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The human cerebral cortex shows hemispheric asymmetry, yet the microstructural basis of this asymmetry remains incompletely understood. Here, we probe layer-specific microstructural asymmetry using one post-mortem male brain. Overall, anterior and posterior regions show leftward and rightward asymmetry respectively, but this pattern varies across cortical layers. A similar anterior-posterior pattern is observed using in vivo Human Connectome Project (N = 1101) T1w/T2w microstructural data, with average cortical asymmetry showing the strongest similarity with post-mortem-based asymmetry of layer III. Moreover, microstructural asymmetry is found to be heritable, varies as a function of age and sex, and corresponds to intrinsic functional asymmetry. We also observe a differential association of language and markers of mental health with microstructural asymmetry patterns at the individual level, illustrating a functional divergence between inferior-superior and anterior-posterior microstructural axes, possibly anchored in development. Last, we could show concordant evidence with alternative in vivo microstructural measures: magnetization transfer (N = 286) and quantitative T1 (N = 50). Together, our study highlights microstructural asymmetry in the human cortex and its functional and behavioral relevance., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Declarative memory encompasses episodic and semantic divisions. Episodic memory captures singular events with specific spatiotemporal relationships, whereas semantic memory houses context-independent knowledge. Behavioural and functional neuroimaging studies have revealed common and distinct neural substrates of both memory systems, implicating mesiotemporal lobe (MTL) regions such as the hippocampus and distributed neocortices. Here, we explored declarative memory system reorganization in patients with unilateral temporal lobe epilepsy (TLE) as a human disease model to test the impact of variable degrees of MTL pathology on memory function. Our cohort included 31 patients with TLE and 60 age- and sex-matched healthy controls, and all participants underwent episodic and semantic retrieval tasks during a multimodal MRI session. The functional MRI tasks were closely matched in terms of stimuli and trial design. Capitalizing on non-linear connectome gradient-mapping techniques, we derived task-based functional topographies during episodic and semantic memory states, in both the MTL and neocortical networks. Comparing neocortical and hippocampal functional gradients between TLE patients and healthy controls, we observed a marked topographic reorganization of both neocortical and MTL systems during episodic memory states. Neocortical alterations were characterized by reduced functional differentiation in TLE across lateral temporal and midline parietal cortices in both hemispheres. In the MTL, in contrast, patients presented with a more marked functional differentiation of posterior and anterior hippocampal segments ipsilateral to the seizure focus and pathological core, indicating perturbed intrahippocampal connectivity. Semantic memory reorganization was also found in bilateral lateral temporal and ipsilateral angular regions, whereas hippocampal functional topographies were unaffected. Furthermore, leveraging MRI proxies of MTL pathology, we observed alterations in hippocampal microstructure and morphology that were associated with TLE-related functional reorganization during episodic memory. Moreover, correlation analysis and statistical mediation models revealed that these functional alterations contributed to behavioural deficits in episodic memory, but again not in semantic memory in patients. Altogether, our findings suggest that semantic processes rely on distributed neocortical networks, whereas episodic processes are supported by a network involving both the hippocampus and the neocortex. Alterations of such networks can provide a compact signature of state-dependent reorganization in conditions associated with MTL damage, such as TLE., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Multimodal neuroimaging grants a powerful in vivo window into the structure and function of the human brain. Recent methodological and conceptual advances have enabled investigations of the interplay between large-scale spatial trends - or gradients - in brain structure and function, offering a framework to unify principles of brain organization across multiple scales. Strong community enthusiasm for these techniques has been instrumental in their widespread adoption and implementation to answer key questions in neuroscience. Following a brief review of current literature on this framework, this perspective paper will highlight how pragmatic steps aiming to make gradient methods more accessible to the community propelled these techniques to the forefront of neuroscientific inquiry. More specifically, we will emphasize how interest for gradient methods was catalyzed by data sharing, open-source software development, as well as the organization of dedicated workshops led by a diverse team of early career researchers. To this end, we argue that the growing excitement for brain gradients is the result of coordinated and consistent efforts to build an inclusive community and can serve as a case in point for future innovations and conceptual advances in neuroinformatics. We close this perspective paper by discussing challenges for the continuous refinement of neuroscientific theory, methodological innovation, and real-world translation to maintain our collective progress towards integrated models of brain organization., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Drug-resistant temporal lobe epilepsy (TLE) has been associated with hippocampal pathology. Most surgical treatment strategies, including resection and responsive neurostimulation (RNS), focus on this disease epicenter; however, imaging alterations distant from the hippocampus, as well as emerging data from responsive neurostimulation trials, suggest conceptualizing TLE as a network disorder., Objective: To assess whether brain networks connected to areas of atrophy in the hippocampus align with the topography of distant neuroimaging alterations and RNS response., Design, Setting, and Participants: This retrospective case-control study was conducted between July 2009 and June 2022. Data collection for this multicenter, population-based study took place across 4 tertiary referral centers in Montréal, Canada; Querétaro, México; Nanjing, China; and Salt Lake City, Utah. Eligible patients were diagnosed with TLE according to International League Against Epilepsy criteria and received either neuroimaging or neuroimaging and RNS to the hippocampus. Patients with encephalitis, traumatic brain injury, or bilateral TLE were excluded., Main Outcomes and Measures: Spatial alignment between brain network topographies., Results: Of the 110 eligible patients, 94 individuals diagnosed with TLE were analyzed (51 [54%] female; mean [SD] age, 31.3 [10.9] years). Hippocampal thickness maps in TLE were compared to 120 healthy control individuals (66 [55%] female; mean [SD] age, 29.8 [9.5] years), and areas of atrophy were identified. Using an atlas of normative connectivity (n = 1000), 2 brain networks were identified that were functionally connected to areas of hippocampal atrophy. The first network was defined by positive correlations to temporolimbic, medial prefrontal, and parietal regions, whereas the second network by negative correlations to frontoparietal regions. White matter changes colocalized to the positive network (t93 = -3.82; P = 2.44 × 10-4). In contrast, cortical atrophy localized to the negative network (t93 = 3.54; P = 6.29 × 10-3). In an additional 38 patients (20 [53%] female; mean [SD] age, 35.8 [11.3] years) treated with RNS, connectivity between the stimulation site and atrophied regions within the negative network was associated with seizure reduction (t212 = -2.74; P = .007)., Conclusions and Relevance: The findings in this study indicate that distributed pathology in TLE may occur in brain networks connected to the hippocampal epicenter. Connectivity to these same networks was associated with improvement following RNS. A network approach to TLE may reveal therapeutic targets outside the traditional target in the hippocampus.

