Sex hormone-binding globulin (SHBG) is the high-affinity binding protein for androgens and estrogens. According to the free hormone hypothesis, SHBG modulates the bioactivity of sex steroids by limiting their diffusion into target tissues. Still, the in vivo physiological role of circulating SHBG remains unclear, especially since mice and rats lack circulating SHBG post-natally. To test the free hormone hypothesis in vivo, we examined total and free sex steroid concentrations and bioactivity on target organs in mice expressing a human SHBG transgene. SHBG increased total androgen and estrogen concentrations via hypothalamic-pituitary feedback regulation and prolonged ligand half-life. Despite markedly raised total sex steroid concentrations, free testosterone was unaffected while sex steroid bioactivity on male and female reproductive organs was attenuated. This occurred via a ligand-dependent, genotype-independent mechanism according to in vitro seminal vesicle organ cultures. These results provide compelling support for the determination of free or bioavailable sex steroid concentrations in medicine, and clarify important comparative differences between translational mouse models and human endocrinology.

The aim of the present experimental series was to investigate the role of the medial frontal region including the supplementary motor area in the coordination between posture and movement in a bimanual load lifting task. The seated subject was instructed to maintain in a horizontal position one forearm (postural arm) which was loaded with a 1 kg weight. The unloading was performed either by the experimenter (imposed unloading) or by a voluntary movement of the other arm (voluntary unloading). In normal individuals, with the voluntary unloading, the movement control was accompanied by an anticipatory adjustment of the postural forearm flexor activity, which resulted in the maintenance of the forearm position despite the unloading. The anticipatory postural adjustments were impaired in 4 out of 5 patients with unilateral lesion of the SMA region; the defect was observed mainly when the postural forearm was contralateral to the lesion. No change in the anticipatory postural adjustment was observed in one patient with complete callosal section. This finding indicates that the coordination between the posture and movement in this task is not organized through callosal fibers linking the cortices on both sides but rather at a subcortical level. The anticipatory postural adjustments were abolished in two patients with spastic hemiparesis when the postural forearm was the spastic arm. It is suggested that the SMA region contralateral to the postural forearm, together with other premotor or motor areas, may select the circuits responsible for the phasic postural adjustments which are necessary to ensure postural maintenance, whereas the motor cortex contralateral to the voluntary movement controls both the movement and, via collaterals, the preselected circuits responsible for the associated postural adjustments.

Having a creative mind is one of the gateways for achieving fabulous success and remarkable progress in professional, personal and social life. Therefore, a better understanding of the neural correlates and the underlying neural mechanisms related to creative ideation is crucial and valuable. However, the current literature on neural systems and circuits underlying creative cognition, and on how creative drives such as motivation, mood states, and reward could shape our creative mind through the associated neuromodulatory systems [i.e., the dopaminergic (DA), the noradrenergic (NE) and the serotonergic (5-HT) system] seems to be insufficient to explain the creative ideation and production process. One reason might be that the mentioned systems and processes are usually investigated in isolation and independent of each other. Through this review, we aim at advancing the current state of knowledge by providing an integrative view on the interactions between neural systems underlying the creative cognition and the creative drive and associated neuromodulatory systems (see Figure 1 ).

SummaryThe Mirror Neuron System (MNS) plays a crucial role in action perception and imitative behavior, which is suggested to be impaired in Autism Spectrum Disorders (ASDs). In this review, we discuss the plausibility and empirical evidence of a neural interaction between the MNS, action perception, empathy, imitative behavior, and their impact on social decision making in ASDs. To date, there is no consensus regarding a particular theory in ASDs and its underlying mechanisms. Some theories have completely focused on social difficulties, others have emphasized sensory aspects. Based on the current studies, we suggest a multilayer neural network model including the MNS on a first layer and transforming this information to a higher layer network responsible for reasoning. Future studies with ASD participants combining behavioral tasks with neuroimaging methods and transcranial brain stimulation as well as computational modeling can help validate and complement this suggested model. Moreover, we propose applying the behavioral paradigms, and the neurophysiological markers mentioned in this review article for evaluating psychiatric treatment approaches in ASDs. The investigation of modulating effects of different treatment approaches on the neurophysiological markers of the MNS can help find specific subgroups of ASDs patients and support tailored psychiatric interventions.