A randomized controlled trial of alpha phase-locked auditory stimulation to treat symptoms of sleep onset insomnia.

Sleep onset insomnia is a pervasive problem that contributes significantly to the poor health outcomes associated with insufficient sleep. Auditory stimuli phase-locked to slow-wave sleep oscillations have been shown to augment deep sleep, but it is unknown whether a similar approach can be used to accelerate sleep onset. The present randomized controlled crossover trial enrolled adults with objectively verified sleep onset latencies (SOLs) greater than 30 min to test the effect of auditory stimuli delivered at specific phases of participants' alpha oscillations prior to sleep onset. During the intervention week, participants wore an electroencephalogram (EEG)-enabled headband that delivered acoustic pulses timed to arrive anti-phase with alpha for 30 min (Stimulation). During the Sham week, the headband silently recorded EEG. The primary outcome was SOL determined by blinded scoring of EEG records. For the 21 subjects included in the analyses, stimulation had a significant effect on SOL according to a linear mixed effects model (p = 0.0019), and weekly average SOL decreased by 10.5 ± 15.9 min (29.3 ± 44.4%). These data suggest that phase-locked acoustic stimulation can be a viable alternative to pharmaceuticals to accelerate sleep onset in individuals with prolonged sleep onset latencies. Trial Registration: This trial was first registered on clinicaltrials.gov on 24/02/2023 under the name Sounds Locked to ElectroEncephalogram Phase For the Acceleration of Sleep Onset Time (SLEEPFAST), and assigned registry number NCT05743114.

A wearable EEG system for closed-loop neuromodulation of sleep-related oscillations.

Objective.Healthy sleep plays a critical role in general well-being. Enhancement of slow-wave sleep by targeting acoustic stimuli to particular phases of delta (0.5-2 Hz) waves has shown promise as a non-invasive approach to improve sleep quality. Closed-loop stimulation during other sleep phases targeting oscillations at higher frequencies such as theta (4-7 Hz) or alpha (8-12 Hz) could be another approach to realize additional health benefits. However, systems to track and deliver stimulation relative to the instantaneous phase of electroencephalogram (EEG) signals at these higher frequencies have yet to be demonstrated outside of controlled laboratory settings.Approach.Here we examine the feasibility of using an endpoint-corrected version of the Hilbert transform (ecHT) algorithm implemented on a headband wearable device to measure alpha phase and deliver phase-locked auditory stimulation during the transition from wakefulness to sleep, during which alpha power is greatest. First, the ecHT algorithm is implementedin silicoto evaluate the performance characteristics of this algorithm across a range of sleep-related oscillatory frequencies. Secondly, a pilot sleep study tests feasibility to use the wearable device by users in the home setting for measurement of EEG activity during sleep and delivery of real-time phase-locked stimulation.Main results.The ecHT is capable of computing the instantaneous phase of oscillating signals with high precision, allowing auditory stimulation to be delivered at the intended phases of neural oscillations with low phase error. The wearable system was capable of measuring sleep-related neural activity with sufficient fidelity for sleep stage scoring during the at-home study, and phase-tracking performance matched simulated results. Users were able to successfully operate the system independently using the companion smartphone app to collect data and administer stimulation, and presentation of auditory stimuli during sleep initiation did not negatively impact sleep onset.Significance.This study demonstrates the feasibility of closed-loop real-time tracking and neuromodulation of a range of sleep-related oscillations using a wearable EEG device. Preliminary results suggest that this approach could be used to deliver non-invasive neuromodulation across all phases of sleep.

The development of an unsupervised hierarchical clustering analysis of dual-polarization weather surveillance radar observations to assess nocturnal insect abundance and diversity.

Contemporary analyses of insect population trends are based, for the most part, on a large body of heterogeneous and short-term datasets of diurnal species that are representative of limited spatial domains. This makes monitoring changes in insect biomass and biodiversity difficult. What is needed is a method for monitoring that provides a consistent, high-resolution picture of insect populations through time over large areas during day and night. Here, we explore the use of X-band weather surveillance radar (WSR) for the study of local insect populations using a high-quality, multi-week time series of nocturnal moth light trapping data. Specifically, we test the hypotheses that (i) unsupervised data-driven classification algorithms can differentiate meteorological and biological phenomena, (ii) the diversity of the classes of bioscatterers are quantitatively related to the diversity of insects as measured on the ground and (iii) insect abundance measured at ground level can be predicted quantitatively based on dual-polarization Doppler WSR variables. Adapting the quasi-vertical profile analysis method and data clustering techniques developed for the analysis of hydrometeors, we demonstrate that our bioscatterer classification algorithm successfully differentiates bioscatterers from hydrometeors over a large spatial scale and at high temporal resolutions. Furthermore, our results also show a clear relationship between biological and meteorological scatterers and a link between the abundance and diversity of radar-based bioscatterer clusters and that of nocturnal aerial insects. Thus, we demonstrate the potential utility of this approach for landscape scale monitoring of biodiversity.

