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Mark C Vital,1 Kevin Y Jong,1 Clarise E Trinh,1 Tomy Starck,2 David Sretavan3 1Houston Eye Associates, Houston, TX, USA; 2UltraVision, San Antonio, TX, USA; 3Centricity Vision Inc., Carlsbad, CA, USACorrespondence: Mark C Vital, Houston Eye Associates, 2855 Gramercy Street, Houston, TX, 77025, USA, Tel +1 713 668 6828, Fax +1 832 553-7154, Email MVital@HoustonEye.comPurpose: To compare endothelial cell density (ECD), percentage of hexagonal cells (%Hex) and coefficient of variation (CV) in cell size following lens cataract surgery with phacoemulsification performed using Continuous Curvilinear Capsulorhexis (CCC) or Precision Pulse Capsulotomy (PPC).Patients and Methods: Sixty-seven subjects were randomly assigned to undergo lens cataract removal with the capsulotomy step performed using either CCC or PPC. Specular microscopy images were obtained pre-operatively, 1 month and 3 months after surgery. ECD, %Hex and CV were analyzed in a masked fashion by an independent reading center.Results: The mean percentage ECD loss at 1 month was 11.5% in the CCC group and 12.3% in the PPC group (P = 0.818; t-test). At 3 months, the mean percentage ECD loss was 11.7% in the CCC group and 12.4% in the PPC group (P = 0.815; t-test). The mean %Hex at 1 month was 54.3% in the CCC group and 54.7% in the PPC group (P = 0.695; t-test). At 3 months, the mean %Hex was 56.2% in the CCC group and 54.7% in the PPC group (P = 0.278; t-test). The CV at 1 month was 34.4% in the CCC group and 34.3% in the PPC group (P = 0.927; t-test). At 3 months, the CV was 32.7% in the CCC group and 33.4% in the PPC group (P = 0.864; t-test).Conclusion: No differences in ECD loss, %Hex and CV were observed between patients who received CCC or PPC. PPC use during cataract surgery does not result in any increased endothelial cell loss beyond that normally associated with this surgery.Keywords: automated capsulotomy, zepto, corneal endothelium

Abstract: The rotational spectrum of an enriched sample of HCC 15N was measured in the range 8–27GHz by means of a waveguide Fourier transform microwave spectrometer. New transitions were also measured in the millimetre- and submillimetre ranges. These measurements combined with the available rovibrational and rotational data [Fayt et al., J. Mol. Struct. 695–696 (2004) 295], with many newly assigned infrared bands, were used for a global rovibrational analysis of all vibrational states up to 1700cm−1. A full set of 243 molecular parameters for the modes v 4–v 7 has been deduced. [Copyright &y& Elsevier]

Nitrogen (N) is essential for plant growth and protein synthesis but global reactive N losses, mainly from food systems, induce strong environmental impacts. N losses after human excretion are often overlooked because, in Western societies, they partly occur as inert N 2 , following denitrification in wastewater treatment plants (WWTP), and losses in waters are often small compared to diffuse agricultural emissions. Yet N from human excretions could be used for crop fertilization, potentially with very high recycling rates via source separation. In this study we use unique operational data from the ∼20,000 French WWTPs to produce a N mass-balance of excretions in the French sanitation system. Even though 75 % of WWTPs' sludge is spread on crops, only 10 % of the excreted N is recycled and 50 % of N is lost to the atmosphere, mainly through WWTP nitrification-denitrification. The remaining 40 % ends up in water or in diffuse losses in the ground, of which about half is lost outside of the WWTPs' discharge system, through sewers storm water and individual autonomous systems. While WWTPs removal efficiency increased in the 2000s, it has been followed by a decade of stagnation, reaching 70 % at the national level. This national average hides regional discrepancies, from 60 to 85 % in the 6 French water agencies basins. These differences closely correlate with the classification as "N sensitive areas" and is mainly due to large WWTPs which handle most of the N load. Recycling all N in excretions could supply 10 % of domestic protein consumption in the current French food system, and up to 30 % if it is prioritized towards crop production for human consumption. Redesigning the food system (decrease of nutrient losses, more plant-based diets) could further increase this contribution., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: Young children in Sub-Saharan Africa (SSA), particularly those from resource-limited settings, are heavily burdened by anemia and malaria. While malaria infected children frequently become anemic (hemoglobin < 110 g/L), anemia is a strongly multifactorial disease with many other risk factors than malaria. Due to the complex and often overlapping contributors to anemia, it remains challenging to isolate the true impact of malaria on population level hemoglobin concentrations., Methods: We quantified the malaria-induced effect on hemoglobin levels in children