ARIA has a billion-dollar budget and big aspirations for tackling everything from epilepsy to Alzheimer's. The UK's Advanced Research and Innovation Agency (ARIA) was established in 2023 with the goal of pursuing "high-risk, high-reward" moonshots in sectors ranging from bolstering food security to new ways of ramping up human immunity . With more than £1 billion (about $1.3 billion) worth of government funding earmarked between now and 2030, one of ARIA's most ambitious programs is a £69 million initiative that aims to develop more tailored ways of modulating the human brain. The hope is to eventually address an entire range of disorders, from epilepsy to Alzheimer's. Reports have previously estimated that this suite of neurological conditions costs the UK economy tens of billions of dollars each year.

Here we note our problem definition of pre-training is fundamentally different from domain adaptation [S1, S2, S3, S4, S5, S6]1 in order to prevent any confusion between this work and domain adaptation methods. DA applies a model trained on a pre-training dataset (i.e., source dataset) to a different target dataset [21, 42]. In contrast, self-supervised pre-training has four key differences with domain adaptation. In contrast, domain adaptation methods usually restrict pre-training and target datasets to have the same feature space (but possible different distributions), e.g., [S22, S18, S19, S20, S13]. In summary, to support transfer learning across different time series datasets, a pre-training approach needs a capability to capture a generalizable property of time series, one that is shared across different time series datasets regardless of the specific semantic meaning of a time series signal (e.g., ECG, EMG, acceleration, vibration), conditions of data acquisition (e.g., variation across subjects and devices), sampling frequencies, etc. This work develops a self-supervised contrastive pre-training strategy that fulfills these requirements by injecting an appropriate inductive bias (called Time-Frequency Consistency, TF-C, into the model (Sec. Further, we clarify that the term'self-supervised' has different meanings in DA and in pretraining [S23, S24, S25, S26]. The'self-supervised domain adaptation' [S27, S16, S21, S15] or'unsupervised domain adaptation' [S1, S22, S28, S11, S14] means that there are no labels in the target dataset, however that still requires labels in the pre-training dataset. In contrast, 'self-supervised pretraining' [S29, S30, S31] (i.e., the problem studied here, in line with a breadth of existing literature on pre-training) indicates the setting where no labels are available in pre-training. Up to the submission of this manuscript, there is no existing contrastive augmentations in time series' frequency domain. There are two models, CoST [49] and BTSF [50], that involved frequency domain in contrastive learning, however, the proposed TF-C is fundamentally different with them in the following aspects. We take BTSF as an example while the differences also apply to CoST. Problem definitions for both papers are different. Our method is designed to produce generalizable representations that can transfer to a different time series dataset (going from pre-training to a fine-tuning dataset) for the purpose of transfer learning.

Further, we clarify that the term 'self-supervised' has different meanings in DA and in pretraining [S23, S24, S25, S26]. Problem definitions for both papers are different.

Pathophysiolpgical modelling of brain systems from microscale to macroscale remains difficult in group comparisons partly because of the infeasibility of modelling the interactions of thousands of neurons at the scales involved. Here, to address the challenge, we present a novel approach to construct differential causal networks directly from electroencephalogram (EEG) data. The proposed network is based on conditionally coupled neuronal circuits which describe the average behaviour of interacting neuron populations that contribute to observed EEG data. In the network, each node represents a parameterised local neural system while directed edges stand for node-wise connections with transmission parameters. The network is hierarchically structured in the sense that node and edge parameters are varying in subjects but follow a mixed-effects model. A novel evolutionary optimisation algorithm for parameter inference in the proposed method is developed using a loss function derived from Chen-Fliess expansions of stochastic differential equations. The method is demonstrated by application to the fitting of coupled Jansen-Rit local models. The performance of the proposed method is evaluated on both synthetic and real EEG data. In the real EEG data analysis, we track changes in the parameters that characterise dynamic causality within brains that demonstrate epileptic activity. We show evidence of network functional disruptions, due to imbalance of excitatory-inhibitory interneurons and altered epileptic brain connectivity, before and during seizure periods.

In the past 20 years, mice with glowing cables sprouting from their heads have become a staple of neuroscience. They reflect the rise of optogenetics, in which neurons are engineered to contain light-sensitive proteins called opsins, allowing pulses of light to turn them on or off. The method has powered thousands of basic experiments into the brain circuits that drive behavior and underlie disease. As this research tool matured, hopes arose for using it as a treatment, too. Compared with the electrical or magnetic brain stimulation approaches already in use, optogenetics offers a way to more precisely target and manipulate the exact cell types underlying brain disorders.

