arXiv subjects

Bethany Little

Publications and source records attributed to Bethany Little.

11 recordsLinked to original sources

arXiv2025

Normative Modelling in Neuroimaging: A Practical Guide for Researchers

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.

q-bio.NC↗

arXiv2024

CMOS-fabricated ultraviolet light modulators using low-loss alumina piezo-optomechanical photonic circuits

Ultra-violet (UV) and near-UV wavelengths are necessary for many important optical transitions for quantum technologies and various sensing mechanisms for biological and chemical detection. However, all well-known photonic platforms have excessively high losses in the UV, which has prevented photonic integrated circuits (PICs) being used to address these and other important application spaces. Photonic waveguides using low-loss alumina cores have emerged as a promising solution because of almunia's large optical bandgap and the high quality of films enabled by atomic layer deposition. However, to the best of our knowledge, active alumina PICs have only been realized using thermo-optic tuning, which precludes switching speeds shorter than one microsecond, high circuit densities, and cryogenically compatible operation. Here, we introduce a CMOS-fabricated, piezo-optomechanical PIC platform using alumina waveguides with low optical losses at UV wavelengths and aluminum nitride piezoelectric strain actuators, which solves the issues associated with thermal tuning. We demonstrate a high-performance, reconfigurable optical filter operating at wavelengths as low as 320 nm. The filter has a 6 nanosecond switching time, a loaded linewidth of 3.3 GHz, tuning rate of -120 MHz/V, and a hold power less than 20 nW.

physics.optics↗

arXiv2024

Brain Morphology Normative modelling platform for abnormality and Centile estimation: Brain MoNoCle

Normative models of brain structure estimate the effects of covariates such as age and sex using large samples of healthy controls. These models can then be applied to e.g. smaller clinical cohorts to distinguish disease effects from other covariates. However, these advanced statistical modelling approaches can be difficult to access, and processing large healthy cohorts is computationally demanding. Thus, accessible platforms with pre-trained normative models are needed. We present such a platform for brain morphology analysis as an open-source web application https://cnnplab.shinyapps.io/BrainMoNoCle/, with six key features: (i) user-friendly web interface, (ii) individual and group outputs, (iii) multi-site analysis, (iv) regional and whole-brain analysis, (v) integration with existing tools, and (vi) featuring multiple morphology metrics. Using a diverse sample of 3,276 healthy controls across 21 sites, we pre-trained normative models on various metrics. We validated the models with a small sample of individuals with bipolar disorder, showing outputs that aligned closely with existing literature only after applying our normative modelling. Using a cohort of people with temporal lobe epilepsy, we showed that individual-level abnormalities were in line with seizure lateralisation. Finally, with the ability to investigate multiple morphology measures in the same framework, we found that biological covariates are better explained in specific morphology measures, and for applications, only some measures are sensitive to the disease process. Our platform offers a comprehensive framework to analyse brain morphology in clinical and research settings. Validations confirm the superiority of normative models and the advantage of investigating a range of brain morphology metrics together.

q-bio.NC↗

arXiv2024

Unsupervised Machine Learning Identifies Latent Ultradian States in Multi-Modal Wearable Sensor Signals

Wearable sensors such as smartwatches have become ubiquitous in recent years, allowing the easy and continual measurement of physiological parameters such as heart rate, physical activity, body temperature, and blood glucose in an every-day setting. This multi-modal data offers the potential to identify latent states occurring across physiological measures, which may represent important bio-behavioural states that could not be observed in any single measure. Here we present an approach, utilising a hidden semi-Markov model, to identify such states in data collected using a smartwatch, electrocardiogram, and blood glucose monitor, over two weeks from a sample of 9 participants. We found 26 latent ultradian states across the sample, with many occurring at particular times of day. Here we describe some of these, as well as their association with subjective mood and time use diaries. These methods provide a novel avenue for developing insights into the physiology of everyday life.