Complex structural and functional changes occurring in typical and atypical development necessitate multidimensional approaches to better understand the risk of developing psychopathology. Here, we simultaneously examined structural and functional brain network patterns in relation to dimensions of psychopathology in the Adolescent Brain Cognitive Development dataset. Several components were identified, recapitulating the psychopathology hierarchy, with the general psychopathology ( p ) factor explaining most covariance with multimodal imaging features, while the internalizing, externalizing, and neurodevelopmental dimensions were each associated with distinct morphological and functional connectivity signatures. Connectivity signatures associated with the p factor and neurodevelopmental dimensions followed the sensory-to-transmodal axis of cortical organization, which is related to the emergence of complex cognition and risk for psychopathology. Results were consistent in two separate data subsamples, supporting generalizability, and robust to variations in analytical parameters. Our findings help in better understanding biological mechanisms underpinning dimensions of psychopathology, and could provide brain-based vulnerability markers., Competing Interests: Declarations of interest: None

Well-documented sleep datasets from healthy adults are important for sleep pattern analysis and comparison with a wide range of neuropsychiatric disorders. Currently, available sleep datasets from healthy adults are acquired using low-density arrays with a minimum of four electrodes in a typical sleep montage. The low spatial resolution is thus prohibitive for the analysis of the spatial structure of sleep. Here we introduce an open-access sleep dataset from 29 healthy adults (13 female, aged 32.17 ± 6.30 years) acquired at the Montreal Neurological Institute. The dataset includes overnight polysomnograms with high-density scalp electroencephalograms incorporating 83 electrodes, electrocardiogram, electromyogram, electrooculogram, and an average of electrode positions using manual co-registrations and sleep scoring annotations. Data characteristics and group-level analysis of sleep properties were assessed. The database can be accessed through ( https://doi.org/10.17605/OSF.IO/R26FH ). This is the first high-density electroencephalogram open sleep database from healthy adults, allowing researchers to investigate sleep physiology at high spatial resolution. We expect that this database will serve as a valuable resource for studying sleep physiology and for benchmarking sleep pathology., (© 2024. The Author(s).)

Background: In clinical practice, challenges in identifying patients with uncomplicated urinary tract infections (uUTIs) at risk of antibiotic nonsusceptibility may lead to inappropriate prescribing and contribute to antibiotic resistance. We developed predictive models to quantify risk of nonsusceptibility to 4 commonly prescribed antibiotic classes for uUTI, identify predictors of nonsusceptibility to each class, and construct a corresponding risk categorization framework for nonsusceptibility., Methods: Eligible females aged ≥12 years with Escherichia coli-caused uUTI were identified from Optum's de-identified Electronic Health Record dataset (1 October 2015-29 February 2020). Four predictive models were developed to predict nonsusceptibility to each antibiotic class and a risk categorization framework was developed to classify patients' isolates as low, moderate, and high risk of nonsusceptibility to each antibiotic class., Results: Predictive models were developed among 87 487 patients. Key predictors of having a nonsusceptible isolate to ≥3 antibiotic classes included number of previous UTI episodes, prior β-lactam nonsusceptibility, prior fluoroquinolone treatment, Census Bureau region, and race. The risk categorization framework classified 8.1%, 14.4%, 17.4%, and 6.3% of patients as having isolates at high risk of nonsusceptibility to nitrofurantoin, trimethoprim-sulfamethoxazole, β-lactams, and fluoroquinolones, respectively. Across classes, the proportion of patients categorized as having high-risk isolates was 3- to 12-fold higher among patients with nonsusceptible isolates versus susceptible isolates., Conclusions: Our predictive models highlight factors that increase risk of nonsusceptibility to antibiotics for uUTIs, while the risk categorization framework contextualizes risk of nonsusceptibility to these treatments. Our findings provide valuable insight to clinicians treating uUTIs and may help inform empiric prescribing in this population., Competing Interests: Potential conflicts of interest. R. K. S. is a paid consultant to GSK. W. Y. C., K. K.-S., D. I., F. K., C. G., M. M., L. P., and J. R. are employees of Analysis Group, Inc., a consultancy that received funding from GSK to conduct this study. A. V. J., F. S. M.-G., P. S., D. F., M. T. P., and J. H. are employees of and shareholders in GSK. R. C. has served as a paid consultant to GSK. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background and Objectives: Neuroimaging studies in patients with temporal lobe epilepsy (TLE) show widespread brain network alterations beyond the mesiotemporal lobe. Despite the critical role of the cerebrovascular system in maintaining whole-brain structure and function, changes in cerebral blood flow (CBF) remain incompletely understood in the disease. Here, we studied whole-brain perfusion and vascular network alterations in TLE and assessed its associations with gray and white matter compromises and various clinical variables., Methods: We included individuals with and without pharmaco-resistant TLE who underwent multimodal 3T MRI, including arterial spin labelling, structural, and diffusion-weighted imaging. Using surface-based MRI mapping, we generated individualized cortico-subcortical profiles of perfusion, morphology, and microstructure. Linear models compared regional CBF in patients with controls and related alterations to morphological and microstructural metrics. We further probed interregional vascular networks in TLE, using graph theoretical CBF covariance analysis. The effects of disease duration were explored to better understand the progressive changes in perfusion. We assessed the utility of perfusion in separating patients with TLE from controls using supervised machine learning., Results: Compared with control participants (n = 38; mean ± SD age 34.8 ± 9.3 years; 20 females), patients with TLE (n = 24; mean ± SD age 35.8 ± 10.6 years; 12 females) showed widespread CBF reductions predominantly in fronto-temporal regions (Cohen d -0.69, 95% CI -1.21 to -0.16), consistent in a subgroup of patients who remained seizure-free after surgical resection of the seizure focus. Parallel structural profiling and network-based models showed that cerebral hypoperfusion may be partially constrained by gray and white matter changes (8.11% reduction in Cohen d ) and topologically segregated from whole-brain perfusion networks (area under the curve -0.17, p < 0.05). Negative effects of progressive disease duration further targeted regional CBF profiles in patients ( r = -0.54, 95% CI -0.77 to -0.16). Perfusion-derived classifiers discriminated patients from controls with high accuracy (71% [70%-82%]). Findings were robust when controlling for several methodological confounds., Discussion: Our multimodal findings provide insights into vascular contributions to TLE pathophysiology affecting and extending beyond mesiotemporal structures and highlight their clinical potential in epilepsy diagnosis. As our work was cross-sectional and based on a single site, it motivates future longitudinal studies to confirm progressive effects, ideally in a multicentric setting.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Network neuroscience offers a unique framework to understand the organizational principles of the human brain. Despite recent progress, our understanding of how the brain is modulated by focal lesions remains incomplete. Resection of the temporal lobe is the most effective treatment to control seizures in pharmaco-resistant temporal lobe epilepsy (TLE), making this syndrome a powerful model to study lesional effects on network organization in young and middle-aged adults. Here, we assessed the downstream consequences of a focal lesion and its surgical resection on the brain's structural connectome, and explored how this reorganization relates to clinical variables at the individual patient level. We included adults with pharmaco-resistant TLE (n = 37) who underwent anterior temporal lobectomy between two imaging time points, as well as age- and sex-matched healthy controls who underwent comparable imaging (n = 31). Core to our analysis was the projection of high-dimensional structural connectome data-derived from diffusion MRI tractography from each subject-into lower-dimensional gradients. We then compared connectome gradients in patients relative to controls before surgery, tracked surgically-induced connectome reconfiguration from pre- to postoperative time points, and examined associations to patient-specific clinical and imaging phenotypes. Before surgery, individuals with TLE presented with marked connectome changes in bilateral temporo-parietal regions, reflecting an increased segregation of the ipsilateral anterior temporal lobe from the rest of the brain. Surgery-induced connectome reorganization was localized to this temporo-parietal subnetwork, but primarily involved postoperative integration of contralateral regions with the rest of the brain. Using a partial least-squares analysis, we uncovered a latent clinical imaging signature underlying this pre- to postoperative connectome reorganization, showing that patients who displayed postoperative integration in bilateral fronto-occipital cortices also had greater preoperative ipsilateral hippocampal atrophy, lower seizure frequency and secondarily generalized seizures. Our results bridge the effects of focal brain lesions and their surgical resections with large-scale network reorganization and interindividual clinical variability, thus offering new avenues to examine the fundamental malleability of the human brain., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

