Electroencephalographic markers of brain development during sevoflurane anesthesia in children aged 0 to 3 years old

Abstract

The general anesthetic sevoflurane acts on GABAergic-interneurons to generate stereotyped oscillations that relate fundamentally to neural circuit architecture. Each year, millions of children require general anesthesia, providing an experiment of nature that allows characterization of the developmental trajectory of GABAergic-inhibitory circuits in the human brain. We used multichannel electroencephalograph recordings in 91 children 0-40 months old. We mapped spatial power and coherence across the cortex. During sevoflurane exposure: (1) slow-delta oscillations are present in all ages; (2) theta and alpha oscillations emerge around 4 months; (3) alpha oscillations increase in power from 4 to 10 months; (4) frontal alpha oscillation predominance emerge at ~6 months; (5) frontal slow oscillations are coherent in the first 6 months of age only; and (6) frontal alpha oscillations become coherent around 10 months and persist in older ages. Our results suggest key developmental milestones are visible in the functional activity of sevoflurane-stimulated GABAergic circuits.

Electroencephalographic features of discontinuous activity in anesthetized infants and children

“…Our results suggest that the raw EEG and spectrogram may be of clinical use to assess an “over-anesthetized” brain in the absence of adequate depth of anesthesia monitors in young infants. Previous work from our group and others has characterized the distinct features of sevoflurane [14,15,20] and propofol [32,33] induced oscillations during the maintenance phase in children, and in particular the associations of specific spectral profiles with behavioral events [14,21,34]. Here we found that changes in these dynamics preceding discontinuous activity can be visualized as well.…”

“…We analyzed only one electrode because discontinuity events occurred simultaneously across all leads (to the limit of our temporal resolution). We focused on F7 because we have previously observed notable changes in frontal oscillations related to anesthetic depth and development [14,15].…”

“…The EEG data collected during general anesthesia have been reported elsewhere: specifically, as a descriptive study on discontinuity during deep levels of anesthesia at 0–3 years old [11], on spectral and coherence patterns during maintenance and emergence anesthesia at 0–6 months and 0–3 yrs old [14,15,21], and in evaluating machine-learning algorithms to predict anesthetic concentration in neonatal animals and human infants at 0–6 months old [22]. A statement on the use of previously published data sets is given in the Supporting Information (S2 File).…”

“…In adults, for example, increased alpha (8-12Hz) oscillations appear during loss of consciousness and are sustained during maintenance anesthesia, reflecting thalamocortical and corticocortical connectivity [13]. In contrast, alpha oscillations in infants are absent from birth until 3-months, gradually appearing until they reflect an adult-like pattern at around 10-months old [14,15].…”