Local Functional Connectivity Density Research Articles

Functional connectivity density aberrance in type 2 diabetes mellitus with and without mild cognitive impairment.

The objective of this study was to investigate alterations in functional connectivity density (FCD) mapping and their impact on functional connectivity (FC) among individuals diagnosed with Type 2 diabetes mellitus (T2DM) across different cognitive states. Moreover, the study sought to explore the potential association between aberrant FCD/FC patterns and clinical or cognitive variables. A total of 211 participants were recruited for this study, consisting of 75 healthy controls (HCs), 89 T2DM patients with normal cognitive function (DMCN), and 47 T2DM patients with mild cognitive impairment (DMCI). The study employed FCD analysis to pinpoint brain regions exhibiting significant FCD alterations. Subsequently, these regions showing abnormal FCD served as seeds for FC analysis. Exploratory partial correlations were conducted to explore the relationship between clinical biochemical indicators, neuropsychological test scores, and altered FCD or FC. The FCD analysis revealed an increased trend in global FCD (gFCD), local FCD (lFCD), and long-range FCD (lrFCD) within the bilateral supramarginal gyrus (SMG) among individuals with DMCN. Additionally, significant lFCD alterations were observed in the right inferior frontal gyrus and left precuneus when comparing DMCN to HCs and DMCI. When comparing individuals with T2DM and healthy controls (HCs), it was revealed that DMCN exhibited significant improvements in FCD. This suggests that the brain may employ specific compensatory mechanisms to maintain normal cognitive function at this stage. Our findings provide a novel perspective on the neural mechanisms involved in cognitive decline associated with T2DM.

The long-term intensive gymnastic training influences functional stability and integration: A resting-state fMRI study

IntroductionLong-term motor skill training has been shown to induce anatomical and functional neuroplasticity. World class gymnasts (WCGs) provide a unique opportunity to investigate the effect of long-term intensive training on neuroplasticity. Previous resting-state fMRI studies have demonstrated a high efficient information processing related to motor and cognitive functions in gymnasts compared with healthy controls (HCs). However, most research treated brain signals as static, overlooking the fact that the brain is a complex and dynamic system. In this study, we employed functional stability, a new metric based on dynamic functional connectivity (FC), to examine the impact of long-term intensive training on the functional architecture in the WCGs. MethodsWe first conducted a voxel-wise analysis of functional stability between the WCGs and HCs. Then, we applied FC density (FCD) to explore whether regions with modified functional stability were also accompanied by changes in connection patterns in the WCGs. We identified overlapping regions showing significant differences in both functional stability and FCD. Finally, we applied seed-based correlation analysis (SCA) to determine the detailed changes in connection patterns between the WCGs and HCs within these overlapping regions. ResultsCompared with the HCs, the WCGs exhibited higher functional stability in the bilateral angular gyrus (AG), bilateral inferior temporal gyrus (ITG), bilateral precentral gyrus, and right superior frontal gyrus and lower functional stability in the bilateral hippocampus, bilateral caudate, right rolandic operculum, left superior temporal gyrus, right middle frontal gyrus, right middle cingular cortex, and right precuneus than the HCs. We found that the bilateral AG and ITG not only showed higher functional stability but also increased global and long-range FCD in the WCGs relative to the HCs. The right precuneus displayed lower functional stability as well as decreased local, long-range, and global FCD in the WCGs. Both AG and ITG showed higher FC with regions in the default mode network (DMN) in the WCGs than in the HCs. ConclusionsThe increased functional stability in the AG and ITG might be associated with enhanced functional integration within the DMN in the WCGs. These findings may offer new spatiotemporal evidence for the impact of long-term intensive training on neuroplasticity.

Functional Connectivity Alterations During Sleep Deprivation: Investigating Key Brain Regions and Networks.

