Coherence and Consciousness: Study of Fronto-Parietal Gamma Synchrony in Patients with Disorders of Consciousness.

Evaluation of consciousness needs to be supported by the evidence of brain activation during external stimulation in patients with unresponsive wakefulness syndrome (UWS). Assessment of patients should include techniques that do not depend on overt motor responses and allow an objective investigation of the spontaneous patterns of brain activity. In particular, electroencephalography (EEG) coherence allows to easily measure functional relationships between pairs of neocortical regions and seems to be closely correlated with cognitive or behavioral measures. Here, we show the contribution of higher order associative cortices of patients with disorder of consciousness (N = 26) in response to simple sensory stimuli, such as visual, auditory and noxious stimulation. In all stimulus modalities an increase of short-range parietal and long-range fronto-parietal coherences in gamma frequencies were seen in the controls and minimally conscious patients. By contrast, UWS patients showed no significant modifications in the EEG patterns after stimulation. Our results suggest that UWS patients can not activate associative cortical networks, suggesting a lack of information integration. In fact, fronto-parietal circuits result to be connectively disrupted, conversely to patients that exhibit some form of consciousness. In the light of this, EEG coherence can be considered a powerful tool to quantify the involvement of cognitive processing giving information about the integrity of fronto-parietal network. This measure can represent a new neurophysiological marker of unconsciousness and help in determining an accurate diagnosis and rehabilitative intervention in each patient.

Nocturnal melatonin regulation in post-traumatic vegetative state: a possible role for melatonin supplementation?

Circadian rhythms were recently proposed as a measure of physiological state and prognosis in disorders of consciousness (DOC). So far, melatonin regulation was never assessed in vegetative state (VS). Aim of our research was to investigate the nocturnal melatonin levels and light-induced melatonin suppression in a cohort of VS patients. We assessed six consecutive patients (four men, age 33.3 ± 9.3 years) with post-traumatic VS and nine age-matched healthy volunteers (five men, age 34.3 ± 8.9 years) on two consecutive nights: one baseline and one light exposure night. During baseline, night subjects were in bed in a dim (<5 lux) room from 10 pm to 8 am. Blood samples were collected hourly 00:30-3:30 am (00:30 = MLT1; 1:30 = MLT2; 2:30 = MLT3; and 3:30 = MLT4). Identical setting was used for melatonin suppression test night, except for the exposure to monochromatic (470 nm) light from 1:30 to 3:30 am. Plasma melatonin levels were evaluated by radioimmunoassay. Magnitude of melatonin suppression was assessed by melatonin suppression score (caMSS) and suppression rate. We searched for group differences in melatonin levels, differences between repeated samples melatonin concentrations during baseline night and light exposure night, and light-induced suppression of melatonin secretion. During baseline night, controls showed an increase of melatonin (MLT4 vs MLT1, p = 0.037), while no significant changes were observed in VS melatonin levels (p = 0.172). Baseline night MLT4 was significantly lower in VS vs controls (p = 0.036). During light-exposure night, controls displayed a significant suppression of melatonin (MLT3 and MLT4 vs MLT2, p = 0.016 and 0.002, respectively), while VS patients displayed no significant changes. The magnitude of light-induced suppression of melatonin levels was statistically different between groups considering control adjusted caMSS (p = 0.000), suppression rate (p = 0.002) and absolute percentage difference (p = 0.012). These results demonstrate for the first time that VS patients present an alteration in night melatonin secretion and reduced light-induced melatonin suppression. These findings confirm previous studies demonstrating a disruption of the circadian system in DOC and suggest a possible benefit from melatonin supplementation in VS.