Disruption of Cortical Connectivity during Remifentanil Administration Is Associated with Cognitive Impairment but Not with Analgesia

Ahmad Khodayari-Rostamabad, Søren S Olesen, Carina Graversen, Lasse P Malver, Geana P Kurita, Per Sjøgren, Lona L Christrup, Asbjørn M Drewes

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

BACKGROUND:: The authors investigated the effect of remifentanil administration on resting electroencephalography functional connectivity and its relationship to cognitive function and analgesia in healthy volunteers.

METHODS:: Twenty-one healthy male adult subjects were enrolled in this placebo-controlled double-blind cross-over study. For each subject, 2.5 min of multichannel electroencephalography recording, a cognitive test of sustained attention (continuous reaction time), and experimental pain scores to bone-pressure and heat stimuli were collected before and after infusion of remifentanil or placebo. A coherence matrix was calculated from the electroencephalogram, and three graph-theoretical measures (characteristic path-length, mean clustering coefficient, and relative small-worldness) were extracted to characterize the overall cortical network properties.

RESULTS:: Compared to placebo, most graph-theoretical measures were significantly altered by remifentanil at the alpha and low beta range (8 to 18 Hz; all P < 0.001). Taken together, these alterations were characterized by an increase in the characteristic path-length (alpha 17% and low beta range 24%) and corresponding decrements in mean clustering coefficient (low beta range -25%) and relative small-worldness (alpha -17% and low beta range -42%). Changes in characteristic path-lengths after remifentanil infusion were correlated to the continuous reaction time index (r = -0.57; P = 0.009), while no significant correlations between graph-theoretical measures and experimental pain tests were seen.

CONCLUSIONS:: Remifentanil disrupts the functional connectivity network properties of the electroencephalogram. The findings give new insight into how opioids interfere with the normal brain functions and have the potential to be biomarkers for the sedative effects of opioids in different clinical settings.

Original languageEnglish
JournalAnesthesiology
Volume122
Issue number1
Pages (from-to)140-149
Number of pages9
ISSN0003-3022
DOIs
Publication statusPublished - 2015

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Analgesia
Electroencephalography
Placebos
Opioid Analgesics
Reaction Time
Cluster Analysis
Pain
Hypnotics and Sedatives
Cross-Over Studies
Cognition
Healthy Volunteers
Hot Temperature
Biomarkers
remifentanil
Cognitive Dysfunction
Pressure
Bone and Bones
Brain

Cite this

Khodayari-Rostamabad, Ahmad ; Olesen, Søren S ; Graversen, Carina ; Malver, Lasse P ; Kurita, Geana P ; Sjøgren, Per ; Christrup, Lona L ; Drewes, Asbjørn M. / Disruption of Cortical Connectivity during Remifentanil Administration Is Associated with Cognitive Impairment but Not with Analgesia. In: Anesthesiology. 2015 ; Vol. 122, No. 1. pp. 140-149.
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title = "Disruption of Cortical Connectivity during Remifentanil Administration Is Associated with Cognitive Impairment but Not with Analgesia",
abstract = "BACKGROUND:: The authors investigated the effect of remifentanil administration on resting electroencephalography functional connectivity and its relationship to cognitive function and analgesia in healthy volunteers.METHODS:: Twenty-one healthy male adult subjects were enrolled in this placebo-controlled double-blind cross-over study. For each subject, 2.5 min of multichannel electroencephalography recording, a cognitive test of sustained attention (continuous reaction time), and experimental pain scores to bone-pressure and heat stimuli were collected before and after infusion of remifentanil or placebo. A coherence matrix was calculated from the electroencephalogram, and three graph-theoretical measures (characteristic path-length, mean clustering coefficient, and relative small-worldness) were extracted to characterize the overall cortical network properties.RESULTS:: Compared to placebo, most graph-theoretical measures were significantly altered by remifentanil at the alpha and low beta range (8 to 18 Hz; all P < 0.001). Taken together, these alterations were characterized by an increase in the characteristic path-length (alpha 17{\%} and low beta range 24{\%}) and corresponding decrements in mean clustering coefficient (low beta range -25{\%}) and relative small-worldness (alpha -17{\%} and low beta range -42{\%}). Changes in characteristic path-lengths after remifentanil infusion were correlated to the continuous reaction time index (r = -0.57; P = 0.009), while no significant correlations between graph-theoretical measures and experimental pain tests were seen.CONCLUSIONS:: Remifentanil disrupts the functional connectivity network properties of the electroencephalogram. The findings give new insight into how opioids interfere with the normal brain functions and have the potential to be biomarkers for the sedative effects of opioids in different clinical settings.",
author = "Ahmad Khodayari-Rostamabad and Olesen, {S{\o}ren S} and Carina Graversen and Malver, {Lasse P} and Kurita, {Geana P} and Per Sj{\o}gren and Christrup, {Lona L} and Drewes, {Asbj{\o}rn M}",
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Disruption of Cortical Connectivity during Remifentanil Administration Is Associated with Cognitive Impairment but Not with Analgesia. / Khodayari-Rostamabad, Ahmad; Olesen, Søren S; Graversen, Carina; Malver, Lasse P; Kurita, Geana P; Sjøgren, Per; Christrup, Lona L; Drewes, Asbjørn M.

