Age-Dependent Changes in the Propofol-Induced Electroencephalogram in Children With Autism Spectrum Disorder

Abstract

Patients with autism spectrum disorder (ASD) often require sedation or general anesthesia. ASD is thought to arise from deficits in GABAergic signaling leading to abnormal neurodevelopment. We sought to investigate differences in how ASD patients respond to the GABAergic drug propofol by comparing the propofol-induced electroencephalogram (EEG) of ASD and neurotypical (NT) patients. This investigation was a prospective observational study. Continuous 4-channel frontal EEG was recorded during routine anesthetic care of patients undergoing endoscopic procedures between July 1, 2014 and May 1, 2016. Study patients were defined as those with previously diagnosed ASD by DSM-V criteria, aged 2–30 years old. NT patients were defined as those lacking neurological or psychiatric abnormalities, aged 2–30 years old. The primary outcome was changes in propofol-induced alpha (8–13 Hz) and slow (0.1–1 Hz) oscillation power by age. A post hoc analysis was performed to characterize incidence of burst suppression during propofol anesthesia. The primary risk factor of interest was a prior diagnosis of ASD. Outcomes were compared between ASD and NT patients using Bayesian methods. Compared to NT patients, slow oscillation power was initially higher in ASD patients (17.05 vs. 14.20 dB at 2.33 years), but progressively declined with age (11.56 vs. 13.95 dB at 22.5 years). Frontal alpha power was initially lower in ASD patients (17.65 vs. 18.86 dB at 5.42 years) and continued to decline with age (6.37 vs. 11.89 dB at 22.5 years). The incidence of burst suppression was significantly higher in ASD vs. NT patients (23.0% vs. 12.2%, p < 0.01) despite reduced total propofol dosing in ASD patients. Ultimately, we found that ASD patients respond differently to propofol compared to NT patients. A similar pattern of decreased alpha power and increased sensitivity to burst suppression develops in older NT adults; one interpretation of our data could be that ASD patients undergo a form of accelerated neuronal aging in adolescence. Our results suggest that investigations of the propofol-induced EEG in ASD patients may enable insights into the underlying differences in neural circuitry of ASD and yield safer practices for managing patients with ASD.

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.…”

Sex differences in neuronal systems function and behaviour: beyond a single diagnosis in autism spectrum disorders

“…Unlike the delta and theta frequencies, the alpha frequency has been studied to a much greater extent in ASD. Some studies identified lower alpha power in central and posterior brain regions in individuals with ASD during sleep and resting states [ 48 , 56 , 59 – 62 ]. This suppression of alpha power was age-independent, occurring in children 4–8 years of age [ 60 , 62 ], adolescents 12–18 years of age [ 59 , 61 ], as well as adults 18 years and older [ 48 , 56 , 62 ].…”

“…Some studies identified lower alpha power in central and posterior brain regions in individuals with ASD during sleep and resting states [ 48 , 56 , 59 – 62 ]. This suppression of alpha power was age-independent, occurring in children 4–8 years of age [ 60 , 62 ], adolescents 12–18 years of age [ 59 , 61 ], as well as adults 18 years and older [ 48 , 56 , 62 ]. In one longitudinal study, Walsh and colleagues [ 62 ] also identified lower frontal alpha power in anesthetized children (mean 5.4 years of age), which continued to decline as they approached early adulthood (mean 22.5 years of age).…”

Case Studies Using the Electroencephalogram to Monitor Anesthesia-Induced Brain States in Children

“…These EEG patterns are consistently present in children >1 year of age. 31 – 33 , 56 Do the same relationships hold for infants?…”

“… 61 , 62 Although autistic patients are thought to have higher anesthetic requirements, evidence from a recent study suggests that they may actually have lower anesthetic requirements: autistic patients are twice as likely to be in a state of burst suppression compared to neurotypically developing children at comparable anesthetic doses. 56 Additionally, even in the absence of clinical epilepsy, the use of antiepileptics such as valproic acid has been associated with decreased anesthetic requirements. 63 Thus, it is possible that autistic patients, by way of their underlying neuropathology, their use of medications to control autism-related comorbidities, or both, could have lower anesthetic requirements.…”