Technological advances in the past decades have begun to enable neuroscientists to address fundamental questions about consciousness in an unprecedented way. Here we review remarkable recent progress in our understanding of cellular-level mechanisms of conscious processing in the brain. Of particular interest are the cortical pyramidal neurons -- or "psychic cells" called by Ramón y Cajal more than 100 years ago -- which have an intriguing cellular mechanism that accounts for selective disruption of feedback signaling in the brain upon anesthetic-induced loss of consciousness. Importantly, a particular class of metabotropic receptors distributed over the dendrites of pyramidal cells are highlighted as the key cellular mechanism. After all, Cajal's instinct over a century ago may turn out to be correct -- we may have just begun to understand whether and how psychic cells indeed generate and control our consciousness.

Anesthetics are crucial in surgical procedures and therapeutic interventions, but they come with side effects and varying levels of effectiveness, calling for novel anesthetic agents that offer more precise and controllable effects. Targeting Gamma-aminobutyric acid (GABA) receptors, the primary inhibitory receptors in the central nervous system, could enhance their inhibitory action, potentially reducing side effects while improving the potency of anesthetics. In this study, we introduce a proteomic learning of GABA receptor-mediated anesthesia based on 24 GABA receptor subtypes by considering over 4000 proteins in protein-protein interaction (PPI) networks and over 1.5 millions known binding compounds. We develop a corresponding drug-target interaction network to identify potential lead compounds for novel anesthetic design. To ensure robust proteomic learning predictions, we curated a dataset comprising 136 targets from a pool of 980 targets within the PPI networks. We employed three machine learning algorithms, integrating advanced natural language processing (NLP) models such as pretrained transformer and autoencoder embeddings. Through a comprehensive screening process, we evaluated the side effects and repurposing potential of over 180,000 drug candidates targeting the GABRA5 receptor. Additionally, we assessed the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of these candidates to identify those with near-optimal characteristics. This approach also involved optimizing the structures of existing anesthetics. Our work presents an innovative strategy for the development of new anesthetic drugs, optimization of anesthetic use, and deeper understanding of potential anesthesia-related side effects.

Medical large language models (LLMs) have gained popularity recently due to their significant practical utility. However, most existing research focuses on general medicine, and there is a need for in-depth study of LLMs in specific fields like anesthesiology. To fill the gap, we introduce Hypnos, a Chinese Anesthesia model built upon existing LLMs, e.g., Llama. Hypnos' contributions have three aspects: 1) The data, such as utilizing Self-Instruct, acquired from current LLMs likely includes inaccuracies. Hypnos implements a cross-filtering strategy to improve the data quality. This strategy involves using one LLM to assess the quality of the generated data from another LLM and filtering out the data with low quality. 2) Hypnos employs a general-to-specific training strategy that starts by fine-tuning LLMs using the general medicine data and subsequently improving the fine-tuned LLMs using data specifically from Anesthesiology. The general medical data supplement the medical expertise in Anesthesiology and enhance the effectiveness of Hypnos' generation. 3) We introduce a standardized benchmark for evaluating medical LLM in Anesthesiology. Our benchmark includes both publicly available instances from the Internet and privately obtained cases from the Hospital. Hypnos outperforms other medical LLMs in anesthesiology in metrics, GPT-4, and human evaluation on the benchmark dataset.

Background: Postoperative nausea and vomiting (PONV) is a frequently observed complication in patients undergoing surgery under general anesthesia. Moreover, it is a frequent cause of distress and dissatisfaction during the early postoperative period. The tools used for predicting PONV at present have not yielded satisfactory results. Therefore, prognostic tools for the prediction of early and delayed PONV were developed in this study with the aim of achieving satisfactory predictive performance. Methods: The retrospective data of adult patients admitted to the post-anesthesia care unit after undergoing surgical procedures under general anesthesia at the Sheba Medical Center, Israel, between September 1, 2018, and September 1, 2023, were used in this study. An ensemble model of machine learning algorithms trained on the data of 54848 patients was developed. The k-fold cross-validation method was used followed by splitting the data to train and test sets that optimally preserve the sociodemographic features of the patients, such as age, sex, and smoking habits, using the Bee Colony algorithm. Findings: Among the 54848 patients, early and delayed PONV were observed in 2706 (4.93%) and 8218 (14.98%) patients, respectively. The proposed PONV prediction tools could correctly predict early and delayed PONV in 84.0% and 77.3% of cases, respectively, outperforming the second-best PONV prediction tool (Koivuranta score) by 13.4% and 12.9%, respectively. Feature importance analysis revealed that the performance of the proposed prediction tools aligned with previous clinical knowledge, indicating their utility. Interpretation: The machine learning-based tools developed in this study enabled improved PONV prediction, thereby facilitating personalized care and improved patient outcomes.

