Publications by authors named "Steven C R Williams"

230 Publications

Simultaneous high-resolution T -weighted imaging and quantitative T mapping at low magnetic field strengths using a multiple TE and multi-orientation acquisition approach.

Magn Reson Med 2022 May 12. Epub 2022 May 12.

Department of Neuroimaging, Kings College London, London, UK.

Purpose: Low magnetic field systems provide an important opportunity to expand MRI to new and diverse clinical and research study populations. However, a fundamental limitation of low field strength systems is the reduced SNR compared to 1.5 or 3T, necessitating compromises in spatial resolution and imaging time. Most often, images are acquired with anisotropic voxels with low through-plane resolution, which provide acceptable image quality with reasonable scan times, but can impair visualization of subtle pathology.

Methods: Here, we describe a super-resolution approach to reconstruct high-resolution isotropic T -weighted images from a series of low-resolution anisotropic images acquired in orthogonal orientations. Furthermore, acquiring each image with an incremented TE allows calculations of quantitative T images without time penalty.

Results: Our approach is demonstrated via phantom and in vivo human brain imaging, with simultaneous 1.5 × 1.5 × 1.5 mm T -weighted and quantitative T maps acquired using a clinically feasible approach that combines three acquisition that require approximately 4-min each to collect. Calculated T values agree with reference multiple TE measures with intraclass correlation values of 0.96 and 0.85 in phantom and in vivo measures, respectively, in line with previously reported brain T values at 150 mT, 1.5T, and 3T.

Conclusion: Our multi-orientation and multi-TE approach is a time-efficient method for high-resolution T -weighted images for anatomical visualization with simultaneous quantitative T imaging for increased sensitivity to tissue microstructure and chemical composition.
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http://dx.doi.org/10.1002/mrm.29273DOI Listing
May 2022

Integrating neuroimaging and gene expression data using the imaging transcriptomics toolbox.

STAR Protoc 2022 Jun 15;3(2):101315. Epub 2022 Apr 15.

Department of Neuroimaging, IoPPN, King's College London, London, UK.

The integration of neuroimaging and transcriptomics data, , is becoming increasingly popular but standardized workflows for its implementation are still lacking. We describe the Imaging Transcriptomics toolbox, a new package that implements a full imaging transcriptomics pipeline using a user-friendly, command line interface. This toolbox allows the user to identify patterns of gene expression which correlates with a specific neuroimaging phenotype and perform gene set enrichment analyses to inform the biological interpretation of the findings using up-to-date methods. For complete details on the use and execution of this protocol, please refer to Martins et al. (2021).
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http://dx.doi.org/10.1016/j.xpro.2022.101315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036395PMC
June 2022

Effective psychological therapy for PTSD changes the dynamics of specific large-scale brain networks.

Hum Brain Mapp 2022 Apr 8. Epub 2022 Apr 8.

Oxford Centre for Anxiety Disorders and Trauma, Department of Experimental Psychology, University of Oxford, Oxford, UK.

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 states while being exposed to trauma-related and neutral pictures. We found that PTSD participants spent less time on two default mode subnetworks involved in different forms of self-referential processing in contrast to PTSD participants after CT-PTSD (mtDMN and dmDMN ) and healthy trauma-exposed controls (only mtDMN ). Furthermore, re-experiencing severity was related to decreased time spent on the default mode subnetwork involved in contextualised retrieval of autobiographical memories, and increased time spent on the salience and visual networks. Overall, our results support the hypothesis that PTSD involves an imbalance in the dynamics of specific large-scale brain network states involved in self-referential processes and threat detection, and suggest that successful CT-PTSD might rebalance this dynamic aspect of brain function.
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http://dx.doi.org/10.1002/hbm.25846DOI Listing
April 2022

Motion corrected silent ZTE neuroimaging.

Magn Reson Med 2022 07 5;88(1):195-210. Epub 2022 Apr 5.

Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Purpose: To develop self-navigated motion correction for 3D silent zero echo time (ZTE) based neuroimaging and characterize its performance for different types of head motion.

Methods: The proposed method termed MERLIN (Motion Estimation & Retrospective correction Leveraging Interleaved Navigators) achieves self-navigation by using interleaved 3D phyllotaxis k-space sampling. Low resolution navigator images are reconstructed continuously throughout the ZTE acquisition using a sliding window and co-registered in image space relative to a fixed reference position. Rigid body motion corrections are then applied retrospectively to the k-space trajectory and raw data and reconstructed into a final, high-resolution ZTE image.

Results: MERLIN demonstrated successful and consistent motion correction for magnetization prepared ZTE images for a range of different instructed motion paradigms. The acoustic noise response of the self-navigated phyllotaxis trajectory was found to be only slightly above ambient noise levels (<4 dBA).

Conclusion: Silent ZTE imaging combined with MERLIN addresses two major challenges intrinsic to MRI (i.e., subject motion and acoustic noise) in a synergistic and integrated manner without increase in scan time and thereby forms a versatile and powerful framework for clinical and research MR neuroimaging applications.
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http://dx.doi.org/10.1002/mrm.29201DOI Listing
July 2022

Imaging transcriptomics: Convergent cellular, transcriptomic, and molecular neuroimaging signatures in the healthy adult human brain.

Cell Rep 2021 12;37(13):110173

Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London SE5 8AF, UK; Department of Information Engineering, University of Padua, Via Gradenigo, 6/b, 35131 Padova, Italy. Electronic address:

The integration of transcriptomic and neuroimaging data, "imaging transcriptomics," has recently emerged to generate hypotheses about potential biological pathways underlying regional variability in neuroimaging features. However, the validity of this approach is yet to be examined in depth. Here, we sought to bridge this gap by performing transcriptomic decoding of the regional distribution of well-known molecular markers spanning different elements of the biology of the healthy human brain. Imaging transcriptomics identifies biological and cell pathways that are consistent with the known biology of a wide range of molecular neuroimaging markers. The extent to which it can capture patterns of gene expression that align well with elements of the biology of the neuroinflammatory axis, at least in healthy controls without a proinflammatory challenge, is inconclusive. Imaging transcriptomics might constitute an interesting approach to improve our understanding of the biological pathways underlying regional variability in a wide range of neuroimaging phenotypes.
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http://dx.doi.org/10.1016/j.celrep.2021.110173DOI Listing
December 2021

Rapid processing and quantitative evaluation of structural brain scans for adaptive multimodal imaging.

