Sleep health reflects interacting demographic, clinical, micro- and macroarchitectural, and neurophysiological factors that may not be captured by single metrics or diagnostic categories. We applied hierarchical clustering to longitudinal Sleep Heart Health Study data from 1,468 adults with complete polysomnographic, demographic/clinical, and pre-sleep electroencephalographic data at two visits separated by 5.19 ± 0.27 years. Forty nonredundant features selected from candidate demographic/clinical, sleep-stage, and pre-sleep spectral measures were clustered independently at each visit. Four reproducible sleep-health phenotypes emerged: a group with preserved deep sleep and favorable mental-health ratings; a large light-sleep group with low N3 and high N1; an older, physically unhealthy group with shorter total and rapid-eye-movement sleep; and a younger, physically healthy group with longer total and rapid-eye-movement sleep. The same population-level structure was evident at both visits, although only 37.7% of participants retained the same cluster assignment, with transitions most directed toward the light-sleep phenotype. An independent analysis of slow-wave morphology, excluded from cluster construction, differentiated all four phenotypes after false-discovery-rate correction. Groups with preserved or healthier sleep showed more numerous, higher-amplitude, steeper, and shorter slow waves, whereas the light-sleep and physically unhealthy groups showed weaker and more prolonged slow waves. Pre-sleep spectral features did not differ significantly across clusters after correction. These findings identify reproducible but individually dynamic sleep-health phenotypes and demonstrate that macro-architectural cluster structure is reflected in independent measures of NREM sleep microarchitecture.

Neurotechnologies and genetic tools for dissecting neural circuit functions have advanced rapidly over the past decade although the development of complementary pharmacological methodologies has comparatively lagged. Understanding the precise pharmacological mechanisms of neuroactive compounds is critical for advancing basic neurobiology and neuropharmacology, as well as for developing more effective treatments for neurological and neuropsychiatric disorders. However, integrating modern tools for assessing neural activity in large-scale neural networks with spatially localized drug delivery remains a major challenge. Here, we present a dual microfluidic-photometry platform that enables simultaneous intracranial drug delivery with neural dynamics recording in the rodent brain. The integrated platform combines a wireless, battery-free, miniaturized fluidic microsystem with optical probes, allowing for spatially and temporally restricted drug delivery while sensing activity-dependent fluorescence using genetically encoded calcium indicators (GECIs), neurotransmitter sensors, and neuropeptide sensors. We demonstrate the performance of this platform for investigating neuropharmacological mechanisms in vivo in behaving mice.

Synthesizing perceivable artificial neural inputs independent of typical sensory channels remains a fundamental challenge in developing next-generation brain-machine interfaces. Establishing a minimally invasive, wirelessly effective and miniaturized platform with long-term stability is crucial for creating research methods and clinically meaningful biointerfaces capable of mediating artificial perceptual feedback. Here we demonstrate a miniaturized, fully implantable transcranial optogenetic neural stimulator designed to generate artificial perceptions by patterning large cortical ensembles wirelessly in real time. Experimentally validated numerical simulations characterized light and heat propagation, whereas neuronal responses were assessed by in vivo electrophysiology and molecular methods. Cue discrimination during operant learning demonstrated the wireless genesis of artificial percepts sensed by mice, where spatial distance across large cortical networks and sequential order-based analyses of discrimination predicted performance. These conceptual and technical advances expand understanding of artificially patterned neural activity and its perception by the brain to guide the evolution of next-generation all-optical brain-machine communication.

