Intrinsic Functional Connectivity Resembles Cortical Architecture at Various Levels of Isoflurane Anesthesia.
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SUBMITTER: Fischer F
PROVIDER: S-EPMC6041950 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Despite their widespread use, the effect of anesthetic agents on the brain's functional architecture remains poorly understood. This is particularly true of alterations that occur beyond the point of induced unconsciousness. Here, we examined the distributed intrinsic connectivity of macaques across six isoflurane levels using resting-state functional MRI (fMRI) following the loss of consciousness. The results from multiple analysis strategies showed stable functional connectivity (FC) patterns between 1.00% and 1.50% suggesting this as a suitable range for anesthetized nonhuman primate resting-state investigations. Dose-dependent effects were evident at moderate to high dosages showing substantial alteration of the functional topology and a decrease or complete loss of interhemispheric cortical FC strength including that of contralateral homologues. The assessment of dynamic FC patterns revealed that the functional repertoire of brain states is related to anesthesia depth and most strikingly, that the number of state transitions linearly decreases with increased isoflurane dosage. Taken together, the results indicate dose-specific spatial and temporal alterations of FC that occur beyond the typically defined endpoint of consciousness. Future work will be necessary to determine how these findings generalize across anesthetic types and extend to the transition between consciousness and unconsciousness.
| S-EPMC6869297 | biostudies-literature
Project description:Animal functional magnetic resonance imaging (fMRI) has provided key insights into the physiological mechanisms underlying healthy and diseased brain states. In non-human primates, resting-state fMRI studies are commonly conducted under isoflurane anesthesia, where anesthetic concentration is used to roughly infer anesthesia depth. However, within the recommended isoflurane concentration range (1.00-1.50%), the brain state can switch from moderate anesthesia characterized by stable slow wave (SW) electroencephalogram (EEG) signals to deep anesthesia characterized by burst suppression (BS), which is electrophysiologically distinct from the resting state. To confirm the occurrence rate of BS activity in common setting of animal fMRI study, we conducted simultaneous resting-state EEG and fMRI experiments on 16 monkeys anesthetized using 0.80-1.30% isoflurane, and detected BS activity in two of them. Datasets either featured with BS or SW activity from these two monkeys were analyzed to investigate the intrinsic functional connectivity (FC) patterns during BS. In datasets with BS activity, we observed robust coupling between the BS pattern (the binary alternation between burst and suppression activity in EEG signal) and filtered BOLD signals in most brain areas, which was associated with a non-specific enhancement in whole brain connectivity. After eliminating the BS coupling effect by regressing out the BS pattern, we detected an overall increase in FC with a few decreased connectivity compared to datasets with SW activity. These affected connections were preferentially distributed within orbitofrontal cortex, between orbitofrontal and prefrontal/cingulate/occipital cortex, and between temporal and parietal cortex. Persistence of the default mode network and recovery of thalamocortical connections were also detected under deep anesthesia with BS activity. Taken together, the observed spatially specific alterations in BS activity induced by isoflurane not only highlight the necessity of EEG monitoring and careful data preprocessing in fMRI studies on anesthetized animals, but also advance our understanding of the underlying multi-phased mechanisms of anesthesia.
| S-EPMC6470287 | biostudies-literature
Project description:Disruption of cortical connectivity likely contributes to loss of consciousness (LOC) during both sleep and general anesthesia, but the degree of overlap in the underlying mechanisms is unclear. Both sleep and anesthesia comprise states of varying levels of arousal and consciousness, including states of largely maintained conscious experience (sleep: N1, REM; anesthesia: sedated but responsive) as well as states of substantially reduced conscious experience (sleep: N2/N3; anesthesia: unresponsive). Here, we tested the hypotheses that (1) cortical connectivity will exhibit clear changes when transitioning into states of reduced consciousness, and (2) these changes will be similar for arousal states of comparable levels of consciousness during sleep and anesthesia. Using intracranial recordings from five adult neurosurgical patients, we compared resting state cortical functional connectivity (as measured by weighted phase lag index, wPLI) in the same subjects across arousal states during natural sleep [wake (WS), N1, N2, N3, REM] and propofol anesthesia [pre-drug wake (WA), sedated/responsive (S), and unresponsive (U)]. Analysis of alpha-band connectivity indicated a transition boundary distinguishing states of maintained and reduced conscious experience in both sleep and anesthesia. In wake states WS and WA, alpha-band wPLI within the temporal lobe was dominant. This pattern was largely unchanged in N1, REM, and S. Transitions into states of reduced consciousness N2, N3, and U were characterized by dramatic changes in connectivity, with dominant connections shifting to prefrontal cortex. Secondary analyses indicated similarities in reorganization of cortical connectivity in sleep and anesthesia. Shifts from temporal to frontal cortical connectivity may reflect impaired sensory processing in states of reduced consciousness. The data indicate that functional connectivity can serve as a biomarker of arousal state and suggest common mechanisms of LOC in sleep and anesthesia.
