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Robert Leech

Publications and source records attributed to Robert Leech.

At least 19 recordsLinked to original sources

GAMBAS: Generalised-Hilbert Mamba for Super-resolution of Paediatric Ultra-Low-Field MRI

Magnetic resonance imaging (MRI) is critical for neurodevelopmental research, however access to high-field (HF) systems in low- and middle-income countries is severely hindered by their cost. Ultra-low-field (ULF) systems mitigate such issues of access inequality, however their diminished signal-to-noise ratio limits their applicability for research and clinical use. Deep-learning approaches can enhance the quality of scans acquired at lower field strengths at no additional cost. For example, Convolutional neural networks (CNNs) fused with transformer modules have demonstrated a remarkable ability to capture both local information and long-range context. Unfortunately, the quadratic complexity of transformers leads to an undesirable trade-off between long-range sensitivity and local precision. We propose a hybrid CNN and state-space model (SSM) architecture featuring a novel 3D to 1D serialisation (GAMBAS), which learns long-range context without sacrificing spatial precision. We exhibit improved performance compared to other state-of-the-art medical image-to-image translation models.

eess.IV

How to set up a psychedelic study: Unique considerations for research involving human participants

Setting up a psychedelic study can be a long, arduous, and kafkaesque process. This rapidly-developing field poses several unique challenges for researchers, necessitating a range of considerations that have not yet been standardised. Many of the complexities inherent to psychedelic research also challenge existing assumptions around, for example, approaches to psychiatric prescribing, the conceptual framing of the placebo effect, and definitions of selfhood. This review paper brings together several of the major psychedelic research teams across the United Kingdom to formalise these unique considerations, identify continuing areas of debate, and provide a practical, experience-based guide, with recommendations for policymakers and future researchers intending to set up a psychedelic research study or clinical trial. We approach this such that the paper can either be read end to end, or treated as a manual: readers can dip into relevant sections as needed.

q-bio.NC

SIM: Surface-based fMRI Analysis for Inter-Subject Multimodal Decoding from Movie-Watching Experiments

Current AI frameworks for brain decoding and encoding, typically train and test models within the same datasets. This limits their utility for brain computer interfaces (BCI) or neurofeedback, for which it would be useful to pool experiences across individuals to better simulate stimuli not sampled during training. A key obstacle to model generalisation is the degree of variability of inter-subject cortical organisation, which makes it difficult to align or compare cortical signals across participants. In this paper we address this through the use of surface vision transformers, which build a generalisable model of cortical functional dynamics, through encoding the topography of cortical networks and their interactions as a moving image across a surface. This is then combined with tri-modal self-supervised contrastive (CLIP) alignment of audio, video, and fMRI modalities to enable the retrieval of visual and auditory stimuli from patterns of cortical activity (and vice-versa). We validate our approach on 7T task-fMRI data from 174 healthy participants engaged in the movie-watching experiment from the Human Connectome Project (HCP). Results show that it is possible to detect which movie clips an individual is watching purely from their brain activity, even for individuals and movies not seen during training. Further analysis of attention maps reveals that our model captures individual patterns of brain activity that reflect semantic and visual systems. This opens the door to future personalised simulations of brain function. Code & pre-trained models will be made available at https://github.com/metrics-lab/sim, processed data for training will be available upon request at https://gin.g-node.org/Sdahan30/sim.

cs.LG

Gradients of brain organization: Smooth sailing from methods development to user community

Multimodal neuroimaging grants a powerful in vivo window into the structure and function of the human brain. Recent methodological and conceptual advances have enabled investigations of the interplay between large-scale spatial trends, or gradients, in brain structure and function, offering a framework to unify principles of brain organization across multiple scales. Strong community enthusiasm for these techniques has been instrumental in their widespread adoption and implementation to answer key questions in neuroscience. Following a brief review of current literature on this framework, this perspective paper will highlight how pragmatic steps aiming to make gradient methods more accessible to the community propelled these techniques to the forefront of neuroscientific inquiry. More specifically, we will emphasize how interest for gradient methods was catalyzed by data sharing, open-source software development, as well as the organization of dedicated workshops led by a diverse team of early career researchers. To this end, we argue that the growing excitement for brain gradients is the result of coordinated and consistent efforts to build an inclusive community and can serve as a case in point for future innovations and conceptual advances in neuroinformatics. We close this perspective paper by discussing challenges for the continuous refinement of neuroscientific theory, methodological innovation, and real-world translation to maintain our collective progress towards integrated models of brain organization.

