Significance: The hypothalamic-pituitary-adrenal axis is a critical neurohormonal network regulating homeostasis and coordinating stress responses. Here we demonstrate that an oscillating pattern of plasma cortisol is important for maintenance of healthy brain responses as measured by functional neuroimaging and behavioral testing. Our data highlight the crucial role of glucocorticoid rhythmicity in ( i ) modulating sleep behavior and working memory performance, and ( ii ) regulating the human brain’s responses under emotional stimulation. Current optimal cortisol replacement therapies for patients with primary or secondary adrenal insufficiently are associated with poor psychological status, and these results suggest that closer attention to aspects of chronotherapy will benefit these patients and may also have major implications for improved glucocorticoid dynamics in stress and psychiatric disease.

Discrimination of eye movements and visual states is a flourishing field of research and there is an urgent need for non-manual EEG-based wheelchair control and navigation systems. This paper presents a novel system that utilizes a brain–computer interface (BCI) to capture electroencephalographic (EEG) signals from human subjects while eye movement and subsequently classify them into six categories by applying a random forests (RF) classification algorithm. RF is an ensemble learning method that constructs a series of decision trees where each tree gives a class prediction, and the class with the highest number of class predictions becomes the model’s prediction. The categories of the proposed random forests brain–computer interface (RF-BCI) are defined according to the position of the subject’s eyes: open, closed, left, right, up, and down. The purpose of RF-BCI is to be utilized as an EEG-based control system for driving an electromechanical wheelchair (rehabilitation device). The proposed approach has been tested using a dataset containing 219 records taken from 10 different patients. The BCI implemented the EPOC Flex head cap system, which includes 32 saline felt sensors for capturing the subjects’ EEG signals. Each sensor caught four different brain waves (delta, theta, alpha, and beta) per second. Then, these signals were split in 4-second windows resulting in 512 samples per record and the band energy was extracted for each EEG rhythm. The proposed system was compared with naïve Bayes, Bayes Network, k-nearest neighbors (K-NN), multilayer perceptron (MLP), support vector machine (SVM), J48-C4.5 decision tree, and Bagging classification algorithms. The experimental results showed that the RF algorithm outperformed compared to the other approaches and high levels of accuracy (85.39%) for a 6-class classification are obtained. This method exploits high spatial information acquired from the Emotiv EPOC Flex wearable EEG recording device and examines successfully the potential of this device to be used for BCI wheelchair technology.

The hypothalamic‐pituitary‐adrenal (HPA) axis is critical for life. It has a circadian rhythm that anticipates the metabolic, immunoregulatory and cognitive needs of the active portion of the day, and retains an ability to react rapidly to perceived stressful stimuli. The circadian variation in glucocorticoids is very ‘noisy’ because it is made up from an underlying approximately hourly ultradian rhythm of glucocorticoid pulses, which increase in amplitude at the peak of circadian secretion. We have shown that these pulses emerge as a consequence of the feedforward–feedback relationship between the actions of corticotrophin hormone (ACTH) on the adrenal cortex and of endogenous glucocorticoids on pituitary corticotrophs. The adrenal gland itself has adapted to respond preferentially to a digital signal of ACTH and has its own feedforward–feedback system that effectively amplifies the pulsatile characteristics of the incoming signal. Glucocorticoid receptor signalling in the body is also adapted to respond in a tissue‐specific manner to oscillating signals of glucocorticoids, and gene transcriptional and behavioural responses depend on the pattern (i.e. constant or pulsatile) of glucocorticoid presentation. During major stressful activation of the HPA, there is a marked remodelling of the pituitary–adrenal interaction. The link between ACTH and glucocorticoid pulses is maintained, although there is a massive increase in the adrenal responsiveness to the ACTH signals.