Propofol-induced GABAergic Tonic Inhibition Diminishes α-rhythms and Induces δ-rhythms in neuronal populations

Anaesthetic agents such as propofol are known to have an effect on both synaptic and extra-synaptic receptors. On the one hand, binding of propofol to GABA A synaptic receptors induces a phasic inhibition, as opposed to tonic inhibition which seems mainly induced by binding to extra-synaptic receptors. On the second hand, under aneasthesia, an increase in amount of slow oscillations, mainly delta (0-4Hz), concurrent to a decrease of alpha oscillations (8-12Hz), is observed in EEG recordings of occipital areas in most mammals including humans. The latter observation cannot be explained by sole phasic inhibition. Therefore, we propose to investigate, through numer- ical simulations, the role of tonic inhibition in the increase (in amount) of slow oscillations under propofol anaesthesia. To account for the biological realism of our simulations, the cortical model includes two neuronal populations, one excitatory modeled by Type I Leaky integrate-and-fire neurons, one inhibitory modeled by Type II Morris-Lecar neurons, the stimulations are noisy, and the intrinsic cellular properties heterogeneous. The cells are connected through exponential conductance-based synapses. We show that, in presence of tonic inhibition, 1) the oscillation frequency of the network decreases as well as subthreshold oscillations, inducing delta-rhythms in EEG-like recordings; 2) simulatneously, the amount of alpha-rhythms decreases supporting experimental evidence about the role of tonic inhibition

Toiminnallisen kytkennällisyyden mittarit aivosähkökäyristä anestesian aikana

Tiivistelmä. Toiminnallisen kytkennällisyyden mittaaminen perustuu aivojen eri osista mitattujen signaalien tai tapahtumien tilastolliseen riippuvuuteen toisistaan. Aivosähkökäyriä saadaan aikaan mittaamalla aivosolujen toimiessaan tuottamien sähköisten potentiaalien muutoksia ajan suhteen eri puolilta aivoja. Aivosähkökäyriä kutsutaan myös elektroenkefalogrammiksi. Niitä voidaan helposti mitata aivojen ulkopuolelta ihon pinnalta. Toiminnallista kytkennällisyyttä voidaan mitata muun muassa aivosähkökäyristä. Anestesia on tila, jossa kohde ei pysty havaitsemaan tai tuntemaan mitään. Usein se saadaan aikaan jonkin aineen avulla hallitusti. Anestesia on siis hallittu tapa saada aivot johonkin muuhun tilaan kuin missä ne ovat hereilläolon aikana. Anestesiaa käytetään hyvin yleisesti potilaan saattamiseksi tiedottomaan tilaan lääketieteellisten toimenpiteiden aikana. Tämän kirjallisuuskatsauksen tarkoituksena on tutkia, minkälaisia menetelmiä tällä hetkellä käytetään toiminnallisen kytkennällisyyden mittaamiseksi aivosähkökäyristä anestesian aikana. Anestesian avulla tapahtuva aivojen hallittu siirtäminen tilasta toiseen mahdollistaa aivojen toiminnan vertailun eri tiloissa, mikä on olennaista toiminnallisen kytkennällisyyden tutkimiseksi. Näin ollen kyseinen yhdistelmä on kiinnostava tutkimuskohde. Lähdeaineistona on käytetty varsin laajaa julkaistujen tutkimusten joukkoa työn aiheeseen liittyen. Katsauksessa esitellään ensin taustatietoa aiheen ymmärtämiseksi ja sitten syvennytään varsin laajaan ja kirjavaan joukkoon menetelmiä. Tutkimusten perusteella tavoitteena on ymmärtää aivojen toimintaa eri tietoisuuden tiloissa. Käytännössä tätä ymmärrystä sovelletaan ainakin anestesian syvyyden mittarien kehittämisessä lääketieteellisiin tarkoituksiin leikkauspotilaan turvallisuuden ja toimenpiteestä toipumisen varmistamiseksi. Menetelmissä ollaan siirrytty kohtalaisen yksinkertaisista signaalien tilastollisen riippuvuuden tarkasteluun perustuvista menetelmistä epälineaarisiin menetelmiin, kytkennällisyyden monimuotoisuuden tarkasteluun ja toiminnallisten verkkojen rakenteen tarkasteluun.Functional connectivity measures from the EEG during anaesthesia. Abstract. Functional connectivity measures are based on the statistical dependence of signals or events measured from different parts of the brain. Electroencephalogram measures the temporal evolution of the electrical potentials, produced by the brain neurons, from different parts of the brain. Electroencephalogram can be easily measured from outside the brain, on top of the skin. Functional connectivity can be measured amongst others from that. Anaesthesia is a state in which the target is not able to observe or feel anything. Usually it is induced with some anaesthetic agent in a controlled manner. Anaesthesia is therefore a controlled way to get the brain to some other state from the state in which it is during wakefulness. Anaesthesia is commonly used to get the patient into an unconscious state during medical operations. The purpose of this literature review is to research what kind of methods are currently used to measure functional connectivity from electroencephalogram data during anaesthesia. The controlled transition of the brain from a state to another with anaesthesia makes it possible to compare the functionality of the brain in different states, which is vital for researching functional connectivity. Therefore this combination is an interesting target for research. A rather large group of research publications relating to the topic of this thesis has been used as the source material. The review first introduces some background information for understanding the topic and then concentrates on a rather large variety of methods. Based on the research, the purpose is to understand the workings of the brain in different states of consciousness. In practice this understanding is applied at least when developing measures of the depth of anaesthesia for medical purposes, to ensure the safety and proper recovery from the operation of a patient. The focus in the methods has been shifted from relatively simple methods based on observing the statistical dependency between signals to nonlinear methods, observing the diversity of connectivity, and observing the structure of functional networks