Precise spatial regulation of site-specific DNA recombination (SSR) in vivo remains a challenge due to limited tunability of current platforms. Here, we present an optogenetic approach that overcome these limitations by employing engineered light-regulated recombinase E-LightR-Cre and tunable wireless implantable optoelectronic devices. E-LightR-Cre meets the key criteria for spatial regulation of SSR in vivo , showing no detectable activity in the dark, while demonstrating robust activation upon blue-light illumination. To achieve local E-LightR-Cre activation in murine lungs, we developed wireless, fully-implantable optoelectronic devices enabling focal illumination with no discernible organ damage. By modulating illumination intensity and duration, we can control the size of the activated area. Local expression of oncogenic KRas-G12D in a photoactivated subpopulation of cells in vitro revealed rapid reprogramming of the mutant expressing cells and their non-activated neighbors. Light-guided activation of E-LightR-Cre in mouse lungs resulted in focal expression of a reporter gene and allowed us to induce local formation of oncogenic lesions in vivo .

Chronic pain severely impairs physical, psychological, and cognitive functions. While opioid-based therapies can be effective, they are limited by tolerance, dependence, and adverse side effects, highlighting the need for safer alternatives. Recent advances in photopharmacology allow precise modulation of pain-related neuronal circuits, offering improved control and effectiveness. For delivery of light, fully implantable, wireless, battery-free optical systems in miniaturized forms offer attractive options relative to alternatives that use conventional bulk hardware and fiber optic tethers. This work presents a technology of this type, based on microscale light-emitting diodes (μ-ILEDs) and near-field communication (NFC) protocols, and optimized to activate photocaged morphine (pc-Mor) in targeted regions of the spinal cord. The unique flexible, lightweight designs ensure stable, minimally invasive operation in small animal model behavioral studies, with efficient power consumption and minimized thermal load on fragile tissues. Experimental results demonstrate effective pain suppression and reduced opioid-related side effects in an animal model of pain, thereby establishing this platform as a promising solution for chronic pain management.

IntroductionOpioid use disorder (OUD) is a serious and persistent problem in the United States with limited non-pharmacological treatment options, especially for the concomitant sleep disorders experienced by most individuals with addiction. While new, non-invasive interventions such as low-intensity focused ultrasound (LIFU) have shown promise in targeting the brain regions impacted throughout addiction and recovery, the devices used are not amenable to outpatient treatment in their current form factor and cannot be used at night during sleep. To bridge this gap and provide a much-needed treatment option for repeated, at-home use, we developed a wearable LIFU device out-of-clinic use.MethodsThis study evaluated the feasibility and acceptability of the portable treatment device among individuals recovering from OUD in an unsupervised, at-home setting. 31 subjects were recruited from a Baltimore, Maryland (USA) outpatient treatment facility and, along with a separate group of 14 healthy controls (HC), were asked to wear a prototype EEG-only (non-LIFU) device for 7 consecutive nights to assess their willingness and adherence to nightly use. Participants used a smartphone application, TrialKit (ePRO), to self-report nightly sleep data (e.g. duration, quality, possible disturbances, and device comfort).ResultsOf the 31 OUD participants recruited, 30 (97%) successfully completed the at-home study, and the majority responded that they would participate in future studies using the head wearable device (OUD, 87%; HC, 71%). OUD participants were statistically more likely than HCs to respond that they would consider using the device in the future to help them sleep (OUD, 70%; HC, 29%). Despite some participants facing technological issues (e.g. lack of reliable phone access or cellular data plans), the OUD group demonstrated high study compliance on par with the healthy control group.DiscussionParticipant’s daily ePRO and exit interview results established that at-home use of advanced treatment technology is feasible in a population group challenged with recovering from OUD. Even more so, numerous participants noted strong willingness to participate in future LIFU-enabled intervention studies to address their persistent sleep issues during recovery.

Comprehensive, continuous quantitative monitoring of intricately orchestrated physiological processes and behavioral states in living organisms can yield essential data for elucidating the function of neural circuits under healthy and diseased conditions, for defining the effects of potential drugs and treatments, and for tracking disease progression and recovery. Here, we report a wireless, battery-free implantable device and a set of associated algorithms that enable continuous, multiparametric physio-behavioral monitoring in freely behaving small animals and interacting groups. Through advanced analytics approaches applied to mechano-acoustic signals of diverse body processes, the device yields heart rate, respiratory rate, physical activity, temperature, and behavioral states. Demonstrations in pharmacological, locomotor, and acute and social stress tests and in optogenetic studies offer unique insights into the coordination of physio-behavioral characteristics associated with healthy and perturbed states. This technology has broad utility in neuroscience, physiology, behavior, and other areas that rely on studies of freely moving, small animal models.

