Executive Control Network Connectivity Research Articles

Abnormal dynamic functional connectivity in young nondisabling intracerebral hemorrhage patients.

Previous resting-state functional magnetic resonance imaging studies on intracerebral hemorrhage patients have focused more on the static characteristics of brain activity, while the time-varying effects during scanning have received less attention. Therefore, the current study aimed to explore the dynamic functional network connectivity changes of intracerebral hemorrhage patients. Using independent component analysis, the sliding window approach, and the k-means clustering analysis method, different dynamic functional network connectivity states were detected from resting-state functional magnetic resonance imaging data of 37 intracerebral hemorrhage patients and 44 healthy controls. The inter-group differences in dynamic functional network connectivity patterns and temporal properties were investigated, followed by correlation analyses between clinical scales and abnormal functional indexes. Ten resting-state networks were identified, and the dynamic functional network connectivity matrices were clustered into four different states. The transition numbers were decreased in the intracerebral hemorrhage patients compared with healthy controls, which was associated with trail making test scores in patients. The cerebellar network and executive control network connectivity in State 1 was reduced in patients, and this abnormal dynamic functional connectivity was positively correlated with the animal fluency test scores of patients. The current study demonstrated the characteristics of dynamic functional network connectivity in intracerebral hemorrhage patients and revealed that abnormal temporal properties and functional connectivity may be related to the performance of different cognitive domains after ictus. These results may provide new insights into exploring the neurocognitive mechanisms of intracerebral hemorrhage.

Executive function deficit in betel quid-dependence: Evidence from functional and effective connectivity of executive control network.

Betel quid (BQ) ranks fourth in global self-administered psychoactive agents, after caffeine, alcohol and nicotine, with 600 million consumers. Patients with BQ dependence (BQD) disorder demonstrate deficits in executive function. However, the neural correlates of the resting-state executive control network (ECN) and BQD-related pathopsychological characteristics still remain unclear. The present study aimed to assess the functional and effective connectivity of the ECN using resting-state functional magnetic resonance imaging (rs-fMRI). Fifty-five BQD individuals and 54 healthy controls (HCs) were recruited in this study. The executive function of all participants was tested by three tasks. Independent component and Granger causal analysis were employed to investigate the functional connectivity within ECN and ECN-related directional effective connectivity, separately. Behavioural results suggested a marked deficit of executive function in BQD individuals. Compared with HCs, BQD individuals showed overall weaker functional connectivity in the ECN, mainly including dorsolateral prefrontal cortex (DLPFC), inferior parietal lobule (IPL) and middle frontal gyrus (MFG). We observed decreased outflow of information from the right DLPFC and IPL to the precentral/pre-supplement motor area (SMA) and increased outflow of information from the MFG to the middle occipital gyrus in BQD individuals. Correlation analysis revealed that the effective connectivity from IPL to precentral/pre-SMA was negatively correlated to the BQD scales in BQD individuals. Our findings revealed impaired executive function, functional connectivity of the ECN and causal interaction between networks in patients with BQD. These results could potentially direct future targets for the prevention and intervention of BQD.

Altered effective connectivity between reward and inhibitory control networks in people with binge eating episodes: A spectral dynamic causal modeling study

BackgroundConverging evidence points to the crucial role of brain connectivity involved in aberrant behavioral control and reward reactivity in the onset and maintenance of binge eating. However, the directional interaction pattern between brain's reward and inhibitory control systems in people with binge eating episodes is largely unknown. MethodsResting-state fMRI data were collected from 36 adults with binge eating episodes (age: 19.05 ± 0.90) and 36 well-matched controls (age: 18.88 ± 0.78). We applied spectral dynamic causal modeling approach to estimate effective connectivity of the executive control network (ECN) and reward network (RN) with 15 predefined regions of interest, and investigate the between-group differences in directional connectivity. ResultsCompared with controls, the positive connections within the ECN were significantly strengthened in individuals with binge eating episodes, while the negative connections from the ECN to RN and from the RN to ECN were significantly weakened. In adults with binge eating episodes, the RN→ECN connectivity was positively related to binge frequency even controlling for age, sex, and body mass index. ConclusionThis study represents an important first step in addressing the role of directional integration between reward and inhibitory control networks in binge eating, and provides novel evidence that the ability of people with binge eating episodes to maintain a balance between inhibitory control and reward reactivity is decreased, as reflected by diminished bidirectional negative effects of prefrontal-subcortical circuitry at rest.

