Delirium is associated with loss of feedback cortical connectivity

Author:

Gjini Klevest1,Casey Cameron23,Kunkel David2,Her Maihlee2,Banks Matthew I.24,Pearce Robert A.2,Lennertz Richard2,Sanders Robert D.56

Affiliation:

1. Department of Neurology University of Wisconsin–Madison Madison Wisconsin USA

2. Department of Anesthesiology University of Wisconsin–Madison Madison Wisconsin USA

3. Pediatric Neuromodulation Laboratory, Waisman Center University of Wisconsin–Madison Madison Wisconsin USA

4. Department of Neuroscience University of Wisconsin–Madison Madison Wisconsin USA

5. Department of Anaesthetics & Institute of Academic Surgery Royal Prince Alfred Hospital Camperdown New South Wales Australia

6. NHMRC Clinical Trials Centre and Central Clinical School University of Sydney Camperdown New South Wales Australia

Abstract

AbstractINTRODUCTIONPost‐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.METHODSHigh‐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.RESULTSMismatch 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.DISCUSSIONDelirium 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.

Funder

National Institutes of Health

Publisher

Wiley

Subject

Psychiatry and Mental health,Cellular and Molecular Neuroscience,Geriatrics and Gerontology,Neurology (clinical),Developmental Neuroscience,Health Policy,Epidemiology

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