Faculty Bibliography

Early identification of high-risk trauma patients in the prehospital setting is crucial for optimizing resource allocation and improving survival. We developed and externally validated a real-time AI model predicting emergency room mortality using 21 prehospital variables. Model development and internal validation utilized the Korean Trauma Data Bank (KTDB; 204,189 patients), and external validation included four South Korean trauma centers (8,358 patients) and one Australian Level 1 center (3,578 patients). Our Prehospital-AI model, an ensemble of XGBoost, LightGBM, and random forest, achieved an AUROC of 0.923 (sensitivity: 0.780, specificity: 0.880) on the test set, outperforming the shock index (AUROC: 0.712). External validation yielded AUROCs of 0.925-0.956 across South Korean centers and 0.895 in the Australian center. Here we show that the Prehospital-AI model enables accurate, real-time risk assessment in the prehospital setting, outperforming traditional triage tools and improving trauma system efficiency. Nonetheless, additional multinational studies are warranted to further evaluate its generalizability across diverse trauma care systems.

Pyramidal cells (PCs) of hippocampal area CA2 exhibit increased excitability in temporal lobe epilepsy (TLE) and in mouse models of TLE. In epileptic mice, selective inhibition of CA2 PCs reduces chronic seizures. Here we asked if activating CA2 PCs increases seizures. Mice expressing Cre recombinase in CA2 PCs (Amigo2-Cre mice) were injected with the convulsant pilocarpine to induce a period of severe seizures (status epilepticus, SE), which leads to chronic seizures after 3-4 weeks (epilepsy). Epileptic mice were injected with a Cre-dependent adeno-associated virus (AAV) to express an excitatory designer receptor exclusively activated by designer drug (eDREADD; hM3Dq) in dorsal CA2 bilaterally and implanted with subdural EEG electrodes. After recovery, mice were recorded continuously using video and EEG for 6 weeks, 3 weeks with drinking water containing the eDREADD activator clozapine-N-oxide (CNO) and 3 weeks without CNO. CA2 activation with CNO caused a significant increase in seizure frequency and duration. Seizures occurred in clusters (many seizures per day over several consecutive days) and mice given water with CNO had a greater maximum number of seizures per day during a cluster compared to water without CNO. CNO had no significant effect in control mice. In naïve Amigo2-Cre mice expressing hM3Dq, pre-treatment with CNO before pilocarpine administration shortened the latency to SE and increased EEG power at the start of SE. Taken together with prior findings, the results suggest that CA2 is a control point for regulating seizures in the pilocarpine mouse model of TLE.

AIM/OBJECTIVE:Postoperative delirium (POD) is a frequent neurological complication following surgery, often leading to poor prognoses. The red blood cell distribution width (RDW) to albumin ratio (RAR), an emerging indicator of inflammation and nutrition, was extensively utilized for prognostic evaluation of neurological disorders in elderly patients. However, the relationship between RAR and POD was not evaluated. This study aimed to investigate the independent risk factors for POD and assess the predictive value of preoperative RAR among elderly patients who had gastrointestinal tumors. METHODS:We conducted a retrospective analysis to collect perioperative data on 203 patients aged 65 years or older undergoing gastrointestinal tumor surgery from November 2023 to August 2024. The risk factors for POD were detected through univariate and multivariate logistic regression analyses. Propensity score matching (PSM) was employed to make their clinical characteristics balanced. RESULTS:Out of 203 patients, 30 (14.8%) experienced POD, with a median age of 70 (range 67-76). Hypertension, creatinine, MCH, and RAR were determined as independent risk factors for POD through multivariate logistic regression analysis. In the post-PSM cohort, RAR was still verified as a factor influencing POD. CONCLUSIONS:Hypertension, creatinine, MCH, and RAR were recognized as independent risk factors for postoperative delirium in patients following gastrointestinal tumor surgery. Particularly, the preoperative RAR served as a more efficient index for predicting POD. TRIAL REGISTRATION/BACKGROUND:Chinese Clinical Trial Center: ChiCTR2400094315.

