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John Suckling

Publications and source records attributed to John Suckling.

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A continually expandable foundation model for brain MRI

Brain magnetic resonance imaging (MRI) is central to neuroscience and clinical assessment, but models are commonly developed for individual diseases, populations or imaging protocols. Foundation models promise more general representations, yet they are usually pretrained once and can lose earlier capabilities when updated with new data. Here we show that Alcmaeon, a three-dimensional brain MRI foundation model pretrained without manual labels on more than 425,000 volumes and derived imaging maps, can be expanded sequentially across clinical domains. Alcmaeon combines volumetric encoding and latent diffusion generation with Graph-Blueprint Pruning (GBP), which protects network modules important to earlier domains while leaving the remaining capacity trainable. Across expansion from healthy ageing and neurodegeneration to developmental, psychiatric and tumour imaging, GBP showed less forgetting than sequential adaptation and elastic weight consolidation across voxel-level reconstruction measures, with its largest advantage after adaptation to tumour imaging. The blueprints provided an inspectable record of how model capacity was protected and reused. Representations from different model levels supported image synthesis, disease classification, survival modelling and postoperative prediction, although no single representation was optimal for every task. These findings provide a route towards brain MRI foundation models that can grow with emerging data while retaining earlier capabilities.

cs.CV

Geometry-Guided Generative Representation for Functional Brain Graphs

In network neuroscience, functional brain systems are often characterized using separate yet related graph-theoretic or spectral descriptors, overlooking how these properties covary and partially overlap across individuals and conditions. We anticipate that dense, weighted functional connectivity graphs lie on a low-dimensional latent geometry along which both topological and spectral structures vary smoothly at the population level. Although graph-based deep learning offers a powerful framework for modeling these brain connectomes, supervised approaches are constrained by the limited availability of labeled data. Existing unsupervised graph representation methods also typically focus on node-level embeddings, which are limited in capturing compact graph-level representations that preserve information from dense functional connectomes. To address these gaps, we learn compact brain graph representations using a graph transformer autoencoder, where domain-specific, aligned functional gradient geometry provides an inductive bias to guide learning. Despite being trained in a fully unsupervised manner, our approach meaningfully separates cognitive states and enables decoding of visual stimuli, with performance further improved by incorporating neural dynamics. In parallel, to enable generation of synthetic brain graphs, we fit a diffusion model to the learned latent representation and decode samples back to dense connectomes.

q-bio.NC

Association-sensory spatiotemporal hierarchy and functional gradient-regularised recurrent neural network with implications for schizophrenia

The human neocortex is functionally organised at its highest level along a continuous sensory-to-association (AS) hierarchy. This study characterises the AS hierarchy of patients with schizophrenia in a comparison with controls. Using a large fMRI dataset (N=355), we extracted individual AS gradients via spectral analysis of brain connectivity, quantified hierarchical specialisation by gradient spread, and related this spread with connectivity geometry. We found that schizophrenia compresses the AS hierarchy indicating reduced functional differentiation. By modelling neural timescale with the Ornstein-Uhlenbeck process, we observed that the most specialised, locally cohesive regions at the gradient extremes exhibit dynamics with a longer time constant, an effect that is attenuated in schizophrenia. To study computation, we used the gradients to regularise subject-specific recurrent neural networks (RNNs) trained on working memory tasks. Networks endowed with greater gradient spread learned more efficiently, plateaued at lower task loss, and maintained stronger alignment to the prescribed AS hierarchical geometry. Fixed point linearisation showed that high-range networks settled into more stable neural states during memory delay, evidenced by lower energy and smaller maximal Jacobian eigenvalues. This gradient-regularised RNN framework therefore links large-scale cortical architecture with fixed point stability, providing a mechanistic account of how gradient de-differentiation could destabilise neural computations in schizophrenia, convergently supported by empirical timescale flattening and model-based evidence of less stable fixed points.

