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.

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 rehabilitation Long-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.

Human EEG shows long-range temporal correlations of oscillation amplitude in Theta, Alpha and Beta bands across a wide age range.

OBJECTIVE: Long-range temporal correlations (LRTC) of EEG amplitude fluctuations in adults reveal power-law statistics and have been interpreted within the framework of self-organized criticality (SOC). In physical systems states of self-organized criticality showing power-law statistics take time to develop. In this paper we have sought evidence for the idea that brain development tends towards SOC through examining the hypothesis that during normal human development a power law behaviour of EEG oscillations is approached with increasing chronological age. METHODS: We examined EEGs from central and parietal electrodes in 36 subjects aged between 0 and 660months during performance of a steady wrist extension task with their dominant hand and applied spectral and detrended fluctuation analysis in 36 subjects to assess long-range temporal correlations of oscillation amplitude in the Theta, Alpha and Beta frequency bands. RESULTS: Our data indicate that at all subject ages power-law statistics dominate the records at Alpha, Beta and Theta frequencies. Small consistent effects of chronological age were detected for amplitude fluctuations at Theta and Beta frequencies. CONCLUSIONS: The data suggest that the scale-free nature of EEG LRTCs is a feature from early childhood through to maturity but that there are changes in the magnitude of these effects with age. SIGNIFICANCE: This study is the first to have explored long-range temporal correlations over a wide range of chronological age.

On the development of human corticospinal oscillations: age-related changes in EEG-EMG coherence and cumulant.

Changes in coherence and cumulant calculated between electroencephalograph (EEG) recorded from the scalp over primary motor cortex and rectified surface electromyograph (EMG) recorded from the contralateral wrist extensor muscles have been studied during development in humans (48 subjects, age 0-59 years). Using the techniques of EEG-EMG coherence and cumulant analysis and pooled coherence and cumulant analysis we demonstrate that between childhood, adolescence and adulthood there are increases in the prevalence and magnitude of coherence at frequencies between 15 and 35 Hz with corresponding development of a tri-phasic feature in the EEG-EMG cumulant. The results show for the first time that changes in the cortical approximately 20 Hz oscillatory drive to human motoneurone pools take place during motor development.

Changes in EMG coherence between long and short thumb abductor muscles during human development.

In adults, motoneurone pools of synergistic muscles that act around a common joint share a common presynaptic drive. Common drive can be revealed by both time domain and frequency domain analysis of EMG signals. Analysis in the frequency domain reveals significant coherence in the range 1-45 Hz, with maximal coherence in low (1-12 Hz) and high (16-32 Hz) ranges. The high-frequency range depends on cortical drive to motoneurones and is coherent with cortical oscillations at approximately 20 Hz frequencies. It is of interest to know whether oscillatory drive to human motoneurone pools changes with development. In the present study we examined age-related changes in coherence between rectified surface EMG signals recorded from the short and long thumb abductor muscles during steady isometric contraction obtained while subjects abducted the thumb against a manipulandum. We analysed EMG data from 36 subjects aged between 4 and 14 years, and 11 adult subjects aged between 22 and 59 years. Using the techniques of pooled coherence analysis and the chi(2) difference of coherence test we demonstrate that between the ages of 7 and 9 years, and 12 and 14 years, there are marked increases in the prevalence and magnitude of coherence at frequencies between 11 and 45 Hz. The data from subjects aged 12-14 years were similar to those obtained from adult controls. The most significant differences between younger children and the older age groups were detected at frequencies close to 20 Hz. We believe that these are the first reported results demonstrating significant late maturational changes in the approximately 20 Hz common oscillatory drive to human motoneurone pools.