A wireless millimetre-scale implantable neural stimulator with ultrasonically powered bidirectional communication.

Clinically approved neural stimulators are limited by battery requirements, as well as by their large size compared with the stimulation targets. Here, we describe a wireless, leadless and battery-free implantable neural stimulator that is 1.7 mm3 and that incorporates a piezoceramic transducer, an energy-storage capacitor and an integrated circuit. An ultrasonic link and a hand-held external transceiver provide the stimulator with power and bidirectional communication. The stimulation protocols were wirelessly encoded on the fly, reducing power consumption and on-chip memory, and enabling protocol complexity with a high temporal resolution and low-latency feedback. Uplink data indicating whether stimulation occurs are encoded by the stimulator through backscatter modulation and are demodulated at the external transceiver. When embedded in ex vivo porcine tissue, the integrated circuit efficiently harvested ultrasonic power, decoded downlink data for the stimulation parameters and generated current-controlled stimulation pulses. When cuff-mounted and acutely implanted onto the sciatic nerve of anaesthetized rats, the device conferred repeatable stimulation across a range of physiological responses. The miniaturized neural stimulator may facilitate closed-loop neurostimulation for therapeutic interventions.

Volitional Modulation of Primary Visual Cortex Activity Requires the Basal Ganglia.

Animals acquire behaviors through instrumental conditioning. Brain-machine interfaces have used instrumental conditioning to reinforce patterns of neural activity directly, especially in frontal and motor cortices, which are a rich source of signals for voluntary action. However, evidence suggests that activity in primary sensory cortices may also reflect internally driven processes, instead of purely encoding antecedent stimuli. Here, we show that rats and mice can learn to produce arbitrary patterns of neural activity in their primary visual cortex to control an auditory cursor and obtain reward. Furthermore, learning was prevented when neurons in the dorsomedial striatum (DMS), which receives input from visual cortex, were optogenetically inhibited, but not during inhibition of nearby neurons in the dorsolateral striatum. After learning, DMS inhibition did not affect production of the rewarded patterns. These data demonstrate that cortico-basal ganglia circuits play a general role in learning to produce cortical activity that leads to desirable outcomes.

Recent advances in neural dust: towards a neural interface platform.

The neural dust platform uses ultrasonic power and communication to enable a scalable, wireless, and batteryless system for interfacing with the nervous system. Ultrasound offers several advantages over alternative wireless approaches, including a safe method for powering and communicating with sub mm-sized devices implanted deep in tissue. Early studies demonstrated that neural dust motes could wirelessly transmit high-fidelity electrophysiological data in vivo, and that theoretically, this system could be miniaturized well below the mm-scale. Future developments are focused on further minimization of the platform, better encapsulation methods as a path towards truly chronic neural interfaces, improved delivery mechanisms, stimulation capabilities, and finally refinements to enable deployment of neural dust in the central nervous system.

Wireless Recording in the Peripheral Nervous System with Ultrasonic Neural Dust.

The emerging field of bioelectronic medicine seeks methods for deciphering and modulating electrophysiological activity in the body to attain therapeutic effects at target organs. Current approaches to interfacing with peripheral nerves and muscles rely heavily on wires, creating problems for chronic use, while emerging wireless approaches lack the size scalability necessary to interrogate small-diameter nerves. Furthermore, conventional electrode-based technologies lack the capability to record from nerves with high spatial resolution or to record independently from many discrete sites within a nerve bundle. Here, we demonstrate neural dust, a wireless and scalable ultrasonic backscatter system for powering and communicating with implanted bioelectronics. We show that ultrasound is effective at delivering power to mm-scale devices in tissue; likewise, passive, battery-less communication using backscatter enables high-fidelity transmission of electromyogram (EMG) and electroneurogram (ENG) signals from anesthetized rats. These results highlight the potential for an ultrasound-based neural interface system for advancing future bioelectronics-based therapies.

Emergence of healing in the Antarctic ozone layer.

Industrial chlorofluorocarbons that cause ozone depletion have been phased out under the Montreal Protocol. A chemically driven increase in polar ozone (or "healing") is expected in response to this historic agreement. Observations and model calculations together indicate that healing of the Antarctic ozone layer has now begun to occur during the month of September. Fingerprints of September healing since 2000 include (i) increases in ozone column amounts, (ii) changes in the vertical profile of ozone concentration, and (iii) decreases in the areal extent of the ozone hole. Along with chemistry, dynamical and temperature changes have contributed to the healing but could represent feedbacks to chemistry. Volcanic eruptions have episodically interfered with healing, particularly during 2015, when a record October ozone hole occurred after the Calbuco eruption.

Composition and physical properties of the Asian Tropopause Aerosol Layer and the North American Tropospheric Aerosol Layer.