How drainage of septic arthritis should be performed remains controversial. The aim of the present study was to compare arthrocentesis (Ac) using double intra-articular needle lavage to arthrotomy (At) as first-line drainage treatment for pediatric hip and knee septic arthritis. The secondary objective was to identify risk factors of second articular drainage. A retrospective review of medical records of children with knee and hip septic arthritis was conducted. Inclusion criteria were: children treated for septic arthritis between 2014 and 2020 with a positive culture of joint fluid. Clinical, biological, radiographical and ultrasound data were recorded at presentation and during follow-up. Patients were divided into 2 groups according to the type of drainage performed: Ac or At. 25 hips and 44 knees were included, 42 treated by Ac (15 hips, 27 knees) and 27 by At (10 hips, 17 knees). There is no significant difference between Ac and At regarding the need for repeated drainage and Ac nor At was reported as risk factor for repeated drainage. The presence of associated musculoskeletal infection (MSI) was a significant risk factor of repeated drainage [odds ratio = 11.8; 95% confidence interval = 1.2-114.2; P  < 0.001]. Significantly more associated MSI ( P  < 0.001), level I virulence germs ( P  < 0.001) and positive blood culture (<0.001) were found in patients who underwent repeated drainage. There was no significant difference between Ac and At regarding rate of repeated drainage. The risk factors for repeated drainage were: associated with MSI, virulent germs and positive blood culture., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Temporal lobe epilepsy (TLE) is typically associated with pathology of the hippocampus, a key structure involved in relational memory, including episodic, semantic, and spatial memory processes. While it is widely accepted that TLE-associated hippocampal alterations underlie memory deficits, it remains unclear whether impairments relate to a specific cognitive domain or multiple ones., Methods: We administered a recently validated task paradigm to evaluate episodic, semantic, and spatial memory in 24 pharmacoresistant TLE patients and 50 age- and sex-matched healthy controls. We carried out two-way analyses of variance to identify memory deficits in individuals with TLE relative to controls across different relational memory domains, and used partial least squares correlation to identify factors contributing to variations in relational memory performance across both cohorts., Results: Compared to controls, TLE patients showed marked impairments in episodic and spatial memory, with mixed findings in semantic memory. Even when additionally controlling for age, sex, and overall cognitive function, between-group differences persisted along episodic and spatial domains. Moreover, age, diagnostic group, and hippocampal volume were all associated with relational memory behavioral phenotypes., Significance: Our behavioral findings show graded deficits across relational memory domains in people with TLE, which provides further insights into the complex pattern of cognitive impairment in the condition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Psoriasis is a major global health burden affecting ~ 60 million people worldwide. Existing studies on psoriasis focused on individual-level health behaviors (e.g. diet, alcohol consumption, smoking, exercise) and characteristics as drivers of psoriasis risk. However, it is increasingly recognized that health behavior arises in the context of larger social, cultural, economic and environmental determinants of health. We aimed to identify the top risk factors that significantly impact the incidence of psoriasis at the neighborhood level using populational data from the province of Quebec (Canada) and advanced tree-based machine learning (ML) techniques., Methods: Adult psoriasis patients were identified using International Classification of Disease (ICD)-9/10 codes from Quebec (Canada) populational databases for years 1997-2015. Data on environmental and socioeconomic factors 1 year prior to psoriasis onset were obtained from the Canadian Urban Environment Health Consortium (CANUE) and Statistics Canada (StatCan) and were input as predictors into the gradient boosting ML. Model performance was evaluated using the area under the curve (AUC). Parsimonious models and partial dependence plots were determined to assess directionality of the relationship., Results: The incidence of psoriasis varied geographically from 1.6 to 325.6/100,000 person-years in Quebec. The parsimonious model (top 9 predictors) had an AUC of 0.77 to predict high psoriasis incidence. Amongst top predictors, ultraviolet (UV) radiation, maximum daily temperature, proportion of females, soil moisture, urbanization, and distance to expressways had a negative association with psoriasis incidence. Nighttime light brightness had a positive association, whereas social and material deprivation indices suggested a higher psoriasis incidence in the middle socioeconomic class neighborhoods., Conclusion: This is the first study to highlight highly variable psoriasis incidence rates on a jurisdictional level and suggests that living environment, notably climate, vegetation, urbanization and neighborhood socioeconomic characteristics may have an association with psoriasis incidence., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Temporal lobe epilepsy (TLE) is the most common pharmaco-resistant epilepsy in adults. While primarily associated with mesiotemporal pathology, recent evidence suggests that brain alterations in TLE extend beyond the paralimbic epicenter and impact macroscale function and cognitive functions, particularly memory. Using connectome-wide manifold learning and generative models of effective connectivity, we examined functional topography and directional signal flow patterns between large-scale neural circuits in TLE at rest. Studying a multisite cohort of 95 patients with TLE and 95 healthy controls, we observed atypical functional topographies in the former group, characterized by reduced differentiation between sensory and transmodal association cortices, with most marked effects in bilateral temporo-limbic and ventromedial prefrontal cortices. These findings were consistent across all study sites, present in left and right lateralized patients, and validated in a subgroup of patients with histopathological validation of mesiotemporal sclerosis and post-surgical seizure freedom. Moreover, they were replicated in an independent cohort of 30 TLE patients and 40 healthy controls. Further analyses demonstrated that reduced differentiation related to decreased functional signal flow into and out of temporolimbic cortical systems and other brain networks. Parallel analyses of structural and diffusion-weighted MRI data revealed that topographic alterations were independent of TLE-related cortical thinning but partially mediated by white matter microstructural changes that radiated away from paralimbic circuits. Finally, we found a strong association between the degree of functional alterations and behavioral markers of memory dysfunction. Our work illustrates the complex landscape of macroscale functional imbalances in TLE, which can serve as intermediate markers bridging microstructural changes and cognitive impairment., Competing Interests: Declaration of Competing Interest The authors report no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Data on non-fatal injuries and visits to the emergency department (ED) for injuries are not readily available. The objective of this paper is to describe injury-related ED visits for people with intellectual and developmental disabilities who are covered by the Medicaid insurance programme., Methods: We aggregated 2010-2016 Medicaid claims data from eight states. Using these data, we identified individuals with intellectual and developmental disabilities and then determined an all-cause ED visit rate, ED visit due to injury rate and admission from ED due to injury rate. Data were stratified by sex and age group. Results were compared with national rates., Results: Medicaid members with intellectual and developmental disabilities visited EDs at approximately 1.8 times the rate of the general population. The ED visit rate due to injury was approximately 1.5 times that observed in the population overall. When ED visits due to injury data were stratified by age and sex, the largest discrepancy was observed in women ages 45-64, who visited EDs due to injury at a rate 2.1 times that of women of the same age in the general population. The admission rate from ED due to injury increased over the study period most notably in the older age groups., Conclusions: While rates and patterns of ED utilisation among Medicaid members with intellectual and developmental disabilities vary by age and gender, our findings suggest this group visits the ED due to injury at rates well above the general population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

