Short-range Functional Connectivity Research Articles

T1-/T2-weighted ratio reveals no alterations to gray matter myelination in temporal lobe epilepsy.

Short-range functional connectivity in the limbic network is increased in patients with temporal lobe epilepsy (TLE), and recent studies have shown that cortical myelin content correlates with fMRI connectivity. We thus hypothesized that myelin may increase progressively in the epileptic network. We compared T1w/T2w gray matter myelin maps between TLE patients and age-matched controls and assessed relationships between myelin and aging. While both TLE patients and healthy controls exhibited increased T1w/T2w intensity with age, we found no evidence for significant group-level aberrations in overall myelin content or myelin changes through time in TLE.

Brain regional homogeneity and its association with age and intelligence in typically developing youth.

Accelerated synaptic pruning and weakening of short-range functional connectivity are characteristic of adolescent brain development. Based on these structural microscopic and system-level functional changes, it was hypothesized that regional homogeneity (ReHo) may decrease with age in the developing brain, and a differential association between ReHo and cognitive performance was expected to depend on age. ReHo maps of typically developing participants were provided by the Attention-Deficit/Hyperactivity Disorder (ADHD)-200 Preprocessed repository. Intelligence quotient was evaluated using the Wechsler Intelligence Scale for Chinese Children-Revised and Wechsler Abbreviated Scale of Intelligence at Peking University and New York University, respectively. Correlations between ReHo and age were examined, along with the interaction effects of ReHo and age on intelligence quotient (IQ), in 121 typically developing youth aged 8-14 years. Of the 400 ROIs tested, ReHo in 105 brain regions was significantly correlated with age (p<0.05, false discovery rate-corrected), among which 102 showed that ReHo decreased with age. In addition, ReHo in 18 brain regions was negatively correlated with age at Bonferroni-corrected thresholds (p<0.05), and most associations were observed in the prefrontal cortex. The interaction analyses suggested that higher ReHo was associated with higher IQ in children, whereas this association was attenuated or reversed in adolescents (p<0.05, uncorrected). ReHo decreased with age in the developing brain and was differentially associated with intelligence in children and adolescents.

Atypical local brain connectivity in pediatric autism spectrum disorder? A coordinate-based meta-analysis of regional homogeneity studies

Despite decades of massive neuroimaging research, the comprehensive characterization of short-range functional connectivity in autism spectrum disorder (ASD) remains a major challenge for scientific advances and clinical translation. From the theoretical point of view, it has been suggested a generalized local over-connectivity that would characterize ASD. This stance is known as the general local over-connectivity theory. However, there is little empirical evidence supporting such hypothesis, especially with regard to pediatric individuals with ASD (age ≤\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\le$$\\end{document} 18 years old). To explore this issue, we performed a coordinate-based meta-analysis of regional homogeneity studies to identify significant changes of local connectivity. Our analyses revealed local functional under-connectivity patterns in the bilateral posterior cingulate cortex and superior frontal gyrus (key components of the default mode network) and in the bilateral paracentral lobule (a part of the sensorimotor network). We also performed a functional association analysis of the identified areas, whose dysfunction is clinically consistent with the well-known deficits affecting individuals with ASD. Importantly, we did not find relevant clusters of local hyper-connectivity, which is contrary to the hypothesis that ASD may be characterized by generalized local over-connectivity. If confirmed, our result will provide a valuable insight into the understanding of the complex ASD pathophysiology.

Abnormal long- and short-range functional connectivity in patients with first-episode drug-naïve melancholic and non-melancholic major depressive disorder