In: Anesthesiology, Vol. 122, No. 1, 2015, p. 140-149.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Disruption of Cortical Connectivity during Remifentanil Administration Is Associated with Cognitive Impairment but Not with Analgesia

AU - Khodayari-Rostamabad, Ahmad

AU - Olesen, Søren S

AU - Graversen, Carina

AU - Malver, Lasse P

AU - Kurita, Geana P

AU - Sjøgren, Per

AU - Christrup, Lona L

AU - Drewes, Asbjørn M

PY - 2015

Y1 - 2015

N2 - BACKGROUND:: The authors investigated the effect of remifentanil administration on resting electroencephalography functional connectivity and its relationship to cognitive function and analgesia in healthy volunteers.METHODS:: Twenty-one healthy male adult subjects were enrolled in this placebo-controlled double-blind cross-over study. For each subject, 2.5 min of multichannel electroencephalography recording, a cognitive test of sustained attention (continuous reaction time), and experimental pain scores to bone-pressure and heat stimuli were collected before and after infusion of remifentanil or placebo. A coherence matrix was calculated from the electroencephalogram, and three graph-theoretical measures (characteristic path-length, mean clustering coefficient, and relative small-worldness) were extracted to characterize the overall cortical network properties.RESULTS:: Compared to placebo, most graph-theoretical measures were significantly altered by remifentanil at the alpha and low beta range (8 to 18 Hz; all P < 0.001). Taken together, these alterations were characterized by an increase in the characteristic path-length (alpha 17% and low beta range 24%) and corresponding decrements in mean clustering coefficient (low beta range -25%) and relative small-worldness (alpha -17% and low beta range -42%). Changes in characteristic path-lengths after remifentanil infusion were correlated to the continuous reaction time index (r = -0.57; P = 0.009), while no significant correlations between graph-theoretical measures and experimental pain tests were seen.CONCLUSIONS:: Remifentanil disrupts the functional connectivity network properties of the electroencephalogram. The findings give new insight into how opioids interfere with the normal brain functions and have the potential to be biomarkers for the sedative effects of opioids in different clinical settings.

AB - BACKGROUND:: The authors investigated the effect of remifentanil administration on resting electroencephalography functional connectivity and its relationship to cognitive function and analgesia in healthy volunteers.METHODS:: Twenty-one healthy male adult subjects were enrolled in this placebo-controlled double-blind cross-over study. For each subject, 2.5 min of multichannel electroencephalography recording, a cognitive test of sustained attention (continuous reaction time), and experimental pain scores to bone-pressure and heat stimuli were collected before and after infusion of remifentanil or placebo. A coherence matrix was calculated from the electroencephalogram, and three graph-theoretical measures (characteristic path-length, mean clustering coefficient, and relative small-worldness) were extracted to characterize the overall cortical network properties.RESULTS:: Compared to placebo, most graph-theoretical measures were significantly altered by remifentanil at the alpha and low beta range (8 to 18 Hz; all P < 0.001). Taken together, these alterations were characterized by an increase in the characteristic path-length (alpha 17% and low beta range 24%) and corresponding decrements in mean clustering coefficient (low beta range -25%) and relative small-worldness (alpha -17% and low beta range -42%). Changes in characteristic path-lengths after remifentanil infusion were correlated to the continuous reaction time index (r = -0.57; P = 0.009), while no significant correlations between graph-theoretical measures and experimental pain tests were seen.CONCLUSIONS:: Remifentanil disrupts the functional connectivity network properties of the electroencephalogram. The findings give new insight into how opioids interfere with the normal brain functions and have the potential to be biomarkers for the sedative effects of opioids in different clinical settings.

U2 - 10.1097/ALN.0000000000000510

DO - 10.1097/ALN.0000000000000510

M3 - Journal article

VL - 122

SP - 140

EP - 149

JO - Anesthesiology

JF - Anesthesiology

SN - 0003-3022

IS - 1

ER -