Ain't no rest for the brain: Neuroimaging and neuroethics in dialogue for patients with disorders of consciousness

The sheer amount of different opinions about what consciousness is highlights its multifaceted character. The clinical study of consciousness in coma survivors provides unique opportunities, not only to better comprehend normal conscious functions, but also to confront clinical and medico-ethical challenges. For example, pain in vegetative state/unresponsive wakefulness syndrome patients (VS/UWS; i.e. awaken, but unconscious) and patients in minimally conscious states (MCS; awaken, with fluctuating signs of awareness) cannot be communicated and needs to be inferred. Behaviorally, we developed the Nociception Coma Scale, a clinical tool which measures patients’ motor, verbal, visual, and facial responsiveness to noxious stimulation. Importantly, the absence of proof of a behavioral response cannot be taken as proof of absence of pain. Functional neuroimaging studies show that patients in VS/UWS exhibit no evidence of control-like brain activity, when painfully stimulated, in contrast to patients in MCS. Similarly, the majority of clinicians ascribe pain perception in MCS patients. Interestingly, their opinions appear less congruent with regards to pain perception in VS/UWS patients, due to personal and cultural differences. The imminent bias in clinical practice due to personal beliefs becomes more ethically salient in complex clinical scenarios, such as end-of-life decisions. Surveys among clinicians show that the majority agrees with treatment withdrawal for VS/UWS, but fewer respondents would do so for MCS patients. For the issue of pain in patients with disorders of consciousness, the more the respondents ascribed pain perception in these states the less they supported treatment withdraw from these patients. Such medico-ethical controversies require an objective and valid assessment of pain (and eventually of consciousness) in noncommunicating patients. Functional neuroimaging during “resting state” (eyes closed, no task performance) is an ideal paradigm to investigate residual cognition in noncommunicating patients, because it does not require sophisticated technical support or subjective input on patients’ behalf. With the ultimate intention to use this paradigm in patients, we first aimed to validate it in controls. We initially found that, in controls, fMRI “resting state” activity correlated with subjective reports of “external” (perception of the environment through the senses) or “internal” awareness (self-related mental processes). Then, using hypnosis, we showed that there was reduced fMRI connectivity in the “external network”, reflecting decreased sensory awareness. When more cerebral networks were tested, increased functional connectivity was observed for most of the studied networks (except the visual). These results indicate that resign state fMRI activity reflects, at least partially, ongoing conscious cognition, which changes under different conditions. Using the resting state paradigm in patients with disorders of consciousness, we vi showed intra- and inter-network connectivity breakdown in sensorysensorimotor and “higher-order” networks, possibly accounting for patients’ limited capacities for conscious cognition. We have further observed positive correlation between the Nociception Coma Scale scores and the pain-related (salience) network connectivity, potentially reflecting nociception-related processes in these patients, measured in the absence of an external stimulus. These results highlight the utility of resting state analyses in clinical settings, where short and simple setups are preferable to activation protocols with somatosensory, visual, and auditory stimulation devices. Especially for neuroimaging studies, it should be stressed that such experimental investigations tackle the necessary conditions supporting conscious processing. The sufficiency of the identified neural correlates accounting for conscious awareness remains to be identified via dynamic and causal information flow investigations. Importantly, the quest of subjectivity in non-communicating patients can be better understood by adopting an interdisciplinary biopsychosocial approach, combining basic neuroscience (bio), psychological-cognitive-emotional processing (psycho), and the influence of different socioeconomic, cultural, and technological factors (social)

Improving somatic health for outpatients with severe mental illness: the development of an intervention

Objective: Patients with severe mental illness (SMI) suffer from more somatic illness than the general population. Possible causes are side effects of neuropsychiatric medication, genetic vulnerability, insufficient health care and lifestyle. This co-morbidity is potentially reversible and augments the costs for health care and diminishes quality of life. Screening on symptoms and risks of somatic diseases and coordination of care are proposed to improve SMI-patients' somatic health status. Methods: A clinical facility was started to improve the somatic health status of patients in an outpatient centre in southern Netherlands. This outpatient centre was added to the specialized care for severe and enduring SMI. The intervention consisted of the inventarisation of side-effects and the detection of gaps in health care provision for 72 patients. This was based on interviewing the patients, laboratory screening, collecting information from their general practitioner and pharmacy. A list was compiled of possible diagnosis and health risks, and a plan of action was made for the treatment. Healthcare consumption, quality of life and general functioning were assessed to analyze cost-effectiveness. Evaluations were performed with the psychiatric care team on the process. Results: Mean annual cost of GP's and medical specialist's consultations were E492. There existed a negative relation between EQ5D VAS and the number of self reported chronic diseases. Conclusion: The authors conclude that the procedure is well feasible, but should be set up in close collaboration with all health care professionals of these patients to make tailor made solutions possible