Near Infrared Spectroscopy and Electroencephalography For an Assessment of Brain Function in patients with Disorders of Consciousness

There is growing evidence that some of the patients presenting with the Vegetative State (VS), also known as Unresponsive Wakefulness State, can respond to environmental stimuli. This response can be detected by using functional brain imaging, including electroencephalography (EEG) or Near Infrared Spectroscopy (NIRS). By definition, the VS patients are awake but not aware, unlike the patients in the Minimally Conscious State (MCS), who have some fluctuating awareness. Since consciousness is impaired in both conditions, these states are also referred as Disorders of Consciousness (DOC) or prolonged Disorders of Consciousness (pDOC) This thesis aims to develop a bedside applicable tool using the EEG and NIRS for brain function assessment in VS and MCS patients. In this study, two experimental protocols have been developed and validated on healthy subjects. The results showed that using the motor imagery and own subject name stimuli, some of the VS patients were able to wilfully modulate their brain activity in response to those stimuli. The results presented in this thesis can be implemented as a part of a protocol for brain function assessment in pDOC patients and can be used for the further studies for better understanding of the brain function in these patients

Functional near infrared spectroscopy as a probe of brain function in people with prolonged disorders of consciousness

Near infrared spectroscopy (NIRS) is a non-invasive technique which measures changes in brain tissue oxygenation. NIRS has been used for continuous monitoring of brain oxygenation during medical procedures carrying high risk of iatrogenic brain ischemia and also has been adopted by cognitive neuroscience for studies on executive and cognitive functions. Until now, NIRS has not been used to detect residual cognitive functions in patients with prolonged disorders of consciousness (pDOC). In this study we aimed to evaluate the brain function of patients with pDOC by using a motor imagery task while recording NIRS. We also collected data from a group of age and gender matched healthy controls while they carried out both real and imagined motor movements to command. We studied 16 pDOC patients in total, split into two groups: five had a diagnosis of Vegetative state/Unresponsive Wakefulness State, and eleven had a diagnosis of Minimally Conscious State. In the control subjects we found a greater oxy-haemoglobin (oxyHb) response during real movement compared with imagined movement. For the between group comparison, we found a main effect of hemisphere, with greater depression of oxyHb signal in the right > left hemisphere compared with rest period for all three groups. A post-hoc analysis including only the two pDOC patient groups was also significant suggesting that this effect was not just being driven by the control subjects. This study demonstrates for the first time the feasibility of using NIRS for the assessment of brain function in pDOC patients using a motor imagery task

The expression of VvMYBPA1 in tobacco remodulates the phenylpropanoid pathway and diverts the synthesis of anthocyanins into condensed tannins in flowers

Patients in Vegetative State (VS), also known as Unresponsive Wakefulness State (UWS) are deemed to be unaware of themselves or their environment. This is different from patients diagnosed with Minimally Conscious state (MCS), who can have intermittent awareness. In both states, there is a severe impairment of consciousness; these disorders are referred to as disorders of consciousness (DOC) and if the state is prolonged, pDOC. There is growing evidence that some patients who are behaviourally in VS/UWS can show neural activation to environmental stimuli and that this response can be detected using functional brain imaging (fMRI/PET) and electroencephalography (EEG). Recently, it has also been suggested that a more reliable detection of brain responsiveness and hence a more reliable differentiation between VS/UWS and MCS requires person-centred and person-specific stimuli, such as the subject's own name stimulus.In this study we obtained event related potential data (ERP) from 12 healthy subjects and 16 patients in pDOC, five of whom were in the VS/UWS and 11 in the Minimally Conscious State (MCS). We used as the ERP stimuli the subjects' own name, others' names and reversed other names. We performed a sensor level analysis using Statistical Parametric Mapping (SPM) software. Using this paradigm in 4 DOC patients (3 in MCS, and 1 in VS/UWS) we detected a statistically significant difference in EEG response to their own name versus other peoples' names with ERP latencies (~300 ms and ~700 ms post stimuli). Some of these differences were similar to those found in a control group of healthy subjects.This study shows the feasibility of using self-relevant stimuli such as a subject's own name for assessment of brain function in pDOC patients. This neurophysiological test is suitable for bed-side/hospital based assessment of pDOC patients. As it does not require sophisticated scanning equipment it can feasibly be used within a hospital or care setting to help professionals tailor medical and psycho-social management for patients

A simple intervention for disorders of consciousness- is there a light at the end of the tunnel?