q-bio.OT

Transformer-based normative modelling for anomaly detection of early schizophrenia

Despite the impact of psychiatric disorders on clinical health, early-stage diagnosis remains a challenge. Machine learning studies have shown that classifiers tend to be overly narrow in the diagnosis prediction task. The overlap between conditions leads to high heterogeneity among participants that is not adequately captured by classification models. To address this issue, normative approaches have surged as an alternative method. By using a generative model to learn the distribution of healthy brain data patterns, we can identify the presence of pathologies as deviations or outliers from the distribution learned by the model. In particular, deep generative models showed great results as normative models to identify neurological lesions in the brain. However, unlike most neurological lesions, psychiatric disorders present subtle changes widespread in several brain regions, making these alterations challenging to identify. In this work, we evaluate the performance of transformer-based normative models to detect subtle brain changes expressed in adolescents and young adults. We trained our model on 3D MRI scans of neurotypical individuals (N=1,765). Then, we obtained the likelihood of neurotypical controls and psychiatric patients with early-stage schizophrenia from an independent dataset (N=93) from the Human Connectome Project. Using the predicted likelihood of the scans as a proxy for a normative score, we obtained an AUROC of 0.82 when assessing the difference between controls and individuals with early-stage schizophrenia. Our approach surpassed recent normative methods based on brain age and Gaussian Process, showing the promising use of deep generative models to help in individualised analyses.

cs.LG

Neuroadaptive electroencephalography: a proof-of-principle study in infants

A core goal of functional neuroimaging is to study how the environment is processed in the brain. The mainstream paradigm involves concurrently measuring a broad spectrum of brain responses to a small set of environmental features preselected with reference to previous studies or a theoretical framework. As a complement, we invert this approach by allowing the investigator to record the modulation of a preselected brain response by a broad spectrum of environmental features. Our approach is optimal when theoretical frameworks or previous empirical data are impoverished. By using a prespecified closed-loop design, the approach addresses fundamental challenges of reproducibility and generalisability in brain research. These conditions are particularly acute when studying the developing brain, where our theories based on adult brain function may fundamentally misrepresent the topography of infant cognition and where there are substantial practical challenges to data acquisition. Our methodology employs machine learning to map modulation of a neural feature across a space of experimental stimuli. Our method collects, processes and analyses EEG brain data in real-time; and uses a neuro-adaptive Bayesian optimisation algorithm to adjust the stimulus presented depending on the prior samples of a given participant. Unsampled stimuli can be interpolated by fitting a Gaussian process regression along the dataset. We show that our method can automatically identify the face of the infant's mother through online recording of their Nc brain response to a face continuum. We can retrieve model statistics of individualised responses for each participant, opening the door for early identification of atypical development. This approach has substantial potential in infancy research and beyond for improving power and generalisability of mapping the individual cognitive topography of brain function.

q-bio.NC

Causal Autoregressive Flows

Two apparently unrelated fields -- normalizing flows and causality -- have recently received considerable attention in the machine learning community. In this work, we highlight an intrinsic correspondence between a simple family of autoregressive normalizing flows and identifiable causal models. We exploit the fact that autoregressive flow architectures define an ordering over variables, analogous to a causal ordering, to show that they are well-suited to performing a range of causal inference tasks, ranging from causal discovery to making interventional and counterfactual predictions. First, we show that causal models derived from both affine and additive autoregressive flows with fixed orderings over variables are identifiable, i.e. the true direction of causal influence can be recovered. This provides a generalization of the additive noise model well-known in causal discovery. Second, we derive a bivariate measure of causal direction based on likelihood ratios, leveraging the fact that flow models can estimate normalized log-densities of data. Third, we demonstrate that flows naturally allow for direct evaluation of both interventional and counterfactual queries, the latter case being possible due to the invertible nature of flows. Finally, throughout a series of experiments on synthetic and real data, the proposed method is shown to outperform current approaches for causal discovery as well as making accurate interventional and counterfactual predictions.