BackgroundWe attempted to explore the common and distinct long- and short-range functional connectivity (FC) patterns of melancholic and non-melancholic major depressive disorder (MDD) and their associations with clinical characteristics. MethodsFifty-nine patients with first-episode drug-naïve MDD, including 31 patients with melancholic features and 28 patients with non-melancholic features, underwent resting-state functional magnetic resonance imaging (fMRI) scanning to examine long- and short-range FC. Thirty-two healthy volunteers were recruited as controls. The support vector machines (SVM) was applied to distinguish the melancholic patients from the non-melancholic patients by using the FC of abnormal brain regions. ResultsCompared to healthy volunteers, patients with MDD showed increased long-range positive FC (lpFC) in the right insula/inferior frontal gyrus and left insula. Relative to non-melancholic patients, melancholic patients displayed decreased lpFC in the right lingual gyrus, decreased short-range positive FC (spFC) in the right middle temporal gyrus and right superior parietal lobule, increased lpFC in the left inferior parietal lobule, and increased spFC in the left middle occipital gyrus/inferior occipital gyrus, left cerebellum VII/IX, and bilateral cerebellum CrusII. Increased lpFC in the left inferior parietal lobule in melancholic patients was correlated with the TEPS abstract anticipatory scores. SVM results showed that FCs of five combinations within different brain regions could distinguish melancholic patients from non-melancholic patients. ConclusionsFC abnormalities in the default mode network and parietal-occipital brain regions may underlie the neurobiology of melancholic MDD. An increased lpFC in the left inferior parietal lobule correlated with anhedonia may be a distinctive neurobiological feature of melancholic MDD.

Altered Long- and Short-Range Functional Connectivity Density in Patients With Thyroid-Associated Ophthalmopathy: A Resting-State fMRI Study.

Background and PurposeAlthough previous neuroimaging studies have demonstrated emotion- and psychology-associated brain abnormalities in patients with thyroid-associated ophthalmopathy (TAO), the changes of brain functional connectivity in TAO were seldom focused. We aimed to investigate interregional and intraregional functional interactions in patients with TAO by using resting-state functional MRI (rs-fMRI) with long- and short-range functional connectivity density (FCD) analysis.MethodsThirty patients with TAO and 30 well-matched healthy controls (HCs) were recruited in our study. Long- and short-range FCD values were calculated and compared between the two groups. Correlations between long- and short-range FCD values and clinical indicators were analyzed.ResultsCompared with HCs, patients with showed both increased long- and short-range FCDs in the left middle frontal gyrus (MFG), orbital part of superior frontal gyrus (ORBsup), and dorsolateral part of superior frontal gyrus (SFGdor); meanwhile, both decreased long- and short-range FCDs in bilateral postcentral gyrus (PoCG), left superior parietal gyrus (SPG), and inferior parietal (IPL). In addition, patients with TAO showed increased short-range FCD in the right SFGdor, bilateral medial part of superior frontal gyrus (SFGmed), left orbital part of middle frontal gyrus (ORBmid), and orbital part of inferior frontal gyrus (ORBinf), as well as decreased short-range FCD in the right supplementary motor area (SMA) and the left paracentral lobule (PCL) than HCs. Moreover, the short-range value in the left SFGdor showed a negative correlation with Montreal Cognitive Assessment (MoCA) score (r = −0.501, p = 0.005).ConclusionOur findings complemented the functional neural mechanism of TAO, and provided potential neuroimaging markers for assessing the psychiatric, visual, and emotional disturbances in patients with TAO.

Relationship between Short-Range and Homotopic Long-Range Resting State Functional Connectivity in Temporal Lobes in Autism Spectrum Disorder.

To investigate the relationship between short-range and homotopic long-range resting state functional connectivity (RSFC) in children with autism spectrum disorder (ASD) and typically developing (TD) children, we analyzed functional near-infrared spectroscopy (fNIRS) RSFC in 25 children with ASD and 22 age-matched TD children. The resting state fNIRS signals, including spontaneous fluctuations in the oxygenated hemoglobin (HbO2) and deoxygenated hemoglobin (Hb) concentrations, were recorded from the bilateral temporal lobes. We found that (1) there was no difference in the short-range RSFC between the left and right hemisphere in either ASD or TD group; (2) both the short-range and homotopic long-range RSFC were weaker in the ASD than TD group; and (3) the short-range RSFC was stronger than the homotopic long-range RSFC in the ASD group, whereas no such difference was observed in the TD group. These observations might be helpful for a better understanding of the underlying cortical mechanism in ASD.

Disrupted balance of long and short-range functional connectivity density in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients: a resting-state fMRI study.

