Konrad Adler-Wagstyl

University College London | UCL · Institute of Neurology

The human cerebral cortex underlies many of our unique strengths and vulnerabilities as a species - but efforts to understand its organization are challenged by reliance on incompatible measurement methods at different spatial scales. Macroscale features such as cortical folding or functional activation are accessed through spatially dense neuroima...

Epilepsy and epilepsy surgery lend themselves well to the application of machine learning (ML) and artificial intelligence (AI) technologies. This is evidenced by the plethora of tools developed for applications such as seizure detection and analysis of imaging and electrophysiological data. However, few of these tools have been directly used to gu...

Introduction: One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualise on structural MRI but are often amenable to surgical resection. We aimed to...

Objective Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors...

Mesoscopic (0.1-0.5 mm) interrogation of the living human brain is critical for a comprehensive understanding of brain structure and function. However, in vivo techniques for mesoscopic imaging have been hampered by the sensitivity challenges of acquiring data at very high resolutions and the lack of analysis tools that can retain fine-scale detail...

Neuroimaging stands to benefit from emerging ultrahigh-resolution 3D histological atlases of the human brain; the first of which is 'BigBrain'. Here, we review recent methodological advances for the integration of BigBrain with multi-modal neuroimaging and introduce a toolbox, 'BigBrainWarp', that combines these developments. The aim of BigBrainWar...

The topological organization of the cerebral cortex provides hierarchical axes, namely gradients, which reveal systematic variations of brain structure and function. However, the hierarchical organization of macroscopic brain morphology and how it constrains cortical function along the organizing axes remains unclear. We map the gradient of cortica...

The MELD Project is an international collaboration aiming to create open-access, robust and generalisable tools for FCD detection. This MRI data protocol details 1) How to get access to the MELD Focal Epilepsies Redcap database 2) Inclusion criteria for the study 3) How to fill in the participant information questionnaire PLEASE NOTE: To take part...

Ultra‐high field MRI across the depth of the cortex has the potential to provide anatomically precise biomarkers and mechanistic insights into neurodegenerative disease like Huntington's disease that show layer‐selective vulnerability. Here we compare multi‐parametric mapping (MPM) measures across cortical depths for a 7T 500 μm whole brain acquisi...

The MELD Project is an international collaboration aiming to create open-access, robust and generalisable tools for FCD detection. This MRI data protocol details 1) The MRI data required / desirable for patients and controls in the MELD focal epilepsies project 2) How to convert the MRI data from dicom to nifti 3) How to ensure all identifiable dat...

Human brain atlases provide spatial reference systems for data characterizing brain organization at different levels, coming from different brains. Cytoarchitecture is a basic principle of the microstructural organization of the brain, as regional differences in the arrangement and composition of neuronal cells are indicators of changes in connecti...

A bstract Neuroimaging stands to benefit from emerging ultrahigh-resolution histological atlases of the human brain; the first of which is “BigBrain”. Ongoing research aims to characterise regional differentiation of cytoarchitecture with BigBrain and to optimise registration of BigBrain with standard neuroimaging templates. Together, this work pav...

High-resolution fMRI in the sub-millimeter regime allows researchers to resolve brain activity across cortical layers and columns non-invasively. While these high-resolution data make it possible to address novel questions of directional information flow within and across brain circuits, the corresponding data analyses are challenged by MRI artifac...

Background Drug-resistant focal epilepsy is often caused by focal cortical dysplasia (FCD). The impact of FCD location on clinical presentation and surgical outcome is largely unknown. We created a large neuroimaging cohort of patients with individually mapped FCDs to determine predictors of lesion location and postsurgical seizure freedom to aid p...

Transmitter receptors constitute a key component of the molecular machinery for intercellular communication in the brain. Recent efforts have mapped the density of diverse transmitter receptors across the human cerebral cortex with an unprecedented level of detail. Here, we distill these observations into key organizational principles. We demonstra...

The MNI CIVET pipeline for automated extraction of cortical surfaces and evaluation of cortical thickness from in-vivo human MRI has been extended for processing macaque brains. Processing is performed based on the NIMH Macaque Template (NMT), as the reference template, with the anatomical parcellation of the surface following the D99 and CHARM atl...

Human brain atlases provide spatial reference systems for data characterizing brain organization at different levels, coming from different brains. Cytoarchitecture is a basic principle of the microstructural organization of the brain, as regional differences in the arrangement and composition of neuronal cells are indicators of changes in connecti...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Transmitter receptors constitute a key component of the molecular machinery for inter-cellular communication in the brain. Recent efforts have mapped the density of diverse transmitter receptors across the human cerebral cortex with an unprecedented level of detail. Here, we distil these observations into key organizational principles. We demonstra...

