Persistent Impact of Antenatal Maternal Anaemia on Child Brain Structure at 6-7 Years of Age: A South African Child Health Study.

Background: The study aim was to determine whether associations of antenatal maternal anaemia with smaller corpus callosum, putamen, and caudate nucleus volumes previously described in children at age 2-3 years persist to age 6-7 years in the Drakenstein Child Health Study (DCHS). Methods: This neuroimaging sub-study was nested within the DCHS, a South African population-based birth cohort. Pregnant women were enrolled (2012-2015) and mother-child dyads were followed prospectively. A sub-group of children had magnetic resonance imaging at 6-7 years of age (2018-2022). Mothers had haemoglobin measurements during pregnancy and a proportion of children were tested postnatally. Maternal anaemia (haemoglobin<11g/dL) and child anaemia were classified using WHO and local guidelines. Linear modeling was used to investigate associations between antenatal maternal anaemia status, maternal haemoglobin concentrations, and regional child brain volumes. Models included potential confounders and were conducted with and without child anaemia to assess the relative roles of antenatal versus postnatal anaemia. Results: Overall, 157 children (Mean [SD] age of 75.54 [4.77] months; 84 [53.50%] male) were born to mothers with antenatal haemoglobin data. The prevalence of maternal anaemia during pregnancy was 31.85% (50/157). In adjusted models, maternal anaemia status was associated with smaller volumes of the total corpus callosum (adjusted percentage difference, -6.77%; p=0.003), left caudate nucleus (adjusted percentage difference, -5.98%, p=0.005), and right caudate nucleus (adjusted percentage difference, -6.12%; p=0.003). Continuous maternal haemoglobin was positively associated with total corpus callosum (ß=0.239 [CI: 0.10 to 0.38]; p<0.001) and caudate nucleus (ß=0.165 [CI: 0.02 to 0.31]; p=0.027) volumes. In a sub-group (n=89) with child haemoglobin data (Mean [SD] age of 76.06[4.84]), the prevalence of antenatal maternal anaemia and postnatal child anaemia was 38.20% (34/89) and 47.19% (42/89), respectively. There was no association between maternal and child anaemia (c2 = 0.799; p=0.372), and child anaemia did not contribute to regional brain volume differences associated with maternal anaemia. Conclusions: Associations between maternal anaemia and regional child brain volumes previously reported at 2-3 years of age were consistent and persisted to 6-7 years of age. Findings support the importance of optimizing antenatal maternal health and reinforce these brain regions as a future research focus on intervention outcomes.

Clinical and neuroimaging predictors of benzodiazepine response in catatonia: A machine learning approach.

Catatonia is a well characterized psychomotor syndrome combining motor, behavioural and neurovegetative signs. Benzodiazepines are the first-choice treatment, effective in 70 % of cases. Currently, the factors associated with benzodiazepine resistance remain unknown. We aimed to develop machine learning models using clinical and neuroimaging data to predict benzodiazepine response in catatonic patients. This study examined a cohort of catatonic patients who underwent standardized clinical evaluation, 3 T brain MRI, and benzodiazepine trial. Based on clinical response, patients were classified as benzodiazepine responders or non-responders. Cortical thickness and regional brain volumes were measured. Two machine learning models (linear model and gradient boosting tree model) were developed to identify predictors of treatment response using clinical, demographic, and neuroimaging data. The cohort included 65 catatonic patients, comprising 30 benzodiazepine responders and 35 non-responders. Using clinical data alone, the linear model achieved 63% precision, 51% recall, a specificity of 61%, and 58% AUC, while the gradient boosting tree (GBT) model attained 46% precision, 60% recall, a specificity of 62% and 64% AUC. Incorporating neuroimaging data improved model performance, with the linear model achieving 66% precision, 57% recall, a specificity of 67%, and 70% AUC, and the GBT model attaining 50% precision, 50% recall, a specificity of 62% and 70% AUC. The integration of imaging data with demographic and clinical information significantly enhanced the predictive performance of the models. The duration of the catatonic syndrome, along with the presence of mitgehen (passive obedience) and immobility/stupor, and the volume of the right medial orbito-frontal cortex emerged as important factors in predicting non-response to benzodiazepines.

