Electroencephalographic Biomarkers, Cerebral Oximetry, and Postoperative Cognitive Function in Adult Noncardiac Surgical Patients: A Prospective Cohort Study.

BACKGROUND: Perioperative neurocognitive disorders are a major public health issue, although there are no validated neurophysiologic biomarkers that predict cognitive function after surgery. This study tested the hypothesis that preoperative posterior electroencephalographic alpha power, alpha frontal-parietal connectivity, and cerebral oximetry would each correlate with postoperative neurocognitive function. METHODS: This was a single-center, prospective, observational study of adult (older than 18 yr) male and female noncardiac surgery patients. Whole-scalp, 16-channel electroencephalography and cerebral oximetry were recorded in the preoperative, intraoperative, and immediate postoperative settings. The primary outcome was the mean postoperative T-score of three National Institutes of Health Toolbox Cognition tests-Flanker Inhibitory Control and Attention, List Sorting Working Memory, and Pattern Comparison Processing Speed. These tests were obtained at preoperative baseline and on the first two postoperative mornings. The lowest average score from the first two postoperative days was used for the primary analysis. Delirium was a secondary outcome (via 3-min Confusion Assessment Method) measured in the postanesthesia care unit and twice daily for the first 3 postoperative days. Last, patient-reported outcomes related to cognition and overall well-being were collected 3 months postdischarge. RESULTS: Sixty-four participants were recruited with a median (interquartile range) age of 59 (48 to 66) yr. After adjustment for baseline cognitive function scores, no significant partial correlation (ρ) was detected between postoperative cognition scores and preoperative relative posterior alpha power (%; ρ = -0.03, P = 0.854), alpha frontal-parietal connectivity (via weight phase lag index; ρ = -0.10, P = 0.570, respectively), or preoperative cerebral oximetry (%; ρ = 0.21, P = 0.246). Only intraoperative frontal-parietal theta connectivity was associated with postoperative delirium (F[1,6,291] = 4.53, P = 0.034). No electroencephalographic or oximetry biomarkers were associated with cognitive or functional outcomes 3 months postdischarge. CONCLUSIONS: Preoperative posterior alpha power, frontal-parietal connectivity, and cerebral oximetry were not associated with cognitive function after noncardiac surgery.

Retrospective study evaluating telehealth antenatal anesthesia consults for high-risk obstetric patients.

BACKGROUND: Telehealth has gained popularity, particularly in the COVID-19 era. The use of telehealth is now being applied to preoperative evaluation clinics in an effort to overcome barriers to antenatal anesthesia assessment of high-risk obstetrical patients. OBJECTIVES: The objective of this study is to determine if the quality of antenatal anesthesia telehealth consults of high-risk obstetric patients is comparable to in-person encounters. This is determined by assessing if telehealth consults are feasible and meet the standards of care, as well as the level of patient satisfaction and ease of use as reported by providers. STUDY DESIGN: This retrospective study assessed patients prior to delivery who completed a video-telehealth anesthesia consultation (51 cases) from November 1st, 2019 to November 30th, 2020 and all of those for patients receiving an in-person anesthesia consultation (171 controls) from November 2017 through October 2019. Our primary hypothesis was that telehealth and in-person consultations would not result in different standards of care. The primary outcome was an indicator of meeting the standard of care, and the difference in proportions between the telehealth and in-person consultation was tested by Fisher's exact test. Our secondary hypotheses were that patients reported high levels of satisfaction and could use telehealth easily and providers could use the platform easily. Secondary outcomes were assessed by using the Consultation and Relational Empathy (CARE) and the Telehealth Usability Questionnaire (TUQ) surveys, respectively. RESULTS: For the primary outcome, 94.1% (48/51) of telehealth and 89.5% (153/171) of in-person visits met the standard of care, indicating no significant difference between groups (p-value = .4204). The CARE score was 46 [41,50] {median [interquartile range]}, (p-value < .0001), indicating patient satisfaction with telehealth. The use-average scores on the TUQ for the patient and provider were 6.67 [6.33, 7] and 6 [5.33, 7] respectively, indicating great system usability. CONCLUSION: This study demonstrates no significant difference in the standard of care between in-person and telehealth visits. Furthermore, telehealth consultation was feasible and associated with high patient satisfaction and platform usability. Preoperative consultation of high-risk obstetric patients using telehealth visits should be routinely considered in clinical practice.Condensation: There is no significant difference in the standard of care between in-person and telehealth antenatal anesthesia consultations, and patients report high satisfaction and platform usability.Telehealth is gaining popularity, but its role in antenatal anesthesia consultation of high risk obstetrical patients has not yet been defined with respect to standard of care, patient satisfaction, and platform usability.There was no significant difference in standard of care between in-person and telehealth antenatal anesthesia consultations, and patients reported high satisfaction and platform usability.Telehealth should be considered as an alternative to in-person antenatal anesthesia consultation of high risk obstetrical patients. It is a particularly attractive alternative to in-person consultation due to cost-savings, increased patient accessibility, and ease of use.

