Closed -loop brain stimulation holds potential as personalized treatment for drug-resistant epilepsy (DRE) but still suffers from limitations that result in highly variable efficacy. First, stimulation is typically delivered upon detection of the seizure to abort rather than prevent it; second, the stimulation parameters are established by trial and error, requiring lengthy rounds of fine -tuning, which delay steady-state therapeutic efficacy. Here, we address these limitations by leveraging the potential of neuromorphic computing. We present a neuromorphic reservoir computing hardware system capable of driving real - time personalized free-run stimulations based on seizure forecasting, wherein each forecast triggers an electrical pulse rather than an arbitrarily predefined fixed -frequency stimulus train. The system achieves 83.33% accuracy in forecasting seizure occurrences during the training phase. We validate the system using hippocampal spheroids coupled to 3D microelectrode array as a simplified testbed, achieving seizure reduction >97% during the real -time processing while primarily using instantaneous stimulation frequencies within 20 Hz, well below what typically used in clinical practice. Our work demonstrates the potential of neuromorphic systems as a next -generation neuromodulation strategy for personalized DRE treatment, leveraging their sparse and event-driven processing for real -time applications. Keywords: Neuromorphic system, drug-resistant epilepsy, seizure forecasting, neuromodulation, closed -loop stimulation, edge-devices.

Deep learning methods are at the forefront of automated epileptic seizure detection and onset zone localization using scalp-EEG. However, the performance of deep learning methods rely heavily on the quality of annotated training datasets. Scalp EEG is susceptible to high noise levels, which in turn leads to imprecise annotations of the seizure timing and characteristics. This label noise presents a significant challenge in model training and generalization. In this paper, we introduce a novel statistical framework that informs a deep learning model of label ambiguity, thereby enhancing the overall seizure detection performance. Our Bayesian UncertaiNty-aware Deep Learning, BUNDL, strategy offers a straightforward and model-agnostic method for training deep neural networks with noisy training labels that does not add any parameters to existing architectures. By integrating domain knowledge into the statistical framework, we derive a novel KL-divergence-based loss function that capitalizes on uncertainty to better learn seizure characteristics from scalp EEG. Additionally, we explore the impact of improved seizure detection on the task of automated onset zone localization. We validate BUNDL using a comprehensive simulated EEG dataset and two publicly available datasets, TUH and CHB-MIT. BUNDL consistently improves the performance of three base models on simulated data under seven types of label noise and three EEG signal-to-noise ratios. Similar improvements were observed in the real-world TUH and CHB-MIT datasets. Finally, we demonstrate that BUNDL improves the accuracy of seizure onset zone localization. BUNDL is specifically designed to address label ambiguities, enabling the training of reliable and trustworthy models for epilepsy evaluation.

Epilepsy represents the most prevalent neurological disease in the world. One-third of people suffering from mesial temporal lobe epilepsy (MTLE) exhibit drug resistance, urging the need to develop new treatments. A key part in anti-seizure medication (ASM) development is the capability of detecting and quantifying epileptic seizures occurring in electroencephalogram (EEG) signals, which is crucial for treatment efficacy evaluation. In this study, we introduced a seizure detection pipeline based on deep learning models applied to raw EEG signals. This pipeline integrates: a new pre-processing technique which segments continuous raw EEG signals without prior distinction between seizure and seizure-free activities; a post-processing algorithm developed to reassemble EEG segments and allow the identification of seizures start/end; and finally, a new evaluation procedure based on a strict seizure events comparison between predicted and real labels. Models training have been performed using a data splitting strategy which addresses the potential for data leakage. We demonstrated the fundamental differences between a seizure classification and a seizure detection task and showed the differences in performance between the two tasks. Finally, we demonstrated the generalization capabilities across species of our best architecture, combining a Convolutional Neural Network and a Transformer encoder. The model was trained on animals' EEGs and tested on humans' EEGs with a F1-score of 93% on a balanced Bonn dataset.

Large Language Models (LLMs) demonstrate remarkable versatility in various NLP tasks but encounter distinct challenges in biomedical due to the complexities of language and data scarcity. This paper investigates LLMs application in the biomedical domain by exploring strategies to enhance their performance for the NER task. Our study reveals the importance of meticulously designed prompts in the biomedical. Strategic selection of in-context examples yields a marked improvement, offering ~15-20\% increase in F1 score across all benchmark datasets for biomedical few-shot NER. Additionally, our results indicate that integrating external biomedical knowledge via prompting strategies can enhance the proficiency of general-purpose LLMs to meet the specialized needs of biomedical NER. Leveraging a medical knowledge base, our proposed method, DiRAG, inspired by Retrieval-Augmented Generation (RAG), can boost the zero-shot F1 score of LLMs for biomedical NER. Code is released at \url{https://github.com/masoud-monajati/LLM_Bio_NER}

Epileptic seizure activity shows complicated dynamics in both space and time. To understand the evolution and propagation of seizures spatially extended sets of data need to be analysed. We have previously described an efficient filtering scheme using variational Laplace that can be used in the Dynamic Causal Modelling (DCM) framework [Friston, 2003] to estimate the temporal dynamics of seizures recorded using either invasive or non-invasive electrical recordings (EEG/ECoG). Spatiotemporal dynamics are modelled using a partial differential equation -- in contrast to the ordinary differential equation used in our previous work on temporal estimation of seizure dynamics [Cooray, 2016]. We provide the requisite theoretical background for the method and test the ensuing scheme on simulated seizure activity data and empirical invasive ECoG data. The method provides a framework to assimilate the spatial and temporal dynamics of seizure activity, an aspect of great physiological and clinical importance.

Epilepsy is one of the most common neurological disorders that greatly impair patient' daily lives. Traditional epileptic diagnosis relies on tedious visual screening by neurologists from lengthy EEG recording that requires the presence of seizure (ictal) activities. Nowadays, there are many systems helping the neurologists to quickly find interesting segments of the lengthy signal by automatic seizure detection. However, we notice that it is very difficult, if not impossible, to obtain long-term EEG data with seizure activities for epilepsy patients in areas lack of medical resources and trained neurologists. Therefore, we propose to study automated epileptic diagnosis using interictal EEG data that is much easier to collect than ictal data. The authors are not aware of any report on automated EEG diagnostic system that can accurately distinguish patients' interictal EEG from the EEG of normal people. The research presented in this paper, therefore, aims to develop an automated diagnostic system that can use interictal EEG data to diagnose whether the person is epileptic. Such a system should also detect seizure activities for further investigation by doctors and potential patient monitoring. To develop such a system, we extract four classes of features from the EEG data and build a Probabilistic Neural Network (PNN) fed with these features. Leave-one-out cross-validation (LOO-CV) on a widely used epileptic-normal data set reflects an impressive 99.5% accuracy of our system on distinguishing normal people's EEG from patient's interictal EEG. We also find our system can be used in patient monitoring (seizure detection) and seizure focus localization, with 96.7% and 77.5% accuracy respectively on the data set.