BackgroundAlzheimer’s disease (AD) is an age-progressive neurodegenerative disorder that affects cognitive function. There have been several functional connectivity (FC) strengths; however, FC density needs more development in AD. Therefore, this study wanted to determine the alternations in resting-state functional connectivity density (FCD) induced by Alzheimer’s and mild cognitive impairment (MCI).MethodsOne hundred and eleven AD patients, 29 MCI patients, and 73 healthy controls (age- and sex-matched) were recruited and assessed using resting-state functional magnetic resonance imaging (MRI) scanning. The ultra-fast graph theory called FCD mapping was used to calculate the voxel-wise short- and long-range FCD values of the brain. We performed voxel-based between-group comparisons of FCD values to show the cerebral regions with significant FCD alterations. We performed Pearson’s correlation analyses between aberrant functional connectivity densities and several clinical variables with adjustment for age and sex.ResultsPatients with cognition decline showed significantly abnormal long-range FCD in the cerebellum crus I, right insula, left inferior frontal gyrus, left superior frontal gyrus, left inferior frontal gyrus, and right middle frontal gyrus. The short-range FCD changed in the cerebellum crus I, left inferior frontal gyrus, left superior occipital gyrus, and right middle frontal gyrus. The long- and short-range functional connectivity in the left inferior frontal gyrus was positively correlated with Mini-mental State Examination (MMSE) scores.ConclusionsFCD in the identified regions reflects mechanism and compensation for loss of cognitive function. These findings could improve the pathology of AD and MCI and supply a neuroimaging marker for AD and MCI.

Altered long- and short-range functional connectivity density associated with poor sleep quality in patients with chronic insomnia disorder: A resting-state fMRI study.

IntroductionPrevious neuroimaging studies have suggested that brain functional impairment and hyperarousal occur during the daytime among patients with chronic insomnia disorder (CID); however, alterations to the brain's intrinsic functional architecture and their association with sleep quality have not yet been documented.MethodsIn this study, our aim was to investigate the insomnia‐related alterations to the intrinsic connectome in patients with CID (n = 27) at resting state, with a data‐driven approach based on graph theory assessment and functional connectivity density (FCD), which can be interpreted as short‐range (intraregional) or long‐range (interregional) mapping.ResultsCompared with healthy controls with good sleep, CID patients showed significantly decreased long‐range FCD in the dorsolateral prefrontal cortices and the putamen. These patients also showed decreased short‐range FCD in their multimodal‐processing regions, executive control network, and supplementary motor‐related areas. Furthermore, several regions showed increased short‐range FCD in patients with CID, implying hyper‐homogeneity of local activity.ConclusionsTogether, these findings suggest that insufficient sleep during chronic insomnia widely affects cortical functional activities, including disrupted FCD and increased short‐range FCD, which is associated with poor sleep quality.

Abnormal degree centrality in end-stage renal disease (ESRD) patients with cognitive impairment: a resting-state functional MRI study.

To investigate functional connectivity (FC) changes in end-stage renal disease (ESRD) patients with and without cognitive impairment (CI) by using resting-state functional magnetic resonance imaging (rs-fMRI). Twenty-three ESRD patients with CI, 22 ESRD patients with non-CI (NCI) and 23 matched healthy controls (HC) were included. Rs-fMRI scans were performed in all subjects. Full-range, long-range, and short-range FC defined voxel-wise based degree centrality (DC) and seed based FC were computed and contrasted among the groups. Compared with HC, the DC value of shortfunctional connectivity (SFC), in ESRD patients have increased on the left supramarginal gyrus, while it reduced on the left insula and right postcentral gyrus in CI and decreased on the right precentral gyrus in NCI. Compared with NCI, the DC value of LFC in CI increased on the left fusiform gyrus, while the DC value of short functional connectivity (SFC) increased on the left middle orbital gyrus. In the seed-based FC analyses, the CI showed significantly decreased FC between the left insula and bilateral middle temporal gyrus, between the left fusiform gyrus and the right hippocampus, and between the left postcentral gyrus and the right parahippocampus compared to HC; the CI showed significantly increased FC between the left precuneus and the left fusiform gyrus, between the left postcentral gyrus and the right precuneus compared with NCI. Positive correlations were found between DC values on the right superior frontal gyrus and LDL and BDST, and between MoCA and the DC values on the left insula and the left postcentral gyrus. The altered degree centrality may serve as early biomarkers for CI in ESRD patients.

Resting-State Functional MRI Study Demonstrates That the Density of Functional Connectivity Density Mapping Changes in Patients with Acute Eye Pain.

