Significant Group-wise Differences Research Articles

Microstructural analysis does not support altered interhemispheric wiring of the human anterior commissure in corpus callosum dysgenesis

BackgroundIndividuals with corpus callosum dysgenesis (CCD) lack the clear disconnection syndrome that is characteristic of individuals in whom the corpus callosum has been surgically severed. One potential explanation for this paradox is that the anterior commissure undergoes neuroplastic remodeling in CCD to improve interhemispheric communication between the brain hemispheres. MethodsA cohort of sixteen individuals with CCD (and sixteen sex and age-matched neurotypical controls) underwent multi-shell diffusion magnetic resonance high-field imaging (dMRI) at 7-Tesla to assess the anatomy of the anterior commissure for evidence of neuroplasticity. ResultsNo significant group-wise differences in midsagittal anterior commissure volumes were detected between the CCD and control cohorts, although there were CCD individuals within the cohort who exhibited volumes that were either substantially larger or smaller than their neurotypical counterparts. Axonal intracellular volume fractions were reduced across the CCD white matter, including regions of the anterior commissure, and tractographic analyses were unable to identify any novel connections projecting through the anterior commissure that were unique to CCD individuals. Finally, variances in the neuroanatomy of the anterior commissure in the CCD cohort did not correlate with performance on neuropsychological tasks that are highly dependent upon interhemispheric communication. ConclusionsThe results of this study indicate that there are individuals within the CCD population in whom it is unlikely that the anterior commissure is the primary substrate for interhemispheric communication. Consequently, other, presently unknown, compensatory mechanisms are likely involved in supporting this function.

Cardioautonomic lability assessed by heart rate variability changes in Royal Canadian Mounted Police cadets during the cadet training program.

The current study examined variations in cardioautonomic lability during the Royal Canadian Mounted Police (RCMP) Cadet Training Program (CTP) between cadets starting their training who did or did not screen positive for one or more mental health disorders (i.e., posttraumatic stress disorder [PTSD], major depressive disorder [MDD], social anxiety disorder [SAD], generalized anxiety disorder [GAD], panic disorder [PD], alcohol use disorder [AUD]). Electrocardiogram (ECG) signals integrated into Hexoskin garments were used to record ECG and heart rate Over the 26-week CTP. There were 31 heart rate variability (HRV) parameters calculated using Kubios Premium HRV analysis software. Mann-Whitney U-tests were used to perform groupwise comparisons of participant raw values and HRV during the CTP. A total of 157 cadets (79% male) were screened for any mental disorder using self-report surveys and then grouped by positive and negative screening. Analyses indicated a statistically significant (p < 0.05) decrease in low frequency (LF): High Frequency (HF) variability during CTP, but only for cadets who endorsed clinically significant anxiety symptoms on the GAD-7 at the start of their training. There were no other statistically significant groupwise differences. The results indicate the participants have excellent cardiac health overall and suggest potentially important differences between groups, such that cadets who endorsed clinically significant anxiety symptoms on the GAD-7 showed less variability in the LF:HF ratio over the course of the CTP. The relatively lower variability suggests decreased parasympathetic tone in those without clinically significant anxiety symptoms. The results also have important implications for future investigations of cardioautonomic dysfunction and chronic hypothalamic pituitary adrenal (HPA) axis deviations in policing populations with anxiety disorders; specifically, cardioautonomic inflexibility related to cardiovascular morbidity and mortality. In any case, the current results provide an important baseline for future cardiac research with cadets and serving officers.

How the body remembers: Examining the default mode and sensorimotor networks during moral injury autobiographical memory retrieval in PTSD

Neural representations of sensory percepts and motor responses constitute key elements of autobiographical memory. However, these representations may remain as unintegrated sensory and motor fragments in traumatic memory, thus contributing toward re-experiencing and reliving symptoms in trauma-related conditions such as post-traumatic stress disorder (PTSD). Here, we investigated the sensorimotor network (SMN) and posterior default mode network (pDMN) using a group independent component analysis (ICA) by examining their functional connectivity during a script-driven memory retrieval paradigm of (potentially) morally injurious events in individuals with PTSD and healthy controls. Moral injury (MI), where an individual acts or fails to act in a morally aligned manner, is examined given its inherent ties to disrupted motor planning and thus sensorimotor mechanisms. Our findings revealed significant differences in functional network connectivity across the SMN and pDMN during MI retrieval in participants with PTSD (n = 65) as compared to healthy controls (n = 25). No such significant group-wise differences emerged during retrieval of a neutral memory. PTSD-related alterations included hyperconnectivity between the SMN and pDMN, enhanced within-network connectivity of the SMN with premotor areas, and increased recruitment of the supramarginal gyrus into both the SMN and the pDMN during MI retrieval. In parallel with these neuroimaging findings, a positive correlation was found between PTSD severity and subjective re-experiencing intensity ratings after MI retrieval. These results suggest a neural basis for traumatic re-experiencing, where reliving and/or re-enacting a past morally injurious event in the form of sensory and motor fragments occurs in place of retrieving a complete, past-contextualized narrative as put forth by Brewin and colleagues (1996) and Conway and Pleydell-Pearce (2000). These findings have implications for bottom-up treatments targeting directly the sensory and motoric elements of traumatic experiences.

