BackgroundAlthough the induction of behavioural unconsciousness during sleep and general anaesthesia has been shown to involve overlapping brain mechanisms, sleep involves cyclic fluctuations between different brain states known as active (paradoxical or rapid eye movement: REM) and quiet (slow-wave or non-REM: nREM) stages whereas commonly used general anaesthetics induce a unitary slow-wave brain state.Methodology/Principal FindingsLong-duration, multi-site forebrain field recordings were performed in urethane-anaesthetized rats. A spontaneous and rhythmic alternation of brain state between activated and deactivated electroencephalographic (EEG) patterns was observed. Individual states and their transitions resembled the REM/nREM cycle of natural sleep in their EEG components, evolution, and time frame (∼11 minute period). Other physiological variables such as muscular tone, respiration rate, and cardiac frequency also covaried with forebrain state in a manner identical to sleep. The brain mechanisms of state alternations under urethane also closely overlapped those of natural sleep in their sensitivity to cholinergic pharmacological agents and dependence upon activity in the basal forebrain nuclei that are the major source of forebrain acetylcholine. Lastly, stimulation of brainstem regions thought to pace state alternations in sleep transiently disrupted state alternations under urethane.Conclusions/SignificanceOur results suggest that urethane promotes a condition of behavioural unconsciousness that closely mimics the full spectrum of natural sleep. The use of urethane anaesthesia as a model system will facilitate mechanistic studies into sleep-like brain states and their alternations. In addition, it could also be exploited as a tool for the discovery of new molecular targets that are designed to promote sleep without compromising state alternations.
State-dependent EEG in the hippocampus (HPC) has traditionally been divided into two activity patterns: theta, a large-amplitude, regular oscillation with a bandwidth of 3-12 Hz, and large-amplitude irregular activity (LIA), a less regular signal with broadband characteristics. Both of these activity patterns have been linked to the memory functions subserved by the HPC. Here we describe, using extracellular field recording techniques in naturally sleeping and urethane-anesthetized rats, a novel state present during deactivated stages of sleep and anesthesia that is characterized by a prominent large-amplitude and slow frequency (Յ1 Hz) rhythm. We have called this activity the hippocampal slow oscillation (SO) because of its similarity and correspondence with the previously described neocortical SO. Almost all hippocampal units recorded exhibited differential spiking behavior during the SO as compared with other states. Although the hippocampal SO occurred in situations similar to the neocortical SO, it demonstrated some independence in its initiation, coordination, and coherence. The SO was abolished by sensory stimulation or cholinergic agonism and was enhanced by increasing anesthetic depth or muscarinic receptor antagonism. Laminar profile analyses of the SO showed a phase shift and prominent current sink-source alternations in stratum lacunosum-moleculare of CA1. This, along with correlated slow oscillatory field and multiunit activity in superficial entorhinal cortex suggests that the hippocampal SO may be coordinated with slow neocortical activity through input arriving via the temporo-ammonic pathway. This novel state may present a favorable milieu for synchronization-dependent synaptic plasticity within and between hippocampal and neocortical ensembles.
Anesthesia is a powerful tool in neuroscientific research, especially in sleep research where it has the experimental advantage of allowing surgical interventions that are ethically problematic in natural sleep. Yet, while it is well documented that different anesthetic agents produce a variety of brain states, and consequently have differential effects on a multitude of neurophysiological factors, these outcomes vary based on dosages, the animal species used, and the pharmacological mechanisms specific to each anesthetic agent. Thus, our aim was to conduct a controlled comparison of spontaneous electrophysiological dynamics at a surgical plane of anesthesia under six common research anesthetics using a ubiquitous animal model, the Sprague-Dawley rat. From this direct comparison, we also evaluated which anesthetic agents may serve as pharmacological proxies for the electrophysiological features and dynamics of unconscious states such as sleep and coma. We found that at a surgical plane, pentobarbital, isoflurane and propofol all produced a continuous pattern of burst-suppression activity, which is a neurophysiological state characteristically observed during coma. In contrast, ketamine-xylazine produced synchronized, slow-oscillatory activity, similar to that observed during slow-wave sleep. Notably, both urethane and chloral hydrate produced the spontaneous, cyclical alternations between forebrain activation (REM-like) and deactivation (non-REM-like) that are similar to those observed during natural sleep. Thus, choice of anesthesia, in conjunction with continuous brain state monitoring, are critical considerations in order to avoid brain-state confounds when conducting neurophysiological experiments.
