Salience Research Articles

Connections that characterize callousness: Affective features of psychopathy are associated with personalized patterns of resting-state network connectivity

BackgroundPsychopathic traits are hypothesized to be associated with dysfunction across three resting-state networks: the default mode (DMN), salience (SN), and central executive (CEN). Past work has not considered heterogeneity in the neural networks of individuals who display psychopathic traits, which is likely critical in understanding the etiology of psychopathy and could underlie different symptom presentations. Thus, this study maps person-specific resting state networks and links connectivity patterns to features of psychopathy. MethodsWe examined resting-state functional connectivity among eight regions of interest in the DMN, SN, and CEN using a person-specific, sparse network mapping approach (Group Iterative Multiple Model Estimation) in a community sample of 22-year-old men from low-income, urban families (N = 123). Associations were examined between a dimensional measure of psychopathic traits and network density (i.e., number of connections within and between networks). ResultsThere was significant heterogeneity in neural networks of participants, which were characterized by person-specific connections and no common connections across the sample. Psychopathic traits, particularly affective traits, were associated with connection density between the DMN and CEN, such that greater density was associated with elevated psychopathic traits. DiscussionFindings emphasize that neural networks underlying psychopathy are highly individualized. However, individuals with high levels of psychopathic traits had increased density in connections between the DMN and CEN, networks that have been linked with self-referential thinking and executive functioning. Taken together, the results highlight the utility of person-specific approaches in modeling neural networks underlying psychopathic traits, which could ultimately inform personalized prevention and intervention strategies.

Altered resting-state functional connectivity in adolescents is associated with PTSD symptoms and trauma exposure.

Alterations in resting-state functional connectivity (rsFC) have been demonstrated in Posttraumatic Stress Disorder (PTSD). However, such reports have primarily focused on adult participants, whereas findings in adolescents with PTSD are mixed and not entirely consistent with the adult literature. Here, we examined rsFC in a non-treatment seeking adolescent sample with posttraumatic stress symptoms (PTSS; n = 59) relative to asymptomatic controls (n = 226). We also examined differences between trauma-exposed and non-exposed control subgroups (TEC n = 73 and Non-TEC n = 153) to examine alterations associated with more general trauma exposure. Finally, we compared the PTSS and TEC groups, to confirm that the reported alterations in PTSS were not driven by trauma exposure. Using a seed-based approach, we examined connectivity of default-mode (DMN) and salience (SN) networks, where alterations have been previously reported. Results suggest that PTSS are associated with less within-DMN connectivity and greater SN-DMN connectivity, as well as altered connectivity with attention regions. Trauma exposure is associated with greater within-SN connectivity. Additionally, we report findings from exploratory connectome-based analysis, which demonstrate a number of topological alterations within DMN in the PTSS group. Overall, our findings replicate prior reports of altered rsFC in PTSD and extend them to non-treatment seeking, trauma-exposed adolescents, who did or did not report PTSS. They specifically highlight SN-DMN desegregation, lower within-DMN and greater within-SN connectivity, as well as altered connectivity with attention regions, in trauma-exposed adolescents. Future research is required to confirm that adolescents with diagnosed PTSD have similar/exacerbated connectivity patterns.

Triple Network Resting State Connectivity Predicts Distress Tolerance and Is Associated with Cocaine Use.

Distress tolerance (DT), a predictor of substance use treatment retention and post-treatment relapse, is associated with task based neural activation in regions located within the salience (SN), default mode (DMN), and executive control networks (ECN). The impact of network connectivity on DT has yet to be investigated. The aim of the present study was to test within and between network resting-state functional connectivity (rsFC) associations with DT, and the impact of cocaine use on this relationship. Twenty-nine adults reporting regular cocaine use (CU) and 28 matched healthy control individuals (HC), underwent resting-state functional magnetic resonance imaging followed by the completion of two counterbalanced, computerized DT tasks. Dual-regression analysis was used to derive within and between network rsFC of the SN, DMN, and lateralized (left and right) ECN. Cox proportional-hazards survival models were used to test the interactive effect of rsFC and group on DT. The association between cocaine use severity, rsFC, and DT was tested within the CU group. Lower LECN and higher DMN-SN rsFC were associated with DT impairment. Greater amount of cocaine use per using day was associated with greater DMN-SN rsFC. The findings emphasize the role of neural resource allocation within the ECN and between DMN-SN on distress tolerance.