A central goal in neuroscience is the development of a comprehensive mapping between structural and functional brain features, which facilitates mechanistic interpretation of brain function. However, the interpretability of structure-function brain models remains limited by a lack of biological detail. Here, we characterize human structural brain networks weighted by multiple white matter microstructural features including total intra-axonal cross-sectional area and myelin content. We report edge-weight-dependent spatial distributions, variance, small-worldness, rich club, hubs, as well as relationships with function, edge length, and myelin. Contrasting networks weighted by the total intra-axonal cross-sectional area and myelin content of white matter tracts, we find opposite relationships with functional connectivity, an edge-length-independent inverse relationship with each other, and the lack of a canonical rich club in myelin-weighted networks. When controlling for edge length, networks weighted by either fractional anisotropy, radial diffusivity, or neurite density show no relationship with whole-brain functional connectivity. We conclude that the co-utilization of structural networks weighted by total intra-axonal cross-sectional area and myelin content could improve our understanding of the mechanisms mediating the structure-function brain relationship., Competing Interests: Competing Interests: The authors have declared that no competing interests exist., (© 2023 Massachusetts Institute of Technology.)

Objective: High-density (HD) electroencephalography (EEG) is increasingly used in presurgical epilepsy evaluation, but it is demanding in time and resources. To overcome these issues, we compared EEG source imaging (ESI) solutions with a targeted density and HD-EEG montage., Methods: HD-EEGs from patients undergoing presurgical evaluation were analyzed. A low-density recording was created by selecting the 25 electrodes of a standard montage from the 83 electrodes of the HD-EEG and adding 8-11 electrodes around the electrode with the highest amplitude interictal epileptiform discharges. The ESI solution from this "targeted" montage was compared to that from the HD-EEG using the distance between peak vertices, sublobar concordance and a qualitative similarity measure., Results: Fifty-eight foci of forty-three patients were included. The median distance between the peak vertices of the two montages was 13.2 mm, irrespective of focus' location. Tangential generators (n = 5/58) showed a higher distance than radial generators (p = 0.04). We found sublobar concordance in 54/58 of the foci (93%). Map similarity, assessed by an epileptologist, had a median score of 4/5., Conclusions: ESI solutions obtained from a targeted density montage show high concordance with those calculated from HD-EEG., Significance: Requiring significantly fewer electrodes, targeted density EEG allows obtaining similar ESI solutions as traditional HD-EEG montage., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Recent theories of cortical organisation suggest features of function emerge from the spatial arrangement of brain regions. For example, association cortex is located furthest from systems involved in action and perception. Association cortex is also 'interdigitated' with adjacent regions having different patterns of functional connectivity. It is assumed that topographic properties, such as distance between regions, constrains their functions, however, we lack a formal description of how this occurs. Here we use variograms, a quantification of spatial autocorrelation, to profile how function changes with the distance between cortical regions. We find function changes with distance more gradually within sensory-motor cortex than association cortex. Importantly, systems within the same type of cortex (e.g., fronto-parietal and default mode networks) have similar profiles. Primary and association cortex, therefore, are differentiated by how function changes over space, emphasising the value of topographical features of a region when estimating its contribution to cognition and behaviour., (© 2023. Springer Nature Limited.)

Introduction: Patients with spinal deformities undergoing corrective surgery are at risk for iatrogenic spinal cord injury (SCI) and subsequent neurological deficit. Intraoperative neurophysiological monitoring (IONM) allows early detection of SCI which enables early intervention resulting in a better prognosis. The primary aim of this literature review was to search if there are threshold values of TcMEP and SSEP in the literature that are widely accepted as alert during IONM. The secondary aim was to update knowledge concerning IONM during scoliosis surgery., Method: PubMed/MEDLINE and Cochrane library electronic databases were used to search publication from 2012 to 2022. The following keywords were used: evoked potential, scoliosis, surgery, intraoperative monitoring and neurophysiological. We included all studies dealing with SSEP and TcMEP monitoring during scoliosis surgery. Two authors reviewed all titles and abstracts to identify studies that met the inclusion criteria., Results: We included 43 papers. Rates of IONM alert and neurological deficit varied from 0.56 to 64% and from 0.15 to 8.3%, respectively. Threshold values varied from a loss of 50 to 90% for TcMEP amplitude, whereas it seems that a loss of 50% in amplitude and/or an increase of 10% of latency is widely accepted for SSEP. Causes of IONM changes most frequently reported were surgical maneuver., Conclusion: Concerning SSEP, a loss of 50% in amplitude and/or an increase of 10% of latency is widely accepted as an alert. For TcMEP, it seems that the use of highest threshold values can avoid unnecessary surgical procedure for the patient without increasing risk of neurological deficit., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Temporal lobe epilepsy (TLE), one of the most common pharmaco-resistant epilepsies, is associated with pathology of paralimbic brain regions, particularly in the mesiotemporal lobe. Cognitive dysfunction in TLE is frequent, and particularly affects episodic memory. Crucially, these difficulties challenge the quality of life of patients, sometimes more than seizures, underscoring the need to assess neural processes of cognitive dysfunction in TLE to improve patient management. Our work harnessed a novel conceptual and analytical approach to assess spatial gradients of microstructural differentiation between cortical areas based on high-resolution MRI analysis. Gradients track region-to-region variations in intracortical lamination and myeloarchitecture, serving as a system-level measure of structural and functional reorganization. Comparing cortex-wide microstructural gradients between 21 patients and 35 healthy controls, we observed a reorganization of this gradient in TLE driven by reduced microstructural differentiation between paralimbic cortices and the remaining cortex with marked abnormalities in ipsilateral temporopolar and dorsolateral prefrontal regions. Findings were replicated in an independent cohort. Using an independent post-mortem dataset, we observed that in vivo findings reflected topographical variations in cortical cytoarchitecture. We indeed found that macroscale changes in microstructural differentiation in TLE reflected increased similarity of paralimbic and primary sensory/motor regions. Disease-related transcriptomics could furthermore show specificity of our findings to TLE over other common epilepsy syndromes. Finally, microstructural dedifferentiation was associated with cognitive network reorganization seen during an episodic memory functional MRI paradigm and correlated with interindividual differences in task accuracy. Collectively, our findings showing a pattern of reduced microarchitectural differentiation between paralimbic regions and the remaining cortex provide a structurally-grounded explanation for large-scale functional network reorganization and cognitive dysfunction characteristic of TLE., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Human behavior is supported by both goal-directed (model-based) and habitual (model-free) decision-making, each differing in its flexibility, accuracy, and computational cost. The arbitration between habitual and goal-directed systems is thought to be regulated by a process known as metacontrol. However, how these systems emerge and develop remains poorly understood. Recently, we found that while children between 5 and 11 years displayed robust signatures of model-based decision-making, which increased during this developmental period, there were substantial individual differences in the display of metacontrol. Here, we inspect the neurocognitive basis of model-based decision-making and metacontrol in childhood and focus this investigation on executive functions, fluid reasoning, and brain structure. A total of 69 participants between the ages of 6-13 completed a two-step decision-making task and an extensive behavioral test battery. A subset of 44 participants also completed a structural magnetic resonance imaging scan. We find that individual differences in metacontrol are specifically associated with performance on an inhibition task and individual differences in thickness of dorsolateral prefrontal, temporal, and superior-parietal cortices. These brain regions likely reflect the involvement of cognitive processes crucial to metacontrol, such as cognitive control and contextual processing., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Co-author Nikolaus Steinbeis is an editor for the FLUX special issue at Developmental Cognitive Neuroscience.., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Fish moving between different thermal environments experience heat exchange via conduction through the body wall and convection from blood flow across the gills. We report a strategy of preventing convective heat loss at the gills during excursions into deep, cold water by the tropical scalloped hammerhead shark ( Sphryna lewini ). Adult scalloped hammerhead sharks dive rapidly and repeatedly from warm (~26°C) surface waters to depths exceeding 800 meters with temperatures as low as 5°C. Biologgers attached to adult sharks show that warm muscle temperatures were maintained throughout the deepest portion of each dive. Substantive cooling only occurred during the latter stages of the ascent phase and, once initiated, was rapid. Heat transfer coefficient modeling indicated that convective heat transfer was suspended, probably by suppressing gill function during deep dives. This previously unobserved strategy has broad similarities to marine mammal "breath hold" diving.

