully characterized. Furthermore, the extent to which these early measures can predict future neurological outcomes has not been determined. The present study sought to perform dynamic measurements of cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) with MRI in the first 3 hours following the return of spontaneous circulation (ROSC) in a rat CA model. It was found that CBF, OEF and CMRO 2 all revealed a time-dependent increase during the first 3 hours after the ROSC. Furthermore, the temporal trajectories of CBF and CMRO 2 , but not OEF, were different across rats and related to neurologic outcomes at a later time (24 hours after the ROSC) (P < .001). Rats who manifested better outcomes revealed faster increases in CBF and CMRO 2 during the acute stage. When investigating physiological parameters measured at a single time point, CBF (ρ = 0.82, P = .004) and CMRO 2 (ρ = 0.80, P = .006) measured at ~ 3 hours post-ROSC were positively associated with neurologic outcome scores at 24 hours. These findings shed light on brain physiological changes following CA, and suggest that MRI measures of brain perfusion and metabolism may provide a potential biomarker to guide post-CA management., (© 2020 John Wiley & Sons, Ltd.)

Objective: A major challenge for controlling a prosthetic arm is communication between the device and the user's phantom limb. We show the ability to enhance phantom limb perception and improve movement decoding through targeted transcutaneous electrical nerve stimulation in individuals with an arm amputation., Approach: Transcutaneous nerve stimulation experiments were performed with four participants with arm amputation to map phantom limb perception. We measured myoelectric signals during phantom hand movements before and after participants received sensory stimulation. Using electroencephalogram (EEG) monitoring, we measured the neural activity in sensorimotor regions during phantom movements and stimulation. In one participant, we also tracked sensory mapping over 2 years and movement decoding performance over 1 year., Main Results: Results show improvements in the participants' ability to perceive and move the phantom hand as a result of sensory stimulation, which leads to improved movement decoding. In the extended study with one participant, we found that sensory mapping remains stable over 2 years. Sensory stimulation improves within-day movement decoding while performance remains stable over 1 year. From the EEG, we observed cortical correlates of sensorimotor integration and increased motor-related neural activity as a result of enhanced phantom limb perception., Significance: This work demonstrates that phantom limb perception influences prosthesis control and can benefit from targeted nerve stimulation. These findings have implications for improving prosthesis usability and function due to a heightened sense of the phantom hand.

Tumor blood vessels are chaotic and abundantly distributed, owing to their heterogeneity. Therefore, imaging techniques which reveal abnormalities of tumor vasculature play significant roles in both mechanistic and clinical diagnostic tumor studies. Photoacoustic (PA) imaging uses the intrinsic characteristics of hemoglobin, to acquire tumor hemodynamic information, while ultrasound (US) imaging provides information about tumoral vessel structures and blood flow. To improve the imaging contrast performance, hydrogel-based microdroplets were designed for both US blood flow and PA imaging in this study. The microdroplets served as carriers for PA contrast agent solution in the innermost part while oil and hydrogel formed the inner and outer layers of the droplets. In vitro experiments firstly demonstrated the dual modality contrast effects of the microdroplets on US flow determination and PA imaging. In vivo experiments were then carried out in both healthy nude mice and nude mice with subcutaneous tumor to validate the contrast effects and to monitor the duration of contrast effects in animals. Using the dual-modality microdroplets, we were able to obtain distinct edges of tumor and blood flow mapping of the tumor microvascular with improved sensitivity up to 11.09 dB for PA and 6.69 dB for US flow. Besides, the in vivo evaluation with microdroplets showed US flow enhancement for more than 60 min. Therefore, the microdroplets are able to provide the contrast effects for both US flow and PA in a relative long duration and have potential to be applied in the tumor related diagnoses and studies.

Neural electrodes are developed for direct communication with neural tissues for theranostics. Although various strategies have been employed to improve performance, creating an intimate electrode-tissue interface with high electrical fidelity remains a great challenge. Here, we report the rational design of a tunnel-like electrode coating comprising poly(3,4-ethylenedioxythiophene) (PEDOT) and carbon nanotubes (CNTs) for highly sensitive neural recording. The coated electrode shows a 50-fold reduction in electrochemical impedance at the biologically relevant frequency of 1 kHz, compared to the bare gold electrode. The incorporation of CNT significantly reinforces the nanotunnel structure and improves coating adhesion by ∼1.5 fold. In vitro primary neuron culture confirms an intimate contact between neurons and the PEDOT-CNT nanotunnel. During acute in vivo nerve recording, the coated electrode enables the capture of high-fidelity neural signals with low susceptibility to electrical noise and reveals the potential for precisely decoding sensory information through mechanical and thermal stimulation. These findings indicate that the PEDOT-CNT nanotunnel composite serves as an active interfacing material for neural electrodes, contributing to neural prosthesis and brain-machine interface.