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Project description:The brain's functional network exhibits many features facilitating functional specialization, integration, and robustness to attack. Using graph theory to characterize brain networks, studies demonstrate their small-world, modular, and "rich-club" properties, with deviations reported in many common neuropathological conditions. Here we estimate the heritability of five widely used graph theoretical metrics (mean clustering coefficient (γ), modularity (Q), rich-club coefficient (ϕnorm), global efficiency (λ), small-worldness (σ)) over a range of connection densities (k=5-25%) in a large cohort of twins (N=592, 84 MZ and 89 DZ twin pairs, 246 single twins, age 23 ± 2.5). We also considered the effects of global signal regression (GSR). We found that the graph metrics were moderately influenced by genetic factors h(2) (γ=47-59%, Q=38-59%, ϕnorm=0-29%, λ=52-64%, σ=51-59%) at lower connection densities (≤ 15%), and when global signal regression was implemented, heritability estimates decreased substantially h(2) (γ=0-26%, Q=0-28%, ϕnorm=0%, λ=23-30%, σ=0-27%). Distinct network features were phenotypically correlated (|r|=0.15-0.81), and γ, Q, and λ were found to be influenced by overlapping genetic factors. Our findings suggest that these metrics may be potential endophenotypes for psychiatric disease and suitable for genetic association studies, but that genetic effects must be interpreted with respect to methodological choices.
| S-EPMC4837693 | biostudies-literature
Project description:This observational, cross-sectional study investigates cortical signatures of developmental dyslexia, particularly from the perspective of behavioral remediation. We employed resting-state fMRI, and compared intrinsic functional connectivity (iFC) patterns of known reading regions (seeds) among three dyslexia groups characterized by (a) no remediation (current reading and spelling deficits), (b) partial remediation (only reading deficit remediated), and (c) full remediation (both reading and spelling deficits remediated), and a group of age- and IQ-matched typically developing children (TDC) (total N?=?44, age range?=?7-15 years). We observed significant group differences in iFC of two seeds located in the left posterior reading network - left intraparietal sulcus (L.IPS) and left fusiform gyrus (L.FFG). Specifically, iFC between L.IPS and left middle frontal gyrus was significantly weaker in all dyslexia groups, irrespective of remediation status/literacy competence, suggesting that persistent dysfunction in the fronto-parietal attention network characterizes dyslexia. Additionally, relative to both TDC and the no remediation group, the remediation groups exhibited stronger iFC between L.FFG and right middle occipital gyrus (R.MOG). The full remediation group also exhibited stronger negative iFC between the same L.FFG seed and right medial prefrontal cortex (R.MPFC), a core region of the default network These results suggest that behavioral remediation may be associated with compensatory changes anchored in L.FFG, which reflect atypically stronger coupling between posterior visual regions (L.FFG-R.MOG) and greater functional segregation between task-positive and task-negative regions (L.FFG-R.MPFC). These findings were bolstered by significant relationships between the strength of the identified functional connections and literacy scores. We conclude that examining iFC can reveal cortical signatures of dyslexia with particular promise for monitoring neural changes associated with behavioral remediation.
