Despite tremendous success in neuroimaging methodology, making large-scale, high-dimensional datasets ready for AI/ML applications remains a critical operational bottleneck. Conventional workflows require extensive manual effort across metadata curation, pipeline execution, post-processing quality control, and data management, a burden that disproportionately excludes laboratories with limited manpower and computational infrastructure. To address this real-world barrier, there is an urgent need for scalable, cost-effective computational platforms that democratize advanced neuroimaging analytics and accelerate discoveries in mental health and clinical translation. Capitalizing on multi-agent LLM breakthroughs, we introduce CyberNeuro, an agentic workbench with a tailored local LLM-model ('WandaMind') for automated neuroimaging and health-data analysis. Driven by four dedicated agents (Planner, Validator, Dispatcher, and Reporter) communicating via a secure MCP bridge and a pinned execution layer, CyberNeuro enables researchers to execute complex workflows using natural language while maintaining clinical-grade data privacy. On the public NeuroBench suite, CyberNeuro increases held-o
Multimodal neuroimaging, integrating functional connectivity from fMRI and structural connectivity from DTI, enables non-invasive analysis of brain networks using graph neural networks. However, demographic factors such as age and sex systematically confound the relationship between brain connectivity and clinical outcomes, causing GNNs to exploit spurious shortcuts rather than learning causally invariant representations. While recent causal GNN methods introduce causality at the graph-modeling level, their causal mechanisms remain domain-agnostic without accounting for the real-world confounders inherent in clinical neuroimaging data. Moreover, brain networks are constructed from atlas-based parcellations where each region exhibits distinct sensitivity to demographic factors, necessitating region-aware adjustment. We propose Artemis, a region-level causal framework that bridges this gap with causal intervention at each brain region independently by learning region-specific confounder representations with lightweight parameters. Our adjustment comprehensively utilized the multimodal functional and structural features for graph reasoning as a plug-in module compatible with arbitrary
Deep learning has revolutionized neuroimage analysis by delivering unprecedented speed and accuracy. However, the narrow scope of many training datasets constrains model robustness and generalizability. This challenge is particularly acute in magnetic resonance imaging (MRI), where image appearance varies widely across pulse sequences and scanner hardware. A recent domain-randomization strategy addresses the generalization problem by training deep neural networks on synthetic images with randomized intensities and anatomical content. By generating diverse data from anatomical segmentation maps, the approach enables models to accurately process image types unseen during training, without retraining or fine-tuning. It has demonstrated effectiveness across modalities including MRI, computed tomography, positron emission tomography, and optical coherence tomography, as well as beyond neuroimaging in ultrasound, electron and fluorescence microscopy, and X-ray microtomography. This tutorial paper reviews the principles, implementation, and potential of the synthesis-driven training paradigm. It highlights key benefits, such as improved generalization and resistance to overfitting, while
A Method for structural-to-functional neuroimage translator
Multi-modality imaging improves disease diagnosis and reveals distinct deviations in tissues with anatomical properties. The existence of completely aligned and paired multi-modality neuroimaging data has proved its effectiveness in brain research. However, collecting fully aligned and paired data is expensive or even impractical, since it faces many difficulties, including high cost, long acquisition time, image corruption, and privacy issues. An alternative solution is to explore unsupervised or weakly supervised learning methods to synthesize the absent neuroimaging data. In this paper, we provide a comprehensive review of cross-modality synthesis for neuroimages, from the perspectives of weakly supervised and unsupervised settings, loss functions, evaluation metrics, imaging modalities, datasets, and downstream applications based on synthesis. We begin by highlighting several opening challenges for cross-modality neuroimage synthesis. Then, we discuss representative architectures of cross-modality synthesis methods under different supervisions. This is followed by a stepwise in-depth analysis to evaluate how cross-modality neuroimage synthesis improves the performance of its do
Neuroimage processing tasks like segmentation, reconstruction, and registration are central to the study of neuroscience. Robust deep learning strategies and architectures used to solve these tasks are often similar. Yet, when presented with a new task or a dataset with different visual characteristics, practitioners most often need to train a new model, or fine-tune an existing one. This is a time-consuming process that poses a substantial barrier for the thousands of neuroscientists and clinical researchers who often lack the resources or machine-learning expertise to train deep learning models. In practice, this leads to a lack of adoption of deep learning, and neuroscience tools being dominated by classical frameworks. We introduce Neuralizer, a single model that generalizes to previously unseen neuroimaging tasks and modalities without the need for re-training or fine-tuning. Tasks do not have to be known a priori, and generalization happens in a single forward pass during inference. The model can solve processing tasks across multiple image modalities, acquisition methods, and datasets, and generalize to tasks and modalities it has not been trained on. Our experiments on coro
