Covert Critical Illness Encephalopathy: Impairments That Escape Detection by Guideline Recommended, Protocolized Assessments.

Objectives: To determine whether cognitive impairments of important severity escape detection by guideline-recommended delirium and encephalopathy screening instruments in critically ill patients.

Design: Cross-sectional study with random patient sampling.

Setting: ICUs of a large referral hospital with protocols implementing the Society of Critical Care Medicine's ICU Liberation Bundle.

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.

Reward contingency gates selective cholinergic suppression of amygdala neurons.

Basal forebrain cholinergic neurons modulate how organisms process and respond to environmental stimuli through impacts on arousal, attention, and memory. It is unknown, however, whether basal forebrain cholinergic neurons are directly involved in conditioned behavior, independent of secondary roles in the processing of external stimuli. Using fluorescent imaging, we found that cholinergic neurons are active during behavioral responding for a reward - even prior to reward delivery and in the absence of discrete stimuli.

Scaling behaviours of deep learning and linear algorithms for the prediction of stroke severity.

Deep learning has allowed for remarkable progress in many medical scenarios. Deep learning prediction models often require 10-10 examples. It is currently unknown whether deep learning can also enhance predictions of symptoms post-stroke in real-world samples of stroke patients that are often several magnitudes smaller.

Potentiation of cholinergic and corticofugal inputs to the lateral amygdala in threat learning.

The amygdala, cholinergic basal forebrain, and higher-order auditory cortex (HO-AC) regulate brain-wide plasticity underlying auditory threat learning. Here, we perform multi-regional extracellular recordings and optical measurements of acetylcholine (ACh) release to characterize the development of discriminative plasticity within and between these brain regions as mice acquire and recall auditory threat memories. Spiking responses are potentiated for sounds paired with shock (CS+) in the lateral amygdala (LA) and optogenetically identified corticoamygdalar projection neurons, although not in neighboring HO-AC units.

Automated detection of immune effector cell-associated neurotoxicity syndrome via quantitative EEG.

Objective: To develop an automated, physiologic metric of immune effector cell-associated neurotoxicity syndrome among patients undergoing chimeric antigen receptor-T cell therapy.

Methods: We conducted a retrospective observational cohort study from 2016 to 2020 at two tertiary care centers among patients receiving chimeric antigen receptor-T cell therapy with a CD19 or B-cell maturation antigen ligand. We determined the daily neurotoxicity grade for each patient during EEG monitoring via chart review and extracted clinical variables and outcomes from the electronic health records.

Associations between early in-hospital medications and the development of delirium in patients with stroke.

Objectives: Patients hospitalized with stroke develop delirium at higher rates than general hospitalized patients. While several medications are associated with existing delirium, it is unknown whether early medication exposures are associated with subsequent delirium in patients with stroke. Additionally, it is unknown whether delirium identification is associated with changes in the prescription of these medications.

Giant Cell Arteritis Presenting With Multiple Cranial Neuropathies - Case Report.

Vision loss accounts for most ophthalmic presentations of giant cell arteritis (GCA), but an important minority of patients present with diplopia and other cranial neuropathies. Here we present the case of an 84-year-old woman with a prior history of multiple cancers who was admitted to our hospital after developing double vision. She was found to have mydriasis, ptosis, and ophthalmoplegia in the right eye (OD) consistent with a combined R CNIII/CNVI neuropathy, as well as highly elevated inflammatory markers.

Potentiated cholinergic and corticofugal inputs support reorganized sensory processing in the basolateral amygdala during auditory threat acquisition and retrieval.

Reappraising neutral stimuli as environmental threats reflects rapid and discriminative changes in sensory processing within the basolateral amygdala (BLA). To understand how BLA inputs are also reorganized during discriminative threat learning, we performed multi-regional measurements of acetylcholine (ACh) release, single unit spiking, and functional coupling in the mouse BLA and higher-order auditory cortex (HO-AC). During threat memory recall, sounds paired with shock (CS+) elicited relatively higher firing rates in BLA units and optogenetically targeted corticoamygdalar (CAmy) units, though not in neighboring HO-AC units.

Thalamus sends information about arousal but not valence to the amygdala.

Rationale: The basolateral amygdala (BLA) and medial geniculate nucleus of the thalamus (MGN) have both been shown to be necessary for the formation of associative learning. While the role that the BLA plays in this process has long been emphasized, the MGN has been less well-studied and surrounded by debate regarding whether the relay of sensory information is active or passive.