Three months-longitudinal changes in relative telomere length, blood chemistries, and self-report questionnaires in meditation practitioners compared to novice individuals during midlife.

Aging accelerates during midlife. Researches have shown the health benefits of mind-body intervention (MBI). However, whether MBI is involved with aging process has not been well understood. In this study, we approach to examine the relations of MBI with this process by investigating an aging marker of the peripheral blood, blood chemistry, and self-report questionnaires. A quasi-experimental design was applied. Experienced MBI practitioners participated in a 3-month intensive meditation training, while the age, gender-matched MBI-naïve controls led a normal daily life. Measurements were taken at before and after the 3 months for relative telomere length (RTL), blood chemistry, and self-report questionnaires including items about sleep quality, somatic symptoms, depression, anxiety, stress, emotional intelligence (EI), and self-regulation. For RTL, the repeated measures analysis of variance showed a significant group*time interaction (P = .013) with a significant post hoc result (P = .030) within the control group: RTL was significantly reduced in the control while it was maintained in the meditation group. In repeated measures analysis of variance for blood chemistries, there were significant group differences between the groups in glucose and total protein. In the post hoc comparison analysis, at post measurements, the meditation group exhibited significantly lower values than the control group in both glucose and total protein. There were significant group-wise differences in the correlations of RTL with triglyceride (TG), high-density lipoprotein (HDL), glutamic oxaloacetic transaminase and glutamic pyruvic transaminase. Any of self-report results did not show significant changes in group*time interaction. However, there were group differences with significant (P < .05) or a tendency (.05 < P < .1) level. There were significant improvements in depression, stress and EI as well as tendencies of improvement in sleep quality and anxiety, in the meditation group compared to the control group. Our results suggest that meditation practice may have a potential to modify aging process in molecular cellular level combined with changes in psychological dimension.

Longitudinal evaluation of proton magnetic resonance spectroscopy metabolites as biomarkers in Huntington's disease.

Proton magnetic resonance spectroscopy is a non-invasive method of exploring cerebral metabolism. In Huntington's disease, altered proton magnetic resonance spectroscopy-determined concentrations of several metabolites have been described; however, findings are often discrepant and longitudinal studies are lacking. Proton magnetic resonance spectroscopy metabolites may represent a source of biomarkers, thus their relationship with established markers of disease progression require further exploration to assess prognostic value and elucidate pathways associated with neurodegeneration. In a prospective single-site controlled cohort study with standardized collection of CSF, blood, phenotypic and volumetric imaging data, we used 3 T proton magnetic resonance spectroscopy in conjunction with the linear combination of model spectra method to quantify seven metabolites (total n-acetylaspartate, total creatine, total choline, myo-inositol, GABA, glutamate and glutathione) in the putamen of 59 participants at baseline (15 healthy controls, 15 premanifest and 29 manifest Huntington's disease gene expansion carriers) and 48 participants at 2-year follow-up (12 healthy controls, 13 premanifest and 23 manifest Huntington's disease gene expansion carriers). Intergroup differences in concentration and associations with CSF and plasma biomarkers; including neurofilament light chain and mutant Huntingtin, volumetric imaging markers; namely whole brain, caudate, grey matter and white matter volume, measures of disease progression and cognitive decline, were assessed cross-sectionally using generalized linear models and partial correlation. We report no significant groupwise differences in metabolite concentration at baseline but found total creatine and total n-acetylaspartate to be significantly reduced in manifest compared with premanifest participants at follow-up. Additionally, total creatine and myo-inositol displayed significant associations with reduced caudate volume across both time points in gene expansion carriers. Although relationships were observed between proton magnetic resonance spectroscopy metabolites and biofluid measures, these were not consistent across time points. To further assess prognostic value, we examined whether baseline proton magnetic resonance spectroscopy values, or rate of change, predicted subsequent change in established measures of disease progression. Several associations were found but were inconsistent across known indicators of disease progression. Finally, longitudinal mixed-effects models revealed glutamine + glutamate to display a slow linear decrease over time in gene expansion carriers. Altogether, our findings show some evidence of reduced total n-acetylaspartate and total creatine as the disease progresses and cross-sectional associations between select metabolites, namely total creatine and myo-inositol, and markers of disease progression, potentially highlighting the proposed roles of neuroinflammation and metabolic dysfunction in disease pathogenesis. However, the absence of consistent group differences, inconsistency between baseline and follow-up, and lack of clear longitudinal change suggests that proton magnetic resonance spectroscopy metabolites have limited potential as Huntington's disease biomarkers.