Alterations in functional connectivity of executive control network reveal influence of indoor toluene on cognition at low concentration

BackgroundThe mechanism for indoor toluene on cognition at low concentrations remains unknown. ObjectiveThe present study combines attention network testing (ANT) and electroencephalography (EEG) to investigate the brain network mechanisms associated with indoor low concentrations of toluene exposure. Methods22 healthy volunteers were exposed for 4 h to four conditions of toluene (0 ppb, 17.5 ppb, 35 ppb, and 70 ppb). Upon exposure to toluene, electroencephalographic activity was recorded and attention network tasks were performed. In this study, the direction transfer function (DTF) has been used to evaluate human brain functional connectivity among neural EEG signals. ResultsWe have evaluated the results of twenty-two subjects who completed all experiments. No significant difference was found between the four toluene conditions in behavioral performance. The DTFs indicated that the frontal cortex is the main brain region of the executive control network. In the 70 ppb condition, theta band DTF values were significantly higher than those in the 0 ppb and 17.5 ppb conditions. Theta band DTF values from the frontal region to other brain regions (DTFs_outflow) in 70 ppb condition were higher than in 0 ppb condition. ConclusionTheta band functional connectivity in the frontal region was significantly enhanced after exposure to toluene at low concentrations. The alternations in neural connectivity demonstrated that more effort was required to accomplish the same tasks when exposed to toluene. These results enable us to understand the early effects of indoor pollutants on cognition and the brain network mechanism.

BDNF and KIBRA Polymorphisms Are Related to Altered Resting State Network Connectivity in Middle Age.

Disease-modifying treatments for Alzheimer's disease (AD) may be more successful if interventions occur early, prior to significant neurodegeneration and subsequent to the onset of clinical symptoms, potentially during middle age. Polymorphisms within BDNF, COMT, and KIBRA have been implicated in AD and relate to episodic memory and executive functioning, two domains that decline early in AD. The purpose of the current study was to use an endophenotype approach to examine in healthy, non-demented middle-aged adults the association between polymorphisms in BDNF, COMT, and KIBRA and functional connectivity within networks related to episodic memory and executive function (i.e., default mode network (DMN), executive control network (ECN), and frontoparietal network (FPN)). Resting state networks were identified using independent component analysis and spatial maps with associated time courses were extracted using a dual regression approach. Functional connectivity within the DMN was associated with polymorphisms in BDNF (rs11030096, rs1491850) and KIBRA (rs1030182, rs6555791, rs6555802) (ps < 0.05), ECN connectivity was associated with polymorphisms in KIBRA (rs10475878, rs6555791) (ps < 0.05), and FPN connectivity was associated with KIBRA rs6555791 (p < 0.05). There were no COMT-related differences in functional connectivity of any of the three networks investigated (ps > 0.05). Our study demonstrates that in middle age, polymorphisms in BDNF and KIBRA are associated with altered functional connectivity in networks that are affected early in AD. Future preclinical work should consider these polymorphisms to further elucidate their role in pathological aging and to aid in the identification of biomarkers.

