Novel applications of sleep pharmacology as delirium therapeutics.

Sleep-wake and circadian disruption (SCD) is a core feature of delirium. It has been hypothesized that SCD contributes to delirium pathogenesis; therefore, interventions that prevent or reverse SCD represent an array of promising opportunities in relation to delirium. This review explores the relationship between sleep-wake/circadian physiology and delirium pathophysiology with a focus on neurotransmitter systems.

Nitrous Oxide Alters Functional Connectivity in Medial Limbic Structures in Treatment-Resistant Major Depression.

While nitrous oxide (NO) has demonstrated antidepressant properties in treatment-resistant major depression (TRD), little is known about neural mechanisms mediating these effects. Employing serial resting-state functional magnetic resonance imaging (rs-fMRI), we compared spatiotemporal effects of inhaled NO on brain functional connectivity in TRD patients (n=14) and non-depressed healthy controls (n=16, CNTL). Participants received sequential, one-hour inhalations of either 50% NO/oxygen or air/oxygen (placebo), with sessions separated by at least one month in random cross-over order.

International Delirium Pathophysiology & Electrophysiology Network for Data sharing (iDEPEND).

In an era of 'big data', we propose that a collaborative network approach will drive a better understanding of the mechanisms of delirium, and more rapid development of therapies. We have formed the International Delirium Pathophysiology & Electrophysiology Network for Data sharing (iDEPEND) group with a key aim to 'facilitate the study of delirium pathogenesis with electrophysiology, imaging, and biomarkers including data acquisition, analysis, and interpretation'. Our initial focus is on studies of electrophysiology as we anticipate this methodology has great potential to enhance our understanding of delirium.

Propofol enhancement of slow wave sleep to target the nexus of geriatric depression and cognitive dysfunction: protocol for a phase I open label trial.

Introduction: Late-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a risk factor for cognitive decline. Slow wave sleep (SWS) has been implicated in key processes including synaptic plasticity and memory.

Daytime dexmedetomidine sedation with closed-loop acoustic stimulation alters slow wave sleep homeostasis in healthy adults.

Background: The alpha-2 adrenergic agonist dexmedetomidine induces EEG patterns resembling those of non-rapid eye movement (NREM) sleep. Fulfilment of slow wave sleep (SWS) homeostatic needs would address the assumption that dexmedetomidine induces functional biomimetic sleep states.

Methods: In-home sleep EEG recordings were obtained from 13 healthy participants before and after dexmedetomidine sedation.

A personalized semi-automatic sleep spindle detection (PSASD) framework.

Background: Sleep spindles are distinct electroencephalogram (EEG) patterns of brain activity that have been posited to play a critical role in development, learning, and neurological disorders. Manual scoring for sleep spindles is labor-intensive and tedious but could supplement automated algorithms to resolve challenges posed with either approaches alone.

New Methods: A Personalized Semi-Automatic Sleep Spindle Detection (PSASD) framework was developed to combine the strength of automated detection algorithms and visual expertise of human scorers.

Rethinking ketamine as a panacea: adverse effects on oxygenation and postoperative outcomes.

Ketamine is receiving renewed interest in perioperative medicine as an anaesthetic adjunct and a treatment for chronic conditions, including depression. Ketamine's complex pharmacologic profile results not only in several desirable effects, such as anaesthesia and analgesia, but also multiple adverse effects affecting the central nervous, cardiovascular, and respiratory systems. In addition to defining patient-centred outcomes in future clinical studies on the perioperative uses of ketamine, careful monitoring for its numerous adverse effects will be paramount.

Ketamine for postoperative avoidance of depressive symptoms: the K-PASS feasibility randomised trial.

Background: Surgical patients with previous depression frequently experience postoperative depressive symptoms. This study's objective was to determine the feasibility of a placebo-controlled trial testing the impact of a sustained ketamine infusion on postoperative depressive symptoms.

Methods: This single-centre, triple-blind, placebo-controlled randomised clinical trial included adult patients with depression scheduled for inpatient surgery.

Persistent Brain Connectivity Changes in Healthy Volunteers Following Nitrous Oxide Inhalation.

Background: Nitrous oxide holds promise in the treatment of major depressive disorder. Its psychotropic effects and NMDA receptor antagonism have led to comparisons with ketamine. Despite longstanding use, persistent effects of nitrous oxide on the brain have not been characterized.

Pro-Con Debate: Electroencephalography-Guided Anesthesia for Reducing Postoperative Delirium.

Postoperative delirium (POD) has significant implications on morbidity, mortality, and health care expenditures. Monitoring electroencephalography (EEG) to adjust anesthetic management has gained interest as a strategy to mitigate POD. In this Pro-Con commentary article, the pro side supports the use of EEG to reduce POD, citing an empiric reduction in POD with processed EEG (pEEG)-guided general anesthesia found in several studies and recent meta-analysis.