Hum Brain Mapp 2022 04 24;43(5):1749-1765. Epub 2021 Dec 24.

Department of Computer Science, Centre for Medical Image Computing, University College London, London, UK.

Current neuroimaging acquisition and processing approaches tend to be optimised for quality rather than speed. However, rapid acquisition and processing of neuroimaging data can lead to novel neuroimaging paradigms, such as adaptive acquisition, where rapidly processed data is used to inform subsequent image acquisition steps. Here we first evaluate the impact of several processing steps on the processing time and quality of registration of manually labelled T -weighted MRI scans. Subsequently, we apply the selected rapid processing pipeline both to rapidly acquired multicontrast EPImix scans of 95 participants (which include T -FLAIR, T , T *, T -FLAIR, DWI and ADC contrasts, acquired in ~1 min), as well as to slower, more standard single-contrast T -weighted scans of a subset of 66 participants. We quantify the correspondence between EPImix T -FLAIR and single-contrast T -weighted scans, using correlations between voxels and regions of interest across participants, measures of within- and between-participant identifiability as well as regional structural covariance networks. Furthermore, we explore the use of EPImix for the rapid construction of morphometric similarity networks. Finally, we quantify the reliability of EPImix-derived data using test-retest scans of 10 participants. Our results demonstrate that quantitative information can be derived from a neuroimaging scan acquired and processed within minutes, which could further be used to implement adaptive multimodal imaging and tailor neuroimaging examinations to individual patients.
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http://dx.doi.org/10.1002/hbm.25755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8886661PMC
April 2022

Self-blame in major depression: a randomised pilot trial comparing fMRI neurofeedback with self-guided psychological strategies.

Psychol Med 2021 Dec 2:1-11. Epub 2021 Dec 2.

Department of Psychological Medicine, Centre for Affective Disorders,London,UK.

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, n = 35 completers). Participants completed three weekly self-guided sessions to rebalance self-blaming biases.

Results: As predicted, neurofeedback led to a training-induced reduction in rSATL-BA25 connectivity for self-blame v. other-blame. Both interventions were safe and resulted in a 46% reduction on the Beck Depression Inventory-II, our primary outcome, with no group differences. Secondary analyses, however, revealed that patients without DSM-5-defined anxious distress showed a superior response to neurofeedback compared with the psychological intervention, and the opposite pattern in anxious MDD. As predicted, symptom remission was associated with increases in self-esteem and this correlated with the frequency with which participants employed the psychological strategies in daily life.

Conclusions: These findings suggest that self-blame-rebalance neurofeedback may be superior over a solely psychological intervention in non-anxious MDD, although further confirmatory studies are needed. Simple self-guided strategies tackling self-blame were beneficial, but need to be compared against treatment-as-usual in further trials. https://doi.org/10.1186/ISRCTN10526888.
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http://dx.doi.org/10.1017/S0033291721004797DOI Listing
December 2021

Transcriptional and cellular signatures of cortical morphometric remodelling in chronic pain.

Pain 2022 Jun 23;163(6):e759-e773. Epub 2021 Sep 23.

Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

Abstract: Chronic pain is a highly debilitating and difficult to treat condition, which affects the structure of the brain. Although the development of chronic pain is moderately heritable, how disease-related alterations at the microscopic genetic architecture drive macroscopic brain abnormalities is currently largely unknown. Here, we examined alterations in morphometric similarity (MS) and applied an integrative imaging transcriptomics approach to identify transcriptional and cellular correlates of these MS changes, in 3 independent small cohorts of patients with distinct chronic pain syndromes (knee osteoarthritis, low back pain, and fibromyalgia) and age-matched and sex-matched pain-free controls. We uncover a novel pattern of cortical MS remodelling involving mostly small-to-medium MS increases in the insula and limbic cortex (none of these changes survived stringent false discovery rate correction for the number of regions tested). This pattern of changes is different from that observed in patients with major depression and cuts across the boundaries of specific pain syndromes. By leveraging transcriptomic data from Allen Human Brain Atlas, we show that cortical MS remodelling in chronic pain spatially correlates with the brain-wide expression of genes related to pain and broadly involved in the glial immune response and neuronal plasticity. Our findings bridge levels to connect genes, cell classes, and biological pathways to in vivo imaging correlates of chronic pain. Although correlational, our data suggest that cortical remodelling in chronic pain might be shaped by multiple elements of the cellular architecture of the brain and identifies several pathways that could be prioritized in future genetic association or drug development studies.
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http://dx.doi.org/10.1097/j.pain.0000000000002480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8940732PMC
June 2022

Ordinal SuStaIn: Subtype and Stage Inference for Clinical Scores, Visual Ratings, and Other Ordinal Data.

Front Artif Intell 2021 12;4:613261. Epub 2021 Aug 12.

Centre for Medical Image Computing, University College London, London, United Kingdom.

Subtype and Stage Inference (SuStaIn) is an unsupervised learning algorithm that uniquely enables the identification of subgroups of individuals with distinct pseudo-temporal disease progression patterns from cross-sectional datasets. SuStaIn has been used to identify data-driven subgroups and perform patient stratification in neurodegenerative diseases and in lung diseases from continuous biomarker measurements predominantly obtained from imaging. However, the SuStaIn algorithm is not currently applicable to discrete ordinal data, such as visual ratings of images, neuropathological ratings, and clinical and neuropsychological test scores, restricting the applicability of SuStaIn to a narrower range of settings. Here we propose 'Ordinal SuStaIn', an ordinal version of the SuStaIn algorithm that uses a scored events model of disease progression to enable the application of SuStaIn to ordinal data. We demonstrate the validity of Ordinal SuStaIn by benchmarking the performance of the algorithm on simulated data. We further demonstrate that Ordinal SuStaIn out-performs the existing continuous version of SuStaIn (Z-score SuStaIn) on discrete scored data, providing much more accurate subtype progression patterns, better subtyping and staging of individuals, and accurate uncertainty estimates. We then apply Ordinal SuStaIn to six different sub-scales of the Clinical Dementia Rating scale (CDR) using data from the Alzheimer's disease Neuroimaging Initiative (ADNI) study to identify individuals with distinct patterns of functional decline. Using data from 819 ADNI1 participants we identified three distinct CDR subtype progression patterns, which were independently verified using data from 790 ADNI2 participants. Our results provide insight into patterns of decline in daily activities in Alzheimer's disease and a mechanism for stratifying individuals into groups with difficulties in different domains. Ordinal SuStaIn is broadly applicable across different types of ratings data, including visual ratings from imaging, neuropathological ratings and clinical or behavioural ratings data.
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http://dx.doi.org/10.3389/frai.2021.613261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387598PMC
August 2021