Spinal fMRI demonstrates segmental organisation of functionally connected networks in the cervical spinal cord: A test-retest reliability study.

Resting functional magnetic resonance imaging (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 characterise functional connectivity relationships in the cervical cord and assess their between-session test-retest reliability in 23 young healthy volunteers. Resting-state networks were estimated in two ways (1) by estimating seed-to-voxel connectivity maps and (2) by calculating seed-to-seed correlations. 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. Spatial overlap of clusters derived from seed-to-voxel analysis between sessions was examined using Dice coefficients. Following seed-to-voxel 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 level, with more sparse connections observed between segments. Additionally, strongest correlations were observed between within-segment ipsilateral dorsal-ventral connections, followed by within-segment dorso-dorsal and ventro-ventral connections. Test-retest reliability of these networks was mixed. Reliability was poor when assessed on a voxelwise level, with more promising indications of reliability when examining the average signal within clusters. Reliability of correlation strength between seeds was highly variable, with the highest reliability achieved in ipsilateral dorsal-ventral and dorso-dorsal/ventro-ventral connectivity. However, the spatial overlap of networks between sessions was excellent. We demonstrate that while test-retest reliability of cervical spinal resting-state networks is mixed, their spatial extent is similar across sessions, suggesting that these networks are characterised by a consistent spatial representation over time.

Reliability of quantitative sensory testing in the assessment of somatosensory function after high-frequency stimulation-induced sensitisation of central nociceptive pathways.

ABSTRACT: The high frequency stimulation (HFS) model can be used alongside quantitative sensory testing (QST) to assess the sensitisation of central nociceptive pathways. However, the validity and between-session reliability of using QST z -score profiles to measure changes in mechanical and thermal afferent pathways in the HFS model are poorly understood. In this study, 32 healthy participants underwent QST before and after HFS (5× 100 Hz trains; 10× electrical detection threshold) in the same heterotopic skin area across 2 repeated sessions. The only mechanical QST z -score profiles that demonstrated a consistent gain of function across repeated test sessions were mechanical pain threshold (MPT) and mechanical pain sensitivity (MPS), which were associated with moderate and good reliability, respectively. There was no relationship between HFS intensity and MPT and MPS z -score profiles. There was no change in low intensity, but a consistent facilitation of high-intensity pin prick stimuli in the mechanical stimulus response function across repeated test sessions. There was no change in cold pain threshold (CPT) and heat pain threshold (HPT) z -score profiles across session 1 and 2, which were associated with moderate and good reliability, respectively. There were inconsistent changes in the sensitivity to innocuous thermal QST parameters, with cool detection threshold (CDT), warm detection threshold (WDT), and thermal sensory limen (TSL) all producing poor reliability. These data suggest that HFS-induced changes in MPS z -score profiles is a reliable way to assess experimentally induced central sensitisation and associated secondary mechanical hyperalgesia in healthy participants.

An expert-novice comparison of lifeguard specific vigilance performance.

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 that time, bather number, and drowning duration has a substantial influence on lifeguard specific drowning detection performance. PRACTICAL APPLICATIONS: It is hoped that the outcome of the study will have applied application in highlighting the critical need for lifeguard organizations to be aware of a lifeguard's capacity to sustain attention, and for researchers to explore methods for minimizing any decrement in vigilance performance.

Development of neonatal-specific sequences for portable ultralow field magnetic resonance brain imaging: a prospective, single-centre, cohort study.