Anterior insula regulates brain network transitions that gate conscious access.

Conscious access to sensory information is likely gated at an intermediate site between primary sensory and transmodal association cortices, but the structure responsible remains unknown. We perform functional neuroimaging to determine the neural correlates of conscious access using a volitional mental imagery task, a report paradigm not confounded by motor behavior. Titrating propofol to loss of behavioral responsiveness in healthy volunteers creates dysfunction of the anterior insular cortex (AIC) in association with an impairment of dynamic transitions of default-mode and dorsal attention networks. Candidate subcortical regions mediating sensory gating or arousal (thalamus, basal forebrain) fail to show this association. The gating role of the AIC is consistent with findings in awake participants, whose conscious access is predicted by pre-stimulus AIC activity near perceptual threshold. These data support the hypothesis that AIC, situated at an intermediate position of the cortical hierarchy, regulates brain network transitions that gate conscious access.

Asymmetric neural dynamics characterize loss and recovery of consciousness.

Anesthetics are known to disrupt neural interactions in cortical and subcortical brain circuits. While the effect of anesthetic drugs on consciousness is reversible, the neural mechanism mediating induction and recovery may be different. Insight into these distinct mechanisms can be gained from a systematic comparison of neural dynamics during slow induction of and emergence from anesthesia. To this end, we used functional magnetic resonance imaging (fMRI) data obtained in healthy volunteers before, during, and after the administration of propofol at incrementally adjusted target concentrations. We analyzed functional connectivity of corticocortical and subcorticocortical networks and the temporal autocorrelation of fMRI signal as an index of neural processing timescales. We found that en route to unconsciousness, temporal autocorrelation across the entire brain gradually increased, whereas functional connectivity gradually decreased. In contrast, regaining consciousness was associated with an abrupt restoration of cortical but not subcortical temporal autocorrelation and an abrupt boost of subcorticocortical functional connectivity. Pharmacokinetic effects could not account for the difference in neural dynamics between induction and emergence. We conclude that the induction and recovery phases of anesthesia follow asymmetric neural dynamics. A rapid increase in the speed of cortical neural processing and subcorticocortical neural interactions may be a mechanism that reboots consciousness.

Cortical Oscillations and Connectivity During Postoperative Recovery.

