Steve C R Williams

BackgroundAutism is a heterogeneous neurodevelopmental condition accompanied by differences in brain connectivity. Structural connectivity in autism has mainly been investigated within the white matter. However, many genetic variants associated with autism highlight genes related to synaptogenesis and axonal guidance, thus also implicating differences in intrinsic (i.e., gray matter) connections in autism. Intrinsic connections may be assessed in vivo via so-called intrinsic global and local wiring costs.MethodsHere, we examined intrinsic global and local wiring costs in the brain of 359 individuals with autism and 279 healthy control participants ages 6 to 30 years from the EU-AIMS LEAP (Longitudinal European Autism Project). FreeSurfer was used to derive surface mesh representations to compute the estimated length of connections required to wire the brain within the gray matter. Vertexwise between-group …

A comprehensive search of published literature in brain volumetry was conducted in three autoimmune diseases — systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and ulcerative colitis (UC) — with the intention of performing a meta-analysis of published data. Due to the lack of data in RA and UC, the reported meta-analysis was limited to SLE. The MEDLINE database was searched for studies from 1988 to March 2022. A total of 175 papers met the initial inclusion criteria, and 16 were included in a random-effects meta-analysis. The reduction in the number of papers included in the final analysis is primarily due to the lack of overlap in measured and reported brain regions. A significantly lower volume was seen in patients with SLE in the hippocampus, corpus callosum, and total gray matter volume measurements as compared to age- and sex-matched controls. There were not enough studies to …

Adults with antisocial personality disorder with (ASPD + P) and without (ASPD – P) psychopathy commit the majority of violent crimes. Empathic processing abnormalities are particularly prominent in psychopathy, but effective pharmacological interventions have yet to be identified. Oxytocin modulates neural responses to fearful expressions in healthy populations. The current study investigates its effects in violent antisocial men. In a placebo-controlled, randomized crossover design, 34 violent offenders (19 ASPD + P; 15 ASPD – P) and 24 healthy non-offenders received 40 IU intranasal oxytocin or placebo and then completed an fMRI morphed faces task examining the implicit processing of fearful facial expressions. Increasing intensity of fearful facial expressions failed to appropriately modulate activity in the bilateral mid-cingulate cortex in violent offenders with ASPD + P, compared with those with …

Objective Neuropharmacological changes in visual snow syndrome (VSS) are poorly understood. We aimed to use receptor target maps combined with resting functional magnetic resonance imaging (fMRI) data to identify which neurotransmitters might modulate brain circuits involved in VSS. Methods We used Receptor‐Enriched Analysis of Functional Connectivity by Targets (REACT) to estimate and compare the molecular‐enriched functional networks related to 5 neurotransmitter systems of patients with VSS (n = 24), healthy controls (HCs; n = 24), and migraine patients ([MIG], n = 25, 15 of whom had migraine with aura [MwA]). For REACT we used receptor density templates for the transporters of noradrenaline, dopamine, and serotonin, GABA‐A and NMDA receptors, as well as 5HT1B and 5HT2A receptors, and estimated the subject‐specific voxel‐wise maps of functional connectivity (FC). We then …

Objectives Rheumatoid arthritis (RA) and ulcerative colitis (UC) are two autoimmune diseases where patients report high levels of fatigue, pain, and depression. The effect of systemic inflammation from these diseases is likely affecting the brain, however, it is unknown whether there are measurable neuroanatomical changes and whether these are a contributing factor to these central symptoms. Methods We included 258 RA patients with 774 age and sex matched controls and 249 UC patients with 747 age and sex matched controls in a case control study utilising the UK Biobank dataset. We used imaging derived phenotypes (IDPs) to determine whether there were differences in (1) hippocampal volume and (2) additional subcortical brain volumes between patients compared to controls and if there were common regions affected between these two diseases. Results Patients with UC had moderately smaller hippocampi compared to age and sex matched controls (difference: 134.15 mm3, SD ± 64.76, p = 0.035). This result was not seen in RA patients. RA patients had a significantly smaller amygdala volume than age and sex matched controls (difference: 91.27 mm3, SD ± 30.85, p = 0.0021, adjusted p value = 0.012). This result was not seen in UC patients. All other subcortical structures analysed were comparable between the patients and control groups. Conclusion These results indicate there are subcortical brain differences between UC, RA and controls but different regions of the limbic system are preferentially affected by UC and RA. This study may provide evidence for different neurodegenerative mechanisms in distinct autoimmune …

