Psilocybin desynchronizes brain networks.

1The relationship between the acute effects of psychedelics and their persisting neurobiological and psychological effects is poorly understood. Here, we tracked brain changes with longitudinal precision functional mapping in healthy adults before, during, and for up to 3 weeks after oral psilocybin and methylphenidate (17 MRI visits per participant) and again 6+ months later. Psilocybin disrupted connectivity across cortical networks and subcortical structures, producing more than 3-fold greater acute changes in functional networks than methylphenidate. These changes were driven by desynchronization of brain activity across spatial scales (area, network, whole brain). Psilocybin-driven desynchronization was observed across association cortex but strongest in the default mode network (DMN), which is connected to the anterior hippocampus and thought to create our sense of self. Performing a perceptual task reduced psilocybin-induced network changes, suggesting a neurobiological basis for grounding, connecting with physical reality during psychedelic therapy. The acute brain effects of psilocybin are consistent with distortions of space-time and the self. Psilocybin induced persistent decrease in functional connectivity between the anterior hippocampus and cortex (and DMN in particular), lasting for weeks but normalizing after 6 months. Persistent suppression of hippocampal-DMN connectivity represents a candidate neuroanatomical and mechanistic correlate for psilocybin's pro-plasticity and anti-depressant effects.

Rapid sequence tandem intubation to navigate a subglottic obstruction.

Emergency airway management requires matching the appropriate intubation tools to anticipated obstacles. Video laryngoscopy and flexible endoscopy are often used for difficult airways. Here we describe a case where neither method alone was anticipated to be sufficient. A 53-year-old female with an obstructing lung mass required intubation for a mixed type 1 and 2 respiratory failure. Chest x-ray revealed a tortuous subglottic obstruction. The patient could not be temporized on maximized non-invasive airway support. These factors made tandem intubation, sequentially using video laryngoscopy and flexible endoscopic intubation, an appropriate intubation strategy. In this case report we describe the rationale and technique for a rapid sequence tandem intubation.

Emergency Department-initiated High-flow Nasal Cannula for COVID-19 Respiratory Distress.

INTRODUCTION: Patients with coronavirus disease 2019 (COVID-19) can develop rapidly progressive respiratory failure. Ventilation strategies during the COVID-19 pandemic seek to minimize patient mortality. In this study we examine associations between the availability of emergency department (ED)-initiated high-flow nasal cannula (HFNC) for patients presenting with COVID-19 respiratory distress and outcomes, including rates of endotracheal intubation (ETT), mortality, and hospital length of stay. METHODS: We performed a retrospective, non-concurrent cohort study of patients with COVID-19 respiratory distress presenting to the ED who required HFNC or ETT in the ED or within 24 hours following ED departure. Comparisons were made between patients presenting before and after the introduction of an ED-HFNC protocol. RESULTS: Use of HFNC was associated with a reduced rate of ETT in the ED (46.4% vs 26.3%, P <0.001) and decreased the cumulative proportion of patients who required ETT within 24 hours of ED departure (85.7% vs 32.6%, P <0.001) or during their entire hospitalization (89.3% vs 48.4%, P <0.001). Using HFNC was also associated with a trend toward increased survival to hospital discharge; however, this was not statistically significant (50.0% vs 68.4%, P = 0.115). There was no impact on intensive care unit or hospital length of stay. Demographics, comorbidities, and illness severity were similar in both cohorts. CONCLUSIONS: The institution of an ED-HFNC protocol for patients with COVID-19 respiratory distress was associated with reductions in the rate of ETT. Early initiation of HFNC is a promising strategy for avoiding ETT and improving outcomes in patients with COVID-19.

Improving mental health in U.S. Veterans using mHealth tools: A pilot study.

