2009 Clinical Scholar Research Award
During Award Period
Centre for Functional MRI of the Brain
Nuffield Department of Anaesthetics
University of Oxford
Oxford, United Kingdom
Mater Private Healthcare Group
Dr. Ni Mhuircheartaigh’s Research
The “thalamocortical switch” and consciousness; is interruption of thalamocortical transmission the cause or a consequence of induction of general anaesthesia by propofol.
Slow-wave activity saturation and thalamocortical isolation during propofol anesthesia in humans.
Ní Mhuircheartaigh R, Warnaby C, Rogers R, Jbabdi S, Tracey I.
The altered state of consciousness produced by general anesthetics is associated with a variety of changes in the brain’s electrical activity. Under hyperpolarizing influences such as anesthetic drugs, cortical neurons oscillate at ~1 Hz, which is measurable as slow waves in the electroencephalogram (EEG). We have administered propofol anesthesia to 16 subjects and found that, after they had lost behavioral responsiveness (response to standard sensory stimuli), each individual’s EEG slow-wave activity (SWA) rose to saturation and then remained constant despite increasing drug concentrations. We then simultaneously collected functional magnetic resonance imaging and EEG data in 12 of these subjects during propofol administration and sensory stimulation. During the transition to SWA saturation, the thalamocortical system became isolated from sensory stimuli, whereas internal thalamocortical exchange persisted. Rather, an alternative and more fundamental cortical network (which includes the precuneus) responded to all sensory stimulation. We conclude that SWA saturation is a potential individualized indicator of perception loss that could prove useful for monitoring depth of anesthesia and studying altered states of consciousness.
The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil.
Bingel U, Wanigasekera V, Wiech K, Ni Mhuircheartaigh R, Lee MC, Ploner M, Tracey I.
Evidence from behavioral and self-reported data suggests that the patients’ beliefs and expectations can shape both therapeutic and adverse effects of any given drug. We investigated how divergent expectancies alter the analgesic efficacy of a potent opioid in healthy volunteers by using brain imaging. The effect of a fixed concentration of the μ-opioid agonist remifentanil on constant heat pain was assessed under three experimental conditions using a within-subject design: with no expectation of analgesia, with expectancy of a positive analgesic effect, and with negative expectancy of analgesia (that is, expectation of hyperalgesia or exacerbation of pain). We used functional magnetic resonance imaging to record brain activity to corroborate the effects of expectations on the analgesic efficacy of the opioid and to elucidate the underlying neural mechanisms. Positive treatment expectancy substantially enhanced (doubled) the analgesic benefit of remifentanil. In contrast, negative treatment expectancy abolished remifentanil analgesia. These subjective effects were substantiated by significant changes in the neural activity in brain regions involved with the coding of pain intensity. The positive expectancy effects were associated with activity in the endogenous pain modulatory system, and the negative expectancy effects with activity in the hippocampus. On the basis of subjective and objective evidence, we contend that an individual’s expectation of a drug’s effect critically influences its therapeutic efficacy and that regulatory brain mechanisms differ as a function of expectancy. We propose that it may be necessary to integrate patients’ beliefs and expectations into drug treatment regimes alongside traditional considerations in order to optimize treatment outcomes.
Read Dr. Ni Mhuircheartaigh’s recent publications and articles.
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