q-bio.NC

Uncovering Neuroimaging Biomarkers of Brain Tumor Surgery with AI-Driven Methods

Brain tumor resection is a highly complex procedure with profound implications for survival and quality of life. Predicting patient outcomes is crucial to guide clinicians in balancing oncological control with preservation of neurological function. However, building reliable prediction models is severely limited by the rarity of curated datasets that include both pre- and post-surgery imaging, given the clinical, logistical and ethical challenges of collecting such data. In this study, we develop a novel framework that integrates explainable artificial intelligence (XAI) with neuroimaging-based feature engineering for survival assessment in brain tumor patients. We curated structural MRI data from 49 patients scanned pre- and post-surgery, providing a rare resource for identifying survival-related biomarkers. A key methodological contribution is the development of a global explanation optimizer, which refines survival-related feature attribution in deep learning models, thereby improving both the interpretability and reliability of predictions. From a clinical perspective, our findings provide important evidence that survival after oncological surgery is influenced by alterations in regions related to cognitive and sensory functions. These results highlight the importance of preserving areas involved in decision-making and emotional regulation to improve long-term outcomes. From a technical perspective, the proposed optimizer advances beyond state-of-the-art XAI methods by enhancing both the fidelity and comprehensibility of model explanations, thus reinforcing trust in the recognition patterns driving survival prediction. This work demonstrates the utility of XAI-driven neuroimaging analysis in identifying survival-related variability and underscores its potential to inform precision medicine strategies in brain tumor treatment.

eess.IV

The Explanation Necessity for Healthcare AI

Explainability is a critical factor in enhancing the trustworthiness and acceptance of artificial intelligence (AI) in healthcare, where decisions directly impact patient outcomes. Despite advancements in AI interpretability, clear guidelines on when and to what extent explanations are required in medical applications remain lacking. We propose a novel categorization system comprising four classes of explanation necessity (self-explainable, semi-explainable, non-explainable, and new-patterns discovery), guiding the required level of explanation; whether local (patient or sample level), global (cohort or dataset level), or both. To support this system, we introduce a mathematical formulation that incorporates three key factors: (i) robustness of the evaluation protocol, (ii) variability of expert observations, and (iii) representation dimensionality of the application. This framework provides a practical tool for researchers to determine the appropriate depth of explainability needed, addressing the critical question: When does an AI medical application need to be explained, and at what level of detail?

cs.AI

Contrastive-Adversarial and Diffusion: Exploring pre-training and fine-tuning strategies for sulcal identification

In the last decade, computer vision has witnessed the establishment of various training and learning approaches. Techniques like adversarial learning, contrastive learning, diffusion denoising learning, and ordinary reconstruction learning have become standard, representing state-of-the-art methods extensively employed for fully training or pre-training networks across various vision tasks. The exploration of fine-tuning approaches has emerged as a current focal point, addressing the need for efficient model tuning with reduced GPU memory usage and time costs while enhancing overall performance, as exemplified by methodologies like low-rank adaptation (LoRA). Key questions arise: which pre-training technique yields optimal results - adversarial, contrastive, reconstruction, or diffusion denoising? How does the performance of these approaches vary as the complexity of fine-tuning is adjusted? This study aims to elucidate the advantages of pre-training techniques and fine-tuning strategies to enhance the learning process of neural networks in independent identical distribution (IID) cohorts. We underscore the significance of fine-tuning by examining various cases, including full tuning, decoder tuning, top-level tuning, and fine-tuning of linear parameters using LoRA. Systematic summaries of model performance and efficiency are presented, leveraging metrics such as accuracy, time cost, and memory efficiency. To empirically demonstrate our findings, we focus on a multi-task segmentation-classification challenge involving the paracingulate sulcus (PCS) using different 3D Convolutional Neural Network (CNN) architectures by using the TOP-OSLO cohort comprising 596 subjects.

eess.IV

Solving the enigma: Enhancing faithfulness and comprehensibility in explanations of deep networks

The accelerated progress of artificial intelligence (AI) has popularized deep learning models across various domains, yet their inherent opacity poses challenges, particularly in critical fields like healthcare, medicine, and the geosciences. Explainable AI (XAI) has emerged to shed light on these 'black box' models, aiding in deciphering their decision-making processes. However, different XAI methods often produce significantly different explanations, leading to high inter-method variability that increases uncertainty and undermines trust in deep networks' predictions. In this study, we address this challenge by introducing a novel framework designed to enhance the explainability of deep networks through a dual focus on maximizing both accuracy and comprehensibility in the explanations. Our framework integrates outputs from multiple established XAI methods and leverages a non-linear neural network model, termed the 'explanation optimizer,' to construct a unified, optimal explanation. The optimizer evaluates explanations using two key metrics: faithfulness (accuracy in reflecting the network's decisions) and complexity (comprehensibility). By balancing these, it provides accurate and accessible explanations, addressing a key XAI limitation. Experiments on multi-class and binary classification in 2D object and 3D neuroscience imaging confirm its efficacy. Our optimizer achieved faithfulness scores 155% and 63% higher than the best XAI methods in 3D and 2D tasks, respectively, while also reducing complexity for better understanding. These results demonstrate that optimal explanations based on specific quality criteria are achievable, offering a solution to the issue of inter-method variability in the current XAI literature and supporting more trustworthy deep network predictions