Menstrual Cycle-Related Changes in Women with Schizophrenia: A Resting-State fMRI Study

Introduction: Different influences of ovarian hormones in schizophrenia (SCZ) have been reported, but no study to date has assessed their effects on the brain dynamics at rest. The present study aimed to examine the hormonal and clinical changes related to the menstrual cycle and alterations in the resting-state functional connectivity (RS-FC) depending on cycle phase and/or hormonal fluctuations in SCZ. Method: This study was conducted based on both between- and within-subject experimental designs, including 13 clinically stable female patients with SCZ (32 ± 7.7 years) and 13 healthy women (30 ± 7.3 years). RS-functional magnetic resonance imaging (fMRI) scanning, as well as hormonal and clinical assessments, was applied to each participant twice during two cycle phases: early follicular and mid-luteal. Results: A difference in mid-luteal progesterone levels was found between groups, with a large effect size (Cohen’s d) of 0.8 (p < 0.05). Also, the estradiol levels negatively correlated with the negative symptom severity of the patients during their mid-luteal phase. In the patients, estrogen positively correlated with the auditory network connectivity in the left amygdala during the early follicular phase. In the controls, progesterone had positive correlations with the connectivity of the posterior default mode and the left frontoparietal networks in the bilateral precuneus during the early follicular phase and had a negative correlation with the executive control network connectivity in the mid-luteal phase. Conclusion: The present study showed hormonal differences between groups and suggested that the levels of cycle-dependent hormones might be associated with the changes in clinical symptom severity and the RS-FC in the groups. Our RS-fMRI findings warrant further investigation.

Altered executive control network connectivity in anti-NMDA receptor encephalitis.

ObjectiveThe goal of this study was to examine whether the static functional connectivity (FC) of the executive control network (ECN) and the temporal properties of dynamic FC states in the ECN can characterize the underlying nature of anti‐N‐methyl‐d‐aspartate (anti‐NMDA) receptor encephalitis and their correlations with cognitive functions.MethodsIn total, 21 patients with anti‐NMDA receptor encephalitis past the acute stage and 23 healthy controls (HCs) underwent a set of neuropsychological tests and participated in a resting‐state fMRI study to analyse the static FC of the ECN and the temporal properties of dynamic FC states in the ECN. In addition, correlation analyses were performed to determine the correlations between the FC metrics and cognitive performance.ResultsPatients with anti‐NMDA receptor encephalitis past the acute stage showed significant cognitive impairments compared to HCs. In accord with the results of neuropsychological tests, static intrinsic FC alterations and changed dynamic FC metrics of ECN were observed in the patients. Importantly, we observed significant correlations between altered ECN metrics and working memory, information processing speed, executive function performance in the patients.InterpretationOur findings suggest that cognitive impairments in patients with anti‐NMDA receptor encephalitis past the acute stage are likely related to altered static and dynamic ECN connectivity. These observations may enhance our understanding of the pathophysiological mechanisms underlying cognitive function in this population.

NIMG-14. RESTING STATE EXECUTIVE CONTROL AND SALIENCE NETWORK CONNECTIVITY IN CLINICALLY STABLE LOWER GRADE GLIOMA COVARIES WITH COGNITIVE PERFORMANCE

Abstract BACKGROUND Survival outcomes for patients with lower grade gliomas (LrGG) are improving. However, injury from tumor growth and consequences of treatment often leads to impaired cognition, particularly in cognitive domains reliant on distributed functional networks and intact white-matter tracts. Resting state functional MRI (rsfMRI) is a method of investigating the integrity of these functional networks. METHODS This study investigated rsfMRI connectivity in 21 patients with clinically stable LrGG compared to age- and gender-matched healthy controls, and associated imaging measures with cognitive outcomes. Data were acquired for 12 cognitive tests administered within one week of imaging. RsfMRI and T1-weighted images for 21 research controls were acquired from OpenNeuro datasets. RsfMRI data were processed and analyzed using the CONN toolbox using CONN’s standard regions of interest (ROI) for the 8 canonical networks as seeds, and cognitive test scores as covariates, with a threshold for T tests of p&amp;lt; .001 uncorrected. RESULTS Median age was 48 years old (range 27-67). There were 6 astrocytomas, IDHmut; 3 astrocytomas IDH-wt, 8 oligodendrogliomas, and 4 NOS. Thirteen had left hemisphere tumors (8 frontal, 3 parietal, 2 temporal), and 6 right (5 frontal, 1 temporal). Fourteen had previously recieved radiotherapy. There was significantly lower connectivity in frontoparietal executive control and the salience networks in LrGG patients versus controls. Within patients, lower executive control network connectivity covaried with worse performance on executive measures (FAS, Tower of London, Trails-A, Animal Naming, FrSBe), and attention and working memory measures (Digit Symbol, HVLT). Lower salience network connectivity covaried with poorer performance on executive measures (FrSBe, FAS) and attention and working memory measures (Digit Span, HVLT, WAIS-WM). CONCLUSION In clinically stable LrGG, rsfMRI measures of network connectivity are potentially useful markers to monitor and track, given the concordance with cognition, and could help guide cognitive assessment and rehabilitation.