Sleep deprivation (SD) has emerged as a significant public health concern because of its adverse effects on cognition and behavior. However, the influence of circadian rhythms on SD and brain activities has been less studied. This study employed functional magnetic resonance imaging (fMRI) and functional connectivity density (FCD) metrics to investigate the interaction between sleep pressure and circadian rhythms during SD. Thirty-six volunteers with good sleep habits underwent a sleep deprivation trial. Sleepiness was assessed using the Stanford Sleepiness Scale (SSS) at multiple time points, and fMRI scans were conducted to derive global and local FCD (gFCD and iFCD) values. This study focused on specific brain regions and networks, including the thalamus, the frontoparietal network (FPN), and the default mode network (DMN). Analysis indicated significant changes in gFCD and iFCD values in several key brain regions. A strong correlation was found between sleepiness and both gFCD and iFCD values in certain areas, such as the left superior temporal gyrus and left thalamus. The gFCD values in these regions showed a gradual increase across sessions, while iFCD values in the right superior frontal gyrus decreased. This study revealed that SD leads to enhanced functional activities in the DMN and thalamus and decreased activity in the FPN. These changes in brain activity were significantly correlated with increases in sleepiness, as measured by the SSS. Our findings underscore the importance of understanding the neural underpinnings of SD and could guide future clinical interventions aimed at mitigating its effects.

Deficits in brain default mode network connectivity mediate the relationship between poor sleep quality and anxiety severity.

Chronic insomnia disorder (CID) is a prevalent sleep disorder that frequently cooccurs with anxiety. The association between insomnia and anxiety has been established; however, the neurobiological basis of this relationship remains unclear. This study aimed to investigate the neural markers of CID patients with and without anxiety and to determine whether specific neural connectivity mediates the relationship between insomnia and anxiety. This study included 180 participants, comprising CID patients with anxiety (CID-A), CID patients without anxiety (CID-NA), and good sleep controls. All participants completed self-reported measures of sleep quality and anxiety severity and underwent functional magnetic resonance imaging. Brain functional integration was measured using functional connectivity density (FCD) and resting-state functional connectivity (rsFC). Correlation and mediation analyses were used to examine the relationships among brain connectivity, sleep quality, and anxiety severity. The CID-NA and CID-A groups showed decreased local FCD in the medial prefrontal cortex (mPFC) and disrupted rsFC between the precuneus and other brain regions. Only the CID-A group exhibited altered long-range FCD in the precuneus and the rsFC between the anterior default mode network (DMN, e.g. mPFC) and posterior DMN (e.g. precuneus). Mediation analysis revealed DMN dysconnectivity underlying the association between poor sleep quality and anxiety symptoms. This study identified shared and distinct brain circuit disruptions in the CID-NA and CID-A groups, with deficits in DMN connectivity as a potential neural mechanism through which disrupted sleep augments anxiety. These findings may facilitate the development of personalized therapies for insomnia and associated anxiety problems.

Distinct profiles of functional connectivity density aberrance in Alzheimer's disease and mild cognitive impairment.

Investigating the neuroimaging changes from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is of great significance. However, the details about the distinct functional characteristics of AD and MCI remain unknown. In this study, we investigated distinct profiles of functional connectivity density (FCD) differences between AD and MCI compared with the normal population, aiming to depict the progressive brain changes from MCI to AD. As a data-driven method, FCD measures the profiles of FC for the given voxel at different scales. Resting-state functional magnetic resonance imaging (fMRI) images were obtained from patients with AD and MCI and matched healthy controls (HCs). One-way ANCOVA was used to investigate (global, long-range, and local) FCD differences among the three groups followed by post-hoc analysis controlling age, sex, and head motion. The three groups exhibited significant global FCD differences in the superior frontal gyrus. The post-hoc results further showed that patients with AD had a significant increase in global FCD values than those with MCI and HCs. Patients with MCI exhibited an increased trend compared with HCs. We further identified brain regions contributing to the observed global FCD differences by conducting seed-based FC analysis. We also identified that the observed global FCD differences were the additive effects of altered FC between the superior frontal gyrus and the posterior default model network. These results depicted the global information communication capability impairment in AD and MCI providing a new insight into the progressive brain changes from MCI to AD.

The altered functional connectivity density related to cognitive impairment in alcoholics.