cs.CV

An explainable three dimension framework to uncover learning patterns: A unified look in variable sulci recognition

The significant features identified in a representative subset of the dataset during the learning process of an artificial intelligence model are referred to as a 'global' explanation. 3D global explanations are crucial in neuroimaging, where a complex representational space demands more than basic 2D interpretations. However, current studies in the literature often lack the accuracy, comprehensibility, and 3D global explanations needed in neuroimaging and beyond. To address this gap, we developed an explainable artificial intelligence (XAI) 3D-Framework capable of providing accurate, low-complexity global explanations. We evaluated the framework using various 3D deep learning models trained on a well-annotated cohort of 596 structural MRIs. The binary classification task focused on detecting the presence or absence of the paracingulate sulcus, a highly variable brain structure associated with psychosis. Our framework integrates statistical features (Shape) and XAI methods (GradCam and SHAP) with dimensionality reduction, ensuring that explanations reflect both model learning and cohort-specific variability. By combining Shape, GradCam, and SHAP, our framework reduces inter-method variability, enhancing the faithfulness and reliability of global explanations. These robust explanations facilitated the identification of critical sub-regions, including the posterior temporal and internal parietal regions, as well as the cingulate region and thalamus, suggesting potential genetic or developmental influences. Our XAI 3D-Framework leverages global explanations to uncover the broader developmental context of specific cortical features. This approach advances the fields of deep learning and neuroscience by offering insights into normative brain development and atypical trajectories linked to mental illness, paving the way for more reliable and interpretable AI applications in neuroimaging.

cs.CV

Deep Learning in current Neuroimaging: a multivariate approach with power and type I error control but arguable generalization ability

Discriminative analysis in neuroimaging by means of deep/machine learning techniques is usually tested with validation techniques, whereas the associated statistical significance remains largely under-developed due to their computational complexity. In this work, a non-parametric framework is proposed that estimates the statistical significance of classifications using deep learning architectures. In particular, a combination of autoencoders (AE) and support vector machines (SVM) is applied to: (i) a one-condition, within-group designs often of normal controls (NC) and; (ii) a two-condition, between-group designs which contrast, for example, Alzheimer's disease (AD) patients with NC (the extension to multi-class analyses is also included). A random-effects inference based on a label permutation test is proposed in both studies using cross-validation (CV) and resubstitution with upper bound correction (RUB) as validation methods. This allows both false positives and classifier overfitting to be detected as well as estimating the statistical power of the test. Several experiments were carried out using the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, the Dominantly Inherited Alzheimer Network (DIAN) dataset, and a MCI prediction dataset. We found in the permutation test that CV and RUB methods offer a false positive rate close to the significance level and an acceptable statistical power (although lower using cross-validation). A large separation between training and test accuracies using CV was observed, especially in one-condition designs. This implies a low generalization ability as the model fitted in training is not informative with respect to the test set. We propose as solution by applying RUB, whereby similar results are obtained to those of the CV test set, but considering the whole set and with a lower computational cost per iteration.

stat.ML

A connection between the pattern classification problem and the General Linear Model for statistical inference

A connection between the General Linear Model (GLM) in combination with classical statistical inference and the machine learning (MLE)-based inference is described in this paper. Firstly, the estimation of the GLM parameters is expressed as a Linear Regression Model (LRM) of an indicator matrix, that is, in terms of the inverse problem of regressing the observations. In other words, both approaches, i.e. GLM and LRM, apply to different domains, the observation and the label domains, and are linked by a normalization value at the least-squares solution. Subsequently, from this relationship we derive a statistical test based on a more refined predictive algorithm, i.e. the (non)linear Support Vector Machine (SVM) that maximizes the class margin of separation, within a permutation analysis. The MLE-based inference employs a residual score and includes the upper bound to compute a better estimation of the actual (real) error. Experimental results demonstrate how the parameter estimations derived from each model resulted in different classification performances in the equivalent inverse problem. Moreover, using real data the aforementioned predictive algorithms within permutation tests, including such model-free estimators, are able to provide a good trade-off between type I error and statistical power.

