Pupil dilation response elicited by violations of auditory regularities is a promising but challenging approach to probe consciousness at the bedside

Sangare, Aude; Quirins, Marion; Marois, Clémence; Valente, Mélanie; Weiss, Nicolas; Perez, Pauline; Ben Salah, Amina; Munoz-Musat, Esteban; Demeret, Sophie; Rohaut, Benjamin; Sitt, Jacobo D.; Eymond, Cecile; Naccache, Lionel

doi:10.1038/s41598-023-47806-1

Cited by 3 publications

(2 citation statements)

References 52 publications

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“…Whether pupillometry with mental arithmetic works equally well in acute DoC caused by traumatic and other non-anoxic brain injuries remains to be seen. Notably, however, pupillometry with mental arithmetic appears to have greater potential than pupillometry combined with the auditory 'local global' paradigm, 13 probably because of the larger cognitive load that comes with mental arithmetic. Head-to-head studies comparing automated pupillometry with fMRI-and EEG-based active paradigms are required to investigate this further.…”

Section: Discussionmentioning

confidence: 99%

Automated pupillometry to detect residual consciousness in acute brain injury

Othman,

Olsen,

Hansen

et al. 2024

Preprint

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Background. Identifying residual consciousness in patients with disorders of consciousness (DoC) in the intensive care unit (ICU) is crucial for treatment decisions, but sensitive low-cost bedside markers are missing. We investigated whether automated pupillometry combined with passive and active cognitive paradigms can identify residual consciousness in ICU patients with traumatic or non-traumatic DoC. Methods. In a prospective observational cohort study, clinically low- or unresponsive ICU patients with traumatic and non-traumatic DoC were enrolled from neurological and non-neurological ICUs at a tertiary referral center (Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark). Age- and sex-matched healthy volunteers served as controls. Participants with eye disorders were excluded. Patients were categorized into those without (coma or unresponsive wakefulness syndrome, ≤UWS) or with (minimally conscious state or better, ≥MCS) clinical signs of residual consciousness. Using automated pupillometry, we recorded pupillary dilation as a response to passive (visual and auditory stimuli) and active (mental arithmetic) cognitive paradigms, with success criteria depending on the specific task (e.g., ≥ 3 of 5 pupillary dilations on 5 consecutive mental arithmetic tasks). Results. We obtained 699 pupillometry recordings at 178 time points from 91 brain-injured ICU patients (mean age 60±13.8 years; 31% women; 49.5% non-traumatic brain injuries). Recordings were also obtained from 26 matched controls (59±14.8 years, 38% women). Passive paradigms yielded limited distinctions between patient groups and controls. However, active paradigms involving mental arithmetic enabled discrimination between different states of consciousness. With mental arithmetic of moderate complexity, ≥ 3 pupillary dilations were seen in 50.0% ≥MCS patients and 17.8% ≤UWS patients (OR 4.56; 95% CI 2.09–10.10, p < 0.001). In comparison, 76.9% healthy controls responded with ≥ 3 pupillary dilations (p = 0.028). Results remained consistent across sensitivity analyses using different thresholds for success. Spearman's Rank analysis underscored the robust association between pupillary dilations during mental arithmetic and consciousness levels (rho = 1, p = 0.017). Notably, one behaviorally unresponsive patient demonstrated persistent command-following behavior two weeks before overt signs of awareness, suggesting a state of prolonged CMD. Conclusions. Automated pupillometry combined with mental arithmetic can identify cognitive efforts, and hence residual consciousness, in ICU patients with acute DoC.

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Section: Discussionmentioning

confidence: 99%

Automated pupillometry to detect residual consciousness in acute brain injury

Othman,

Olsen,

Hansen

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Whether pupillometry with mental arithmetic works equally well in acute DoC caused by traumatic and other non-anoxic brain injuries remains to be seen. Notably, however, pupillometry with mental arithmetic appears to have greater potential than pupillometry combined with the auditory 'local global' paradigm, 13 probably because of the larger cognitive load that comes with mental arithmetic. Head-to-head studies comparing automated pupillometry with fMRI-and EEGbased active paradigms are required to investigate this further.…”

