Mauro F. Larra

For whom the bell (curve) tolls: Cortisol rapidly affects memory retrieval by an inverted U-shaped dose–response relationship

Stress and cortisol are generally considered to impair declarative memory retrieval, although opposite results have also been reported. Dose-dependent effects and differences between genomic and non-genomic cortisol effects are possible reasons for these discrepancies. The aim of the current experiment was to assess the non-genomic effects of escalating doses of intravenous cortisol on cued recall of socially relevant information in humans. 40 participants (age range 20-30 years; 20 females) learned associations between male faces with a neutral facial expression and descriptions of either positive or negative social behaviors and were tested one week later in a cued recall paradigm. Escalating doses of cortisol (0, 3, 6, 12, 24 mg) were administered 8 min before testing according to a between-subjects design. An inverted U-shaped dose-response relationship between salivary cortisol levels and recall performance was observed, with moderate elevation of salivary cortisol resulting in the best recall performance. This is the first study in humans demonstrating that cortisol rapidly modulates declarative memory retrieval via a dose-dependent, non-genomic mechanism that follows an inverted U-shaped curve. Our result further emphasizes the importance of fast cortisol effects for human cognition.

Intranasal insulin increases regional cerebral blood flow in the insular cortex in men independently of cortisol manipulation

Insulin and cortisol play a key role in the regulation of energy homeostasis, appetite, and satiety. Little is known about the action and interaction of both hormones in brain structures controlling food intake and the processing of neurovisceral signals from the gastrointestinal tract. In this study, we assessed the impact of single and combined application of insulin and cortisol on resting regional cerebral blood flow (rCBF) in the insular cortex. After standardized periods of food restriction, 48 male volunteers were randomly assigned to receive either 40 IU intranasal insulin, 30 mg oral cortisol, both, or neither (placebo). Continuous arterial spin labeling (CASL) sequences were acquired before and after pharmacological treatment. We observed a bilateral, locally distinct rCBF increase after insulin administration in the insular cortex and the putamen. Insulin effects on rCBF were present regardless of whether participants had received cortisol or not. Our results indicate that insulin, but not cortisol, affects blood flow in human brain structures involved in the regulation of eating behavior. Hum Brain Mapp 35:1944–1956, 2014.

Heart rate response to post-learning stress predicts memory consolidation

Stressful experiences are often well remembered, an effect that has been explained by beta-adrenergic influences on memory consolidation. Here, we studied the impact of stress induced heart rate (HR) responses on memory consolidation in a post-learning stress paradigm. 206 male and female participants saw 52 happy and angry faces immediately before being exposed to the Cold Pressor Test or a non-stressful control procedure. Memory for the faces and their respective expression was tested twice, after 30 min and on the next day. High HR responders (in comparison to low HR responders as well as to the non-stressful control group) showed enhanced recognition memory one day after learning. Our results show that beta-adrenergic activation elicited shortly after learning enhances memory consolidation and that the stress induced HR response is a predictor for this effect.

Enhanced stress response by a bilateral feet compared to a unilateral hand Cold Pressor Test

Abstract The Cold Pressor Test (CPT) is a frequently employed laboratory stress protocol. However, with many experimental designs the application in its classic form (immersion of the dominant hand into ice-water) is problematic as unilateral stimulation may need to be avoided and/or hands are required for further measurements. Here, we describe a simple modification of the classic CPT in which both feet are immersed into ice-water and compare the evoked neuroendocrine stress response to the classic CPT in a within-subjects design. Twenty-four healthy participants were exposed to each of both CPT versions on two subsequent days in randomized order. Heart rate, blood pressure, salivary alpha-amylase and cortisol were measured at baseline and during or after CPT exposition, respectively, along with subjective ratings of pain and stress. The bilateral feet CPT induced marked increases in all measured stress parameters. Moreover, with the exception of blood pressure, autonomic and endocrine responses were enhanced compared to the classic CPT. The bilateral feet CPT thus is a valid and simple modification and may be useful when the application of the classic CPT is unfeasible or a stronger neuroendocrine stress response is of interest.

Respiratory modulation of startle eye blink: a new approach to assess afferent signals from the respiratory system

Current approaches to assess interoception of respiratory functions cannot differentiate between the physiological basis of interoception, i.e. visceral-afferent signal processing, and the psychological process of attention focusing. Furthermore, they typically involve invasive procedures, e.g. induction of respiratory occlusions or the inhalation of CO2-enriched air. The aim of this study was to test the capacity of startle methodology to reflect respiratory-related afferent signal processing, independent of invasive procedures. Forty-two healthy participants were tested in a spontaneous breathing and in a 0.25 Hz paced breathing condition. Acoustic startle noises of 105 dB(A) intensity (50 ms white noise) were presented with identical trial frequency at peak and on-going inspiration and expiration, based on a new pattern detection method, involving the online processing of the respiratory belt signal. The results show the highest startle magnitudes during on-going expiration compared with any other measurement points during the respiratory cycle, independent of whether breathing was spontaneous or paced. Afferent signals from slow adapting phasic pulmonary stretch receptors may be responsible for this effect. This study is the first to demonstrate startle modulation by respiration. These results offer the potential to apply startle methodology in the non-invasive testing of interoception-related aspects in respiratory psychophysiology. This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.

