Top-down threat bias in pain perception is predicted by higher segregation between resting-state networks.

Top-down processes such as expectations have a strong influence on pain perception. Predicted threat of impending pain can affect perceived pain even more than the actual intensity of a noxious event. This type of threat bias in pain perception is associated with fear of pain and low pain tolerance, and hence the extent of bias varies between individuals. Large-scale patterns of functional brain connectivity are important for integrating expectations with sensory data. Greater integration is necessary for sensory integration; therefore, here we investigate the association between system segregation and top-down threat bias in healthy individuals. We show that top-down threat bias is predicted by less functional connectivity between resting-state networks. This effect was significant at a wide range of network thresholds and specifically in predefined parcellations of resting-state networks. Greater system segregation in brain networks also predicted higher anxiety and pain catastrophizing. These findings highlight the role of integration in brain networks in mediating threat bias in pain perception.

White matter microstructure predicts measures of clinical symptoms in chronic back pain patients.

Chronic back pain (CBP) has extensive clinical and social implications for its sufferers and is a major source of disability. Chronic pain has previously been shown to have central neural factors underpinning it, including the loss of white matter (WM), however traditional methods of analyzing WM microstructure have produced mixed and unclear results. To better understand these factors, we assessed the WM microstructure of 50 patients and 40 healthy controls (HC) using diffusion-weighted imaging. The data were analyzed using fixel-based analysis (FBA), a higher-order diffusion modelling technique applied to CBP for the first time here. Subjects also answered questionnaires relating to pain, disability, catastrophizing, and mood disorders, to establish the relationship between fixelwise metrics and clinical symptoms. FBA determined that, compared to HC, CBP patients had: 1) lower fibre density (FD) in several tracts, specifically the right anterior and bilateral superior thalamic radiations, right spinothalamic tract, right middle cerebellar peduncle, and the body and splenium of corpus callosum; 2) higher FD in the genu of corpus callosum; and 3) lower FDC - a combined fibre density and cross-section measure - in the bilateral spinothalamic tracts and right anterior thalamic radiation. Exploratory correlations showed strong negative relationships between fixelwise metrics and clinical questionnaire scores, especially pain catastrophizing. These results have important implications for the intake and processing of sensory data in CBP that warrant further investigation.

Resting state functional connectivity in SLE patients and association with cognitive impairment and blood-brain barrier permeability.

OBJECTIVE: Extensive blood-brain barrier (BBB) leakage has been linked to cognitive impairment in SLE. This study aimed to examine the associations of brain functional connectivity (FC) with cognitive impairment and BBB dysfunction among patients with SLE. METHODS: Cognitive function was assessed by neuropsychological testing (n = 77). Resting-state FC (rsFC) between brain regions, measured by functional MRI (n = 78), assessed coordinated neural activation in 131 regions across five canonical brain networks. BBB permeability was measured by dynamic contrast-enhanced MRI (n = 61). Differences in rsFC were compared between SLE patients with cognitive impairment (SLE-CI) and those with normal cognition (SLE-NC), between SLE patients with and without extensive BBB leakage, and with healthy controls. RESULTS: A whole-brain rsFC comparison found significant differences in intra-network and inter-network FC in SLE-CI vs SLE-NC patients. The affected connections showed a reduced negative rsFC in SLE-CI compared with SLE-NC and healthy controls. Similarly, a reduced number of brain-wide connections was found in SLE-CI patients compared with SLE-NC (P = 0.030) and healthy controls (P = 0.006). Specific brain regions had a lower total number of brain-wide connections in association with extensive BBB leakage (P = 0.011). Causal mediation analysis revealed that 64% of the association between BBB leakage and cognitive impairment in SLE patients was mediated by alterations in FC. CONCLUSION: SLE patients with cognitive impairment had abnormalities in brain rsFC which accounted for most of the association between extensive BBB leakage and cognitive impairment.

Functional Significance of Human Resting-State Networks Hubs Identified Using MEG During the Transition From Childhood to Adulthood.