Rates of PTSD remain elevated among U.S. Veterans, highlighting a need for innovative management tools. Previous studies have shown mobile apps to have positive effects on PTSD symptoms, but few apps have been examined systematically. This pilot study evaluated the perceived effectiveness and usability of Mindset, a novel mobile app that monitors user stress level via heart rate to encourage e-therapy use. The study sample included 30 community-residing Veterans who completed baseline assessments. They used the Mindset app and associated smartwatch until their approximate 1-month follow-up. Self-reported assessments included pre- and post-deployment experiences; experience with Mindset; and standard screeners for PTSD (PCL-M), anxiety (GAD-7), depression (PHQ-9), and alcohol use problems (AUDIT). Among the 24 participants who completed follow-up interviews, a significant decrease (p < 0.05) was found in PCL-M, PHQ-9, and modified AUDIT scores. Respondents reported moderate to high acceptance and satisfaction with Mindset features, though considerable frustration with the associated smartwatch. These findings highlight mHealth apps such as Mindset as potentially useful tools for PTSD and depression symptom management. These findings are also encouraging in the context of the current COVID-19 pandemic, which may accelerate further innovation and implementation of mHealth technologies to improve mental health self-care.

Distinct phase-amplitude couplings distinguish cognitive processes in human attention.

Spatial attention is the cognitive function that coordinates the selection of visual stimuli with appropriate behavioral responses. Recent studies have reported that phase-amplitude coupling (PAC) of low and high frequencies covaries with spatial attention, but differ on the direction of covariation and the frequency ranges involved. We hypothesized that distinct phase-amplitude frequency pairs have differentiable contributions during tasks that manipulate spatial attention. We investigated this hypothesis with electrocorticography (ECoG) recordings from participants who engaged in a cued spatial attention task. To understand the contribution of PAC to spatial attention we classified cortical sites by their relationship to spatial variables or behavioral performance. Local neural activity in spatial sites was sensitive to spatial variables in the task, while local neural activity in behavioral sites correlated with reaction time. We found two PAC frequency clusters that covaried with different aspects of the task. During a period of cued attention, delta-phase/high-gamma (DH) PAC was sensitive to cue direction in spatial sites. In contrast, theta-alpha-phase/beta-low-gamma-amplitude (TABL) PAC robustly correlated with future reaction times in behavioral sites. Finally, we investigated the origins of TABL PAC and found it corresponded to behaviorally relevant, sharp waveforms, which were also coupled to a low frequency rhythm. We conclude that TABL and DH PAC correspond to distinct mechanisms during spatial attention tasks and that sharp waveforms are elements of a coupled dynamical process.

Electrophysiological Sequelae of Hemispherotomy in Ipsilateral Human Cortex.

Objectives: Hemispheric disconnection has been used as a treatment of medically refractory epilepsy and evolved from anatomic hemispherectomy to functional hemispherectomies to hemispherotomies. The hemispherotomy procedure involves disconnection of an entire hemisphere with limited tissue resection and is reserved for medically-refractory epilepsy due to diffuse hemispheric disease. Although it is thought to be effective by preventing seizures from spreading to the contralateral hemisphere, the electrophysiological effects of a hemispherotomy on the ipsilateral hemisphere remain poorly defined. The objective of this study was to evaluate the effects of hemispherotomy on the electrophysiologic dynamics in peri-stroke and dysplastic cortex. Methods: Intraoperative electrocorticography (ECoG) was recorded from ipsilateral cortex in 5 human subjects with refractory epilepsy before and after hemispherotomy. Power spectral density, mutual information, and phase-amplitude coupling were measured from the ECoG signals. Results: Epilepsy was a result of remote perinatal stroke in three of the subjects. In two of the subjects, seizures were a consequence of dysplastic tissue: one with hemimegalencephaly and the second with Rasmussen's encephalitis. Hemispherotomy reduced broad-band power spectral density in peri-stroke cortex. Meanwhile, hemispherotomy increased power in the low and high frequency bands for dysplastic cortex. Functional connectivity was increased in lower frequency bands in peri-stroke tissue but not affected in dysplastic tissue after hemispherotomy. Finally, hemispherotomy reduced band-specific phase-amplitude coupling in peristroke cortex but not dysplastic cortex. Significance: Disconnecting deep subcortical connections to peri-stroke cortex via a hemispherotomy attenuates power of oscillations and impairs the transfer of information from large-scale distributed brain networks to the local cortex. Hence, hemispherotomy reduces heterogeneity between neighboring cortex while impairing phase-amplitude coupling. In contrast, dysfunctional networks in dysplastic cortex lack the normal connectivity with distant networks. Therefore hemispherotomy does not produce the same effects.

