Attentional effects of noradrenaline vary with arousal level: selective activation of thalamic pulvinar in humans.
Subjects sedated by noradrenergic alpha2 agonists can switch rapidly from a state of extremely low to almost full consciousness following phasic increases in arousal or cognitive demand. Such flexibility is not displayed by traditional sedatives, such as the benzodiazepine diazepam. Experimentally, the phasic modulation of alpha2 effect by arousing or distracting stimuli can counteract the deleterious cognitive effects of alpha2 agonists. We used behavioural and fMRI indices of brain function to investigate the phasic modulatory effect that presentation of loud white noise would have on attentional dysfunction induced by administration of dexmedotomidine, an alpha2 agonist. Dexmedotomidine and midazolam were compared to placebo during performance of a target detection task, which was presented in the presence or absence of white noise. Compared to placebo, both dexmedotomidine and midazolam impaired task performance. This impairment was significantly attenuated by presentation of white noise in the dexmedotomidine condition only. This functional improvement corresponded to selective increase in activity of left medial pulvinar nucleus of the thalamus. This regional increase is suggested to index increases in phasic arousal, which counteract dexmedotomidine's detrimental attentional effects. Finally, despite sedating subjects to equivalent degrees, dexmedotomidine and midazolam had strikingly different regional effects on task-induced brain activity. Therefore, for the same level of sedation, the behavioural and anatomical attributes identifying the quality of sedation can vary.
Coull
Jennifer T
JT
Wellcome Department of Cognitive Neurology, Institute of Neurology, London WC1N 3BG, UK. jcoull@lnf.cnrs-mrs.fr
Jones
Matt E P
ME
Egan
Talmage D
TD
Frith
Chris D
CD
Maze
Mervyn
M
D000161:Acoustic Stimulation; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D001143:Arousal / Q000187:drug effects*; D001288:Attention / Q000187:drug effects*; D020927:Dexmedetomidine / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010296:Parietal Lobe / Q000187:drug effects; D010775:Photic Stimulation; D011597:Psychomotor Performance / Q000187:drug effects; D020649:Pulvinar / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D014796:Visual Perception / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D008874:Midazolam; D009638:Norepinephrine