Neurodevelopment of children exposed to prolonged anesthesia in infancy: GABA study interim analysis of resting-state brain networks at 2, 4, and 10-months old.

BACKGROUND: Previous studies have raised concerns regarding neurodevelopmental impacts of early exposures to general anesthesia and surgery. Electroencephalography (EEG) can be used to study ontogeny of brain networks during infancy. As a substudy of an ongoing study, we examined measures of functional connectivity in awake infants with prior early and prolonged anesthetic exposures and in control infants. METHODS: EEG functional connectivity was assessed using debiased weighted phase lag index at source and sensor levels and graph theoretical measures for resting state activity in awake infants in the early anesthesia (n = 26 at 10 month visit, median duration of anesthesia = 4 [2, 7 h]) and control (n = 38 at 10 month visit) groups at ages approximately 2, 4 and 10 months. Theta and low alpha frequency bands were of primary interest. Linear mixed models incorporated impact of age and cumulative hours of general anesthesia exposure. RESULTS: Models showed no significant impact of cumulative hours of general anesthesia exposure on debiased weighted phase lag index, characteristic path length, clustering coefficient or small-worldness (conditional R2 0.05-0.34). An effect of age was apparent in many of these measures. CONCLUSIONS: We could not demonstrate significant impact of general anesthesia in the first months of life on early development of resting state brain networks over the first postnatal year. Future studies will explore these networks as these infants grow older.

Electroencephalographic delta and alpha oscillations reveal phase-amplitude coupling in paediatric patients undergoing sevoflurane-based general anaesthesia.

BACKGROUND: Sevoflurane-induced anaesthesia generates frontal alpha oscillations as early as 6 months of age, whereas strong delta oscillations are present at birth. In adults, delta oscillations and alpha oscillations are coupled: the phase of delta waves modulates the amplitude of alpha oscillations in a phenomenon known as phase-amplitude coupling. We hypothesise that delta-alpha phase-amplitude coupling exists in young children and is a feature of sevoflurane-based general anaesthesia distinct from emergence after anaesthesia. METHODS: Electroencephalographic data from 31 paediatric patients aged 10 months to 3 yr undergoing elective surgery with sevoflurane-based anaesthesia were analysed retrospectively. Delta-alpha phase-amplitude coupling was evaluated during maintenance of anaesthesia and during emergence. RESULTS: Delta-alpha phase-amplitude coupling was observed in the study population. Strength of phase-amplitude coupling, represented by the delta-alpha mean amplitude vector, was greater during general anaesthesia than during emergence (Wilcoxon paired signed-rank test, Z=3.107, P=0.002). Frontal alpha amplitude during anaesthesia was not uniformly distributed across all delta phases. During general anaesthesia, alpha power was restricted to the positive phase of the delta wave (omnibus circular uniformity, general anaesthesia: P<0.001, mean phase: 114º; 99% confidence interval: 90º-139º; emergence: P=0.35, mean phase 181º, 99% confidence interval: 110º-253º). CONCLUSIONS: Sevoflurane-based anaesthesia is associated with delta-alpha phase-amplitude coupling in paediatric patients. These findings improve our understanding of cortical dynamics in children undergoing general anaesthesia, which might improve paediatric intraoperative depth of anaesthesia monitoring techniques.

Emerging functional connectivity patterns during sevoflurane anaesthesia in the developing human brain.

BACKGROUND: Spectral-based EEG is used to monitor anaesthetic state during surgical procedures in adults. Spectral EEG features that can resemble the patterns seen in adults emerge in children after the age of 10 months and cannot distinguish wakefulness and anaesthesia in the youngest children. There is a need to explore alternative EEG measures. We hypothesise that functional connectivity is one of the measures that can help distinguish between consciousness states in children. METHODS: An EEG data set of children undergoing sevoflurane general anaesthesia (age 0-3 yr) was reanalysed using debiased weighted phase lag index as a measure of functional connectivity in wakefulness (n=38) and anaesthesia (n=73). Network topology measures were compared between states in 0- to 6-, 6- to 10-, and >10-month-old children. RESULTS: Functional connectivity was reduced in anaesthesia vs wakefulness in delta band (n=cluster of 17 significant connections; P=0.013; 58% connections surviving thresholding in wakefulness and 49% in anaesthesia). Network density and node degree were lower in anaesthesia even in the youngest children (0.57 in wakefulness; 0.48 in anaesthesia; t [9]=3.39; P=0.029; G=0.98; confidence interval [CI] [0.25-1.77]). Modularity was higher in anaesthesia (0-6 months: 0.16 in wakefulness and 0.19 in anaesthesia, t [9]=-2.95, P=0.04, G=-0.85, CI [-1.60 to -0.16]; >10 months: 0.16 vs 0.21, t [13]=-6.45, P<0.001, G=-1.62, CI [-2.49 to -0.85]) and decreased with age (ρ [73]=-0.456; P<0.001). CONCLUSIONS: Anaesthesia modulates functional connectivity. Increased segregation into a more modular structure in anaesthesia decreases with age as adult-like features develop. These findings advance our understanding of the network architecture underlying the effects of anaesthesia on the developing brain.