Cortical hubs identified within resting-state networks (RSNs), areas of the cortex that have a higher-than-average number of connections, are known to be critical to typical cognitive functioning and are often implicated in disorders leading to abnormal cognitive functioning. Functionally defined cortical hubs are also known to change with age in the developing, maturing brain, mostly based on studies carried out using fMRI. We have recently used magnetoencephalography (MEG) to study the maturation trajectories of RSNs and their hubs from age 7 to 29 in 131 healthy participants with high temporal resolution. We found that maturation trajectories diverge as a function of the underlying cortical rhythm. Specifically, we found the beta band (13-30 Hz)-mediated RSNs became more locally efficient with maturation, i.e., more organized into clusters and connected with nearby regions, while gamma (31-80 Hz)-mediated RSNs became more globally efficient with maturation, i.e., prioritizing faster signal transmission between distant cortical regions. We also found that different sets of hubs were associated with each of these networks. To better understand the functional significance of this divergence, we wanted to examine the cortical functions associated with the identified hubs that grew or shrunk with maturation within each of these networks. To that end, we analyzed the results of the prior study using Neurosynth, a platform for large-scale, automated synthesis of fMRI data that links brain coordinates with their probabilistically associated terms. By mapping the Neurosynth terms associated with each of these hubs, we found that maturing hubs identified in the gamma band RSNs were more likely to be associated with bottom-up processes while maturing hubs identified in the beta band RSNs were more likely to be associated with top-down functions. The results were consistent with the idea that beta band-mediated networks preferentially support the maturation of top-down processing, while the gamma band-mediated networks preferentially support the maturation of bottom-up processing.

Top-down threat bias in pain perception is predicted by intrinsic structural and functional connections of the brain.

Top-down processes such as expectations play a key role in pain perception. In specific contexts, inferred threat of impending pain can affect perceived pain more than the noxious intensity. This biasing effect of top-down threats can affect some individuals more strongly than others due to differences in fear of pain. The specific characteristics of intrinsic brain characteristics that mediate the effects of top-down threat bias are mainly unknown. In this study, we examined whether threat bias is associated with structural and functional brain connectivity. The variability in the top-down bias was mapped to the microstructure of white matter in diffusion weighted images (DWI) using MRTrix3. Mean functional connectivity of five canonical resting state networks was tested for association with bias scores and with the identified DWI metrics. We found that the fiber density of the splenium of the corpus callosum was significantly low in individuals with high top-down threat bias (FWE corrected with 5000 permutations, p < 0.05). The mean functional connectivity within the language/memory and between language/memory and default mode networks predicted the bias scores. Functional connectivity within language memory networks predicted the splenium fiber density, higher pain catastrophizing and lower mindful awareness. Probabilistic tractography showed that the identified region in the splenium connected several sensory regions and high-order parietal regions between the two hemispheres, indicating the splenium's role in sensory integration. These findings demonstrate that individuals who show more change in pain with changes in the threat of receiving a stronger noxious stimulus have lower structural connectivity in the pathway necessary for integrating top-down cue information with bottom-up sensory information. Conversely, systems involved in memory recall, semantic and self-referential processing are more strongly connected in people with top-down threat bias.

Role of autoantibodies and blood-brain barrier leakage in cognitive impairment in systemic lupus erythematosus.

OBJECTIVE: Cognitive impairment is common in patients with SLE but the cause is unknown. The current cross-sectional study examined the association between select SLE-related autoantibodies, other serological biomarkers and extensive blood-brain barrier (BBB) leakage in patients with SLE with and without cognitive impairment. In addition, we determined whether the relationship between SLE autoantibodies, other biomarkers and cognitive impairment differed depending on the presence or absence of concurrent extensive BBB leakage. METHODS: Consecutive patients with SLE, recruited from a single academic medical centre, underwent formal neuropsychological testing for assessment of cognitive function. On the same day, BBB permeability was determined using dynamic contrast-enhanced MRI scanning. SLE autoantibodies and other serological biomarkers were measured. Regression modelling was used to determine the association between cognitive impairment, extensive BBB leakage and autoantibodies/biomarkers. RESULTS: There were 102 patients with SLE; 90% were female and 88% were Caucasian, with a mean±SD age of 48.9±13.8 years. The mean±SD SLE disease duration was 14.8±11.0 years. Impairment in one or more cognitive tests was present in 47 of 101 (47%) patients and included deficits in information processing speed (9%), attention span (21%), new learning (8%), delayed recall (15%) and executive abilities (21%). Extensive BBB leakage was present in 20 of 79 (25%) patients and was associated with cognitive impairment (15 of 20 (75%) vs 24 of 59 (41%); p=0.01) and shorter disease duration (median (IQR): 7 (8-24 years) vs 15 (2-16 years); p=0.02). No serological parameters were associated with extensive BBB leakage and there was no statistically significant association between cognitive impairment and circulating autoantibodies even after adjusting for BBB leakage. CONCLUSIONS: Extensive BBB leakage alone was associated with cognitive impairment. These findings suggest that BBB leakage is an important contributor to cognitive impairment, regardless of circulating SLE-related autoantibodies.