| S-EPMC3569450 | biostudies-literature
Project description:IntroductionCorrelated low-frequency fluctuations of resting-state functional magnetic resonance imaging (rsfMRI) signals have been widely used for inferring intrinsic brain functional connectivity (FC). In animal studies, accurate estimate of anesthetic effects on rsfMRI signals is demanded for reliable interpretations of FC changes. We have previously shown that inter-regional FC can reliably delineate local millimeter-scale circuits within digit representations of primary somatosensory cortex (S1) subregions (areas 3a, 3b, and 1) in monkeys under isoflurane anesthesia. The goals of this study are to determine (1) the general effects of isoflurane on rsfMRI signals in the S1 circuit and (2) whether the effects are functional- and regional- dependent, by quantifying the relationships between isoflurane levels, power and inter-regional correlation coefficients in digit and face regions of distinct S1 subregions.MethodsFunctional MRI data were collected from male adult squirrel monkeys at three different isoflurane levels (1.25%, 0.875%, and 0.5%). All scans were acquired on a 9.4T magnet with a 3-cm-diameter surface transmit-receive coil centered over the S1 cortex. Power and seed-based inter-regional functional connectivity analyses were subsequently performed.ResultsAs anesthesia level increased, we observed (1) diminishing amplitudes of signal fluctuations, (2) reduced power of fluctuations in the low-frequency band used for connectivity measurements, (3) decreased inter-voxel connectivity around seed regions, and (4) weakened inter-regional FC across all pairs of regions of interest (digit-to-digit). The low-frequency power measures derived from rsfMRI signals from control muscle regions, however, did not exhibit any isoflurane level-related changes. Within the isoflurane dosage range we tested, the inter-regional functional connectivity differences were still detectable, and the effects of isoflurane did not differ across region-of-interest (ROI) pairs.ConclusionOur data demonstrate that isoflurane induced similar dose-dependent suppressive effects on the power of rsfMRI signals and local fine-scale FC across functionally related but distinct S1 subregions.
| S-EPMC5167001 | biostudies-literature
Project description:ObjectiveGrowing evidence has implicated dysfunction of the thalamus and its projection cortical targets in depression. However, the anatomical specificity of thalamo-cortical connectivity in major depressive disorder (MDD) remains unknown due to the regional heterogeneity of the thalamus and limited methods to examine this.MethodsResting-state fMRI was collected on 70 MDD patients and 70 healthy controls. The thalamus was parcellated based on connectivity with six predefined cortical regions of interest (ROIs). The segmented thalamic nuclei were used as seeds to map connectivity with the rest of the whole brain. The cortical-to-thalamus connectivity values and thalamus-based connectivity maps were compared between groups.ResultsThe cortical ROIs demonstrated correlations with spatially distinct zones within the thalamus. We found a trend toward reduced parietal ROI-to-thalamus connectivity in MDD. Importantly, MDD patients demonstrated reduced connectivity between prefrontal and parietal thalamus ROIs and bilateral middle frontal gyrus (MFG) and the right posterior default mode network (DMN) and between the prefrontal and motor thalamus ROIs and lateral temporal regions. Conversely, increased connectivity emerged between the motor thalamus ROI and right MFG and right medial frontal gyrus/anterior cingulate; between motor/somatosensory thalamus ROIs and right posterior DMN; between prefrontal/somatosensory thalamus ROIs and cerebellum; and between the parietal thalamus ROI and left insula.ConclusionsThis study is the first to examine the anatomical specificity of thalamo-cortical connectivity disturbances in MDD. Subjects with MDD demonstrated altered thalamo-cortical connectivity characterized by a complex pattern of region-dependent hypo- or hyperconnectivity. We therefore speculate that selectively modulating the connectivity of thalamo-cortical circuitry may be a potential novel therapeutic mechanism for MDD.
