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Compelling evidence suggests the need for more data per individual to reliably map the functional organization of the human connectome. As the notion that ‘more data is better’ emerges as a golden rule for functional connectomics, researchers find themselves grappling with the challenges of how to obtain the desired amounts of data per participant in a practical manner, particularly for retrospective data aggregation. Increasingly, the aggregation of data across all fMRI scans available for an individual is being viewed as a solution, regardless of scan condition (e.g., rest, task, movie). A number of open questions exist regarding the aggregation process and the impact of different decisions on the reliability of resultant aggregate data. We leveraged the availability of highly sampled test-retest datasets to systematically examine the impact of data aggregation strategies on the reliability of cortical functional connectomics. Specifically, we compared functional connectivity estimates derived after concatenating from: 1) multiple scans under the same state, 2) multiple scans under different states (i.e. hybrid or general functional connectivity), and 3) subsets of one long scan. We also varied connectivity processing (i.e. global signal regression, ICA-FIX, and task regression) and estimation procedures. When the total number of time points is equal, and the scan state held constant, concatenating multiple shorter scans had a clear advantage over a single long scan. However, this was not necessarily true when concatenating across different fMRI states (i.e. task conditions), where the reliability from the aggregate data varied across states. Concatenating fewer numbers of states that are more reliable tends to yield higher reliability. Our findings provide an overview of multiple dependencies of data concatenation that should be considered to optimize reliability in analysis of functional connectivity data.

Brain extraction (a.k.a. skull stripping) is a fundamental step in the neuroimaging pipeline as it can affect the accuracy of downstream preprocess such as image registration, tissue classification, etc. Most brain extraction tools have been designed for and applied to human data and are often challenged by non-human primates (NHP) data. Amongst recent attempts to improve performance on NHP data, deep learning models appear to outperform the traditional tools. However, given the minimal sample size of most NHP studies and notable variations in data quality, the deep learning models are very rarely applied to multi-site samples in NHP imaging. To overcome this challenge, we used a transfer-learning framework that leverages a large human imaging dataset to pretrain a convolutional neural network (i.e. U-Net Model), and then transferred this to NHP data using a small NHP training sample. The resulting transfer-learning model converged faster and achieved more accurate performance than a similar U-Net Model trained exclusively on NHP samples. We improved the generalizability of the model by upgrading the transfer-learned model using additional training datasets from multiple research sites in the Primate Data-Exchange (PRIME-DE) consortium. Our final model outperformed brain extraction routines from popular MRI packages (AFNI, FSL, and FreeSurfer) across a heterogeneous sample from multiple sites in the PRIME-DE with less computational cost (20 s~10 min). We also demonstrated the transfer-learning process enables the macaque model to be updated for use with scans from chimpanzees, marmosets, and other mammals (e.g. pig). Our model, code, and the skull-stripped mask repository of 136 macaque monkeys are publicly available for unrestricted use by the neuroimaging community at https://github.com/HumanBrainED/NHP-BrainExtraction.

The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted people's lifestyles, changing sleep patterns. This study investigated changes in sleep patterns and disturbances in South Koreans over the past decade, including during the pandemic. We compared data from the Korean Sleep Headache Society Phase I survey (n = 2484; conducted in 2010) and the National Sleep Survey of South Korea 2022 (n = 3729; conducted in 2022), involving participants aged 20-69 years. Changes in sleep schedule, sleep duration, social jet lag, insomnia, and daytime sleepiness were explored. Workday bedtimes were advanced and free-day bedtimes and workday and free-day waking times were delayed during the pandemic. Increased circadian preference for eveningness and social jet lag were noted. A significant decrease in sleep duration and sleep efficiency, along with an increased prevalence of insomnia and daytime sleepiness, was noted with age- and sex-specific variations. Over the past decade, including during the COVID-19 pandemic, sleep habits have changed significantly and sleep problems worsened. This study emphasize the need for more comprehensive public health strategies and research to facilitate sleep recovery in the post-pandemic period within a society known for its high prevalence of sleep deprivation.