Automated anesthesia promises to enable more precise and personalized anesthetic administration and free anesthesiologists from repetitive tasks, allowing them to focus on the most critical aspects of a patient's surgical care. Current research has typically focused on creating simulated environments from which agents can learn. These approaches have demonstrated good experimental results, but are still far from clinical application. In this paper, Policy Constraint Q-Learning (PCQL), a data-driven reinforcement learning algorithm for solving the problem of learning anesthesia strategies on real clinical datasets, is proposed. Conservative Q-Learning was first introduced to alleviate the problem of Q function overestimation in an offline context. A policy constraint term is added to agent training to keep the policy distribution of the agent and the anesthesiologist consistent to ensure safer decisions made by the agent in anesthesia scenarios. The effectiveness of PCQL was validated by extensive experiments on a real clinical anesthesia dataset. Experimental results show that PCQL is predicted to achieve higher gains than the baseline approach while maintaining good agreement with the reference dose given by the anesthesiologist, using less total dose, and being more responsive to the patient's vital signs. In addition, the confidence intervals of the agent were investigated, which were able to cover most of the clinical decisions of the anesthesiologist. Finally, an interpretable method, SHAP, was used to analyze the contributing components of the model predictions to increase the transparency of the model.

The study of brain states, ranging from highly synchronous to asynchronous neuronal patterns like the sleep-wake cycle, is fundamental for assessing the brain's spatiotemporal dynamics and their close connection to behavior. However, the development of new techniques to accurately identify them still remains a challenge, as these are often compromised by the presence of noise, artifacts, and suboptimal recording quality. In this study, we propose a two-stage computational framework combining Hopfield Networks for artifact data preprocessing with Convolutional Neural Networks (CNNs) for classification of brain states in rat neural recordings under different levels of anesthesia. To evaluate the robustness of our framework, we deliberately introduced noise artifacts into the neural recordings. We evaluated our hybrid Hopfield-CNN pipeline by benchmarking it against two comparative models: a standalone CNN handling the same noisy inputs, and another CNN trained and tested on artifact-free data. Performance across various levels of data compression and noise intensities showed that our framework can effectively mitigate artifacts, allowing the model to reach parity with the clean-data CNN at lower noise levels. Although this study mainly benefits small-scale experiments, the findings highlight the necessity for advanced deep learning and Hopfield Network models to improve scalability and robustness in diverse real-world settings.

Accurately predicting anesthetic effects is essential for target-controlled infusion systems. The traditional (PK-PD) models for Bispectral index (BIS) prediction require manual selection of model parameters, which can be challenging in clinical settings. Recently proposed deep learning methods can only capture general trends and may not predict abrupt changes in BIS. To address these issues, we propose a transformer-based method for predicting the depth of anesthesia (DOA) using drug infusions of propofol and remifentanil. Our method employs long short-term memory (LSTM) and gate residual network (GRN) networks to improve the efficiency of feature fusion and applies an attention mechanism to discover the interactions between the drugs. We also use label distribution smoothing and reweighting losses to address data imbalance. Experimental results show that our proposed method outperforms traditional PK-PD models and previous deep learning methods, effectively predicting anesthetic depth under sudden and deep anesthesia conditions.

Automated object recognition in medical images can facilitate medical diagnosis and treatment. In this paper, we automatically segmented supraclavicular nerves in ultrasound images to assist in injecting peripheral nerve blocks. Nerve blocks are generally used for pain treatment after surgery, where ultrasound guidance is used to inject local anesthetics next to target nerves. This treatment blocks the transmission of pain signals to the brain, which can help improve the rate of recovery from surgery and significantly decrease the requirement for postoperative opioids. However, Ultrasound Guided Regional Anesthesia (UGRA) requires anesthesiologists to visually recognize the actual nerve position in the ultrasound images. This is a complex task given the myriad visual presentations of nerves in ultrasound images, and their visual similarity to many neighboring tissues. In this study, we used an automated nerve detection system for the UGRA Nerve Block treatment. The system can recognize the position of the nerve in ultrasound images using Deep Learning techniques. We developed a model to capture features of nerves by training two deep neural networks with skip connections: two extended U-Net architectures with and without dilated convolutions. This solution could potentially lead to an improved blockade of targeted nerves in regional anesthesia.

Ultrasound-guided nerve block anesthesia (UGNB) is a high-tech visual nerve block anesthesia method that can observe the target nerve and its surrounding structures, the puncture needle's advancement, and local anesthetics spread in real-time. The key in UGNB is nerve identification. With the help of deep learning methods, the automatic identification or segmentation of nerves can be realized, assisting doctors in completing nerve block anesthesia accurately and efficiently. Here, we establish a public dataset containing 320 ultrasound images of brachial plexus (BP). Three experienced doctors jointly produce the BP segmentation ground truth and label brachial plexus trunks. We design a brachial plexus segmentation system (BPSegSys) based on deep learning. BPSegSys achieves experienced-doctor-level nerve identification performance in various experiments. We evaluate BPSegSys' performance in terms of intersection-over-union (IoU), a commonly used performance measure for segmentation experiments. Considering three dataset groups in our established public dataset, the IoU of BPSegSys are 0.5238, 0.4715, and 0.5029, respectively, which exceed the IoU 0.5205, 0.4704, and 0.4979 of experienced doctors. In addition, we show that BPSegSys can help doctors identify brachial plexus trunks more accurately, with IoU improvement up to 27%, which has significant clinical application value.

Summary: A new deep learning algorithm is able to quantify arousal and awareness in humans at the same time. New research supported by the EU-funded HBP SGA3 and DoCMA projects is giving scientists new insight into human consciousness. Led by Korea University and projects' partner University of Liège (Belgium), the research team has developed an explainable consciousness indicator (ECI) to explore different components of consciousness. Their findings were published in the journal Nature Communications. Consciousness can be described as having two components: arousal (i.e.