Alcohol use disorder (AUD) is one of the most common substance use disorders contributing to both behavioral and cognitive impairments in patients with AUD. Recent neuroimaging studies point out that AUD is a typical disorder featured by altered functional connectivity. However, the details about how voxel-wise functional coordination remain unknown. Here, we adopted a newly proposed method named functional connectivity density (FCD) to depict altered voxel-wise functional coordination in AUD. The novel functional imaging technique, FCD, provides a comprehensive analytical method for brain's “scale-free” networks. We applied resting-state functional MRI (rs-fMRI) toward subjects to obtain their FCD, including global FCD (gFCD), local FCD (lFCD), and long-range FCD (lrFCD). Sixty-one patients with AUD and 29 healthy controls (HC) were recruited, and patients with AUD were further divided into alcohol-related cognitive impairment group (ARCI, n = 11) and non-cognitive impairment group (AUD-NCI, n = 50). All subjects were asked to stay stationary during the scan in order to calculate the resting-state gFCD, lFCD, and lrFCD values, and further investigate the abnormal connectivity alterations among AUD-NCI, ARCI, and HC. Compared to HC, both AUD groups exhibited significantly altered gFCD in the left inferior occipital lobe, left calcarine, altered lFCD in right lingual, and altered lrFCD in ventromedial frontal gyrus (VMPFC). It is notable that gFCD of the ARCI group was found to be significantly deviated from AUD-NCI and HC in left medial frontal gyrus, which changes probably contributed by the impairment in cognition. In addition, no significant differences in gFCD were found between ARCI and HC in left parahippocampal, while ARCI and HC were profoundly deviated from AUD-NCI, possibly reflecting a compensation of cognition impairment. Further analysis showed that within patients with AUD, gFCD values in left medial frontal gyrus are negatively correlated with MMSE scores, while lFCD values in left inferior occipital lobe are positively related to ADS scores. In conclusion, patients with AUD exhibited significantly altered functional connectivity patterns mainly in several left hemisphere brain regions, while patients with AUD with or without cognitive impairment also demonstrated intergroup FCD differences which correlated with symptom severity, and patients with AUD cognitive impairment would suffer less severe alcohol dependence. This difference in symptom severity probably served as a compensation for cognitive impairment, suggesting a difference in pathological pathways. These findings assisted future AUD studies by providing insight into possible pathological mechanisms.

Differential Abnormality in Functional Connectivity Density in Preclinical and Early-Stage Alzheimer's Disease.

BackgroundBoth subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) have a high risk of progression to Alzheimer's disease (AD). While most of the available evidence described changes in functional connectivity (FC) in SCD and aMCI, there was no confirmation of changes in functional connectivity density (FCD) that have not been confirmed. Therefore, the purpose of this study was to investigate the specific alterations in resting-state FCD in SCD and aMCI and further assess the extent to which these changes can distinguish the preclinical and early-stage AD.MethodsA total of 57 patients with SCD, 59 patients with aMCI, and 78 healthy controls (HC) were included. The global FCD, local FCD, and long-range FCD were calculated for each voxel to identify brain regions with significant FCD alterations. The brain regions with abnormal FCD were then used as regions of interest for FC analysis. In addition, we calculated correlations between neuroimaging alterations and cognitive function and performed receiver-operating characteristic analyses to assess the diagnostic effect of the FCD and FC alterations on SCD and aMCI.ResultsFCD mapping revealed significantly increased global FCD in the left parahippocampal gyrus (PHG.L) and increased long-range FCD in the left hippocampus for patients with SCD when compared to HCs. However, when compared to SCD, patients with aMCI showed significantly decreased global FCD and long-range FCD in the PHG.L. The follow-up FC analysis further revealed significant variations between the PHG.L and the occipital lobe in patients with SCD and aMCI. In addition, patients with SCD also presented significant changes in FC between the left hippocampus, the left cerebellum anterior lobe, and the inferior temporal gyrus. Moreover, changes in abnormal indicators in the SCD and aMCI groups were significantly associated with cognitive function. Finally, combining FCD and FC abnormalities allowed for a more precise differentiation of the clinical stages.ConclusionTo our knowledge, this study is the first to investigate specific alterations in FCD and FC for both patients with SCD and aMCI and confirms differential abnormalities that can serve as potential imaging markers for preclinical and early-stage Alzheimer's disease (AD). Also, it adds a new dimension of understanding to the diagnosis of SCD and aMCI as well as the evaluation of disease progression.