The autonomic brain: Multi-dimensional generative hierarchical modelling of the autonomic connectome.

Cortex 2021 10 23;143:164-179. Epub 2021 Jul 23.

Queen Square Institute of Neurology, University College London, UK.

The autonomic nervous system governs the body's multifaceted internal adaptation to diverse changes in the external environment, a role more complex than is accessible to the methods-and data scales-hitherto used to illuminate its operation. Here we apply generative graphical modelling to large-scale multimodal neuroimaging data encompassing normal and abnormal states to derive a comprehensive hierarchical representation of the autonomic brain. We demonstrate that whereas conventional structural and functional maps identify regions jointly modulated by parasympathetic and sympathetic systems, only graphical analysis discriminates between them, revealing the cardinal roles of the autonomic system to be mediated by high-level distributed interactions. We provide a novel representation of the autonomic system-a multidimensional, generative network-that renders its richness tractable within future models of its function in health and disease.
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http://dx.doi.org/10.1016/j.cortex.2021.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500219PMC
October 2021

Neural mapping of prepulse-induced startle reflex modulation as indices of sensory information processing in healthy and clinical populations: A systematic review.

Hum Brain Mapp 2021 11 20;42(16):5495-5518. Epub 2021 Aug 20.

Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Startle reflex is modulated when a weaker sensory stimulus ("prepulse") precedes a startling stimulus ("pulse"). Prepulse Inhibition (PPI) is the attenuation of the startle reflex (prepulse precedes pulse by 30-500 ms), whereas Prepulse Facilitation (PPF) is the enhancement of the startle reflex (prepulse precedes pulse by 500-6000 ms). Here, we critically appraise human studies using functional neuroimaging to establish brain regions associated with PPI and PPF. Of 10 studies, nine studies revealed thalamic, striatal and frontal lobe activation during PPI in healthy groups, and activation deficits in the cortico-striato-pallido-thalamic circuitry in schizophrenia (three studies) and Tourette Syndrome (two studies). One study revealed a shared network for PPI and PPF in frontal regions and cerebellum, with PPF networks recruiting superior medial gyrus and cingulate cortex. The main gaps in the literature are (i) limited PPF research and whether PPI and PPF operate on separate/shared networks, (ii) no data on sex differences in neural underpinnings of PPI and PPF, and (iii) no data on neural underpinnings of PPI and PPF in other clinical disorders.
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http://dx.doi.org/10.1002/hbm.25631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519869PMC
November 2021

Characterizing the Clinical Features and Atrophy Patterns of -Related Frontotemporal Dementia With Disease Progression Modeling.

Neurology 2021 08 22;97(9):e941-e952. Epub 2021 Jun 22.

From the Department of Neuroimaging (A.L.Y., S.C.R.W.), Institute of Psychiatry, Psychology and Neuroscience, King's College London; Departments of Computer Science (A.L.Y., D.C.A.) and Medical Physics and Biomedical Engineering (D.M.C.), Centre for Medical Image Computing, University College London; Dementia Research Centre (M.B., L.L.R., R.S.C., G.P., E.T., D.M.C., C.V.G., L.J., J.D.R.), Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK; Department of Neurology (J.v.S., L.J., H.S.), Erasmus Medical Centre, Rotterdam, the Netherlands; Cognitive Disorders Unit (F.M.), Department of Neurology, Donostia University Hospital; Neuroscience Area (F.M.), Biodonostia Health Research Institute, San Sebastian, Gipuzkoa, Spain; Alzheimer's Disease and Other Cognitive Disorders Unit (R.S.-V.), Neurology Service, Hospital Clínic, Institut d'Investigacións Biomèdiques August Pi I Sunyer, University of Barcelona, Spain; Neurology Unit (B.B.), Department of Clinical and Experimental Sciences, University of Brescia, Italy; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, CHU de Québec, and Faculté de Médecine (R.L.), Université Laval, Québec; Sunnybrook Health Sciences Centre, Sunnybrook Research Institute (M.M.), and Tanz Centre for Research in Neurodegenerative Diseases (M.C.T.), University of Toronto, Canada; Center for Alzheimer Research (C.G.), Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Bioclinicum, Karolinska Institutet; Unit for Hereditary Dementias (C.G.), Theme Aging, Karolinska University Hospital, Solna, Sweden; Fondazione Ca'Granda (D.G.), IRCCS Ospedale Policlinico; University of Milan (D.G.), Centro Dino Ferrari, Italy; Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust (J.B.R.), University of Cambridge, UK; Department of Clinical Neurological Sciences (E.F.), University of Western Ontario, London, Canada; Department of Neurodegenerative Diseases (M.S.), Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen; Center for Neurodegenerative Diseases (DZNE) (M.S.), Tübingen, Germany; Laboratory for Cognitive Neurology, Department of Neurosciences (R.V.), and Leuven Brain Institute (R.V.), KU Leuven; Neurology Service (R.V.), University Hospitals Leuven, Belgium; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Fondazione IRCCS Istituto Neurologico Carlo Besta (F.T.), Milan, Italy; University Hospital of Coimbra (HUC), Neurology Service (I.S.), and Center for Neuroscience and Cell Biology (I.S.), Faculty of Medicine, University of Coimbra, Portugal; Department of Psychiatry, McGill University Health Centre (S.D.), and McConnell Brain Imaging Centre, Montreal Neurological Institute (S.D.), McGill University, Montreal, Canada; Nuffield Department of Clinical Neurosciences (C.B.), Medical Sciences Division, University of Oxford; Division of Neuroscience and Experimental Psychology (A.G.), Wolfson Molecular Imaging Centre, University of Manchester, UK; Departments of Geriatric Medicine and Nuclear Medicine (A.G.), University of Duisburg-Essen; Department of Neurology (J.L., A.D.), Ludwig-Maximilians Universität München; German Center for Neurodegenerative Diseases (DZNE) (J.L.); Munich Cluster of Systems Neurology (SyNergy) (J.L.), Munich; Department of Neurology (M.O.), University of Ulm, Germany; Departments of Neuroscience, Psychology, Drug Research, and Child Health (S.S.), University of Florence; and IRCCS Don Gnocchi (S.S.), Florence, Italy.