Monitoring intracellular calcium is central to understanding cell signaling across nearly all cell types and organisms. Fluorescent genetically encoded calcium indicators (GECIs) remain the standard tools for in vivo calcium imaging, but require intense excitation light, leading to photobleaching, background autofluorescence and phototoxicity. Bioluminescent GECIs, which generate light enzymatically, eliminate these artifacts but have been constrained by low dynamic range and suboptimal calcium affinities. Here we show that CaBLAM ('calcium bioluminescence activity monitor'), an engineered bioluminescent calcium indicator, achieves an order-of-magnitude improvement in signal contrast and a tunable affinity matched to physiological cytosolic calcium. CaBLAM enables single-cell and subcellular activity imaging at video frame rates in cultured neurons and sustained imaging over hours in awake, behaving animals. These capabilities establish CaBLAM as a robust and general alternative to fluorescent GECIs, extending calcium imaging to regimes where excitation light is undesirable or infeasible.

Precision-targeted ultrasonic neuromodulation offers immense potential for studying brain function and treating neurological diseases. Yet, its application has been limited by challenges in achieving precise spatio-temporal control and monitoring of ultrasound effects on brain circuits. Here we show that transcranial ultrasound elicits direct and highly focal responses, which can be dynamically steered at spatio-temporal scales relevant for neural function. Furthermore, holographic transcranial ultrasound stimulation allows direct control of the stimulated volume and actively modulates local and mid-range network projections, effectively lowering the activation threshold by an order of magnitude. To better understand this previously unexplored excitability regime not fully explained by the conventional pressure-frequency dyad, we developed a dual modelling framework, where both an empirical and a mechanistic model were constructed to capture the intricacies of holographic transcranial ultrasound stimulation. These models achieve qualitative agreement with our experimental results, suggesting that these findings are predominantly driven by putative network interactions. Our results bring insight on the complex interaction mechanisms of ultrasound with neural tissue and highlight its potential for the noninvasive interfacing of distributed brain networks.

Transcranial AC stimulation (tACS) of the cerebellum can entrain spiking activity in the Purkinje cells (PCs) of the cerebellar cortex and, through their projections, the cells in the cerebellar nuclei (CN). In this paper, we investigated if the cells in the motor thalamus (Mthal) can also be modulated (i.e. spikes entrained) via the CN-Mthal projections in rodents. A total of 82 thalamic cells were found, presumably in the Mthal by their stereotaxic coordinates, that were modulated by tACS of the cerebellum. Out of the 346 cells isolated, the thalamic cells with shorter action potentials and regular firing patterns had a higher probability of modulation by cerebellar stimulation than the cells with wider action potentials. The modulation level had a tuning curve with a maximum around 100-200 Hz. Spike histograms over the stimulation cycle transitioned between unimodal and bimodal distributions depending on the frequency. Most cells had a unimodal distribution at low frequencies, a bimodal distribution for frequencies between 80-125 Hz, and then a unimodal one for frequencies above 150 Hz. In addition, tACS of the motor cortex (MC) was also tested in a subset of thalamic cells. Unlike cerebellar stimulation, modulation levels peaked at two distinct frequencies, presumably due to entrainment through multiple MC-Mthal pathways with different preferred frequencies. The results demonstrate the feasibility of modulating a deep brain structure such as the thalamus through multi-synaptic pathways by stimulation of the cerebellar cortex (and the motor cortex) using a non-invasive neuromodulation method.

The autonomic nervous system (ANS) plays a vital role in health care for both acute care and chronic diseases. The traditional view of the ANS is to divide it into individual organ systems and study the separate components with a reductionist approach, which has been proven insufficient. Here, we argue that a holistic network-level view of the ANS is critical for generating new insights and deepening our understanding of its complex and dynamic functions. In this review, we treat the ANS as such a coordinated and dynamic network. We advocate for studying its interactions with major organ systems and the central nervous system using continuous and longitudinal monitoring in ambulatory and at-home settings rather than clinic-based snapshots. We first briefly review ANS physiology, then outline our network perspective, and finally highlight cutting-edge research directions and emerging engineering innovations in ANS monitoring, modeling, and modulation that benefit from this network-level view.