BackgroundOff-target central nervous system (CNS) effects are associated with androgen receptor (AR)-targeting treatments for prostate cancer. Darolutamide is a structurally distinct AR inhibitor with low blood–brain barrier penetration.ObjectiveWe compared cerebral blood flow (CBF) in grey matter and specific regions related to cognition after darolutamide, enzalutamide, or placebo administration, using arterial spin-label magnetic resonance imaging (ASL-MRI).MethodsThis phase I, randomized, placebo-controlled, three-period crossover study administered single doses of darolutamide, enzalutamide, or placebo to 23 healthy males (aged 18–45 years) at 6-week intervals. ASL-MRI mapped CBF 4 h post-treatment. Treatments were compared using paired t-tests.ResultsDrug concentrations during scans confirmed similar unbound exposure of darolutamide and enzalutamide, with complete washout between …

BackgroundAlthough many studies have explored atypicalities in gray matter (GM) and white matter (WM) morphology of autism, most of them relied on unimodal analyses that did not benefit from the likelihood that different imaging modalities may reflect common neurobiology. We aimed to establish brain patterns of modalities that differentiate between individuals with and without autism and explore associations between these brain patterns and clinical measures in the autism group.MethodsWe studied 183 individuals with autism and 157 nonautistic individuals (age range, 6–30 years) in a large, deeply phenotyped autism dataset (EU-AIMS LEAP [European Autism Interventions—A Multicentre Study for Developing New Medications Longitudinal European Autism Project]). Linked independent component analysis was used to link all participants’ GM volume and WM diffusion tensor images, and group …

Catatonia is a well characterized psychomotor syndrome that has recognizable motor, affective, behavioural and vegetative manifestations. Despite recent demonstration that catatonia is often associated with brain imaging abnormalities, there is currently no consensus or guidelines about the role of brain imaging. In this study, we assessed the feasibility of brain imaging in a series of patients with catatonia in a routine clinical setting and estimated the prevalence of clinically relevant radiological abnormalities.Sixty patients with catatonia were evaluated against sixty non-healthy controls subjects with headache. The MRI reports were reviewed, and MRI scans were also interpreted by neuroradiologists using a standardised MRI assessment.In this cohort, more than 85% of brain scans of patients with catatonia revealed abnormalities. The most frequently reported abnormalities in the catatonic group were white matter …

Background Overgeneralised self-blame and worthlessness are key symptoms of major depressive disorder (MDD) and have previously been associated with self-blame-selective changes in connectivity between right superior anterior temporal lobe (rSATL) and subgenual frontal cortices. Another study showed that remitted MDD patients were able to modulate this neural signature using functional magnetic resonance imaging (fMRI) neurofeedback training, thereby increasing their self-esteem. The feasibility and potential of using this approach in symptomatic MDD were unknown. Method This single-blind pre-registered randomised controlled pilot trial probed a novel self-guided psychological intervention with and without additional rSATL-posterior subgenual cortex (BA25) fMRI neurofeedback, targeting self-blaming emotions in people with insufficiently recovered MDD and early treatment-resistance (n = 43 …

PurposeTo develop a second-order and slice-specific linear shimming technique and investigate its efficiency in the mitigation of signal loss and distortions, and the increase of temporal signal-to-noise ratio (tSNR) within the spinal cord during functional Magnetic Resonance Imaging (fMRI) of the human cervical spinal cord.MethodsAll scans were performed on a General Electric Discovery MR750 3 T scanner, using a head, neck and spine coil and a neurovascular array. To improve B0 homogeneity, a field map was acquired, and second-order shims (SOS) were optimized over manually defined regions of interest (ROIs). Signal loss from dephasing by susceptibility-induced gradients was reduced by optimizing slice-specific x-, y- and z-shims to maximize signal within the spinal cord. Spectral-spatial excitation pulses were used in both the slice-specific linear shimming calibration scan and fMRI acquisitions. The …