Objective: Temporal lobe epilepsy (TLE) is the most common pharmacoresistant epilepsy in adults. Here we profiled local neural function in TLE in vivo, building on prior evidence that has identified widespread structural alterations. Using resting-state functional magnetic resonance imaging (rs-fMRI), we mapped the whole-brain intrinsic neural timescales (INT), which reflect temporal hierarchies of neural processing. Parallel analysis of structural and diffusion MRI data examined associations with TLE-related structural compromise. Finally, we evaluated the clinical utility of INT., Methods: We studied 46 patients with TLE and 44 healthy controls from two independent sites, and mapped INT changes in patients relative to controls across hippocampal, subcortical, and neocortical regions. We examined region-specific associations to structural alterations and explored the effects of age and epilepsy duration. Supervised machine learning assessed the utility of INT for identifying patients with TLE vs controls and left- vs right-sided seizure onset., Results: Relative to controls, TLE showed marked INT reductions across multiple regions bilaterally, indexing faster changing resting activity, with strongest effects in the ipsilateral medial and lateral temporal regions, and bilateral sensorimotor cortices as well as thalamus and hippocampus. Findings were similar, albeit with reduced effect sizes, when correcting for structural alterations. INT reductions in TLE increased with advancing disease duration, yet findings differed from the aging effects seen in controls. INT-derived classifiers discriminated patients vs controls (balanced accuracy, 5-fold: 76% ± 2.65%; cross-site, 72%-83%) and lateralized the focus in TLE (balanced accuracy, 5-fold: 96% ± 2.10%; cross-site, 95%-97%), with high accuracy and cross-site generalizability. Findings were consistent across both acquisition sites and robust when controlling for motion and several methodological confounds., Significance: Our findings demonstrate atypical macroscale function in TLE in a topography that extends beyond mesiotemporal epicenters. INT measurements can assist in TLE diagnosis, seizure focus lateralization, and monitoring of disease progression, which emphasizes promising clinical utility., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Higher-order cognition is hypothesized to be implemented via distributed cortical networks that are linked via long-range connections. However, it is unknown how computational advantages of long-range connections reflect cortical microstructure and microcircuitry., Methods: We investigated this question by (i) profiling long-range cortical connectivity using resting-state functional magnetic resonance imaging (MRI) and cortico-cortical geodesic distance mapping, (ii) assessing how long-range connections reflect local brain microarchitecture, and (iii) examining the microarchitectural similarity of regions connected through long-range connections., Results: Analysis of 2 independent datasets indicated that sensory/motor areas had more clustered short-range connections, while transmodal association systems hosted distributed, long-range connections. Meta-analytical decoding suggested that this topographical difference mirrored shifts in cognitive function, from perception/action towards emotional/social processing. Analysis of myelin-sensitive in vivo MRI as well as postmortem histology and transcriptomics datasets established that gradients in functional connectivity distance are paralleled by those present in cortical microarchitecture. Notably, long-range connections were found to link spatially remote regions of association cortex with an unexpectedly similar microarchitecture., Conclusions: By mapping covarying topographies of long-range functional connections and cortical microcircuits, the current work provides insights into structure-function relations in human neocortex., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Stereo-electroencephalography (SEEG)-derived epilepsy networks are used to better understand a patient's epilepsy; however, a unimodal approach provides an incomplete picture. We combine tractography and SEEG to determine the relationship between spike propagation and the white matter architecture and to improve our understanding of spike propagation mechanisms., Methods: Probablistic tractography from diffusion imaging (dMRI) of matched subjects from the Human Connectome Project (HCP) was combined with patient-specific SEEG-derived spike propagation networks. Two regions-of-interest (ROIs) with a significant spike propagation relationship constituted a Propagation Pair., Results: In 56 of 59 patients, Propagation Pairs were more often tract-connected as compared to all ROI pairs (p < 0.01; d = -1.91). The degree of spike propagation between tract-connected ROIs was greater (39 ± 21%) compared to tract-unconnected ROIs (31 ± 18%; p < 0.0001). Within the same network, ROIs receiving propagation earlier were more often tract-connected to the source (59.7%) as compared to late receivers (25.4%; p < 0.0001)., Conclusions: Brain regions involved in spike propagation are more likely to be connected by white matter tracts. Between nodes, presence of tracts suggests a direct course of propagation, whereas the absence of tracts suggests an indirect course of propagation., Significance: We demonstrate a logical and consistent relationship between spike propagation and the white matter architecture., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

Introduction: Racial/ethnic differences in diagnostic and treatment services have been identified for a range of health conditions and outcomes. The current study aimed to analyze whether there are racial/ethnic differences in the timing of diagnostic testing and treatments for males with Duchenne muscular dystrophy (DMD)., Methods: Diagnostic and clinical data for male individuals with DMD born during 1990-2010 were analyzed from eight sites (Arizona, Colorado, Georgia, Iowa, Piedmont Region of North Carolina, Western New York, South Carolina, and Utah) of the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). Seven milestones related to diagnosis/treatment experiences were selected as outcomes. Times to each milestone were estimated and compared by four racial/ethnic groups using Kaplan-Meier estimation and Cox proportional-hazards models. Times between initial evaluation or diagnostic testing and later milestones were also compared by race/ethnicity., Results: We identified 682 males with definite or probable DMD of whom 61.7% were non-Hispanic white, 20.5% Hispanic, 10.6% other, and 7.2% non-Hispanic black. Seven milestone events were studied (initial evaluation, first neurology/neuromuscular visit, diagnosis, corticosteroid treatment first offered, corticosteroid treatment started, first electrocardiogram or echocardiogram, and first pulmonary function test). The first five milestone events occurred at an older age for non-Hispanic black individuals compared to non-Hispanic white individuals. Time to first offering of corticosteroids and initiation of corticosteroid therapy was later for Hispanic individuals compared to non-Hispanic white individuals. When accounting for timing of initial evaluation/diagnosis, offering of corticosteroids continued to occur later, but first pulmonary testing occurred earlier, among Hispanic individuals compared to non-Hispanic whites. No significant delays remained for non-Hispanic black individuals after accounting for later initial evaluation/diagnosis., Conclusion: We described racial/ethnic differences in ages at selected diagnostic and treatment milestones. The most notable differences were significant delays for five of seven milestones in non-Hispanic black individuals, which appeared to be attributable to later initial evaluation/diagnosis. Findings for Hispanic individuals were less consistent. Efforts to address barriers to early evaluation and diagnosis for non-Hispanic black children with DMD may promote more timely initiation of recommended disease monitoring and interventions., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Introduction: The time required to reach clinical remission varies in patients with chronic urticaria (CU). The objective of this study is to develop a predictive model using a machine learning methodology to predict time to clinical remission for patients with CU., Methods: Adults with ≥ 2 ICD-9/10 relevant CU diagnosis codes/CU-related treatment > 6 weeks apart were identified in the Optum deidentified electronic health record dataset (January 2007 to June 2019). Clinical remission was defined as ≥ 12 months without CU diagnosis/CU-related treatment. A random survival forest was used to predict time from diagnosis to clinical remission for each patient based on clinical and demographic features available at diagnosis. Model performance was assessed using concordance, which indicates the degree of agreement between observed and predicted time to remission. To characterize clinically relevant groups, features were summarized among cohorts that were defined based on quartiles of predicted time to remission., Results: Among 112,443 patients, 73.5% reached clinical remission, with a median of 336 days from diagnosis. From 1876 initial features, 176 were retained in the final model, which predicted a median of 318 days to remission. The model showed good performance with a concordance of 0.62. Patients with predicted longer time to remission tended to be older with delayed CU diagnosis, and have more comorbidities, more laboratory tests, higher body mass index, and polypharmacy during the 12-month period before the first CU diagnosis., Conclusions: Applying machine learning to real-world data enabled accurate prediction of time to clinical remission and identified multiple relevant demographic and clinical variables with predictive value. Ongoing work aims to further validate and integrate these findings into clinical applications for CU management., (© 2022. The Author(s).)