Symptoms reported by Canadians posted in Havana are linked with reduced white matter fibre density.

Diplomats representing the USA have reported with unusual neurologic symptoms and MRI changes after being posted in Havana, Cuba between late 2016 and 2018. Here, we examined white matter microstructure and network connectivity of individuals stationed in Havana, using diffusion-weighted MRI, fixel-based analysis and structural connectomics as implemented in MRtrix3. MRI data acquisition and clinical assessments were done in a total of 24 diplomats and their family members and 40 healthy controls. The diplomat data were grouped into an exposed cohort (n = 16) and an unexposed cohort (n = 10), and among these, two individuals were assessed before and after potential exposure. Fixel-based analysis revealed a reduction in fibre density in two specific regions: the fornix and the splenium, in exposed individuals, relative to unexposed individuals and healthy controls. Post hoc analyses showed the effect remained present (P < 0.05) in both regions when comparing exposed and unexposed diplomats; and reduced fibre density was correlated with longer time period stationed in Cuba after age correction. Reduction of fibre density was also found to be linked with clinical symptoms of persistent migraine, tinnitus, sound sensitivity and fatigue. Network statistical comparisons revealed decreased structural connectivity in two distinct networks, comprising subcortical and cortical systems in exposed individuals, relative to unexposed and normative data. While the cause for the differences between the groups remains unknown, our results reveal region-specific white matter injury, that is, significantly correlated with clinical symptoms.

Distinct networks of periaqueductal gray columns in pain and threat processing.

Noxious events that can cause physical damage to the body are perceived as threats. In the brainstem, the periaqueductal gray (PAG) ensures survival by generating an appropriate response to these threats. Hence, the experience of pain is coupled with threat signaling and interfaces in the dl/l and vlPAG columns. In this study, we triangulate the functional circuits of the dl/l and vlPAG by using static and time-varying functional connectivity (FC) in multiple fMRI scans in healthy participants (n = 37, 21 female). The dl/l and vlPAG were activated during cue, heat, and rating periods when the cue signaled a high threat of experiencing heat pain and when the incoming intensity of heat pain was unknown. Responses were significantly lower after low threat cues. The two regions responded similarly to the cued conditions but showed prominent distinctions in the extent of FC with other brain regions. Thus, both static and time-varying FC showed significant differences in the functional circuits of dl/l and vlPAG in rest and task scans. The dl/lPAG consistently synchronized with the salience network and the thalamus, suggesting a role in threat detection, while the vlPAG exhibited more widespread synchronization and frequently connected with memory/language and sensory regions. Hence, these two PAG regions process heat pain when stronger pain is expected or when it is uncertain, and preferentially synchronize with distinct brain circuits in a reproducible manner. The dl/lPAG seems more directly involved in salience detection, while the vlPAG seems engaged in contextualizing threats.

Long-term alterations in somatosensory functioning in survivors of childhood cancer.

ABSTRACT: Cancer and its treatment can have lasting consequences on somatosensation, including pain, which is often underrecognized and undertreated. Research characterizing the impact of cancer on pain and sensory processing in survivors of childhood cancer is scarce. This study aimed to quantify generalized differences in pain and sensory processing in survivors of childhood cancer compared with reference data using a standardized thermal and mechanical quantitative sensory testing (QST) protocol. The association between demographic, clinical (eg, leukemia vs other cancers and treatment exposures), and psychosocial (eg, anxiety and pain catastrophizing) variables and sensitivity to pain and sensory stimuli were also evaluated. Participants were 56 survivors of various types of childhood cancer (52% male, Mage = 13.5 years, SD = 3.2, range = 8-17 years). On average, children were 7 years (SD = 4.1, range = 1.2-16.5) post treatment. Almost all participants (86%) had at least 1 abnormal QST parameter compared with age- and sex-matched reference data; however, few participants self-reported the presence of sensory abnormalities. Generally, participants exhibited reduced sensitivity across the QST parameters examined (Ps < 0.05, ds = 0.40-3.45). A significant minority (45%) also exhibited pain sensitization (P <0.001, d = 0.42). Several risk factors for changes in sensory processing were identified, including current age, history of leukemia, certain treatment exposures (eg, vincristine cumulative dose, major surgery, and bone marrow or stem cell transplant), time off treatment, and higher anxiety and pain catastrophizing scores. Overall, this study demonstrated that somatosensory changes are prevalent in survivors of childhood cancer years after the completion of treatment. Future research is needed to understand long-term implications of altered somatosensation in this complex population.