Default mode dysfunction underpins suicidal activity in mood disorders.

Suicide is a serious and not uncommon consequence of mood disorders that occurs primarily when individuals are depressed. Understanding the neurobiology of suicidal activity (thoughts or behaviors) is likely to facilitate prevention. Seventy-nine adult depressed mood disorder patients (MDP), of which 25 had attempted suicide at least once, and 66 healthy controls (HC) participated in this study. Resting-state functional MRI was used to identify neural activity differences between suicide attempters (SA) and non-attempters (NA). Specifically, differences were examined in functional connectivity both within and between four large cognitive networks [Executive Control (ECN), Default Mode (DMN), Salience (SN), and Basal Ganglia (BGN)] and their respective associations with suicidal activity. Compared to HCs, patients had greater posterior DMN activity, but less activity in the BGN, and less low-frequency spectral power in the dorso-medial DMN. Furthermore, increased posterior DMN activity in SA was associated with recent suicidal activity, whereas NA had reduced BGN activity and less dorso-medial DMN spectral power, the latter being associated with lifelong suicidal thinking. SA also had greater activity in midline circuitry compared to both HC and NA, and the pattern of BGN and DMN co-activity differed between SA and NA. DMN engagement raises the possibility that suicidal activity in mood disorder patients may be a consequence of impaired self-referential thought processing. Furthermore, differential BGN and DMN co-activation according to suicide attempt status suggests that attempting suicide perhaps alters cognitive flexibility. These insights are potentially useful for understanding the neural basis of suicide activity.

Knowing What It Makes: How Product Transformation Salience Increases Recycling

Recycling campaigns abound, but do consumers think about what becomes of those recyclables? This research proposes that product transformation salience (thinking about recyclables turning into new ...

T10. Stress-Induced Salience Network Connectivity is Predictive of Post-Traumatic Stress Levels

There are substantial individual differences in large-scale network responses to stress including Salience (SN), Default Mode (DMN) and Central Executive Networks (CEN). Here, we investigate whether individual differences in stress-induced network connectivity changes (i.e., delta-FC) represent a vulnerability factor, or an acquired factor for posttraumatic stress disorder (PTSD) symptoms, in a longitudinal study among N=241 police recruits.

Network abnormalities among non‐manifesting Parkinson disease related LRRK2 mutation carriers

Non-manifesting carriers (NMC) of the G2019S mutation in the LRRK2 gene represent an "at risk" group for future development of Parkinson's disease (PD) and have demonstrated task related fMRI changes. However, resting-state networks have received less research focus, thus this study aimed to assess the integrity of the motor, default mode (DMN), salience (SAL), and dorsal attention (DAN) networks among this unique population by using two different connectivity measures: interregional functional connectivity analysis and Dependency network analysis (DEP NA). Machine learning classification methods were used to distinguish connectivity between the two groups of participants. Forty-four NMC and 41 non-manifesting non-carriers (NMNC) participated in this study; while no behavioral differences on standard questionnaires could be detected, NMC demonstrated lower connectivity measures in the DMN, SAL, and DAN compared to NMNC but not in the motor network. Significant correlations between NMC connectivity measures in the SAL and attention were identified. Machine learning classification separated NMC from NMNC with an accuracy rate above 0.8. Reduced integrity of non-motor networks was detected among NMC of the G2019S mutation in the LRRK2 gene prior to identifiable changes in connectivity of the motor network, indicating significant non-motor cerebral changes among populations "at risk" for future development of PD.

