The hippocampus, a critical brain structure involved in memory processing and various neurodegenerative and psychiatric disorders, comprises three key subregions: the dentate gyrus (DG), Cornu Ammonis 1 (CA1), and Cornu Ammonis 3 (CA3). Accurate segmentation of these subregions from histological tissue images is essential for advancing our understanding of disease mechanisms, developmental dynamics, and therapeutic interventions. However, no existing methods address the automated segmentation of hippocampal subregions from tissue images, particularly from immunohistochemistry (IHC) images. To bridge this gap, we introduce a novel set of four comprehensive murine hippocampal IHC datasets featuring distinct staining modalities: cFos, NeuN, and multiplexed stains combining cFos, NeuN, and either {\Delta}FosB or GAD67, capturing structural, neuronal activity, and plasticity associated information. Additionally, we propose ROIsGAN, a region-guided U-Net-based generative adversarial network tailored for hippocampal subregion segmentation. By leveraging adversarial learning, ROIsGAN enhances boundary delineation and structural detail refinement through a novel region-guided discriminator loss combining Dice and binary cross-entropy loss. Evaluated across DG, CA1, and CA3 subregions, ROIsGAN consistently outperforms conventional segmentation models, achieving performance gains ranging from 1-10% in Dice score and up to 11% in Intersection over Union (IoU), particularly under challenging staining conditions. Our work establishes foundational datasets and methods for automated hippocampal segmentation, enabling scalable, high-precision analysis of tissue images in neuroscience research. Our generated datasets, proposed model as a standalone tool, and its corresponding source code are publicly available at: https://github.com/MehediAzim/ROIsGAN
Modeling episodic memory (EM) remains a significant challenge in both neuroscience and AI, with existing models either lacking interpretability or struggling with practical applications. This paper proposes the Vision-Language Episodic Memory (VLEM) framework to address these challenges by integrating large-scale pretrained models with hippocampal attractor dynamics. VLEM leverages the strong semantic understanding of pretrained models to transform sensory input into semantic embeddings as the neocortex, while the hippocampus supports stable memory storage and retrieval through attractor dynamics. In addition, VLEM incorporates prefrontal working memory and the entorhinal gateway, allowing interaction between the neocortex and the hippocampus. To facilitate real-world applications, we introduce EpiGibson, a 3D simulation platform for generating episodic memory data. Experimental results demonstrate the VLEM framework's ability to efficiently learn high-level temporal representations from sensory input, showcasing its robustness, interpretability, and applicability in real-world scenarios.
Diffusion models have been used extensively for high quality image and video generation tasks. In this paper, we propose a novel conditional diffusion model with spatial attention and latent embedding (cDAL) for medical image segmentation. In cDAL, a convolutional neural network (CNN) based discriminator is used at every time-step of the diffusion process to distinguish between the generated labels and the real ones. A spatial attention map is computed based on the features learned by the discriminator to help cDAL generate more accurate segmentation of discriminative regions in an input image. Additionally, we incorporated a random latent embedding into each layer of our model to significantly reduce the number of training and sampling time-steps, thereby making it much faster than other diffusion models for image segmentation. We applied cDAL on 3 publicly available medical image segmentation datasets (MoNuSeg, Chest X-ray and Hippocampus) and observed significant qualitative and quantitative improvements with higher Dice scores and mIoU over the state-of-the-art algorithms. The source code is publicly available at https://github.com/Hejrati/cDAL/.
Large language models based Multi Agent Systems (MAS) have demonstrated promising performance for enhancing the efficiency and accuracy of code generation tasks. However,most existing methods follow a conventional sequence of planning, coding, and debugging,which contradicts the growth-driven nature of human learning process. Additionally,the frequent information interaction between multiple agents inevitably involves high computational costs. In this paper,we propose Cogito,a neurobiologically inspired multi-agent framework to enhance the problem-solving capabilities in code generation tasks with lower cost. Specifically,Cogito adopts a reverse sequence: it first undergoes debugging, then coding,and finally planning. This approach mimics human learning and development,where knowledge is acquired progressively. Accordingly,a hippocampus-like memory module with different functions is designed to work with the pipeline to provide quick retrieval in similar tasks. Through this growth-based learning model,Cogito accumulates knowledge and cognitive skills at each stage,ultimately forming a Super Role an all capable agent to perform the code generation task. Extensive experiments against representative baselines demonstrate the superior performance and efficiency of Cogito. The code is publicly available at https://anonymous.4open.science/r/Cogito-0083.