BACKGROUND: The objective of this study was to test whether postoperative electroencephalographic (EEG) biomarkers, parietal alpha power and frontal-parietal connectivity, were associated with measures of clinical recovery in adult surgical patients. METHODS: This is a secondary analysis of a prospective cohort study that analyzed intraoperative connectivity patterns in adult surgical patients (N=53). Wireless, whole-scalp EEG data were collected in the postanesthesia care unit and assessed for relevance to clinical and neurocognitive recovery. Parietal alpha power and frontal-parietal connectivity (estimated by weighted phase lag index) were tested for associations with postanesthesia care unit discharge readiness and University of Michigan Sedation Scale scores upon postoperative admission. Bivariable correlation and regression models were constructed to test for unadjusted associations, then multivariable regression models were constructed to adjust for confounding. RESULTS: Postoperative EEG patterns were characterized by a predominance of alpha parietal power and frontal-parietal connectivity. Neither relative parietal alpha power (% alpha, -0.25; 95% confidence interval [CI], -1.41 to 0.90; P=0.657) nor alpha frontal-parietal connectivity (weighted phase lag index, -82; 95% CI, -237 to 73; P=0.287) were associated with time until postanesthesia discharge criteria were met. Furthermore, neither alpha power (-0.03; 95% CI, -0.07 to 0.01; P=0.206) nor alpha frontal-parietal connectivity (-4.2; 95% CI, -11 to 2.6; P=0.226) were associated with sedation scores upon initial assessment. CONCLUSIONS: In a pragmatic study investigating clinically relevant endpoints of postoperative recovery, we found no correlation with surrogate measures of brain neurodynamics. These data contribute to the overall impetus of developing anesthetic-invariant and generalizable markers of brain recovery.

Dynamic Cortical Connectivity during General Anesthesia in Surgical Patients.

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.

Home-based Cognitive Prehabilitation in Older Surgical Patients: A Feasibility Study.

BACKGROUND: Cognitive training is beneficial in various clinical settings, although its perioperative feasibility and impact remain unknown. The objective of this pilot study was to determine the feasibility of home-based cognitive prehabilitation before major surgery in older adults. MATERIALS AND METHODS: Sixty-one patients were enrolled, randomized, and allocated to either a home-based preoperative cognitive training regimen or no training before surgery. Outcomes included postoperative delirium incidence (primary outcome; assessed with the 3D-Confusion Assessment Method), perioperative cognitive function based on NIH Toolbox measures, hospital length of stay, and physical therapy session participation. Reasons for declining enrollment were reported, as were reasons for opting out of the training program. RESULTS: Postoperative delirium incidence was 6 of 23 (26%) in the prehabilitation group compared with 5 of 29 (17%) in the control group (P=0.507). There were no significant differences between groups in NIH Toolbox cognitive function scoring, hospital length of stay, or physical therapy participation rates. Study feasibility data were also collected and reported. The most common reasons for declining enrollment were lack of computer access (n=19), time commitment (n=9), and feeling overwhelmed (n=9). In the training group, only 5 of 29 (17%) included patients were able to complete the prescribed 7 days of training, and 14 of 29 (48%) opted out of training once home. Most common reasons were feeling overwhelmed (n=4) and computer difficulties (n=3). CONCLUSIONS: Short-term, home-based cognitive training before surgery is unlikely to be feasible for many older patients. Barriers to training include feeling overwhelmed, technical issues with training, and preoperative time commitment.

Brain imaging reveals covert consciousness during behavioral unresponsiveness induced by propofol.

Detecting covert consciousness in behaviorally unresponsive patients by brain imaging is of great interest, but a reproducible model and evidence from independent sources is still lacking. Here we demonstrate the possibility of using general anesthetics in a within-subjects study design to test methods or statistical paradigms of assessing covert consciousness. Using noninvasive neuroimaging in healthy volunteers, we identified a healthy study participant who was able to exhibit the specific fMRI signatures of volitional mental imagery while behaviorally unresponsive due to sedation with propofol. Our findings reveal a novel model that may accelerate the development of new approaches to reproducibly detect covert consciousness, which is difficult to achieve in patients with heterogeneous and sometimes clinically unstable neuropathology.

Neurophysiologic Correlates of Ketamine Sedation and Anesthesia: A High-density Electroencephalography Study in Healthy Volunteers.