under 5 years of age, leveraging data from 7,384 twins and other multiples, aged 6 to 59 months, from 57 nationally representative Demographic and Health Surveys (DHSs) from 23 SSA countries from 2006 to 2019. The quasi-experimental twin fixed-effect design let us minimize the impact of potential confounders that do not vary between twins., Results: Our analyses of twins revealed a malaria-induced hemoglobin decrease in infected twins of 9 g/L (95% CI -10; -7, p <0.001). The relative risk of severe anemia was higher (RR = 3.01, 95% CI 1.79; 5.1, p <0.001) among malaria positive children, compared to malaria negative children. Conversely, malaria positive children are only half as likely to be non-anemic (RR = 0.51, 95% CI 0.43; 0.61, p <0.001)., Conclusion: Even after rigorous control for confounding through a twin fixed-effects study design, malaria substantially decreased hemoglobin levels among SSA twins, rendering them much more susceptible to severe anemia. This effect reflects the population-level effect of malaria on anemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Starck, Dambach, Rouamba, Tinto, Osier, Oldenburg, Adam, Bärnighausen, Jaenisch and Bulstra.)

Objectives: Paraplegia is a devastating complication in aortic aneurysm surgery. Modifying the spinal cord vasculature is a promising method in spinal cord protection. The aim of this study was to assess whether the spinal cord can be primed by occluding thoracic segmental arteries before simulated aneurysm repair in a porcine model., Methods: Twelve piglets were randomly assigned to the priming group (6) and the control group (6). Eight uppermost thoracic segmental arteries were occluded at 5-minute intervals in the priming group before a 25-minute aortic crossclamp. In the control group, the aorta was crossclamped for 25 minutes. During the first 5 minutes, 8 segmental arteries were occluded. After the aortic crossclamping, piglets were observed under anesthesia for 5 hours and followed up 5 days postoperatively. Near-infrared spectroscopy, motor-evoked potentials, blood samples, neurology with the modified Tarlov score, and histopathology of the spinal cord were assessed., Results: The median Tarlov score during the first postoperative day was higher in the priming group than in the control group (P = .001). At the end, 50% of the control animals had paraplegia compared with 0% of paraplegia in the priming group. The mean regional histopathologic score differed between the priming group and the control group (P = .02). The priming group had higher motor-evoked potentials during the operation at separate time points. The lactate levels were lower in the priming group compared with the control group (P g  = .001, P g×t  = .18)., Conclusions: Acute priming protects the spinal cord from ischemic injury in an experimental aortic crossclamp model., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Although the association between malaria and anaemia is widely studied in patient cohorts, the population-representative causal effects of malaria on anaemia remain unknown. This study estimated the malaria-induced decrease in haemoglobin levels among young children in malaria-endemic Burkina Faso., Methods: The study was based on pooled individual-level nationally representative health survey data (2010-2011, 2014, 2017-2018) from 17 599 children under 5 years of age. This data was used to estimate the effects of malaria on haemoglobin concentration, controlling for household fixed-effects, age, and sex in a series of regression analyses. The fixed-effects controlled for observed and unobserved confounding on the household level and allowed to determine the impact of malaria infection status on haemoglobin levels and anaemia prevalence. Furthermore, the diagnostic results from microscopy and rapid diagnostic tests were leveraged to provide a quasi-longitudinal perspective of acute and prolonged effects after malaria infection., Results: The prevalence of both malaria (survey prevalence ranging from 17.4% to 65.2%) and anaemia (survey prevalence ranging from 74% to 88.2%) was very high in the included surveys. Malaria was estimated to significantly reduce haemoglobin levels, with an overall effect of - 7.5 g/dL (95% CI - 8.5, - 6.5). Acute malaria resulted in a - 7.7 g/dL (95% CI - 8.8, - 6.6) decrease in haemoglobin levels. Recent malaria without current parasitaemia decreased haemoglobin concentration by - 7.1 g/dL (95% CI - 8.3, - 5.9). The in-sample predicted prevalence of severe anaemia was 9.4% among malaria positives, but only 2.2% among children without malaria., Conclusion: Malaria infection has a strong detrimental effect on haemoglobin levels among young children in Burkina Faso. This effect seems to carry over even after acute infection, indicating prolonged haemoglobin reductions even after successful parasite-elimination. The quasi-experimental fixed-effect approach adds a population level perspective to existing clinical evidence., (© 2021. The Author(s).)