Polymorphisms of genes related to the hypothalamic-pituitary-adrenal axis influence the cortisol awakening response as well as self-perceived stress

The hypothalamus-pituitary-adrenal (HPA) axis is a crucial endocrine system for coping with stress. A reliable and stable marker for the basal state of that system is the cortisol awakening response (CAR). We examined the influence of variants of four relevant candidate genes; the mineralocorticoid receptor gene (MR), the glucocorticoid receptor gene (GR), the serotonin transporter gene (5-HTT) and the gene encoding the brain-derived neurotrophic factor (BDNF) on CAR and self-perceived stress in 217 healthy subjects. We found that polymorphisms of GR influenced both, the basal state of the HPA axis as well as self-perceived stress. MR only associated with self-perceived stress and 5-HTT only with CAR. BDNF did not affected any of the investigated indices. In summary, we suggest that GR variants together with the CAR and supplemented with self reports on perceived stress might be useful indicators for the basal HPA axis activity.

Rapid cortisol enhancement of psychomotor and startle reactions to side-congruent stimuli in a focused cross-modal choice reaction time paradigm

The stress hormone cortisol has been shown to affect hemodynamic activity of human brain structures, presumably via a nongenomic mechanism. However, behavioral implications of this finding remain unknown. In a placebo-controlled, blinded, cross-over design the rapid effects of IV hydrocortisone (5mg) on cross-modal integration of simultaneous, unilateral visual and acoustic signals in a challenging startle and reaction time (RT) paradigm were studied. On two separate days 1 week apart, 24 male volunteers responded by button push to either up- or down pointing triangles presented in random sequence in the periphery of one of the visual hemi-fields. Visual targets were accompanied by unilateral acoustic startle noise bursts, presented at the same or opposite side. Saccadic latency, manual RT, and startle eye blink responses were recorded. Faster manual reactions and increased startle eye blink responses were observed 11-20 min after hydrocortisone administration when visual targets and unilateral acoustic startle noises were presented in the same sensory hemi-field, but not when presented in opposite sensory hemi-fields. Our results suggest that a nongenomic, cortisol-sensitive mechanism enhances psychomotor and startle reactions when stimuli occur in the same sensory hemi-field. Such basic cognitive effects of cortisol may serve rapid adaptation and protection against danger stimuli in stressful contexts.

Cardiac cycle time effects on mask inhibition.

Research on the interaction of the cardiovascular and the central nervous system has demonstrated inhibitory effects associated with baroreceptor stimulation. One way of examining baroreceptor influence on behavior and central nervous processes is by making use of naturally occurring variations in baroreceptor stimulation in the course of the cardiac cycle. In terms of perceptual and sensorimotor processes, until today, research has focused primarily on cardiac cycle time effects on the perception of and reaction to simple stimuli. The present study is the first to investigate modulatory effects of variations in baroreceptor activity in the context of a more complex stimulus configuration using a visual masking task in which a target has to be selected against an interfering mask. The results suggest that baroreceptor stimulation enhances inhibitory processes needed to solve perceptual interference.

The socially evaluated handgrip test: Introduction of a novel, time-efficient stress protocol

Most widely-used stress-induction procedures (such as the TSST and the Cold Pressor Test) require considerable effort and overhead in terms of preparation, logistics, and staff recruitment. Moreover, while known to reliably induce HPA axis activation, especially when combined with social self-threat, most conventional laboratory stressors cannot be flexibly adapted to elicit either a mainly autonomic or an additional endocrine stress response. Being a promising alternative approach, a new version of the isometric handgrip test enriched by a social-evaluative component was evaluated in the present study. On two consecutive sessions, forty participants (20 women) performed a handgrip task at both 45% (stress) and 10% (control) of maximum voluntary isometric contraction lasting for 3min. During the stress test, continuous visual feedback on performance was given. Participants in the social-evaluative condition (50%) were observed and evaluated by a previously unknown person of the opposite sex, whereas in the standard condition feedback was provided via a computer monitor. Cardiovascular measures (heart rate, blood pressure) as well as additional indices of autonomic reactivity (skin conductance, heart-rate variability) were registered before, during, and after stress induction. Moreover, changes in salivary cortisol and in subjective well-being were assessed. Relative to control, significant increases in cardiovascular and sympathetic activity were found, irrespective of experimental group. Importantly, however, additional social evaluation resulted in elevated cortisol levels. Furthermore, evidence for reduced vagal tone during sustained socially evaluated handgrip emerged. In conclusion, the socially evaluated handgrip test represents a versatile, time-efficient method to induce stress in small laboratory settings.

Cardiac cycle time effects on selection efficiency in vision

The effect of cardiac cycle time on attentional selection was investigated in an experiment in which participants classified target letters in a visual selection task. Stimulus onsets were aligned to the R wave of the electrocardiogram and stimuli presented either during the ventricular systole or diastole. Selection efficiency was operationalized as difference in target selection performance under conditions of homogeneous and heterogeneous distractors. Differences in performance (i.e., the impact selection difficulty had on the ability to select the target) were attenuated for stimuli presented during the ventricular systole compared to the diastole. Increased baroafferent signal transmission during the systole appears to reduce interference of highly distracting stimuli on visual selection efficiency.