Recent studies revealed layers of enhanced aerosol scattering in the upper troposphere and lower stratosphere over Asia (Asian Tropopause Aerosol Layer (ATAL)) and North America (North American Tropospheric Aerosol Layer (NATAL)). We use a sectional aerosol model (Community Aerosol and Radiation Model for Atmospheres (CARMA)) coupled with the Community Earth System Model version 1 (CESM1) to explore the composition and optical properties of these aerosol layers. The observed aerosol extinction enhancement is reproduced by CESM1/CARMA. Both model and observations indicate a strong gradient of the sulfur-to-carbon ratio from Europe to the Asia on constant pressure surfaces. We found that the ATAL is mostly composed of sulfates, surface-emitted organics, and secondary organics; the NATAL is mostly composed of sulfates and secondary organics. The model also suggests that emission increases in Asia between 2000 and 2010 led to an increase of aerosol optical depth of the ATAL by 0.002 on average which is consistent with observations. KEY POINTS: The Asian Tropopause Aerosol Layer is composed of sulfate, primary organics, and secondary organics The North American Tropospheric Aerosol Layer is mostly composed of sulfate and secondary organics Aerosol Optical Depth of Asian Tropopause Aerosol Layer increases by 0.002 from 2000 to 2010.

Activation of Group I and Group II Metabotropic Glutamate Receptors Causes LTD and LTP of Electrical Synapses in the Rat Thalamic Reticular Nucleus.

Compared with the extensive characterization of chemical synaptic plasticity, electrical synaptic plasticity remains poorly understood. Electrical synapses are strong and prevalent among the GABAergic neurons of the rodent thalamic reticular nucleus. Using paired whole-cell recordings, we show that activation of Group I metabotropic glutamate receptors (mGluRs) induces long-term depression of electrical synapses. Conversely, activation of the Group II mGluR, mGluR3, induces long-term potentiation of electrical synapses. By testing downstream targets, we show that modifications induced by both mGluR groups converge on the same signaling cascade--adenylyl cyclase to cAMP to protein kinase A--but with opposing effects. Furthermore, the magnitude of modification is inversely correlated to baseline coupling strength. Thus, electrical synapses, like their chemical counterparts, undergo both strengthening and weakening forms of plasticity, which should play a significant role in thalamocortical function.

Evaluations of tropospheric aerosol properties simulated by the community earth system model with a sectional aerosol microphysics scheme.

A sectional aerosol model (CARMA) has been developed and coupled with the Community Earth System Model (CESM1). Aerosol microphysics, radiative properties, and interactions with clouds are simulated in the size-resolving model. The model described here uses 20 particle size bins for each aerosol component including freshly nucleated sulfate particles, as well as mixed particles containing sulfate, primary organics, black carbon, dust, and sea salt. The model also includes five types of bulk secondary organic aerosols with four volatility bins. The overall cost of CESM1-CARMA is approximately ∼2.6 times as much computer time as the standard three-mode aerosol model in CESM1 (CESM1-MAM3) and twice as much computer time as the seven-mode aerosol model in CESM1 (CESM1-MAM7) using similar gas phase chemistry codes. Aerosol spatial-temporal distributions are simulated and compared with a large set of observations from satellites, ground-based measurements, and airborne field campaigns. Simulated annual average aerosol optical depths are lower than MODIS/MISR satellite observations and AERONET observations by ∼32%. This difference is within the uncertainty of the satellite observations. CESM1/CARMA reproduces sulfate aerosol mass within 8%, organic aerosol mass within 20%, and black carbon aerosol mass within 50% compared with a multiyear average of the IMPROVE/EPA data over United States, but differences vary considerably at individual locations. Other data sets show similar levels of comparison with model simulations. The model suggests that in addition to sulfate, organic aerosols also significantly contribute to aerosol mass in the tropical UTLS, which is consistent with limited data.

Retrograde changes in presynaptic function driven by dendritic mTORC1.

Mutations that alter signaling through the mammalian target of rapamycin complex 1 (mTORC1), a well established regulator of neuronal protein synthesis, have been linked to autism and cognitive dysfunction. Although previous studies have established a role for mTORC1 as necessary for enduring changes in postsynaptic function, here we demonstrate that dendritic mTORC1 activation in rat hippocampal neurons also drives a retrograde signaling mechanism promoting enhanced neurotransmitter release from apposed presynaptic terminals. This novel mode of synaptic regulation conferred by dendritic mTORC1 is locally implemented, requires downstream synthesis of brain-derived neurotrophic factor as a retrograde messenger, and is engaged in an activity-dependent fashion to support homeostatic trans-synaptic control of presynaptic function. Our findings thus reveal that mTORC1-dependent translation in dendrites subserves a unique mode of synaptic regulation, highlighting an alternative regulatory pathway that could contribute to the social and cognitive dysfunction that accompanies dysregulated mTORC1 signaling.