For the first time, we propose using a multiple instance learning based convolution-free transformer model, called Multiple Instance Neuroimage Transformer (MINiT), for the classification of T1weighted (T1w) MRIs. We first present several variants of transformer models adopted for neuroimages. These models extract non-overlapping 3D blocks from the input volume and perform multi-headed self-attention on a sequence of their linear projections. MINiT, on the other hand, treats each of the non-overlapping 3D blocks of the input MRI as its own instance, splitting it further into non-overlapping 3D patches, on which multi-headed self-attention is computed. As a proof-of-concept, we evaluate the efficacy of our model by training it to identify sex from T1w-MRIs of two public datasets: Adolescent Brain Cognitive Development (ABCD) and the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA). The learned attention maps highlight voxels contributing to identifying sex differences in brain morphometry. The code is available at https://github.com/singlaayush/MINIT.
With the arrival of the big data era, more and more data are becoming readily available in various real-world applications and those data are usually highly heterogeneous. Taking computational medicine as an example, we have both Electronic Health Records (EHR) and medical images for each patient. For complicated diseases such as Parkinson's and Alzheimer's, both EHR and neuroimaging information are very important for disease understanding because they contain complementary aspects of the disease. However, EHR and neuroimage are completely different. So far the existing research has been mainly focusing on one of them. In this paper, we proposed a framework, Memory-Based Graph Convolution Network (MemGCN), to perform integrative analysis with such multi-modal data. Specifically, GCN is used to extract useful information from the patients' neuroimages. The information contained in the patient EHRs before the acquisition of each brain image is captured by a memory network because of its sequential nature. The information contained in each brain image is combined with the information read out from the memory network to infer the disease state at the image acquisition timestamp. To fur
We present a cross-modality generation framework that learns to generate translated modalities from given modalities in MR images without real acquisition. Our proposed method performs NeuroImage-to-NeuroImage translation (abbreviated as N2N) by means of a deep learning model that leverages conditional generative adversarial networks (cGANs). Our framework jointly exploits the low-level features (pixel-wise information) and high-level representations (e.g. brain tumors, brain structure like gray matter, etc.) between cross modalities which are important for resolving the challenging complexity in brain structures. Our framework can serve as an auxiliary method in clinical diagnosis and has great application potential. Based on our proposed framework, we first propose a method for cross-modality registration by fusing the deformation fields to adopt the cross-modality information from translated modalities. Second, we propose an approach for MRI segmentation, translated multichannel segmentation (TMS), where given modalities, along with translated modalities, are segmented by fully convolutional networks (FCN) in a multichannel manner. Both of these two methods successfully adopt th
As the field of neuroimaging grows, it can be difficult for scientists within the field to gain and maintain a detailed understanding of its ever-changing landscape. While collaboration and citation networks highlight important contributions within the field, the roles of and relations among specific areas of study can remain quite opaque. Here, we apply techniques from network science to map the landscape of neuroimaging research documented in the journal NeuroImage over the past decade. We create a network in which nodes represent research topics, and edges give the degree to which these topics tend to be covered in tandem. The network displays small-world architecture, with communities characterized by common imaging modalities and medical applications, and with bridges that integrate these distinct subfields. Using node-level analysis, we quantify the structural roles of individual topics within the neuroimaging landscape, and find high levels of clustering within the structural MRI subfield as well as increasing participation among topics related to psychiatry. The overall prevalence of a topic is unrelated to the prevalence of its neighbors, but the degree to which a topic be
Simulating images representative of neurodegenerative diseases is important for predicting patient outcomes and for validation of computational models of disease progression. This capability is valuable for secondary prevention clinical trials where outcomes and screening criteria involve neuroimaging. Traditional computational methods are limited by imposing a parametric model for atrophy and are extremely resource-demanding. Recent advances in deep learning have yielded data-driven models for longitudinal studies (e.g., face ageing) that are capable of generating synthetic images in real-time. Similar solutions can be used to model trajectories of atrophy in the brain, although new challenges need to be addressed to ensure accurate disease progression modelling. Here we propose Degenerative Adversarial NeuroImage Net (DaniNet) --- a new deep learning approach that learns to emulate the effect of neurodegeneration on MRI by simulating atrophy as a function of ages, and disease progression. DaniNet uses an underlying set of Support Vector Regressors (SVRs) trained to capture the patterns of regional intensity changes that accompany disease progression. DaniNet produces whole output