Sleep is a physiological state necessary for memory processing, learning and brain plasticity. Patients with disorders of consciousness (DOC) show none or minimal sign of awareness of themselves or their environment but appear to have sleep-wake cycles. The aim of our study was to assess baseline circadian rhythms and sleep in patients with DOC; to optimize circadian rhythm using an intervention combining blue light, melatonin and caffeine, and to identify the impact of this intervention on brain function using event related potentials. We evaluated baseline circadian rhythms and sleep in 17 patients with DOC with 24-h polysomnography (PSG) and 4-hourly saliva melatonin measurements for 48 h. Ten of the 17 patients (5 female, age 30–71) were then treated for 5 weeks with melatonin each night and blue light and caffeine treatment in the mornings. Behavioral assessment of arousal and awareness [Coma recovery scale-revised (CRS-R)], 24-h polysomnography and 4-hourly saliva melatonin measurements, oddball mismatch negativity (MMN) and subject's own name (SON) experiments were performed twice at baseline and following intervention. Baseline sleep was abnormal in all patients. Cosinor analysis of saliva melatonin results revealed that averaged baseline % rhythmicity was low (M: 31%, Range: 13–66.4%, SD: 18.4). However, increase in % Melatonin Rhythm following intervention was statistically significant (p = 0.012). 7 patients showed improvement of CRS-R scores with intervention and this was statistically significant (p = 0.034). All the patients who had improvement of clinical scores also had statistically significant improvement of neurophysiological responses on MMN and SON experiments at group level (p = 0.001). Our study shows that sleep and circadian rhythms are severely deranged in DOC but optimization is possible with melatonin, caffeine and blue light treatment. Clinical and physiological parameters improved with this simple and inexpensive intervention. Optimization of sleep and circadian rhythms should be integrated into rehabilitation programs for people with DOC

A rehabilitation unit at night : environmental characteristics of patient rooms

PURPOSE: The aim of this study was first of all to investigate the sound, light, temperature and humidity levels in a rehabilitation ward and to establish whether the measured levels were within the recommended levels or not; secondly to explore influence of the type of the patient rooms on obtained measurements. METHODS: Measurements of environmental characteristics were recorded on three non-consecutive nights by data loggers in a 12-bedded residential neurological rehabilitation unit for patients with disorders of consciousness. The obtained measurements were compared with the recommendations of the World Health Organization and the Society of Light and Lighting. RESULTS: Recordings were within recommended levels for light and humidity overnight. Average noise levels were above the recommended levels. There were abrupt increases of light and noise levels which were high enough to cause sleep fragmentation. Mean temperature levels were higher than recommended. CONCLUSIONS: Our results indicated that the patients are at risk of disturbed sleep for the duration of their stay in rehabilitation unit. Exposure to generally high noise levels, as well as the sudden increases of noise and light intensities can prevent reaching restful night-time sleep and may negatively impact on rehabilitation process due to impaired memory, learning and well-being. Implications for Rehabilitation Standards for ward based hospital environments to minimize sleep disturbance exist and can be used to examine the environmental characteristics of patients' rooms in different healthcare settings including rehabilitation units. This study shows that measurements of environmental factors were not always within the recommended levels in the rehabilitation unit and presence of abrupt increase of noise and light levels are likely to cause sleep disturbance of patients. Assessment of current practice, education and training of night staff to raise awareness on importance of sleep and environmental factors and development of strategies are required in order to improve quality of sleep in rehabilitation settings

A simple intervention for disorders of consciousness- is there a light at the end of the tunnel?