Acute stress alters the ‘default’ brain processing

Active adaptation to acute stress is essential for coping with daily life challenges. The stress hormone cortisol, as well as large scale re-allocations of brain resources have been implicated in this adaptation. Stress-induced shifts between large-scale brain networks, including salience (SN), central executive (CEN) and default mode networks (DMN), have however been demonstrated mainly under task-conditions. It remains unclear whether such network shifts also occur in the absence of ongoing task-demands, and most critically, whether these network shifts are predictive of individual variation in the magnitude of cortisol stress-responses.In a sample of 335 healthy participants, we investigated stress-induced functional connectivity changes (delta-FC) of the SN, CEN and DMN, using resting-state fMRI data acquired before and after a socially evaluated cold-pressor test and a mental arithmetic task. To investigate which network changes are associated with acute stress, we evaluated the association between cortisol increase and delta-FC of each network.Stress-induced cortisol increase was associated with increased connectivity within the SN, but with decreased coupling of DMN at both local (within network) and global (synchronization with brain regions also outside the network) levels.These findings indicate that acute stress prompts immediate connectivity changes in large-scale resting-state networks, including the SN and DMN in the absence of explicit ongoing task-demands. Most interestingly, this brain reorganization is coupled with individuals’ cortisol stress-responsiveness. These results suggest that the observed stress-induced network reorganization might function as a neural mechanism determining individual stress reactivity and, therefore, it could serve as a promising marker for future studies on stress resilience and vulnerability.

Salience network connectivity and social processing in children with nonverbal learning disability or autism spectrum disorder.

Nonverbal learning disability (NVLD) is a putative neurodevelopmental disorder characterized by spatial processing deficits as well as social deficits similar to those characteristic of autism spectrum disorder (ASD). Nonetheless, NVLD may be a distinct disorder that is differentially associated with the functioning and connectivity of the salience (SN) and default mode (DMN) networks that support social processing. Thus, we sought to assess and compare connectivity across these networks in children with NVLD, ASD, and typically developing children. Resting-state fMRI data were examined in 17 children with NVLD, 17 children with ASD selected from the Autism Brain Imaging Data Exchange (ABIDE), and 40 TD children (20 from ABIDE). Average DMN and SN functional connectivity and pairwise region-to-region connectivity were compared across groups. Associations with social impairment and IQ were assessed. Children with NVLD showed reduced connectivity between SN regions (anterior insula to anterior cingulate and to rostral prefrontal cortex [rPFC]), whereas children with ASD showed greater connectivity between SN regions (supramarginal gyrus to rPFC) relative to the other groups. Both clinical groups showed higher levels of parent-reported social problems, which related to altered SN connectivity in the NVLD group. No differences were detected in overall average connectivity within or between networks. The social deficits common across children with NVLD and ASD may derive from distinct alterations in connectivity within the SN. Such findings represent the first step toward identifying a neurobiological signature of NVLD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Segregation of salience network predicts treatment response of depression to repetitive transcranial magnetic stimulation.

BackgroundThe present study tested the hypothesis that network segregation, a graph theoretic measure of functional organization of the brain, is correlated with treatment response in patients with major depressive disorder (MDD) undergoing repetitive transcranial magnetic stimulation (rTMS).MethodsNetwork segregation, calculated from resting state functional magnetic resonance imaging scans, was measured in 32 patients with MDD who entered a sham-controlled, double-blinded, randomized trial of rTMS to the left dorsolateral prefrontal cortex, and a cohort of 20 healthy controls (HCs). Half of the MDD patients received sham treatment in the blinded phase, followed by active rTMS in the open-label phase. The analyses focused on segregation of the following networks: default mode (DMN), salience (SN), fronto-parietal (FPN), cingulo-opercular (CON), and memory retrieval (MRN).ResultsThere was no differential change in network segregation comparing sham to active treatment. However, in the combined group of patients who completed active rTMS treatment (in the blinded plus open-label phases), higher baseline segregation of SN significantly predicted more symptom improvement after rTMS. Compared to HCs at baseline, MDD patients showed decreased segregation in DMN, and trend-level decreases in SN and MRN.ConclusionThe results highlight the importance of network segregation in MDD, particularly in the SN, where more normal baseline segregation of SN may predict better treatment response to rTMS in depression.

