Low Frontal Alpha Power Is Associated With the Propensity for Burst Suppression: An Electroencephalogram Phenotype for a "Vulnerable Brain"

Abstract

Background: A number of recent studies have reported an association between intraoperative burst suppression and postoperative delirium. These studies suggest that anesthesia-induced burst suppression may be an indicator of underlying brain vulnerability. A prominent feature of electroencephalogram (EEG) under propofol and sevoflurane anesthesia is the frontal alpha oscillation. This frontal alpha oscillation is known to decline significantly during aging and is generated by prefrontal brain regions that are particularly prone to age-related neurodegeneration. Given that burst suppression and frontal alpha oscillations are both associated with brain vulnerability, we hypothesized that anesthesia-induced frontal alpha power could also be associated with burst suppression.

Methods: We analyzed EEG data from a previously reported cohort in which 155 patients received propofol (n = 60) or sevoflurane (n = 95) as the primary anesthetic. We computed the EEG spectrum during stable anesthetic maintenance and identified whether or not burst suppression occurred during the anesthetic. We characterized the relationship between burst suppression and alpha power using logistic regression. We proposed 5 different models consisting of different combinations of potential contributing factors associated with burst suppression: (1) a Base Model consisting of alpha power; (2) an Extended Mechanistic Model consisting of alpha power, age, and drug dosing information; (3) a Clinical Confounding Factors Model consisting of alpha power, hypotension, and other confounds; (4) a Simplified Model consisting only of alpha power and propofol bolus administration; and (5) a Full Model consisting of all of these variables to control for as much confounding as possible.

Results: All models show a consistent significant association between alpha power and burst suppression while adjusting for different sets of covariates, all with consistent effect size estimates. Using the Simplified Model, we found that for each decibel decrease in alpha power, the odds of experiencing burst suppression increased by 1.33-fold.

Conclusions: In this study, we show how a decrease in anesthesia-induced frontal alpha power is associated with an increased propensity for burst suppression, in a manner that captures individualized information above and beyond a patient's chronological age. Lower frontal alpha band power is strongly associated with higher propensity for burst suppression and, therefore, potentially higher risk of postoperative neurocognitive disorders. We hypothesize that low frontal alpha power and increased propensity for burst suppression together characterize a "vulnerable brain" phenotype under anesthesia that could be mechanistically linked to brain metabolism, cognition, and brain aging.

Conflict of interest statement

Conflicts of Interest: See Disclosures at the end of the article.

Figures

Figure 1.

Logistic regression fit for the Base Model. Alpha power is strongly associated with burst suppression. The empirical probabilities of burst suppression were estimated as a function of alpha power by calculating the proportions of subjects showing burst suppression in 20 equally spaced bins across the range of observed alpha power. As alpha power decreases from >15 to

Figure 2.

Electroencephalogram spectrograms from individual patients illustrating the relationship between power in anesthesia-induced alpha band activity and burst suppression. Top, The spectrogram shows an example of a patient with high alpha power and no burst suppression. Bottom, The spectrogram shows an example of a different patient with low alpha power and prolonged burst suppression.

Figure 3.

Electroencephalogram spectrograms from individual patients illustrating the variation in power in anesthesia-induced alpha band activity spanning young, middle-aged, and older adults. Top, There is an overall decreasing trend in alpha power with increasing age, comparing a 30-year-old patient and an 81-year-old patient. Bottom, On the other hand, at a given age, there can also be significant variation in frontal alpha power, comparing 2 middle-aged patients of comparable age.

Figure 4.

Odds ratios for burst suppression with different levels of alpha power, based on the Simplified Model. After adjusting for propofol bolus rate, for each decibel decrease in alpha power, the odds of experiencing burst suppression increase by 1.33-fold (95% CI, 1.19–1.49). CI indicates confidence interval.

Figure 5.

The receiving operating characteristic curves for the Base Model, the Extended Mechanistic Model, the Clinical Confounding Factors Model, the Simplified Model, and the Full Model. All of the models have comparable AUCs (0.801, 0.845, 0.800, 0.821, and 0.851 respectively). The colored area around each curve represents the 95% confidence interval. AUC indicates area under the curve.

Figure 6.

The “vulnerable brain” under anesthesia: a hypothesis linking metabolism, brain oscillations, burst suppression, and cognitive decline. Decreased astrocytic AG in prefrontal cortex fails to provide adequate metabolic support for neuronal oxidative phosphorylation (1) and sustained synaptic neurotransmission (2). Burst suppression is thought to occur when the brain has an inadequate supply of ATP. If metabolism is compromised as in (1) and (2), further depression of brain metabolism by anesthetic drugs via impaired mitochondrial function (3) results in a higher propensity for burst suppression. Astrocytes support brain metabolism, but are also thought to support brain oscillations through their highly connected syncytial networks. In the aging brain with preexisting neuromodulatory deficits, general anesthesia further inhibits subcortical neuromodulatory inputs on astrocyte syncytial networks (4) and suppresses astrocyte–neuron metabolic interactions, leading to less robust brain oscillations. Ach indicates acetylcholine; AG, aerobic glycolysis; ATP, adenosine triphosphate; NE, norepinephrine.