Segmentation of cellular structures in electron microscopy (EM) images is fundamental to analyzing the morphology of neurons and glial cells in the healthy and diseased brain tissue. Current neuronal segmentation applications are based on convolutional neural networks (CNNs) and do not effectively capture global relationships within images. Here, we present DendriteSAM, a vision foundation model based on Segment Anything, for interactive and automatic segmentation of dendrites in EM images. The model is trained on high-resolution EM data from healthy rat hippocampus and is tested on diseased rat and human data. Our evaluation results demonstrate better mask quality compared to the original and other fine-tuned models, leveraging the features learned during training. This study introduces the first implementation of vision foundation models in dendrite segmentation, paving the path for computer-assisted diagnosis of neuronal anomalies.
Continual learning (CL) in medical imaging presents a unique challenge, requiring models to adapt to new domains while retaining previously acquired knowledge. We introduce NCAdapt, a Neural Cellular Automata (NCA) based method designed to address this challenge. NCAdapt features a domain-specific multi-head structure, integrating adaptable convolutional layers into the NCA backbone for each new domain encountered. After initial training, the NCA backbone is frozen, and only the newly added adaptable convolutional layers, consisting of 384 parameters, are trained along with domain-specific NCA convolutions. We evaluate NCAdapt on hippocampus segmentation tasks, benchmarking its performance against Lifelong nnU-Net and U-Net models with state-of-the-art (SOTA) CL methods. Our lightweight approach achieves SOTA performance, underscoring its effectiveness in addressing CL challenges in medical imaging. Upon acceptance, we will make our code base publicly accessible to support reproducibility and foster further advancements in medical CL.
Medical image registration is a critical process that aligns various patient scans, facilitating tasks like diagnosis, surgical planning, and tracking. Traditional optimization based methods are slow, prompting the use of Deep Learning (DL) techniques, such as VoxelMorph and Transformer-based strategies, for faster results. However, these DL methods often impose significant resource demands. In response to these challenges, we present NCA-Morph, an innovative approach that seamlessly blends DL with a bio-inspired communication and networking approach, enabled by Neural Cellular Automata (NCAs). NCA-Morph not only harnesses the power of DL for efficient image registration but also builds a network of local communications between cells and respective voxels over time, mimicking the interaction observed in living systems. In our extensive experiments, we subject NCA-Morph to evaluations across three distinct 3D registration tasks, encompassing Brain, Prostate and Hippocampus images from both healthy and diseased patients. The results showcase NCA-Morph's ability to achieve state-of-the-art performance. Notably, NCA-Morph distinguishes itself as a lightweight architecture with significantly fewer parameters; 60% and 99.7% less than VoxelMorph and TransMorph. This characteristic positions NCA-Morph as an ideal solution for resource-constrained medical applications, such as primary care settings and operating rooms.
Accurate hippocampus segmentation in brain MRI is critical for studying cognitive and memory functions and diagnosing neurodevelopmental disorders. While high-field MRIs provide detailed imaging, low-field MRIs are more accessible and cost-effective, which eliminates the need for sedation in children, though they often suffer from lower image quality. In this paper, we present a novel deep-learning approach for the automatic segmentation of bilateral hippocampi in low-field MRIs. Extending recent advancements in infant brain segmentation to underserved communities through the use of low-field MRIs ensures broader access to essential diagnostic tools, thereby supporting better healthcare outcomes for all children. Inspired by our previous work, Co-BioNet, the proposed model employs a dual-view structure to enable mutual feature learning via high-frequency masking, enhancing segmentation accuracy by leveraging complementary information from different perspectives. Extensive experiments demonstrate that our method provides reliable segmentation outcomes for hippocampal analysis in low-resource settings. The code is publicly available at: https://github.com/himashi92/LoFiHippSeg.