stat.ML

Stochastic encoding of graphs in deep learning allows for complex analysis of gender classification in resting-state and task functional brain networks from the UK Biobank

Classification of whole-brain functional connectivity MRI data with convolutional neural networks (CNNs) has shown promise, but the complexity of these models impedes understanding of which aspects of brain activity contribute to classification. While visualization techniques have been developed to interpret CNNs, bias inherent in the method of encoding abstract input data, as well as the natural variance of deep learning models, detract from the accuracy of these techniques. We introduce a stochastic encoding method in an ensemble of CNNs to classify functional connectomes by gender. We applied our method to resting-state and task data from the UK BioBank, using two visualization techniques to measure the salience of three brain networks involved in task- and resting-states, and their interaction. To regress confounding factors such as head motion, age, and intracranial volume, we introduced a multivariate balancing algorithm to ensure equal distributions of such covariates between classes in our data. We achieved a final AUROC of 0.8459. We found that resting-state data classifies more accurately than task data, with the inner salience network playing the most important role of the three networks overall in classification of resting-state data and connections to the central executive network in task data.

q-bio.NC

Single-participant structural connectivity matrices lead to greater accuracy in classification of participants than function in autism in MRI

In this work, we introduce a technique of deriving symmetric connectivity matrices from regional histograms of grey-matter volume estimated from T1-weighted MRIs. We then validated the technique by inputting the connectivity matrices into a convolutional neural network (CNN) to classify between participants with autism and age-, motion-, and intracranial-volume-matched controls from six different databases (29,288 total connectomes, mean age = 30.72, range 0.42-78.00, including 1555 subjects with autism). We compared this method to similar classifications of the same participants using fMRI connectivity matrices as well as univariate estimates of grey-matter volumes. We further applied graph-theoretical metrics on output class activation maps to identify areas of the matrices that the CNN preferentially used to make the classification, focusing particularly on hubs. Our results gave AUROCs of 0.7298 (69.71% accuracy) when classifying by only structural connectivity, 0.6964 (67.72% accuracy) when classifying by only functional connectivity, and 0.7037 (66.43% accuracy) when classifying by univariate grey matter volumes. Combining structural and functional connectivities gave an AUROC of 0.7354 (69.40% accuracy). Graph analysis of class activation maps revealed no distinguishable network patterns for functional inputs, but did reveal localized differences between groups in bilateral Heschl's gyrus and upper vermis for structural connectivity. This work provides a simple means of feature extraction for inputting large numbers of structural MRIs into machine learning models.

q-bio.QM

Ensemble Deep Learning on Large, Mixed-Site fMRI Datasets in Autism and Other Tasks

Deep learning models for MRI classification face two recurring problems: they are typically limited by low sample size, and are abstracted by their own complexity (the "black box problem"). In this paper, we train a convolutional neural network (CNN) with the largest multi-source, functional MRI (fMRI) connectomic dataset ever compiled, consisting of 43,858 datapoints. We apply this model to a cross-sectional comparison of autism (ASD) vs typically developing (TD) controls that has proved difficult to characterise with inferential statistics. To contextualise these findings, we additionally perform classifications of gender and task vs rest. Employing class-balancing to build a training set, we trained 3$\times$300 modified CNNs in an ensemble model to classify fMRI connectivity matrices with overall AUROCs of 0.6774, 0.7680, and 0.9222 for ASD vs TD, gender, and task vs rest, respectively. Additionally, we aim to address the black box problem in this context using two visualization methods. First, class activation maps show which functional connections of the brain our models focus on when performing classification. Second, by analyzing maximal activations of the hidden layers, we were also able to explore how the model organizes a large and mixed-centre dataset, finding that it dedicates specific areas of its hidden layers to processing different covariates of data (depending on the independent variable analyzed), and other areas to mix data from different sources. Our study finds that deep learning models that distinguish ASD from TD controls focus broadly on temporal and cerebellar connections, with a particularly high focus on the right caudate nucleus and paracentral sulcus.

q-bio.QM