Patterns of functional connectivity alterations induced by alcohol reflect somatostatin interneuron expression in the human cerebral cortex

Acute alcohol administration affects functional connectivity, yet the underlying mechanism is unknown. Previous work suggested that a moderate dose of alcohol reduces the activity of gamma-aminobutyric acidergic (GABAergic) interneurons, thereby leading to a state of pyramidal disinhibition and hyperexcitability. The present study aims to relate alcohol-induced changes in functional connectivity to regional genetic markers of GABAergic interneurons. Healthy young adults (N = 15, 5 males) underwent resting state functional MRI scanning prior to alcohol administration, immediately and 90 min after alcohol administration. Functional connectivity density mapping was performed to quantify alcohol-induced changes in resting brain activity between conditions. Patterns of differences between conditions were related to regional genetic markers that express the primary GABAergic cortical interneuron subtypes (parvalbumin, somatostatin, and 5-hydroxytryptamine receptor 3A) obtained from the Allen Human Brain Atlas. Acute alcohol administration increased local functional connectivity density within the visual cortex, sensorimotor cortex, thalamus, striatum, and cerebellum. Patterns of alcohol-induced changes in local functional connectivity density inversely correlated with somatostatin cortical gene expression. These findings suggest that somatostatin-expressing interneurons modulate alcohol-induced changes in functional connectivity in healthy individuals.

Integrated Functional Neuroimaging, Monoamine Neurotransmitters, and Behavioral Score on Depressive Tendency in Intensive Care Unit Medical Staffs Induced by Sleep Deprivation After Night Shift Work.

BackgroundIntensive care unit (ICU) medical staffs undergoing sleep deprivation with perennial night shift work were usually at high risk of depression. However, shift work on depression-related resting-state functional magnetic resonance imaging was still not fully understood. The objective of this study was to explore the effects of sleep deprivation in ICU medical staffs after one night of shift work on brain functional connectivity density (FCD) and Hamilton Depression Rating Scale (HAMD) scores. Also, serum neurotransmitter concentrations of serotonin (5-HT) and norepinephrine (NE) were obtained simultaneously.MethodsA total of 21 ICU medical staffs without psychiatric history were recruited. All participants received HAMD score assessment and resting-state functional magnetic resonance imaging scans at two time points: one at rested wakefulness and the other after sleep deprivation (SD) accompanied with one night of shift work. Global FCD, local FCD, and long-range FCD (lrFCD) were used to evaluate spontaneous brain activity in the whole brain. In the meantime, peripheral blood samples were collected for measurement of serum 5-HT and NE levels. All these data were acquired between 7:00 and 8:00 am to limit the influence of biological rhythms. The correlations between the FCD values and HAMD scores and serum levels of neurotransmitters were analyzed concurrently.ResultsFunctional connectivity density mapping manifested that global FCD was decreased in the right medial frontal gyrus and the anterior cingulate gyrus, whereas lrFCD was decreased mainly in the right medial frontal gyrus. Most of these brain areas with FCD differences were components of the default mode network and overlapped with the medial prefrontal cortex. The lrFCD in the medial frontal gyrus showed a negative correlation with HAMD scores after SD. Compared with rested wakefulness, serum levels of 5-HT and NE decreased significantly, whereas HAMD scores were higher after SD within subjects.ConclusionsOur study suggested that sleep deprivation after night shift work can induce depressive tendency in ICU medical staffs, which might be related to alterative medial prefrontal cortex, raised HAMD scores, and varying monoamine neurotransmitters.