Divergent patterns of loss of interpersonal warmth in frontotemporal dementia syndromes are predicted by altered intrinsic network connectivity.

Loss of warmth is well-documented in behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA) at a group level, and has been linked to salience (SN) and semantic-appraisal (SAN) network atrophy. However, clinical observations of individual patients show much greater heterogeneity, thus measuring this clinical variability and identifying the underlying neurologic mechanisms is a critical step for understanding the symptom profile of any one patient. We used reliable change indexes with premorbid and current informant-based evaluations to characterize patterns of change on the warmth subscale of the Interpersonal Adjective Scale (IAS) questionnaire in 132 patients (21 bvFTD, 19 svPPA, 22 nonfluent variant primary progressive aphasia [nfvPPA], 37 Alzheimer's disease [AD]) and 33 healthy older adults. We investigated whether individual differences in warmth change were reflected in SN or SAN functional connectivity, or structural volume of individual brain regions in these two networks. Though one subset of patients showed significant drop in warmth to abnormally low levels (bvFTD: 38%; svPPA: 21%; nfvPPA: 5%; AD: 11%), a second subset significantly dropped but remained within the clinically normal range (bvFTD: 33%; svPPA: 21%; nfvPPA: 9%; AD: 5%), and a third subset did not drop and stayed in the clinically normal range (bvFTD: 29%; svPPA: 58%; nfvPPA: 86%; AD: 84%). Furthermore, interpersonal warmth score was strongly predicted by SN functional connectivity (p < .01), but not by SAN functional connectivity or by structural volume in these networks. Our results extend earlier group-level findings by showing wide individual variability in degree of disease-related reduction of interpersonal warmth and SN functional connectivity in bvFTD and svPPA, and highlight new approaches to revealing how brain connectivity predicts behavior on an individual patient level. Our findings suggest that measures of interpersonal warmth can provide important clinical information about changes in underlying brain networks, and help clinicians and clinical researchers better identify which bvFTD and svPPA patients are at greater risk for interpersonal disruption.

Large-scale brain functional network topology disruptions underlie symptom heterogeneity in children with attention-deficit/hyperactivity disorder.

Accumulating evidence suggests brain network dysfunction in attention-deficit/hyperactivity disorder (ADHD). Whether large-scale brain network connectivity patterns reflect clinical heterogeneity in ADHD remains to be fully understood. This study aimed to characterize the differential within- and between-network functional connectivity (FC) changes in children with ADHD combined (ADHD-C) or inattentive (ADHD-I) subtypes and their associations with ADHD symptoms. We studied the task-free functional magnetic resonance imaging (fMRI) data of 58 boys with ADHD and 28 demographically matched healthy controls. We measured within- and between-network connectivity of both low-level (sensorimotor) and high-level (cognitive) large-scale intrinsic connectivity networks and network modularity. We found that children with ADHD-C but not those with ADHD-I exhibited hyper-connectivity within the anterior default mode network (DMN) compared with controls. Additionally, children with ADHD-C had higher inter-network FC between the left executive control (ECN) and the salience (SN) networks, between subcortical and visual networks, and between the DMN and left auditory networks than controls, while children with ADHD-I did not show differences compared with controls. Similarly, children with ADHD-C but not ADHD-I showed lower network modularity compared with controls. Importantly, these observed abnormal inter-network connectivity and network modularity metrics were associated with Child Behavioral Checklist (CBCL) attention-deficit/hyperactivity problems and internalizing problems in children with ADHD. This study revealed relatively greater loss of brain functional network segregation in childhood ADHD combined subtype compared to the inattentive subtype, suggesting differential large-scale functional brain network topology phenotype underlying childhood ADHD heterogeneity.