Background: Most data on COVID-19 was collected in hospitalized cases. Much less is known about the spectrum of disease in entire populations. In this study, we examine a representative cohort of primarily symptomatic cases in an administrative district in Southern Germany., Methods: We contacted all confirmed SARS-CoV-2 cases in the administrative district. Consenting participants answered a retrospective survey either via a telephone, electronically or via mail. Clinical and sociodemographic features were compared between hospitalized and non-hospitalized patients. Additionally, we assessed potential risk factors for hospitalization and time to hospitalization in a series of regression models., Results: We included 897 participants in our study, 69% out of 1,305 total cases in the district with a mean age of 47 years (range 2-97), 51% of which were female and 47% had a pre-existing illness. The percentage of asymptomatic, mild, moderate (leading to hospital admission) and critical illness (requiring mechanical ventilation) was 54 patients (6%), 713 (79%), 97 (11%) and 16 (2%), respectively. Seventeen patients (2%) died. The most prevalent symptoms were fatigue (65%), cough (62%) and dysgeusia (60%). The risk factors for hospitalization included older age (OR 1.05 per year increase; 95% CI 1.04-1.07) preexisting lung conditions (OR 3.09; 95% CI 1.62-5.88). Female sex was a protective factor (OR 0.51; 95% CI 0.33-0.77)., Conclusion: This representative analysis of primarily symptomatic COVID-19 cases confirms age, male sex and preexisting lung conditions but not cardiovascular disease as risk factors for severe illness. Almost 80% of infection take a mild course, whereas 13% of patients suffer moderate to severe illness., Trial Registration: German Clinical Trials Register, DRKS00022926. URL: https://www.drks.de/drks&#95;web/setLocale&#95;EN.do., Competing Interests: The authors have declared that no competing interests exist.

Surgical repair of thoracic aorta can compromise blood flow of the spinal cord. To mitigate spinal cord ischemia (SCI) additional protection methods are needed. In experimental studies remote ischemic preconditioning (RIPC) has proven to be an effective method of protecting organs from ischemia. The aim of the study was to assess efficacy of RIPC in spinal cord protection in a chronic porcine model. Sixteen piglets were assigned into the RIPC group (8) and the control group (8). RIPC was performed using blood pressure cuff in a 5-minute ischemia followed by a 5-minute reperfusion repeating cycles 4 times. The left subclavian artery and all segmental arteries above diaphragm were ligated at 5-minute intervals to accomplish SCI. The follow-up comprised a 4-hour intensive monitoring and a 7-day recovery phase. Blood samples were obtained, motor-evoked potentials and near-infrared spectroscopy (NIRS) of longitudinal back muscles were measured. Paraplegia was assessed every day postoperatively. Histopathological analysis of the spinal cord was performed after 7 days. NIRS values 4 hours after SCI were higher in the RIPC group, 45.5 (44.5-47.0), than in the control group, 41.5 (40.5-44.0) (P = 0.042). Nadir value of NIRS was 43.4 (39.3-46.0) in the RIPC group and 38.9 (38.-40.0) in the control group (P = 0.014). On the first postoperative day the RIPC group reached modified Tarlov score of 3 (2-3) vs 2 (1-2) in the control group (P = 0.024). RIPC hastens the recovery from SCI during the first postoperative day., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Our goal was to discover attention- and inhibitory control-related differences in the main oscillations of the brain of children who stutter (CWS) compared to typically developed children (TDC)., Methods: We performed a time-frequency analysis using wavelets, fast Fourier transformation (FFT) and the Alpha/Theta power ratio of EEG data collected during a visual Go/Nogo task in 7-9 year old CWS and TDC, including also the time window between consecutive tasks., Results: CWS showed significantly reduced occipital alpha power and Alpha/Theta ratio in the "resting" or preparatory period between visual stimuli especially in the Nogo condition., Conclusions: The CWS demonstrate reduced inhibition of the visual cortex and information processing in the absence of visual stimuli, which may be related to problems in attentional gating., Significance: Occipital alpha