Functional connectivity density alterations in children with strabismus and amblyopia based on resting-state functional magnetic resonance imaging (fMRI)

PurposeTo explore functional connectivity density (FCD) values of brain areas in children with strabismus and amblyopia (SA) based on blood oxygen level-dependent (BOLD) signals.MethodsThis study recruited 26 children (14 male, 12 females) with SA and 26 healthy children (14 male, 12 female) as healthy controls (HCs). Both groups matched in age, gender, educational level and socioeconomic background. While resting, all participants underwent fMRI scanning and global FCD (gFCD) and local FCD (lFCD) values were calculated. Receiver operating characteristic (ROC) curves were created to investigate whether there was a significant difference between children with SA and healthy controls.ResultsWhen compared with healthy controls, children with SA had significantly lower gFCD values in the right cerebellum, left putamen, and right superior frontal gyrus; however, the same metrics showed opposite changes in the right angular gyrus, left middle cingulate gyrus, left angular gyrus, right superior parietal gyrus, and right middle frontal gyrus. In children with SA, lFCD values were found to be remarkably decreased in regions of the middle right temporal pole, right cerebellum, left putamen, left hippocampus, right hippocampus, left thalamus, left cerebellum; values were increased in the right superior parietal gyrus as compared with healthy controls.ConclusionWe noted abnormal neural connectivity in some brain areas of children with SA; detailing such connectivity aberrations is useful in exploring the pathophysiology of SA and providing useful information for future clinical management.

Habenular and mediodorsal thalamic connectivity predict persistent weight loss after laparoscopic sleeve gastrectomy.

The aim of this study was to investigate laparoscopic sleeve gastrectomy (LSG)-induced changes in connectivity between regions involved with reward/antireward and cognitive control and the extent to which these changes persist after surgery and predict sustainable weight loss. Whole-brain local functional connectivity density (lFCD) was studied in 25 participants with obesity who underwent resting-state functional MRI before (PreLSG), 1 month after (PostLSG1 ), and 12 months after (PostLSG12 ) LSG and compared with 25 normal-weight controls. Regions with significant time effects of LSG on functional connectivity density were identified for subsequent seed-based connectivity analyses and to examine associations with behavior. LSG significantly increased lFCD in the mediodorsal thalamic nucleus (MD) and in the habenula (Hb) at PostLSG12 compared with PreLSG/PostLSG1 , whereas it decreased lFCD in the posterior cingulate cortex/precuneus (PCC/PreCun) at PostLSG1 /PostLSG12 , and these changes were associated with reduction in BMI. In contrast, controls had no significant lFCD differences between baseline and repeated measures. MD had stronger connectivity with PreCun and Hb at PostLSG12 compared with PreLSG/PostLSG1 , and the increased MD-left PreCun and Hb-MD connectivity correlated with decreases in hunger and BMI, respectively. PCC/PreCun had stronger connectivity with the insula at PostLSG1-12 . The findings highlight the importance of reward and interoceptive regions as well as that of regions mediating negative emotions in the long-term therapeutic benefits of LSG.

Functional connectivity density alterations in middle-age retinal detachment patients.

ObjectiveMiddle‐age patients with retinal detachment (RD) exhibit a loss of visual information, and previous studies of functional magnetic resonance imaging (fMRI) have demonstrated abnormal spontaneous activity in the RD brain. Therefore, this study assessed changes in local functional connectivity density (lFCD) and long‐range functional connectivity density (longFCD) in middle‐age RD patients during resting‐state FC.MethodsIn total, 32 middle‐age patients with RD (18 men and 14 women), and 32 age‐, sex‐, and education‐matched normal controls (NCs) (18 men and 14 women) were recruited and underwent functional magnetic resonance examination in the resting state. Two‐sample t test was performed to compare lFCD and longFCD between groups. Receiver operating characteristic (ROC) curves were generated to distinguish middle‐age RD patients from NCs.ResultsCompared with NCs, middle‐age RD patients demonstrated increased lFCD values in the right inferior temporal gyrus, and increased longFCD values in the bilateral inferior frontal gyri, left superior and middle frontal gyrus, bilateral inferior temporal gyri, and left cerebellum posterior lobe. Middle‐age RD patient exhibited decreased lFCD values in the left cuneus, right lingual gyrus, and left middle frontal gyrus. They also had lower longFCD values in the left lingual gyrus and left inferior occipital gyrus. ROC curve analysis showed excellent accuracy of the specific areas under the curve.ConclusionOur results reveal that middle‐age RD patients exhibited variations of binarized lFCD and longFCD in specific brain areas, which provides insight into the pathological mechanism of RD patients with acute visual loss.