Recent studies found that in voxel-based neuroimage analysis, detecting and differentiating "procedural bias" that are introduced during the preprocessing steps from lesion features, not only can help boost accuracy but also can improve interpretability. To the best of our knowledge, GSplit LBI is the first model proposed in the literature to simultaneously capture both procedural bias and lesion features. Despite the fact that it can improve prediction power by leveraging the procedural bias, it may select spurious features due to the multicollinearity in high dimensional space. Moreover, it does not take into account the heterogeneity of these two types of features. In fact, the procedural bias and lesion features differ in terms of volumetric change and spatial correlation pattern. To address these issues, we propose a "two-groups" Empirical-Bayes method called "FDR-HS" (False-Discovery-Rate Heterogenous Smoothing). Such method is able to not only avoid multicollinearity, but also exploit the heterogenous spatial patterns of features. In addition, it enjoys the simplicity in implementation by introducing hidden variables, which turns the problem into a convex optimization scheme
Neuroimaging data analysis often involves \emph{a-priori} selection of data features to study the underlying neural activity. Since this could lead to sub-optimal feature selection and thereby prevent the detection of subtle patterns in neural activity, data-driven methods have recently gained popularity for optimizing neuroimaging data analysis pipelines and thereby, improving our understanding of neural mechanisms. In this context, we developed a deep convolutional architecture that can identify discriminating patterns in neuroimaging data and applied it to electroencephalography (EEG) recordings collected from 25 subjects performing a hand motor task before and after a rest period or a bout of exercise. The deep network was trained to classify subjects into exercise and control groups based on differences in their EEG signals. Subsequently, we developed a novel method termed the cue-combination for Class Activation Map (ccCAM), which enabled us to identify discriminating spatio-temporal features within definite frequency bands (23--33 Hz) and assess the effects of exercise on the brain. Additionally, the proposed architecture allowed the visualization of the differences in the p
Causally linking disease-related factors to image-derived biomarkers provides a powerful pathway to understanding disease mechanisms. Despite growing interest in applying causal artificial intelligence (AI) approaches for this task, these methods still need to be adapted for complex medical images, and especially, neuroimaging. However, the lack of ground-truth data presents a barrier to development. To bridge this gap, we developed and tested a method for generating synthetic neuroimages, which adhere to a user-specified causal structure describing the non-image to image variable relationships, permitting the creation of ground-truth neuroimaging datasets. In the simulated T1-weighted magnetic resonance images, anatomical variability is modeled by sampling from a subspace estimated from real data and deforming a template image to create unique simulated subjects. Causal relationships are encoded via precise volumetric changes of any region-of-interest without unwanted global artifacts. We achieved relative volume errors of 0.3-2.66% for the targeted regions-of-interest and demonstrate their statistically significant causal relationships, while maintaining mean absolute errors for
Neuroimaging has profoundly enhanced our understanding of the human brain by characterizing its structure, function, and connectivity through modalities like MRI, fMRI, EEG, and PET. These technologies have enabled major breakthroughs across the lifespan, from early brain development to neurodegenerative and neuropsychiatric disorders. Despite these advances, the brain is a complex, multiscale system, and neuroimaging measurements are correspondingly high-dimensional. This creates major statistical challenges, including measurement noise, motion-related artifacts, substantial inter-subject and site/scanner variability, and the sheer scale of modern studies. This paper explores statistical opportunities and challenges in neuroimaging across four key areas: (i) brain development from birth to age 20, (ii) the adult and aging brain, (iii) neurodegeneration and neuropsychiatric disorders, and (iv) brain encoding and decoding. After a quick tutorial on major imaging technologies, we review cutting-edge studies, underscore data and modeling challenges, and highlight research opportunities for statisticians. We conclude by emphasizing that close collaboration among statisticians, neurosci
Alzheimer's disease (AD) is a progressive neurodegenerative disease with high inter-patient variance in rate of cognitive decline. AD progression prediction aims to forecast patient cognitive decline and benefits from incorporating multiple neuroimaging modalities. However, existing multimodal models fail to make accurate predictions when many modalities are missing during inference, as is often the case in clinical settings. To increase multimodal model flexibility under high modality missingness, we introduce PerM-MoE, a novel sparse mixture-of-experts method that uses independent routers for each modality in place of the conventional, single router. Using T1-weighted MRI, FLAIR, amyloid beta PET, and tau PET neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we evaluate PerM-MoE, state-of-the-art Flex-MoE, and unimodal neuroimaging models on predicting two-year change in Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores under varying levels of modality missingness. PerM-MoE outperforms the state of the art in most variations of modality missingness and demonstrates more effective utility of experts than Flex-MoE.