Dynamics of brain connectivity after stroke.

Recovery from a stroke is a dynamic time-dependent process, in which the central nervous system reorganises to accommodate for the impact of the injury. The purpose of this paper is to review recent longitudinal studies of changes in brain connectivity after stroke. A systematic review of research papers reporting functional or effective connectivity at two or more time points in stroke patients was conducted. Stroke leads to an early reduction of connectivity in the motor network. With recovery time, the connectivity increases and can reach the same levels as in healthy participants. The increase in connectivity is correlated with functional motor gains. A new, more randomised pattern of connectivity may then emerge in the longer term. In some instances, a pattern of increased connectivity even higher than in healthy controls can be observed, and is related either to a specific time point or to a specific neural structure. Rehabilitation interventions can help improve connectivity between specific regions. Moreover, motor network connectivity undergoes reorganisation during recovery from a stroke and can be related to behavioural recovery. A detailed analysis of changes in connectivity pattern may enable a better understanding of adaptation to a stroke and how compensatory mechanisms in the brain may be supported by rehabilitation.

HIV and age underlie specific patterns of brain abnormalities and cognitive changes in high functioning patients.

OBJECTIVE: Findings on the influence of age and HIV on brain and cognition remain equivocal, particularly in aviremic subjects without other age or HIV-related comorbidities. We aimed to (a) examine the effect of HIV status and age on structural brain measurements and cognition, and (b) apply the machine learning technique to identify brain morphometric and cognitive features that are most discriminative between aviremic subjects with HIV on stable combination antiretroviral therapy (cART) and healthy controls. METHOD: Fifty-three HIV-seropositive patients and 62 healthy controls underwent neuropsychological testing (executive functions, attention, memory, learning, psychomotor speed, fluency) and volumetric MRI scans. Voxel-based morphometry, ANCOVAs, machine learning, and multivariate regression were conducted to determine the between group differences in terms of relationship of HIV status, age, and their interaction on neurocognitive and structural brain measures. RESULTS: Volume and gray matter (GM) thickness of the caudate, parahippocampus, insula, and inferior frontal gyrus were smaller in seropositive subjects in comparison with healthy controls (HC). They also performed worse in complex attention and cognitive fluency tasks. Support vector machine (SVM) analysis revealed that the best between-groups classification accuracy was obtained based on cognitive scores encompassing complex attention and psychomotor speed, as well as volumetric measures of white matter and total gray matter; third, fourth, and lateral ventricles; amygdala; caudate; and putamen. Both voxel-based morphometry (VBM) and regression analysis yielded that HIV and aging independently increase brain vulnerability and cognitive worsening. CONCLUSION: Patients with HIV on effective cART demonstrate smaller volumetric measures and worse cognitive functioning relative to seronegative individuals. There is no interaction between HIV infection and aging. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Muscle co-contraction patterns in robot-mediated force field learning to guide specific muscle group training.

BACKGROUND: Muscle co-contraction is a strategy of increasing movement accuracy and stability employed in dealing with force perturbation of movement. It is often seen in neuropathological populations. The direction of movement influences the pattern of co-contraction, but not all movements are easily achievable for populations with motor deficits. Manipulating the direction of the force instead, may be a promising rehabilitation protocol to train movement with use of a co-contraction reduction strategy. Force field learning paradigms provide a well described procedure to evoke and test muscle co-contraction. OBJECTIVE: The aim of this study was to test the muscle co-contraction pattern in a wide range of arm muscles in different force-field directions utilising a robot-mediated force field learning paradigm of motor adaptation. METHOD: Forty-two participants volunteered to participate in a study utilising robot-mediated force field motor adaptation paradigm with a clockwise or counter-clockwise force field. Kinematics and surface electromyography (EMG) of eight arm muscles were measured. RESULTS: Both muscle activation and co-contraction was earlier and stronger in flexors in the clockwise condition and in extensors in the counter-clockwise condition. CONCLUSIONS: Manipulating the force field direction leads to changes in the pattern of muscle co-contraction.