Background And Objective: Mutations in the gene cause frontotemporal dementia (FTD). Most previous studies investigating the neuroanatomical signature of mutations have grouped all different mutations together and shown an association with focal atrophy of the temporal lobe. The variability in atrophy patterns between each particular mutation is less well-characterized. We aimed to investigate whether there were distinct groups of mutation carriers based on their neuroanatomical signature.

Methods: We applied Subtype and Stage Inference (SuStaIn), an unsupervised machine learning technique that identifies groups of individuals with distinct progression patterns, to characterize patterns of regional atrophy in associated FTD within the Genetic FTD Initiative (GENFI) cohort study.

Results: Eighty-two mutation carriers were analyzed, the majority of whom had P301L, IVS10+16, or R406W mutations, along with 48 healthy noncarriers. SuStaIn identified 2 groups of mutation carriers with distinct atrophy patterns: a temporal subtype, in which atrophy was most prominent in the hippocampus, amygdala, temporal cortex, and insula; and a frontotemporal subtype, in which atrophy was more localized to the lateral temporal lobe and anterior insula, as well as the orbitofrontal and ventromedial prefrontal cortex and anterior cingulate. There was one-to-one mapping between IVS10+16 and R406W mutations and the temporal subtype and near one-to-one mapping between P301L mutations and the frontotemporal subtype. There were differences in clinical symptoms and neuropsychological test scores between subtypes: the temporal subtype was associated with amnestic symptoms, whereas the frontotemporal subtype was associated with executive dysfunction.

Conclusion: Our results demonstrate that different mutations give rise to distinct atrophy patterns and clinical phenotype, providing insights into the underlying disease biology and potential utility for patient stratification in therapeutic trials.
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http://dx.doi.org/10.1212/WNL.0000000000012410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408507PMC
August 2021

Accessible pediatric neuroimaging using a low field strength MRI scanner.

Neuroimage 2021 09 17;238:118273. Epub 2021 Jun 17.

Center for Neuroimaging Sciences, King's College, London, United Kingdom.

Magnetic resonance imaging (MRI) has played an increasingly relevant role in understanding infant, child, and adolescent neurodevelopment, providing new insight into developmental patterns in neurotypical development, as well as those associated with potential psychopathology, learning disorders, and other neurological conditions. In addition, studies have shown the impact of a child's physical and psychosocial environment on developing brain structure and function. A rate-limiting complication in these studies, however, is the high cost and infrastructural requirements of modern MRI systems. High costs mean many neuroimaging studies typically include fewer than 100 individuals and are performed predominately in high resource hospitals and university settings within high income countries (HICs). As a result, our knowledge of brain development, particularly in children who live in lower and middle income countries (LMICs) is relatively limited. Low field systems, with magnetic fields less than 100mT offer the promise of lower scanning costs and wide-spread global adoption, but routine low field pediatric neuroimaging has yet to be demonstrated. Here we present the first pediatric MRI data collected on a low cost and assessable 64mT scanner in children 6 weeks to 16 years of age and replicate brain volumes estimates and developmental trajectories derived from 3T MRI data. While preliminary, these results illustrate the potential of low field imaging as a viable complement to more conventional high field imaging systems, and one that may further enhance our knowledge of neurodevelopment in LMICs where malnutrition, psychosocial adversities, and other environmental exposures may profoundly affect brain maturation.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118273DOI Listing
September 2021

In vivo multi-parametric manganese-enhanced MRI for detecting amyloid plaques in rodent models of Alzheimer's disease.

Sci Rep 2021 06 14;11(1):12419. Epub 2021 Jun 14.

BRAIN Centre (Biomarker Research and Imaging for Neuroscience), Department of Neuroimaging, King's College London, The James Black Centre, 125 Coldharbour Lane, London, SE5 9NU, UK.

Amyloid plaques are a hallmark of Alzheimer's disease (AD) that develop in its earliest stages. Thus, non-invasive detection of these plaques would be invaluable for diagnosis and the development and monitoring of treatments, but this remains a challenge due to their small size. Here, we investigated the utility of manganese-enhanced MRI (MEMRI) for visualizing plaques in transgenic rodent models of AD across two species: 5xFAD mice and TgF344-AD rats. Animals were given subcutaneous injections of MnCl and imaged in vivo using a 9.4 T Bruker scanner. MnCl improved signal-to-noise ratio but was not necessary to detect plaques in high-resolution images. Plaques were visible in all transgenic animals and no wild-types, and quantitative susceptibility mapping showed that they were more paramagnetic than the surrounding tissue. This, combined with beta-amyloid and iron staining, indicate that plaque MR visibility in both animal models was driven by plaque size and iron load. Longitudinal relaxation rate mapping revealed increased manganese uptake in brain regions of high plaque burden in transgenic animals compared to their wild-type littermates. This was limited to the rhinencephalon in the TgF344-AD rats, while it was most significantly increased in the cortex of the 5xFAD mice. Alizarin Red staining suggests that manganese bound to plaques in 5xFAD mice but not in TgF344-AD rats. Multi-parametric MEMRI is a simple, viable method for detecting amyloid plaques in rodent models of AD. Manganese-induced signal enhancement can enable higher-resolution imaging, which is key to visualizing these small amyloid deposits. We also present the first in vivo evidence of manganese as a potential targeted contrast agent for imaging plaques in the 5xFAD model of AD.
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http://dx.doi.org/10.1038/s41598-021-91899-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203664PMC
June 2021

Silent zero TE MR neuroimaging: Current state-of-the-art and future directions.