Multimodal magnetic resonance imaging (MRI) has accelerated human neuroscience by fostering the analysis of brain microstructure, geometry, function, and connectivity across multiple scales and in living brains. The richness and complexity of multimodal neuroimaging, however, demands processing methods to integrate information across modalities and to consolidate findings across different spatial scales. Here, we present micapipe, an open processing pipeline for multimodal MRI datasets. Based on BIDS-conform input data, micapipe can generate i) structural connectomes derived from diffusion tractography, ii) functional connectomes derived from resting-state signal correlations, iii) geodesic distance matrices that quantify cortico-cortical proximity, and iv) microstructural profile covariance matrices that assess inter-regional similarity in cortical myelin proxies. The above matrices can be automatically generated across established 18 cortical parcellations (100-1000 parcels), in addition to subcortical and cerebellar parcellations, allowing researchers to replicate findings easily across different spatial scales. Results are represented on three different surface spaces (native, conte69, fsaverage5), and outputs are BIDS-conform. Processed outputs can be quality controlled at the individual and group level. micapipe was tested on several datasets and is available at https://github.com/MICA-MNI/micapipe, documented at https://micapipe.readthedocs.io/, and containerized as a BIDS App http://bids-apps.neuroimaging.io/apps/. We hope that micapipe will foster robust and integrative studies of human brain microstructure, morphology, function, cand connectivity., (Copyright © 2022. Published by Elsevier Inc.)

Multimodal neuroimaging grants a powerful window into the structure and function of the human brain at multiple scales. Recent methodological and conceptual advances have enabled investigations of the interplay between large-scale spatial trends (also referred to as gradients) in brain microstructure and connectivity, offering an integrative framework to study multiscale brain organization. Here, we share a multimodal MRI dataset for Microstructure-Informed Connectomics (MICA-MICs) acquired in 50 healthy adults (23 women; 29.54 ± 5.62 years) who underwent high-resolution T1-weighted MRI, myelin-sensitive quantitative T1 relaxometry, diffusion-weighted MRI, and resting-state functional MRI at 3 Tesla. In addition to raw anonymized MRI data, this release includes brain-wide connectomes derived from (i) resting-state functional imaging, (ii) diffusion tractography, (iii) microstructure covariance analysis, and (iv) geodesic cortical distance, gathered across multiple parcellation scales. Alongside, we share large-scale gradients estimated from each modality and parcellation scale. Our dataset will facilitate future research examining the coupling between brain microstructure, connectivity, and function. MICA-MICs is available on the Canadian Open Neuroscience Platform data portal ( https://portal.conp.ca ) and the Open Science Framework ( https://osf.io/j532r/ )., (© 2022. The Author(s).)

Ongoing brain function is largely determined by the underlying wiring of the brain, but the specific rules governing this relationship remain unknown. Emerging literature has suggested that functional interactions between brain regions emerge from the structural connections through mono- as well as polysynaptic mechanisms. Here, we propose a novel approach based on diffusion maps and Riemannian optimization to emulate this dynamic mechanism in the form of random walks on the structural connectome and predict functional interactions as a weighted combination of these random walks. Our proposed approach was evaluated in two different cohorts of healthy adults (Human Connectome Project, HCP; Microstructure-Informed Connectomics, MICs). Our approach outperformed existing approaches and showed that performance plateaus approximately around the third random walk. At macroscale, we found that the largest number of walks was required in nodes of the default mode and frontoparietal networks, underscoring an increasing relevance of polysynaptic communication mechanisms in transmodal cortical networks compared to primary and unimodal systems., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier Inc.)

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes., (© 2022. The Author(s).)

Calcium signaling is crucial for many physiological processes and can mobilize intracellular calcium stores in response to environmental sensory stimuli. The endolysosomal two-pore channel (TPC), regulated by the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP), is one of the key components in calcium signaling. However, its role in neuronal physiology remains largely unknown. Here, we investigated to what extent the acoustic thresholds differed between the WT mice and the TPC KO mice. We determined the thresholds based on the auditory brainstem responses (ABRs) at five frequencies (between 4 and 32 kHz) and found no threshold difference between the WT and KO in virgin female mice. Surprisingly, in lactating mothers (at P9-P10), the thresholds were higher from 8 to 32 kHz in the TPC KO mice compared to the WT mice. This result indicates that in the TPC KO mice, physiological events occurring during parturition altered the detection of sounds already at the brainstem level, or even earlier.