Blood-brain barrier leakage in systemic lupus erythematosus is associated with gray matter loss and cognitive impairment.

OBJECTIVES: To examine the association between blood-brain barrier (BBB) integrity, brain volume and cognitive dysfunction in adult patients with systemic lupus erythematosus (SLE). METHODS: A total of 65 ambulatory patients with SLE and 9 healthy controls underwent dynamic contrast-enhanced MRI scanning, for quantitative assessment of BBB permeability. Volumetric data were extracted using the VolBrain pipeline. Global cognitive function was evaluated using a screening battery consisting of tasks falling into five broad cognitive domains, and was compared between patients with normal versus extensive BBB leakage. RESULTS: Patients with SLE had significantly higher levels of BBB leakage compared with controls (p=0.04). Extensive BBB leakage (affecting over >9% of brain volume) was identified only in patients with SLE (16/65; 24.6%), who also had smaller right and left cerebral grey matter volumes compared with controls (p=0.04). Extensive BBB leakage was associated with lower global cognitive scores (p=0.02), and with the presence of impairment on one or more cognitive tasks (p=0.01). CONCLUSION: Our findings provide evidence for a link between extensive BBB leakage and changes in both brain structure and cognitive function in patients with SLE. Future studies should investigate the mechanisms underlying BBB-mediated cognitive impairment, validate the diagnostic utility of BBB imaging, and determine the potential of targeting the BBB as a therapeutic strategy in patients with SLE.

Brain network topology predicts participant adherence to mental training programs.

Adherence determines the success and benefits of mental training (e.g., meditation) programs. It is unclear why some participants engage more actively in programs for mental training than others. Understanding neurobiological factors that predict adherence is necessary for understanding elements of learning and to inform better designs for new learning regimens. Clustering patterns in brain networks have been suggested to predict learning performance, but it is unclear whether these patterns contribute to motivational aspects of learning such as adherence. This study tests whether configurations of brain connections in resting-state fMRI scans can be used to predict adherence to two programs: meditation and creative writing. Results indicate that greater system segregation and clustering predict the number of practice sessions and class participation in both programs at a wide range of network thresholds (corrected p value < 0.05). At a local level, regions in subcortical circuitry such as striatum and accumbens predicted adherence in all subjects. Furthermore, there were also some important distinctions between groups: Adherence to meditation was predicted by connectivity within local network of the anterior insula and default mode network; and in the writing program, adherence was predicted by network neighborhood of frontal and temporal regions. Four machine learning methods were applied to test the robustness of the brain metric for classifying individual capacity for adherence and yielded reasonable accuracy. Overall, these findings underscore the fact that adherence and the ability to perform prescribed exercises is associated with organizational patterns of brain connectivity.

Hippocampal circuits underlie improvements in self-reported anxiety following mindfulness training.

INTRODUCTION: Mindfulness meditation has successfully been applied to cultivate skills in self-regulation of emotion, as it employs the unbiased present moment awareness of experience. This heightened attention to and awareness of sensory experience has been postulated to create an optimal therapeutic exposure condition and thereby improve extinction learning. We recently demonstrated increased connectivity in hippocampal circuits during the contextual retrieval of extinction memory following mindfulness training. METHODS: Here, we examine the role of structural changes in hippocampal subfields following mindfulness training in a randomized controlled longitudinal study using a two-day fear-conditioning and extinction protocol. RESULTS: We demonstrate an association between mindfulness training-related increases in subiculum and decreased hippocampal connectivity to lateral occipital regions during contextual retrieval of extinguished fear. Further, we demonstrate an association between decreased connectivity and decreases in self-reported anxiety following mindfulness training. CONCLUSIONS: The results highlight the role of the subiculum in gating interactions with contextual stimuli during memory retrieval and, also, the mechanisms through which mindfulness training may foster resilience.

Threat Prediction from Schemas as a Source of Bias in Pain Perception.