Status epilepticus during the COVID-19 pandemic in Cologne, Germany: data from a retrospective, multicentre registry

BackgroundThe “coronavirus disease 2019” (COVID-19) pandemic, caused by the “severe-acute-respiratory-syndrome-coronavirus 2” (SARS-CoV-2), challenges healthcare systems worldwide and impacts not only COVID-19 patients but also other emergencies. To date, data are scarce on the extent to which the COVID-19 pandemic impacted status epilepticus (SE) and its treatment.ObjectiveTo assess the influence of the COVID-19 pandemic on the incidence, management and outcome of SE patients.Study designThis is a retrospective, multicentre trial, approved by the University of Cologne (21-1443-retro).MethodsAll SE patients from the urban area of Cologne transmitted to all acute neurological departments in Cologne between 03/2019 and 02/2021 were retrospectively analysed and assessed for patient characteristics, SE characteristics, management, and outcome in the first pandemic year compared to the last pre-pandemic year.Results157 pre-pandemic (03/2019–02/2020) and 171 pandemic (from 03/2020 to 02/2021) SE patients were included in the analyses. Acute SARS-CoV-2 infections were rarely detected. Patient characteristics, management, and outcome did not reveal significant groupwise differences. In contrast, regarding prehospital management, a prolonged patient transfer to the hospital and variations in SE aetiologies compared to the last pre-pandemic year were observed with less chronic vascular and more cryptogenic and anoxic SE cases. No infections with SARS-CoV-2 occurred during inpatient stays.ConclusionsSARS-CoV-2 infections did not directly affect SE patients, but the transfer of SE patients to emergency departments was delayed. Interestingly, SE aetiology rates shifted, which warrants further exploration. Fears of contracting an in-hospital SARS-CoV-2-infection were unfounded due to consequent containment measures.

Prediction of prostate cancer grade using fractal analysis of perfusion MRI: retrospective proof-of-principle study

ObjectivesMultiparametric MRI has high diagnostic accuracy for detecting prostate cancer, but non-invasive prediction of tumor grade remains challenging. Characterizing tumor perfusion by exploiting the fractal nature of vascular anatomy might elucidate the aggressive potential of a tumor. This study introduces the concept of fractal analysis for characterizing prostate cancer perfusion and reports about its usefulness for non-invasive prediction of tumor grade.MethodsWe retrospectively analyzed the openly available PROSTATEx dataset with 112 cancer foci in 99 patients. In all patients, histological grading groups specified by the International Society of Urological Pathology (ISUP) were obtained from in-bore MRI-guided biopsy. Fractal analysis of dynamic contrast-enhanced perfusion MRI sequences was performed, yielding fractal dimension (FD) as quantitative descriptor. Two-class and multiclass diagnostic accuracy was analyzed using area under the curve (AUC) receiver operating characteristic analysis, and optimal FD cutoffs were established. Additionally, we compared fractal analysis to conventional apparent diffusion coefficient (ADC) measurements.ResultsFractal analysis of perfusion allowed accurate differentiation of non-significant (group 1) and clinically significant (groups 2–5) cancer with a sensitivity of 91% (confidence interval [CI]: 83–96%) and a specificity of 86% (CI: 73–94%). FD correlated linearly with ISUP groups (r2 = 0.874, p < 0.001). Significant groupwise differences were obtained between low, intermediate, and high ISUP group 1–4 (p ≤ 0.001) but not group 5 tumors. Fractal analysis of perfusion was significantly more reliable than ADC in predicting non-significant and clinically significant cancer (AUCFD = 0.97 versus AUCADC = 0.77, p < 0.001).ConclusionFractal analysis of perfusion MRI accurately predicts prostate cancer grading in low-, intermediate-, and high-, but not highest-grade, tumors.Key Points• In 112 prostate carcinomas, fractal analysis of MR perfusion imaging accurately differentiated low-, intermediate-, and high-grade cancer (ISUP grade groups 1–4).• Fractal analysis detected clinically significant prostate cancer with a sensitivity of 91% (83–96%) and a specificity of 86% (73–94%).• Fractal dimension of perfusion at the tumor margin may provide an imaging biomarker to predict prostate cancer grading.