PurposeBrain function in patients with acute eye pain (EP) has not been extensively studied. An understanding of the alterations in short-range functional connectivity density (shortFCD) and long-range functional connectivity density (longFCD) in patients with EP remains elusive. The aim of the present study was to compare the functional connectivity density (FCD) between patients with EP and healthy controls (HCs) using resting-state functional connectivity.MethodsA total of 40 patients with EP (26 males and 14 females) and 40 HCs (26 males and 14 females) of similar age underwent functional magnetic resonance (MR) examination at the resting state. The shortFCD and longFCD values were compared using the one-sample t-test. The differences between patients with EP and the HCs were evaluated using receiver operating characteristic (ROC) curves.ResultsIn the patients with EP, significantly reduced shortFCD values were observed in the left posterior lobe of the cerebellum, right inferior parietal lobule, and left anterior lobe of the cerebellum, and significantly reduced longFCD values were observed in both the left and right posterior lobe of the cerebellum. Significantly increased shortFCD values were also observed in both superior frontal gyri (Brodmann area 6), and increased longFCD values were observed in the left inferior temporal gyrus and left superior frontal gyri (Brodmann area 11). Compared with the HCs, less reduction was noted among the shortFCD values of patients with EP in the right posterior lobe of the cerebellum, right supramarginal gyrus, left middle temporal gyrus, bilateral superior frontal gyri, and bilateral caudate nuclei.ConclusionEP patients shown variation of binarized shortFCD and long FCD in brain areas including premotor cortex, ventral cortical visual system, newest part of the cerebellum, cerebellum control unconscious proprioception, inhibition of involuntary movement, somatosensory association cortex, nucleus involving reward system and ventral cortical visual system which might provide an explanation of brain functional compensation for chronic eye pain and visual impairment in the EP patients.

Sleep State Modulates Resting-State Functional Connectivity in Neonates.

The spontaneous cerebral activity that gives rise to resting-state networks (RSNs) has been extensively studied in infants in recent years. However, the influence of sleep state on the presence of observable RSNs has yet to be formally investigated in the infant population, despite evidence that sleep modulates resting-state functional connectivity in adults. This effect could be extremely important, as most infant neuroimaging studies rely on the neonate to remain asleep throughout data acquisition. In this study, we combine functional near-infrared spectroscopy with electroencephalography to simultaneously monitor sleep state and investigate RSNs in a cohort of healthy term born neonates. During active sleep (AS) and quiet sleep (QS) our newborn neonates show functional connectivity patterns spatially consistent with previously reported RSN structures. Our three independent functional connectivity analyses revealed stronger interhemispheric connectivity during AS than during QS. In turn, within hemisphere short-range functional connectivity seems to be enhanced during QS. These findings underline the importance of sleep state monitoring in the investigation of RSNs.

Influence of More Than 5 Years of Continuous Exposure to Antipsychotics on Cerebral Functional Connectivity of Chronic Schizophrenia.

To explore the effect of long-term antipsychotics use on the strength of functional connectivity (FC) in the brains of patients with chronic schizophrenia. We collected resting-state functional magnetic resonance imaging from 15 patients with continuously treated chronic schizophrenia (TCS), 19 patients with minimally TCS (MTCS), and 20 healthy controls (HCs). Then, we evaluated and compared the whole-brain FC strength (FCS; including full-range, short-range, and long-range FCS) among patients with TCS, MTCS, and HCs. Patients with TCS and MTCS showed reduced full-/short-range FC compared with the HCs. No significant differences in the whole-brain FCS (including full-range, short-range, and long-range FCS) or clinical characteristics were identified between patients with TCS and MTCS. Additionally, the FCS in the right fusiform gyrus, right inferior temporal gyrus, and right inferior occipital gyrus negatively correlated with the duration of illness and positively correlated with onset age across all patients with chronic schizophrenia. Regardless of the long-term use of antipsychotics, patients with chronic schizophrenia show decreased FC compared with healthy individuals. For some patients with chronic schizophrenia, the influence of long-term and minimal/short-term antipsychotic exposure on resting-state FC was similar. The decreased full- and short-range FCS in the right fusiform gyrus, right inferior temporal gyrus, and right inferior occipital gyrus may be an ongoing pathological process that is not altered by antipsychotic interventions in patients with chronic schizophrenia. Large-sample, long-term follow-up studies are still needed for further exploration.