We herein report the case of a 57-year-old man with esophageal cancer who was found to have a double aortic arch and right-sided descending aorta. Traditional approaches such as the Ivor Lewis and McKeown were excluded because the descending aorta would obscure the surgical field, and a neck anastomosis with the conduit through the ring could result in compression. We therefore opted for a left thoracoabdominal incision, allowing excellent exposure while reserving the possibility of placing the conduit substernally.
Background The incidence of depression, anxiety, and post-traumatic stress disorders is reported to be as high as 50% in trauma patients. The perpetual negative emotions and state of mind in these disorders predisposes patients to negative mental health outcomes. Mindfulness, on the other hand, helps people to process their experience and emotions in a non-judgmental manner, and recently, there has been increased utilization of mindfulness-based therapies for the treatment of mental health conditions. This proof-of-concept study evaluates the use of a mindfulness-based online application in patients admitted to the trauma service at a Level 1 Trauma Centre. Methods Trauma patients who were English speaking, over the age of 18, and without brain injury or pre-existing neurocognitive disorder were included. Participants completed the Depression Anxiety Stress Scale (DASS)-21 to assess level of depression, anxiety, and stress, and the Connor-Davidson Resilience Scale (CD-RISC) to assess level of resiliency. Then, after 28 consecutive days of practicing mindfulness using the app ‘Stop, Breathe, and Think,’ the questionnaires were repeated and an exit survey conducted. Results For this study, 13 participants were enrolled, 2 withdrew, and 5 were lost to follow-up. The mean DASS-21 score at time enrollment was 16.4 and was 11.2 at follow-up ( p = 0.10). There were no differences between the level of depression and stress from enrollment to follow-up, but there was significant decrease in anxiety symptoms from 7.2 to 3.0 (<0.05). CD-RISC scores at enrollment and follow-up were 77.8 and 81 ( p = 0.23), respectively. At the time of exit interview, 67% of patients continued to use the application three to four times a week and 67% responded they plan to continue using the application. In addition, 83% of patients always or often felt better after practicing mindfulness and stated they would recommend the application to others. Conclusions Mindfulness shows promising potential to decrease psychological distress in trauma patients.
Background There is a known significant risk of negative mental health consequences following traumatic injury, yet no standard approach to prevent psychiatric illness in trauma patients currently exists. Mindfulness-based psychotherapies have been shown to reduce symptoms of post-traumatic stress disorder, depression and anxiety and improve resiliency, however it is unknown whether a mindfulness intervention immediately following traumatic injury would lead to diminished mental health consequences. Methods Multi-system trauma patients at the University of Alberta Hospital (N = 63) and the Foothills Hospital (N = 60) were assigned to the experimental and control groups respectively. Patients in the experimental group were asked to use the guided mindfulness application “Stop, Breathe & Think” for 28 consecutive days. All patients completed the Depression Anxiety Stress Scale (DASS-21) and Connor-Davidson Resilience Scale (CD-RISC) 48 hours and 28 days following admission. An exit interview was conducted for patients in the experimental group. Results There was no significant difference in mean enrollment DASS-21 scores, mean enrollment CD-RISC scores, mean follow-up DASS-21 scores and mean follow-up CD-RISC scores between experimental and control groups. Paired t-tests of mean admission and mean follow-up DASS-21 and CD-RISC scores were not significantly different in the experimental group. Paired t-tests of mean admission and follow-up CD-RISC scores were not significantly different in the control group whereas mean followup DASS-21 scores were decreased in the control group relative to enrolment DASS-21 scores (p = 0.014). Patients reported improved mood after use of mindfulness, and most planned to continue using the therapy and would recommend it to others. Conclusion Our study did not demonstrate an objective benefit of mindfulness intervention immediately following traumatic injury. Exit interview data suggests that a web-based mindfulness intervention may be beneficial for certain trauma patients however further research is required to identify those most likely to realize substantial gains.
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