oscillation is elementary in the control and inhibition of visual attention and the lack of occipital alpha modulation indicate fundamental differences in the regulation of visual information processing in CWS. Our findings support the view of stuttering as part of a wide-ranging brain dysfunction most likely involving also attentional and inhibitory networks., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Paraplegia is one of the most severe complications occurring after the repair of thoracic and thoracoabdominal aortic aneurysms. Remote ischemic preconditioning (RIPC) has been shown to mitigate neurologic damage, and this study assessed its efficacy in preventing spinal cord ischemia., Methods: The study randomized 16 female pigs into an RIPC group (n = 8) and a control group (n = 8). The RIPC group underwent four cycles of 5-minute ischemia-reperfusion episodes by intermittent occlusion of the left iliac artery. All animals underwent systematic closure of the left subclavian artery and segmental arteries of the descending thoracic aorta to the level of diaphragm. Motor-evoked potential monitoring was performed in both hind limbs. Continuous electrocardiogram and hemodynamics were monitored, and pulmonary artery blood samples were collected. A neurologic assessment was performed 6 hours after the procedure. The thoracic and lumbar portions of the spinal cord were collected for histologic and immunohistochemical analysis., Results: The bilateral motor-evoked potential amplitude responses were higher in the RIPC group (p < 0.05) than in the control group; the difference was detected already before spinal cord ischemia. Paraplegia occurred in 1 control animal. Immunohistochemical total scores of antioxidant response regulator nuclear factor erythroid 2-related factor 2 were better in the RIPC group (11.0; range, 8.5 to 14.0) than in the control group (5.2; range, 1.0 to 9.0; p = 0.023)., Conclusions: RIPC induces electrophysiologic changes in the central nervous system that may confer spinal cord protection extending the resistance to ischemia. The significantly higher nuclear factor erythroid 2-related factor 2 scores suggest better neuronal cell protection against oxidative stress in the RIPC group., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Surgical repair of thoracoabdominal aneurysm jeopardizes the vascularization of the spinal cord, and therefore, despite improvement in surgical techniques, still carries the risk of paraplegia. This study aimed to demonstrate the possible protective effects of remote ischemic preconditioning (RIPC) on the preservation of spinal cord function after segmental artery (SA) occlusion., Methods: Twenty piglets were randomized into the RIPC group (n = 10) and the control group (n = 10). The RIPC group underwent transient left hind limb ischemia before systematic left subclavian artery and SA occlusion at the level of the diaphragm. Motor-evoked potential (MEP) monitoring was performed from the hind limbs. Afterward, the thoracic and lumbar spinal cords were harvested and analyzed., Results: The elevation of the MEP amplitude after RIPC was statistically significant, whereas amplitude was consistently decreased in the control group. Additionally, the onset latency was significantly shorter after RIPC during SA occlusion. The control group reached a 50% decrease of MEP amplitude in the right hind limb sooner than did the experimental group., Conclusions: Remote ischemic preconditioning preserves spinal cord function after left subclavian artery and SA occlusion, as indicated by the MEP amplitudes., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The changes in functional brain organization associated with paediatric epilepsy are largely unknown. Since children with epilepsy are at risk of developing learning difficulties even before or shortly after the onset of epilepsy, we assessed the functional organization of memory and language in paediatric patients with temporal lobe epilepsy (TLE) at an early stage in epilepsy., Methods: Functional magnetic resonance imaging was used to measure the blood oxygenation level-dependent (BOLD) response to four cognitive tasks measuring reading, story listening, memory encoding and retrieval in a population-based group of children with TLE of unknown cause (n = 21) and of normal intelligence and a healthy age and gender-matched control group (n = 