Longitudinal decreases in suicidal ideation are associated with increases in salience network coherence in depressed adolescents

BackgroundSuicidal ideation (SI) is an important predictor of suicide attempt, yet SI is difficult to predict. Given that SI begins in adolescence when brain networks are maturing, it is important to understand associations between network functioning and changes in severity of SI. MethodsThirty-three depressed adolescents were administered the Columbia-Suicide Severity Rating Scale to assess SI and completed resting-state fMRI at baseline (T1) and 6 months later (T2). We computed coherence in the executive control (ECN), default mode (DMN), salience (SN), and non-relevant noise networks and then examined the association between changes in brain network coherence and changes in SI severity from T1 to T2. ResultsA greater reduction in severity of SI was associated with a stronger increase in SN coherence from T1 to T2. There were no associations between the other networks and SI. LimitationsWe cannot generalize our findings to more psychiatrically diverse samples. More time-points are necessary to understand the trajectory of SI and SN coherence change. ConclusionsOur finding that reductions in SI are associated with increases in SN coherence extends previous cross-sectional results documenting a negative association between SI severity and SN coherence. The SN is involved in coordinating activation of ECN and DMN in response to salient information. Given this regulatory role of the SN, the association between SN coherence and SI suggests that adolescents with reduced SN coherence might more easily engage in harmful thoughts. Thus, the SN may be particularly relevant as a target for treatment applications in depressed adolescents.

Development of human electrophysiological brain networks.

Functional activity in the human brain is intrinsically organized into independently active, connected brain regions. These networks include sensorimotor systems, as well as higher-order cognitive networks such as the default mode network (DMN), which dominates activity when the brain is at rest, and the frontoparietal (FPN) and salience (SN) networks, which are often engaged during demanding tasks. Evidence from functional magnetic resonance imaging (fMRI) suggests that although sensory systems are mature by the end of childhood, the integrity of the FPN and SN develops throughout adolescence. There has been little work to corroborate these findings with electrophysiology. Using magnetoencephalography (MEG) recordings of 48 participants (aged 9–25 yr) at rest, we find that beta-band functional connectivity within the FPN, SN, and DMN continues to increase through adolescence, whereas connectivity in the visual system is mature by late childhood. In contrast to fMRI results, but replicating the MEG findings of Schäfer et al. (Schäfer CB, Morgan BR, Ye AX, Taylor MJ, Doesburg SM. Hum Brain Mapp 35: 5249–5261, 2014), we also see that connectivity between networks increases rather than decreases with age. This suggests that the development of coordinated beta-band oscillations within and between higher-order cognitive networks through adolescence might contribute to the developing abilities of adolescents to focus their attention and coordinate diverse aspects of mental activity.NEW & NOTEWORTHY Using magnetoencephalography to assess beta frequency oscillations, we show that functional connectivity within higher-order cognitive networks increases from childhood, reaching adult values by age 20 yr. In contrast, connectivity within a primary sensory (visual) network reaches adult values by age 14 yr. In contrast to functional MRI findings, connectivity between cognitive networks matures at a rate similar to within-network connectivity, suggesting that coordination of beta oscillations both within and between networks is associated with maturation of cognitive skills.

Dysconnectivity of Large-Scale Functional Networks in Early Psychosis: A Meta-analysis.

