Hand position-dependent modulation of errors in vibrotactile temporal order judgments:the effects of transcranial magnetic stimulation to the human posterior parietal cortex

The ability to decide which of the two stimuli is presented first can be probed using a temporal order judgment (TOJ) task. When the stimuli are delivered to the fingers, TOJ decisions can be confounded by the fact that the hands can be moved to different locations in space. How and where this confounded information is processed in the brain is poorly understood. In the present set of experiments, we addressed this knowledge gap by using single-pulse transcranial magnetic stimulation (TMS) to disrupt processing in the right or left posterior parietal cortex (PPC) during a vibrotactile TOJ task with stimuli applied to the right and left index fingers. In the first experiment, participants held their hands in an uncrossed configuration, and we found that when the index finger contralateral to the site of TMS was stimulated first, there was a significant increase in TOJ errors. This increase did not occur when stimuli were delivered to the ipsilateral finger first. In the second experiment, participants held their hands in a crossed configuration and the pattern of errors was reversed relative to the first experiment. In both the first two experiments, significant increases in TOJ error were present with TMS over either hemisphere, regardless of arm configuration; however, they were larger overall following TMS over the right PPC. Control experiments using sham TMS indicated the systematic modulation in error was not due to nonspecific effects of the stimulation. Additionally, we showed that these TMS-induced changes in TOJ errors were not due to a reduced ability to detect the timing of the vibrotactile stimuli. Taken together, these results demonstrate that both the right and left PPC contribute to the processing underlying vibrotactile TOJs by integrating vibrotactile information and proprioceptive information related to arm position in space

A precision functional atlas of personalized network topography and probabilities

Although the general location of functional neural networks is similar across individuals, there is vast person-to-person topographic variability. To capture this, we implemented precision brain mapping functional magnetic resonance imaging methods to establish an open-source, method-flexible set of precision functional network atlases-the Masonic Institute for the Developing Brain (MIDB) Precision Brain Atlas. This atlas is an evolving resource comprising 53,273 individual-specific network maps, from more than 9,900 individuals, across ages and cohorts, including the Adolescent Brain Cognitive Development study, the Developmental Human Connectome Project and others. We also generated probabilistic network maps across multiple ages and integration zones (using a new overlapping mapping technique, Overlapping MultiNetwork Imaging). Using regions of high network invariance improved the reproducibility of executive function statistical maps in brain-wide associations compared to group average-based parcellations. Finally, we provide a potential use case for probabilistic maps for targeted neuromodulation. The atlas is expandable to alternative datasets with an online interface encouraging the scientific community to explore and contribute to understanding the human brain function more precisely

Lateralized Connectivity between Globus Pallidus and Motor Cortex is Associated with Freezing of Gait in Parkinson’s Disease

Freezing of gait (FoG) is a brief, episodic absence or marked reduction of forward progression of the feet, despite the intention to walk, that is common in people with Parkinson’s disease (PD). We hypothesized that not only motor, but higher level cognitive and attention areas may be impaired in freezers. In this study, we aimed to characterize differences in cortical and subcortical functional connectivity specific to FoG. We examined resting state neuroimaging and objective measures of FoG severity and gait from 103 individuals (28 PD + FoG, 36 PD − FoG and 39 healthy controls). Inertial sensors were used to quantify freezing severity and gait. Groups with and without FoG were matched on age, disease severity, cognitive status, and levodopa medication. MRI data was processed using surface-based registration. High-quality imaging data were used to characterize differences in connectivity specific to FoG using a pre-defined set of Regions of Interest (ROIs) and validated using whole-brain connectivity analysis. Associations between functional connectivity and objective measures of FoG were determined via predictive modeling using hold-out cross validation. We found that connectivity between the left globus pallidus (GP) and left somatosensory cortex and between two brain areas in the default and insular/vestibular networks exhibited significant differences specific to FoG and were also strong and significant predictors of FoG severity. Our findings suggest that the interplay among motor, default and vestibular areas of the left cortex are critical in the pathology of FoG

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Network Linkages to Predict Bank Distress

Building on the literature on systemic risk and financial contagion, the paper introduces estimated network linkages into an early-warning model to predict bank distress among European banks. We use multivariate extreme value theory to estimate equity-based tail-dependence networks, whose links proxy for the markets' view of bank interconnectedness in case of elevated financial stress. The paper finds that early warning models including estimated tail dependencies consistently outperform bank-specific benchmark models with- out networks. The results are robust to variation in model specification and also hold in relation to simpler benchmarks of contagion. Generally, this paper gives direct support for measures of interconnectedness in early-warning models, and moves toward a unified representation of cyclical and cross-sectional dimensions of systemic risk

Data Sets

Contains network ROIs for various dataset

Masonic Institute for the Developing Brain (MIDB) Precision Brain Atlas

A collection of neural network atlase