Goal-conditioned hierarchical reinforcement learning (HRL) decomposes complex reaching tasks into a sequence of simple subgoal-conditioned tasks, showing significant promise for addressing long-horizon planning in large-scale environments. This paper bridges the goal-conditioned HRL based on graph-based planning to brain mechanisms, proposing a hippocampus-striatum-like dual-controller hypothesis. Inspired by the brain mechanisms of organisms (i.e., the high-reward preferences observed in hippocampal replay) and instance-based theory, we propose a high-return sampling strategy for constructing memory graphs, improving sample efficiency. Additionally, we derive a model-free lower-level Q-function gradient penalty to resolve the model dependency issues present in prior work, improving the generalization of Lipschitz constraints in applications. Finally, we integrate these two extensions, High-reward Graph and model-free Gradient Penalty (HG2P), into the state-of-the-art framework ACLG, proposing a novel goal-conditioned HRL framework, HG2P+ACLG. Experimentally, the results demonstrate that our method outperforms state-of-the-art goal-conditioned HRL algorithms on a variety of long-horizon navigation tasks and robotic manipulation tasks.
Understanding the structural growth of paediatric brains is a key step in the identification of various neuro-developmental disorders. However, our knowledge is limited by many factors, including the lack of automated image analysis tools, especially in Low and Middle Income Countries from the lack of high field MR images available. Low-field systems are being increasingly explored in these countries, and, therefore, there is a need to develop automated image analysis tools for these images. In this work, as a preliminary step, we consider two tasks: 1) automated quality assurance and 2) hippocampal segmentation, where we compare multiple approaches. For the automated quality assurance task a DenseNet combined with appearance-based transformations for synthesising artefacts produced the best performance, with a weighted accuracy of 82.3%. For the segmentation task, registration of an average atlas performed the best, with a final Dice score of 0.61. Our results show that although the images can provide understanding of large scale pathologies and gross scale anatomical development, there still remain barriers for their use for more granular analyses.
Delineating and classifying individual cells in microscopy tissue images is inherently challenging yet remains essential for advancements in medical and neuroscientific research. In this work, we propose a new deep learning framework, CISCA, for automatic cell instance segmentation and classification in histological slices. At the core of CISCA is a network architecture featuring a lightweight U-Net with three heads in the decoder. The first head classifies pixels into boundaries between neighboring cells, cell bodies, and background, while the second head regresses four distance maps along four directions. The outputs from the first and second heads are integrated through a tailored post-processing step, which ultimately produces the segmentation of individual cells. The third head enables the simultaneous classification of cells into relevant classes, if required. We demonstrate the effectiveness of our method using four datasets, including CoNIC, PanNuke, and MoNuSeg, which are publicly available H&Estained datasets that cover diverse tissue types and magnifications. In addition, we introduce CytoDArk0, the first annotated dataset of Nissl-stained histological images of the mammalian brain, containing nearly 40k annotated neurons and glia cells, aimed at facilitating advancements in digital neuropathology and brain cytoarchitecture studies. We evaluate CISCA against other state-of-the-art methods, demonstrating its versatility, robustness, and accuracy in segmenting and classifying cells across diverse tissue types, magnifications, and staining techniques. This makes CISCA well-suited for detailed analyses of cell morphology and efficient cell counting in both digital pathology workflows and brain cytoarchitecture research.
Incomplete Hippocampal Inversion (IHI), sometimes called hippocampal malrotation, is an atypical anatomical pattern of the hippocampus found in about 20% of the general population. IHI can be visually assessed on coronal slices of T1 weighted MR images, using a composite score that combines four anatomical criteria. IHI has been associated with several brain disorders (epilepsy, schizophrenia). However, these studies were based on small samples. Furthermore, the factors (genetic or environmental) that contribute to the genesis of IHI are largely unknown. Large-scale studies are thus needed to further understand IHI and their potential relationships to neurological and psychiatric disorders. However, visual evaluation is long and tedious, justifying the need for an automatic method. In this paper, we propose, for the first time, to automatically rate IHI. We proceed by predicting four anatomical criteria, which are then summed up to form the IHI score, providing the advantage of an interpretable score. We provided an extensive experimental investigation of different machine learning methods and training strategies. We performed automatic rating using a variety of deep learning models (conv5-FC3, ResNet and SECNN) as well as a ridge regression. We studied the generalization of our models using different cohorts and performed multi-cohort learning. We relied on a large population of 2,008 participants from the IMAGEN study, 993 and 403 participants from the QTIM/QTAB studies as well as 985 subjects from the UKBiobank. We showed that deep learning models outperformed a ridge regression. We demonstrated that the performances of the conv5-FC3 network were at least as good as more complex networks while maintaining a low complexity and computation time. We showed that training on a single cohort may lack in variability while training on several cohorts improves generalization.