Sex differences in insular functional connectivity in response to noxious visceral stimulation in rats

Insular cortex (INS) plays a critical role in pain processing and shows sex differences in functional activation during noxious visceral stimulation. Less is known regarding functional interactions within the INS and between this structure and other parts of the brain. Cerebral blood flow mapping was performed using [14C]-iodoantipyrine perfusion autoradiography in male and female rats during colorectal distension (CRD) or no distension (controls). Forty regions of interest (ROIs) were defined anatomically to represent the granular, dysgranular, and agranular INS along the anterior-posterior (A-P) axis. Inter-ROI correlation matrices were calculated for each group to characterize intra-insular functional connectivity (FC). Results showed a clear FC segregation within the INS into an anterior (rostral to bregma +2.4 mm), a posterior (caudal to bregma −1.2 mm), and a mid INS subregion in between. Female controls showed higher FC density compared to males. During CRD, intra-insular FC density decreased greatly in females, but only modestly in males, with a loss of long-range connections between the anterior and mid INS noted in both sexes. New functional organization was characterized in both sexes by a cluster in the mid INS and primarily short-range FC along the A-P axis. Seed correlation analysis during CRD showed sex differences in FC of the anterior and mid agranular INS with the medial prefrontal cortex, thalamus, and brainstem areas (periaqueductal gray, parabrachial nucleus), suggesting sex differences in the modulatory aspect of visceral pain processing. Our findings suggest presence of substantial sex differences in visceral pain processing at the level of the insula.

Long-term reactions to pulsatile tinnitus are marked by weakened short-range functional connectivity within a brain network in the right temporal lobe.

There have been recent efforts to characterize brain functional activity features in patients with pulsatile tinnitus (PT). These efforts have revealed evidence of aberrant functional connectivity (FC) of the right middle temporal gyrus (MTG) in PT patients with prolonged disease duration. To assess the possible predictive effect of aberrant FC of MTG in PT patients with prolonged disease duration. Retrospective. Thirty-four patients with recent-onset PT (RPTIN), 24 patients with long-term PT (LPTIN), and 35 age-, gender-, and education-matched healthy controls were enrolled. 3.0T MRI system and echo-planar imaging (EPI) sequence, 3D brain volume imaging (BRAVO) sequence. Functional MRI data preprocessing was performed in Data Processing & Analysis for Brain Imaging (DPABI) and Statistical Parametric Mapping (SPM) 8. The FC analyses were conducted using the software REST. One-way analysis of covariance was conducted between three groups with age and gender as covariates, and post-hoc analysis was used to identify the sources of group effects. Pearson's correlation analysis was conducted for the z-values of altered FC strength in the PT group and the clinical data. Among hubs belonging to the executive control network, the default mode network (DMN), and limbic network, the strength of FC was mainly decreased in the patient groups compared with normal controls (P < 0.05). Relative to RPTIN patients and normal controls, LPTIN patients were further characterized by significantly decreased FC between several short-range brain regions adjacent to the seed (P < 0.05). Finally, disease duration was negatively correlated with decreased FC between the seed and right fusiform gyrus/parahippocampal gyrus, right inferior frontal gyrus, and right MTG (a brain area adjacent to the seed region). Long-term reactions to PT mainly involved weakened short-range FC, especially within a functional network in the right temporal lobe. 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Disrupted Balance of Long- and Short-Range Functional Connectivity Density in Type 2 Diabetes Mellitus: A Resting-State fMRI Study.

Previous studies have shown that type 2 diabetes mellitus (T2DM) can accelerate the rate of cognitive decline in patients. As an organ with high energy consumption, the brain network balances between lower energy consumption and higher information transmission efficiency. However, T2DM may modify the proportion of short- and long-range connections to adapt to the inadequate energy supply and to respond to various cognitive tasks under the energy pressure caused by homeostasis alterations in brain glucose metabolism. On the basis of the above theories, this study determined the abnormal functional connections of the brain in 32 T2DM patients compared with 32 healthy control (HC) subjects using long- and short-range functional connectivity density (FCD) analyses with resting-state fMRI data. The cognitive function level in these patients was also evaluated by neuropsychological tests. Moreover, the characteristics of abnormal FCD and their relationships with cognitive impairment were investigated in T2DM patients. Compared with the HC group, T2DM patients exhibited decreased long-range FCD in the left calcarine and left lingual gyrus and increased short-range FCD in the right angular gyrus and medial part of the left superior frontal gyrus (p < 0.05, Gaussian random-field theory corrected). In T2DM patients, the FCD z scores of the medial part of the left superior frontal gyrus were negatively correlated with the time cost in part B of the Trail Making Test (ρ = -0.422, p = 0.018). In addition, the FCD z scores of the right angular gyrus were negatively correlated with the long-term delayed recall scores of the Auditory Verbal Learning Test (ρ = -0.356, p = 0.049) and the forward scores of the Digital Span Test (ρ = -0.373, p = 0.039). T2DM patients exhibited aberrant long-range and short-range FCD patterns, which may suggest brain network reorganization at the expense of losing the integration of long-range FCD to adapt to the deficiency in energy supply. These changes may be associated with cognitive decline in T2DM patients.