Using pupil size and heart rate to infer affective states during behavioral neurophysiology and neuropsychology experiments.

BACKGROUND: Nonhuman primates (NHPs) are a valuable research model because of their behavioral, physiological and neuroanatomical similarities to humans. In the absence of language, autonomic activity can provide crucial information about cognitive and affective states during single-unit recording, inactivation and lesion studies. Methods standardized for use in humans are not easily adapted to NHPs and detailed guidance has been lacking. NEW METHOD: We provide guidance for monitoring heart rate and pupil size in the behavioral neurophysiology setting by addressing the methodological issues, pitfalls and solutions for NHP studies. The methods are based on comparative physiology to establish a rationale for each solution. We include examples from both electrophysiological and lesion studies. RESULTS: Single-unit recording, pupil responses and heart rate changes represent a range of decreasing temporal resolution, a characteristic that impacts experimental design and analysis. We demonstrate the unexpected result that autonomic measures acquired before and after amygdala lesions are comparable despite disruption of normal autonomic function. COMPARISON WITH EXISTING METHODS: Species and study design differences can render standard techniques used in human studies inappropriate for NHP studies. We show how to manage data from small groups typical of NHP studies, data from the short behavioral trials typical of neurophysiological studies, issues associated with longitudinal studies, and differences in anatomy and physiology. CONCLUSIONS: Autonomic measurement to infer cognitive and affective states in NHP is neither off-the-shelf nor onerous. Familiarity with the issues and solutions will broaden the use of autonomic signals in NHP single unit and lesion studies.

Disruptions of network connectivity predict impairment in multiple behavioral domains after stroke.

Deficits following stroke are classically attributed to focal damage, but recent evidence suggests a key role of distributed brain network disruption. We measured resting functional connectivity (FC), lesion topography, and behavior in multiple domains (attention, visual memory, verbal memory, language, motor, and visual) in a cohort of 132 stroke patients, and used machine-learning models to predict neurological impairment in individual subjects. We found that visual memory and verbal memory were better predicted by FC, whereas visual and motor impairments were better predicted by lesion topography. Attention and language deficits were well predicted by both. Next, we identified a general pattern of physiological network dysfunction consisting of decrease of interhemispheric integration and intrahemispheric segregation, which strongly related to behavioral impairment in multiple domains. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains. These results link key organizational features of brain networks to brain-behavior relationships in stroke.

Effects of amygdala lesions on reward-value coding in orbital and medial prefrontal cortex.

We examined the contribution of the amygdala to value signals within orbital prefrontal cortex (OFC) and medial prefrontal cortex (MFC). On each trial, monkeys chose between two stimuli that were associated with different quantities of reward. In intact monkeys, as expected, neurons in both OFC and MFC signaled the reward quantity associated with stimuli. Contrasted with MFC, OFC contained a larger proportion of neurons encoding reward quantity and did so with faster response latencies. Removing the amygdala eliminated these differences, mainly by decreasing value coding in OFC. Similar decreases occurred in OFC immediately before and after reward delivery. Although the amygdala projects to both OFC and MFC, we found that it has its greatest influence over reward-value coding in OFC. Notably, amygdala lesions did not abolish value coding in OFC, which shows that OFC's representations of the value of objects, choices, and outcomes depends, in large part, on other sources.