Effect of Maternal Supplementation of Lutein on Brain Functional Organization of Offspring in a Piglet Model

Abstract Objectives Lutein preferentially accumulates in human eyes and brains across the lifespan and is associated with visual and cognitive function. Dietary lutein intake during gestation and lactation may influence the development of neuronal networks of the infants. This study aims to provide preliminary data on the effect of maternal lutein supplementation during perinatal period on brain functional organization of the offspring. Methods Pregnant sows (n = 6) were fed a corn-based control diet (CON) or CON supplemented with lutein (LUT, 2 mg/kg BW/day) from late gestation to lactation for 60 days. Piglets (n = 7 in each group) underwent magnetic resonance imaging (MRI) to acquire anatomical, diffusion tensor imaging, and resting-state functional MRI (rs-fMRI) data at weaning (21d old). Using a sparse dictionary learning approach, six resting-state networks were examined that resembles that of humans. Results Piglets from LUT-fed sows showed a 7.7% decreased functional connectivity in executive control network and 13.2% decrease in cerebellum network compared to that of CON piglets, suggesting perinatal LUT supplementation may suppress the activation of executive and motor function at resting state in infants. In addition, piglets from LUT-fed sows had a 10.3% decrease in functional connectivity in the visual network encompassing primary, secondary, and associative visual cortex and an 8% lower connectivity within auditory network encompassing superior temporal gyrus and auditory cortex in comparison to that of CON piglets, indicating maternal LUT supplementation may lead to a lower functional activation of the intrinsic visual and auditory networks of offspring at weaning. Slight changes in sensorimotor and default mode networks were also observed. Moreover, perinatal lutein supplementation did not change mean diffusivity, fractional anisotropy, and fiber length in hippocampus, the key component of memory formation and cognitive development. Conclusions Maternal supplementation of lutein may alter the functional organization of the offspring within multiple intrinsic networks at resting state that may underlie the functional outcomes of cognitive development of the offspring at weaning. Funding Sources Georgia Experimental Agricultural Station, Faculty research grant from Office or Research at the UGA, and Division of Research at PCOM.

Diagnostic and Predictive Neuroimaging Biomarkers for Posttraumatic Stress Disorder