Altered Long- and Short-Range Functional Connectivity Density in Healthy Subjects After Sleep Deprivations.

Objective: To investigate the brain functional organization induced by sleep deprivation (SD) using functional connectivity density (FCD) analysis.Methods: Twenty healthy subjects (12 female, 8 male; mean age, 20.6 ± 1.9 years) participated a 24 h sleep deprivation (SD) design. All subjects underwent the MRI scan and attention network test twice, once during rested wakefulness (RW) status, and the other was after 24 h acute SD. FCD was divided into the shortFCD and longFCD. Receiver operating characteristic (ROC) curve was used to evaluate the discriminating ability of those FCD differences in brain areas during the SD status from the RW status, while Pearson correlations was used to evaluate the relationships between those differences and behavioral performances.Results: Subjects at SD status exhibited lower accuracy rate and longer reaction time relative to RW status. Compared with RW, SD had a significant decreased shortFCD in the left cerebellum posterior lobe, right cerebellum anterior lobe, and right orbitofrontal cortex, and increased shortFCD in the left occipital gyrus, bilateral thalamus, right paracentral lobule, bilateral precentral gyrus, and bilateral postcentral gyrus. Compared with RW, SD had a significant increased longFCD in the right precentral gyrus, bilateral postcentral gyrus, and right visuospatial network, and decreased longFCD in the default mode network. The area under the curve values of those specific FCD differences in brain areas were (mean ± std, 0.933 ± 0.035; 0.863~0.977). Further ROC curve analysis demonstrated that the FCD differences in those brain areas alone discriminated the SD status from the RW status with high degree of sensitivities (89.19 ± 6%; 81.3~100%) and specificities (89.15 ± 6.87%; 75~100%). Reaction time showed a negative correlation with the right orbitofrontal cortex (r = −0.48, p = 0.032), and accuracy rate demonstrated a positive correlation with the right default mode network (r = 0.573, p = 0.008).Conclusions: The longFCD and shortFCD analysis might be potential indicator biomarkers to locate the underlying altered intrinsic brain functional organization disturbed by SD. SD sustains the cognitive performance by the decreased high-order cognition related areas and the arousal and sensorimotor related areas.

Abnormal coherence and sleep composition in children with Angelman syndrome: a retrospective EEG study

BackgroundAngelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, speech and motor impairments, epilepsy, abnormal sleep, and phenotypic overlap with autism. Individuals with AS display characteristic EEG patterns including high-amplitude rhythmic delta waves. Here, we sought to quantitatively explore EEG architecture in AS beyond known spectral power phenotypes. We were motivated by studies of functional connectivity and sleep spindles in autism to study these EEG readouts in children with AS.MethodsWe analyzed retrospective wake and sleep EEGs from children with AS (age 4–11) and age-matched neurotypical controls. We assessed long-range and short-range functional connectivity by measuring coherence across multiple frequencies during wake and sleep. We quantified sleep spindles using automated and manual approaches.ResultsDuring wakefulness, children with AS showed enhanced long-range EEG coherence across a wide range of frequencies. During sleep, children with AS showed increased long-range EEG coherence specifically in the gamma band. EEGs from children with AS contained fewer sleep spindles, and these spindles were shorter in duration than their neurotypical counterparts.ConclusionsWe demonstrate two quantitative readouts of dysregulated sleep composition in children with AS—gamma coherence and spindles—and describe how functional connectivity patterns may be disrupted during wakefulness. Quantitative EEG phenotypes have potential as biomarkers and readouts of target engagement for future clinical trials and provide clues into how neural circuits are dysregulated in children with AS.