stat.ML

Fine-tuning neural excitation/inhibition for tailored ketamine use in treatment-resistant depression

The glutamatergic modulator ketamine has been shown to rapidly reduce depressive symptoms in patients with treatment-resistant major depressive disorder (TRD). Although its mechanisms of action are not fully understood, changes in cortical excitation/inhibition (E/I) following ketamine administration are well documented in animal models and could represent a potential biomarker of treatment response. Here, we analyse neuromagnetic virtual electrode timeseries collected from the primary somatosensory cortex in 18 unmedicated patients with TRD and in an equal number of age-matched healthy controls during a somatosensory 'airpuff' stimulation task. These two groups were scanned as part of a clinical trial of ketamine efficacy under three conditions: a) baseline; b) 6-9 hours following subanesthetic ketamine infusion; and c) 6-9 hours following placebo-saline infusion. We obtained estimates of E/I interaction strengths by using Dynamic Causal Modelling (DCM) on the timeseries, thereby allowing us to pinpoint, under each scanning condition, where each subject's dynamics lie within the Poincaré diagram - as defined in dynamical systems theory. We demonstrate that the Poincaré diagram offers classification capability for TRD patients, in that the further the patients' coordinates were shifted (by virtue of ketamine) toward the stable (top-left) quadrant of the Poincaré diagram, the more their depressive symptoms improved. The same relationship was not observed by virtue of a placebo effect - thereby verifying the drug-specific nature of the results. We show that the shift in neural dynamics required for symptom improvement necessitates an increase in both excitatory and inhibitory coupling. We present accompanying MATLAB code made available in a public repository, thereby allowing for future studies to assess individually-tailored treatments of TRD.

q-bio.QM

The principle of stationary action in neural systems

The principle of stationary action is a cornerstone of modern physics, providing a powerful framework for investigating dynamical systems found in classical mechanics through to quantum field theory. However, computational neuroscience, despite its heavy reliance on concepts in physics, is anomalous in this regard as its main equations of motion are not compatible with a Lagrangian formulation and hence with the principle of stationary action. Taking the Dynamic Causal Modelling neuronal state equation, Hodgkin-Huxley model, and the Leaky Integrate-and-Fire model as examples, we show that it is possible to write complex oscillatory forms of these equations in terms of a single Lagrangian. We therefore bring mathematical descriptions in computational neuroscience under the remit of the principle of stationary action and use this reformulation to express symmetries and associated conservation laws arising in neural systems.

q-bio.NC

Bayesian optimization for automatic design of face stimuli

Investigating the cognitive and neural mechanisms involved with face processing is a fundamental task in modern neuroscience and psychology. To date, the majority of such studies have focused on the use of pre-selected stimuli. The absence of personalized stimuli presents a serious limitation as it fails to account for how each individual face processing system is tuned to cultural embeddings or how it is disrupted in disease. In this work, we propose a novel framework which combines generative adversarial networks (GANs) with Bayesian optimization to identify individual response patterns to many different faces. Formally, we employ Bayesian optimization to efficiently search the latent space of state-of-the-art GAN models, with the aim to automatically generate novel faces, to maximize an individual subject's response. We present results from a web-based proof-of-principle study, where participants rated images of themselves generated via performing Bayesian optimization over the latent space of a GAN. We show how the algorithm can efficiently locate an individual's optimal face while mapping out their response across different semantic transformations of a face; inter-individual analyses suggest how the approach can provide rich information about individual differences in face processing.

