RESUMO
INTRODUCTION: Post-operative delirium (POD) is associated with increased morbidity and mortality but is bereft of treatments, largely due to our limited understanding of the underlying pathophysiology. We hypothesized that delirium reflects a disturbance in cortical connectivity that leads to altered predictions of the sensory environment. METHODS: High-density electroencephalogram recordings during an oddball auditory roving paradigm were collected from 131 patients. Dynamic causal modeling (DCM) analysis facilitated inference about the neuronal connectivity and inhibition-excitation dynamics underlying auditory-evoked responses. RESULTS: Mismatch negativity amplitudes were smaller in patients with POD. DCM showed that delirium was associated with decreased left-sided superior temporal gyrus (l-STG) to auditory cortex feedback connectivity. Feedback connectivity also negatively correlated with delirium severity and systemic inflammation. Increased inhibition of l-STG, with consequent decreases in feed-forward and feed-back connectivity, occurred for oddball tones during delirium. DISCUSSION: Delirium is associated with decreased feedback cortical connectivity, possibly resulting from increased intrinsic inhibitory tone. HIGHLIGHTS: Mismatch negativity amplitude was reduced in patients with delirium. Patients with postoperative delirium had increased feedforward connectivity before surgery. Feedback connectivity was diminished from left-side superior temporal gyrus to left primary auditory sensory area during delirium. Feedback connectivity inversely correlated with inflammation and delirium severity.
Assuntos
Delírio , Potenciais Evocados Auditivos , Humanos , Retroalimentação , Potenciais Evocados Auditivos/fisiologia , Eletroencefalografia , Inflamação , Estimulação Acústica/métodosRESUMO
Bistability occurs when two alternative percepts can be derived from the same physical stimulus. To identify the neural correlates of specific subjective experiences we used a bistable auditory stimulus and determined whether the two perceptual states could be distinguished electrophysiologically. Fourteen participants underwent magnetoencephalography while reporting their perceptual experience while listening to a continuous bistable stream of auditory tones. Participants reported bistability with a similar overall proportion of the two alternative percepts (52% vs 48%). At the individual level, sensor space electrophysiological discrimination between the percepts was possible in 9/14 participants with canonical variate analysis (CVA) or linear support vector machine (SVM) analysis over space and time dimensions. Classification was possible in 14/14 subjects with non-linear SVM. Similar effects were noted in an unconstrained source space CVA analysis (classifying 10/14 participants), linear SVM (classifying 9/14 subjects) and non-linear SVM (classifiying 13/14 participants). Source space analysis restricted to a priori ROIs showed discrimination was possible in the right and left auditory cortex with each classification approach but in the right intraparietal sulcus this was only apparent with non-linear SVM and only in a minority of particpants. Magnetoencephalography can be used to objectively classify auditory experiences from individual subjects.
Assuntos
Córtex Auditivo/fisiologia , Percepção Auditiva/fisiologia , Estimulação Acústica/métodos , Adulto , Mapeamento Encefálico/métodos , Potenciais Evocados Auditivos/fisiologia , Feminino , Humanos , Magnetoencefalografia/métodos , Masculino , Máquina de Vetores de Suporte , Adulto JovemRESUMO
Dexmedetomidine (Dex), an alpha(2)-adrenoceptor agonist, is an effective analgesic and sedative drug in adults; however, little information is available about its efficacy in pediatric populations. Some anesthetics exhibit an age-dependent analgesic effect, e.g., nitrous oxide, being relatively ineffective in newborn rats. We investigated the analgesic and hypnotic efficacy of Dex using 6 cohorts of Fischer rats aged 7, 15, 19, 23, and 29 days and adults exposed to either Dex (10 or 50 microg/kg) or saline subcutaneously. Formalin plantar testing was used to mimic inflammatory pain, and its effect was assessed using immunohistochemical (c-Fos staining) and behavioral methods. The hypnotic action of Dex was assessed by loss of righting reflex. Formalin administration produced a typical nociceptive response in each age group; these nociceptive responses were significantly attenuated by Dex 50 microg/kg at all ages (P < 0.05), whereas Dex 10 microg/kg had little effect. Neonatal rats showed the greatest hypnotic sensitivity to Dex (P < 0.05).