Our sensory impressions of pain are generally thought to represent the noxious properties of an agent but can be influenced by the predicted level of threat. Predictions can be sourced from higher-order cognitive processes, such as schemas, but the extent to which schemas can influence pain perception relative to bottom-up sensory inputs and the underlying neural underpinnings of such a phenomenon are unclear. Here, we investigate how threat predictions generated from learning a cognitive schema lead to inaccurate sensory impressions of the pain stimulus. Healthy male and female participants first detected a linear association between cue values and stimulus intensity and rated pain to reflect the linear schema when compared with uncued heat stimuli. The effect of bias on pain ratings was reduced when prediction errors (PEs) increased, but pain perception was only partially updated when measured against stepped increases in PEs. Cognitive, striatal, and sensory regions graded their responses to changes in predicted threat despite the PEs (p < 0.05, corrected). Individuals with more catastrophic thinking about pain and with low mindfulness were significantly more reliant on the schema than on the sensory evidence from the pain stimulus. These behavioral differences mapped to variability in responses of the striatum and ventromedial prefrontal cortex. Thus, this study demonstrates a significant role of higher-order schemas in pain perception and indicates that pain perception is biased more toward predictions and less toward nociceptive inputs in individuals who report less mindfulness and more fear of pain.SIGNIFICANCE STATEMENT This study demonstrates that threat predictions generated from cognitive schemas continue to influence pain perception despite increasing prediction errors arising in pain pathways. Individuals first formed a cognitive schema of linearity in the relationship between the cued threat value and the stimulus intensity. Subsequently, the linearity was reduced gradually, and participants partially updated their evaluations of pain in relation to the stepped increases in prediction errors. Individuals who continued to rate pain based more on the predicted threat than on changes in nociceptive inputs reported high pain catastrophizing and less mindful-awareness scores. These two affects mapped to activity in the ventral and dorsal striatum, respectively. These findings direct us to a significant role of top-down processes in pain perception.

Strengthened Hippocampal Circuits Underlie Enhanced Retrieval of Extinguished Fear Memories Following Mindfulness Training.

BACKGROUND: The role of hippocampus in context-dependent recall of extinction is well recognized. However, little is known about how intervention-induced changes in hippocampal networks relate to improvements in extinction learning. In this study, we hypothesized that mindfulness training creates an optimal exposure condition by heightening attention and awareness of present moment sensory experience, leading to enhanced extinction learning, improved emotion regulation, and reduced anxiety symptoms. METHODS: We tested this hypothesis in a randomized controlled longitudinal study design using a 2-day fear conditioning and extinction protocol. The mindfulness training group included 42 participants (28 women) and the control group included 25 participants (15 women). RESULTS: We show that mindfulness training is associated with differential engagement of the right supramarginal gyrus as well as hippocampal-cortical reorganization. We also report enhanced hippocampal connectivity to the primary sensory cortex during retrieval of extinguished stimuli following mindfulness training. CONCLUSIONS: These findings suggest hippocampal-dependent changes in contextual retrieval as one plausible neural mechanism through which mindfulness-based interventions enhance fear extinction and foster stress resilience.

Placebo Effect: Theory, Mechanisms and Teleological Roots.

Why pain can be relieved with placebos is heavily debated. The term "placebo effect," implies that the placebo treatment induces pain relief which is imprecise because it is the mental cueing to the context of treatment and not the placebo itself that can reduce pain. This essay reverts to fundamentals of perception that have been used to explain how context generates predictions that can in turn effect the process of processing, organizing and interpreting of sensory inputs received from the periphery. We reinterpret placebo effect as a neurobiological phenomenon that occurs through the process of reward and aversive learning. The brain uses learnt information to generate predictions. The perceptual processes adjust the experience of pain to fit with the predictions generated from prior information. Placebo effect is thus understandably a result of the expectations and mental states that result from engaging in the process of treatment. These processes have teleological roots in ancient medicine and are the context that produces these responses is transforming with the evolution of modern medicine. Thus, when placebo effect is observed, the potent agent that induces pain reduction is not the placebo itself, but the mental cueing to the context of taking treatment.

Common and Dissociable Neural Activity After Mindfulness-Based Stress Reduction and Relaxation Response Programs.