•The clinical significance of Epstein-Barr virus (EBV) DNA in CSF of individuals with suspected CNS infection remains unclear.•EBV DNA in CSF is occasionally found in the immunocompetent population.•EBV was frequently found together with other microbes in CSF and associated with encephalitis and poor prognosis. Polymerase chain reaction (PCR)-based testing of cerebrospinal fluid (CSF) samples has greatly facilitated the diagnosis of central nervous system (CNS) infections. However, the clinical significance of Epstein-Barr virus (EBV) DNA in CSF of individuals with suspected CNS infection remains unclear. We wanted to gain a better understanding of EBV as an infectious agent in immunocompetent patients with CNS disorders. We identified cases of EBV-associated CNS infections and reviewed their clinical and laboratory characteristics. The study population was drawn from patients with EBV PCR positivity in CSF who visited Pusan National University Hospital between 2010 and 2019. Of the 780 CSF samples examined during the 10-year study period, 42 (5.4 %) were positive for EBV DNA; 9 of the patients (21.4 %) were diagnosed with non-CNS infectious diseases, such as optic neuritis, Guillain-Barré syndrome, and idiopathic intracranial hypotension, and the other 33 cases were classified as CNS infections (22 as encephalitis and 11 as meningitis). Intensive care unit admission (13/33 patients, 39.3 %) and presence of severe neurological sequelae at discharge (8/33 patients, 24.2 %) were relatively frequent. In 10 patients (30.3 %), the following pathogens were detected in CSF in addition to EBV: varicella-zoster virus (n = 3), cytomegalovirus (n = 2), herpes simplex virus 1 (n = 1), herpes simplex virus 2 (n = 1), Streptococcus pneumomiae (n = 2), and Enterococcus faecalis (n = 1). The EBV-only group (n = 23) and the co-infection group (n = 10) did not differ in age, gender, laboratory data, results of brain imaging studies, clinical manifestations, or prognosis; however, the co-infected patients had higher CSF protein levels. EBV DNA in CSF is occasionally found in the immunocompetent population; the virus was commonly associated with encephalitis and poor prognosis, and frequently found together with other microbes in CSF.

Background Spontaneous intracranial hypotension and post-dural puncture headache are both caused by a loss of cerebrospinal fluid but present with different pathogeneses. We compared these two conditions concerning their clinical characteristics, brain imaging findings, and responses to epidural blood patch treatment. Methods We retrospectively reviewed the records of patients with intracranial hypotension admitted to the Neurology ward of the Pusan National University Hospital between January 1, 2011, and December 31, 2019, and collected information regarding age, sex, disease duration, hospital course, headache intensity, time to the appearance of a headache after sitting, associated phenomena (nausea, vomiting, auditory symptoms, dizziness), number of epidural blood patch treatments, and prognosis. The brain MRI signs of intracranial hypotension were recorded, including three qualitative signs (diffuse pachymeningeal enhancement, venous distention of the lateral sinus, subdural fluid collection), and six quantitative signs (pituitary height, suprasellar cistern, prepontine cistern, mamillopontine distance, the midbrain-pons angle, and the angle between the vein of Galen and the straight sinus). Results A total of 105 patients (61 spontaneous intracranial hypotension patients and 44 post-dural puncture headache patients) who met the inclusion criteria were reviewed. More patients with spontaneous intracranial hypotension required epidural blood patch treatment than those with post-dural puncture headache (70.5% (43/61) vs. 45.5% (20/44); p  = 0.01) and the spontaneous intracranial hypotension group included a higher proportion of patients who underwent epidural blood patch treatment more than once (37.7% (23/61) vs. 13.6% (6/44); p  = 0.007). Brain MRI showed signs of intracranial hypotension in both groups, although the angle between the vein of Galen and the straight sinus was greater in the post-dural puncture headache group (median [95% Confidence Interval]: 85° [68°-79°] vs. 74° [76°-96°], p  = 0.02). Conclusions Patients with spontaneous intracranial hypotension received more epidural blood patch treatments and more often needed multiple epidural blood patch treatments . Although both groups showed similar brain MRI findings, the angle between the vein of Galen and the straight sinus differed significantly between the groups.

Background Dilated perivascular spaces (DPVS), known as one of imaging markers in cerebral small vessel disease, may be found in patients with moyamoya disease (MMD). However, little is known about DPVS in MMD. The purpose of this study was to investigate the distribution pattern of dPVS in children and adults with MMD and determine whether it is related to steno-occlusive changes of MMD. Methods DPVS was scored in basal ganglia (BG) and white matter (WM) on T2-weighted imaging, using a validated 4-point semi-quantitative score. The degree of dPVS was classified as high (score > 2) or low (score ≤ 2) grade. The steno-occlusive changes on MR angiography (MRA) was scored using a validated MRA grading. Asymmetry of DPVS and MRA grading was defined as a difference of 1 grade or higher between hemispheres. Results Fifty-one patients with MMD (mean age 24.9 ± 21.1 years) were included. Forty-five (88.2%) patients had high WM-DPVS grade (degree 3 or 4). BG-DPVS was found in 72.5% of all patients and all were low grade (degree 1 or 2). The distribution patterns of DPVS degree in BG ( P  = 1.000) and WM ( P  = 0.767) were not different between child and adult groups. The asymmetry of WM-DPVS (26%) and MRA grade (42%) were significantly correlated to each other (Kendall’s tau-b = 0.604, P  < 0.001). Conclusions DPVS of high grade in MMD is predominantly found in WM, which was not different between children and adults. The correlation between asymmetry of WM-DPVS degree and MRA grade suggests that weak cerebral artery pulsation due to steno-occlusive changes may affect WM-DPVS in MMD.