Section: Active Cognitive Paradigms Can Differentiate Between Degrees...mentioning

confidence: 99%

Automated pupillometry to detect residual consciousness in acute brain injury

Othman,

Olsen,

Tanderup Hansen

et al. 2024

Preprint

View full text Add to dashboard Cite

BackgroundIdentifying residual consciousness in patients with disorders of consciousness (DoC) in the intensive care unit (ICU) is crucial for treatment decisions, but sensitive low-cost bedside markers are missing. We investigated whether automated pupillometry combined with passive and active cognitive paradigms can identify residual consciousness in ICU patients with traumatic or non-traumatic DoC.MethodsIn a prospective observational cohort study, clinically low- or unresponsive ICU patients with traumatic and non-traumatic DoC were enrolled from neurological and non-neurological ICUs at a tertiary referral center (Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark). Age- and sex-matched healthy volunteers served as controls. Participants with eye disorders were excluded. Patients were categorized into those without (coma or unresponsive wakefulness syndrome, ≤UWS) or with (minimally conscious state or better, ≥MCS) clinical signs of residual consciousness. Using automated pupillometry, we recorded pupillary dilation as a response to passive (visual and auditory stimuli) and active (mental arithmetic) cognitive paradigms, with success criteria depending on the specific task (e.g., ≥3 of 5 pupillary dilations on 5 consecutive mental arithmetic tasks).ResultsWe obtained 699 pupillometry recordings at 178 time points from 91 brain-injured ICU patients (mean age 60±13.8 years; 31% women; 49.5% non-traumatic brain injuries). Recordings were also obtained from 26 matched controls (59±14.8 years, 38% women). Passive paradigms yielded limited distinctions between patient groups and controls. However, active paradigms involving mental arithmetic enabled discrimination between different states of consciousness. With mental arithmetic of moderate complexity, ≥3 pupillary dilations were seen in 50.0% ≥MCS patients and 17.8% ≤UWS patients (OR 4.56; 95% CI 2.09-10.10,p<0.001). In comparison, 76.9% healthy controls responded with ≥3 pupillary dilations (p=0.028). Results remained consistent across sensitivity analyses using different thresholds for success. Spearman’s Rank analysis underscored the robust association between pupillary dilations during mental arithmetic and consciousness levels (rho=1,p=0.017). Notably, one behaviorally unresponsive patient demonstrated persistent command-following behavior two weeks before overt signs of awareness, suggesting a state of prolonged CMD.ConclusionsAutomated pupillometry combined with mental arithmetic can identify cognitive efforts, and hence residual consciousness, in ICU patients with acute DoC.

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Covert Consciousness in Acute Brain Injury Revealed by Automated Pupillometry and Cognitive Paradigms

Othman,

Olsen,

Hansen

et al. 2024

Neurocrit Care

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Background Identifying covert consciousness in intensive care unit (ICU) patients with coma and other disorders of consciousness (DoC) is crucial for treatment decisions, but sensitive low-cost bedside markers are missing. We investigated whether automated pupillometry combined with passive and active cognitive paradigms can detect residual consciousness in ICU patients with DoC. Methods We prospectively enrolled clinically low-response or unresponsive patients with traumatic or nontraumatic DoC from ICUs of a tertiary referral center. Age-matched and sex-matched healthy volunteers served as controls. Patients were categorized into clinically unresponsive (coma or unresponsive wakefulness syndrome) or clinically low-responsive (minimally conscious state or better). Using automated pupillometry, we recorded pupillary dilation to passive (visual and auditory stimuli) and active (mental arithmetic) cognitive paradigms, with task-specific success criteria (e.g., ≥ 3 of 5 pupillary dilations on five consecutive mental arithmetic tasks). Results We obtained 699 pupillometry recordings at 178 time points from 91 ICU patients with brain injury (mean age 60 ± 13.8 years, 31% women, and 49.5% nontraumatic brain injuries). Recordings were also obtained from 26 matched controls (59 ± 14.8 years, 38% women). Passive paradigms yielded limited distinctions between patients and controls. However, active paradigms enabled discrimination between different states of consciousness. With mental arithmetic of moderate complexity, ≥ 3 pupillary dilations were seen in 17.8% of clinically unresponsive patients and 50.0% of clinically low-responsive patients (odds ratio 4.56, 95% confidence interval 2.09–10.10; p < 0.001). In comparison, 76.9% healthy controls responded with ≥ 3 pupillary dilations (p = 0.028). Results remained consistent across sensitivity analyses using different thresholds for success. Spearman’s rank analysis underscored the robust association between pupillary dilations during mental arithmetic and consciousness levels (rho = 1, p = 0.017). Notably, one behaviorally unresponsive patient demonstrated persistent command-following behavior 2 weeks before overt signs of awareness, suggesting prolonged cognitive motor dissociation. Conclusions Automated pupillometry combined with mental arithmetic can identify cognitive efforts, and hence covert consciousness, in ICU patients with acute DoC.

show abstract

Pupil dilation response elicited by violations of auditory regularities is a promising but challenging approach to probe consciousness at the bedside

Cited by 3 publications

References 52 publications

Automated pupillometry to detect residual consciousness in acute brain injury

Automated pupillometry to detect residual consciousness in acute brain injury

Automated pupillometry to detect residual consciousness in acute brain injury

Covert Consciousness in Acute Brain Injury Revealed by Automated Pupillometry and Cognitive Paradigms

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