BackgroundComorbidity between posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) has been commonly overlooked by studies examining resting-state functional connectivity patterns in PTSD. The current study used a data-driven approach to identify resting-state functional connectivity biomarkers to 1) differentiate individuals with PTSD (with or without MDD) from trauma-exposed healthy control subjects (TEHCs), 2) compare individuals with PTSD alone with those with comorbid PTSD+MDD, and 3) explore the clinical utility of the identified biomarkers by testing their associations with clinical symptoms and treatment response. MethodsResting-state magnetic resonance images were obtained from 51 individuals with PTSD alone, 52 individuals with PTSD+MDD, and 76 TEHCs. Of the 103 individuals with PTSD, 55 were enrolled in prolonged exposure treatment. A support vector machine model was used to identify resting-state functional connectivity biomarkers differentiating individuals with PTSD (with or without MDD) from TEHCs and differentiating individuals with PTSD alone from those with PTSD+MDD. The associations between the identified features and symptomatology were tested with Pearson correlations. ResultsThe support vector machine model achieved 70.6% accuracy in discriminating between individuals with PTSD and TEHCs and achieved 76.7% accuracy in discriminating between individuals with PTSD alone and those with PTSD+MDD for out-of-sample prediction. Within-network connectivity in the executive control network, prefrontal network, and salience network discriminated individuals with PTSD from TEHCs. The basal ganglia network played an important role in differentiating individuals with PTSD alone from those with PTSD+MDD. PTSD scores were inversely correlated with within–executive control network connectivity (p < .001), and executive control network connectivity was positively correlated with treatment response (p < .001). ConclusionsResults suggest that unique brain-based abnormalities differentiate individuals with PTSD from TEHCs, differentiate individuals with PTSD from those with PTSD+MDD, and demonstrate clinical utility in predicting levels of symptomatology and treatment response.

Can the Executive Control Network be Used to Diagnose Parkinson's Disease and as an Efficacy Indicator of Deep Brain Stimulation?

Objective The aim of this work was to investigate whether there are differences in the executive control network (ECN) between patients with Parkinson's disease (PD) before and after deep brain stimulation (DBS) surgery and to explore how deep brain stimulation (DBS) surgery affects ECN connectivity in patients with PD. Methods Resting-state magnetic resonance imaging (MRI) data were obtained from 23 patients with Parkinson's disease preoperatively (pre-PD) and postoperatively (post-PD) and 14 normal controls (CN). The right dorsolateral prefrontal cortex (DLPFC) was used as the seed region of interest (ROI) to study the characteristics of the functional connectivity of the ECN in these subjects. Results There were differences in the ECN among PD patients before and after surgery and between the CN. Compared with the CN group, the pre-PD patients showed significantly reduced functional connectivity (FC) between the DLPFC and the left inferior frontal gyrus, left precuneus, left cerebellum posterior lobe, right middle frontal gyrus, right inferior parietal gyrus, right posterior central gyrus, right precuneus, and right inferior frontal gyrus. Compared to the CN group, the post-PD patients showed significantly reduced FC between the DLPFC and left inferior frontal gyrus, left precuneus, left cerebellum posterior lobe, right middle frontal gyrus, right inferior frontal gyrus, and right parietal lobule. There is no difference in the ECN between the pre-PD patients and the post-PD patients. Conclusions The FC of ECN in PD patients was different from that in normal controls, but the FC of the ECN in patients with PD may not be altered by DBS. This suggests that the ECN may be considered an imaging biomarker for the identification of PD but may not be a good imaging biomarker for the evaluation of DBS efficacy.

Neuroimaging correlates of cognitive changes after bariatric surgery.

Obesity has been associated with cognitive deficits and increased risk for developing dementia. Bariatric surgery may result in improved cognitive function; however, the underlying structural and functional brain correlates are unclear. This longitudinal study explores the hypothesis that specific brain regions and networks underlie cognitive changes after bariatric surgery. University Hospital, United States. Seventeen patients were recruited for this prospective cohort study, including 9 patients undergoing bariatric surgery, and 8 age-, sex-, and education level-matched healthy, nonobese control patients. Bariatric patients underwent longitudinal neuropsychologic tests and magnetic resonance imaging (MRI) scans both before and 6 months after surgery. One patient was lost to follow-up. The same neuropsychologic tests and MRI scans were performed for control patients. Differences in MRI and neuropsychologic testing between bariatric patients and control patients, and longitudinal changes within bariatric patients were assessed. At baseline, bariatric patients demonstrated deficits in cognitive function relative to control patients, including pattern comparison (P = .009) and picture sequence memory (P = .004), which improved after significant weight loss. Baseline cognitive deficits in bariatric patients were accompanied by significantly lower left executive control network connectivity on resting-state functional MRI relative to control patients (P = .028), but differences resolved or diminished after bariatric surgery. Longitudinal improvements in pattern comparison performance correlated significantly with increases in left executive control network connectivity (r = .819; P = .013). No significant group or longitudinal differences were found in brain perfusion or brain white matter lesions. Individuals with obesity undergoing bariatric surgery exhibit deficits in cognitive function and specific alterations of brain networks; however, cognitive performance can improve, and executive control network connectivity can increase after weight loss from bariatric surgery.