Synthesizing perceivable artificial neural inputs independent of typical sensory channels remains a fundamental challenge in the development of next-generation brain-machine interfaces. Establishing a minimally invasive, wirelessly effective, and miniaturized platform with long-term stability is crucial for creating a clinically meaningful interface capable of mediating artificial perceptual feedback. In this study, we demonstrate a miniaturized fully implantable wireless transcranial optogenetic encoder designed to generate artificial perceptions through digitized optogenetic manipulation of large cortical ensembles. This platform enables the spatiotemporal orchestration of large-scale cortical activity for remote perception genesis via real-time wireless communication and control, with optimized device performance achieved by simulation-guided methods addressing light and heat propagation during operation. Cue discrimination during operant learning demonstrates the wireless genesis of artificial percepts sensed by mice, where spatial distance across large cortical networks and sequential order-based analyses of discrimination performance reveal principles that adhere to general perceptual rules. These conceptual and technical advancements expand our understanding of artificial neural syntax and its perception by the brain, guiding the evolution of next-generation brain-machine communication.

Neurotechnologies and genetic tools for dissecting neural circuit functions have advanced rapidly over the past decade, although the development of complementary pharmacological methodologies has comparatively lagged. Understanding the precise pharmacological mechanisms of neuroactive compounds is critical for advancing basic neurobiology and neuropharmacology, as well as for developing more effective treatments for neurological and neuropsychiatric disorders. However, integrating modern tools for assessing neural activity in large-scale neural networks with spatially localized drug delivery remains a major challenge. Here, we present a dual microfluidic-photometry platform that enables simultaneous intracranial drug delivery with neural dynamics monitoring in the rodent brain. The integrated platform combines a wireless, battery-free, miniaturized fluidic microsystem with optical probes, allowing for spatially and temporally specific drug delivery while recording activity-dependent fluorescence using genetically encoded calcium indicators (GECIs), neurotransmitter sensors GRABNEand GRABDA, and neuropeptide sensors. We demonstrate the performance this platform for investigating neuropharmacological mechanisms in vivo and characterize its efficacy in probing precise mechanistic actions of neuroactive compounds across several rapidly evolving neuroscience domains.

Fully implantable wireless systems for the recording and modulation of neural circuits that do not require physical tethers or batteries allow for studies that demand the use of unconstrained and freely behaving animals in isolation or in social groups. Moreover, feedback-control algorithms that can be executed within such devices without the need for remote computing eliminate virtual tethers and any associated latencies. Here we report a wireless and battery-less technology of this type, implanted subdermally along the back of freely moving small animals, for the autonomous recording of electroencephalograms, electromyograms and body temperature, and for closed-loop neuromodulation via optogenetics and pharmacology. The device incorporates a system-on-a-chip with Bluetooth Low Energy for data transmission and a compressed deep-learning module for autonomous operation, that offers neurorecording capabilities matching those of gold-standard wired systems. We also show the use of the implant in studies of sleep-wake regulation and for the programmable closed-loop pharmacological suppression of epileptic seizures via feedback from electroencephalography. The technology can support a broader range of applications in neuroscience and in biomedical research with small animals.

