Ghrelin modulates encoding-related brain function without enhancing memory formation in humans.

Ghrelin regulates energy homeostasis in various species and enhances memory in rodent models. In humans, the role of ghrelin in cognitive processes has yet to be characterized. Here we show in a double-blind randomized crossover design that acute administration of ghrelin alters encoding-related brain activity, however does not enhance memory formation in humans. Twenty-one healthy young male participants had to memorize food- and non-food-related words presented on a background of a virtual navigational route while undergoing fMRI recordings. After acute ghrelin administration, we observed decreased post-encoding resting state fMRI connectivity between the caudate nucleus and the insula, amygdala, and orbitofrontal cortex. In addition, brain activity related to subsequent memory performance was modulated by ghrelin. On the next day, however, no differences were found in free word recall or cued location-word association recall between conditions; and ghrelin's effects on brain activity or functional connectivity were unrelated to memory performance. Further, ghrelin had no effect on a cognitive test battery comprising tests for working memory, fluid reasoning, creativity, mental speed, and attention. In conclusion, in contrast to studies with animal models, we did not find any evidence for the potential of ghrelin acting as a short-term cognitive enhancer in humans.

Oxytocin and cortisol concentrations in adults with and without autism spectrum disorder in response to physical exercise.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, whose core symptoms consist of deficits in social interaction and communication as well as restricted and repetitive behavior. Brain oxytocin (OXT) has been associated with various prosocial behaviors, and might, therefore, be involved in the pathogenesis of disorders associated with socio-emotional dysfunctions such as ASD. However, significant associations between central and peripheral OXT levels may only be present in response to physiological or stressful stimuli but were not shown under baseline conditions. In this study, we, therefore, investigated salivary and plasma OXT in response to physical exercise in adults with ASD (n â€‹= â€‹33, mean age: 36.8 â€‹± â€‹10.7 years) without intellectual impairment (IQ â€‹> â€‹70) and neurotypical controls (n â€‹= â€‹31, mean age: 31.0 â€‹± â€‹11.7 years). To stimulate the OXT system, we used rapid cycling and measured cortisol (CORT) concentrations to monitor the physiological stress response. When controlling for age, neither salivary OXT (p â€‹= â€‹.469), plasma OXT (p â€‹= â€‹.297) nor CORT (p â€‹= â€‹.667) concentrations significantly differed between groups at baseline. In addition, neither OXT nor CORT concentrations significantly differed between groups after physical exercise. Social anxiety traits were negatively correlated with plasma, but not saliva OXT concentrations in neurotypicals at baseline, while empathetic traits were positively correlated with saliva, but not plasma concentrations in autistic patients at baseline. No significant correlations between salivary and plasma OXT concentrations were found at any time point. Future studies including adult participants should investigate the effect of age on CORT and OXT concentrations in response to stress.

Differences in the insulin tolerance test in patients with brain damage depending on posture.

OBJECTIVE: The insulin tolerance test (ITT) is the gold standard for the diagnosis of GH deficiency (GHD) and hypocortisolism. As hypopituitarism is a common disorder after traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH), the test is increasingly used in patients with pre-existing brain damage. DESIGN: A cross-sectional, observational study. METHODS: Fifty-six patients (41 TBI and 15 SAH) were tested with the ITT (0.15 IE/kg body weight, mean glucose 33 mg/dl). In 38 patients, the test was performed in a supine position; the other 18 patients were in a sitting position during the ITT. RESULTS: Hypocortisolism and GHD were more often diagnosed in a supine than in a sitting position (hypocortisolism: 55.3% supine versus 0% sitting, P<0.0001; GHD: 42.1% supine versus 11.1% sitting, P=0.03). Patients in a sitting position suffered more often from symptoms such as tachycardia (61.1% sitting versus 15.8% supine, P=0.001), trembling (22.2 vs 7.9%, NS), and sweating (66.7 vs 28.9%, P=0.007). There were no significant differences between the groups in drowsiness (72.2% sitting versus 65.8% supine, NS), dizziness (44.4 vs 44.7%, NS), and fatigue (33.3 vs 15.8%, NS). Because of somnolence, the hypoglycemic state could only be stopped with i.v. administration of glucose in 25 supine patients (66%). In contrast, none of the 18 patients (0%) tested in a sitting position got somnolent or was in need of i.v. application of glucose (P<0.001). CONCLUSIONS: In patients with brain injury, posture might affect rates of diagnosing GHD and hypocortisolism and sympathetic symptoms in the ITT. These findings are exploratory and need replication in a standardized setting.