Objectives: We seek to understand the role the MGN has within the thalamoamgydala circuit in the formation of associative learning.

EEG-based grading of immune effector cell-associated neurotoxicity syndrome.

CAR-T cell therapy is an effective cancer therapy for multiple refractory/relapsed hematologic malignancies but is associated with substantial toxicity, including Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Improved detection and assessment of ICANS could improve management and allow greater utilization of CAR-T cell therapy, however, an objective, specific biomarker has not been identified. We hypothesized that the severity of ICANS can be quantified based on patterns of abnormal brain activity seen in electroencephalography (EEG) signals.

Learned Motor Patterns Are Replayed in Human Motor Cortex during Sleep.

Consolidation of memory is believed to involve offline replay of neural activity. While amply demonstrated in rodents, evidence for replay in humans, particularly regarding motor memory, is less compelling. To determine whether replay occurs after motor learning, we sought to record from motor cortex during a novel motor task and subsequent overnight sleep.

Associations Between Stroke Localization and Delirium: A Systematic Review and Meta-Analysis.

Objectives: Delirium is common among patients with acute stroke and associated with worse outcomes. However, it is unclear which stroke locations or types are most associated with delirium.

Materials And Methods: We systematically reviewed studies of patients with acute stroke that reported stroke locations and types by delirium status.

ICU delirium burden predicts functional neurologic outcomes.

Background: We investigated the effect of delirium burden in mechanically ventilated patients, beginning in the ICU and continuing throughout hospitalization, on functional neurologic outcomes up to 2.5 years following critical illness.

Methods: Prospective cohort study of enrolling 178 consecutive mechanically ventilated adult medical and surgical ICU patients between October 2013 and May 2016.

A functional topography within the cholinergic basal forebrain for encoding sensory cues and behavioral reinforcement outcomes.

Basal forebrain cholinergic neurons (BFCNs) project throughout the cortex to regulate arousal, stimulus salience, plasticity, and learning. Although often treated as a monolithic structure, the basal forebrain features distinct connectivity along its rostrocaudal axis that could impart regional differences in BFCN processing. Here, we performed simultaneous bulk calcium imaging from rostral and caudal BFCNs over a 1-month period of variable reinforcement learning in mice.

Evaluation and Management of Delirium.

Delirium, sometimes referred to as encephalopathy, is an acute confusional state that is both common in hospitalized patients and associated with poor outcomes. For patients, families, and caregivers, delirium can be a traumatic experience. While delirium is one of the most common diagnoses encountered by the consulting neurologist, the majority of the time it will have been previously unrecognized as such by the care team.

Physiological Assessment of Delirium Severity: The Electroencephalographic Confusion Assessment Method Severity Score (E-CAM-S).

Objectives: Delirium is a common and frequently underdiagnosed complication in acutely hospitalized patients, and its severity is associated with worse clinical outcomes. We propose a physiologically based method to quantify delirium severity as a tool that can help close this diagnostic gap: the Electroencephalographic Confusion Assessment Method Severity Score (E-CAM-S).

Design: Retrospective cohort study.

Clinical Electroencephalography Findings and Considerations in Hospitalized Patients With Coronavirus SARS-CoV-2.

Background And Purpose: Reports have suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes neurologic manifestations including encephalopathy and seizures. However, there has been relatively limited electrophysiology data to contextualize these specific concerns and to understand their associated clinical factors. Our objective was to identify EEG abnormalities present in patients with SARS-CoV-2, and to determine whether they reflect new or preexisting brain pathology.

Electroencephalographic Abnormalities are Common in COVID-19 and are Associated with Outcomes.

Objective: The aim was to determine the prevalence and risk factors for electrographic seizures and other electroencephalographic (EEG) patterns in patients with Coronavirus disease 2019 (COVID-19) undergoing clinically indicated continuous electroencephalogram (cEEG) monitoring and to assess whether EEG findings are associated with outcomes.

Methods: We identified 197 patients with COVID-19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns.

OpBox: Open Source Tools for Simultaneous EEG and EMG Acquisition from Multiple Subjects.

electrophysiology experiments require the collection of data from multiple subjects, often for extended periods. Studying multiple subjects for extended periods can be made more efficient through simultaneous recordings, but scaling up recordings to accommodate larger numbers of subjects simultaneously requires coordination and consideration of costs and flexibility. To facilitate this process, we have developed OpBox, an open source set of tools to acquire electroencephalography (EEG) and electromyography (EMG) flexibly from multiple rodent subjects simultaneously.