BACKGROUND: Previous studies have demonstrated inconsistent neurophysiologic effects of ketamine, although discrepant findings might relate to differences in doses studied, brain regions analyzed, coadministration of other anesthetic medications, and resolution of the electroencephalograph. The objective of this study was to characterize the dose-dependent effects of ketamine on cortical oscillations and functional connectivity. METHODS: Ten healthy human volunteers were recruited for study participation. The data were recorded using a 128-channel electroencephalograph during baseline consciousness, subanesthetic dosing (0.5 mg/kg over 40 min), anesthetic dosing (1.5 mg/kg bolus), and recovery. No other sedative or anesthetic medications were administered. Spectrograms, topomaps, and functional connectivity (weighted and directed phase lag index) were computed and analyzed. RESULTS: Frontal theta bandwidth power increased most dramatically during ketamine anesthesia (mean power ± SD, 4.25 ± 1.90 dB) compared to the baseline (0.64 ± 0.28 dB), subanesthetic (0.60 ± 0.30 dB), and recovery (0.68 ± 0.41 dB) states; P < 0.001. Gamma power also increased during ketamine anesthesia. Weighted phase lag index demonstrated theta phase locking within anterior regions (0.2349 ± 0.1170, P < 0.001) and between anterior and posterior regions (0.2159 ± 0.1538, P < 0.01) during ketamine anesthesia. Alpha power gradually decreased with subanesthetic ketamine, and anterior-to-posterior directed connectivity was maximally reduced (0.0282 ± 0.0772) during ketamine anesthesia compared to all other states (P < 0.05). CONCLUSIONS: Ketamine anesthesia correlates most clearly with distinct changes in the theta bandwidth, including increased power and functional connectivity. Anterior-to-posterior connectivity in the alpha bandwidth becomes maximally depressed with anesthetic ketamine administration, suggesting a dose-dependent effect.

Asynchronous changes in phenology of migrating Broad-tailed Hummingbirds and their early-season nectar resources.

Phenological advancements driven by climate change are especially pronounced at higher latitudes, so that migrants from lower latitudes may increasingly arrive at breeding grounds after the appearance of seasonal resources. To explore this possibility, we compared dates of first arrival of Broad-tailed Hummingbirds (Selasphorus platycercus) to dates of flowering of plants they visit for nectar. Near the southern limit of the breeding range, neither hummingbird arrival nor first flowering dates have changed significantly over the past few decades. At a nearby migration stopover site, first flowering of a major food plant has advanced, but peak flowering has not. Near the northern limit of the breeding range, first and peak flowering of early-season food plants have shifted to earlier dates, resulting in a shorter interval between appearance of first hummingbirds and first flowers. If phenological shifts continue at current rates, hummingbirds will eventually arrive at northern breeding grounds after flowering begins, which could reduce their nesting success. These results support the prediction that migratory species may experience the greatest phenological mismatches at the poleward limits of their migration. A novel hypothesis based on these results posits that the poleward limit for some species may contract toward lower latitudes under continued warming.

Phenotypic plasticity and adaptive evolution contribute to advancing flowering phenology in response to climate change.

Anthropogenic climate change has already altered the timing of major life-history transitions, such as the initiation of reproduction. Both phenotypic plasticity and adaptive evolution can underlie rapid phenological shifts in response to climate change, but their relative contributions are poorly understood. Here, we combine a continuous 38 year field survey with quantitative genetic field experiments to assess adaptation in the context of climate change. We focused on Boechera stricta (Brassicaeae), a mustard native to the US Rocky Mountains. Flowering phenology advanced significantly from 1973 to 2011, and was strongly associated with warmer temperatures and earlier snowmelt dates. Strong directional selection favoured earlier flowering in contemporary environments (2010-2011). Climate change could drive this directional selection, and promote even earlier flowering as temperatures continue to increase. Our quantitative genetic analyses predict a response to selection of 0.2 to 0.5 days acceleration in flowering per generation, which could account for more than 20 per cent of the phenological change observed in the long-term dataset. However, the strength of directional selection and the predicted evolutionary response are likely much greater now than even 30 years ago because of rapidly changing climatic conditions. We predict that adaptation will likely be necessary for long-term in situ persistence in the context of climate change.