Wireless battery-free optogenetic devices enable behavioral neuroscience studies in groups of animals with minimal interference to natural behavior. Real-time independent control of optogenetic stimulation through near-field communication dramatically expands the realm of applications of these devices in broad contexts of neuroscience research. Dissemination of these tools with advanced functionalities to the neuroscience community requires protocols for device manufacturing and experimental implementation. This protocol describes detailed procedures for fabrication, encapsulation and implantation of recently developed advanced wireless devices in head- and back-mounted forms. In addition, procedures for standard implementation of experimental systems in mice are provided. This protocol aims to facilitate the application of wireless optogenetic devices in advanced optogenetic experiments involving groups of freely moving rodents and complex environmental designs. The entire protocol lasts ~3–5 weeks. The authors present detailed procedures to fabricate, encapsulate and implant advanced wireless battery-free devices in head- and back-mounted forms in order to facilitate optogenetic experiments in freely moving rodents.

Cessation of cannabinoid use in humans often leads to a withdrawal state that includes sleep disruption. Despite important health implications, little is known about how cannabinoid abstention affects sleep architecture, in part because spontaneous cannabinoid withdrawal is difficult to model in animals. In concurrent work we report that repeated administration of the high-efficacy cannabinoid 1 (CB1) receptor agonist AM2389 to mice for 5 days led to heightened locomotor activity and paw tremor following treatment discontinuation, potentially indicative of spontaneous cannabinoid withdrawal. Here, we performed parallel studies to examine effects on sleep. Using implantable electroencephalography (EEG) and electromyography (EMG) telemetry we examined sleep and neurophysiological measures before, during, and after 5 days of twice-daily AM2389 injections. We report that AM2389 produces decreases in locomotor activity that wane with repeated treatment, whereas discontinuation produces rebound increases in activity that persist for several days. Likewise, AM2389 initially produces profound increases in slow-wave sleep (SWS) and decreases in rapid eye movement (REM) sleep, as well as consolidation of sleep. By the third AM2389 treatment, this pattern transitions to decreases in SWS and total time sleeping. This pattern persists following AM2389 discontinuation and is accompanied by emergence of sleep fragmentation. Double-labeling immunohistochemistry for hypocretin/orexin (a sleep-regulating peptide) and c-Fos (a neuronal activity marker) in lateral hypothalamus revealed decreases in c-Fos/orexin+ cells following acute AM2389 and increases following discontinuation, aligning with the sleep changes. These findings indicate that AM2389 profoundly alters sleep in mice and suggest that sleep disruption following treatment cessation reflects spontaneous cannabinoid withdrawal.

Focused ultrasound (FUS) is a powerful tool for noninvasive modulation of deep brain activity with promising therapeutic potential for refractory epilepsy; however, tools for examining FUS effects on specific cell types within the deep brain do not yet exist. Consequently, how cell types within heterogeneous networks can be modulated and whether parameters can be identified to bias these networks in the context of complex behaviors remains unknown. To address this, we developed a fiber Photometry Coupled focused Ultrasound System (PhoCUS) for simultaneously monitoring FUS effects on neural activity of subcortical genetically targeted cell types in freely behaving animals. We identified a parameter set that selectively increases activity of parvalbumin interneurons while suppressing excitatory neurons in the hippocampus. A net inhibitory effect localized to the hippocampus was further confirmed through whole brain metabolic imaging. Finally, these inhibitory selective parameters achieved significant spike suppression in the kainate model of chronic temporal lobe epilepsy, opening the door for future noninvasive therapies.

High-performance eco- and bio-resorbable magnesium–iodine batteries with >1.8 V output power cardiac pacemakers, wireless environmental monitors, thermal sensors, microcontrollers, and Bluetooth systems.

Advanced technologies for controlled delivery of light to targeted locations in biological tissues are essential to neuroscience research that applies optogenetics in animal models. Fully implantable, miniaturized devices with wireless control and power-harvesting strategies offer an appealing set of attributes in this context, particularly for studies that are incompatible with conventional fiber-optic approaches or battery-powered head stages. Limited programmable control and narrow options in illumination profiles constrain the use of existing devices. The results reported here overcome these drawbacks via two platforms, both with real-time user programmability over multiple independent light sources, in head-mounted and back-mounted designs. Engineering studies of the optoelectronic and thermal properties of these systems define their capabilities and key design considerations. Neuroscience applications demonstrate that induction of interbrain neuronal synchrony in the medial prefrontal cortex shapes social interaction within groups of mice, highlighting the power of real-time subject-specific programmability of the wireless optogenetic platforms introduced here.