Prog Nucl Magn Reson Spectrosc 2021 04 26;123:73-93. Epub 2021 Mar 26.

Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; ASL Europe, GE Healthcare, Munich, Germany.

Magnetic Resonance Imaging (MRI) scanners produce loud acoustic noise originating from vibrational Lorentz forces induced by rapidly changing currents in the magnetic field gradient coils. Using zero echo time (ZTE) MRI pulse sequences, gradient switching can be reduced to a minimum, which enables near silent operation.Besides silent MRI, ZTE offers further interesting characteristics, including a nominal echo time of TE = 0 (thus capturing short-lived signals from MR tissues which are otherwise MR-invisible), 3D radial sampling (providing motion robustness), and ultra-short repetition times (providing fast and efficient scanning).In this work we describe the main concepts behind ZTE imaging with a focus on conceptual understanding of the imaging sequences, relevant acquisition parameters, commonly observed image artefacts, and image contrasts. We will further describe a range of methods for anatomical and functional neuroimaging, together with recommendations for successful implementation.
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http://dx.doi.org/10.1016/j.pnmrs.2021.03.002DOI Listing
April 2021

Developmental changes in fronto-striatal glutamate and their association with functioning during inhibitory control in autism spectrum disorder and obsessive compulsive disorder.

Neuroimage Clin 2021 10;30:102622. Epub 2021 Mar 10.

Department of Cognitive Neuroscience, Donders Institute of Brain, Cognition and Behaviour, Radboud University Medical Center, the Netherlands; Donders Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, the Netherlands. Electronic address:

Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) show overlapping symptomatology and deficits in inhibitory control, which are associated with altered functioning and glutamatergic signaling in fronto-striatal circuitry. These parameters have never been examined together. The purpose of the current study was to investigate functioning during inhibitory control and its association with fronto-striatal glutamate concentrations across these disorders using a multi-center, longitudinal approach. Adolescents with ASD (n = 24), OCD (n = 15) and controls (n = 35) underwent two magnetic resonance imaging (MRI) sessions with a one-year interval. This included proton magnetic resonance spectroscopy (H-MRS; n = 74) and functional MRI during an inhibitory control task (n = 53). We investigated H-MRS data and fMRI data separately as well as integrated in a multimodal analysis using linear models focusing on diagnosis and continuous measures of overlapping compulsivity symptoms. ACC glutamate was reduced over time in the ASD group compared with controls, while striatal glutamate decreased over time independent of diagnosis. Increased compulsive behavior seemed to be associated with increased striatal activity during failed inhibitory control. The integrated analyses showed differential involvement of increased striatal glutamate during failed but decreased striatal glutamate during successful inhibitory control in the OCD group compared to controls and ASD, suggesting different underlying mechanisms for OCD compared to ASD.
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http://dx.doi.org/10.1016/j.nicl.2021.102622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022251PMC
July 2021

Revealing the mechanisms behind novel auditory stimuli discrimination: An evaluation of silent functional MRI using looping star.

Hum Brain Mapp 2021 06 17;42(9):2833-2850. Epub 2021 Mar 17.

Department of Neuroimaging, King's College London, London, UK.

Looping Star is a near-silent, multi-echo, 3D functional magnetic resonance imaging (fMRI) technique. It reduces acoustic noise by at least 25dBA, with respect to gradient-recalled echo echo-planar imaging (GRE-EPI)-based fMRI. Looping Star has successfully demonstrated sensitivity to the cerebral blood-oxygen-level-dependent (BOLD) response during block design paradigms but has not been applied to event-related auditory perception tasks. Demonstrating Looping Star's sensitivity to such tasks could (a) provide new insights into auditory processing studies, (b) minimise the need for invasive ear protection, and (c) facilitate the translation of numerous fMRI studies to investigations in sound-averse patients. We aimed to demonstrate, for the first time, that multi-echo Looping Star has sufficient sensitivity to the BOLD response, compared to that of GRE-EPI, during a well-established event-related auditory discrimination paradigm: the "oddball" task. We also present the first quantitative evaluation of Looping Star's test-retest reliability using the intra-class correlation coefficient. Twelve participants were scanned using single-echo GRE-EPI and multi-echo Looping Star fMRI in two sessions. Random-effects analyses were performed, evaluating the overall response to tones and differential tone recognition, and intermodality analyses were computed. We found that multi-echo Looping Star exhibited consistent sensitivity to auditory stimulation relative to GRE-EPI. However, Looping Star demonstrated lower test-retest reliability in comparison with GRE-EPI. This could reflect differences in functional sensitivity between the techniques, though further study is necessary with additional cognitive paradigms as varying cognitive strategies between sessions may arise from elimination of acoustic scanner noise.
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http://dx.doi.org/10.1002/hbm.25407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127154PMC
June 2021

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years.

Hum Brain Mapp 2022 01 17;43(1):431-451. Epub 2021 Feb 17.

Laboratory of Psychiatric Neuroimaging, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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http://dx.doi.org/10.1002/hbm.25364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675431PMC
January 2022

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Hum Brain Mapp 2022 01 11;43(1):452-469. Epub 2021 Feb 11.

Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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http://dx.doi.org/10.1002/hbm.25320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675429PMC
January 2022

Cholinergic modulation of disorder-relevant human defensive behaviour in generalised anxiety disorder.

Transl Psychiatry 2021 01 5;11(1):13. Epub 2021 Jan 5.

Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Drugs that are clinically effective against anxiety disorders modulate the innate defensive behaviour of rodents, suggesting these illnesses reflect altered functioning in brain systems that process threat. This hypothesis is supported in humans by the discovery that the intensity of threat-avoidance behaviour is altered by the benzodiazepine anxiolytic lorazepam. However, these studies used healthy human participants, raising questions as to their validity in anxiety disorder patients, as well as their generalisability beyond GABAergic benzodiazepine drugs. BNC210 is a novel negative allosteric modulator of the alpha 7 nicotinic acetylcholine receptor and we recently used functional Magnetic Resonance Imaging to show it reduced amygdala responses to fearful faces in generalised anxiety disorder patients. Here we report the effect of BNC210 on the intensity of threat-avoidance behaviour in 21 female GAD patients from the same cohort. We used the Joystick Operated Runway Task as our behavioural measure, which is a computerised human translation of the Mouse Defense Test Battery, and the Spielberger state anxiety inventory as our measure of state affect. Using a repeated-measures, within-subjects design we assessed the effect of BNC210 at two dose levels versus placebo (300 mg and 2000 mg) upon two types of threat-avoidance behaviour (Flight Intensity and Risk Assessment Intensity). We also tested the effects of 1.5 mg of the benzodiazepine lorazepam as an active control. BNC210 significantly reduced Flight Intensity relative to placebo and the low dose of BNC210 also significantly reduced self-reported state anxiety. Risk Assessment Intensity was not significantly affected. Results show both human defensive behaviour and state anxiety are influenced by cholinergic neurotransmission and there provide converging evidence that this system has potential as a novel target for anxiolytic pharmacotherapy.
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http://dx.doi.org/10.1038/s41398-020-01141-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791022PMC
January 2021

Patterns of Mitochondrial TSPO Binding in Cerebral Small Vessel Disease: An PET Study With Neuropathological Comparison.

Front Neurol 2020 16;11:541377. Epub 2020 Oct 16.

Department of Neuroimaging, Institute of Psychiatry Psychology & Neuroscience, King's College London, London, United Kingdom.

Small vessel disease (SVD) is associated with cognitive impairment in older age and be implicated in vascular dementia. Post-mortem studies show proliferation of activated microglia in the affected white matter. However, the role of inflammation in SVD pathogenesis is incompletely understood and better biomarkers are needed. We hypothesized that expression of the 18 kDa translocator protein (TSPO), a marker of microglial activation, would be higher in SVD. Positron emission tomography (PET) was performed with the second-generation TSPO ligand [C]PBR28 in 11 participants with SVD. TSPO binding was evaluated by a two-tissue compartment model, with and without a vascular binding component, in white matter hyperintensities (WMH) and normal-appearing white matter (NAWM). In post-mortem tissue, in a separate cohort of individuals with SVD, immunohistochemistry was performed for TSPO and a pan-microglial marker Iba1. Kinetic modeling showed reduced tracer volume and blood volume fraction in WMH compared with NAWM, but a significant increase in vascular binding. Vascular [C]PBR28 binding was also increased compared with normal-appearing white matter of healthy participants free of SVD. Immunohistochemistry showed a diffuse increase in microglial staining (with Iba1) in sampled tissue in SVD compared with control samples, but with only a subset of microglia staining positively for TSPO. Intense TSPO staining was observed in the vicinity of damaged small blood vessels, which included perivascular macrophages. The results suggest an altered phenotype of activated microglia, with reduced TSPO expression, in the areas of greatest white matter ischemia in SVD, with implications for the interpretation of TSPO PET studies in older individuals or those with vascular risk factors.
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http://dx.doi.org/10.3389/fneur.2020.541377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596201PMC
October 2020

Linking Pain Sensation to the Autonomic Nervous System: The Role of the Anterior Cingulate and Periaqueductal Gray Resting-State Networks.

Front Neurosci 2020 27;14:147. Epub 2020 Feb 27.

Department of Neuroimaging, King's College London, London, United Kingdom.

There are bi-directional interactions between the autonomic nervous system (ANS) and pain. This is likely underpinned by a substantial overlap between brain areas of the central autonomic network and areas involved in pain processing and modulation. To date, however, relatively little is known about the neuronal substrates of the ANS-pain association. Here, we acquired resting state fMRI scans in 21 healthy subjects at rest and during tonic noxious cold stimulation. As indicators of autonomic function, we examined how heart rate variability (HRV) frequency measures were influenced by tonic noxious stimulation and how these variables related to participants' pain perception and to brain functional connectivity in regions known to play a role in both ANS regulation and pain perception, namely the right dorsal anterior cingulate cortex (dACC) and periaqueductal gray (PAG). Our findings support a role of the cardiac ANS in brain connectivity during pain, linking functional connections of the dACC and PAG with measurements of low frequency (LF)-HRV. In particular, we identified a three-way relationship between the ANS, cortical brain networks known to underpin pain processing, and participants' subjectively reported pain experiences. LF-HRV both at rest and during pain correlated with functional connectivity between the seed regions and other cortical areas including the right dorsolateral prefrontal cortex (dlPFC), left anterior insula (AI), and the precuneus. Our findings link cardiovascular autonomic parameters to brain activity changes involved in the elaboration of nociceptive information, thus beginning to elucidate underlying brain mechanisms associated with the reciprocal relationship between autonomic and pain-related systems.
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http://dx.doi.org/10.3389/fnins.2020.00147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527240PMC
February 2020

Silent myelin-weighted magnetic resonance imaging.

Wellcome Open Res 2020 13;5:74. Epub 2020 Aug 13.

Department of Neuroimaging, King's College London, London, UK.

 Inhomogeneous Magnetization Transfer (ihMT) is an emerging, uniquely myelin-specific magnetic resonance imaging (MRI) contrast. Current ihMT acquisitions utilise fast Gradient Echo sequences which are among the most acoustically noisy MRI sequences, reducing patient comfort during acquisition. We sought to address this by modifying a near silent MRI sequence to include ihMT contrast. A Magnetization Transfer preparation module was incorporated into a radial Zero Echo-Time sequence. Repeatability of the ihMT ratio and inverse ihMT ratio were assessed in a cohort of healthy subjects. We also investigated how head orientation affects ihMT across subjects, as a previous study in a single subject suggests this as a potential confound. We demonstrated that ihMT ratios comparable to existing, acoustically loud, implementations could be obtained with the silent sequence. We observed a small but significant effect of head orientation on inverse ihMTR. Silent ihMT imaging is a comparable alternative to conventional, noisy, alternatives. For all future ihMT studies we recommend careful positioning of the subject within the scanner.
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http://dx.doi.org/10.12688/wellcomeopenres.15845.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431975PMC
August 2020

Occipital cortex and cerebellum gray matter changes in visual snow syndrome.