OBJECTIVE: We investigated common and dissociable neural and psychological correlates of two widely used meditation-based stress reduction programs. METHODS: Participants were randomized to the Relaxation Response (RR; n = 18; 56% female) or the Mindfulness-Based Stress Reduction (MBSR; n = 16; 56% female) programs. Both programs use a "bodyscan" meditation; however, the RR program explicitly emphasizes physical relaxation during this practice, whereas the MBSR program emphasizes mindful awareness with no explicit relaxation instructions. After the programs, neural activity during the respective meditation was investigated using functional magnetic resonance imaging. RESULTS: Both programs were associated with reduced stress (for RR, from 14.1 ± 6.6 to 11.3 ± 5.5 [Cohen's d = 0.50; for MBSR, from 17.7 ± 5.7 to 11.9 ± 5.0 [Cohen's d = 1.02]). Conjunction analyses revealed functional coupling between ventromedial prefrontal regions and supplementary motor areas (p < .001). The disjunction analysis indicated that the RR bodyscan was associated with stronger functional connectivity of the right inferior frontal gyrus-an important hub of intentional inhibition and control-with supplementary motor areas (p < .001, family-wise error [FWE] rate corrected). The MBSR program was uniquely associated with improvements in self-compassion and rumination, and the within-group analysis of MBSR bodyscan revealed significant functional connectivity of the right anterior insula-an important hub of sensory awareness and salience-with pregenual anterior cingulate during bodyscan meditation compared with rest (p = .03, FWE corrected). CONCLUSIONS: The bodyscan exercises in each program were associated with both overlapping and differential functional coupling patterns, which were consistent with each program's theoretical foundation. These results may have implications for the differential effects of these programs for the treatment of diverse conditions.

Maturation trajectories of cortical resting-state networks depend on the mediating frequency band.

The functional significance of resting state networks and their abnormal manifestations in psychiatric disorders are firmly established, as is the importance of the cortical rhythms in mediating these networks. Resting state networks are known to undergo substantial reorganization from childhood to adulthood, but whether distinct cortical rhythms, which are generated by separable neural mechanisms and are often manifested abnormally in psychiatric conditions, mediate maturation differentially, remains unknown. Using magnetoencephalography (MEG) to map frequency band specific maturation of resting state networks from age 7 to 29 in 162 participants (31 independent), we found significant changes with age in networks mediated by the beta (13-30 Hz) and gamma (31-80 Hz) bands. More specifically, gamma band mediated networks followed an expected asymptotic trajectory, but beta band mediated networks followed a linear trajectory. Network integration increased with age in gamma band mediated networks, while local segregation increased with age in beta band mediated networks. Spatially, the hubs that changed in importance with age in the beta band mediated networks had relatively little overlap with those that showed the greatest changes in the gamma band mediated networks. These findings are relevant for our understanding of the neural mechanisms of cortical maturation, in both typical and atypical development.

Dexmedetomidine Disrupts the Local and Global Efficiencies of Large-scale Brain Networks.

BACKGROUND: A clear understanding of the neural basis of consciousness is fundamental to research in clinical and basic neuroscience disciplines and anesthesia. Recently, decreased efficiency of information integration was suggested as a core network feature of propofol-induced unconsciousness. However, it is unclear whether this finding can be generalized to dexmedetomidine, which has a different molecular target. METHODS: Dexmedetomidine was administered as a 1-µg/kg bolus over 10 min, followed by a 0.7-µg · kg · h infusion to healthy human volunteers (age range, 18 to 36 yr; n = 15). Resting-state functional magnetic resonance imaging data were acquired during baseline, dexmedetomidine-induced altered arousal, and recovery states. Zero-lag correlations between resting-state functional magnetic resonance imaging signals extracted from 131 brain parcellations were used to construct weighted brain networks. Network efficiency, degree distribution, and node strength were computed using graph analysis. Parcellated brain regions were also mapped to known resting-state networks to study functional connectivity changes. RESULTS: Dexmedetomidine significantly reduced the local and global efficiencies of graph theory-derived networks. Dexmedetomidine also reduced the average brain connectivity strength without impairing the degree distribution. Functional connectivity within and between all resting-state networks was modulated by dexmedetomidine. CONCLUSIONS: Dexmedetomidine is associated with a significant drop in the capacity for efficient information transmission at both the local and global levels. These changes result from reductions in the strength of connectivity and also manifest as reduced within and between resting-state network connectivity. These findings strengthen the hypothesis that conscious processing relies on an efficient system of information transfer in the brain.