cs.LG

Fighting seizures with seizures: diffusion and stability in neural systems

Seizure activity is a ubiquitous and pernicious pathophysiology that, in principle, should yield to mathematical treatments of (neuronal) ensemble dynamics - and therefore interventions on stochastic chaos. A seizure can be characterised as a deviation of neural activity from a stable dynamical regime, i.e. one in which signals fluctuate only within a limited range. In silico treatments of neural activity are an important tool for understanding how the brain can achieve stability, as well as how pathology can lead to seizures and potential strategies for mitigating instabilities, e.g. via external stimulation. Here, we demonstrate that the (neuronal) state equation used in Dynamic Causal Modelling generalises to a Fokker-Planck formalism when propagation of neuronal activity along structural connections is considered. Using the Jacobian of this generalised state equation, we show that an initially unstable system can be rendered stable via a reduction in diffusivity (i.e., connectivity that disperses neuronal fluctuations). We show, for neural systems prone to epileptic seizures, that such a reduction can be achieved via external stimulation. Specifically, we show that this stimulation should be applied in such a way as to temporarily mirror epileptic activity in the areas adjoining an affected brain region - thus 'fighting seizures with seizures'. We offer proof of principle using simulations based on functional neuroimaging data collected from patients with idiopathic generalised epilepsy, in which we successfully suppress pathological activity in a distinct sub-network. Our hope is that this technique can form the basis for real-time monitoring and intervention devices that are capable of suppressing or even preventing seizures in a non-invasive manner.

q-bio.NC

Seizure intervention via diffusion mechanisms

We begin by demonstrating that the neuronal state equation from Dynamic Causal Modelling takes on the form of the discretized Fokker-Planck equation upon the inclusion of local activity gradients within a network. Using the Jacobian of this modified neuronal state equation, we show that an initially unstable system can be rendered stable via a decrease in diffusivity. Therefore, if a node within the system is known to be unstable due to a tendency toward epileptic seizures for example, then our results indicate that intervention techniques should take the counter-intuitive approach of mirroring activity in the nodes immediately surrounding a pathological region - effectively fighting seizures with seizures. Finally, using a two-region system as an example, we show that one can also tune diffusivity in such a way as to allow for the suppression of oscillatory activity during epileptic seizures.

q-bio.QM

Estimating quantities conserved by virtue of scale invariance in timeseries

In contrast to the symmetries of translation in space, rotation in space, and translation in time, the known laws of physics are not universally invariant under transformation of scale. However, the action can be invariant under change of scale in the special case of a scale free dynamical system that can be described in terms of a Lagrangian, that itself scales inversely with time. Crucially, this means symmetries under change of scale can exist in dynamical systems under certain constraints. Our contribution lies in the derivation of a generalised scale invariant Lagrangian - in the form of a power series expansion - that satisfies these constraints. This generalised Lagrangian furnishes a normal form for dynamic causal models (i.e., state space models based upon differential equations) that can be used to distinguish scale invariance (scale symmetry) from scale freeness in empirical data. We establish face validity with an analysis of simulated data and then show how scale invariance can be identified - and how the associated conserved quantities can be estimated - in neuronal timeseries.

physics.data-an

Analysis of an Automated Machine Learning Approach in Brain Predictive Modelling: A data-driven approach to Predict Brain Age from Cortical Anatomical Measures

The use of machine learning (ML) algorithms has significantly increased in neuroscience. However, from the vast extent of possible ML algorithms, which one is the optimal model to predict the target variable? What are the hyperparameters for such a model? Given the plethora of possible answers to these questions, in the last years, automated machine learning (autoML) has been gaining attention. Here, we apply an autoML library called TPOT which uses a tree-based representation of machine learning pipelines and conducts a genetic-programming based approach to find the model and its hyperparameters that more closely predicts the subject's true age. To explore autoML and evaluate its efficacy within neuroimaging datasets, we chose a problem that has been the focus of previous extensive study: brain age prediction. Without any prior knowledge, TPOT was able to scan through the model space and create pipelines that outperformed the state-of-the-art accuracy for Freesurfer-based models using only thickness and volume information for anatomical structure. In particular, we compared the performance of TPOT (mean accuracy error (MAE): $4.612 \pm .124$ years) and a Relevance Vector Regression (MAE $5.474 \pm .140$ years). TPOT also suggested interesting combinations of models that do not match the current most used models for brain prediction but generalise well to unseen data. AutoML showed promising results as a data-driven approach to find optimal models for neuroimaging applications.

