Poster No:
2474
Submission Type:
Abstract Submission
Authors:
Naji Alnagger1, Javier Montupil2, Paolo Cardone2, Charlotte Martial3, Jitka Annen2, Olivia Gosseries2, Aline Defresne2, Arthur Bonnhomme2, Atakan Şelte4, Robert Sanders5, Vincent Bonhomme2, Coraline Mozin2, Marie Miegebielle2
Institutions:
1University of Liège, Liège, Liège, 2University of Liège, Liège, Liege, 3University of Liège, Liège, Belgium, 4University of Wisconsin-Madison, Madison, WI, 5University of Sydney, Sydney, Sydney
First Author:
Co-Author(s):
Introduction:
Connected consciousness (CC) is defined as the awareness of one's environment [1]. During general anaesthesia, around 5% of patients experience CC after a noxious stimulus [2]. The isolated forearm technique (IFT) consists of inflating a tourniquet on the arm before the injection of a neuromuscular blocker to allow voluntary hand movements. Those who responded to command via hand squeezing were deemed responders, thus demonstrating CC. Using fMRI, we aimed to identify the correlates of CC in responders during anaesthesia.
Methods:
Using the IFT, 26 healthy volunteers were placed under general anaesthesia using remifentanil [constant 1 ng.mL-1 concentration] and propofol [stepwise increase until loss of responsiveness; 5.36(0.78)µg.mL-1] target-controlled infusions, and rocuronium [0.6 mg.Kg-1 single bolus after tourniquet inflation]. After laryngeal mask insertion, propofol was decreased following an up-and-down protocol in accordance with the previous volunteer 1.85(1.17)µg/ml. A noxious electrical stimulation prior to posing closed questions probed responsiveness, yielding 10 responders and 16 non responders. Resting state fMRI sequences were acquired in four conditions: awake (R1), unresponsiveness in all subjects (R2), after noxious stimulation (R3) and recovery (R4). We used meta-analytically derived maps from neurosynth.org to define a set of seven canonical resting-state networks (RSNs): default mode network (DMN), executive control network (ECN), thalamus (THAL), hippocampus (HPC), visual (VIS), and sensorimotor (SM), auditory (AUD) followed by a "dual regression" approach. Network integrity was assessed by mean parameter estimates (PE) for each network from the second stage of the dual regression. The time series from the first step of the dual regression were entered into a general linear model producing PE values representing strength of connectivity between pairs of RSNs. Both within and between network results were entered into a linear mixed-effects model which model incorporated session and group (responder vs. non-responder) as fixed effects, and subject as a random effect in addition to assessing interaction effects between session and group, and further pairwise comparisons between groups within session. Results were considered significant at p<0.05 (FDR corrected).
Results:
In all subjects, several networks showed increased integrity during R2, including SM, AUD, THAL, and VIS. Whilst at R3, only SM showed increased integrity compared to R1. HPC, DMN and ECN showed no significant effect of session across all sessions. There was a significant interaction effect between group and R2 whereby responders show a stronger integrity compared with non-responders in THAL and VIS. There was also a significant interaction effect between group and R3 in AUD as non-responders had higher integrity than non-responders (Figure 1). Pairwise comparisons at R3 showed increases in connectivity between the thalamus and DMN in responders, whilst a decrease in connectivity between the thalamus and ECN, in addition to increased connectivity in responders between HPC and DMN compared to non-responders. There was also a significant interaction effect between group and R3 with SM and AUD (Figure 2).

·Mean parameter estimate values for each resting state network representing the network integrity.

·Pairwise comparisons of between-network connectivity between responders and non-responders during anaesthesia after stimualtion.
Conclusions:
Unresponsiveness is not necessarily related to decreases in integrity of RSNs; in fact, we show increases in the integrity of several RSN. The thalamic hyperactivity pre-emptively displayed by responders during R2 could potentially signal the susceptibility for CC following stimulation. The increased connectivity between SM and AUD could indicate the preservation of auditory function both in hearing the questions and providing a motor response, whilst the increased connectivity between THAL and HPC might drive responders' conserved capacities for memory. Conserved cognition in responders is likely underwritten by the thalamic anchoring of the anticorrelation between the DMN and ECN.
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
Novel Imaging Acquisition Methods:
BOLD fMRI 2
Perception, Attention and Motor Behavior:
Consciousness and Awareness 1
Keywords:
Consciousness
FUNCTIONAL MRI
Thalamus
Other - Anaesthesia; Connected Consciousness
1|2Indicates the priority used for review
Provide references using author date format
[1] Sanders RD. (2017), 'Incidence of Connected Consciousness after Tracheal Intubation: A Prospective, International, Multicenter Cohort Study of the Isolated Forearm Technique', Anesthesiology, 126(2):214-222.
[2] Sanders RD. (2012) 'Unresponsiveness ≠ unconsciousness'. Anesthesiology, 116(4):946-59.