Our research on disorders of consciousness (DOC) focusses on residual cognitive processing and (minimal) consciousness in altered states of awareness, that is, VS, MCS and LIS. Besides this, we are also interested in circadian rhythms in this clinical group.

But what is consciousness? To find a general definition for this term is challenging, wherefore consciousness is mainly a theoretical construct. Behaviourally, consciousness is thought to comprise two factors, which have to be present to a certain extent for normal consciousness to arise. These two factors are wakefulness and awareness and importantly, both factors are necessary and neither of them is sufficient for consciousness on its own. “Healthy consciousness” is characterised by the two factors co-varying. More specifically, during (non-rapid eye movement [REM]) sleep, arousal decreases and awareness of oneself and the environment fades as does consciousness. While in brain death and coma as well as anaesthesia both factors are absent and thus also consciousness is, arousal re-emerges in the vegetative and minimally conscious state (VS and MSC). These two states characterise states people enter when they emerge from coma following severe traumatic brain injury or ischaemic damage due to stroke or cardiac arrest. These two states are characterised by a dissociation of the two factors, while they present with variations in arousal, that is periods of eye opening and closing, awareness remains absent (VS) or strongly fluctuates (MCS). The locked-in syndrome does not denote a DOC state in the strictest sense as patients are thought to be fully conscious despite being paralysed.

Levels of arousal and awareness in sleep, minimally conscious and vegetative state patients as well as locked in syndrome (adapted from Blume et al. (2015))

Current Project

In the current research project (START-grant, awarded to M. Schabus in 10/2014), we are interested in (1) residual cognitive processing in altered states of consciousness (i.e. DOC patients and sleeping healthy subjects), (2) circadian rhythms in DOC patients and (3) sleep in this clinical group.

In the clinical context, the (clinical) assessment of consciousness is often based on behavioral observations of awareness or reports of signs of consciousness. Often, patients are however not able to verbalise conscious experience or “give evidence” of their consciousness (e.g. due to paralysis). One aim of our research therefore is to find neuronal processes that correlate with consciousness [1] in DOC patients, but also in healthy individuals who sleep.

Cognitive Processing in DOC & Sleeping Healthy Individuals
Here, we use the so-called “subject’s own name” (SON) paradigm. The subject’s own name (SON) is thought to be one of the strongest stimuli related to consciousness and self-awareness since it captures attention in a way that almost no other stimuli can [2]. In our research we often use a variation of the classic SON-paradigm by additionally varying the (paralinguistic) emotional content of the presented voice (prosody or familiarity of a voice). Here, the idea is that this may render the stimulus more prone to engage additional attentional resources and thus lead to a stronger brain response [3,4].

Sleep in DOC Patients
It is well known that abnormalities of sleep are extremely common in critical ill and severely brain injured patients (BIPs) [1]. Their sleep mechanisms are generally poorly understood and it is suspected that comatose patients might not show classical circadian cycling of their encephalic electrical activity (EEG). Characteristically, BIPs exhibit more frequent arousals and awakenings than healthy subjects and decreases in rapid eye movement (REM) and slow wave sleep (SWS) are common [2]. Furthermore, sleep disruption can induce sympathetic activation and elevation of blood pressure, which may contribute to patient morbidity. Other factors contributing to sleep abnormalities include acute illness, pain and discomfort, as well as increased alertness induced by continuous exposure to light, bed neighbours, etc. (even during nightly hours). Yet, sleep deprivation is known to have devastating impacts on immune functioning which is especially noteworthy for BIPs [3]. Unfortunately there is little knowledge about the exact sleep patterns experienced by BIPs. In addition certain EEG patterns resembling sleep are considered as favourable prognostic markers and it has been reported that these continue to improve during rehabilitation together with recovery of cognitive functions [5]. In several studies it was shown that especially stage 2 (N2) sleep spindles are favourable for patient’s prognosis and thus carry important information about the residual integrity of brain networks in BIPs. Furthermore, the regular cycling of Non-REM sleep elements (e.g. K-complexes) and REM sleep elements has been related to good outcome (such as full recovery or mild disability) [6,7]. As human spindle generators are located in the thalamus it is tempting to reason that the absence of spindles in coma presumably results from the interruption of either the ascending reticulothalamocortical pathway or thalamo-cortical loops. Likewise absence of sleep-wake cycles is associated with brainstem dysfunction and is indicating poor outcome. Overall PSG studies are in a good position to evaluate the functional integrity of the central nervous system and are an ideal supplement to standardized behavioural scales. We therefore believe that careful examination of sleep in disorders of consciousness is highly warranted.

Circadian Rhythms in DOC Patients
Manifold cognitive and bodily rhythms follow a rhythm with a period length of about 24h, wherefore they are called “circadian rhythms”. Misalignment of rhythms has been ascribed pathological significance in critically ill patients and we know that e.g. jetlag or shift-work, that is, cases in which the rhythms of the body are not aligned with the light-dark cycle, can have detrimental effects on cognition and the immune system. Surprisingly little, however, is known about circadian rhythms in DOC patients although they may for example inform about time windows when patients are maximally responsive. In our research project, we thus also aim at investigating circadian rhythms in DOC patients.

Study Design
Volunteers participating in the study come to the lab in the evening for a full night of recording after having slept in the lab for an adaptation night, during which we screen for sleep disorders. The (SON) paradigm comprises a wake and a sleep condition, among which the wake condition has an active and a passive part. In the passive parts subjects only have to listen to the stimuli while in the active part subjects are instructed to count one stimulus. Auditory stimulation is then continued during sleep.
Besides healthy participants, we also test patients in several clinics in Austria. These patients undergo 48h polysomnography recordings and are tested with the same cognitive paradigms as healthy participants. However, they only undergo the “wake condition”, i.e. they are not stimulated during the night. In addition, we measure body temperature and activity across a whole week to assess patients’s circadian rhythms and find time windows when we expect them to be more awake or responsive.

Study Aim
The results of this study will hopefully contribute to a better understanding of the neuronal processes underlying consciousness. Eventually, it might also lead to improve the diagnosis of patients suffering from disorders of consciousness (DOC). Beyond this, we hope to find a way to pre-specify time windows when patients can be expected to be maximally aroused and thus responsive to stimulation.

References
Schabus, M. (2014). Neuropsychologie bewusster und unbewusster Prozesse (Folien zu Vorlesung). Paris-Lodron Universität Salzburg, Österreich.
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Giudice, R., Lechinger, J., Wislowska, M., Heib, P. J., Hoedlmoser, K. & Schabus, M. (2013). Oscillatory brain responses to own names uttered by unfamiliar and familiar voices (unpublished work). Paris-Lodron Universität Salzburg, Österreich.
Blume C., del Giudice, R, Lechinger J., Wislowska M., Heib D. P. J., Hoedlmoser K., & Schabus, M. (2016). Preferential processing of emotionally and self-relevant stimuli persists in unconscious N2 sleep. Brain and Language. doi:10.1016/j.bandl.2016.02.004
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