q-bio.NC↗

arXiv2023

Multiscale cortical morphometry reveals pronounced regional and scale-dependent variations across the lifespan

Motivation: Characterising the changes in cortical morphology across the lifespan is fundamental for a range of research and clinical applications. Most studies to date have found a monotonic decrease in commonly used morphometrics, such as cortical thickness and volume, across the entire brain with increasing age. Any regional variations reported are subtle changes in the rate of decrease. However, these descriptions of morphological changes have been limited to a single length scale. Here, we delineate the morphological changes associated with the healthy lifespan in multiscale morphometrics. Methods: We applied multiscale morphometric analysis to structural MRI from subjects aged 6-88 years from NKI (n=833) and CamCAN (n=641). These multiscale morphometrics were obtained at both the cortical hemisphere and lobe level. Results: On the level of whole cortical hemispheres, lifespan trajectories show diverging and even opposing trends at different spatial scales, in contrast to the monotonic decreases of volume and thickness described so far. Importantly, larger scales displayed most dramatic changes across the lifespan (up to 60%). More pronounced lobal differences in lifespan trajectories also became apparent in scales over 0.7mm. In a proof-of-principle application in brain age prediction, we also demonstrate added information contributed by multiscale morphometrics. Conclusion: Our study provides a comprehensive multiscale description of lifespan effects on cortical morphology in an age range from 6-88~years. In future, this can form the foundations for a normative model to compare individuals or cohorts, hence identifying multiscale morphological abnormalities. Our results reveal the complementary information contained in different spatial scales, suggesting that morphometrics should not be considered on a single scale, but as functions of length scale.

q-bio.NC↗

arXiv2023

Multivariate brain-cognition associations in euthymic bipolar disorder

Background: People with bipolar disorder (BD) tend to show widespread cognitive impairment compared to healthy controls. Impairments in processing speed (PS), attention, and executive function (EF) may represent 'core' impairments that have a role in wider cognitive dysfunction. Cognitive impairments appear to relate to structural brain abnormalities in BD, but whether core deficits are related to particular brain regions is unclear and much of the research on brain-cognition associations is limited by univariate analysis and small samples. Methods: Euthymic BD patients (n=56) and matched healthy controls (n=26) underwent T1-weighted MRI scans and completed neuropsychological tests of PS, attention, and EF. We utilised public datasets to develop a normative model of cortical thickness (n=5,977) to generate robust estimations of cortical abnormalities in patients. Canonical correlation analysis was used to assess multivariate brain-cognition associations in BD, controlling for age, sex, and premorbid IQ. Results: BD showed impairments on tests of PS, attention, and EF, and abnormal cortical thickness in several brain regions compared to healthy controls. Impairments in tests of PS and EF were most strongly associated with cortical thickness in left inferior temporal, right entorhinal, and right temporal pole areas. Conclusion: Impairments in PS, attention, and EF can be observed in euthymic BD and may be related to abnormal cortical thickness in temporal regions. Future research should continue to leverage multivariate methods to examine complex brain-cognition associations in BD. Future research may benefit from exploring covariance between traditional brain structural morphological metrics such as cortical thickness, cortical volume, and surface area.