Increasingly, studies have identified abnormalities in the functional connectivity (FC) of large-scale neural networks in early psychosis, but the findings thus far have been inconclusive. Therefore, the aim of this study was to identify robust alterations in FC of the default mode (DMN), salience (SN), and central executive networks (CEN), in patients with first-episode psychosis (FEP) using a meta-analytic approach. Included studies were required to be resting-state, seed-to-whole brain, FC neuroimaging studies, comparing FEP patients to healthy controls (HC), with seeds within the boundaries of the region-of-interest networks. Peak effect coordinates and peak t, z, or p values were meta-analyzed using Seed-based d Mapping software. The DMN seeds primarily displayed within-network hypoconnectivity (largest clusters including the middle orbital gyrus; and ventral anterior cingulate gyrus). The SN seeds displayed hypoconnectivity with regions in the DMN and CEN (largest clusters located in the bilateral middle temporal gyri). Review of the limited CEN data revealed hypo- and hyperconnectivity across the networks. Negative symptoms were positively correlated with all DMN FC abnormalities in the FEP group. Antipsychotic-treated patients displayed greater hypoconnectivity than antipsychotic-naïve patients between both the DMN/SN seeds and prefrontal regions. These findings provide substantial evidence of widespread resting-state FC abnormalities of the DMN, SN, and CEN in early psychosis; particularly implicating DMN and SN dysconnectivity as a core deficit underlying the psychopathology of psychosis. Additionally, we highlight the importance of disentangling connectivity abnormalities resulting from disease processes, from those that result from antipsychotic treatment.

Resting-state network connectivity and metastability predict clinical symptoms in schizophrenia

BackgroundThe functional architecture of resting-state networks (RSNs) is defined by their connectivity and metastability. Disrupted RSN connectivity has been amply demonstrated in schizophrenia while the role of metastability remains poorly defined. Here, we undertake a comprehensive characterisation of RSN organization in schizophrenia and test its contribution to the clinical profile of this disorder. MethodsWe extracted RSNs representing the default mode (DMN), central executive (CEN), salience (SAL), language (LAN), sensorimotor (SMN), auditory (AN) and visual (VN) networks from resting-state functional magnetic resonance imaging data obtained from patients with schizophrenia (n = 85) and healthy individuals (n = 48). For each network, we computed its functional cohesiveness and integration and used the Kuramoto order parameter to compute metastability. We used stepwise multiple regression analyses to test these RSN features as predictors of symptom severity in patients. ResultsRSN features respectively explained 14%, 17%, 12% and 5% of the variance in positive, negative, anxious/depressive and agitation/disorganization symptoms. Lower functional integration between the DMN, CEN and SMN primarily contributed to positive symptoms. The functional properties of the SAL network were key predictors of all other symptom dimensions; specifically, lower cohesiveness of the SAL, lower integration of this network with the LAN and higher integration with the CEN respectively contributed to negative, anxious/depressive and disorganization symptoms. Increased SAL metastability was associated with negative symptoms. ConclusionsThese results confirm the primacy of the SAL network for schizophrenia and demonstrate that abnormalities in RSN connectivity and metastability are significant predictors of schizophrenia-related psychopathology.

F11. Altered ‘Default' Processing in the Brain Predicts Individual Differences in Stress Reactivity

Acute stress has been linked to a re-allocation of brain resources resulting in shifts between large-scale brain networks, including default mode (DMN), salience (SN) and central executive (CEN) networks. However, whether individual differences in cortisol stress-responses link to dynamic reorganizations of those networks at rest remains unknown.

Functional segregation loss over time is moderated by APOE genotype in healthy elderly.

We investigated the influence of the apolipoprotein E-ɛ4 allele (APOE-ɛ4) on longitudinal age-related changes in brain functional connectivity (FC) and cognition, in view of mixed cross-sectional findings. One hundred and twenty-two healthy older adults (aged 58-79; 25 APOE-ɛ4 carriers) underwent task-free fMRI scans at baseline. Seventy-eight (16 carriers) had at least one follow-up (every 2 years). Changes in intra- and internetwork FCs among the default mode (DMN), executive control (ECN), and salience (SN) networks, as well as cognition, were quantified using linear mixed models. Cross-sectionally, APOE-ɛ4 carriers had lower functional connectivity between the ECN and SN than noncarriers. Carriers also showed a stronger age-dependent decrease in visuospatial memory performance. Longitudinally, carriers had steeper increase in inter-ECN-DMN FC, indicating loss of functional segregation. The longitudinal change in processing speed performance was not moderated by APOE-ɛ4 genotype, but the brain-cognition association was. In younger elderly, faster loss of segregation was correlated with greater decline in processing speed regardless of genotype. In older elderly, such relation remained for noncarriers but reversed for carriers. APOE-ɛ4 may alter aging by accelerating the change in segregation between high-level cognitive systems. Its modulation on the longitudinal brain-cognition relationship was age-dependent.

