Chikayo Hemmi

Despite the widespread application of general anesthesia since the 19th century, a fundamental understanding of its operating principle and a reliable metric of consciousness remains elusive. We here analyze Loss of Responsiveness (LoR) induced by propofol anesthesia in humans and macaque monkeys. Through application of “highly comparable time series analysis” (hctsa) over 7000 features, we aim to identify LoR metrics common to both humans and macaque monkeys. In Stage 1 analysis, we trained a nearest median classifier using 200 ms data epochs using one macaque individual, and evaluated its classification accuracy on human intracranial data, recorded from one participant. This analysis suggested the existence of univariate features capable of discriminating between awake and propofol-induced unresponsive states in both species. Stage 2 extended the analysis to additional macaque and human recordings to evaluate cross-session and cross-species generalization. We identified many hctsa features that commonly distinguished awake from unresponsive states across sessions and species, in the frontal, but not in parietal and temporal, recordings. In exploratory analyses, we aimed to distinguish loss of responsiveness from consciousness, by additionally analyzing human data under sedated yet conscious state in a within-subject manner. This analysis revealed that frontal, temporal and parietal recordings contain similarly sensitive features and channels as signatures of consciousness. These results support the existence of ECoG time-series features associated with propofol-induced loss of responsiveness across humans and macaques, while also highlighting the challenge to determine whether such features specifically track conscious experience rather than responsiveness.

Dream experiences during sleep provide an excellent opportunity to investigate the neural basis of consciousness. Previous studies have examined the neural correlates of dreaming using electroencephalography (EEG), focusing on spectral power in specific frequency bands. However, findings have been inconsistent, particularly regarding the spatiotemporal characteristics of these correlates, raising questions about whether spectral power in specific brain regions and frequency bands reliably reflects dreaming. In this study, we investigate whether neural correlates reported in a highly influential EEG study generalize to consciousness during evening naps, measured using magnetoencephalography (MEG), which offers more accurate source reconstruction than EEG. In Stage 1, the data acquisition team completed data collection, obtaining MEG data and subjective reports using a targeted serial-awakening paradigm. We test hypotheses regarding the relationship between low- and high-frequency neural power in frontal and posterior regions and conscious experience. We defined data inclusion and exclusion criteria and established pre-specified analytical procedures based on data from two participants. The pilot results from one participant were consistent with the hypotheses concerning low-frequency power across regions, but not with those related to high-frequency power. The other participant provided insufficient evidence for all hypotheses. In Stage 2, an independent analysis team will conduct group-level hypothesis testing according to the pre-specified procedure, using data from the remaining unanalyzed participants (N = 10) who meet the inclusion criteria.

Sleep–wakefulness regulation dynamically evolves along development in a wide range of organisms. While the mechanism regulating sleep in adults is relatively well understood, little is known about its counterpart in early developmental stages. Here, we report a neuropeptidergic circuitry that modulates sleep in developing Drosophila larvae. Through an unbiased screen, we identified the neuropeptide Hugin and its receptor PK2-R1 as critical regulators of larval sleep. Our genetic and behavioral data suggest that HugPC neurons secrete Hugin peptides to activate insulin-producing cells (IPCs), which express a Hugin receptor PK2-R1. IPCs, in turn, release insulin-like peptides (Dilps) to regulate sleep. We further show that the Hugin/PK2-R1 axis is dispensable for adult sleep. Our findings thus reveal the neuromodulatory circuit that regulates developmental sleep in larvae and highlight differential impacts of the same modulatory axis on early-life sleep and adult sleep.

Somatosensory neurons (SSNs) that detect and transduce mechanical, thermal, and chemical stimuli densely innervate an animal’s skin. However, although epidermal cells provide the first point of contact for sensory stimuli, our understanding of roles that epidermal cells play in SSN function, particularly nociception, remains limited. Here, we show that stimulating Drosophila epidermal cells elicits activation of SSNs including nociceptors and triggers a variety of behavior outputs, including avoidance and escape. Further, we find that epidermal cells are intrinsically mechanosensitive and that epidermal mechanically evoked calcium responses require the store-operated calcium channel Orai. Epidermal cell stimulation augments larval responses to acute nociceptive stimuli and promotes prolonged hypersensitivity to subsequent mechanical stimuli. Hence, epidermal cells are key determinants of nociceptive sensitivity and sensitization, acting as primary sensors of noxious stimuli that tune nociceptor output and drive protective behaviors.