q-bio.NC↗

arXiv2022

Effects of anterior temporal lobe resection on cortical morphology

Anterior temporal lobe resection (ATLR) is a surgical procedure to treat drug-resistant temporal lobe epilepsy (TLE). Resection may involve large amounts of cortical tissue. Here, we examine the effects of this surgery on cortical morphology measured in independent variables both near the resection and remotely. We studied 101 individuals with TLE (55 left, 46 right onset) who underwent ATLR. For each individual we considered one pre-surgical MRI and one follow-up MRI 2 to 13 months after surgery. We used our newly developed surface-based method to locally compute traditional morphological variables (average cortical thickness, exposed surface area, and total surface area), and the independent measures $K$, $I$, and $S$, where $K$ measures white matter tension, $I$ captures isometric scaling, and $S$ contains the remaining information about cortical shape. Data from 924 healthy controls was included to account for healthy ageing effects occurring during scans. A SurfStat random field theory clustering approach assessed changes across the cortex caused by ATLR. Compared to preoperative data, surgery had marked effects on all morphological measures. Ipsilateral effects were located in the orbitofrontal and inferior frontal gyri, the pre- and postcentral gyri and supramarginal gyrus, and the lateral occipital gyrus and lingual cortex. Contralateral effects were in the lateral occipital gyrus, and inferior frontal gyrus and frontal pole. The restructuring following ATLR is reflected in widespread morphological changes, mainly in regions near the resection, but also remotely in regions that are structurally connected to the anterior temporal lobe. The causes could include mechanical effects, Wallerian degeneration, or compensatory plasticity. The study of independent measures revealed additional effects compared to traditional measures.

q-bio.NC↗

arXiv2020

Independent components of human brain morphology

Quantification of brain morphology has become an important cornerstone in understanding brain structure. Measures of cortical morphology such as thickness and surface area are frequently used to compare groups of subjects or characterise longitudinal changes. However, such measures are often treated as independent from each other. A recently described scaling law, derived from a statistical physics model of cortical folding, demonstrates that there is a tight covariance between three commonly used cortical morphology measures: cortical thickness, total surface area, and exposed surface area. We show that assuming the independence of cortical morphology measures can hide features and potentially lead to misinterpretations. Using the scaling law, we account for the covariance between cortical morphology measures and derive novel independent measures of cortical morphology. By applying these new measures, we show that new information can be gained; in our example we show that distinct morphological alterations underlie healthy ageing compared to temporal lobe epilepsy, even on the coarse level of a whole hemisphere. We thus provide a conceptual framework for characterising cortical morphology in a statistically valid and interpretable manner, based on theoretical reasoning about the shape of the cortex.

q-bio.NC↗

arXiv2016

Slow light in flight imaging

Slow-light media are of interest in the context of quantum computing and enhanced measurement of quantum effects, with particular emphasis on using slow-light with single photons. We use light-in-flight imaging with a single photon avalanche diode camera-array to image in situ pulse propagation through a slow light medium consisting of heated rubidium vapour. Light-in-flight imaging of slow light propagation enables direct visualisation of a series of physical effects including simultaneous observation of spatial pulse compression and temporal pulse dispersion. Additionally, the single-photon nature of the camera allows for observation of the group velocity of single photons with measured single-photon fractional delays greater than 1 over 1 cm of propagation.

physics.optics↗

arXiv2015

Shifting the Quantum-Classical Boundary: Theory and Experiment for Statistically Classical Optical Fields

The growing recognition that entanglement is not exclusively a quantum property, and does not even originate with Schrödinger's famous remark about it [Proc. Camb. Phil. Soc. 31, 555 (1935)], prompts examination of its role in marking the quantum-classical boundary. We have done this by subjecting correlations of classical optical fields to new Bell-analysis experiments, and report here values of the Bell parameter greater than ${\cal B} = 2.54$. This is many standard deviations outside the limit ${\cal B} = 2$ established by the Clauser-Horne-Shimony-Holt (CHSH) Bell inequality [Phys. Rev. Lett. 23, 880 (1969)], in agreement with our theoretical classical prediction, and not far from the Tsirelson limit ${\cal B} = 2.828...$. These results cast a new light on the standard quantum-classical boundary description, and suggest a reinterpretation of it.

quant-ph↗

arXiv2013

Rapidly reconfigurable optically induced photonic crystals in hot rubidium vapor

Through periodic index modulation, we create two different types of photonic structures in a heated rubidium vapor for controlled reflection, transmission and diffraction of light. The modulation is achieved through the use of the AC Stark effect resulting from a standing-wave control field. The periodic intensity structures create translationally invariant index profiles analogous to photonic crystals in spectral regions of steep dispersion. Experimental results are consistent with modeling.

physics.optics↗