Quantitative magnetic resonance imaging of meniscal pathology ex vivo

ObjectiveTo determine the ability of conventional spin echo (SE) T2 and ultrashort echo time (UTE) T2* relaxation times to characterize pathology in cadaveric meniscus samples.Materials and methodsFrom 10 human donors, 54 triangular (radially cut) meniscus samples were harvested. Meniscal pathology was classified as normal (n = 17), intrasubstance degenerated (n = 33), or torn (n = 4) using a modified arthroscopic grading system. Using a 3-T MR system, SE T2 and UTE T2* values of the menisci were determined, followed by histopathology. Effect of meniscal pathology on relaxation times and histology scores were determined, along with correlation between relaxation times and histology scores.ResultsMean ± standard deviation UTE T2* values for normal, degenerated, and torn menisci were 3.6 ± 1.3 ms, 7.4 ± 2.5 ms, and 9.8 ± 5.7 ms, respectively, being significantly higher in degenerated (p < 0.0001) and torn (p = 0.0002) menisci compared to that in normal. In contrast, the respective mean SE T2 values were 27.7 ± 9.5 ms, 25.9 ± 7.0 ms, and 35.7 ± 10.4 ms, without significant differences between groups (all p > 0.14). In terms of histology, we found significant group-wise differences (each p < 0.05) in fiber organization and inner-tip surface integrity sub-scores, as well as the total score. Finally, we found a significant weak correlation between UTE T2* and histology total score (p = 0.007, Rs2 = 0.19), unlike the correlation between SE T2 and histology (p = 0.09, Rs2 = 0.05).ConclusionUTE T2* values were found to distinguish normal from both degenerated and torn menisci and correlated significantly with histopathology.

Properties of Lexical Diversity in the Narratives of Children With Typical Language Development and Developmental Language Disorder.

Purpose We examined four measures of lexical diversity in the narratives of children with typical language development (TLD) and developmental language disorder (DLD) that comprised the normative sample of the Edmonton Narrative Norms Instrument (Schneider et al., 2005). The purpose was to document the properties of each measure with respect to variations in utterance and sample length, developmental trends, and group differences. Method The sample consisted of 377 picture-elicited, story generation transcripts from children with TLD (n = 300) and DLD (n = 77) aged 4-9 years. We extracted the moving-average type-token ratio (MATTR) and the number of different words from the full sample, from samples equated for the number of utterances, and from samples equated for the total number of words. Results MATTR was the only measure to show no relationships to utterance or sample length. All measures showed significant positive growth with age and significant groupwise differences between children with TLD and DLD. However, the magnitude of age effects and differentiation between groups varied considerably across measures. Across measures, there were significant differences in the number of children with DLD who were identified with low lexical diversity relative to their same-age peers in the TLD group. Conclusion The results of this study support the view that different measures of lexical diversity may be appropriate for different clinical purposes. It is important for clinicians to understand how measures of lexical diversity function in order to make educated choices among measures and ensure appropriate interpretation.

Preliminary Assessment of Intravoxel Incoherent Motion Diffusion-Weighted MRI (IVIM-DWI) Metrics in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects aging populations. Current MRI techniques are often limited in their sensitivity to underlying neuropathological changes. To characterize differences in voxel-based morphometry (VBM), apparent diffusion coefficient (ADC), and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) metrics in aging populations. Additionally, to investigate the connection between cognitive assessments and neuroimaging metrics. Prospective/cross-sectional. In all, 49 subjects, including 13 with AD dementia, 12 with mild cognitive impairment (MCI), and 24 healthy controls (HC). 3T/magnetization-prepared rapid acquisition gradient echo (MP-RAGE) and IVIM-DWI ASSESSMENT: All participants completed a cognitive screening battery prior to MRI. IVIM-DWI maps (pure diffusion coefficient [D], pseudodiffusion coefficient [D*], and perfusion fraction [f]) were generated from a biexponential fit of diffusion MRI data. VBM was performed on the standard T1 -weighted MP-RAGE structural images. Group-wise templates were used to compare across groups. Analysis of covariance (ANCOVA) with gender and age as covariates (familywise error [FWE] corrected, post-hoc comparisons using Bonferroni correction) for group comparisons. Partial-η2 and Hedges' g were used for effect-size analysis. Spearman's correlations (false discovery rate [FDR]-corrected) for the relationship between cognitive scores and imaging. Clusters of significant group-wise differences were found mainly in the temporal lobe, hippocampus, and amygdala using all VBM and IVIM methods (P < 0.05 FWE). While VBM showed significant changes between MCI and AD groups and between HC and AD groups, no significant clusters were observed between HC and MCI using VBM. ADC and IVIM-D demonstrated significant changes, at P < 0.05 FWE, between HC and MCI, notably in the amygdala and hippocampus. Several voxel-based correlations were observed between neuroimaging metrics and cognitive tests within the cognitively impaired groups (P < 0.05 FDR). These findings suggest that IVIM-DWI metrics may be earlier biomarkers for AD-related changes than VBM. The use of these techniques may provide novel insight into subvoxel neurodegenerative processes. 2 TECHNICAL EFFICACY STAGE: 2 J. MAGN. RESON. IMAGING 2020;52:1811-1826.

Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum.

The clinical syndromes of frontotemporal dementia are clinically and neuropathologically heterogeneous, but processes such as neuroinflammation may be common across the disease spectrum. We investigated how neuroinflammation relates to the localization of tau and TDP-43 pathology, and to the heterogeneity of clinical disease. We used PET in vivo with (i) 11C-PK-11195, a marker of activated microglia and a proxy index of neuroinflammation; and (ii) 18F-AV-1451, a radioligand with increased binding to pathologically affected regions in tauopathies and TDP-43-related disease, and which is used as a surrogate marker of non-amyloid-β protein aggregation. We assessed 31 patients with frontotemporal dementia (10 with behavioural variant, 11 with the semantic variant and 10 with the non-fluent variant), 28 of whom underwent both 18F-AV-1451 and 11C-PK-11195 PET, and matched control subjects (14 for 18F-AV-1451 and 15 for 11C-PK-11195). We used a univariate region of interest analysis, a paired correlation analysis of the regional relationship between binding distributions of the two ligands, a principal component analysis of the spatial distributions of binding, and a multivariate analysis of the distribution of binding that explicitly controls for individual differences in ligand affinity for TDP-43 and different tau isoforms. We found significant group-wise differences in 11C-PK-11195 binding between each patient group and controls in frontotemporal regions, in both a regions-of-interest analysis and in the comparison of principal spatial components of binding. 18F-AV-1451 binding was increased in semantic variant primary progressive aphasia compared to controls in the temporal regions, and both semantic variant primary progressive aphasia and behavioural variant frontotemporal dementia differed from controls in the expression of principal spatial components of binding, across temporal and frontotemporal cortex, respectively. There was a strong positive correlation between 11C-PK-11195 and 18F-AV-1451 uptake in all disease groups, across widespread cortical regions. We confirmed this association with post-mortem quantification in 12 brains, demonstrating strong associations between the regional densities of microglia and neuropathology in FTLD-TDP (A), FTLD-TDP (C), and FTLD-Pick's. This was driven by amoeboid (activated) microglia, with no change in the density of ramified (sessile) microglia. The multivariate distribution of 11C-PK-11195 binding related better to clinical heterogeneity than did 18F-AV-1451: distinct spatial modes of neuroinflammation were associated with different frontotemporal dementia syndromes and supported accurate classification of participants. These in vivo findings indicate a close association between neuroinflammation and protein aggregation in frontotemporal dementia. The inflammatory component may be important in shaping the clinical and neuropathological patterns of the diverse clinical syndromes of frontotemporal dementia.

Hearing Thresholds in Young Children With Otitis Media With Effusion With and Without Cleft Palate.

To investigate hearing thresholds in children born with cleft palate and in children with otitis media with effusion but no cleft palate. Prospective longitudinal group comparison study. University hospital. Sixteen children born with nonsyndromic cleft palate with or without cleft lip (CP±L) and 15 age-matched children with otitis media with effusion (OME) but without cleft. Hearing was tested at repeated occasions beginning with neonatal auditory brainstem response (ABR) at 1-4 months of age, and age-appropriate hearing tests from 9 to 36 months of age. The median ABR thresholds in both groups were elevated but did not differ significantly. At 12 months of age, the median 4 frequency averages at 500-1000-2000-4000 Hz (4FA) were indicative of mild hearing loss but significantly better in the CP±L-group than in the group without cleft (P < .01). There were no significant group-wise differences regarding the median 4FA at 24 and 36 months of age, and at 36 months, the median 4FA were normal in both groups. Both groups exhibited a significant improvement over time from the neonatal ABR thresholds to the 4FA at 36 months (CP±L-group P < .05; without CP±L-group P < .01). The hearing loss in children with CP±L was not more severe than among children with OME but without cleft palate; rather, at 12 months of age, the thresholds were significantly better in the CP±L-group than those in the group without cleft. The air conduction thresholds improved with age in both groups.