Medical image analysis using deep learning frameworks has advanced healthcare by automating complex tasks, but many existing frameworks lack flexibility, modularity, and user-friendliness. To address these challenges, we introduce Yucca, an open-source AI framework available at https://github.com/Sllambias/yucca, designed specifically for medical imaging applications and built on PyTorch and PyTorch Lightning. Yucca features a three-tiered architecture: Functional, Modules, and Pipeline, providing a comprehensive and customizable solution. Evaluated across diverse tasks such as cerebral microbleeds detection, white matter hyperintensity segmentation, and hippocampus segmentation, Yucca achieves state-of-the-art results, demonstrating its robustness and versatility. Yucca offers a powerful, flexible, and user-friendly platform for medical image analysis, inviting community contributions to advance its capabilities and impact.
The hippocampus is a crucial brain structure associated with various psychiatric disorders, and its automatic and precise segmentation is essential for studying these diseases. In recent years, deep learning-based methods have made significant progress in hippocampus segmentation. However, training deep neural network models requires substantial computational resources and time, as well as a large amount of labeled training data, which is often difficult to obtain in medical image segmentation. To address this issue, we propose a new parameter-efficient fine-tuning method called LoRA-PT. This method transfers the pre-trained UNETR model on the BraTS2021 dataset to the hippocampus segmentation task. Specifically, the LoRA-PT method categorizes the parameter matrix of the transformer structure into three sizes, forming three 3D tensors. Through tensor singular value decomposition, these tensors are decomposed to generate low-rank tensors with the principal singular values and singular vectors, while the remaining singular values and vectors form the residual tensor. During the fine-tuning, we only update the low-rank tensors, i.e. the principal tensor singular values and vectors, while keeping the residual tensor unchanged. We validated the proposed method on three public hippocampus datasets. Experimental results show that LoRA-PT outperforms existing parameter-efficient fine-tuning methods in segmentation accuracy while significantly reducing the number of parameter updates. Our code is available at https://github.com/WangangCheng/LoRA-PT/tree/LoRA-PT.
This study presents an innovative method for Alzheimer's disease diagnosis using 3D MRI designed to enhance the explainability of model decisions. Our approach adopts a soft attention mechanism, enabling 2D CNNs to extract volumetric representations. At the same time, the importance of each slice in decision-making is learned, allowing the generation of a voxel-level attention map to produce an explainable MRI. To test our method and ensure the reproducibility of our results, we chose a standardized collection of MRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). On this dataset, our method significantly outperforms state-of-the-art methods in (i) distinguishing AD from cognitive normal (CN) with an accuracy of 0.856 and Matthew's correlation coefficient (MCC) of 0.712, representing improvements of 2.4% and 5.3% respectively over the second-best, and (ii) in the prognostic task of discerning stable from progressive mild cognitive impairment (MCI) with an accuracy of 0.725 and MCC of 0.443, showing improvements of 10.2% and 20.5% respectively over the second-best. We achieved this prognostic result by adopting a double transfer learning strategy, which enhanced sensitivity to morphological changes and facilitated early-stage AD detection. With voxel-level precision, our method identified which specific areas are being paid attention to, identifying these predominant brain regions: the hippocampus, the amygdala, the parahippocampal, and the inferior lateral ventricles. All these areas are clinically associated with AD development. Furthermore, our approach consistently found the same AD-related areas across different cross-validation folds, proving its robustness and precision in highlighting areas that align closely with known pathological markers of the disease.
This study investigates the loss of generalization ability in neural networks, revisiting warm-starting experiments from Ash & Adams. Our empirical analysis reveals that common methods designed to enhance plasticity by maintaining trainability provide limited benefits to generalization. While reinitializing the network can be effective, it also risks losing valuable prior knowledge. To this end, we introduce the Hare & Tortoise, inspired by the brain's complementary learning system. Hare & Tortoise consists of two components: the Hare network, which rapidly adapts to new information analogously to the hippocampus, and the Tortoise network, which gradually integrates knowledge akin to the neocortex. By periodically reinitializing the Hare network to the Tortoise's weights, our method preserves plasticity while retaining general knowledge. Hare & Tortoise can effectively maintain the network's ability to generalize, which improves advanced reinforcement learning algorithms on the Atari-100k benchmark. The code is available at https://github.com/dojeon-ai/hare-tortoise.