21)., Results: Significant BOLD response differences were found only in one of the four tasks. In the story listening task, significant differences were found in the right hemispheric temporal structures, thalamus and basal ganglia. Both activation and deactivation differed significantly between the groups, activation being increased and deactivation decreased in the TLE group. Furthermore, the patients with abnormal electroencephalograms (EEGs) showed significantly increased activation bilaterally in the temporal structures, basal ganglia and thalamus relative to those with normal EEGs. The patients with normal interictal EEGs had a significantly stronger deactivation than those with abnormal EEGs or the controls, the differences being located outside the temporal structures., Conclusions: Our results suggest that TLE entails a widespread disruption of brain networks. This needs to be taken into consideration when evaluating learning abilities in patients with TLE. The thalamus seems to play an active role in TLE. The changes in deactivation may reflect neuronal inhibition., (Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Background: Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique enabling visualization and measurement of white matter tracts. Attention deficit hyperactivity disorder (ADHD) has been studied with DTI earlier with variable results, yet there is little research on remitted ADHD., Purpose: To compare the brain white matter between ADHD drug naïve subjects whose ADHD symptoms have mostly subsided and healthy controls., Material and Methods: Tract-based spatial statistics (TBSS) was used to compare 30 subjects with adolescent ADHD with control subjects at the age of 22-23 years. The study population was derived from a population-based Northern Finland Birth Cohort 1986. Fractional anisotropy (FA), mean diffusivity (MD), and measures of diffusion direction (λ1-3) were calculated. Permutation testing was used to test for differences in mean values of FA, MD, and λ1-3 between the groups. The results were corrected for multiple comparisons across the whole white matter skeleton., Results: The ADHD group showed increased FA related to decreased radial diffusivity in the left forceps minor (P < 0.05). In the vicinity along the same tract, axial diffusion was significantly decreased without any significant effect on FA. No between-group difference in MD was observed. Regressor analysis revealed no gender-, IQ- or GAF-related changes. After removal of left handed subjects the statistical significance was only barely lost., Conclusion: In a setting with remitted ADHD, the results may represent a compensatory mechanism in the left forceps minor., (© The Foundation Acta Radiologica 2014.)

Objectives: Seasonal affective disorder (SAD) is a subtype of recurrent unipolar or bipolar depressive disorder with a higher prevalence in winter than in summer. The biological underpinnings of SAD are so far poorly understood. Studies examining SAD have found disturbances between the molecular and connectivity scales. The aim of the study was to explore changes in functional connectivity typical for SAD., Methods: We investigated unmedicated, untreated SAD patients and healthy controls using resting-state functional magnetic resonance imaging (rs-fMRI) utilizing graph theory, a data driven and hypothesis free approach, to model functional networks of the brain., Results: Comparing whole brain network properties using graph theory we observed globally affected network topologies with increasing pathlength in SAD. Nodal changes, however, were highly restricted to bilateral inferior occipital cortex. Interestingly, we found a lateralization where hyper-connectedness was restricted to right inferior occipital cortex and hyper-efficiency was found in the left inferior occipital cortex. Furthermore, we found these nodes became more "hub like" in patients, suggesting a greater functional role., Conclusions: Our work stresses the importance of abnormal intrinsic processing during rest, primarily affecting visual areas and subsequently changing whole brain networks, and thus providing an important hint towards potential future therapeutic approaches.

Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999-2001 at the age of 33-35 years. A follow-up was conducted 9 years later during 2008-2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.