We aimed to find structural brain abnormalities in juvenile myoclonic epilepsy (JME) patients. The volumes of the cerebrum, hippocampus and frontal lobe and the area of the corpus callosum's subdivisions were all semiautomatically measured, and then optimized voxel-based morphometry (VBM) was performed in 19 JME patients and 19 age/gender matched normal controls. The rostrum and rostral body of the corpus callosum and the left hippocampus were significantly smaller than those of the normal controls, whereas the volume of the JME's left frontal lobe was significantly larger than that of the controls. The area of the rostral body had a significant positive correlation with the age of seizure onset (r = 0.56, p = 0.012), and the volume of the right frontal lobe had a significant negative correlation with the duration of disease (r = -0.51, p = 0.025). On the VBM, the gray matter concentration of the prefrontal lobe (bilateral gyri rectus, anterior orbital gyri, left anterior middle frontal gyrus and right anterior superior frontal gyrus) was decreased in the JME group (corrected p < 0.05). The JME patients showed complex structural abnormalities in the corpus callosum, frontal lobe and hippocampus, and also a decreased gray matter concentration of the prefrontal region, which all suggests there is an abnormal neural network in the JME brain.

Sleep deprivation in adolescents is a common but serious public health issue. Adolescents often have a progressive circadian delay and suffer from insufficient sleep during weekdays due to the school schedule. Temporal patterns in internet search activity data can provide relevant information for understanding the characteristic sleep problems of the adolescent population. We aimed to reveal whether adolescents exhibit distinct temporal seasonal and weekly patterns in internet search activity on insomnia compared to adults. We hypothesized that adolescents exhibit larger variations in the internet search volume for insomnia, particularly in association with the school schedule (e.g., academic vacations and weekends). We extracted the daily search volume for insomnia in South Korean adolescents (13-18 years old), adults (19-59 years old), and young adults (19-24 years old) during the years 2016-2019 using NAVER DataLab, the most popular search engine in South Korea. The daily search volume data for each group were normalized with the annual median of each group. The time series of the search volume was decomposed into slow fluctuation (over a year) and fast fluctuation (within a week) using fast Fourier transform. Next, we compared the normalized search volume across months in a year (slow fluctuation) and days in a week (fast fluctuation). In the annual trend, 2-way ANOVA revealed a significant (group) × (month) interaction (P<.001). Adolescents exhibited much greater seasonal variations across a year than the adult population (coefficient of variation=0.483 for adolescents vs 0.131 for adults). The search volume for insomnia in adolescents was notably higher in January, February, and August, which are academic vacation periods in South Korea (P<.001). In the weekly pattern, 2-way ANOVA revealed a significant (group) × (day) interaction (P<.001). Adolescents showed a considerably increased search volume on Sunday and Monday (P<.001) compared to adults. In contrast, young adults demonstrated seasonal and weekly patterns similar to adults. Adolescents demonstrate distinctive seasonal and weekly patterns in internet searches on insomnia (ie, increased search in vacation months and weekend-weekday transitions), which are closely associated with the school schedule. Adolescents' sleep concerns might be potentially affected by the disrupted daily routine and the delayed sleep phase during vacations and weekends. As we demonstrated, comparing various age groups in infodemiology and infoveillance data might be helpful in identifying distinctive features in vulnerable age groups.

1 Introduction Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism due to the dysfunction of a copper transporting P-type ATPase (ATP7B), which leads to copper accumulation mainly in the liver, brain, cornea and kidney [1]. In the absence of comparative neuropathologic MR imaging studies, the nature of dark-signal lesions remains speculative. Since copper is paramagnetic, it is possible that the observed abnormalities in our patient reflect copper deposition.

Characterizing multifaceted individual differences in brain function using neuroimaging is central to biomarker discovery in neuroscience. We provide an integrative toolbox, Reliability eXplorer (ReX), to facilitate the examination of individual variation and reliability as well as the effective direction for optimization of measuring individual differences in biomarker discovery. We also illustrate gradient flows, a two-dimensional field map-based approach to identifying and representing the most effective direction for optimization when measuring individual differences, which is implemented in ReX. The Reliability eXplorer is a tool for assessing measurement reliability in neuroimaging studies.