The MNI CIVET pipeline for automated extraction of cortical surfaces and evaluation of cortical thickness from in-vivo human MRI has been extended for processing macaque brains. Processing is performed based on the NIMH Macaque Template (NMT), as the reference template, with the anatomical parcellation of the surface following the D99 and CHARM atl...

Neurodevelopmental disorders have a heritable component and are associated with region specific alterations in brain anatomy. However, it is unclear how genetic risks for neurodevelopmental disorders are translated into spatially patterned brain vulnerabilities. Here, we integrated cortical neuroimaging data from patients with neurodevelopmental di...

High-resolution fMRI in the sub-millimeter regime allows researchers to resolve brain activity across cortical layers and columns non-invasively. While these high-resolution data make it possible to address novel questions of directional information flow within and across brain circuits, the corresponding data analyses are challenged by MRI artifac...

Objective This retrospective, cross‐sectional study evaluated the feasibility and potential benefits of incorporating deep‐learning on structural magnetic resonance imaging (MRI) into planning stereoelectroencephalography (sEEG) implantation in pediatric patients with diagnostically complex drug‐resistant epilepsy. This study aimed to assess the de...

Histological atlases of the cerebral cortex, such as those made famous by Brodmann and von Economo, are invaluable for understanding human brain microstructure and its relationship with functional organization in the brain. However, these existing atlases are limited to small numbers of manually annotated samples from a single cerebral hemisphere,...

Determining the anatomical source of brain activity non-invasively measured from EEG or MEG sensors is challenging. In order to simplify the source localization problem, many techniques introduce the assumption that current sources lie on the cortical surface. Another common assumption is that this current flow is orthogonal to the cortical surface...

Objective: Focal cortical dysplasia (FCD) lesion detection and subtyping remain challenging on conventional MRI. New diffusion models such as the spherical mean technique (SMT) and neurite orientation dispersion and density imaging (NODDI) provide measurements that potentially produce more specific maps of abnormal tissue microstructure. This stud...

Objective A retrospective, cross-sectional study to evaluate the feasibility and potential benefits of incorporating deep-learning on structural MRI into planning stereoelectroencephalography (sEEG) implantation in paediatric patients with diagnostically complex drug-resistant epilepsy. This study aims to assess the degree of co-localisation betwee...

We studied an accelerated longitudinal cohort of adolescents and young adults (n = 234, two time points) to investigate dynamic reconfigurations in myeloarchitecture. Intracortical profiles were generated using magnetization transfer (MT) data, a myelin-sensitive magnetic resonance imaging contrast. Mixed-effect models of depth specific intracortic...

Determining the anatomical source of brain activity non-invasively measured from EEG or MEG sensors is challenging. In order to simplify the source localization problem, many techniques introduce the assumption that current sources lie on the cortical surface. Another common assumption is that this current flow is orthogonal to the cortical surface...

Structural asymmetries and sexual dimorphism of the human cerebral cortex have been identified in newborns, infants, children, adolescents, and adults. Some of these findings were linked with cognitive and neuropsychiatric disorders, which have roots in altered prenatal brain development. However, little is known about structural asymmetries or sex...

Prediction of Alzheimer’s disease before the onset of symptoms is an important clinical challenge, as it offers the potential for earlier intervention to interrupt disease progression before the development of dementia symptoms, as well as spur new prevention and treatment avenues. In this work, we propose a model that learns how to predict Alzheim...

The biological processes underpinning adolescent brain maturation remain elusive. Expanding on previous work showing age-related changes in cortical morphology, we studied an accelerated longitudinal cohort of adolescents and young adults (n=223, two time points) to investigate dynamic reconfigurations in myeloarchitecture. Intracortical profiles w...

While the role of cortical microstructure in organising neural function is well established, it remains unclear how structural constraints can give rise to more flexible elements of cognition. While nonhuman primate research has demonstrated a close structure-function correspondence, the relationship between microstructure and function remains poor...

Histological atlases of the cerebral cortex, such as those made famous by Brodmann and von Economo, are invaluable for understanding human brain microstructure and its relationship with functional organization in the brain. However, these existing atlases are limited to small numbers of manually annotated samples from a single cerebral hemisphere,...

Neurodevelopmental disorders are highly heritable and associated with spatially-selective disruptions of brain anatomy. The logic that translates genetic risks into spatially patterned brain vulnerabilities remains unclear but is a fundamental question in disease pathogenesis. Here, we approach this question by integrating (i) in vivo neuroimaging...