Ongoing neuronal activity in the CNS waxes and wanes continuously across widespread spatial and temporal scales. In the human brain, these spontaneous fluctuations are salient in blood oxygenation level-dependent (BOLD) signals and correlated within specific brain systems or "intrinsic-connectivity networks." In electrophysiological recordings, both the amplitude dynamics of fast (1-100 Hz) oscillations and the scalp potentials per se exhibit fluctuations in the same infra-slow (0.01-0.1 Hz) frequency range where the BOLD fluctuations are conspicuous. While several lines of evidence show that the BOLD fluctuations are correlated with fast-amplitude dynamics, it has remained unclear whether the infra-slow scalp potential fluctuations in full-band electroencephalography (fbEEG) are related to the resting-state BOLD signals. We used concurrent fbEEG and functional magnetic resonance imaging (fMRI) recordings to address the relationship of infra-slow fluctuations (ISFs) in scalp potentials and BOLD signals. We show here that independent components of fbEEG recordings are selectively correlated with subsets of cortical BOLD signals in specific task-positive and task-negative, fMRI-defined resting-state networks. This brain system-specific association indicates that infra-slow scalp potentials are directly associated with the endogenous fluctuations in neuronal activity levels. fbEEG thus yields a noninvasive, high-temporal resolution window into the dynamics of intrinsic connectivity networks. These results support the view that the slow potentials reflect changes in cortical excitability and shed light on neuronal substrates underlying both electrophysiological and behavioral ISFs.

At present, our knowledge about seasonal affective disorder (SAD) is based mainly up on clinical symptoms, epidemiology, behavioral characteristics and light therapy. Recently developed measures of resting-state functional brain activity might provide neurobiological markers of brain disorders. Studying functional brain activity in SAD could enhance our understanding of its nature and possible treatment strategies. Functional network connectivity (measured using ICA-dual regression), and amplitude of low-frequency fluctuations (ALFF) were measured in 45 antidepressant-free patients (39.78 ± 10.64, 30 ♀, 15 ♂) diagnosed with SAD and compared with age-, gender- and ethnicity-matched healthy controls (HCs) using resting-state functional magnetic resonance imaging. After correcting for Type 1 error at high model orders (inter-RSN correction), SAD patients showed significantly increased functional connectivity in 11 of the 47 identified RSNs. Increased functional connectivity involved RSNs such as visual, sensorimotor, and attentional networks. Moreover, our results revealed that SAD patients compared with HCs showed significant higher ALFF in the visual and right sensorimotor cortex. Abnormally altered functional activity detected in SAD supports previously reported attentional and psychomotor symptoms in patients suffering from SAD. Further studies, particularly under task conditions, are needed in order to specifically investigate cognitive deficits in SAD., (Copyright © 2012 Wiley Periodicals, Inc.)

In resting state functional magnetic resonance imaging (fMRI) studies of autism spectrum disorders (ASDs) decreased frontal-posterior functional connectivity is a persistent finding. However, the picture of the default mode network (DMN) hypoconnectivity remains incomplete. In addition, the functional connectivity analyses have been shown to be susceptible even to subtle motion. DMN hypoconnectivity in ASD has been specifically called for re-evaluation with stringent motion correction, which we aimed to conduct by so-called scrubbing. A rich set of default mode subnetworks can be obtained with high dimensional group independent component analysis (ICA) which can potentially provide more detailed view of the connectivity alterations. We compared the DMN connectivity in high-functioning adolescents with ASDs to typically developing controls using ICA dual-regression with decompositions from typical to high dimensionality. Dual-regression analysis within DMN subnetworks did not reveal alterations but connectivity between anterior and posterior DMN subnetworks was decreased in ASD. The results were very similar with and without motion scrubbing thus indicating the efficacy of the conventional motion correction methods combined with ICA dual-regression. Specific dissociation between DMN subnetworks was revealed on high ICA dimensionality, where networks centered at the medial prefrontal cortex and retrosplenial cortex showed weakened coupling in adolescents with ASDs compared to typically developing control participants. Generally the results speak for disruption in the anterior-posterior DMN interplay on the network level whereas local functional connectivity in DMN seems relatively unaltered.