Electroencephalography theta/beta ratio covaries with mind wandering and functional connectivity in the executive control network.

The ratio between frontal resting‐state electroencephalography (EEG) theta and beta frequency power (theta/beta ratio, TBR) is negatively related to cognitive control. It is unknown which psychological processes during resting state account for this. Increased theta and reduced beta power are observed during mind wandering (MW), and MW is related to decreased connectivity in the executive control network (ECN) and increased connectivity in the default mode network (DMN). The goal of this study was to test if MW‐related fluctuations in TBR covary with such functional variation in ECN and DMN connectivity and if this functional variation is related to resting‐state TBR. Data were analyzed for 26 participants who performed a 40‐min breath‐counting task and reported the occurrence of MW episodes while EEG was measured and again during magnetic resonance imaging. Frontal TBR was higher during MW than controlled thought and this was marginally related to resting‐state TBR. DMN connectivity was higher and ECN connectivity was lower during MW. Greater ECN connectivity during focus than MW was correlated to lower TBR during focus than MW. These results provide the first evidence of the neural correlates of TBR and its functional dynamics and further establish TBR's usefulness for the study of executive control, in normal and potentially abnormal psychology.

Functional segregation of executive control network and frontoparietal network in Alzheimer's disease

Functional connectivity pattern altered of default mode network (DMN) is gaining more attention as a potential noninvasive biomarker to diagnose incipient Alzheimer's disease. However, the changed functional connectivity except for DMN, the longitudinal changes in executive control network (ECN) and frontoparietal network (FPN) also has attracted wide interest. Moreover, AD-related functional connectivity abnormalities within the DMN are well replicated research, but the (increased/decreased and reduced) functional connectivity in ECN and FPN weren't receive adequate attention. To address the above issues, in this paper, we adopt sparse inverse covariance estimation (SICE) approach to investigate the changed functional connectivity of ECN and FPN on the ADNI2 dataset. Our experimental results indicate the left superior frontal gyrus (SFGmed.L) and left thalamus (THA.L) regions of ECN has shown increased functional connectivity, the left anterior cingulate (ACG.L) region of ECN has shown decreased functional connectivity. The Superior Parietal Gyrus (SPG) regions and left paracentral lobule (PCL.L) of FPN has shown increased functional connectivity, the left supramarginal gyrus (SMG.L) regions has shown decreased functional connectivity in AD patients. On the other hand, the ACG.L regions in ECN, SMG.L and left inferior parietal (IPL.L) in FPN have shown significantly reduced functional connectivity. These results demonstrate that increased/decreased functional connectivity and reduced functional connectivity not only within DMN, but also associated with ECN and FPN. It also suggest that AD is associated with the characteristics of large-scale functional networks, and these changed functional connectivity possibly as a potential noninvasive biomarker to diagnose incipient Alzheimer's disease.

Investigating executive control network and default mode network dysfunction in major depressive disorder