Altered local and distant functional connectivity density in chronic migraine: a resting-state functional MRI study.

Previous studies have indicated disrupted functional connectivity in multiple brain regions and resting-state networks in episodic migraine, but it is unclear how brain network property is disrupted in chronic migraine. Using resting-state functional magnetic resonance imaging and voxel-wise functional connectivity density analysis, we examined the large-scale functional connectivity pattern over the whole brain in 17 patients with chronic migraine without medication overuse compared to 35 healthy controls. The associations between functional connectivity density and clinical variables were also explored. Compared with controls, chronic migraine patients showed decreased local and distant functional connectivity density in the dorsolateral and medial prefrontal cortexes and precuneus and increased local and distant functional connectivity density in the hippocampal complex. The patients also presented increased local functional connectivity density in the orbital frontal gyrus and cerebellum and increased distant functional connectivity density in the temporal pole. Moreover, local functional connectivity density in several brain regions, such as the left superior temporal gyrus and dorsal anterior cingulate cortex, was found to be correlated with headache frequency or pain intensity. Chronic migraine is associated with functional connectivity alterations in regions involved in multisensory integration, affective and cognitive processing, and pain modulation. Both local and distant functional connectivity density are complementary biomarkers for investigating the neural mechanism of this disorder. Some local functional connectivity density alterations may be useful for assessing the disease burden of chronic migraine.

Alterations of local functional connectivity in lifespan: A resting-state fMRI study.

IntroductionAs aging attracted attention globally, revealing changes in brain function across the lifespan was largely concerned. In this study, we aimed to reveal the changes of functional networks of the brain (via local functional connectivity, local FC) in lifespan and explore the mechanism underlying them.Materials and MethodsA total of 523 healthy participants (258 males and 265 females) aged 18–88 years from part of the Cambridge Center for Ageing and Neuroscience (CamCAN) were involved in this study. Next, two data‐driven measures of local FC, local functional connectivity density (lFCD) and four‐dimensional spatial‐temporal consistency of local neural activity (FOCA), were calculated, and then, general linear models were used to assess the changes of them in lifespan.ResultsLocal functional connectivity (lFCD and FOCA) within visual networks (VN), sensorimotor network (SMN), and default mode network (DMN) decreased across the lifespan, while within basal ganglia network (BGN), local connectivity was increased across the lifespan. And, the fluid intelligence decreased within BGN while increased within VN, SMN, and DMN.ConclusionThese results might suggest that the decline of executive control and intrinsic cognitive ability in the aging population was related to the decline of functional connectivity in VN, SMN, and DMN. Meanwhile, BGN might play a regulatory role in the aging process to compensate for the dysfunction of other functional systems. Our findings may provide important neuroimaging evidence for exploring the brain functional mechanism in lifespan.

Classifying Autism Spectrum Disorder Using the Temporal Statistics of Resting-State Functional MRI Data With 3D Convolutional Neural Networks.