Subject-level resting-state fMRI (RS-fMRI) spatial independent component analysis (sICA) may provide new ways to analyze the data when performed in the sliding time window. However, whether principal component analysis (PCA) and voxel-wise variance normalization (VN) are applicable pre-processing procedures in the sliding-window context, as they are for regular sICA, has not been addressed so far. Also model order selection requires further studies concerning sliding-window sICA. In this paper we have addressed these concerns. First, we compared PCA-retained subspaces concerning overlapping parts of consecutive temporal windows to answer whether in-window PCA and VN can confound comparisons between sICA analyses in consecutive windows. Second, we compared the PCA subspaces between windowed and full data to assess expected comparability between windowed and full-data sICA results. Third, temporal evolution of dimensionality estimates in RS-fMRI data sets was monitored to identify potential challenges in model order selection in a sliding-window sICA context. Our results illustrate that in-window VN can be safely used, in-window PCA is applicable with most window widths and that comparisons between windowed and full data should not be performed from a subspace similarity point of view. In addition, our studies on dimensionality estimates demonstrated that there are sustained, periodic and very case-specific changes in signal-to-noise ratio within RS-fMRI data sets. Consequently, dimensionality estimation is needed for well-founded model order determination in the sliding-window case. The observed periodic changes correspond to a frequency band of ≤0.1 Hz, which is commonly associated with brain activity in RS-fMRI and become on average most pronounced at window widths of 80 and 60 time points (144 and 108 s, respectively). Wider windows provided only slightly better comparability between consecutive windows, and 60 time point or shorter windows also provided the best comparability with full-data results. Further studies are needed to determine the cause for dimensionality variations., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Functional resting-state connectivity has been shown to be altered in certain adult epilepsy populations, but few connectivity studies have been performed on pediatric epilepsy patients. Here functional connectivity was measured in pediatric, non-lesional temporal lobe epilepsy patients with normal intelligence and compared with that in age and gender-matched healthy controls using the independent component analysis method. We hypothesized that children with non-lesional temporal lobe epilepsy have disrupted functional connectivity within resting-state networks. Significant differences were demonstrated between the two groups, pointing to a decrease in connectivity. When the results were analyzed according to the interictal electroencephalogram findings, however, the connectivity disruptions were seen in different networks. In addition, increased connectivity and abnormally anti-correlated thalamic activity was detected only in the patients with abnormal electroencephalograms. In summary, connectivity disruptions are already to be seen at an early stage of epilepsy, and epileptiform activity seems to affect connectivity differently. The results indicate that interictal epileptiform activity may lead to reorganization of the resting-state brain networks, but further studies would be needed in order to understand the pathophysiology behind this phenomenon., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Resting-state networks (RSNs) can be reliably and reproducibly detected using independent component analysis (ICA) at both individual subject and group levels. Altering ICA dimensionality (model order) estimation can have a significant impact on the spatial characteristics of the RSNs as well as their parcellation into sub-networks. Recent evidence from several neuroimaging studies suggests that the human brain has a modular hierarchical organization which resembles the hierarchy depicted by different ICA model orders. We hypothesized that functional connectivity between-group differences measured with ICA might be affected by model order selection. We investigated differences in functional connectivity using so-called dual regression as a function of ICA model order in a group of unmedicated seasonal affective disorder (SAD) patients compared to normal healthy controls. The results showed that the detected disease-related differences in functional connectivity alter as a function of ICA model order. The volume of between-group differences altered significantly as a function of ICA model order reaching maximum at model order 70 (which seems to be an optimal point that conveys the largest between-group difference) then stabilized afterwards. Our results show that fine-grained RSNs enable better detection of detailed disease-related functional connectivity changes. However, high model orders show an increased risk of false positives that needs to be overcome. Our findings suggest that multilevel ICA exploration of functional connectivity enables optimization of sensitivity to brain disorders.

