Optimizing Circadian Rhythm and Characterizing Brain Function in Disorders of Consciousness

Sleep is a physiological state where memory processing, learning and brain plasticity occur. Patients with prolonged disorders of consciousness (PDOC) show no or minimal signs of awareness of themselves or their environment but appear to have sleep-wake cycles. The main aim of this thesis was to investigate effect of circadian rhythm and sleep optimization on brain functions of patients with PDOC. In the first instance, sleep and circadian rhythms of patients with PDOC were investigated using polysomnography and saliva melatonin measurements. The investigations that were performed at the baseline suggested that both circadian rhythmicity and sleep were severely deranged in PDOC patients. This was followed by the interventional stage of the research where an attempt was made to optimize circadian rhythm and sleep by giving blue light, caffeine and melatonin in a small cohort of patients. To measure the effects of the intervention, we used a variety of assessments: Coma Recovery Scale-Revised (CRS-R) to measure changes in awareness; PSG for assessment of sleep, melatonin for assessment of circadian rhythm; and, event-related potential measures including mismatch negativity (MMN) and subject’s own name (SON) paradigms. Our results showed that it is possible to improve sleep and circadian rhythms of patients with PDOC, and most importantly, this improvement leads to increase in Coma Recovery Scale-Revised scores. Individually, those patients who responded well to the intervention also showed improvements in their functional brain imaging assessments

Exploring end-of-life decision-making in China for disorders of consciousness.

peer reviewed[en] OBJECTIVES: We aim to investigate the ethical attitudes of the Chinese population toward withdrawal of life-sustaining treatment (WLST) in disorders of consciousness (DoC) patients. METHODS: A self-administered questionnaire concerning WLST was distributed to Chinese medical professionals and non-medical participants between February and July 2022. Statistical analysis included chi-square tests and logistic regressions. RESULTS: A total of 1223 Chinese participants responded to the questionnaire (39% of whom were medical professionals). Less than one third of participants reported positive attitudes towards withdrawing artificial nutrition and hydration (ANH), antibiotics, and do-not-resuscitation (DNR) orders in patients with unresponsive wakefulness syndrome (UWS) (30%, 24%, 24%) and minimally conscious state (MCS) (23%, 19%, 15%). More respondents agreed with WLST in UWS compared to MCS (p  5000 RMB and medical profession (p < 0.05). Most participants deemed patient's will (78%), families' wishes (67%), and financial burden (63%) to be crucial factors when considering WLST. CONCLUSIONS: Chinese respondents exhibit a relatively low propensity to accept WLST in DoC. Ethical attitudes toward WLST resulted to be affected by individual characteristics of responders. These results call for developing better regulations for identifying qualified surrogate decision-makers and reducing legal ambiguities

Neuromodulation of Vegetative State through Spinal Cord Stimulation: Where Are We Now and Where Are We Going?

Background: Vegetative state (VS) is a complex condition that represents a challenging frontier for medicine and neuroscience research. Nowadays there is no scientifically validated treatment for VS patients, and their chronic long-term assistance is very demanding for healthcare systems worldwide. Objectives: The present paper is a systematic review of the role of spinal cord stimulation (SCS) as a treatment of patients with VS. Methods: Published literature on this topic was analyzed systematically. Clinical and epidemiological characteristics of VS, present therapeutic options and social costs of VS were also evaluated. Results: Only 10 papers have been published since 1988, and overall 308 VS patients have been treated with SCS worldwide; 51.6% displayed a clinical improvement and an amelioration of the environmental interaction. These effects are probably mediated by the stimulation of the reticular formation-thalamus-cortex pathway and by cerebral blood flow augmentation induced by SCS. Conclusions: The experience on this topic is still very limited, and on this basis it is still hard to make any rigorous assessment. However, the most recent experiments represent significant progress in the research on this topic and display SCS as a possible therapeutic tool in the treatment of VS

Finding a way in: A review and practical evaluation of fMRI and EEG for detection and assessment in disorders of consciousness

Diagnoses and assessments of cognitive function in disorders of consciousness (DOC) are notoriously prone to error due to their reliance on behavioural measures. As a result, researchers have turned to functional neuroimaging and electrophysiological techniques with the goal of developing more effective methods of detecting awareness and assessing cognition in these patients. This article reviews functional magnetic resonance imaging (fMRI) and electroenchphalography (EEG)-based studies of cognition and consciousness in DOC, including assessment of basic sensory, perceptual, language, and emotional processing; studies for detection of conscious awareness; paradigms for the establishment of communication in the absence of behaviour; and functional connectivity studies. The advantages and limitations of fMRI and EEG-based measures are examined as research and clinical tools in this population and an explanation offered for the rediscovery of the unique advantages of EEG in the study of DOC

Mental Imagery for the Detection of Awareness: Evaluating the Convergence of Functional Magnetic Resonance Imaging and Electroencephalographic Assessments

The accurate diagnosis of disorders of consciousness presents substantial difficulty because of the reliance on behaviour-based assessment tools. A patient may be covertly aware but unable to indicate their state due to physical impairments. Neuroimaging researchers have begun to seek alternate methods of assessment that rely on brain responses rather than behavioural ones. To this end, mental imagery has been employed as a voluntary cognitive activity that can be measured with fMRI or EEG to indicate awareness. In this dissertation I examine the advantages and limitations of these two imaging techniques and argue that EEG is more suitable for this patient population. I expand upon existing mental imagery research by exploring additional tasks that have not been applied to this problem, in order to address three previously unanswered questions that are central to the development of imagery-based diagnostic tools. First, do individuals differ on which imagery tasks produce the most reliable activation? Second, can the robustness of brain activation during imagery be predicted from familiarity with the imagined activity? Third, do fMRI and EEG provide converging evidence about individual imagery performance? In order to answer these questions, 6 mental imagery tasks were examined using simultaneous EEG and fMRI recordings, in combination with participant ratings. The findings revealed that, of the mental imagery tasks studied, mental arithmetic consistently produced the most robust activation at the single subject level. Additionally, there was no relationship between participants’ familiarity with an activity and the level of brain activation during performance. The key finding demonstrated that EEG and fMRI were in agreement on both of these questions, lending support to the increasing use of EEG over fMRI in disorders of consciousness.Doctor of Philosophy (PhD

Neuroscientific deconstruction of the ideologised »hopelessness« of the vegetative state

Recent neuroscientific research challenges today's prejudice of a vegetative state as a «hopeless» state. The results from these findings not only destroy the actual existing prejudices about people in a vegetative state, but they also provide a new insight into the epistemological problematics of the accurate diagnostic process of the actual state, followed up with ethical and social implications. They also provide a better understanding of the mere nature of consciousness and awareness, implying the moral and social responsibility towards these people, and at the same time leaving no place for «hopelessness». Therefore, the primary aim of this article is to demonstrate how, with the development of these new insights into the state of disorders of consciousness, side by side, from the mere beginning has been developing prejudice of «hopelessness», as a side-effect of insufficient and inadequate knowledge related to the nature of consciousness in the vegetative state. This conformity prejudice has had direct influence on clinical decision-making regarding artificial life-sustaining measures: from hydration and nutrition withdrawal, to do not resuscitate orders, and finally to ventilator withdrawal, retaining that the person has no hope for recovery after the determination of the vegetative state diagnosis. Furthermore, this prejudice of «hopelessness» has not only deeply paved the morally doubtful way for performing passive euthanasia, but was, even more, misused and politicised as one of the main arguments and examples of the pro-euthanasia movements in the fight for euthanasia legalisation