The identification of meaningful functional magnetic resonance imaging (fMRI) biomarkers requires measures that reliably capture brain performance across different subjects and over multiple scanning sessions. Recent developments in fMRI acquisition, such as the introduction of multiband (MB) protocols and in‐plane acceleration, allow for increased scanning speed and improved temporal resolution. However, they may also lead to reduced temporal signal to noise ratio and increased signal leakage between simultaneously excited slices. These methods have been adopted in several scanning modalities including diffusion weighted imaging and fMRI. To our knowledge, no study has formally compared the reliability of the same resting‐state fMRI (rs‐fMRI) metrics (amplitude of low‐frequency fluctuations; seed‐to‐voxel and region of interest [ROI]‐to‐ROI connectivity) across conventional single‐band fMRI and …

Receptor-enriched analysis of functional connectivity by targets (REACT) is a strategy to enrich functional MRI (fMRI) data with molecular information on the neurotransmitter distribution density in the human brain, providing a biological basis to the functional connectivity (FC) analysis. Although this approach has been used in BOLD fMRI studies only so far, extending its use to ASL imaging would provide many advantages, including the more direct link of ASL with neuronal activity compared to BOLD and its suitability for pharmacological MRI studies assessing drug effects on baseline brain function. Here, we applied REACT to simultaneous ASL/BOLD resting-state fMRI data of 29 healthy subjects and estimated the ASL and BOLD FC maps related to six molecular systems. We then compared the ASL and BOLD FC maps in terms of spatial similarity, and evaluated and compared the test–retest reproducibility of …

We present an empirically benchmarked framework for sex-specific normative modeling of brain morphometry that can inform about the biological and behavioral significance of deviations from typical age-related neuroanatomical changes and support future study designs. This framework was developed using regional morphometric data from 37,407 healthy individuals (53% female; aged 3–90 years) following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The Multivariate Factorial Polynomial Regression (MFPR) emerged as the preferred algorithm optimized using nonlinear polynomials for age and linear effects of global measures as covariates. The MFPR models showed excellent accuracy across the lifespan and within distinct age-bins, and …

Resting fMRI studies have identified intrinsic spinal cord activity, which forms organised motor (ventral) and sensory (dorsal) resting-state networks. However, to facilitate the use of spinal fMRI in, for example, clinical studies, it is crucial to first assess the reliability of the method, particularly given the unique anatomical, physiological, and methodological challenges associated with acquiring the data. Here we demonstrate a novel implementation for acquiring BOLD-sensitive resting-state spinal fMRI, which was used to characterise functional connectivity relationships in the cervical cord and assess their test-retest reliability in 23 young healthy volunteers. Resting-state networks were estimated in two ways: (1) by extracting the mean timeseries from anatomically constrained seed masks and estimating voxelwise connectivity maps and (2) by calculating seed-to-seed correlations between extracted mean timeseries. Seed regions corresponded to the four grey matter horns (ventral/dorsal and left/right) of C5-C8 segmental levels. Test-retest reliability was assessed using the intraclass correlation coefficient (ICC) in the following ways: for each voxel in the cervical spine; each voxel within an activated cluster; the mean signal as a summary estimate within an activated cluster; and correlation strength in the seed-to-seed analysis. Spatial overlap of clusters derived from voxelwise analysis between sessions was examined using Dice coefficients. Following voxelwise analysis, we observed distinct unilateral dorsal and ventral organisation of cervical spinal resting-state networks that was largely confined in the rostro-caudal extent to each spinal segmental …

BackgroundDisruptive behavior disorders (DBD) are heterogeneous at the clinical and the biological level. Therefore, the aims were to dissect the heterogeneous neurodevelopmental deviations of the affective brain circuitry and provide an integration of these differences across modalities.MethodsWe combined two novel approaches. First, normative modeling to map deviations from the typical age-related pattern at the level of the individual of (i) activity during emotion matching and (ii) of anatomical images derived from DBD cases (n = 77) and controls (n = 52) aged 8–18 years from the EU-funded Aggressotype and MATRICS consortia. Second, linked independent component analysis to integrate subject-specific deviations from both modalities.ResultsWhile cases exhibited on average a higher activity than would be expected for their age during face processing in regions such as the amygdala when compared …