Background: Magnetic Resonance (MR) imaging is key for investigation of suspected newborn brain abnormalities. Access is limited in low-resource settings and challenging in infants needing intensive care. Portable ultralow field (ULF) MRI is showing promise in bedside adult brain imaging. Use in infants and children has been limited as brain-tissue composition differences necessitate sequence modification. The aim of this study was to develop neonatal-specific ULF structural sequences and test these across a range of gestational maturities and pathologies to inform future validation studies. Methods: Prospective cohort study within a UK neonatal specialist referral centre. Infants undergoing 3T MRI were recruited for paired ULF (64mT) portable MRI by convenience sampling from the neonatal unit and post-natal ward. Key inclusion criteria: 1) Infants with risk or suspicion of brain abnormality, or 2) preterm and term infants without suspicion of major genetic, chromosomal or neurological abnormality. Exclusions: presence of contra-indication for MR scanning. ULF sequence parameters were optimised for neonatal brain-tissues by iterative and explorative design. Neuroanatomic and pathologic features were compared by unblinded review, informing optimisation of subsequent sequence generations in a step-wise manner. Main outcome: visual identification of healthy and abnormal brain tissues/structures. ULF MR spectroscopy, diffusion, susceptibility weighted imaging, arteriography, and venography require pre-clinical technical development and have not been tested. Findings: Between September 23, 2021 and October 25, 2022, 102 paired scans were acquired in 87 infants; 1.17 paired scans per infant. Median age 9 days, median postmenstrual age 40+2 weeks (range: 31+3-53+4). Infants had a range of intensive care requirements. No adverse events observed. Optimised ULF sequences can visualise key neuroanatomy and brain abnormalities. In finalised neonatal sequences: T2w imaging distinguished grey and white matter (7/7 infants), ventricles (7/7), pituitary tissue (5/7), corpus callosum (7/7) and optic nerves (7/7). Signal congruence was seen within the posterior limb of the internal capsule in 10/11 infants on finalised T1w scans. In addition, brain abnormalities visualised on ULF optimised sequences have similar MR signal patterns to 3T imaging, including injury secondary to infarction (6/6 infants on T2w scans), hypoxia-ischaemia (abnormal signal in basal ganglia, thalami and white matter 2/2 infants on T2w scans, cortical highlighting 1/1 infant on T1w scan), and congenital malformations: polymicrogyria 3/3, absent corpus callosum 2/2, and vermian hypoplasia 3/3 infants on T2w scans. Sequences are susceptible to motion corruption, noise, and ULF artefact. Non-identified pathologies were small or subtle. Interpretation: On unblinded review, optimised portable MR can provide sufficient contrast, signal, and resolution for neuroanatomical identification and detection of a range of clinically important abnormalities. Blinded validation studies are now warranted. Funding: The Bill and Melinda Gates Foundation, the MRC, the Wellcome/EPSRC Centre for Medical Engineering, the MRC Centre for Neurodevelopmental Disorders, and the National Institute for Health Research (NIHR) Biomedical Research Centres based at Guy's and St Thomas' and South London & Maudsley NHS Foundation Trusts and King's College London.

Molecular-enriched functional connectivity in the human brain using multiband multi-echo simultaneous ASL/BOLD fMRI.

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 each modality. We found robust spatial patterns of molecular-enriched FC for both modalities, moderate similarity between BOLD and ASL FC maps and comparable reproducibility for all but one molecular-enriched functional networks. Our findings showed that ASL is as informative as BOLD in detecting functional circuits associated with specific molecular pathways, and that the two modalities may provide complementary information related to these circuits.

Abnormal Glutamatergic and Serotonergic Connectivity in Visual Snow Syndrome and Migraine with Aura.

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 performed voxel-wise comparisons of these maps among HCs, MIG, and VSS. RESULTS: Patients with VSS had reduced FC in glutamatergic networks localized in the anterior cingulate cortex (ACC) compared to HCs and patients with migraine, and reduced FC in serotoninergic networks localized in the insula, temporal pole, and orbitofrontal cortex compared to controls, similar to patients with migraine with aura. Patients with VSS also showed reduced FC in 5HT2A -enriched networks, largely localized in occipito-temporo-parietal association cortices. As revealed by subgroup analyses, these changes were independent of, and analogous to, those found in patients with migraine with aura. INTERPRETATION: Our results show that glutamate and serotonin are involved in brain connectivity alterations in areas of the visual, salience, and limbic systems in VSS. Importantly, altered serotonergic connectivity is independent of migraine in VSS, and simultaneously comparable to that of migraine with aura, highlighting a shared biology between the disorders. ANN NEUROL 2023;94:873-884.

Comparison of Cerebral Blood Flow in Regions Relevant to Cognition After Enzalutamide, Darolutamide, and Placebo in Healthy Volunteers: A Randomized Crossover Trial.