Major depressive disorder (MDD) is a mental disorder that causes a persistent feeling of sadness and loss of interest. It affects how you feel, think and behave and can lead to a variety of emotional and physical problems. Previous investigated the MDD has primarily focused on interpreting the abnormal functional connectivity of different brain regions, rather than entire brain networks. Although recent studies have found depression-related abnormalities functional connectivity of the brain networks, it is not clear the certain brain regions or the various functional networks as a whole are involved in the emotional dysregulation of depression. Moreover, abnormal functional connectivity regions are well replicated research, however, default mode network (DMN) and executive control network (ECN) haven’t received adequately examined in MDD. To address the above issues, in this paper, we adopt sparse inverse covariance estimation (SICE) approach to investigate the functional connectivity both DMN and ECN. Our experimental results show functional connectivity of ECN have significantly changed in MDD, where the anterior cingulate cortex (ACG.R) region and the thalamus region (THA.R) have shown increased functional connectivity compared with normal control, the superior frontal gyrus (SFGmed.R) region has shown decreased functional connectivity. Moreover, the precuneus lobule (PCUN.L) region and posterior cingulate cortex (PCG.L) of DMN have shown increased functional connectivity. These results may suggest that MDD is associated with large-scale functional networks, rather than the portions of brain regions. These changed functional connectivity may provide more neuroimaging biomarker for MDD diagnosis.

Eating in the absence of hunger in young children is related to brain reward network hyperactivity and reduced functional connectivity in executive control networks

Recent work has implicated disinhibited eating behaviours (DEB) as a potential pathway toward obesity development in children. However, the underlying neurobiology of disinhibited eating behaviours in young, healthy weight children, prior to obesity development, remains unknown. This study tested the relationship between DEB and intrinsic neuronal activity and connectivity in young children without obesity. Brain networks implicated in overeating including reward, salience and executive control networks, and the default mode network were investigated. DEB was measured by the eating in the absence of hunger (EAH) paradigm with postlunch kilocalories consumed from highly palatable foods (EAH kcal) used as the predictor. Intrinsic neuronal activity within and connectivity between specified networks were measured via resting-state functional magnetic resonance imaging. Eighteen typically developing children (mean age=5.8years) were included. EAH kcal was positively associated with activity of the nucleus accumbens, a major reward network hub (P<0.05, corrected). EAH kcal was negatively associated with intrinsic prefrontal cortex connectivity to the striatum (P<0.01, corrected). These results suggest that neural aspects of DEB are detectable in young children without obesity, providing a potential tool to better understand the development of obesity in this population.

DRD2 methylation is associated with executive control network connectivity and severity of alcohol problems among a sample of polysubstance users.

Chronic exposure to alcohol and other drugs of abuse has been associated with deleterious consequences, including functional connectivity deficits within neural networks associated with executive control. Altered functional connectivity within the executive control network (ECN) might underlie the progressive inability to control consumption of alcohol and other drugs as substance use disorders progress. Genetic and epigenetic factors have been associated with substance use disorders (SUDs). For example, dopamine receptor 2 (DRD2) functioning has been associated with alcohol use disorder (AUD) and related phenotypes, including correlates of executive functioning. The present study aims to explore the relationship between a continuous measure of alcohol-related problems, epigenetic markers (methylation) within the DRD2 gene, and functional connectivity within the ECN among a sample of polysubstance users. A community sample of 658 subjects, whose consumption of alcohol, nicotine, and cannabis span across a spectrum of quantity and frequency of use, were obtained across previous studies in polysubstance using populations. Resting state functional magnetic resonance imaging was analyzed to identify intrinsic connectivity networks using a priori regions of interest. Methylation measurement of functionally relevant sites within the DRD2 gene was achieved via pyrosequencing. Regression-based models, including mediation and moderation models, tested the association between DRD2 methylation, functional connectivity within intrinsic neural networks (including the ECN), and severity of alcohol problems. Results suggest that average DRD2 methylation was negatively associated with right ECN (RECN) and left ECN (LECN) connectivity, but not associated with other networks tested, and DRD2 methylation was significantly associated with alcohol problems severity. Mediation models were not supported, although moderation models suggested that connectivity between edges within the RECN moderated the relationship between DRD2 methylation and AUD severity. Results support a theoretical model in which epigenetic factors are associated with neurobiological correlates of alcohol consumption among a sample of polysubstance users.

A Preliminary High-Definition Fiber Tracking Study of the Executive Control Network in Blast-Induced Traumatic Brain Injury.