STUDY OBJECTIVE:Throughout the coronavirus disease 2019 pandemic, many emergency departments have been using passive protective enclosures ("intubation boxes") during intubation. The effectiveness of these enclosures remains uncertain. We sought to quantify their ability to contain aerosols using industry standard test protocols.METHODS:We tested a commercially available passive protective enclosure representing the most common design and compared this with a modified enclosure that incorporated a vacuum system for active air filtration during simulated intubations and negative-pressure isolation. We evaluated the enclosures by using the same 3 tests air filtration experts use to certify class I biosafety cabinets: visual smoke pattern analysis using neutrally buoyant smoke, aerosol leak testing using a test aerosol that mimics the size of virus-containing particulates, and air velocity measurements.RESULTS:Qualitative evaluation revealed smoke escaping from all passive enclosure openings. Aerosol leak testing demonstrated elevated particle concentrations outside the enclosure during simulated intubations. In contrast, vacuum-filter-equipped enclosures fully contained the visible smoke and test aerosol to standards consistent with class I biosafety cabinet certification.CONCLUSION:Passive enclosures for intubation failed to contain aerosols, but the addition of a vacuum and active air filtration reduced aerosol spread during simulated intubation and patient isolation.

The military lifestyle often includes continuous operations whether in training or deployed environments. These stressful environments present unique challenges for service members attempting to achieve consolidated, restorative sleep. The significant mental and physical derangements caused by degraded metabolic, cardiovascular, skeletomuscular, and cognitive health often result from insufficient sleep and/or circadian misalignment. Insufficient sleep and resulting fatigue compromises personal safety, mission success, and even national security. In the long-term, chronic insufficient sleep and circadian rhythm disorders have been associated with other sleep disorders (e.g., insomnia, obstructive sleep apnea, and parasomnias). Other physiologic and psychologic diagnoses such as post-traumatic stress disorder, cardiovascular disease, and dementia have also been associated with chronic, insufficient sleep. Increased co-morbidity and mortality are compounded by traumatic brain injury resulting from blunt trauma, blast exposure, and highly physically demanding tasks under load. We present the current state of science in human and animal models specific to service members during- and post-military career. We focus on mission requirements of night shift work, sustained operations, and rapid re-entrainment to time zones. We then propose targeted pharmacological and non-pharmacological countermeasures to optimize performance that are mission- and symptom-specific. We recognize a critical gap in research involving service members, but provide tailored interventions for military health care providers based on the large body of research in health care and public service workers.

The military lifestyle often includes continuous operations whether in training or deployed environments. These stressful environments present unique challenges for service members attempting to achieve consolidated, restorative sleep. The significant mental and physical derangements caused by degraded metabolic, cardiovascular, skeletomuscular, and cognitive health often result from insufficient sleep and/or circadian misalignment. Insufficient sleep and resulting fatigue compromises personal safety, mission success, and even national security. In the long-term, chronic insufficient sleep and circadian rhythm disorders have been associated with other sleep disorders (e.g., insomnia, obstructive sleep apnea, and parasomnias). Other physiologic and psychologic diagnoses such as post-traumatic stress disorder, cardiovascular disease, and dementia have also been associated with chronic, insufficient sleep. Increased co-morbidity and mortality are compounded by traumatic brain injury resulting from blunt trauma, blast exposure, and highly physically demanding tasks under load. We present the current state of science in human and animal models specific to service members during- and post-military career. We focus on mission requirements of night shift work, sustained operations, and rapid re-entrainment to time zones. We then propose targeted pharmacological and non-pharmacological countermeasures to optimize performance that are mission- and symptom-specific. We recognize a critical gap in research involving service members, but provide tailored interventions for military health care providers based on the large body of research in health care and public service workers.