BACKGROUND: Off-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. OBJECTIVE: We 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). METHODS: This 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. RESULTS: Drug concentrations during scans confirmed similar unbound exposure of darolutamide and enzalutamide, with complete washout between treatments. A significant localized 5.2% (p = 0.01) and 5.9% (p < 0.001) CBF reduction in the temporo-occipital cortices was observed for enzalutamide versus placebo and versus darolutamide, respectively, with no significant differences for darolutamide versus placebo. Enzalutamide reduced CBF in all prespecified regions, with significant reductions versus placebo (3.9%, p = 0.045) and versus darolutamide (4.4%, p = 0.037) in the left and right dorsolateral prefrontal cortices, respectively. Darolutamide showed minimal changes in CBF versus placebo in cognition-relevant regions. CONCLUSIONS: Darolutamide did not significantly alter CBF, consistent with its low blood-brain barrier penetration and low risk of CNS-related adverse events. A significant reduction in CBF was observed with enzalutamide. These results may be relevant to cognitive function with early and extended use of second-generation AR inhibitors, and warrant further investigation in patients with prostate cancer. TRIAL REGISTRATION NUMBER: NCT03704519; date of registration: October 2018.

Androgens, or male sex hormones, bind to androgen receptors within prostate cells and can cause growth of prostate cancer. The treatment of prostate cancer often includes drugs that bind to androgen receptors, called androgen receptor inhibitors, keeping androgens from binding to the receptors and preventing prostate cancer growth. In clinical studies, these drugs may have adverse effects on the central nervous system, or brain, including dizziness, falls, and impaired thinking and problem solving. This study compared the effects of two androgen receptor inhibitors, darolutamide and enzalutamide, and placebo on blood flow in the brain. Blood flow was measured by a type of magnetic resonance imaging in healthy men after receiving a single dose of treatment. Blood flow in the brain was reduced by enzalutamide compared with both placebo and darolutamide. Darolutamide did not decrease brain blood flow. This lack of effect on brain blood flow is in line with preclinical studies that showed darolutamide's limited ability to cross the blood­brain barrier, which is the naturally occurring barrier that protects the brain from harmful substances. In clinical studies of patients with prostate cancer treated with darolutamide, adverse effects on the brain have occurred in similar proportions of patients receiving darolutamide and placebo. In contrast, enzalutamide treatment has an increased risk of adverse effects on the brain versus placebo. The results of this study provide information on the effects of these androgen receptor inhibitors on brain blood flow that may be related to their adverse effects on the brain and its functioning.

A meta-analysis of structural MRI studies of the brain in systemic lupus erythematosus (SLE).

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 perform a meta-analysis for RA and UC; instead, we include a summary of published volumetric studies. The meta-analyses revealed structural brain abnormalities in patients with SLE, suggesting that lower global brain volumes are associated with disease status. This volumetric difference was seen in both the hippocampus and corpus callosum and total gray matter volume measurements. These results indicate both gray and white matter involvements in SLE and suggest there may be both localized and global reductions in brain volume.

Feasibility and usefulness of brain imaging in catatonia.

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 abnormalities (n = 44), followed by brain atrophy (n = 27). There was no evidence for significant differences in the frequency of abnormalities found in radiology reports and standardised neuroradiological assessments. The frequency of abnormalities was similar to that found in a population of non-healthy controls subjects with headache. This study shows that MRI is feasible in patients with catatonia and that brain imaging abnormalities are common findings in these patients. Most frequently, white matter abnormalities and diffuse brain atrophy are observed.

Comparing the test-retest reliability of resting-state functional magnetic resonance imaging metrics across single band and multiband acquisitions in the context of healthy aging.

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 different MB acquisitions, with and without in-plane acceleration, across three sessions. In this study, 24 healthy older adults were scanned over three visits, on weeks 0, 1, and 4, and, on each occasion, underwent a conventional single band rs-fMRI scan and three different rs-fMRI scans with MB factors 4 and 6, with and without in-plane acceleration. Across all three rs-fMRI metrics, the reliability scores were highest with MB factor 4 with no in-plane acceleration for cortical areas and with conventional single band for subcortical areas. Recommendations for future research studies are discussed.