Gamma-hydroxybutyrate increases brain resting-state functional connectivity of the salience network and dorsal nexus in humans

According to the triple network hypothesis the brain is equipped with three core neurocognitive networks: the default mode (DMN), the salience (SN), and the central executive (CEN) network. Moreover, the so called dorsal nexus, has met growing interest as it is a hub region connecting these three networks. Assessment of resting-state functional connectivity (rsFC) of these networks enables the elucidation of drug-induced brain alterations. Gamma-hydroxybutyrate (GHB) is a GHB/GABA-B receptor agonist that induces a paradoxical state of mixed stimulation and sedation at moderate doses, which makes it a valuable tool to investigate neural signatures of subjective drug effects. Employing a placebo-controlled, double-blind, randomized, cross-over design, we assessed the effects of GHB (35 mg/kg p. o.) in 19 healthy male subjects on DMN-, SN-, CEN-, and dorsal nexus-rsFC measured by functional magnet resonance imaging and applying independent component as well as seed-based analyses, while subjective drug effects were investigated using visual analog scales (VAS). Subjectively, GHB increased VAS ratings of a general drug effect, stimulation, and sedation. Intrinsic DMN-, and CEN-rsFC remained largely unchanged under GHB, but the drug increased SN-DMN-rsFC and SN-dorsal nexus-rsFC, while dorsal nexus-rsFC was reciprocally increased to both the SN (right anterior insula) and to the CEN (right middle frontal gyrus). Increased sedation significantly predicted the observed SN-dorsal nexus-rsFC. In conclusion, GHB generates a unique stimulant/sedative subjective state that is paralleled by a complex pattern of increased functional connectivity encompassing all three core neurocognitive networks of the brain, while increased SN-dorsal nexus-rsFC was demonstrated to be a potential signature of the sedative component of the drug effect.

Disrupted Brain Intrinsic Networks and Executive Dysfunction in Cirrhotic Patients without Overt Hepatic Encephalopathy.

Patients with cirrhosis often exhibit cognitive deficits, particularly executive dysfunction, which is considered a predictor of overt hepatic encephalopathy (OHE). We examined brain intrinsic networks associated with executive function to investigate the neural basis of this cognitive deficiency in cirrhosis. Resting-state functional MRI data were acquired from 20 cirrhotic patients and 18 healthy controls. Seed-based correlation analysis was used to identify the three well-known networks associated with executive function, including executive control (ECN), default mode (DMN), and salience (SN) networks. Functional connectivity (FC) within each network was compared between groups and correlated with patient executive performance (assessed by the Stroop task). Patients showed decreased FC between the ECN seed (right dorsolateral prefrontal cortex) and several regions (including right middle/inferior frontal gyrus, left inferior frontal gyrus, bilateral inferior/superior parietal lobules, bilateral middle/inferior temporal gyrus, and right medial frontal gyrus), between the DMN seed [posterior cingulate cortex (PCC)] and several regions (including bilateral medial frontal gyrus, bilateral anterior cingulate cortex, bilateral superior frontal gyrus, bilateral precuneus/PCC, left supramarginal gyrus, and left middle temporal gyrus), and between the SN seed (right anterior insula) and right supramarginal gyrus. FC strength in the ECN and SN was negatively correlated with patient performance during the Stroop task. Disrupted functional integration in the core brain cognitive networks, which is reflected by reductions in FC, occurs before OHE bouts and may play an important role in the neural mechanism of executive dysfunction associated with cirrhosis.