Primary Open Angle Glaucoma Is Associated With Functional Brain Network Reorganization.

Background: Resting-state functional magnetic resonance imaging (rs-fMRI) is commonly employed to study changes in functional brain connectivity. The recent hypothesis of a brain involvement in primary open angle Glaucoma has sprung interest for neuroimaging studies in this classically ophthalmological pathology.Object: We explored a putative reorganization of functional brain networks in Glaucomatous patients, and evaluated the potential of functional network disruption indices as biomarkers of disease severity in terms of their relationship to clinical variables as well as select retinal layer thicknesses.Methods: Nineteen Glaucoma patients and 16 healthy control subjects (age: 50–76, mean 61.0 ± 8.2 years) underwent rs-fMRI examination at 3T. After preprocessing, rs-fMRI time series were parcellated into 116 regions using the Automated Anatomical Labeling atlas and adjacency matrices were computed based on partial correlations. Graph-theoretical measures of integration, segregation and centrality as well as group-wise and subject-wise disruption index estimates (which use regression of graph-theoretical metrics across subjects to quantify overall network changes) were then generated for all subjects. All subjects also underwent Optical Coherence Tomography (OCT) and visual field index (VFI) quantification. We then examined associations between brain network measures and VFI, as well as thickness of retinal nerve fiber layer (RNFL) and macular ganglion cell layer (MaculaGCL).Results: In Glaucoma, group-wise disruption indices were negative for all graph theoretical metrics. Also, we found statistically significant group-wise differences in subject-wise disruption indexes in all local metrics. Two brain regions serving as hubs in healthy controls were not present in the Glaucoma group. Instead, three hub regions were present in Glaucoma patients but not in controls. We found significant associations between all disruption indices and VFI, RNFL as well as MaculaGCL. The disruption index based on the clustering coefficient yielded the best discriminative power for differentiating Glaucoma patients from healthy controls [Area Under the ROC curve (AUC) 0.91, sensitivity, 100%; specificity, 78.95%].Conclusions: Our findings support a possible relationship between functional brain changes and disease severity in Glaucoma, as well as alternative explanations for motor and cognitive symptoms in Glaucoma, possibly pointing toward an inclusion of this pathology in the heterogeneous group of disconnection syndromes.

Disruption of brain network organization in primary open angle glaucoma.

Resting-state functional magnetic resonance imaging (rs-fMRI) is commonly employed to study changes in functional brain connectivity. Recently, the hypothesis of a brain involvement in primary open angle glaucoma has sprung interest for neuroimaging studies in this pathology. The purpose of this study is to evaluate a putative reorganization of brain networks in glaucomatous patients through graph-theoretical measures of integration, segregation and centrality by exploiting a multivariate networks association measure and a recently introduced global and local brain network disruption index. Nineteen glaucoma patients and sixteen healthy control subjects (age: 50 - 76, mean 61 years) underwent rs-fMRI examination at 3T. After preprocessing, rs-fMRI time series were parcellated into 116 regions (AAL atlas), adjacency matrices were computed based on partial correlations and graph-theoretical measures of integration, segregation and centrality as well as group-wise and subject-wise disruption index estimates were generated for all subjects. We found that the group-wise disruption index was negative and statistically different from 0 in for all graph theoretical metrics. Additionally, statistically significant group-wise differences in subject-wise disruption indexes were found in all local metrics. The differences in local network measures highlight cerebral reorganization of brain networks in glaucoma patients, supporting the interpretation of glaucoma as central nervous system disease, likely part of the heterogeneous group of recently described disconnection syndromes.

LOCALIZING DIFFERENTIALLY EVOLVING COVARIANCE STRUCTURES VIA SCAN STATISTICS.