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

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.

Oxytocin normalizes the implicit processing of fearful faces in psychopathy: a randomized crossover study using fMRI.

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 ASPD - P. Oxytocin abolished these group differences. This represents evidence of neurochemical modulation of the empathic processing of others' distress in psychopathy.

Test-retest reliability of time-varying patterns of brain activity across single band and multiband resting-state functional magnetic resonance imaging in healthy older adults.

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, 24 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 MB 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.

The influence of stimulus onset asynchrony, task order, sex and hormonal contraception on prepulse inhibition and prepulse facilitation: Methodological considerations for drug and imaging research.

BACKGROUND: Prepulse-induced startle modulation occurs when a weak sensory stimulus ('prepulse') is presented before a startling sensory stimulus ('pulse'), producing an inhibited (Prepulse Inhibition, PPI) or facilitated (Prepulse Facilitation, PPF) startle response. We recently identified several gaps and outlined future lines of enquiry to enable a fuller understanding of the neurobiology of PPI and PPF in healthy and clinical populations. However, before embarking on these studies, it is important to consider how task and population characteristics affect these phenomena in healthy humans. METHODS: We examined PPI and PPF in separate tasks, with counterbalanced task order across participants in one session, using a range of stimulus onset asynchronies (SOAs), in 48 healthy adults (23 men, 25 women; 10 hormonal contraceptive users) to determine which SOAs produce the strongest PPI and PPF and also explored how sex and hormonal contraception might influence PPI and PPF under these experimental conditions. RESULTS: Both PPI and PPF were affected by SOA, with greatest PPI observed at 60 and 120 ms, and greatest PPF at 4500 and 6000 ms. PPI was influenced by sex (more PPI in men than women) and hormonal contraception, whereas PPF was affected by task order (greater PPF when the PPF task followed, rather than preceded, the PPI task). CONCLUSIONS: Our findings indicate that studies of PPI and PPF need to consider, not only sex and hormonal status of study participants, but also task characteristics and presentation order to reduce variance and increase replicability across studies.

Reliability of multi-site UK Biobank MRI brain phenotypes for the assessment of neuropsychiatric complications of SARS-CoV-2 infection: The COVID-CNS travelling heads study.

INTRODUCTION: Magnetic resonance imaging (MRI) of the brain could be a key diagnostic and research tool for understanding the neuropsychiatric complications of COVID-19. For maximum impact, multi-modal MRI protocols will be needed to measure the effects of SARS-CoV-2 infection on the brain by diverse potentially pathogenic mechanisms, and with high reliability across multiple sites and scanner manufacturers. Here we describe the development of such a protocol, based upon the UK Biobank, and its validation with a travelling heads study. A multi-modal brain MRI protocol comprising sequences for T1-weighted MRI, T2-FLAIR, diffusion MRI (dMRI), resting-state functional MRI (fMRI), susceptibility-weighted imaging (swMRI), and arterial spin labelling (ASL), was defined in close approximation to prior UK Biobank (UKB) and C-MORE protocols for Siemens 3T systems. We iteratively defined a comparable set of sequences for General Electric (GE) 3T systems. To assess multi-site feasibility and between-site variability of this protocol, N = 8 healthy participants were each scanned at 4 UK sites: 3 using Siemens PRISMA scanners (Cambridge, Liverpool, Oxford) and 1 using a GE scanner (King's College London). Over 2,000 Imaging Derived Phenotypes (IDPs), measuring both data quality and regional image properties of interest, were automatically estimated by customised UKB image processing pipelines (S2 File). Components of variance and intra-class correlations (ICCs) were estimated for each IDP by linear mixed effects models and benchmarked by comparison to repeated measurements of the same IDPs from UKB participants. Intra-class correlations for many IDPs indicated good-to-excellent between-site reliability. Considering only data from the Siemens sites, between-site reliability generally matched the high levels of test-retest reliability of the same IDPs estimated in repeated, within-site, within-subject scans from UK Biobank. Inclusion of the GE site resulted in good-to-excellent reliability for many IDPs, although there were significant between-site differences in mean and scaling, and reduced ICCs, for some classes of IDP, especially T1 contrast and some dMRI-derived measures. We also identified high reliability of quantitative susceptibility mapping (QSM) IDPs derived from swMRI images, multi-network ICA-based IDPs from resting-state fMRI, and olfactory bulb structure IDPs from T1, T2-FLAIR and dMRI data. CONCLUSION: These results give confidence that large, multi-site MRI datasets can be collected reliably at different sites across the diverse range of MRI modalities and IDPs that could be mechanistically informative in COVID brain research. We discuss limitations of the study and strategies for further harmonisation of data collected from sites using scanners supplied by different manufacturers. These acquisition and analysis protocols are now in use for MRI assessments of post-COVID patients (N = 700) as part of the ongoing COVID-CNS study.