While the role of cortical microstructure in organising neural function is well established, it remains unclear how structural constraints can give rise to more flexible elements of cognition. While non-human primate research has demonstrated a close structure-function correspondence, the relationship between microstructure and function remains poo...

Histological sections offer high spatial resolution to examine laminar architecture of the human cerebral cortex; however, they are restricted by being 2D, hence only regions with sufficiently optimal cutting planes can be analyzed. Conversely, noninvasive neuroimaging approaches are whole brain but have relatively low resolution. Consequently, cor...

Focal cortical dysplasia is a congenital abnormality of cortical development and the leading cause of surgically remediable drug-resistant epilepsy in children. Post-surgical outcome is improved by presurgical lesion detection on structural MRI. Automated computational techniques have improved detection of focal cortical dysplasias in adults but ha...

Histological sections offer high spatial resolution to examine laminar architecture of the human cerebral cortex, however, they are restricted by being 2D, hence only regions with sufficiently optimal cutting planes can be analyzed. Conversely, non-invasive neuroimaging approaches are whole-brain but have relatively low resolution. Consequently, co...

Objective Focal cortical dysplasia (FCD) is a major pathology in patients undergoing surgical resection to treat pharmacoresistant epilepsy. Magnetic resonance imaging (MRI) postprocessing methods may provide essential help for detection of FCD. In this study, we utilized surface‐based MRI morphometry and machine learning for automated lesion detec...

Multiple studies have measured cortical thickness from MRI since the advent of high contrast and 1 mm³ resolution anatomical acquisitions and the development of advanced image processing algorithms. In this chapter we provide an overview of the methods for extracting cortical thickness, focusing on the two dominant packages in the field, FreeSurfer...

Focal cortical dysplasia is a congenital abnormality of cortical development and the leading cause of surgically remediable drug-resistant epilepsy in children. Post-surgical outcome is improved by presurgical lesion detection on structural MRI. Automated computational techniques have improved detection of focal cortical dysplasias in adults but ha...

Macroscopic cortical networks are important for cognitive function, but it remains challenging to construct anatomically plausible individual structural connectomes from human neuroimaging. We introduce a new technique for cortical network mapping, based on inter-regional similarity of multiple morphometric parameters measured using multimodal MRI....

Macroscopic cortical networks are important for cognitive function, but it remains challenging to construct anatomically plausible individual structural connectomes from human neuroimaging. We introduce a new technique for cortical network mapping based on inter-regional similarity of multiple morphometric parameters measured using multimodal MRI....

MRI provides a powerful tool to investigate brain structure in living humans. However a major challenge is interpreting the biological underpinnings of changes at this scale. This dissertation describes investigations into the problem of linking microscale post mortem cortical cytoarchitecture with millimeter-scale measures of cortical anatomy acce...

Human functional magnetic resonance imaging (fMRI) brain networks have a complex topology comprising integrative components, e.g. long-distance inter-modular edges, that are theoretically associated with higher biological cost. Here, we estimated intra-modular degree, inter-modular degree and connection distance for each of 285 cortical nodes in mu...

Graph theoretical methods have been widely used to investigate the topology of large-scale human brain networks constructed from resting state functional magnetic resonance imaging (fMRI). It has been demonstrated that such human functional connectomes have a complex topology comprising integrative components, such as hubs and inter-modular edges,...

How does human brain structure mature during adolescence? We used MRI to measure cortical thickness and intra-cortical myelination in 297 population volunteers aged 14-24 years. We found, and replicated, that association cortical areas were thicker and less myelinated than primary cortical areas at 14 years. However, association cortex had faster r...

Common mechanisms in aging and obesity are hypothesized to increase susceptibility to neurodegeneration, however direct evidence in support of this hypothesis is lacking. We therefore performed a cross-sectional analysis of MRI-based brain structure on a population-based cohort of healthy adults. Study participants were originally part of the Cambr...

In vivo structural neuroimaging can reliably identify changes to cortical morphology and its regional variation but cannot yet relate these changes to specific cortical layers. We propose, however, that by synthesizing principles of cortical organisation, including relative contributions of different layers to sulcal and gyral thickness, regional p...

Human fMRI brain networks have a complex topology comprising integrative components, e.g., long distance inter-modular edges, that are theoretically associated with higher biological cost. Here, we estimated intra-modular degree, inter-modular degree and connection distance for each of 285 cortical nodes in multiecho fMRI data from 38 healthy adult...

MRI, enabling in vivo analysis of cortical morphology, offers a powerful tool in the assessment of brain development and pathology. One of the most ubiquitous measures used - the thickness of the cortex - shows abnormalities in a number of diseases and conditions, but the functional and biological correlates of such alterations are unclear. If the...