Blast-induced traumatic brain injury (bTBI) is common in veterans of the Iraq- and Afghanistan-era conflicts. However, the typical subtlety of neural alterations and absence of definitive biomarkers impede clinical detection on conventional imaging. This preliminary study examined the structure and functional correlates of executive control network (ECN) white matter in veterans to investigate the clinical utility of using high-definition fiber tracking (HDFT) to detect chronic bTBI. Demographically similar male veterans (N = 38) with and without bTBI (ages 24 to 50 years) completed standardized neuropsychological testing and magnetic resonance imaging. Quantitative HDFT metrics of subcortical-dorsolateral prefrontal cortex (DLPFC) tracts were derived. Moderate-to-large group effects were observed on HDFT metrics. Relative to comparisons, bTBI demonstrated elevated quantitative anisotropy (QA) and reduced right hemisphere volume of all examined tracts, and reduced fiber count and increased generalized fractional anisotropy in the right DLPFC-putamen tract and DLPFC-thalamus, respectively. The Group × Age interaction effect on DLPFC-caudate tract volume was large; age negatively related to volume in the bTBI group, but not comparison group. Groups performed similarly on the response inhibition measure. Performance (reaction time and commission errors) robustly correlated with HDFT tract metrics (QA and tract volume) in the comparison group, but not bTBI group. Results support anomalous density and integrity of ECN connectivity, particularly of the right DLPFC-putamen pathway, in bTBI. Results also support exacerbated aging in veterans with bTBI. Similar ECN function despite anomalous microstructure could reflect functional compensation in bTBI, although alternate interpretations are explored.

Evaluating functional connectivity of executive control network and frontoparietal network in Alzheimer’s disease

Investigating the early Alzheimer’s disease (AD) more emphasizes sensitive and specific biomarkers, which can help the clinicians to monitor the progression and treatments of AD. Among these biomarkers, default mode network (DMN) functional connectivity is gaining more attention as a potential noninvasive biomarker to diagnose incipient Alzheimer's disease. However, besides changed functional connectivity of DMN, other functional networks haven’t yet been examined systematically. Recent brain imaging studies reported that a number of reproducible and robust functional networks, which were distributed in distant neuroanatomic areas. Inspired by these works, in this paper, we apply sparse representation to the whole brain signals to identify these reproducible networks and detect partly affected brain regions of Alzheimer’s disease, then adopt sparse inverse covariance estimation (SICE) approach to investigate the changed functional connectivity of intrinsic connectivity networks. Our experimental results show that besides DMN, AD is also affected by others large scale functional brain networks and regions, e.g., executive control network (ECN), frontoparietal network (FPN), where in the superior frontal gyrus (SFGmed) and middle frontal gyrus (MFG) of ECN and in the part paracentral Lobule (PCL) of FPN have an increased functional connectivity, as well as in the Superior Parietal Gyrus (SPG) regions of FPN has shown decreased connectivity. The results may suggest AD is associated with larger scale functional networks and causes the functional connectivity change of many different brain regions. It also proves that these networks may sometimes work together to perform tasks, and such changed functional connectivity may provide a useful baseline for early AD diagnosis.

Influence of cerebrovascular disease on brain networks in prodromal and clinical Alzheimer's disease.

Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer's disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer's disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer's disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks-the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer's disease patients with and without cerebrovascular disease. Alzheimer's disease patients without cerebrovascular disease, but not Alzheimer's disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer's disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer's disease patients with and without cerebrovascular disease. Across Alzheimer's disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer's disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer's disease patients with cerebrovascular disease showed increased executive control network structural covariance compared to controls. Our findings demonstrate the differential neural network structural and functional changes in Alzheimer's disease with and without cerebrovascular disease, suggesting that the underlying pathology of Alzheimer's disease patients with cerebrovascular disease might differ from those without cerebrovascular disease and reflect a combination of more severe cerebrovascular disease and less severe Alzheimer's disease network degeneration phenotype.