q-bio.NC

Dynamic causal modelling of phase-amplitude interactions

Models of coupled oscillators are used to describe a wide variety of phenomena in neuroimaging. These models typically rest on the premise that oscillator dynamics do not evolve beyond their respective limit cycles, and hence that interactions can be described purely in terms of phase differences. Whilst mathematically convenient, the restrictive nature of phase-only models can limit their explanatory power. We therefore propose a generalisation of dynamic causal modelling that incorporates both phase and amplitude. This allows for the separate quantifications of phase and amplitude contributions to the connectivity between neural regions. We establish, using model-generated data and simulations of coupled pendula, that phase-only models perform well only under weak coupling conditions. We also show that, despite their higher complexity, phase-amplitude models can describe strongly coupled systems more effectively than their phase-only counterparts. We relate our findings to four metrics commonly used in neuroimaging: the Kuramoto order parameter, cross-correlation, phase-lag index, and spectral entropy. We find that, with the exception of spectral entropy, the phase-amplitude model is able to capture all metrics more effectively than the phase-only model. We then demonstrate, using local field potential recordings in rodents and functional magnetic resonance imaging in macaque monkeys, that amplitudes in oscillator models play an important role in describing neural dynamics in anaesthetised brain states.

q-bio.QM

Network constraints in scale free dynamical systems

Scale free dynamics are observed in a variety of physical and biological systems. These include neural activity in which evidence for scale freeness has been reported using a range of imaging modalities. Here, we derive the ways in which connections within a network must transform - relative to system size - in order to maintain scale freeness and test these theoretical transformations via simulations. First, we explore the known invariance of planetary motion for orbits varying in size. Using parametric empirical Bayesian modelling and a generic dynamical systems model, we show that we recover Kepler's third law from orbital timeseries, using our proposed transformations; thereby providing construct validation. We then demonstrate that the dynamical critical exponent is inversely proportional to the time rescaling exponent, in the context of coarse graining operations. Using murine calcium imaging data, we then show that the dynamical critical exponent can be estimated in an empirical biological setting. Specifically, we compare dynamical critical exponents - associated with spontaneous and task states in two regions of imaged cortex - that are classified as task-relevant and task-irrelevant. We find, consistently across animals, that the task-irrelevant region exhibits higher dynamical critical exponents during spontaneous activity than during task performance. Conversely, the task-relevant region is associated with higher dynamical critical exponents in task vs. spontaneous states. These data support the idea that higher dynamical critical exponents, within relevant cortical structures, underwrite neuronal processing due to the implicit increase in cross-scale information transmission.

physics.bio-ph

Interpretable brain age prediction using linear latent variable models of functional connectivity

Neuroimaging-driven prediction of brain age, defined as the predicted biological age of a subject using only brain imaging data, is an exciting avenue of research. In this work we seek to build models of brain age based on functional connectivity while prioritizing model interpretability and understanding. This way, the models serve to both provide accurate estimates of brain age as well as allow us to investigate changes in functional connectivity which occur during the ageing process. The methods proposed in this work consist of a two-step procedure: first, linear latent variable models, such as PCA and its extensions, are employed to learn reproducible functional connectivity networks present across a cohort of subjects. The activity within each network is subsequently employed as a feature in a linear regression model to predict brain age. The proposed framework is employed on the data from the CamCAN repository and the inferred brain age models are further demonstrated to generalize using data from two open-access repositories: the Human Connectome Project and the ATR Wide-Age-Range.

stat.AP

The Noether charges of all analytic Lagrangians associated with a scale invariant action

Here we consider scale invariant dynamical systems within a classical particle description of Lagrangian mechanics. We begin by showing the condition under which a spatial and temporal scale transformation of such a system can lead to a symmetry by leaving the action unchanged. We then derive the form of all analytic Lagrangians that possess such a symmetry under change of scale. Finally, we write down the Noether charges of all analytic Lagrangians that are associated with a scale invariant action.

physics.class-ph