Neurotransmitter receptor densities are associated with changes in regional Cerebral blood flow during clinical ongoing pain.

Arterial spin labelling (ASL) plays an increasingly important role in neuroimaging pain research but does not provide molecular insights regarding how regional cerebral blood flow (rCBF) relates to underlying neurotransmission. Here, we integrate ASL with positron emission tomography (PET) and brain transcriptome data to investigate the molecular substrates of rCBF underlying clinically relevant pain states. Two data sets, representing acute and chronic ongoing pain respectively, were utilised to quantify changes in rCBF; one examining pre-surgical versus post-surgical pain, and the second comparing patients with painful hand Osteoarthritis to a group of matched controls. We implemented a whole-brain spatial correlation analysis to explore associations between change in rCBF (ΔCBF) and neurotransmitter receptor distributions derived from normative PET templates. Additionally, we utilised transcriptomic data from the Allen Brain Atlas to inform distributions of receptor expression. Both datasets presented significant correlations of ΔCBF with the µ-opioid and dopamine-D2 receptor expressions, which play fundamental roles in brain activity associated with pain experiences. ΔCBF also correlated with the gene expression distributions of several receptors involved in pain processing. Overall, this is the first study illustrating the molecular basis of ongoing pain ASL indices and emphasises the potential of rCBF as a biomarker in pain research.

Simultaneous high-resolution T2 -weighted imaging and quantitative T2 mapping at low magnetic field strengths using a multiple TE and multi-orientation acquisition approach.

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 T2 -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 T2 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 mm3 T2 -weighted and quantitative T2 maps acquired using a clinically feasible approach that combines three acquisition that require approximately 4-min each to collect. Calculated T2 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 T2 values at 150 mT, 1.5T, and 3T. CONCLUSION: Our multi-orientation and multi-TE approach is a time-efficient method for high-resolution T2 -weighted images for anatomical visualization with simultaneous quantitative T2 imaging for increased sensitivity to tissue microstructure and chemical composition.

The effect of learning to drum on behavior and brain function in autistic adolescents.

This current study aimed to investigate the impact of drum training on behavior and brain function in autistic adolescents with no prior drumming experience. Thirty-six autistic adolescents were recruited and randomly assigned to one of two groups. The drum group received individual drum tuition (two lessons per week over an 8-wk period), while the control group did not. All participants attended a testing session before and after the 8-wk period. Each session included a drumming assessment, an MRI scan, and a parent completing questionnaires relating to the participants' behavioral difficulties. Results showed that improvements in drumming performance were associated with a significant reduction in hyperactivity and inattention difficulties in drummers compared to controls. The fMRI results demonstrated increased functional connectivity in brain areas responsible for inhibitory control, action outcomes monitoring, and self-regulation. In particular, seed-to-voxel analyses revealed an increased functional connectivity in the right inferior frontal gyrus and the right dorsolateral prefrontal cortex. A multivariate pattern analysis demonstrated significant changes in the medial frontal cortex, the left and right paracingulate cortex, the subcallosal cortex, the left frontal pole, the caudate, and the left nucleus accumbens. In conclusion, this study investigates the impact of a drum-based intervention on neural and behavioral outcomes in autistic adolescents. We hope that these findings will inform further research and trials into the potential use of drum-based interventions in benefitting clinical populations with inhibition-related disorders and emotional and behavioral difficulties.