Recent results in coupled or temporal graphical models offer schemes for estimating the relationship structure between features when the data come from related (but distinct) longitudinal sources. A novel application of these ideas is for analyzing group-level differences, i.e., in identifying if trends of estimated objects (e.g., covariance or precision matrices) are different across disparate conditions (e.g., gender or disease). Often, poor effect sizes make detecting the differential signal over the full set of features difficult: for example, dependencies between only a subset of features may manifest differently across groups. In this work, we first give a parametric model for estimating trends in the space of SPD matrices as a function of one or more covariates. We then generalize scan statistics to graph structures, to search over distinct subsets of features (graph partitions) whose temporal dependency structure may show statistically significant group-wise differences. We theoretically analyze the Family Wise Error Rate (FWER) and bounds on Type 1 and Type 2 error. Evaluating on US census data, we identify groups of states with cultural and legal overlap related to baby name trends and drug usage. On a cohort of individuals with risk factors for Alzheimer's disease (but otherwise cognitively healthy), we find scientifically interesting group differences where the default analysis, i.e., models estimated on the full graph, do not survive reasonable significance thresholds.

The influences of smartphone use on the status of the tear film and ocular surface.

PurposeTo investigate the influences of smartphone use on ocular symptoms, status of the tear film, and oxidative stress indices in the tears and at the ocular surface.MethodsEighty healthy volunteers were enrolled in the study. Subjective symptoms and asthenopia were evaluated using the ocular surface disease index (OSDI), visual analogue scale (VAS), and computer vision syndrome (CVS) score before and after smartphone or computer display (control) use. The status of the tear film was evaluated using fluorescein film break-up time (FBUT), non-invasive keratograph break up time (NIKBUT), Schirmer score, keratoepitheliopathy (KEP), and tear meniscus height (TMH). Oxidative stress markers in the tear film including hexanoyl lysine (HEL), 4-hydroxy-2-nonenal (4-HNE), malondialdehyde (MDA), and 8-oxo-2’-deoxyguanosine (8-OHdG) in the tear film were measured using ELISA. Reactive oxygen species (ROS) at the ocular surface were measured through 2’,7’-dichloro-dihydrofluorescein diacetate. All measurements were conducted at baseline, and after use for 1 and 4 h.ResultsAll parameters showed no significant group-wise differences at baseline. Scores of OSDI, VAS, fatigue, burning sensation, and dryness showed significant increases after 1 and 4 h of smartphone use compared with those at baseline (all P < 0.05). The smartphone group showed higher OSDI, fatigue, burning, and dryness scores than the control group at 4 h. Smartphone use showed significantly decreased FBUT and NIBUT at 4 h than those at baseline (P < 0.01). In the smartphone group, the concentration of HEL significantly increased at 4 h compared with that at baseline and 1 h (P < 0.01). Both groups showed increased ROS with higher value in the smartphone group versus the control group at 4 h (P < 0.01).ConclusionsSmartphone use could not only aggravate subjective symptom indices such as the OSDI, VAS, and CVS but also induce tear film instability and oxidative stress indices in the tears and at the ocular surface.

Early breast milk exposure modifies brain connectivity in preterm infants

Preterm infants are at increased risk of alterations in brain structure and connectivity, and subsequent neurocognitive impairment. Breast milk may be more advantageous than formula feed for promoting brain development in infants born at term, but uncertainties remain about its effect on preterm brain development and the optimal nutritional regimen for preterm infants. We test the hypothesis that breast milk exposure is associated with improved markers of brain development and connectivity in preterm infants at term equivalent age.We collected information about neonatal breast milk exposure and brain MRI at term equivalent age from 47 preterm infants (mean postmenstrual age [PMA] 29.43 weeks, range 23.28–33.0). Network-Based Statistics (NBS), Tract-based Spatial Statistics (TBSS) and volumetric analysis were used to investigate the effect of breast milk exposure on white matter water diffusion parameters, tissue volumes, and the structural connectome.Twenty-seven infants received exclusive breast milk feeds for ≥75% of days of in-patient care and this was associated with higher connectivity in the fractional anisotropy (FA)-weighted connectome compared with the group who had < 75% of days receiving exclusive breast milk feeds (NBS, p = 0.04). Within the TBSS white matter skeleton, the group that received ≥75% exclusive breast milk days exhibited higher FA within the corpus callosum, cingulum cingulate gyri, centrum semiovale, corticospinal tracts, arcuate fasciculi and posterior limbs of the internal capsule compared with the low exposure group after adjustment for PMA at birth, PMA at image acquisition, bronchopulmonary dysplasia, and chorioamnionitis (p < 0.05). The effect on structural connectivity and tract water diffusion parameters was greater with ≥90% exposure, suggesting a dose effect. There were no significant groupwise differences in brain volumes.Breast milk feeding in the weeks after preterm birth is associated with improved structural connectivity of developing networks and greater FA in major white matter fasciculi.