Sleep is a physiological state necessary for memory processing, learning and brain plasticity. Patients with disorders of consciousness (DOC) show none or minimal sign of awareness of themselves or their environment but appear to have sleep-wake cycles. The aim of our study was to assess baseline circadian rhythms and sleep in patients with DOC; to optimize circadian rhythm using an intervention combining blue light, melatonin and caffeine, and to identify the impact of this intervention on brain function using event related potentials. We evaluated baseline circadian rhythms and sleep in 17 patients with DOC with 24-h polysomnography (PSG) and 4-hourly saliva melatonin measurements for 48 h. Ten of the 17 patients (5 female, age 30-71) were then treated for 5 weeks with melatonin each night and blue light and caffeine treatment in the mornings. Behavioral assessment of arousal and awareness [Coma recovery scale-revised (CRS-R)], 24-h polysomnography and 4-hourly saliva melatonin measurements, oddball mismatch negativity (MMN) and subject's own name (SON) experiments were performed twice at baseline and following intervention. Baseline sleep was abnormal in all patients. Cosinor analysis of saliva melatonin results revealed that averaged baseline % rhythmicity was low ( : 31%, Range: 13-66.4%, : 18.4). However, increase in % Melatonin Rhythm following intervention was statistically significant ( = 0.012). 7 patients showed improvement of CRS-R scores with intervention and this was statistically significant ( = 0.034). All the patients who had improvement of clinical scores also had statistically significant improvement of neurophysiological responses on MMN and SON experiments at group level ( = 0.001). Our study shows that sleep and circadian rhythms are severely deranged in DOC but optimization is possible with melatonin, caffeine and blue light treatment. Clinical and physiological parameters improved with this simple and inexpensive intervention. Optimization of sleep and circadian rhythms should be integrated into rehabilitation programs for people with DOC. [Abstract copyright: Copyright © 2022 Yelden, James, Duport, Kempny, Farmer, Leff and Playford.

Late recovery of awareness in prolonged disorders of consciousness – a cross-sectional cohort study

Purpose: To detect any improvement of awareness in prolonged disorders of consciousness in the long term. Methods: A total of 34 patients with prolonged disorders of consciousness (27 vegetative state and seven minimally conscious state; 16 males; aged 21–73) were included in the study. All patients were initially diagnosed with vegetative/minimally conscious state on admission to our specialist neurological rehabilitation unit. Re-assessment was performed 2–16 years later using Coma Recovery Scale-Revised. Results: Although remaining severely disabled, 32% of the patients showed late improvement of awareness evidenced with development of non-reflexive responses such as reproducible command following and localization behaviors. Most of the late recoveries occurred in patients with subarachnoid hemorrhage (5/11, 45.5%). The ages of patients within the late recovery group (Mean = 45, SD = 11.4) and non-recovery group (Mean = 43, SD = 15.5) were not statistically different (p = 0.76). Conclusions: This study shows that late improvements in awareness are not exceptional in non-traumatic prolonged disorders of consciousness cases. It highlights the importance of long-term follow up of patients with prolonged disorders of consciousness, regardless of the etiology, age, and time passed since the brain injury. Long-term follow up will help clinicians to identify patients who may benefit from further assessment and rehabilitation. Although only one patient achieved recovery of function, recovery of awareness may have important ethical implications especially where withdrawal of artificial nutrition and hydration is considered.Implications for rehabilitationLong-term regular follow-up of people with prolonged disorders of consciousness is important.Albeit with poor functional outcomes late recovery of awareness is possible in both traumatic and non-traumatic prolonged disorders of consciousness cases.Recovery of awareness has significant clinical and ethical implications especially where withdrawal of artificial nutrition and hydration is considered

Expression and Impact of Vaspin on In Vitro Oocyte Maturation through MAP3/1 and PRKAA1 Signalling Pathways

International audienceOocyte maturation is a critical stage in embryo production and female reproduction. The aims of this study were to determine: (i) the mRNA and protein expression of vaspin and its receptor 78-kDa glucose-regulated (GRP78) in porcine cumulus-oocyte complexes (COCs) by real-time PCR and Western blot analysis, respectively, and their localisation by immunofluorescence; and (ii) the effects of vaspin on in vitro oocyte maturation (IVM) and the involvement of mitogen ERK1/2 (MAP3/1)-and AMPKα (PRKAA1)-activated kinases in the studied processes. Porcine COCs were matured in vitro for 22 h or 44 h with vaspin at a dose of 1 ng/mL and nuclear maturation assessed by Hoechst 33342 or DAPI staining and the measurement of progesterone (P4) level in the maturation medium. We showed that vaspin and GRP78 protein expression increased in oocytes and cumulus cells after IVM. Moreover, vaspin enhanced significantly porcine oocyte IVM and P4 concentration, as well as MAP3/1 phosphorylation, while decreasing PRKAA1. Using pharmacological inhibitors of MAP3/1 (PD98059) and PRKAA1 (Compound C), we observed that the effect of vaspin was reversed to the control level by all studied parameters. In conclusion, vaspin, by improving in vitro oocyte maturation via MAP3/1 and PRKAA1 kinase pathways, can be a new factor to improve in vitro fertilisation protocols