Normative modelling is an increasingly common statistical technique in neuroimaging that estimates population-level benchmarks in brain structure. It enables the quantification of individual deviations from expected distributions whilst accounting for biological and technical covariates without requiring large, matched control groups. This makes it a powerful alternative to traditional case-control studies for identifying brain structural alterations associated with pathology. Despite the availability of numerous modelling approaches and several toolboxes with pre-trained models, the distinct strengths and limitations of normative modelling make it difficult to determine how and when to implement them appropriately. This review offers practical guidance and outlines statistical considerations for clinical researchers using normative modelling in neuroimaging. Through a worked example using clinical epilepsy data, we outline considerations for responsible implementation of pre-trained normative models, to support their broad and rigorous adoption in neuroimaging research.
Neuroimaging provides essential tools for characterizing brain activity by quantifying connectivity strength between remote regions, using different modalities that capture different aspects of connectivity. Yet, decoding meaningful neural signatures must contend with modality-specific challenges, including measurement noise, spatial and temporal distortions, heterogeneous acquisition protocols, and limited sample sizes. A unifying perspective emerges when these data are expressed through symmetric positive definite (SPD)-valued representations: across neuroimaging modalities, SPD-valued representations naturally give rise to SPD matrices that capture dependencies between sensors or brain regions. Endowing the SPD space with Riemannian metrics equips it with a non-Euclidean geometric structure, enabling principled statistical modeling and machine learning on the resulting manifold. This review consolidates machine learning methodologies that operate on the SPD manifold under a unified framework termed SPD matrix learning. SPD matrix learning brings conceptual clarity across multiple modalities, establishes continuity with decades of geometric statistics in neuroimaging, and positio
In this tutorial, we explore Variational Autoencoders (VAEs), an essential framework for unsupervised learning, particularly suited for high-dimensional datasets such as neuroimaging. By integrating deep learning with Bayesian inference, VAEs enable the generation of interpretable latent representations. This tutorial outlines the theoretical foundations of VAEs, addresses practical challenges such as convergence issues and over-fitting, and discusses strategies like the reparameterization trick and hyperparameter optimization. We also highlight key applications of VAEs in neuroimaging, demonstrating their potential to uncover meaningful patterns, including those associated with neurodegenerative processes, and their broader implications for analyzing complex brain data.
Computational neuroimaging involves analyzing brain images or signals to provide mechanistic insights and predictive tools for human cognition and behavior. While diffusion models have shown stability and high-quality generation in natural images, there is increasing interest in adapting them to analyze brain data for various neurological tasks such as data enhancement, disease diagnosis and brain decoding. This survey provides an overview of recent efforts to integrate diffusion models into computational neuroimaging. We begin by introducing the common neuroimaging data modalities, follow with the diffusion formulations and conditioning mechanisms. Then we discuss how the variations of the denoising starting point, condition input and generation target of diffusion models are developed and enhance specific neuroimaging tasks. For a comprehensive overview of the ongoing research, we provide a publicly available repository at https://github.com/JoeZhao527/dm4neuro.