Delirium is associated with loss of feedback cortical connectivity.

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.

Magnetoencephalographic Correlates of Perceptual State During Auditory Bistability.

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.

Dexmedetomidine exerts dose-dependent age-independent antinociception but age-dependent hypnosis in Fischer rats.

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).