Assessment of linear and nonlinear/complex heartbeat dynamics in subclinical depression (dysphoria)

Objective: Depression is one of the leading causes of disability worldwide. Most previous studies have focused on major depression, and studies on subclinical depression, such as those on so-called dysphoria, have been overlooked. Indeed, dysphoria is associated with a high prevalence of somatic disorders, and a reduction of quality of life and life expectancy. In current clinical practice, dysphoria is assessed using psychometric questionnaires and structured interviews only, without taking into account objective pathophysiological indices. To address this problem, in this study we investigated heartbeat linear and nonlinear dynamics to derive objective autonomic nervous system biomarkers of dysphoria. Approach: Sixty undergraduate students participated in the study: according to clinical evaluation, 24 of them were dysphoric. Extensive group-wise statistics was performed to characterize the pathological and control groups. Moreover, a recursive feature elimination algorithm based on a K-NN classifier was carried out for the automatic recognition of dysphoria at a single-subject level. Main results: The results showed that the most significant group-wise differences referred to increased heartbeat complexity (particularly for fractal dimension, sample entropy and recurrence plot analysis) with regards to the healthy controls, confirming dysfunctional nonlinear sympatho-vagal dynamics in mood disorders. Furthermore, a balanced accuracy of 79.17% was achieved in automatically distinguishing dysphoric patients from controls, with the most informative power attributed to nonlinear, spectral and polyspectral quantifiers of cardiovascular variability. Significance: This study experimentally supports the assessment of dysphoria as a defined clinical condition with specific characteristics which are different both from healthy, fully euthymic controls and from full-blown major depression.

Abnormal functional connectivity density in sleep-deprived subjects.

Sleep deprivation (SD) can alter the intrinsic brain functional organization. However, its effects on intrinsic low-frequency connectivity in the whole brain have not been well characterized. In this study, we used voxel-based functional connectivity density (FCD) analysis to investigate the effects of SD on the spontaneous functional organization of the brain. Thirty-seven healthy participants underwent this within-subject crossover functional magnetic resonance imaging (fMRI) study during rested wakefulness (RW) and after 36h of total sleep deprivation (TSD). Decreased long-/short-range FCDs were observed in the posterior cingulate cortex, precuneus, inferior parietal lobule, dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, and ventromedial prefrontal cortex. Increased long-/short-range FCDs were found in the sensory integration and arousal regulating areas, including the postcentral gyrus, thalamus, superior temporal gyrus, and occipital-temporal cortex. Moreover, a significant negative correlation was found between the short-range FCD of the PCC and the reaction time of Psychomotor Vigilance Task. In the present study, spontaneous functional organization with significant group-wise differences between RW and TSD sessions was identified. Our findings extend our understanding of the neural mechanism of how brain activity is altered in sleep-deprived individuals.

Autism Spectrum Disorder Related Functional Connectivity Changes in the Language Network in Children, Adolescents and Adults

Autism spectrum disorder (ASD) is a neurodevelopmental disability with global implication. Altered brain connectivity in the language network has frequently been reported in ASD patients using task-based functional magnetic resonance imaging (fMRI) compared to typically developing (TD) participants. Most of these studies have focused on a specific age group or mixed age groups with ASD. In the current study, we investigated age-related changes in functional connectivity related measure, degree centrality (DC), in the language network across three age groups with ASD (113 children, 113 adolescents and 103 adults) using resting-state fMRI data collected from the autism brain imaging data exchange repository. We identified regions with significant group-wise differences between ASD and TD groups for three age cohorts using DC based on graph theory. We found that both children and adolescents with ASD showed decreased DC in Broca’s area compared to age-matched TD groups. Adults with ASD showed decreased DC in Wernicke’s area compared to TD adults. We also observed increased DC in the left inferior parietal lobule (IPL) and left middle temporal gyrus (MTG) for children with ASD compared to TD children and for adults with ASD compared to TD adults, respectively. Overall, functional differences occurred in key language processing regions such as the left inferior frontal gyrus (IFG) and superior temporal gyrus (STG) related to language production and comprehension across three age cohorts. We explored correlations between DC values of our findings with autism diagnostic observation schedule (ADOS) scores related to severity of ASD symptoms in the ASD group. We found that DC values of the left IFG demonstrated negative correlations with ADOS scores in children and adolescents with ASD. The left STG showed significant negative correlations with ADOS scores in adults with ASD. These results might shed light on the language network regions that should be further explored for prognosis, diagnosis, and monitoring of ASD in three age groups.