Resting-state functional magnetic resonance imaging (rs-fMRI) data are 4-dimensional volumes (3-space + 1-time) that have been posited to reflect the underlying mechanisms of information exchange between brain regions, thus making it an attractive modality to develop diagnostic biomarkers of brain dysfunction. The enormous success of deep learning in computer vision has sparked recent interest in applying deep learning in neuroimaging. But the dimensionality of rs-fMRI data is too high (~20 M), making it difficult to meaningfully process the data in its raw form for deep learning experiments. It is currently not clear how the data should be engineered to optimally extract the time information, and whether combining different representations of time could provide better results. In this paper, we explored various transformations that retain the full spatial resolution by summarizing the temporal dimension of the rs-fMRI data, therefore making it possible to train a full three-dimensional convolutional neural network (3D-CNN) even on a moderately sized [~2,000 from Autism Brain Imaging Data Exchange (ABIDE)-I and II] data set. These transformations summarize the activity in each voxel of the rs-fMRI or that of the voxel and its neighbors to a single number. For each brain volume, we calculated regional homogeneity, the amplitude of low-frequency fluctuations, the fractional amplitude of low-frequency fluctuations, degree centrality, eigenvector centrality, local functional connectivity density, entropy, voxel-mirrored homotopic connectivity, and auto-correlation lag. We trained the 3D-CNN on a publically available autism dataset to classify the rs-fMRI images as being from individuals with autism spectrum disorder (ASD) or from healthy controls (CON) at an individual level. We attained results competitive on this task for a combined ABIDE-I and II datasets of ~66%. When all summary measures were combined the result was still only as good as that of the best single measure which was regional homogeneity (ReHo). In addition, we also applied the support vector machine (SVM) algorithm on the same dataset and achieved comparable results, suggesting that 3D-CNNs could not learn additional information from these temporal transformations that were more useful to differentiate ASD from CON.

Functional connectivity density abnormalities and anxiety in primary insomnia patients.

Primary insomnia (PI) is strongly associated with emotional dysregulation. However, the neurobiological pathology of the association between PI and emotional dysregulation is limited. Previous studies have indicated an impact of PI on the emotional regulatory system, but the specificity of this finding remains to be confirmed. A sample of 27 primary insomnia patients (PIs) and 32 matched healthy controls (HCs) was recruited for this study. The functional connectivity density (FCD) was used to assess the spontaneous functional brain organization in PIs. Then, we identified whether the local (lFCD) and global FCD (gFCD) abnormalities can be the potential biomarker for emotion level in PIs. Our findings suggested that PIs exhibited higher levels of anxiety and depression, and the levels of anxiety and depression is associated with the insomnia severity. We also found that PIs showed both lower lFCD and gFCD in several regions (i.e. thalamus, anterior cingulate cortex (ACC), insula). Furthermore, the lower gFCD values of left ACC and right insula were associated with their anxiety level in PIs, which demonstrated their potential biomarker for anxiety in PIs. Our results demonstrated that the relationship between the insomnia severity and the anxiety level could be partially mediated by gFCD of the ACC and insula. The current study improved our understanding of the anxiety in PIs and provided helpful information for future therapeutic development for PIs.

Effects of the 5-HT2A and DRD3 genotypes on cortical morphology and functional connectivity density in drug-naïve first episode schizophrenia

The 5-hydroxytryptamine 2A receptor (5-HT2A) and dopamine D3 receptor (DRD3) have been extensively studied as promising candidate genes for schizophrenia. Magnetic resonance imaging studies have demonstrated that schizophrenia is associated with widespread structural and functional abnormalities in the brain. Serotonin and dopamine receptors play crucial roles in the development of the human cerebral cortex and brain activity. However, how the 5-HT2A and DRD3 genes impact brain structure and function in schizophrenia remains unknown. In the present study, we investigated the main effect of disease state and the interaction effect between disease state and genotype of these two genes on cortical volume, thickness, surface area and functional connectivity density (FCD) in fifty-five drug-naïve first episode schizophrenia patients and fifty-three healthy controls. We found that the differences in local FCD (lFCD) and global FCD (gFCD) between patients and healthy controls were predominantly located in brain hub regions. The significant interaction effects of disease state and 5-HT2A and DRD3 genes on brain structure and function were mainly located in the temporal cortex. Our findings may help to improve the understanding of the relationship between 5-HT2A and DRD3 genotypes and schizophrenia pathogenesis.

Abnormal Functional Connectivity in Cognitive Control Network, Default Mode Network, and Visual Attention Network in Internet Addiction: A Resting-State fMRI Study.