Light irradiation is considered an ideal non-invasive stimulus that enables precise tumour treatment with flexible, facile, and spatiotemporal control. Photodynamic therapy (PDT) is an important clinically relevant therapeutic modality that has proven to compensate for the reduced therapeutic efficacy of conventional chemotherapy. However, oxygen consumption during PDT can result in an inadequate oxygen supply which reduces photodynamic efficacy. In our quest to circumvent the limitations of chemotherapy and photodynamic therapy, we have engineered a robust and smart "all-in-one" nanoparticle-based drug delivery system capable of overcoming biological barriers and leveraging on several synergistic cancer cell killing mechanisms. The fabricated Targeted Micellar Nanoprobe (TMNP) had exceptionally high encapsulation efficiencies of a hydrophobic drug simvastatin (SV) and a photosensitizer protoporphyrin IX (PpIX) due to the ℼ-ℼ stacking of the aromatic groups of SV and PpIX and strong hydrophobic interactions with the alkyl chains of the carrier. In-vitro results demonstrated that TMNP exhibited excellent colloidal stability, biocompatibility and drug retaining capability in physiological condition. Under light irradiation, TMNP causes the accelerated generation of reactive oxygen species (ROS) which subsequently damages the mitochondria. On further evaluation of the mechanisms behind the superior anti-cancer effect of TMNP, we concluded that TMNP causes synergistic apoptosis and necrosis along with cell cycle arrest at the G1-S phase and elicits anti-angiogenic effects. Taking into consideration that these promising results on 2D monolayer cell cultures might not translate into similar results in animal models, we developed 3D multicellular tumour spheroids (MCs) as an intermediate step to bridge the gap between 2-D cell experiments and in-vivo studies. TMNPs showed enhanced penetration and growth inhibition on MCs. In addition, the modelling of the transport of TMNP in the tumour exhibited the improved effective delivery volume. Overall, TMNPs could potentially be used for image-guided delivery of the therapeutic payloads for precise cancer treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Electrical excitation of neural tissue has wide applications, but how electrical stimulation interacts with neural tissue remains to be elucidated. Here, we propose a new theory, named the Circuit-Probability theory, to reveal how this physical interaction happen. The relation between the electrical stimulation input and the neural response can be theoretically calculated. We show that many empirical models, including strength-duration relationship and linear-non-linear-Poisson model, can be theoretically explained, derived, and amended using our theory. Furthermore, this theory can explain the complex non-linear and resonant phenomena and fit in vivo experiment data. In this letter, we validated an entirely new framework to study electrical stimulation on neural tissue, which is to simulate voltage waveforms using a parallel RLC circuit first, and then calculate the excitation probability stochastically., (Copyright © 2020 Wang, Wang, Thow, Lee, Peh, Ng, He, Thakor and Lee.)

Olfactory perception is intrinsically tied to emotional processing, in both behavior and neurophysiology. Despite advances in olfactory-affective neuroscience, it is unclear how separate attributes of odor stimuli contribute to olfactoryinduced emotions, especially within the positive segment of the hedonic dimension to avoid potential cross-valence confounds. In this study, we examined how pleasantness and intensity of fragrances relate to different grades of positive affect. Our results show that greater odor pleasantness and intensity are independently associated with stronger positive affect. Pleasantness has a greater influence than intensity in evoking a positive vs. neutral affect, whereas intensity is more impactful than pleasantness in evoking an extreme positive vs. positive response. Autonomic response, as assessed by the galvanic skin response (GSR) was found to decrease with increasing pleasantness but not intensity. This clarifies how olfactory and affective processing induce significant downstream effects in peripheral physiology and self-reported affective experience, pertinent to the thriving field of olfactory neuromarkerting.

Decoding olfactory cognition has been generating significant interest in recent years due to a wide range of applications, from diagnosing neurodegenerative disorders to consumer research and traditional medicine. In this study, we have investigated whether changes in odor stimuli evaluation across repeated stimuli presentation can be attributed to changes in brain perception of the stimuli. Epoch intervals representing olfactory sensory perception were extracted from electroencephalography (EEG) signals using minimum variance distortionless response (MVDR)-based single trial event related potential (ERP) approach to understand the evoked response to high pleasantness and low pleasantness stimuli. We found statistically significant changes in self reported stimuli evaluation between initial and final trials (p < 0.05) for both stimuli categories. However, the changes in ERP amplitude were found to be statistically significant only for the high pleasantness stimuli. This implies that olfactory stimuli of higher hedonic value recruit high-order cognitive processing that may be responsible for initial increased ERP response, as well as for rapid subsequent adaptation in processing the stimuli.

Objective: Recent development of sensory stimulation techniques demonstrates the ability to elicit touch-like phantom sensations in upper limb amputees. The cortical processing of this phantom sensation and the corresponding influences on sensorimotor functional connectivity have not been studied. We hypothesize that sensory stimulation has a profound impact on the sensorimotor cortical functional interactions, which will be uncovered by dynamic functional connectivity (dFC) analysis of amputees' electroencephalogram (EEG) recordings., Approach: We investigated dFC between cortical areas associated with somatosensory, motor, visual, and multisensory processing functions using EEG signals. We applied dFC to the EEG of two amputees performing hand movements with and without sensory stimulation and compared the results with those from three able-bodied subjects. We quantified the changes due to sensory stimulation using dFC metrics, namely temporal distance, number of connection paths, temporal global and local efficiencies, and clustering coefficient., Main Results: We show a significant effect of sensory stimulation on functional connectivity in the amputee brains, with notable facilitation on multisensory processing among the cortical systems involved in sensorimotor processing. The dFC metrics reveal that sensory stimulation enhances the speed of information transfer (shown by decreases in temporal distance) and the number of connection paths between the brain systems involved in sensorimotor processing, including primary somatosensory and motor, and higher order processing regions., Significance: This is the first work to reveal dynamic communication between somatosensory, motor, and higher order processing regions in the cortex of amputees in response to sensory stimulation. We believe that our work provides crucial insights into the cortical impact of sensory stimulation in amputees, which may lead to the design of personalized brain-informed sensory feedback paradigms. This in turn may lead to building novel Machine to Brain Interfaces involving sensory feedback and the resultant enhanced motor performance.