Gamma-burst cortical activity in awake behaving macaques.

Electrophysiological recordings during ketamine anesthesia have revealed a slow alternating pattern of high- and low-frequency activity (a "gamma-burst" pattern) that develops along with the onset of general anesthesia. We examine the role of NMDA receptor antagonism in generating the gamma-burst pattern and the link between gamma-bursts and dissociative anesthesia by comparing the effects of ketamine with those of the highly selective NMDA receptor antagonist CGS 19755 on multi-site intracranial electrophysiology and behavior in rhesus macaques. The data show NMDA antagonism alone drives gamma-burst activity, and that it can do so without causing anesthesia.

Treatment-Resistant Late-Life Depression: A Review of Clinical Features, Neuropsychology, Neurobiology, and Treatment.

Major depression is common in older adults (≥ 60 years of age), termed late-life depression (LLD). Up to 30% of these patients will have treatment-resistant late-life depression (TRLLD), defined as depression that persists despite two adequate antidepressant trials. TRLLD is challenging for clinicians, given several etiological factors (eg, neurocognitive conditions, medical comorbidities, anxiety, and sleep disruption).

Targeting Slow Wave Sleep Deficiency in Late-Life Depression: A Case Series With Propofol.

Slow wave sleep (SWS), characterized by large electroencephalographic oscillations, facilitates crucial physiologic processes that maintain synaptic plasticity and overall brain health. Deficiency in older adults is associated with depression and cognitive dysfunction, such that enhancing sleep slow waves has emerged as a promising target for novel therapies. Enhancement of SWS has been noted after infusions of propofol, a commonly used anesthetic that induces electroencephalographic patterns resembling non-rapid eye movement sleep.

Awareness with Recall: Review and Guide to Electroencephalographic Depth-of-Anesthesia Monitoring.

Awareness with recall is an uncommon but potentially devastating neurological complication following perioperative care. End-tidal anesthetic gas concentration alarms can supplement usual care to reduce risk. Processed electroencephalographic (EEG) measures provided by depth-of-anesthesia monitors may be helpful, particularly for high-risk patients.

American Delirium Society 2022 Year in Review: Highlighting the Year's Most Impactful Delirium Research.

Background: Since 2015, the American Delirium Society (ADS) Research Committee has conducted an annual survey of the delirium literature for presentation in its year-in-review session. Our objectives were to describe the review process used for the 2021-2022 and to summarise the selected publications.

Methods: Each member of the ADS Research Committee nominated up to 6 publications considered to be the most impactful primary delirium research published from September 1, 2021, to July 31, 2022.

Central-positive complexes in ECT-induced seizures: Possible evidence for thalamocortical mechanisms.

Objective: Central-positive complexes (CPCs) are elicited during electroconvulsive therapy (ECT) as generalized high-amplitude waveforms with maximum positive voltage over the vertex. While these complexes have been qualitatively assessed in previous literature, quantitative analyses are lacking. This study aims to characterize CPCs across temporal, spatial, and spectral domains.

Correlating electroconvulsive therapy response to electroencephalographic markers: Study protocol.

Introduction: Electroconvulsive therapy (ECT) is an effective intervention for patients with major depressive disorder (MDD). Despite longstanding use, the underlying mechanisms of ECT are unknown, and there are no objective prognostic biomarkers that are routinely used for ECT response. Two electroencephalographic (EEG) markers, sleep slow waves and sleep spindles, could address these needs.

Postoperative Delirium Severity and Recovery Correlate With Electroencephalogram Spectral Features.

Background: Delirium is an acute syndrome characterized by inattention, disorganized thinking, and an altered level of consciousness. A reliable biomarker for tracking delirium does not exist, but oscillations in the electroencephalogram (EEG) could address this need. We evaluated whether the frequencies of EEG oscillations are associated with delirium onset, severity, and recovery in the postoperative period.

Associations of environmental and lifestyle factors with spatial navigation in younger and older adults.

Objective: Advanced age is associated with prominent impairment in allocentric navigation dependent on the hippocampus. This study examined whether age-related impairment in allocentric navigation and strategy selection was associated with sleep disruption or circadian rest-activity fragmentation. Further, we examined whether associations with navigation were moderated by perceived stress and physical activity.

Quiescence during burst suppression and postictal generalized EEG suppression are distinct patterns of activity.

Objective: Periods of low-amplitude electroencephalographic (EEG) signal (quiescence) are present during both anesthetic-induced burst suppression (BS) and postictal generalized electroencephalographic suppression (PGES). PGES following generalized seizures induced by electroconvulsive therapy (ECT) has been previously linked to antidepressant response. The commonality of quiescence during both BS and PGES motivated trials to recapitulate the antidepressant effects of ECT using high doses of anesthetics.