Introduction: Lifeguards must maintain alertness and monitor an aquatic space across extended periods. However, lifeguard research has yet to investigate a lifeguard’s ability to maintain performance over time and whether this is influenced by years of certified experience or the detection difficulty of a drowning incident. The aim of this study was to examine whether lifeguard experience, drowning duration, bather number, and time on task influences drowning detection performance. Method: A total of 30 participants took part in nine 60-minute lifeguard specific tasks that included 11 drowning events occurring at five-minute intervals. Each task had manipulated conditions that acted as the independent variables, including bather number and drowning duration. Results: The experienced group detected a greater number of drowning events per task, compared to novice and naïve groups. Findings further highlighted …

Relationship between cortical glutamatergic metabolite levels and hippocampal activity in schizotypy Yong-ming Wang1, Alice Eger Page 1 1 Relationship between cortical glutamatergic metabolite levels and hippocampal activity in schizotypy Yong-ming Wang1, Alice Egerton1, Katrina McMullen2, Anna McLaughlin1, Veena Kumari3,4, David J Lythgoe2, Gareth J Barker2, Steve CR Williams2, Fernando Zelaya2, Gemma Modinos1,2* 1 Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom 2 Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom 3 Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom 4 Centre for Cognitive Neuroscience, College of Health and Life Sciences, Brunel …

Most neuroimaging modalities use regular grids of voxels to represent the three-dimensional space occupied by the brain. However, a regular 3D voxel grid does not reflect the anatomical and topological complexity represented by the brain’s white matter connections. In contrast, tractography reconstructions based on diffusion MRI provide a closer characterisation of the white matter pathways followed by the neuronal fibres interconnecting different brain regions. In this work, we introduce hypervoxels as a new methodological framework that combines the spatial encoding capabilities of multidimensional voxels with the anatomical and topological information found in tractography data. We provide a detailed description of the framework and evaluate the benefits of using hypervoxels by carrying out comparative voxel and hypervoxel cluster inference analyses on diffusion MRI data from a neuroimaging study on amyotrophic lateral sclerosis (ALS). Compared to the voxel analyses, the use of hypervoxels improved the detection of effects of interest in the data in terms of statistical significance levels and spatial distribution across white matter regions known to be affected in ALS. In these regions, the hypervoxel results also identified specific white matter pathways that resolve the anatomical ambiguity otherwise observed in the results from the voxel analyses. The observed increase in sensitivity and specificity can be explained by the superior ability of hypervoxel-based methods to represent and disentangle the anatomical overlap of white matter connections. Based on this premise, we expect that the use of hypervoxels should improve the analysis …

In posttraumatic stress disorder (PTSD), re‐experiencing of the trauma is a hallmark symptom proposed to emerge from a de‐contextualised trauma memory. Cognitive therapy for PTSD (CT‐PTSD) addresses this de‐contextualisation through different strategies. At the brain level, recent research suggests that the dynamics of specific large‐scale brain networks play an essential role in both the healthy response to a threatening situation and the development of PTSD. However, very little is known about how these dynamics are altered in the disorder and rebalanced after treatment and successful recovery. Using a data‐driven approach and fMRI, we detected recurring large‐scale brain functional states with high temporal precision in a population of healthy trauma‐exposed and PTSD participants before and after successful CT‐PTSD. We estimated the total amount of time that each participant spent on each of the …

Leading Eigenvector Dynamics Analysis (LEiDA) is an analytic approach that characterizes brain activity recorded with functional Magnetic Resonance Imaging (fMRI) as a succession of discrete phase-locking patterns, or states, that consistently recur over time across all participants. LEiDA allows for the extraction of three state-related measures which have previously been key to gaining a better understanding of brain dynamics in both healthy and clinical populations: the probability of occurrence of a given state, its lifetime and the probability of switching from one state to another. The degree to which test-retest reliability of the LEiDA measures may be affected by increasing MRI multiband (MB) factors in comparison with single band sequences is yet to be established. In this study, twenty-four healthy older adults were scanned over three sessions, on weeks 0, 1 and 4. On each visit, they underwent a conventional single band resting-state fMRI (rs-fMRI) scan and three different MB rs-fMRI scans, with MB factors of 4, with and without in-plane acceleration, and 6 without in-plane acceleration. We found test-retest reliability scores to be significantly higher with multiband factor 4 with and without in-plane acceleration for most cortical networks. These findings will inform the choice of acquisition parameters for future studies and clinical trials.