The tribe Dacini (Diptera: Tephritidae) contains over 930 recognised species and has been widely studied due to the economic importance of some taxa, such as the Oriental fruit fly Bactrocera dorsalis. Despite the attention this group has received, very few phylogenetic reconstructions have comprehensively sampled taxa from a single biogeographic region, thereby limiting our capacity to address more targeted evolutionary questions. To study the evolution of diet breadth and male lure response, two key traits fundamental to understanding dacine diversity and the biology of pest taxa, we analysed 273 individuals representing 144 described species from Australia (80% continental coverage), the Pacific, and select close relatives from South-east Asia to estimate a dated molecular phylogenetic reconstruction of the Dacini. We utilised seven loci with a combined total of 4,332 nucleotides, to estimate both Bayesian and Maximum Likelihood phylogenies of the tribe. Consistent with other molecular phylogenies of the tribe, there was a high level of disagreement between the placement of species in the phylogeny and their current subgeneric and species-complex level taxonomies. The Australian fauna exhibit high levels of endemism, with radiations of both exclusively Australian clades, and clades that originate elsewhere (e.g. the Bactrocera dorsalis species group). Bidirectional movement of species has occurred between Papua New Guinea and Australia, with evidence for multiple incursions over evolutionary time. The Bactrocera aglaiae species group emerged sister to all other Bactrocera species examined. Divergence time estimates were ∼ 30 my younger than previously reported for this group, with the tribe diverging from its most recent common ancestor ∼ 43 mya. Ancestral trait reconstruction and tests for trait phylogenetic signal revealed a strong signal for the evolution of male lure response across the tree, with cue-lure/raspberry ketone lure response the ancestral trait. Methyl eugenol response has arisen on multiple, independent occasions. The evolution of host breadth exhibited a weaker signal; yet, basal groups were more likely to be host specialists. Both the evolution of lure response and host fruit use provide predictive information for the outbreak management of understudied pest fruit flies for which direct inference of these features may be lacking. Our results, which parallel those of earlier research into the closely-related African Dacus spp., demonstrate how geographically focussed taxon coverage allows Dacini phylogenetics to more explicitly test evolutionary hypotheses, thereby progressing our understanding of the evolution of this highly diverse and recently-radiated group of flies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In this population-based retrospective cohort study, increased influenza vaccination coverage was temporally associated with a reduction in ambulatory antibiotic use in children. After adjustment for yearly vaccine effectiveness, antibiotic prescription rate declined by 3/1000 person-months for each 1% increase in influenza vaccination coverage between 2012 and 2017 in South Carolina (P < 0.001)., Competing Interests: P.B.B. served as a research advisory board member of CutisPharma, Synthetic Biologics and on Advisory board and speaker’s bureau of Melinta Therapeutics. He also received a grant from ALK Abello, Inc. JJ served as an advisory board member of Merck & Co. and on the speaker’s bureau for bioMérieux. The remaining authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aimed to develop and validate a predictive algorithm for unsatisfactory response to initial pulmonary arterial hypertension (PAH) therapy using health insurance claims., Methods: Adult patients with PAH initiated on a first PAH therapy (index date) were identified from Optum's de-identified Clinformatics Data Mart Database (1/1/2010-12/31/2019). A random survival forest algorithm was developed using patient-month data and predicted the "survival function" (i.e. risk of not having unsatisfactory response) over time. For each patient-month observation, risk factors were assessed in the 12 months prior. Unsatisfactory response was defined as the first instance of (1) new PAH therapy, (2) PAH-related hospitalization or emergency room visit, (3) lung transplant or atrial septostomy, (4) PAH-related death or (5) chronic oxygen therapy initiation. To facilitate use in clinical practice, a simplified risk score was also developed based on a linear combination of the most important risk factors identified in the algorithm., Results: In total, 4781 patients were included (median age = 69.0 years; 58.6% female). Over a median follow-up of 14.0 months, 3169 (66.3%) had an unsatisfactory response. The most important risk factors included in the algorithm were healthcare resource use (i.e. PAH-related outpatient visits, pulmonologist visits, cardiologist visits, all-cause hospitalizations), time since first PAH diagnosis, time since index date, Charlson Comorbidity Index, dyspnea, and age. Predictive accuracy was good for the full algorithm (C-statistic: 0.732) but was slightly lower for the simplified risk score (C-statistic: 0.668)., Conclusion: The present claims-based algorithm performed well in predicting time to unsatisfactory response following initial PAH therapy.

Epilepsy is one of the most common chronic neurological conditions, traditionally defined as a disorder of recurrent seizures. Cognitive and affective dysfunction are increasingly recognized as core disease dimensions and can affect patient well-being, sometimes more than the seizures themselves. Connectome-based approaches hold immense promise for revealing mechanisms that contribute to dysfunction and to identify biomarkers. Our review discusses emerging multimodal neuroimaging and connectomics studies that highlight network substrates of cognitive/affective dysfunction in the common epilepsies. We first discuss work in drug-resistant epilepsy syndromes, that is, temporal lobe epilepsy, related to mesiotemporal sclerosis (TLE), and extratemporal epilepsy (ETE), related to malformations of cortical development. While these are traditionally conceptualized as 'focal' epilepsies, many patients present with broad structural and functional anomalies. Moreover, the extent of distributed changes contributes to difficulties in multiple cognitive domains as well as affective-behavioral challenges. We also review work in idiopathic generalized epilepsy (IGE), a subset of generalized epilepsy syndromes that involve subcortico-cortical circuits. Overall, neuroimaging and network neuroscience studies point to both shared and syndrome-specific connectome signatures of dysfunction across TLE, ETE, and IGE. Lastly, we point to current gaps in the literature and formulate recommendations for future research., (© 2022 Massachusetts Institute of Technology.)

Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Brain structure scaffolds intrinsic function, supporting cognition and ultimately behavioral flexibility. However, it remains unclear how a static, genetically controlled architecture supports flexible cognition and behavior. Here, we synthesize genetic, phylogenetic and cognitive analyses to understand how the macroscale organization of structure-function coupling across the cortex can inform its role in cognition. In humans, structure-function coupling was highest in regions of unimodal cortex and lowest in transmodal cortex, a pattern that was mirrored by a reduced alignment with heritable connectivity profiles. Structure-function uncoupling in macaques had a similar spatial distribution, but we observed an increased coupling between structure and function in association cortices relative to humans. Meta-analysis suggested regions with the least genetic control (low heritable correspondence and different across primates) are linked to social-cognition and autobiographical memory. Our findings suggest that genetic and evolutionary uncoupling of structure and function in different transmodal systems may support the emergence of complex forms of cognition., (© 2022. The Author(s).)

While reading, our mind can wander to unrelated autobiographical information, creating a perceptually decoupled state detrimental to narrative comprehension. To understand how this mind-wandering state emerges, we asked whether retrieving autobiographical content necessitates functional disengagement from visual input. In Experiment 1, brain activity was recorded using functional magnetic resonance imaging (fMRI) in an experimental situation mimicking naturally occurring mind-wandering, allowing us to precisely delineate neural regions involved in memory and reading. Individuals read expository texts and ignored personally relevant autobiographical memories, as well as the opposite situation. Medial regions of the default mode network (DMN) were recruited during memory retrieval. In contrast, left temporal and lateral prefrontal regions of the DMN, as well as ventral visual cortex, were recruited when reading for comprehension. Experiment two used functional connectivity both at rest and during tasks to establish that (i) DMN regions linked to memory are more functionally decoupled from regions of ventral visual cortex than regions in the same network engaged when reading; and (ii) individuals with more self-generated mental contents and poorer comprehension, while reading in the lab, showed more decoupling between visually connected DMN sites important for reading and primary visual cortex. A similar pattern of connectivity was found in Experiment 1, with greater coupling between this DMN site and visual cortex when participants reported greater focus on reading in the face of conflict from autobiographical memory cues; moreover, the retrieval of personally relevant memories increased the decoupling of these sites. These converging data suggest we lose track of the narrative when our minds wander because generating autobiographical mental content relies on cortical regions within the DMN which are functionally decoupled from ventral visual regions engaged during reading., Competing Interests: MZ, BB, XW, DV, KK, JR, RR, RV, DM, JS, EJ No competing interests declared, (© 2022, Zhang et al.)