Internet addiction (IA) has become a global mental and social problem, which may lead to a series of psychiatric symptoms including uncontrolled use of internet, and lack of concentration. However, the exact pathophysiology of IA remains unclear. Most of functional connectivity studies were based on pre-selected regions of interest (ROI), which could not provide a comprehensive picture of the communication abnormalities in IA, and might lead to limited or bias observations. Using local functional connectivity density (lFCD), this study aimed to explore the whole-brain abnormalities of functional connectivity in IA. We evaluated the whole-brain lFCD resulting from resting-state fMRI data in 28 IA individuals and 30 demographically matched healthy control subjects (HCs). The correlations between clinical characteristics and aberrant lFCD were also assessed. Compared with HCs, subjects with IA exhibited heightened lFCD values in the right dorsolateral prefrontal cortex (DLPFC), left parahippocampal gyrus (PHG), and cerebellum, and the bilateral middle cingulate cortex (MCC) and superior temporal pole (STP), as well as decreased lFCD values in the right inferior parietal lobe (IPL), and bilateral calcarine and lingual gyrus. Voxel-based correlation analysis revealed the significant correlations between the Young's Internet Addiction Test (IAT) score and altered lFCD values in the left PHG and bilateral STP. These findings revealed the hyper-connectivity in cognitive control network and default mode network as well as the hypo-connectivity in visual attention network, verifying the common mechanism in IA and substance addiction, and the underlying association between IA, and attention deficit/hyperactivity disorder in terms of neurobiology.

Electronic-Sports Experience Related to Functional Enhancement in Central Executive and Default Mode Areas.

Electronic-sports (e-sports) is a form of organized, online, multiplayer video game competition, which requires both action skills and the ability and process of forming and adapting a strategy (referred to as strategization hereafter) to achieve goals. Over the past few decades, research has shown that video gaming experience has an important impact on the plasticity of the sensorimotor, attentional, and executive brain areas. However, little research has examined the relationship between e-sports experience and the plasticity of brain networks that are related to strategization. Using resting-state fMRI data and the local functional connectivity density (lFCD) analysis, this study investigated the relationship between e-sports experience (League of Legends [LOL] in this study) and brain plasticity by comparing between top-ranking LOL players and lower-ranking (yet experienced) LOL players. Results showed that the top-ranking LOL players had superior local functional integration in the executive areas compared to lower-ranking players. Furthermore, the top-ranking players had higher lFCD in the default mode areas, which have been found related to various subprocesses (e.g., memory and planning) essential for strategization. Finally, the top-ranking players' lFCD was related to their LOL expertise rank level, as indicated by a comprehensive score assigned by the gaming software based on players' gaming experience and expertise. Thus, the result showed that the local functional connectivity in central executive and default mode brain areas was enhanced in the top-ranking e-sports players, suggesting that e-sports experience is related to the plasticity of the central executive and default mode areas.

The impact of SNAP25 on brain functional connectivity density and working memory in ADHD

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopment disorder. The deficit in working memory is a central cognitive impairment in ADHD. The SNAP-25 is a neurotransmitter vesicular docking protein whose MnlI polymorphism (rs3746544) is located in the 3′-untranslated region (3′-UTR) and known to be linked to ADHD, but the underlying mechanism of this polymorphism remains unclear. Using a functional connectivity density (FCD) mapping method based on resting-state functional magnetic resonance imaging in a sample of male children diagnosed with ADHD, we first investigated the correlation between SNAP-25 rs3746544 and FCD hubs. Compared with rs3746544 G-allele carriers, TT homozygous, which confers a high risk for ADHD, exhibited significantly decreased local and long-range FCD in anterior cingulate cortex, and decreased local FCD in the dorsal lateral prefrontal cortex. Moreover, both higher local and long-range FCD could predict better WM capacity. The current findings provide new insights into the underlying neural mechanisms linking SNAP-25 rs3746544 with the risk for ADHD via the endophenotype of brain functional connectivity.