| S-EPMC6490069 | biostudies-literature
Project description:BACKGROUND:Functional connectivity across the cortex has been posited to be important for consciousness and anesthesia, but functional connectivity patterns during the course of surgery and general anesthesia are unknown. The authors tested the hypothesis that disrupted cortical connectivity patterns would correlate with surgical anesthesia. METHODS:Surgical patients (n = 53) were recruited for study participation. Whole-scalp (16-channel) wireless electroencephalographic data were prospectively collected throughout the perioperative period. Functional connectivity was assessed using weighted phase lag index. During anesthetic maintenance, the temporal dynamics of connectivity states were characterized via Markov chain analysis, and state transition probabilities were quantified. RESULTS:Compared to baseline (weighted phase lag index, 0.163, ± 0.091), alpha frontal-parietal connectivity was not significantly different across the remaining anesthetic and perioperative epochs, ranging from 0.100 (± 0.041) to 0.218 (± 0.136) (P > 0.05 for all time periods). In contrast, there were significant increases in alpha prefrontal-frontal connectivity (peak = 0.201 [0.154, 0.248]; P < 0.001), theta prefrontal-frontal connectivity (peak = 0.137 [0.091, 0.182]; P < 0.001), and theta frontal-parietal connectivity (peak = 0.128 [0.084, 0.173]; P < 0.001) during anesthetic maintenance. Additionally, shifts occurred between states of high prefrontal-frontal connectivity (alpha, beta) with suppressed frontal-parietal connectivity, and high frontal-parietal connectivity (alpha, theta) with reduced prefrontal-frontal connectivity. These shifts occurred in a nonrandom manner (P < 0.05 compared to random transitions), suggesting structured transitions of connectivity during general anesthesia. CONCLUSIONS:Functional connectivity patterns dynamically shift during surgery and general anesthesia but do so in a structured way. Thus, a single measure of functional connectivity will likely not be a reliable correlate of surgical anesthesia.
| S-EPMC6520139 | biostudies-literature
Project description:An advanced understanding of the neurophysiologic changes that occur with aging may help improve care for older, vulnerable surgical patients. The objective of this study was to determine age-related changes in cortical connectivity patterns during surgical anesthesia. This was a substudy analysis of a prospective, observational study characterizing cortical connectivity during surgical anesthesia in adult patients (n = 45) via whole-scalp (16-channel) electroencephalography. Functional connectivity was estimated using a weighted phase lag index (wPLI), which was classified into a discrete set of states through k-means analysis. Temporal dynamics were quantified by occurrence rate and state transition probabilities. The mean global connectivity state transition probability [13.4% (±8.1)] was not correlated with age (ρ = 0.100, p = 0.513). Increasing age was inversely correlated with prefrontal-frontal alpha-beta connectivity (ρ = -0.446, p = 0.002) and positively correlated with frontal-parietal theta connectivity (ρ = 0.414, p = 0.005). After adjusting for anesthetic-related confounders, prefrontal-frontal alpha-beta connectivity remained significantly associated with age (β = -0.625, 95% CI -0.99 to -0.26; p = 0.001), while frontal-parietal theta connectivity was no longer significant (β = 0.436, 95% CI -0.03 to 0.90; p = 0.066). Specific transition states were also examined. Between frontal-parietal connectivity states, transitioning from theta-alpha to theta-dominated connectivity positively correlated with age (ρ = 0.545, p = 0.001). Dynamic connectivity states during surgical anesthesia, particularly involving alpha and theta bandwidths, maybe an informative measure to assess neurophysiologic changes that occur with aging.
| S-EPMC6967734 | biostudies-literature
Project description:Human beings are social animals and they vary in the degree to which they share information about themselves with others. Although brain networks involved in self-related cognition have been identified, especially via the use of resting-state experiments, the neural circuitry underlying individual differences in the sharing of self-related information is currently unknown. Therefore, we investigated the intrinsic functional organization of the brain with respect to participants' degree of self-related information sharing using resting state functional magnetic resonance imaging and self-reported social media use. We conducted seed-based correlation analyses in cortical midline regions previously shown in meta-analyses to be involved in self-referential cognition: the medial prefrontal cortex (MPFC), central precuneus (CP), and caudal anterior cingulate cortex (CACC). We examined whether and how functional connectivity between these regions and the rest of the brain was associated with participants' degree of self-related information sharing. Analyses revealed associations between the MPFC and right dorsolateral prefrontal cortex (DLPFC), as well as the CP with the right DLPFC, the left lateral orbitofrontal cortex and left anterior temporal pole. These findings extend our present knowledge of functional brain connectivity, specifically demonstrating how the brain's intrinsic functional organization relates to individual differences in the sharing of self-related information.
| S-EPMC4780087 | biostudies-other