Neurology 2020 09 5;95(13):e1792-e1799. Epub 2020 Aug 5.

From the Headache Group, Department of Basic and Clinical Neuroscience (F.P., P.J.G.), Centre for Neuroimaging Sciences, Department of Neuroimaging (M.B., O.O., S.C.R.W.), and Department of Old Age Psychiatry, Institute of Psychiatry, Psychology & Neuroscience (D.F.), King's College London; NIHR-Wellcome Trust King's Clinical Research Facility, SLaM Biomedical Research Centre (F.P., P.J.G.), King's College Hospital, London, UK; and Advanced Baby Imaging Laboratory (M.B.), Warren Alpert School of Medicine at Brown University, Providence, RI.

Objective: To determine whether regional gray and white matter differences characterize the brain of patients with visual snow syndrome, a newly defined neurologic condition, we used a voxel-based morphometry approach.

Methods: In order to investigate whole brain morphology directly, we performed an MRI study on patients with visual snow syndrome (n = 24) and on age- and sex-matched healthy volunteers (n = 24). Voxel-based morphometry was used to determine volumetric differences in patients with visual snow. We further analyzed cerebellar anatomy directly using the high-resolution spatially unbiased atlas template of the cerebellum.

Results: Compared to healthy controls, patients with visual snow syndrome had increased gray matter volume in the left primary and secondary visual cortices, the left visual motion area V5, and the left cerebellar crus I/lobule VI area. These anatomical alterations could not be explained by clinical features of the condition.

Conclusion: Patients with visual snow syndrome have subtle, significant neuroanatomical differences in key visual and lateral cerebellar areas, which may in part explain the pathophysiologic basis of the disorder.
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http://dx.doi.org/10.1212/WNL.0000000000010530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682819PMC
September 2020

Subacute Changes in -Acetylaspartate (NAA) Following Ischemic Stroke: A Serial MR Spectroscopy Pilot Study.

Diagnostics (Basel) 2020 Jul 16;10(7). Epub 2020 Jul 16.

Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London SE5 8AF, UK.

Preservation of neuronal tissue is crucial for recovery after stroke, but studies suggest that prolonged neuronal loss occurs following acute ischaemia. This study assessed the temporal pattern of neuronal loss in subacute ischemic stroke patients using H magnetic resonance spectroscopy, in parallel with functional recovery at 2, 6 and 12 weeks after stroke. Specifically, we measured -acetylaspartate (NAA), choline, myoinositol, creatine and lactate concentrations in the ipsilesional and contralesional thalamus of 15 first-ever acute ischaemic stroke patients and 15 control participants and correlated MRS concentrations with motor recovery, measured at 12 weeks using the Fugl-Meyer scale. NAA in the ipsilesional thalamus fell significantly between 2 and 12 weeks (10.0 to 7.97 mmol/L, = 0.003), while choline, myoinositol and lactate concentrations increased ( = 0.025, = 0.031, = 0.001, respectively). Higher NAA concentrations in the ipsilesional thalamus at 2 and 12 weeks correlated with higher Fugl Meyer scores at 12 weeks ( = 0.004 and = 0.006, respectively). While these results should be considered preliminary given the modest sample size, the progressive fall in NAA and late increases in choline, myoinositol and lactate may indicate progressive non-ischaemic neuronal loss, metabolically depressed neurons and/or diaschisis effects, which have a detrimental effect on motor recovery. Interventions that can potentially limit this ongoing subacute tissue damage may improve stroke recovery.
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http://dx.doi.org/10.3390/diagnostics10070482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399797PMC
July 2020

Sustained perturbation in functional connectivity induced by cold pain.

Eur J Pain 2020 10 27;24(9):1850-1861. Epub 2020 Jul 27.

Department of Neuroimaging, King's College London, London, UK.

Background: Functional connectivity (FC) perturbations have been reported in multiple chronic pain phenotypes, but the nature of reported changes varies between cohorts and may relate to the consequences of living with chronic-pain related comorbidities, such as anxiety and depression. Healthy volunteer studies provide opportunities to study the effects of tonic noxious stimulation independently of these sequelae. Connectivity changes in task negative and positive networks, for example, the default mode and salience networks (DMN/SN), respectively, have been described, but how these and other connectivity networks, for example, those governing descending pain control are affected by the presence of tonic, noxious stimulation in healthy, pain-free individuals, remains unknown.

Method: In 20 healthy volunteers, we assessed FC prior to, during, and following tonic cold painful stimulation in the ventromedial prefrontal cortex (vmPFC), rostral anterior insula (rAI), subgenual anterior cingulate cortex (ACC) and periaqueductal grey (PAG). We also recorded subjectively reported pain using a computerised visual analogue scale.

Results: We saw DMN FC changes during painful stimulation and that inter-network connectivity between the rAI with the vmPFC increased during pain, whereas PAG-precuneus FC decreased. Pain-induced FC alterations persisted following noxious stimulation. FC changes related to the magnitude of individuals' subjectively reported pain.

Conclusions: We demonstrate FC changes during and following tonic cold-pain in healthy participants. Similarities between our findings and reports of patients with chronic pain suggest that some FC changes observed in these patients may relate to the presence of an ongoing afferent nociceptive drive.

Significance: How pain-related resting state networks are affected by tonic cold-pain remains unknown. We investigated functional connectivity alterations during and following tonic cold pain in healthy volunteers. Cold pain perturbed the functional connectivity of the ventro-medial prefrontal cortex, anterior insula, and the periacquaductal grey area. These connectivity changes were associated with the magnitude of individuals' reported pain. We suggest that some connectivity changes described in chronic pain patients may be due to an ongoing afferent peripheral drive.
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http://dx.doi.org/10.1002/ejp.1633DOI Listing
October 2020

Drum training induces  long-term plasticity in the cerebellum and connected cortical thickness.