Spatial independent components analysis (sICA) has become a widely applied data-driven method for fMRI data, especially for resting-state studies. These sICA approaches are often based on iterative estimation algorithms and there are concerns about accuracy due to noise. Repeatability measures such as ICASSO, RAICAR and ARABICA have been introduced as remedies but information on their effects on estimates is limited. The contribution of this study was to provide more of such information and test if the repeatability analyses are necessary. We compared FastICA-based ordinary and repeatability approaches concerning mixing vector estimates. Comparisons included original FastICA, FSL4 Melodic FastICA and original and modified ICASSO. The effects of bootstrapping and convergence threshold were evaluated. The results show that there is only moderate improvement due to repeatability measures and only in the bootstrapping case. Bootstrapping attenuated power from time courses of resting-state network related ICs at frequencies higher than 0.1 Hz and made subsets of low frequency oscillations more emphasized IC-wise. The convergence threshold did not have a significant role concerning the accuracy of estimates. The performance results suggest that repeatability measures or strict converge criteria might not be needed in sICA analyses of fMRI data. Consequently, the results in existing sICA fMRI literature are probably valid in this sense. A decreased accuracy of original bootstrapping ICASSO was observed and corrected by using centrotype mixing estimates but the results warrant for thorough evaluations of data-driven methods in general. Also, given the fMRI-specific considerations, further development of sICA methods is strongly encouraged., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Recent findings on intracortical EEG measurements show that the synchrony of localized neuronal networks is altered in epileptogenesis, leading to generalized seizure activity via connector hubs in the neuronal networks. Regional homogeneity (ReHo) analysis of blood oxygen level-dependent (BOLD) signals has demonstrated localized signal synchrony and disease-related alterations in a number of instances. We wanted to find out whether the ReHo of resting-state activity can be used to detect regional signal synchrony alterations in children with non-lesional temporal lobe epilepsy (TLE). Twenty-one TLE patients were compared with age and gender-matched healthy controls. Significantly increased ReHo was discovered in the posterior cingulate gyrus and the right medial temporal lobe of the patients, and they also had significantly decreased ReHo in the cerebellum compared with the healthy controls. However, the alterations in ReHo differed between the patients with normal and abnormal interictal EEGs, the latter showing significantly increased ReHo in the right fusiform gyrus and significantly decreased ReHo in the right medial frontal gyrus relative to the controls, while those with normal EEGs had significantly increased ReHo in the right inferior temporal gyrus and the left posterior cingulate gyrus. We conclude that altered BOLD signal synchrony can be detected in the cerebral and cerebellar cortices of children with TLE even in the absence of interictal EEG abnormalities., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Recent evidence on resting-state networks in functional (connectivity) magnetic resonance imaging (fcMRI) suggests that there may be significant spatial variability of activity foci over time. This study used a sliding time window approach with the spatial domain-independent component analysis (SliTICA) to detect spatial maps of resting-state networks over time. The study hypothesis was that the spatial distribution of a functionally connected network would present marked variability over time. The spatial stability of successive sliding-window maps of the default mode network (DMN) from fcMRI data of 12 participants imaged in the resting state was analyzed. Control measures support previous findings on the stability of independent component analysis in measuring sliding-window sources accurately. The spatial similarity of successive DMN maps varied over time at low frequencies and presented a 1/f power spectral pattern. SliTICA maps show marked temporal variation within the DMN; a single voxel was detected inside a group DMN map in maximally 82% of time windows. Mapping of incidental connectivity reveals centrifugally increasing connectivity to the brain cortex outside the DMN core areas. In conclusion, SliTICA shows marked spatial variance of DMN activity in time, which may offer a more comprehensive measurement of the overall functional activity of a network.

Functional MRI measured with blood oxygen dependent (BOLD) contrast in the absence of intermittent tasks reflects spontaneous activity of so-called resting state networks (RSN) of the brain. Group level independent component analysis (ICA) of BOLD data can separate the human brain cortex into 42 independent RSNs. In this study we evaluated age-related effects from primary motor and sensory, and, higher level control RSNs. One hundred sixty-eight healthy subjects were scanned and divided into three groups: 55 adolescents (ADO, 13.2 ± 2.4 years), 59 young adults (YA, 22.2 ± 0.6 years), and 54 older adults (OA, 42.7 ± 0.5 years), all with normal IQ. High model order group probabilistic ICA components (70) were calculated and dual-regression analysis was used to compare 21 RSN's spatial differences between groups. The power spectra were derived from individual ICA mixing matrix time series of the group analyses for frequency domain analysis. We show that primary sensory and motor networks tend to alter more in younger age groups, whereas associative and higher level cognitive networks consolidate and re-arrange until older adulthood. The change has a common trend: both spatial extent and the low frequency power of the RSN's reduce with increasing age. We interpret these result as a sign of normal pruning via focusing of activity to less distributed local hubs.