In order to thrive in hostile and ever-changing natural environments, mammalian brains evolved to store large amounts of knowledge about the world and continually integrate new information while avoiding catastrophic forgetting. Despite the impressive accomplishments, large language models (LLMs), even with retrieval-augmented generation (RAG), still struggle to efficiently and effectively integrate a large amount of new experiences after pre-training. In this work, we introduce HippoRAG, a novel retrieval framework inspired by the hippocampal indexing theory of human long-term memory to enable deeper and more efficient knowledge integration over new experiences. HippoRAG synergistically orchestrates LLMs, knowledge graphs, and the Personalized PageRank algorithm to mimic the different roles of neocortex and hippocampus in human memory. We compare HippoRAG with existing RAG methods on multi-hop question answering and show that our method outperforms the state-of-the-art methods remarkably, by up to 20%. Single-step retrieval with HippoRAG achieves comparable or better performance than iterative retrieval like IRCoT while being 10-30 times cheaper and 6-13 times faster, and integrating HippoRAG into IRCoT brings further substantial gains. Finally, we show that our method can tackle new types of scenarios that are out of reach of existing methods. Code and data are available at https://github.com/OSU-NLP-Group/HippoRAG.
The hippocampus has been associated with both spatial cognition and episodic memory formation, but integrating these functions into a unified framework remains challenging. Here, we demonstrate that forming discrete memories of visual events in sparse autoencoder neurons can produce spatial tuning similar to hippocampal place cells. We then show that the resulting very high-dimensional code enables neurons to discretize and tile the underlying image space with minimal overlap. Additionally, we extend our results to the auditory domain, showing that neurons similarly tile the frequency space in an experience-dependent manner. Lastly, we show that reinforcement learning agents can effectively perform various visuo-spatial cognitive tasks using these sparse, very high-dimensional representations.
This paper introduces a new technique to measure the feature dependency of neural network models. The motivation is to better understand a model by querying whether it is using information from human-understandable features, e.g., anatomical shape, volume, or image texture. Our method is based on the principle that if a model is dependent on a feature, then removal of that feature should significantly harm its performance. A targeted feature is "removed" by collapsing the dimension in the data distribution that corresponds to that feature. We perform this by moving data points along the feature dimension to a baseline feature value while staying on the data manifold, as estimated by a deep generative model. Then we observe how the model's performance changes on the modified test data set, with the target feature dimension removed. We test our method on deep neural network models trained on synthetic image data with known ground truth, an Alzheimer's disease prediction task using MRI and hippocampus segmentations from the OASIS-3 dataset, and a cell nuclei classification task using the Lizard dataset.
This paper presents a comprehensive study focused on disentangling hippocampal shape variations from diffusion tensor imaging (DTI) datasets within the context of neurological disorders. Leveraging a Mesh Variational Autoencoder (VAE) enhanced with Supervised Contrastive Learning, our approach aims to improve interpretability by disentangling two distinct latent variables corresponding to age and the presence of diseases. In our ablation study, we investigate a range of VAE architectures and contrastive loss functions, showcasing the enhanced disentanglement capabilities of our approach. This evaluation uses synthetic 3D torus mesh data and real 3D hippocampal mesh datasets derived from the DTI hippocampal dataset. Our supervised disentanglement model outperforms several state-of-the-art (SOTA) methods like attribute and guided VAEs in terms of disentanglement scores. Our model distinguishes between age groups and disease status in patients with Multiple Sclerosis (MS) using the hippocampus data. Our Mesh VAE with Supervised Contrastive Learning shows the volume changes of the hippocampus of MS populations at different ages, and the result is consistent with the current neuroimaging literature. This research provides valuable insights into the relationship between neurological disorder and hippocampal shape changes in different age groups of MS populations using a Mesh VAE with Supervised Contrastive loss. Our code is available at https://github.com/Jakaria08/Explaining_Shape_Variability