Sci Rep 2020 06 22;10(1):10116. Epub 2020 Jun 22.

King's College London, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, London, UK.

It is unclear to what extent cerebellar networks show long-term plasticity and accompanied changes in cortical structures. Using drumming as a demanding multimodal motor training, we compared cerebellar lobular volume and white matter microstructure, as well as cortical thickness of 15 healthy non-musicians before and after learning to drum, and 16 age matched novice control participants. After 8 weeks of group drumming instruction, 3 ×30 minutes per week, we observed the cerebellum significantly changing its grey (volume increase of left VIIIa, relative decrease of VIIIb and vermis Crus I volume) and white matter microstructure in the inferior cerebellar peduncle. These plastic cerebellar changes were complemented by changes in cortical thickness (increase in left paracentral, right precuneus and right but not left superior frontal thickness), suggesting an interplay of cerebellar learning with cortical structures enabled through cerebellar pathways.
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http://dx.doi.org/10.1038/s41598-020-65877-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308330PMC
June 2020

Towards a neuroscience-based theory of personality: within-subjects dissociation of human brain activity during pursuit and goal conflict.

Personal Neurosci 2019 31;2:e4. Epub 2019 Jul 31.

Department of Psychology, City, University of London, London, UK.

As demonstrated by neuroimaging data, the human brain contains systems that control responses to threat. The revised Reinforcement Sensitivity Theory of personality predicts that individual differences in the reactivity of these brain systems produce anxiety and fear-related personality traits. Here we discuss some of the challenges in testing this theory and, as an example, present a pilot study that aimed to dissociate brain activity during pursuit by threat and goal conflict. We did this by translating the Mouse Defense Test Battery for human fMRI use. In this version, dubbed the Joystick Operated Runway Task (JORT), we repeatedly exposed 24 participants to pursuit and goal conflict, with and without threat of electric shock. The runway design of JORT allowed the effect of threat distance on brain activation to be evaluated independently of context. Goal conflict plus threat of electric shock caused deactivation in a network of brain areas that included the fusiform and middle temporal gyri, as well as the default mode network core, including medial frontal regions, precuneus and posterior cingulate gyrus, and laterally the inferior parietal and angular gyri. Consistent with earlier research, we also found that imminent threat activated the midbrain and that this effect was significantly stronger during the simple pursuit condition than during goal conflict. Also consistent with earlier research, we found significantly greater hippocampal activation during goal conflict than pursuit by imminent threat. In conclusion, our results contribute knowledge to theories linking anxiety disorders to altered functioning in defensive brain systems and also highlight challenges in this research domain.
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http://dx.doi.org/10.1017/pen.2019.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219687PMC
July 2019

Impaired connectivity within neuromodulatory networks in multiple sclerosis and clinical implications.

J Neurol 2020 Jul 26;267(7):2042-2053. Epub 2020 Mar 26.

Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

There is mounting evidence regarding the role of impairment in neuromodulatory networks for neurodegenerative diseases, such as Parkinson's and Alzheimer's disease. However, the role of neuromodulatory networks in multiple sclerosis (MS) has not been assessed. We applied resting-state functional connectivity and graph theory to investigate the changes in the functional connectivity within neuromodulatory networks including the serotonergic, noradrenergic, cholinergic, and dopaminergic systems in MS. Twenty-nine MS patients and twenty-four age- and gender-matched healthy controls performed clinical and cognitive assessments including the expanded disability status score, symbol digit modalities test, and Hamilton Depression rating scale. We demonstrated a diffuse reorganization of network topography (P < 0.01) in serotonergic, cholinergic, noradrenergic, and dopaminergic networks in patients with MS. Serotonergic, noradrenergic, and cholinergic network functional connectivity derangement was associated with disease duration, EDSS, and depressive symptoms (P < 0.01). Derangements in serotonergic, noradrenergic, cholinergic, and dopaminergic network impairment were associated with cognitive abilities (P < 0.01). Our results indicate that functional connectivity changes within neuromodulatory networks might be a useful tool in predicting disability burden over time, and could serve as a surrogate endpoint to assess efficacy for symptomatic treatments.
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http://dx.doi.org/10.1007/s00415-020-09806-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320961PMC
July 2020

Neurocognitive correlates of working memory and emotional processing in postpartum psychosis: an fMRI study.

Psychol Med 2021 07 16;51(10):1724-1732. Epub 2020 Mar 16.

Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Background: Postpartum psychosis (PP) is a severe postpartum disorder. While working memory and emotional processing-related brain function are consistently impaired in psychoses unrelated to the puerperium, no studies have investigated them in PP.

Methods: Twenty-four women at risk of developing PP (11 developed an episode - PE; 13 remained well - NPE) and 20 healthy postpartum women completed two functional magnetic resonance imaging tasks within a year of delivery: working memory (n-back) and emotional face recognition (fearful faces). We compared women at-risk of PP to controls, as well as NPE, PE, and controls to test for potential effects of a PP episode occurrence.

Results: Women at-risk of PP and PE showed hyperactivation of lateral visual areas, precuneus, and posterior cingulate during the n-back task. The at-risk group as a whole, as well as the PE and NPE groups, showed hyperconnectivity of the right dorsolateral prefrontal cortex (DLPFC) with various parieto-occipito-temporo-cerebellar regions compared to controls during several n-back conditions. Increases in connectivity between the right DLPFC and ipsilateral middle temporal gyrus were observed in the PE group compared to NPE during 2-back. During the fearful faces task, at-risk women as a group showed hyperactivation of fronto-cingulo-subcortical regions, and hypoconnectivity between the left amygdala and ipsilateral occipito-parietal regions compared to controls. No significant performance differences were observed.

Conclusions: These results present preliminary evidence of a differential nature of functional brain abnormalities in PP compared to the typically observed reduced connectivity with the DLPFC in psychoses unrelated to puerperium, such as bipolar disorder.
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http://dx.doi.org/10.1017/S0033291720000471DOI Listing
July 2021
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