Complex spatial connectivity patterns, such as interictal suppression and ictal propagation, complicate accurate drug-resistant epilepsy (DRE) seizure detection using stereotactic electroencephalography (SEEG) and traditional machine learning methods. Two critical challenges remain:(1)a low signal-to-noise ratio in functional connectivity estimates, making it difficult to learn seizure-related interactions; and (2)expert labels for spatial pathological connectivity patterns are difficult to obtain, meanwhile lacking the patterns' representation to improve seizure detection. To address these issues, we propose a novel node-graph dual contrastive learning framework, Seizure-NGCLNet, to learn SEEG interictal suppression and ictal propagation patterns for detecting DRE seizures with high precision. First, an adaptive graph augmentation strategy guided by centrality metrics is developed to generate seizure-related brain networks. Second, a dual-contrastive learning approach is integrated, combining global graph-level contrast with local node-graph contrast, to encode both spatial structural and semantic epileptogenic features. Third, the pretrained embeddings are fine-tuned via a top-k localized graph attention network to perform the final classification. Extensive experiments on a large-scale public SEEG dataset from 33 DRE patients demonstrate that Seizure-NGCLNet achieves state-of-the-art performance, with an average accuracy of 95.93%, sensitivity of 96.25%, and specificity of 94.12%. Visualizations confirm that the learned embeddings clearly separate ictal from interictal states, reflecting suppression and propagation patterns that correspond to the clinical mechanisms. These results highlight Seizure-NGCLNet's ability to learn interpretable spatial pathological patterns, enhancing both seizure detection and seizure onset zone localization.

In recent years, machine learning has become an increasingly powerful tool for supporting seizure detection and monitoring in epilepsy care. Traditional approaches focus on identifying seizures only after they begin, which limits the opportunity for early intervention and proactive treatment. In this study, we propose a novel approach that integrates both real-time seizure detection and prediction, aiming to capture subtle temporal patterns in EEG data that may indicate an upcoming seizure. Our approach was evaluated using the CHB-MIT Scalp EEG Database, which includes 969 hours of recordings and 173 seizures collected from 23 pediatric and young adult patients with drug-resistant epilepsy. To support seizure detection, we implemented a range of supervised machine learning algorithms, including K-Nearest Neighbors, Logistic Regression, Random Forest, and Support Vector Machine. The Logistic Regression achieved 90.9% detection accuracy with 89.6% recall, demonstrating balanced performance suitable for clinical screening. Random Forest and Support Vector Machine models achieved higher accuracy (94.0%) but with 0% recall, failing to detect any seizures, illustrating that accuracy alone is insufficient for evaluating medical ML models with class imbalance. For seizure prediction, we employed Long Short-Term Memory (LSTM) networks, which use deep learning to model temporal dependencies in EEG data. The LSTM model achieved 89.26% prediction accuracy. These results highlight the potential of developing accessible, real-time monitoring tools that not only detect seizures as traditionally done, but also predict them before they occur. This ability to predict seizures marks a significant shift from reactive seizure management to a more proactive approach, allowing patients to anticipate seizures and take precautionary measures to reduce the risk of injury or other complications.

Epilepsy is a chronic neurological condition characterized by recurrent seizures, with global prevalence estimated at 50 million people worldwide. While progress in high-throughput sequencing has allowed for broad-based transcriptomic profiling of brain tissues, the deciphering of these highly complex datasets remains one of the challenges. To address this issue, in this paper we propose a new analysis pipeline that integrates the power of deep learning strategies with GPU-acceleration computation for investigating Gene expression patterns in epilepsy. Specifically, our proposed approach employs GPT-2 XL, a transformer-based Large Language Model (LLM) with 1.5 billion parameters for genomic sequence analysis over the latest NVIDIA H100 Tensor Core GPUs based on Hopper architecture. Our proposed method enables efficient preprocessing of RNA sequence data, gene sequence encoding, and subsequent pattern identification. We conducted experiments on two epilepsy datasets including GEO accession GSE264537 and GSE275235. The obtained results reveal several significant transcriptomic modifications, including reduced hippocampal astrogliosis after ketogenic diet treatment as well as restored excitatory-inhibitory signaling equilibrium in zebrafish epilepsy model. Moreover, our results highlight the effectiveness of leveraging LLMs in combination with advanced hardware acceleration for transcriptomic characterization in neurological diseases.

Despite the impressive performance of LLM-powered agents, their adoption for Electronic Health Record (EHR) data access remains limited by the absence of benchmarks that adequately capture real-world clinical data access flows. In practice, two core challenges hinder deployment: query ambiguity from vague user questions and value mismatch between user terminology and database entries. To address this, we introduce EHR-ChatQA an interactive database question answering benchmark that evaluates the end-to-end workflow of database agents: clarifying user questions, using tools to resolve value mismatches, and generating correct SQL to deliver accurate answers. To cover diverse patterns of query ambiguity and value mismatch, EHR-ChatQA assesses agents in a simulated environment with an LLM-based user across two interaction flows: Incremental Query Refinement (IncreQA), where users add constraints to existing queries, and Adaptive Query Refinement (AdaptQA), where users adjust their search goals mid-conversation. Experiments with state-of-the-art LLMs (e.g., o4-mini and Gemini-2.5-Flash) over five i.i.d. trials show that while agents achieve high Pass@5 of 90-95% (at least one of five trials) on IncreQA and 60-80% on AdaptQA, their Pass^5 (consistent success across all five trials) is substantially lower by 35-60%. These results underscore the need to build agents that are not only performant but also robust for the safety-critical EHR domain. Finally, we provide diagnostic insights into common failure modes to guide future agent development.

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.