Background: Melatonin synchronizes central but also peripheral oscillators (fetal adrenal gland, pancreas, liver, kidney, heart, lung, fat, gut, etc.), allowing temporal organization of biological functions through circadian rhythms (24-hour cycles) in relation to periodic environmental changes and therefore adaptation of the individual to his/her internal and external environment. Measures of melatonin are considered the best peripheral indices of human circadian timing based on an internal 24-hour clock.Methods: First, the pharmacology of melatonin (biosynthesis and circadian rhythms, pharmacokinetics and mechanisms of action) is described, allowing a better understanding of the short and long term effects of melatonin following its immediate or prolonged release. Then, research related to the physiological effects of melatonin is reviewed.Results: The physiological effects of melatonin are various and include detoxification of free radicals and antioxidant actions, bone formation and protection, reproduction, and cardiovascular, immune or body mass regulation. Also, protective and therapeutic effects of melatonin are reported, especially with regard to brain or gastrointestinal protection, psychiatric disorders, cardiovascular diseases and oncostatic effects.Conclusion: This review highlights the high number and diversity of major melatonin effects and opens important perspectives for measuring melatonin as a biomarker (biomarker of early identification of certain disorders and also biomarker of their follow-up) and using melatonin with clinical preventive and therapeutic applications in newborns, children and adults based on its physiological regulatory effects.

Objectives: The lack of agreement regarding assessment methods is responsible for the variability in the reported rate of occurrence of spatial neglect after stroke. The aim of this study was to assess the sensitivity of different tests of neglect after right hemisphere stroke. Methods: Two hundred and six subacute right hemisphere stroke patients were given a test battery including a preliminary assessment of anosognosia and of visual extinction, a clinical assessment of gaze orientation and of personal neglect, and paper and pencil tests of spatial neglect in the peripersonal space. Patients were compared with a previously reported control group. A subgroup of patients (n=69) received a behavioural assessment of neglect in daily life situations. Results: The most sensitive paper and pencil measure was the starting point in the cancellation task. The whole battery was more sensitive than any single test alone. About 85% of patients presented some degree of neglect on at least one measure. An important finding was that behavioural assessment of neglect in daily life was more sensitive than any other single measure of neglect. Behavioural neglect was considered as moderate to severe in 36% of cases. A factorial analysis revealed that paper and pencil tests were related to two underlying factors. Dissociations were found between extrapersonal neglect, personal neglect, anosognosia, and extinction. Anatomical analyses showed that neglect was more common and severe when the posterior association cortex was damaged. Conclusions: The automatic rightward orientation bias is the most sensitive clinical measure of neglect. Behavioural assessment is more sensitive than any single paper and pencil test. The results also support the assumption that neglect is a heterogeneous disorder.

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After right posterior brain damage, patients may ignore events occurring on their left, a condition known as unilateral neglect. Although de®cits at different levels of impairment may be at work in different patients, the frequency and severity of attentional problems in neglect patients have been repeatedly underlined. Recent advances in the knowledge of the mechanisms of spatial attention in normals may help characterizing these de®cits. The present review focuses on studies exploring several aspect of attentional processing in unilateral neglect, with particular reference to the dichotomy between`exogenous', or stimulus-related, and`endogenous', or strategy-driven, orienting of attention. A large amount of neuropsychological evidence suggests that a basic mechanism leading to left neglect behavior is an impaired exogenous orienting toward left-sided targets. In contrast, endogenous processes seem to be relatively preserved, if slowed, in left unilateral neglect. Other component de®cits, such as a general slowing of the operations of spatial attention, might contribute to neglect behavior. These results are presented and discussed, and their implications for hemispheric specialization in attentional orienting and for the mechanisms of visual consciousness are explored. q

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Left unilateral neglect, a dramatic condition which impairs awareness of left-sided events, has been classically reported after right hemisphere cortical lesions involving the inferior parietal region. More recently, the involvement of long range white matter tracts has been highlighted, consistent with the idea that awareness of events occurring in space depends on the coordinated activity of anatomically distributed brain regions. Damage to the superior longitudinal fasciculus (SLF), linking parietal to frontal cortical regions, or to the inferior longitudinal fasciculus (ILF), connecting occipital and temporal lobes, has been described in neglect patients. In this study, four right-handed patients with right hemisphere strokes underwent a high definition anatomical MRI with diffusion tensor imaging (DTI) sequences and a pencil and paper neglect battery of tests. We used DTI tractography to visualise the SLF, ILF and the inferior fronto-occipital fasciculus (IFOF), a pathway running the depth of the temporal lobe, not hitherto associated with neglect. Two patients with cortical involvement of the inferior parietal and superior temporal regions, but intact and symmetrical fasciculi, showed no signs of neglect. The other two patients with signs of left neglect had superficial damage to the inferior parietal cortex and white matter damage involving the IFOF. These findings suggest that superficial damage to the inferior parietal cortex per se may not be sufficient to produce visual neglect. In some cases, a lesion to the direct connections between ventral occipital and frontal regions (ie, IFOF) may contribute to the manifestation of neglect by impairing the top down modulation of visual areas from the frontal cortex.

The frequency of occurrence of right neglect was, as expected, much lower than that reported in a study using the same assessment battery in right brain damage stroke patients. Nevertheless, neglect was found in a substantial proportion of patients at a subacute stage, suggesting that it should be considered in the rehabilitation planning of left brain damage stroke patients.