Impact of previous episodes of hepatic encephalopathy on short-term brain function recovery after liver transplantation: a functional connectivity strength study.

Neuropsychological studies have documented an incomplete reversal of pre-existing cognitive dysfunction in cirrhotic patients after liver transplantation (LT) and have found this is more severe in patients with hepatic encephalopathy (HE). In this study, we aimed to investigate the impact of prior HE episodes on post-transplantation brain function recovery. Resting-state functional magnetic resonance imaging data was collected from 30 healthy controls and 33 cirrhotic patients (HE, n = 15 and noHE, n = 18) before and one month after LT. Long- and short-range functional connectivity strength (FCS) analysis indicated that before transplantation both noHE and HE groups showed diffuse FCS abnormalities relative to healthy controls. For the noHE group, the abnormal FCS found before LT largely returned to normal levels after LT, except for in the cerebellum, precuneus, and orbital middle frontal gyrus. However, the abnormal FCS prior to LT was largely preserved in the HE group, including high-level cognition-related (frontal and parietal lobes) and vision-related areas (occipital lobe, cuneus, and precuneus). In addition, comparisons between HE and noHE groups revealed that weaker FCS in default mode network (DMN) in HE group persisted from pre- to post- LT. Correlation analysis showed that changes in FCS in the left postcentral and right middle frontal gyrus correlated with alterations in neuropsychological performance and ammonia levels. In conclusion, the findings in this study demonstrate potential adverse effects of pre-LT episode of HE on post-LT brain function recovery, and reveal that DMN may be the most affected brain region by HE episodes, which can't be reversed by LT.

Differential effects of antidepressant treatment on long-range and short-range functional connectivity strength in patients with major depressive disorder

AbstarctAlthough we have some basic understanding of the neurochemical mechanisms of the antidepressants, the network-level effect of antidepressant treatment is still not fully understood. This study was conducted to investigate the effects of antidepressant on functional brain networks of patients with major depressive disorder (MDD). We performed resting-state fMRI scans on 20 first-episode drug-naive MDD patients at baseline and after escitalopram medication for 8 weeks. Twenty healthy controls also received MRI scans with an 8-week interval. The graph theory indices, long- and short-range functional connectivity strength (FCS), were computed to characterize the brain connectivity. The analysis of covariance was conducted on FCS maps of patients and controls to obtain the interaction effect of group and time, which indicate treatment-related effect. Following treatment, increased long-range FCS in the bilateral posterior cingulate cortex/precuneus and right thalamus in MDD patients at baseline were reduced. Meanwhile, increased short-range FCS in the bilateral ventromedial prefrontal cortex and left amygdala in patients were reduced, while reduced short-range FCS in the right parahippocampal gyrus was increased. Results suggest that the brain regions associated with negative emotional processing and regulation, and self-referential function could be modulated by escitalopram treatment; long- and short-range FCS are differentially affected by antidepressant.

Abnormal long- and short-range functional connectivity in adolescent-onset schizophrenia patients: A resting-state fMRI study

BackgroundHuman brain is a topologically complex network embedded in anatomical space, and anatomical distance may affect functional connectivity (FC) in schizophrenia. However, little is known if and how this effect occurs in adolescent-onset schizophrenia (AOS). MethodsWe explored long- and short-range FC through resting-state functional magnetic resonance imaging in 48 first-episode, drug-naive AOS patients and 31 healthy controls, and we examined if these abnormalities could be utilized to separate patients from controls using receiver operating characteristic curves and support vector machines (SVM). ResultsPatients had increased long-range positive FC (lpFC) and short-range positive FC (spFC) in the right middle frontal gyrus and right superior medial prefrontal cortex within the anterior default mode network (DMN), decreased lpFC and spFC in several regions of the posterior DMN, and decreased lpFC within the important hubs of salience network (SN). The decreased lpFC in the left superior temporal gyrus was positively correlated with cognitive impairment. We found that SVM has high accuracy (up to 92.4%) in classifying patients and control. ConclusionDisrupted anatomical distance would underlie network-level dysconnectivity, highlighting the importance of the DMN and SN in the neurodevelopment of schizophrenia. Abnormalities of long- and short-range FC in brain regions could discriminate patients from controls with high accuracy.