Pseudocontinuous arterial spin labeling reveals dissociable effects of morphine and alcohol on regional cerebral blood flow

We have examined sensitivity and specificity of pseudocontinuous arterial spin labeling (PCASL) to detect global and regional changes in cerebral blood flow (CBF) in response to two different psychoactive drugs. We tested alcohol and morphine in a placebo-controlled, double-blind randomized study in 12 healthy young men. Drugs were administered intravenously. Validated pharmacokinetic protocols achieved minimal intersubject and intrasubject variance in plasma drug concentration. Permutation-based statistical testing of a mixed effect repeated measures model revealed a widespread increase in absolute CBF because of both morphine and alcohol. Conjunction analysis revealed overlapping effects of morphine and alcohol on absolute CBF in the left anterior cingulate, right hippocampus, right insula, and left primary sensorimotor areas. Effects of morphine and alcohol on relative CBF (obtained from z-normalization of absolute CBF maps) were significantly different in the left putamen, left frontoparietal network, cerebellum, and the brainstem. Corroborating previous PET results, our findings suggest that PCASL is a promising tool for central nervous system drug research

Fear inhibition in high trait anxiety.

Trait anxiety is recognized as an individual risk factor for the development of anxiety disorders but the neurobiological mechanisms remain unknown. Here we test whether trait anxiety is associated with impaired fear inhibition utilizing the AX+/BX- conditional discrimination procedure that allows for the independent evaluation of startle fear potentiation and inhibition of fear. Sixty undergraduate students participated in the study--High Trait Anxious: n = 28 and Low Trait Anxious: n = 32. We replicated earlier findings that a transfer of conditioned inhibition for startle responses requires contingency awareness. However, contrary to the fear inhibition hypothesis, our data suggest that high trait anxious individuals show a normal fear inhibition of conditioned startle responding. Only at the cognitive level the high trait anxious individuals showed evidence for impaired inhibitory learning of the threat cue. Together with other findings where impaired fear inhibition was only observed in those PTSD patients who were either high on hyperarousal symptoms or with current anxiety symptoms, we question whether impaired fear inhibition is a biomarker for the development of anxiety disorders

High trait anxiety: a challenge for disrupting fear memory reconsolidation.

Disrupting reconsolidation may be promising in the treatment of anxiety disorders but the fear-reducing effects are thus far solely demonstrated in the average organism. A relevant question is whether disrupting fear memory reconsolidation is less effective in individuals who are vulnerable to develop an anxiety disorder. By collapsing data from six previous human fear conditioning studies we tested whether trait anxiety was related to the fear-reducing effects of a pharmacological agent targeting the process of memory reconsolidation--n = 107. Testing included different phases across three consecutive days each separated by 24 h. Fear responding was measured by the eye-blink startle reflex. Disrupting the process of fear memory reconsolidation was manipulated by administering the β-adrenergic receptor antagonist propranolol HCl either before or after memory retrieval. Trait anxiety uniquely predicted the fear-reducing effects of disrupting memory reconsolidation: the higher the trait anxiety, the less fear reduction. Vulnerable individuals with the propensity to develop anxiety disorders may need higher dosages of propranolol HCl or more retrieval trials for targeting and changing fear memory. Our finding clearly demonstrates that we cannot simply translate observations from fundamental research on fear reduction in the average organism to clinical practice

Ambulatory measurement of cortisol: Where do we stand, and which way to follow?

Accumulating evidence supports the harmful effects of stress on health, including the development and progress of psychopathology (e.g. anxiety disorders), metabolic disorders (e.g. diabetes type II), inflammatory disturbances, and cardiovascular disease. These harmful effects are often expressed as disturbances in cortisol levels, patterns, or responses. Unfortunately, at present, cortisol assessment is only performed in the laboratory. This hinders rapid quantification, let alone being determined by individuals themselves, with self-testing devices or sensors. More accurate and timely detection of cortisol may have important implications for the prevention, diagnosis, and treatment of stress-related disorders as well as for those suffering from adrenal insufficiencies. The present review provides an overview of the most promising and challenging technologies for cortisol measurement. An important first conclusion might be that almost all reviewed technologies were at the proof-of-concept stage, meaning it was premature to interpret the findings in light of regulatory requirements for in vitro diagnostics. Nevertheless, several promising proto-types, including electrochemical sensors with wearable potential, were found and are consequently discussed. Overall the findings suggest that with significant additional investments and research efforts in the coming years, accurate, rapid, and repeated cortisol assessment in everyday life can become reality

Main features of our previous studies on fear memory reconsolidation.

<p>FPS: Fear potentiated startle. SCR: Skin conductance responding. CS: Conditioned stimulus. US: Unconditioned stimulus. Note that in our current study the CSa stimulus always represents the CS1+ whereas the CSb stimulus always represents the unreinforced control stimulus, which either consists of the CS2 [Kindt et al. 2009, Soeter & Kindt 2010, 2012b] or the CS3 stimulus [Soeter & Kindt 2011, 2012a].</p

Schematic of the basic experimental procedure.

<p>Schematic of the basic experimental procedure.</p

Mean values (SD) of the systolic and diastolic blood pressure in mmHg and amylase level in U-ml for the combined propranolol HCl conditions.

<p>Mean values (SD) of the systolic and diastolic blood pressure in mmHg and amylase level in U-ml for the combined propranolol HCl conditions.</p

Results from the Hierarchical Multiple Regression analyses.

<p>Note that R² = .09 for Step I (<i>p</i><0.05) and Δ R² = .03 for Step II (<i>p</i>>0.05).</p>*<p><i>p</i><0.05.</p