Epilepsy is a disorder of brain networks. A better understanding of structural and dynamic network properties may improve epilepsy diagnosis, treatment, and prognostics. Hubs are brain regions with high connectivity to other parts of the brain and are typically situated along the brain's most efficient communication pathways, supporting large-scale brain wiring and many higher order neural functions. The visualization and analysis of hubs offers a perspective on regional and global network organization and can provide novel insights into brain disorders and epilepsy. By notably supporting the interaction between various brain networks, hubs may be implicated in seizure spread and in epilepsy-related phenotypes. In this review, we will discuss the growing literature on atypical hub organization in common epilepsy syndromes, both related to neuroimaging of brain structure and function, and related to neurophysiological data from magneto- and electroencephalographic measures of neural dynamics. With studies increasingly exploring the clinical utility of network neuroscience approaches, we highlight the potential of hub mapping as a candidate biomarker of cognitive dysfunction and postsurgical seizure outcome. We will conclude the review with a discussion of current limitations and outlook for future research., (© 2022 International League Against Epilepsy.)

The temporal lobe is implicated in higher cognitive processes and is one of the regions that underwent substantial reorganization during primate evolution. Its functions are instantiated, in part, by the complex layout of its structural connections. Here, we identified low-dimensional representations of structural connectivity variations in human temporal cortex and explored their microstructural underpinnings and associations to macroscale function. We identified three eigenmodes which described gradients in structural connectivity. These gradients reflected inter-regional variations in cortical microstructure derived from quantitative magnetic resonance imaging and postmortem histology. Gradient-informed models accurately predicted macroscale measures of temporal lobe function. Furthermore, the identified gradients aligned closely with established measures of functional reconfiguration and areal expansion between macaques and humans, highlighting their potential role in shaping temporal lobe function throughout primate evolution. Findings were replicated in several datasets. Our results provide robust evidence for three axes of structural connectivity in human temporal cortex with consistent microstructural underpinnings and contributions to large-scale brain network function., (© The Author(s) 2021. Published by Oxford University Press.)

Autism spectrum disorder (ASD) is commonly understood as an alteration of brain networks, yet case-control analyses against typically-developing controls (TD) have yielded inconsistent results. Here, we devised a novel approach to profile the inter-individual variability in functional network organization and tested whether such idiosyncrasy contributes to connectivity alterations in ASD. Studying a multi-centric dataset with 157 ASD and 172 TD, we obtained robust evidence for increased idiosyncrasy in ASD relative to TD in default mode, somatomotor and attention networks, but also reduced idiosyncrasy in lateral temporal cortices. Idiosyncrasy increased with age and significantly correlated with symptom severity in ASD. Furthermore, while patterns of functional idiosyncrasy were not correlated with ASD-related cortical thickness alterations, they co-localized with the expression patterns of ASD risk genes. Notably, we could demonstrate that patterns of atypical idiosyncrasy in ASD closely overlapped with connectivity alterations that are measurable with conventional case-control designs and may, thus, be a principal driver of inconsistency in the autism connectomics literature. These findings support important interactions between inter-individual heterogeneity in autism and functional signatures. Our findings provide novel biomarkers to study atypical brain development and may consolidate prior research findings on the variable nature of connectome level anomalies in autism., (© 2021. The Author(s).)

Episodic memory is the ability to remember events from our past accurately. The process of pattern separation is hypothesized to underpin this ability and is defined as the capacity to orthogonalize memory traces, to maximize the features that make them unique. Contemporary cognitive neuroscience suggests that pattern separation entails complex interactions between the hippocampus and neocortex, where specific hippocampal subregions shape neural reinstatement in the neocortex. To test this hypothesis, the current work studied both healthy controls and patients with temporal lobe epilepsy who presented with hippocampal structural anomalies. We measured neural activity in all participants using functional MRI while they retrieved memorized items or lure items, which shared features with the target. Behaviourally, patients with temporal lobe epilepsy were less able to exclude lures than controls and showed a reduction in pattern separation. To assess the hypothesized relationship between neural patterns in the hippocampus and neocortex, we identified the topographic gradients of intrinsic connectivity along neocortical and hippocampal subfield surfaces and determined the topographic profile of the neural activity accompanying pattern separation. In healthy controls, pattern separation followed a graded topography of neural activity, both along the hippocampal long axis (and peaked in anterior segments that are more heavily engaged in transmodal processing) and along the neocortical hierarchy running from unimodal to transmodal regions (peaking in transmodal default mode regions). In patients with temporal lobe epilepsy, however, this concordance between task-based functional activations and topographic gradients was markedly reduced. Furthermore, person-specific measures of concordance between task-related activity and connectivity gradients in patients and controls were related to inter-individual differences in behavioural measures of pattern separation and episodic memory, highlighting the functional relevance of the observed topographic motifs. Our work is consistent with an emerging understanding that successful discrimination between memories with similar features entails a shift in the locus of neural activity away from sensory systems, a pattern that is mirrored along the hippocampal long axis and with respect to neocortical hierarchies. More broadly, our study establishes topographic profiling using intrinsic connectivity gradients, capturing the functional underpinnings of episodic memory processes in a manner that is sensitive to their reorganization in pathology., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Neuroimaging stands to benefit from emerging ultrahigh-resolution 3D histological atlases of the human brain; the first of which is 'BigBrain'. Here, we review recent methodological advances for the integration of BigBrain with multi-modal neuroimaging and introduce a toolbox, 'BigBrainWarp', that combines these developments. The aim of BigBrainWarp is to simplify workflows and support the adoption of best practices. This is accomplished with a simple wrapper function that allows users to easily map data between BigBrain and standard MRI spaces. The function automatically pulls specialised transformation procedures, based on ongoing research from a wide collaborative network of researchers. Additionally, the toolbox improves accessibility of histological information through dissemination of ready-to-use cytoarchitectural features. Finally, we demonstrate the utility of BigBrainWarp with three tutorials and discuss the potential of the toolbox to support multi-scale investigations of brain organisation., Competing Interests: CP, JR, LL, CL, TG, KW, JD, SV, LC, AK, KA, AE, TD, BB none, PT None, (© 2021, Paquola et al.)

Prior research has shown a role of the medial temporal lobe, particularly the hippocampal-parahippocampal complex, in spatial cognition. Here, we developed a new paradigm, the conformational shift spatial task (CSST), which examines the ability to encode and retrieve spatial relations between unrelated items. This task is short, uses symbolic cues, incorporates two difficulty levels, and can be administered inside the scanner. A cohort of 48 healthy young adults underwent the CSST, together with a set of behavioral measures and multimodal magnetic resonance imaging (MRI). Inter-individual differences in CSST performance correlated with scores on an established spatial memory paradigm, but neither with episodic memory nor mnemonic discrimination, supporting specificity. Analyzing high-resolution structural MRI data, individuals with better spatial memory showed thicker medial and lateral temporal cortices. Functional relevance of these findings was supported by task-based functional MRI analysis in the same participants and ad hoc meta-analysis. Exploratory resting-state functional MRI analyses centered on clusters of morphological effects revealed additional modulation of intrinsic network integration, particularly between lateral and medial temporal structures. Our work presents a novel spatial memory paradigm and supports an integrated structure-function substrate in the human temporal lobe. Task paradigms are programmed in python and made open access., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

In this cross-sectional population-based study, women had significantly higher crude incidence rates of both community-associated Clostridioides difficile infection (CA-CDI) and ambulatory antibiotic prescriptions compared to men in South Carolina in 2015. After adjustments for antibiotic prescription rates, there was no difference in the incidence rates of CA-CDI between the genders.